Chronic Demyelinating Polyneuropathy Research Articles

Vagal cross-sectional area correlates with parasympathetic dysfunction in Parkinson's disease.

The aim of this prospective study was to investigate autonomic function in Parkinson's disease with a multidimensional approach including clinical evaluation tools, head-up tilt test and morphological studies of the vagus nerve. Head-up tilt test parameters including high frequency power of the heart frequency interval, the ratio of low frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval) to the high frequency and low frequency power of systolic blood pressure were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively, in 80 patients with Parkinson's disease. We examined the cross-sectional area of the vagus nerves bilaterally using nerve ultrasound and compared mean values with a control group of healthy subjects (n = 40) as well as patients with chronic inflammatory demyelinating polyneuropathy (n = 76). The cross-sectional area of right/left vagus nerve of Parkinson's patients was significantly lower compared to the right/left vagus nerve of the control group and of chronic demyelinating polyneuropathy patients. Furthermore, the cross-sectional area of the right vagus nerve was significantly larger from the one of the left vagus nerve for all groups. Based on tilt test, 43 patients (disease duration 7 ± 5, age at evaluation 71 ± 9, Hoehn and Yahr score 2.8 ± 8) were diagnosed with autonomic dysfunction (orthostatic hypertension n = 11, chronotropic incompetence n = 31, postural orthostatic tachycardia syndrome n = 1). Patients with orthostatic hypotension showed significantly higher Unified Parkinson's Disease Rating Scale-III values than those with chronotropic incompetence. The cross-sectional area of the vagus nerve correlated inversely with heart rate in rest and supine position and positively with tilt test parameters representing parasympathetic modulation through vagal activity [high frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval)] at rest. We demonstrate for the first time that morphological characteristics of the vagus nerve correlate with parameters of parasympathetic function from the spectral analysis of cardiovascular parameters in tilt test for Parkinson's patients. This correlation reveals the impact of the atrophy of vagal atrophy for autonomic function in Parkinson's disease. Nerve ultrasound of the vagus nerve could potentially be used as an adjunct to tilt table examination to diagnose autonomic dysfunction.

Chronic inflammatory demyelinating polyneuropathy and Type 1 lepra reaction: a rare association

Lepra reactions are important causes of the disability and deformity associated with leprosy. Normal body tissues suffer during these periods of hypersensitivity response mounted by the body against the antigens of Mycobacterium leprae. Chronic demyelinating polyneuropathy manifesting several years after reversal reaction is reported in the literature. It is attributed to the autoimmune reaction precipitated by the exposure of neural antigens (following the injury caused by the Type 1 lepra reaction) to the body’s immune system. Here we report a patient who presented with chronic inflammatory demyelinating polyneuropathy during a Type 1 lepra reaction.

T30. Sural nerve conduction studies in differentiation of hereditary and inflammatory demyelinating polyneuropathies

Introduction Nerve Conduction Studies (NCS) are invaluable tools for diagnosis and classification of polyneuropathies. However, differentiation of different types of demyelinating polyneuropathies may sometimes be difficult. Detection of demyelination and differentiation of inflammatory and hereditary polyneuropathies are mainly based on motor NCS. We aimed in this study to examine the role of sural nerve sensory NCS in differentiation of inflammatory and hereditary polyneuropathies. Methods Nineteen patients with chronic demyelinating polyneuropathy (CIDP), 16 patients with Guillain Barre syndrome (GBS) and 23 patients with hereditary motor sensory neuropathy with PMP22 duplication were included. In all patients, sural nerve was examined unilaterally or bilaterally with surface electrodes (13 patients) or near nerve technique (45 patients). In case of bilaterally examined sural nerves, right side was chosen for analysis. Results were compared to laboratory controls. The pathophysiological state of sural nerve was classified as normal, axonal loss or demyelinating according to ESTEEM criteria (Tankisi et al., 2005). Results The mean conduction velocity (CV) was higher in CIDP (42.6 ± 5.6) and GBS (46.5 ± 8.1) than patients with PMP22 duplication (22.5 ± 5.3) (p 35 m/s). Sural NCS showed demyelination in all patients with PMP22 duplication and in 2 GBS whereas none of the CIDP patients had demyelination of the sural nerve. Normal sural nerve was seen in 10 GBS and in 5 CIDP patients whereas sural NCS showed axonal loss in 4 GBS and in 14 CIDP. Conclusion Sural NCS may help in differentiation of inflammatory and hereditary demyelination polyneuropathies. Demyelinating changes in sural nerve are characteristic for PMP22 duplication whereas axonal loss is mostly seen in CIDP and normal sural nerve NCS in GBS.

