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PubMedDate not supplied

[The role of autonomic cardiovascular neuropathy in pathogenesis of ischemic heart disease in patients with diabetes mellitus].

INTRODUCTION: Diabetes is strongly associated with macrovascular complications, among which ischemic heart disease is the major cause of mortality. Autonomic neuropathy increases the risk of complications, which calls for an early diagnosis. The aim of this study was to determine both presence and extent of cardiac autonomic neuropathy, in regard to the type of diabetes mellitus, as well as its correlation with coronary disease and major cardiovascular risk factors. MATERIAL AND METHODS: We have examined 90 subjects, classified into three groups, with 30 patients each: those with type 1 diabetes, type 2 diabetes and control group of healthy subjects. All patients underwent cardiovascular tests (Valsalva maneuver, deep breathing test, response to standing, blood pressure response to standing sustained, handgrip test), electrocardiogram, treadmill exercise test and filled out a questionnaire referring to major cardiovascular risk factors: smoking, obesity, hypertension, and dyslipidemia. RESULTS: Our results showed that cardiovascular autonomic neuropathy was more frequent in type 2 diabetes, manifesting as autonomic neuropathy. In patients with autonomic neuropathy, regardless of the type of diabetes, the treadmill test was positive, i.e. strongly correlating with coronary disease. In regard to coronary disease risk factors, the most frequent correlation was found for obesity and hypertension. DISCUSSION: Cardiovascular autonomic neuropathy is considered to be the principal cause of arteriosclerosis and coronary disease. Our results showed that the occurrence of cardiovascular autonomic neuropathy increases the risk of coronary disease due to dysfunction of autonomic nervous system. CONCLUSIONS: Cardiovascular autonomic neuropathy is a common complication of diabetes that significantly correlates with coronary disease. Early diagnosis of cardiovascular autonomic neuropathy points to increased cardiovascular risk, providing a basis for preventive and therapeutic measures.

Autonomic Nervous System Diseases↗

PubMed1995

Phospholipid and glutamic acid decarboxylase autoantibodies in diabetic neuropathy.

OBJECTIVE: To determine the prevalence and significance of phospholipid autoantibodies (PLAs) and glutamic acid decarboxylase (GAD) autoantibodies in the circulation of normal patients and diabetic patients with and without neuropathy. RESEARCH DESIGN AND METHODS: We measured PLAs in a total of 78 patients (a diabetic group with somatic or autonomic neuropathy [n = 40] another group without neuropathy [n = 38]), and GAD autoantibodies in a subset of 22 patients. RESULTS: PLAs are found in 2% of the general population. We found PLAs in 32% of the diabetic population without neuropathy, in 88% of those with neuropathy, in 55% of those with retinopathy, and in 25% of those with established nephropathy. The frequencies of immunoglobulins in the neuropathic group were: IgG = 78%, IgM = 33%, and IgA = 23%. There was no correlation between PLAs and microalbuminuria, macrovascular disease, fibrinogen, duration of diabetes, or neuropathy, but there was a strong correlation with total neuropathy score. Sera with high PLA IgG titers bound to the surface of neuroblastoma cells and inhibited cell growth. Antibodies to GAD65 were present in 32% and to GAD67 in 0% of patients. No titers of GAD65, GAD67, or the GAD65 ratio were associated with the degree of neuropathy of the presence of PLAs. CONCLUSIONS: PLAs occur frequently in the sera of patients with diabetes and correlate with the extent of neuropathy, suggesting a role for PLAs in the etiology thereof. The measurement of PLAs may constitute a marker for ongoing damage to nerves.

Analysis of Variance↗

PubMed1999

Postural characteristics of diabetic neuropathy.

