Incidence of diabetic neuropathy which fulfills electrophysiologic criteria of CIDP]

In order to examine the specificity of the diagnostic criteria of CIDP, we studied 543 patients with diabetic neuropathy without clinical evidence of CIDP (307 men and 236 women, aged 60.4 +/- 11.1 years old). Moderate or severe neuropathy patients, whose polyneuropathy index (PNI) was below 80% of the normal, counted 169. Twenty out of 169 diabetic patients fulfilled the electrophysiologic criteria of CIDP. This number corresponded to more than 3.7% of the total diabetics. Motor conduction velocity category was fulfilled in 90%, conduction block in 65%, distal motor latency in 70% and F-wave latency category in 90% of 20 patients. Incomplete conduction block in the peroneal nerve and abnormally prolonged distal latency in the median nerve were frequent. These findings may reflect an overlaying focal compression. Decreased motor conduction velocity or prolonged F-wave latency were observed almost equally in every nerve. Electrophysiologic diagnostic criteria of CIDP was prepared to confirm the demyelinating nature of the neuropathy, and other demyelinating diseases should be ruled out. Diabetic patient who fulfilled this criteria was not rare. This fact is important, because clinical and CSF criteria of CIDP will be cleared in most of the diabetic patients; some diabetic neuropathy can be diagnosed as probable CIDP.     

Sensorimotor neuropathy resembling CIDP in patients receiving FK506

FK506 is an important immunosuppressant that has shown great promise in the treatment of autoimmune diseases. Approximately 5% of patients receiving FK506 develop major central nervous system toxicity, but the peripheral nerves are usually spared During 1990–1991, some 1000 patients received liver transplants under FK506 immunosuppression. Of these, 3 patients developed severe multifocal demyelinating sensorimotor polyneuropathy 2–10 weeks after initiation of FK506 therapy. Improvement followed plasmapheresis or intravenous immunoglobulin (IVIG), suggesting an immune-mediated cases. Although autoimmune neuropathy has been previously reported in immunedeficient states such as Hodgkin's disease and AIDS, it is not an expected complication of immunosuppresissive therapy. However, other have shown that this phenomeno can be produced in rats with cyclosporine A (CsA), whose effects on T-cell subsets are similar to those seen with FK506. These T-cell subset changes may have precipitated this dysimmune neuropathy in our patients. © 1994 John & Sons, Inc.     

Psychiatry--family practice liaison: a collaborative approach to clinical training

In view of the growing need for effective liaison between psychiatry and family practice programs, some of the models for educational and clinical liaison are discussed, and a clinical training program is described in which psychiatry and family practice educators work collaboratively in the training of both family practice and psychiatry residents and medical students. The program is offered as a model for providing comprehensive clinical training to residents and students and comprehensive clinical care to patients.     

Anti-SGPG antibody in CIDP: nosological position of IgM anti-MAG/SGPG antibody-associated neuropathy

Polyneuropathy with monoclonal gammopathy usually is considered a nosological entity different from chronic inflammatory demyelinating polyneuropathy (CIDP). Criteria proposed by the American Academy of Neurology AIDS Task Force (1991), however, show monoclonal gammopathy to be a condition concurrent with CIDP. The purpose of this study was to clarify the nosological relationship between CIDP and IgM anti-myelin-associated glycoprotein (MAG)/sulfated glucuronyl paragloboside (SGPG)-associated polyneuropathy. We investigated IgM anti-MAG/SGPG antibody in 85 CIDP patients by various methods, then examined the relation of M-protein to the presence of IgM anti-MAG/SGPG antibody. In our large study, 17 (20%) of 85 CIDP patients had high IgM anti-SGPG antibody titers in the enzyme-linked immunosorbent assay. This was confirmed by thin-layer chromatography-immunostaining for IgM anti-SGPG antibody and immunoblotting for IgM anti-MAG antibody. Immunoelectrophoresis and immunofixation, respectively, detected IgM M-protein in 6 (35%) and 13 (76%) of the 17 CIDP patients. We conclude that some patients with IgM anti-MAG/SGPG antibody with or without monoclonal gammopathy may be diagnosed as having CIDP, when patients are diagnosed according to the current CIDP criteria.     

New trends in the etiopathogenesis of diabetic peripheral neuropathy.

Neuropathy is well recognized as a major complication of insulin-dependent diabetes mellitus in adults, resulting in significant morbidity and possibly an increased mortality. Both the peripheral and autonomic nervous systems can be involved, and adolescents with diabetes can show early evidence of neuropathy. The pathogenesis of diabetic neuropathy remains unclear but is thought to involve various mechanisms. This complication can be traced to the metabolic effects of hyperglycemia and/or other effects of insulin deficiency on the various constituents of the peripheral nerve. The polyol pathway and/or nonenzymatic glycation affecting one or more cell types in the multicellular constituents of the peripheral nerve appear likely to have an inciting role. The role of other factors, such as possible direct neurotrophic effects of insulin and insulin-related growth factors, seems to be relevant.     