Acute clinical onset chronic inflammatory demyelinating polyneuropathy in a dog

We report a case of acute-onset ambulatory paraparesis with electrophysiological abnormalities compatible with axonal and demyelinating lesions in a Rottweiler dog. Although the clinical findings were compatible with acute canine idiopathic polyneuropathy, postmortem investigations revealed a chronic demyelinating polyneuropathy affecting the nerve roots. Due to the combination of acute clinical presentation and chronic pathologic features, this case is consistent with the acute-onset form of chronic inflammatory demyelinating polyneuropathy (A-CIDP).

Axonal prion protein is required for peripheral myelin maintenance

The integrity of peripheral nerves relies on communication between axons and Schwann cells. The axonal signals that ensure myelin maintenance are distinct from those that direct myelination and are largely unknown. Here we show that ablation of the prion protein PrP(C) triggers a chronic demyelinating polyneuropathy (CDP) in four independently targeted mouse strains. Ablation of the neighboring Prnd locus, or inbreeding to four distinct mouse strains, did not modulate the CDP. CDP was triggered by depletion of PrP(C) specifically in neurons, but not in Schwann cells, and was suppressed by PrP(C) expression restricted to neurons but not to Schwann cells. CDP was prevented by PrP(C) variants that undergo proteolytic amino-proximal cleavage, but not by variants that are nonpermissive for cleavage, including secreted PrP(C) lacking its glycolipid membrane anchor. These results indicate that neuronal expression and regulated proteolysis of PrP(C) are essential for myelin maintenance.

PO32-FR-17 Chronic demyelinating polyneuropathy (CIDP) and relapsing remitting central demyelination: spreading autoimmunity from peripheral to central myelin?

PO32-FR-17 Chronic demyelinating polyneuropathy (CIDP) and relapsing remitting central demyelination: spreading autoimmunity from peripheral to central myelin?

NMP010 Chronic demyelinating polyneuropathy in children

Childhood chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized with large clinical, physiological, and immunological variability. Progressive course is rare in children. Long-term follow up of 4 children with early onset CIDP is presented. A two years old boy manifested progressive weakness and areflexia associated with CNS involvement developed after viral infection (patient 1), with relapses during intercurrent infections and development of severe axonal damage on EMG. Three-year-old boy (patient2) manifested initially progressive muscle weakness during 6 months with spontaneous regression, followed by 2 severe relapses at the age of 5 and 6 years. Decreased ASA activity was present in the patient 1 (17.6), and his family members (24.1−40nmol/mg/h). Arterial hypertension up to 20/12kPa was present in two patients in initial phase associated with muscle stiffness, occasional meningism, and left ventricular (LV) hypertrophy in one of them (patient 4). Subsequently, they both developed 2 mild relapses, at the age of 3.5−6 years. Clinical outcome was excellent in 2 cases and good in 2 cases although clinical course, therapy response and electrophysiological outcome was quite different in the only patient with low arylsulphatase A activity. Demyelination might develop in central and peripheral nervous system associated with arterial hypertension or inflammatory myopathy in patients with progressive course of CIDP.

Rituximab in chronic inflammtory demyelinating polyneuropathy associated with diabetes mellitus

Background: Some patients with diabetes mellitus (DM) develop a peripheral neuropathy indistinguishable from chronic demyelinating polyneuropathy (CIDP). Immune-mediated mechanisms are involved in the pathogenesis of demyelinating neuropathy in DM and in CIDP. Immunotherapy, including intravenous immunoglobulin (IVIg) is effective in idiopathic CIDP and CIDP-DM. Despite treatment with IVIg, CIDP may remain clinically active. It has been reported that CIDP may respond to Rituximab (RTX), a chimeric humanized monoclonal antibody against CD20+ antigen on B-lymphocytes. We reported a patient with CIDP associated with DM increasingly less responsive to IVIg who was treated with RTX.