OBJECTIVE: To explore the posturographic correlates of diabetic neuropathy by comparing the performances of three groups of diabetic patients (severe, moderate, and absent neuropathy) with those of normal subjects and four clinical control groups. RESEARCH DESIGN AND METHODS: Using the Interactive Balance System (Tetrax, Ramat Gan, Israel), based on the assessment of the interaction of vertical pressure fluctuations on four independent platforms, one for each heel and toe part, respectively, posturographic examinations were given to 28 diabetic patients (8 with severe, 12 with moderate, and 8 with no peripheral neuropathy), 30 normal control subjects, and a clinical control group of 52 patients (14 with stage II Parkinson's disease, 13 with brain damage, 7 with whiplash, and 19 with peripheral vestibular pathology). The following posturographic parameters were evaluated; 1) general stability; 2) Fourier analysis showing patterns of sway intensity within eight frequency bands between 0.1 and 3 Hz; 3) weight distribution; 4) synchronization of sway; and 5) performance patterns for eight positions, requiring closure of eyes and standing on an elastic surface, as well as left, right, back, and downward head turns. RESULTS: For positions with closed eyes, diabetic patients with severe and moderate neuropathy were significantly less stable than normal subjects and diabetic patients without neuropathy, but diabetic patients with severe and moderate neuropathy turned out to be as equally unstable as clinical control subjects. However, for sway intensity within the band of 0.5 to 1.00 Hz on positions with lateral head turn with occluded vision, neuropathic diabetic patients performed significantly worse than did both normal and clinical control subjects. The same posturographic parameter also differed significantly between normal subjects and diabetic patients without neuropathy. CONCLUSIONS: As reported in previous studies, general instability in diabetic neuropathy is not a sufficiently characteristic correlate of the syndrome. On the other hand, spectral analysis of sway on stressful positions involving head turning appears to differentiate diabetic neuropathy from other disorders involving postural disturbances.

Brain Damage, Chronic↗

PubMedDate not supplied

Auditory brainstem evoked potentials in insulin-dependent diabetics with and without peripheral neuropathy.

Auditory Brainstem Evoked Potentials (ABEP) were recorded from 33 insulin-dependent diabetes mellitus (IDDM) patients (17 with diabetic peripheral neuropathy and 16 without) as well as from 20 normals. Pure-tone audiometry, speech reception threshold and discrimination were also evaluated. Sub-clinical pure-tone threshold elevation was observed for IDDM patients with neuropathy. Pure-tone thresholds of IDDM patients without neuropathy were not significantly different from those of normals. ABEP abnormality (at 10/sec click rate) was observed in 31% of IDDM patients with neuropathy, rising to 44% when 55/sec click rate measures were included. Abnormalities included bilateral and symmetrical peak-latency prolongations for all waves, greater for the later waves, and prolongation of V-I and V-III interpeak latency differences, all at 10/sec, and only prolonged peak latency for I at increased rate. Abnormalities coincided with microangiopathy and peripheral neuropathy. The incidence of ABEP abnormality for IDDM patients without neuropathy was only 12%, unilateral and sporadic in nature. As a group, IDDM patients with neuropathy had significantly prolonged IV and V peak-latencies, compared with the normals, or with the IDDM patients without peripheral neuropathy. In contrast, IDDM patients without neuropathy resembled the normals in all respects. ABEP have proven useful in understanding the variety of pathologies underlying the clinical manifestation of diabetes.

Adolescent↗

PubMed2001

Molecular basis of hereditary neuropathies.

Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B) and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (P0 or MPZ) gene. The molecular defect in CMT1C is unknown. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy, also of undetermined cause. Forms of CMT2 map to chromosome 1p36 (CMT2A), chromosome 3p (CMT2B), chromosome 7p (CMT2D), and to chromosome 8p21 (CMT2E). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset, demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene or the P0 gene and shares considerable clinical and pathologic features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes originating from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosomes 8q, 10q, and 11q. Hereditary neuralgic amyotrophy (familial brachial plexus neuropathy) is an autosomal dominant disorder causing painful, recurrent brachial plexopathies and maps to chromosome 17q25.

Brachial Plexus Neuritis↗

PubMed2000

Subclinical diabetic neuropathy: a common complication in Saudi diabetics.