Electrophysiologic correlations with clinical outcomes in CIDP

Data are lacking on correlations between changes in nerve conduction (NC) studies and treatment response in chronic inflammatory demyelinating polyneuropathy (CIDP). This report examined data from a randomized, double‐blind trial of immune globulin intravenous, 10% caprylate/chromatography purified (IGIV‐C [Gamunex]; n = 59) versus placebo (n = 58) every 3 weeks for up to 24 weeks in CIDP. Motor NC results and clinical measures were assessed at baseline and endpoint/week 24. Improvement from baseline in adjusted inflammatory neuropathy cause and treatment score correlated with improvement in proximally evoked compound muscle action potential (CMAP) amplitudes (r = ?0.53; P < 0.001) of all nerves tested and with improvement in CMAP amplitude of the most severely affected motor nerve (r = ?0.36; P < 0.001). Correlations were observed between improvement in averaged CMAP amplitudes and dominant‐hand grip strength (r = 0.44; P < 0.001) and Medical Research Council sum score (r = 0.38; P < 0.001). Overall, the change in electrophysiologic measures of NC in CIDP correlated with clinical response to treatment. Muscle Nerve, 2010     

New trend in pathogenesis of diabetic neuropathy]

The pathogenesis of diabetic neuropathy remains unclear, although several factors have been implicated in its pathogenesis. We have examined possible roles of decreased production of nitric oxide, ion channel dysfunction and decreased capacity of nerve regeneration. STZ-induced diabetic rats showed decreases in nociceptive threshold and NADPH-diaphorase positive neurons, nNOS level and cGMP content of DRG at 12 weeks after induction of diabetes. The rats injected by L-NAME, potent nNOS inhibitor, showed decreased nociceptive threshold, although D-NAME, inactive in nNOS inhibition, did not. These results suggest that decreased NO production might be involved in hyperalgesia in diabetic rats. Both hyperglycemia and decreased Na/K-ATPase activity are thought to be characteristic features of diabetic neuropathy. To investigate the presence of ion channel abnormality in diabetic nerves, a Vaseline-gap voltage clamp technique was applied for a single myelinated fibers under 30 mM high glucose plus 0.1 mM ouabain. Since K current was increased, a Ca activated K channel blocker was applied and this increase was shown to be suppressed. Furthermore, Ca channel blockers all suppressed increased K currents, suggesting that the condition induced an increase of Ca influx, thereby increasing Ca activated K currents through K channels. The data are important in that diabetic condition may induce both Ca influx, leading to nerve degeneration, and increased K current, resulting in decreased nerve conduction. Nerve regeneration has been known to be disturbed in diabetic condition. We have shown a decrease in nerve elongation rate in diabetic rats after crush of sciatic nerve, although this decrease was not ameliorated by ARI. Furthermore, Wallerian degeneration was shown to be delayed in diabetic nerves, leading to delayed nerve regeneration. Hyperphosphorylation of both medium and high molecular weight neurofilaments that might be induced by protein kinases including CDK 5 may be involved in the mechanism.     

MRI of the cauda equina in CIDP: clinical correlations.

Isolated reports have documented enhancement and/or enlargement of spinal nerve roots on magnetic resonance imaging (MRI) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). This work examines those findings in a consecutive series of 16 patients with CIDP, with blinded comparison to MRI in 13 disease controls, including five patients with Charcot-Marie-Tooth disease type 1A. MRI sequences consisted of T1 weighted sagittal and axial views, before and after administration of gadolinium. Blinded MRI interpretation was performed independently by two neuroradiologists. MRI results were correlated with data collected from chart review. Enhancement of the cauda equina was seen in 11 of 16 CIDP patients (69%), and in none of 13 control subjects. Nerve roots were enlarged, most significantly in the extraforaminal region, in three CIDP patients, and in one patient with Charcot-Marie-Tooth type 1A. MRI findings did not correlate with disease activity and severity, nor with any clinical or laboratory features in patients with CIDP.     

Diagnostic approach to peripheral neuropathy

Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx) tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG). EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block) and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG). Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF) examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.     

Th1 shift in CIDP versus Th2 shift in vasculitic neuropathy in CSF

To investigate the intra- and extracellular levels of various cytokines and chemokines in CSF in chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy (VN), 16 cytokines, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, IFN-gamma, TNF-alpha, G-CSF, MCP-1 and MIP-1beta, were measured in CSF supernatant by a multiplexed fluorescent bead-based immunoassay and intracellular production of IFN-gamma and IL-4 in CSF CD4+ T cells were simultaneously measured by flow cytometry in 14 patients with CIDP, 8 patients with VN and 25 patients with other noninflammatory neurologic diseases (OND). In the CSF supernatant, a significant increase of IL-17, IL-8 and IL-6, and a significant decrease of IL-4, IL-5 and IL-7 levels were detected in pretreated CIDP as compared with OND. A significant increase of IL-6, IL-8 and IL-10 levels was found in pretreated VN. Both IL-17 and IL-8 levels correlated strongly with CSF protein levels in CIDP, although the correlation of IL-6 levels was weak. In CSF CD4+ T cells, IFN-gamma+ IL-4- cell percentages were markedly elevated in CIDP compared with OND, but not in VN, resulting in a significant increase of intracellular IFN-gamma/IL-4 ratio in CIDP, even in the absence of CSF pleocytosis. The nonresponders to intravenous immunoglobulins (IVIGs) showed a significantly lower IFN-gamma- IL-4+ CD4+ T cell percentage, and tended to have a higher intracellular IFN-gamma/IL-4 ratio than the responders in CSF. Marked upregulation of Th1 cytokine, IL-17, and downregulation of Th2 cytokines, together with infiltration of IFN-gamma-producing CD4+ T cells are useful markers for CIDP, while several Th2 cytokines are upregulated in VN in CSF.