Dejerine-Sottas disease and hereditary demyelinating polyneuropathy of infancy.

Dejerine-Sottas disease (DSD) was originally described as a hypertrophic polyneuropathy characterized by onset in infancy or early childhood in patients born to unaffected parents. The clinical features included distal sensory changes with ataxia; pes cavus, at times with kyphoscoliosis; motor deficit and atrophy predominating in the distal lower limbs and progressing toward the proximal limbs following a length-dependent pattern; palpable nerve hypertrophy; and Argyll-Robertson pupils. The morphological hallmark was the extensive nerve and root hypertrophy associated with demyelination-remyelination of surviving, originally myelinated axons and profuse Schwann-cell proliferation forming onion bulbs. Wide variations in clinical manifestations of chronic demyelinating polyneuropathies of early onset in children born to unaffected parents have now been reported, with only some of the characteristics required in the original study, and at least seven genes encoding the myelin proteins P0, PMP22, the transcriptional factor EGR2, and others have been implicated. Thus, DSD is now a component of the hereditary demyelinating polyneuropathies of infancy that also include subsets of the recently individualized CMT4 neuropathies. The presumed recessive transmission of patients with DSD should be confirmed by molecular genetic analysis, which is still negative in a significant proportion of patients. The nerve biopsy can be useful in patients in whom genealogical or DNA abnormalities in favor of a genetic disorder are missing, because in a few patients with a progressive or relapsing course the diagnosis of early-onset chronic inflammatory demyelinating polyneuropathy must be considered.

Antibody testing in peripheral neuropathies: a critical approach

A number of autoantibodies that induce inflammation on autoimmune peripheral neuropathies have been described. We review the techniques to measure autoantibodies and assess the usefulness of antibody assays in acquired acute demyelinating neuropathies such as Guillain-Barre syndrome (GBS) and chronic acquired demyelinating neuropathies including CIDP, multifocal motor neuropathy and MGUS neuropathy. In acute acquired demyelinating neuropathies associations of clinical characteristics and specific infections and the presence of anti-ganglioside antibodies have been found. Since diagnostic criteria have been available to subclassify Guillain-Barre syndrome in different clinical variants including clinical, electrophysiological, pathological and immunological findings, several varieties have been described: pure motor forms, sensory forms, primary axonal and primary demyelinating varieties. However, further studies are necessary to validate the usefulness of this subclassification with respect to treatment and prognosis. This is particularly important if subgrouping of GBS patients may lead to more individualised treatment. It has been suggested that for the IgG anti-GM1-positive subgroup of GBS patients, IVlg therapy may be the more efficacious treatment than plasmapheresis. The spectrum of chronic acquired demyelinating polyneuropathies cover different entities that have recently been categorised in three major groups: chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN) and MGUS neuropathy. Though the majority of CIDP patients respond well to immunotherapy, no constant autoantibody activity has been reported. In MMN serum antibodies, mostly IgM to the ganglioside GM1 or less frequently to asialo-GM1, GD1a or GM2 have been reported by ELISA in a variable proportion of MMN patients with a prevalence for anti-GM1 IgM in most large series, ranging from 30 to 60%. The reasons for these discrepant figures are still unclear but may be related to differences in the ELISA procedure or in the controls used to establish normal reference values. Antibodies to the myelin-associated glycoprotein (MAG) are detected in 50 to 60% of patients with neuropathy and immunoglobulin M (IgM) monoclonal gammopathy. Most patients have a slowly progressive, sensory or sensorimotor, demyelinating polyneuropathy. A causal relation between anti-MAG antibodies and neuropathy is supported because pathologic studies of sural nerve biopsies of patients with neuropathy and anti-MAG IgM monoclonal gammopathy show demyelination associated with IgM deposits on the affected myelin sheaths. We conclude that testing for serum autoantibodies should never be the first step in the work-up of peripheral neuropathy but an additional diagnostic measure after careful clinical and electrophysiological evaluation. High quality standards for a diagnostic antibody test should be applied. In our experience anti-MAG antibodies are a valuable marker that is relevant for diagnosis. Patients with chronic demyelinating polyneuropathies should be screened for anti-MAG antibodies. We test all our patients with lower motor neuron disease or motor neuropathies for anti-GM1 antibodies. We do not routinely test for anti-GM1 or related gangliosides in Guillain-Barre syndrome as the results have not yet a definite impact on the diagnosis or treatment regimen.