OBJECTIVE: To determine the prevalence of sub clinical diabetic neuropathy in Saudi diabetics and the risk factors associated with symptomatic diabetic neuropathy. METHODS: A prospective study of Saudi diabetics attending King Abdulaziz University Hospital out patient clinic from January 1998 until April 1999. Detailed information of each patients' age, sex, body mass index, type and duration of diabetes mellitus, mode of treatment, degree of blood glucose control, presence of hypertension, hyperlipidemia, smoking, family history of diabetes mellitus and hypertension were recorded. Patients were assessed for diabetic neuropathy using the Michigan Neuropathy Program. Patients who were asymptomatic and scored less than 2 on simple clinical examination were referred to a neurologist for a complete neurological examination and nerve conduction studies. RESULTS: A total of 237 patients were studied with a mean age of 54.19 years and mean duration of diabetes 10.6 years. Symptomatic diabetic neuropathy was present in 132 (56%) patients while subclinical neuropathy was present in 58 (57%) of asymptomatic patients. Old age, type II diabetes with long duration, poor control and smoking were risk factors associated with symptomatic diabetic neuropathy (p<0.001, p=0.09, p<0.001, p=0.04, p=0.08). CONCLUSION: Subclinical diabetic neuropathy is common. Early diagnosis is important for possible prevention of late neuropathic complications (foot ulcers and infections). Prolonged poorly controlled diabetes mellitus, old age and smoking are risk factors for symptomatic diabetic neuropathy. Meticulous blood glucose control is important for nerve function protection. Researches are urgently needed for satisfactory therapy.

Age Distribution↗

PubMed2001

VEGF gene transfer for diabetic neuropathy.

Among diabetics, peripheral neuropathy is common and ultimately accounts for significant morbidity. The ultimate consequence of such sensory defects involving the lower extremities may be foot ulceration initiated by trauma that is inapparent to the patient. Such ulcerations often lead to lower extremity amputation, a complication that is 15 times higher in diabetic versus non-diabetic patients. Preliminary clinical studies have demonstrated improvement in signs and symptoms of sensory neuropathy in patients with lower extremity vascular occlusive disease following intramuscular injection of naked DNA encoding vascular endothelial growth factor (VEGF). To determine if such a strategy could be applied to diabetic patients, including those without evidence of large vessel occlusive disease, we investigated the hypothesis that experimental diabetic neuropathy results from destruction of the vasa nervorum and can be reversed by administration of an angiogenic growth factor. In two different animal models of diabetics, nerve blood flow and the number of vasa nervorum were found to be markedly attenuated resulting in severe peripheral neuropathy. In contrast, following VEGF gene transfer, vascularity and blood flow in nerves of treated animals were similar to those of non-diabetic controls; constitutive overexpression of VEGF resulted in restoration of large and small fiber peripheral nerve function. These findings implicate microvascular disruption as the basis for diabetic neuropathy and suggest that angiogenic growth factors may constitute a novel treatment strategy for this pernicious disorder. Accordingly, we now seek to address the following two objectives: 1. Objective #1: is to evaluate the safety and impact of phVEGF165 gene transfer on sensory neuropathy in patients with diabetes and associated macrovascular disease involving the lower extremities. 2. Objective #2: is to evaluate the safety and impact of phVEGF165 gene transfer on sensory neuropathy in patients with diabetes without macrovascular disease involving the lower extremities. The protocol outlined in this Investigational New Drug Application has been designed as a Phase I/II, single-site, dose escalating, double-blind, placebo controlled study to evaluate the safety and impact of phVEGF165 gene transfer on sensory neuropathy in patients with diabetes with or without macrovascular disease involving the lower extremities. Diabetic males or females > 21 years old with sensory neuropathy with or without macrovascular disease will be eligible. A total of 192 patients will be recruited into two arms of the study (each arm consisting of 96 patients) over a period of 4 years (the fifth year will be limited to follow-up examinations). The 96 patients in each of the two arms of the study will comprise 3 cohorts, each consisting of 32 patients. Within each of these cohorts, patients will be randomized to receive phVEGF165 or placebo based upon a 3:1 randomization ratio. Thus, at the completion of the study, 24 patients will have each received a given dose (1, 2, or 4 mg phVEGF165) and 24 patients will have received placebo. Doses will be employed in a serial dose-escalating fashion. The entire volume of the study drug will be divided and delivered in 8 intramuscular injections administered into the foot, calf muscle, or distal thigh muscle of the affected extremity. Following the initial set of injections, repeat treatment with an identical dose will be provided 2 and 4 weeks after initial treatment.

Adult↗

PubMed2001

[Co-occurrence of diabetic gastropathy and cardiovascular vegetative neuropathy in patients with diabetes type 1. ].

UNLABELLED: The occurrence of autonomic neuropathy in patients with diabetes is associated with increased incidence of cardio-vascular events and increased mortality. The character of such process is not clear yet and the question if the damage to autonomic nerves equally involves particular organs and systems is open. The aim of the study was to assess the concordance of cardio-vascular neuropathy with diabetic gastropathy in type 1 diabetic patients. The study involved 42 subjects with type 1 diabetes mellitus (age 36.7 +/- 8.3 years; duration of the disease 14.8 +/- 33 years). Gastric emptying of solid food was assessed scintigraphically. T1/2 max and residual isotope activity (expressed as the percentage of initial value) at 45th minute of the study were estimated. Autonomic cardio-vascular neuropathy was assessed based on the Ewing battery tests results. RESULTS: 11 of all subjects (group A) showed normal or increased gastric emptying of solid foods (T1/2 max 36.6 +/- 9.3 min, residual activity 39.6 +/- 12.1%) and 31 remaining subjects (group B) demonstrated delayed gastric emptying (T1/2 max 89.2 +/- 11.4 min, residual activity 74.6 +/- 5.2%), which was regarded as diabetic gastropathy symptom. 31 (74%) of all subjects were diagnosed with cardio-vascular neuropathy, 18 of them (43%) showed early autonomic neuropathy and remaining 13 (31%) presented decided cardio-vascular neuropathy. In group A2 (18%) subjects were diagnosed with early and 5 subjects (45%) with decided neuropathy. In group B early and decided autonomic neuropathy was present in 16 (51%) and 8 (26%) subjects. No statistically important difference between both groups was found. CONCLUSIONS: The results of the study support the thesis of a disseminated nature of the diabetic autonomic neuropathy and of not concomitant involvement of autonomic nervous system in particular organs and systems of the human body.

Adult↗

PubMed2006

Esophageal motility disorders in diabetics with and without neuropathy.

OBJECTIVE: To detect the presence of esophageal motor disorders in diabetic patients, and to establish whether there is any difference between patients with and without neuropathy. METHODS: Fifty-six diabetic patients admitted at Department of Medicine at Ziauddin Medical University Hospital, Karachi were selected to observe if manometeric findings were different in diabetic patients with and without diabetic neuropathy. RESULTS: Poor glycemic control was observed amongst patients with diabetic neuropathy as compared to those without neuropathy. Double peaked peristalsis and failure of peristalsis was more common in patients with diabetic neuropathy as compared to those without neuropathy. High amplitude and broader wave peristalsis and hypertensive lower esophageal sphincter was found in patients without neuropathy. Aperistalsis and multiple peaked waves were equally prevalent in patients with and without neuropathy. CONCLUSION: Poor glycemic control was found in patients with diabetic neuropathy, double peaked and failed peristalsis was the most common manometric abnormality among them.

Adult↗

PubMed2006

Clinically diagnosed diabetic neuropathy: frequency, types and severity.