Clinical spectrum of chronic acquired demyelinating polyneuropathies

A number of presentations of chronic demyelinating polyneuropathy have been identified, each distinguished by its phenotypic pattern. In addition to classic chronic inflammatory demyelinating polyneuropathy (CIDP), which is characterized clinically by symmetric proximal and distal weakness and sensory loss, several regional variants can be recognized: multifocal motor neuropathy (MMN: asymmetric and pure motor), multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy (asymmetric, sensory, and motor), and distal acquired demyelinating symmetric (DADS) neuropathy (symmetric, distal, sensory, and motor). There are also temporal, pathological, and disease-associated variants. This review describes a clinical scheme for approaching the chronic acquired demyelinating polyneuropathies that leads to a rational use of supportive laboratory studies and treatment options. In addition, we propose new diagnostic criteria for CIDP that more accurately reflect current clinical practice. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 311–324, 2001

Terminal latency index and modified F ratio in distinction of chronic demyelinating neuropathies

Objective: To evaluate indexes calculated from standard electrophysiological data in differentiating chronic demyelinating polyneuropathy (CDP).Methods: Nerve conduction study of upper limbs was investigated in 19 chronic inflammatory demyelinating polyneuropathy (CIDP) patients, 25 anti-myelin-associated glycoprotein/sulfated glucuronyl paragloboside antibodies (MAG/SGPG) CDP patients, 13 Charcot-Marie-Tooth disease type 1A (CMT1A) patients and 22 controls. Terminal latency index (TLI) was used to compare the wrist-to-thenar muscle segment with the elbow-to-wrist conduction velocity. Modified F ratio (MFR) was used to compare the spinal cord-to-elbow segment latency with that of the wrist-to-thenar muscle segment.Results: Compared with controls, TLI was decreased in 21 anti-MAG/SGPG CDP patients while MFR was either decreased or was normal. In 16 CIDP patients, MFR was increased while TLI was either normal or increased. In CMT1A both TLI and MFR were in normal ranges. The sensitivity of MFR as a supportive finding in CIDP was found to be 84% and its specificity 89%. The sensitivity of TLI as a mean of diagnosis of anti-MAG/SGPG CDP was found to be 93% and its specificity 90%.Conclusion: The results of TLI and MFR facilitates distinction between different types of CDP. In CIDP, MFR was significantly higher and TLI showed no change; in the anti-MAG/SGPG CDP, TLI and MFR were significantly lower; in CMT1A, TLI and MFR showed no change in comparison with the controls.

Clinical spectrum of chronic acquired demyelinating polyneuropathies.

A number of presentations of chronic demyelinating polyneuropathy have been identified, each distinguished by its phenotypic pattern. In addition to classic chronic inflammatory demyelinating polyneuropathy (CIDP), which is characterized clinically by symmetric proximal and distal weakness and sensory loss, several regional variants can be recognized: multifocal motor neuropathy (MMN: asymmetric and pure motor), multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy (asymmetric, sensory, and motor), and distal acquired demyelinating symmetric (DADS) neuropathy (symmetric, distal, sensory, and motor). There are also temporal, pathological, and disease-associated variants. This review describes a clinical scheme for approaching the chronic acquired demyelinating polyneuropathies that leads to a rational use of supportive laboratory studies and treatment options. In addition, we propose new diagnostic criteria for CIDP that more accurately reflect current clinical practice.

P137 Comparative electrophysiologic findings in chronic demyelinating polyneuropathy (CDP)

P137 Comparative electrophysiologic findings in chronic demyelinating polyneuropathy (CDP)