OBJECTIVE: Studies of frequency of occurrence of diabetic neuropathy are few, and available studies were limited to the southern part of Nigeria. The objectives of the study were to determine the frequency of occurrence and grades of diabetes peripheral neuropathy using clinical measures. PATIENTS AND METHODS: Consecutive patients with diabetes mellitus attending the Jos University Teaching Hospital were recruited as the study population, including 120 diabetics and 60 age-matched, nondiabetic controls. A standard proforma based on the Michigan Neuropathy Screening Instrument (MNSI) was employed to screen for diabetic neuropathy. RESULTS: The frequency of occurrence of diabetic peripheral neuropathy was 75%. For the specific types of peripheral neuropathy, sensorimotor neuropathy was the commonest (40.4%, chi(2)=29.1; p<0.001). There was no significant difference, with severity of peripheral neuropathy among diabetics, when compared by gender. (Chi square=3.03, P value=0.081). CONCLUSION: The frequency of occurrence of peripheral neuropathy among diabetics in Jos University Teaching Hospital from this study is rather high.

Adult↗

PubMed1995

Diabetic neuropathies.

There is a family of diabetic neuropathies that mimic the entire spectrum of peripheral neuropathies. Distal sensory neuropathy is the most common. In small-fibre neuropathy, autonomic failure and loss of sense of pain and temperature are prominent. Painfulness is seen in a number of diabetic neuropathies. The asymmetric neuropathies are distinctive and are probably caused by a combination of microvascular and immune-mediated mechanisms. The pathogenesis of diabetic neuropathy is probably multifactorial. Hyperglycaemia is central to any pathogenic scheme whereby nerve blood flow is reduced by an effect on microvessels mediated by perturbations such as oxidative stress, reduction of nitric oxide, prostaglandins and an increase in endothelin. It may also affect nerve fibres directly. Recent clinical trials have clearly demonstrated the importance of strict glycaemic control. There is also support for essential fatty acids, antioxidants and aldose reductase inhibitors. Treatment of diabetic neuropathy is focused on improving glycaemic control and treatment of symptoms. The precise role of other modalities of treatment of diabetic neuropathy remain to be firmly established.

Behavior Therapy↗

PubMed2026

Omics in hereditary optic neuropathies: A systematic review of clinical studies with an integrated point of view.

Hereditary optic neuropathies are characterized by bilateral visual loss due to the degeneration of retinal ganglion cells, resulting in optic nerve degeneration and atrophy. Although the genetic origin of the main isolated and syndromic hereditary optic neuropathies has been characterized, the clinical phenotypes exhibit significant and poorly understood variability in both penetrance and expressivity. Additionally, the genetic and environmental factors that influence the onset of these optic neuropathies remain poorly understood, with limited biomarkers to predict disease progression or as readouts for therapeutic trials. Data-driven omics strategies allow deep phenotyping to improve our understanding of pathophysiological mechanisms and to search for new biomarkers and therapeutic targets. We explore whether the omics strategies applied to patients with hereditary optic neuropathies have provided such new insights. MEDLINE, Web of Science and EMBASE databases were screened for studies with terms relating to hereditary optic neuropathies, transcriptomics, epigenomics, proteomics, metabolomics and lipidomics in clinical studies exploring patients' samples. Out of 1244 references identified, 22 articles were included after double-masked data curation. These articles focused only on the 3 main forms of hereditary optic neuropathies, namely, OPA1-related dominant optic atrophy (n = 4), Leber hereditary optic neuropathy (n = 13), and Wolfram syndrome (n = 5). While the methodological designs and results of these studies were highly heterogeneous, they revealed molecular alterations that we have attempted to discuss at the integrated multi-omics level. This data integration highlighted several common pathophysiological mechanisms such as energetic impairment, endoplasmic reticulum stress, proteotoxic and oxidative stresses, lipid remodeling and altered amino acid and purine metabolisms, while suggesting potential new biomarkers and therapeutic targets. These findings underscore the potential of integrated multi-omics approaches to deepen our understanding of the phenotypic complexity of hereditary optic neuropathies and to support the development of innovative diagnostic and therapeutic strategies.

Humans↗

PubMed2004

The diagnostic yield of a standardized approach to idiopathic sensory-predominant neuropathy.

BACKGROUND: Peripheral neuropathy is a common problem that often prompts a lengthy and expensive diagnostic evaluation. A rational, evidence-based diagnostic approach to peripheral neuropathy is desirable. Prior studies have focused on all patients presenting to a tertiary referral center with a diagnosis of unclassified neuropathy. However, most patients with peripheral neuropathy have primarily sensory symptoms. This study focuses on patients with sensory-predominant neuropathy. The goal was to develop a focused diagnostic algorithm that can be easily applied in a general medical setting. METHODS: Patients referred with predominantly sensory symptoms and no previously defined cause were included and evaluated using a standard diagnostic approach. RESULTS: Among 138 patients, 25% had at least 1 first-degree relative with symptoms suggestive of neuropathy. Among laboratory studies, a 2-hour oral glucose tolerance test had the highest diagnostic yield (61%) and was more sensitive than other measures of glucose metabolism. Vitamin B(12) deficiency was identified in 2 patients. Results of serum protein electrophoresis, immunofixation, and antinuclear antibody testing were abnormal in less than 5% of patients, and these rates are similar to those found in the general population. Using this approach, only 31% of patients completing the recommended evaluation were found to have an idiopathic neuropathy. CONCLUSIONS: Patients with sensory-predominant neuropathy should be tested for glucose tolerance and vitamin B(12) concentration. The significance of abnormalities of serum protein electrophoresis and antinuclear antibodies is uncertain. Other tests should be performed only when the clinical scenario is suggestive. Patients with atypical features may benefit from referral to a peripheral neuropathy center.

Adult↗

PubMed2006

Peripheral neuropathy in primary sjogren syndrome: a population-based study.

BACKGROUND: Neurological manifestations appear to be frequently involved in patients with primary Sjögren syndrome (PSS). OBJECTIVE: To investigate the involvement of the peripheral nervous system, including small-diameter nerve fibers, in an unselected cohort of patients who fulfilled the new international criteria for PSS. DESIGN: Cross-sectional study. SETTING: Stavanger University Hospital. Patients Sixty-two patients with PSS (mean +/- SD age, 57.1 +/- 14.6 years). INTERVENTIONS: Clinical neurologic examinations, conventional nerve conduction studies, and skin punch biopsies. MAIN OUTCOME MEASURES: Signs of large-diameter and small-diameter peripheral nerve fiber neuropathy as determined by clinical examination, nerve conduction studies, and densities of intraepidermal nerve fibers in skin punch biopsy specimens. RESULTS: Seventeen patients (27%) were diagnosed as having neuropathy after clinical examination. The results of nerve conduction studies were abnormal in 34 patients (55%): 19 patients (31%) had motor neuropathy, 8 (13%) had sensory neuropathy, and 7 (11%) had sensorimotor neuropathy. Two patients had intraepidermal nerve fiber densities less than 3.4 fibers per millimeter, fitting the morphologic criteria for small-diameter nerve fiber neuropathy. CONCLUSIONS: Peripheral neuropathy occurs in a large proportion of patients with PSS, in most cases as a subclinical demyelinating neuropathy. Small-diameter nerve fiber neuropathy is not a frequent finding in these patients.

Adult↗

PubMed1999

Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis-Sumner syndrome.

We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty-two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti-GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.

Adult↗

PubMed2005

IgM deposits on skin nerves in anti-myelin-associated glycoprotein neuropathy.

Anti-myelin-associated glycoprotein (anti-MAG) neuropathy is a chronic demyelinating neuropathy with predominant involvement of large sensory fibers and deposits of IgM and complement on sural nerve myelinated fibers. We assessed the presence of IgM deposits on skin myelinated nerve fibers and the involvement of unmyelinated axons in anti-MAG neuropathy. Skin biopsies were performed in 14 patients with anti-MAG neuropathy, in 8 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and in 2 patients with IgM paraproteinemic neuropathy. Biopsies were taken at the proximal thigh in 20 patients, at the distal leg in 21 patients, at the proximal arm in 13 patients, and at the hand or fingertip in 10 patients. We found IgM deposits on dermal myelinated fibers in all anti-MAG neuropathy patients, with a greater prevalence at the distal site of the extremities. Deposits were located throughout the length of the fibers and at the paranodal loops. CIDP and IgM paraproteinemic neuropathies did not show any deposit of IgM. Anti-MAG neuropathy and CIPD patients showed a decrease in epidermal nerve fiber density reflecting an associated axonal loss. In anti-MAG neuropathy, both large- and small-diameter nerve fibers are affected, and specific deposits of IgM are found on skin myelinated nerve fibers.

Biopsy↗

PubMed1991

Neuropathy associated with monoclonal gammopathies of undetermined significance.

Monoclonal proteins (IgM, IgG, and IgA) in the serum or urine of patients with neuropathy may provide a marker for amyloidosis, myeloma, lymphoma, leukemia, Waldenström's macroglobulinemia, or monoclonal gammopathy of undetermined significance (MGUS). The clinical characteristics, course, and electromyographic features among neuropathies associated with monoclonal IgM (IgM-MGUS, 31 patients), monoclonal IgG (IgG-MGUS, 24 patients), and monoclonal IgA (IgA-MGUS, 10 patients) evaluated between 1980 and 1986 were compared. Four statistically significant differences set IgM-MGUS neuropathies apart from IgG-MGUS and IgA-MGUS neuropathies: (1) higher frequency of sensory loss and ataxia, (2) higher frequency of nerve conduction abnormality--10 attributes were significantly worse (none were significantly better), (3) higher frequency of dispersion of the compound muscle action potential, and (4) higher frequency of IgM-MGUS in the MGUS neuropathy cohort than is characteristic of MGUS without neuropathy seen at our institution or than is encountered in epidemiological surveys. These differences were not thought to be due to selection or severity biases. Neither the amount of IgM nor the estimated size of the monoclonal peak was associated with severity of neuropathy. The type and severity of IgM-MGUS neuropathies with anti-myelin-associated glycoprotein antibodies were not significantly different from those without anti-myelin-associated glycoprotein antibodies. A simple relationship between the presence and amount of IgM-MGUS or anti-myelin-associated glycoprotein antibodies and neuropathy cannot be assumed.

Action Potentials↗

PubMed1995

Pathogenesis and therapy of neuropathies associated with monoclonal gammopathies.

Approximately 10% of patients with peripheral neuropathy of otherwise unknown etiology have an associated monoclonal gammopathy. Both the neuropathies and the monoclonal gammopathies in these patients are heterogeneous, but several distinct clinical syndromes that may respond to specific therapies can be recognized. It is important to recognize these syndromes because monoclonal gammopathies also occur in 1% of the normal adult population, and in some cases, monoclonal gammopathies are coincidental and unrelated to the neuropathy. In patients with IgM monoclonal gammopathies, IgM M proteins frequently have autoantibody activity and are implicated in the pathogenesis of the neuropathy. IgM M proteins that bind to myelin-associated glycoprotein (MAG) have been shown to cause demyelinating peripheral neuropathy; anti-GM1 antibody activity is associated with predominantly motor neuropathy, and anti-sulfatide or chondroitin sulfate antibodies are associated with sensory neuropathy. The IgM monoclonal gammopathies may be malignant or nonmalignant, and polyclonal antibodies with the same specificities are associated with similar clinical presentations in the absence of monoclonal gammopathy. IgG or IgA monoclonal gammopathies are associated with neuropathy in patients with osteosclerotic myeloma or the POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy myeloma, and skin changes). Amyloidosis or cryoglobulinemic neuropathies can occur with either IgM or IgG and IgA monoclonal gammopathies. Therapeutic intervention depends on the specific clinical syndrome but is generally directed at removing the autoantibodies, reducing the number of monoclonal B cells, and interfering with the effector mechanisms.

Adult↗