Chronic Inflammatory Demyelinating Polyneuropathy Patients Research Articles

Treatment of refractory chronic inflammatory demyelinating polyneuropathy with interferon β1B

Sirs: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy [13] characterized by symmetrical sensory and/or motor symptoms persisting for more than 8 weeks. The disease course may be progressive or relapsing [13]. On the basis of randomized trials, high dose intravenous immunoglobulin (IVIg), corticosteroids and plasma exchange have been established as effective treatments for CIDP. The main limitations of these approaches are lack of long term efficacy, difficulties in their use and high costs; thus, alternative immunosuppressive treatments have been proposed (azathioprine, cyclosporine and cyclophosphamide) [2, 9, 11]. The immune-mechanisms responsible for CIDP resemble those implicated in multiple sclerosis (MS) [13], thus making CIDP the peripheral counterpart of MS. In addition, similar to MS, neuropathological studies support heterogeneity of CIDP pathogenesis, with concomitant demyelination and axonal damage [13]. Some studies have recently been performed to evaluate the usefulness of Interferon (IFN) β1a in CIDP patients unresponsive to conventional therapies [1, 7, 14]. We present the case of a 43year-old woman, who in July 1997 complained of progressive weakness in both lower limbs, as well as sensory symptoms. Clinical symptoms persisted until December 1997 and a diagnosis of CIDP was made according to INCAT criteria [3]. Neurological examination revealed generalized areflexia, while an electrophysiological study showed partial conduction block for stimulation at the fibular head of peroneal nerves (–50 % amplitude on the right and –49 % on the left) and absent F wave on the left median nerve and right peroneal nerve. Cerebrospinal fluid analysis produced evidence of albuminocytological dissociation (total protein 82 mg/dL without cells) and isoelectrofocusing was within normal limit. After a first treatment schedule of IVIg with a good response, she became refractory to this treatment. She presented nine relapses throughout 27 months (treated with plasma exchange with transient and partial response) despite the specific drugs used (Figure). In July 2001 she started IFNβ-1b (Betaferon) 8MUI with subcutaneous injections every other day. No other relapses occurred. At present, she has been relapsefree for 40 months and shows marked improvement in clinical conditions (Table 1). Nerve conduction studies also showed marked improvement in motor and sensory velocities (Figure). In April 2002, serological examination showed the presence of anti-thyreoglobulin and anti-thyroid peroxidase antibodies, with an increase in free triiodothyronine and free thyroxin. Autoimmune thyreopathy was diagnosed, and the patient started treatment with an antithyroid drug. IFN beta has been proven efficient in treating MS [4, 5, 12] reducing the number of relapses. Due to clinical similarities between MS and CIDP, there is emerging interest in the use of IFN in CIDP. As far as we know, this is the first report in which IFNβ-1b has been used to treat a CIDP patient. Our patient showed good clinical and neurophysiological response to long-term IFNβ1b treatment (40 months). The stabilization observed was judged by the absence of relapses. IFN beta acts as an immunomodulatory agent, exerting its action at different levels in the inflammatory process. Two recombinant forms of IFN beta are used in clinical practice: IFNβ-1a and INFβ-1b. The use of IFNβ-1a in the treatment of CIDP is controversial, and contradictory results have been reported in different studies [1, 6, 12]. It should be noted that LETTER TO THE EDITORS

Subclinical electrophysiological alterations of phrenic nerve in chronic inflammatory demyelinating polyneuropathy

Alterations of the phrenic nerve (PN) and pulmonary function tests (PFTs) have been described in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This study was aimed at assessing the relationship between PN and respiratory function in CIDP patients without clinical signs of respiratory failure. Bilateral PN and right median nerve conduction studies were carried out along with blood gas analysis and PFTs: maximal inspiratory pressure; maximal expiratory pressure; forced vital capacity. The amplitude of the compound muscle action potential of the PN was seen to be altered in 19/24 (79%) patients and latency in 22 (92%). Eighteen patients (75%) showed at least one abnormal PFTs or CO2 partial pressure value. Electrophysiological alterations of the PN were observed in a high percentage of the CIDP patients studied. No statistically significant correlation was observed between PN and PFTs alterations.

Clinical manifestations of chronic inflammatory demyelinating polyneuropathy with anti-cardiolipin antibodies

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune syndrome where certain autoantibodies define clinicopathologic subgroups. In the present study, serum anti-cardiolipin antibodies (aCL) were evaluated. We investigated aCL in sera from 21 patients diagnosed with CIDP in our hospital between 1991 and 2001. The four CIDP patients with aCL (aCL+) were compared with 17 patients without aCL (aCL-). All aCL+ patients displayed sensory-motor polyneuropathy, with severity and distribution of weakness resembling those in aCL- patients. Anti-nuclear antibody titer of aCL+ patients were significantly higher than those in aCL- patients. None of aCL+ patients presented clinical manifestations of primary anti-phospholipid syndrome (APS), such as thromboses or recurrent abortion. Although the aCL+ patients were older and had more complications and more severe pathologic features than aCL- patients, they responded well to steroid pulse or intravenous immunoglobulin. The aCL in CIDP apparently differ from 'autoimmune' aCL in APS, instead being among the autoantibodies pathologically involved in CIDP subgroups.

Phrenic nerve conduction study in CIDP

Background: Alterations of the phrenic nerve (FN), as well as of the pulmonary function tests (PFTs), have been described in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Objective: Our study was aimed at assessing the relationship between FN conduction study and respiratory function in 24 CIDP patients without clinical signs of respiratory failure. Material and Methods: Bilateral FN and right median nerve conduction studies were accomplished, along with emogasanalysis (EGA) and PFTs: maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), forced vital capacity (FVC) and partial CO2 pressure. Results: The amplitude of the compound muscle action potential (CMAP) of the FN was altered in 19 (79%) of our 24 patients, the latency in 22 (92%). Eighteen patients (75%) showed at least one PFT or the pCO2 abnormal. FN alterations showed a low sensitivity and specificity with respect to PFTs or pCO2. Discussion: Our results demonstrated electrophysiological alterations of the FN in a high percentage of CIDP patients. No significant correlation was observed between FN and PFTs alterations.

Occurrence of nerve entrapment lesion in chronic inflammatory demyelinating polyneuropathy.

To evaluate the occurrence of nerve entrapment syndrome in chronic inflammatory demyelinating polyneuropathy (CIDP). We retrospectively evaluated neurophysiologic results of 41 (25 male and 16 female, mean age 49.8, range 11-87) patients with CIDP. We evaluated the frequency of focal neurophysiologic lesion at entrapment site distinguishing two kinds of lesion: (a) true entrapment; and (b) false entrapment on the basis of nerve conduction results. Occurrence of focal aggression within the entrapment site is similar to that out of the entrapment site in all examined nerves. The entrapment sites are not an elective zone of focal autoimmune aggression in CIDP. Therefore, in CIDP patients a true entrapment, neurophysiologically demonstrated, could be a concomitant pathology and if a severe and persistent entrapment worsens functional deficit and symptoms, a surgical decompression could be useful.

Accumulation of Valpha7.2-Jalpha33 invariant T cells in human autoimmune inflammatory lesions in the nervous system.

T cells expressing an invariant TCR alpha chain and NK cell markers are expected to exhibit unique functions. Whereas much attention has been paid to CD1d-restricted NKT cells, a second NKT cell population bearing an invariant AV19-AJ33 TCR has recently been identified in mice and humans. Selection and/or expansion of this population require B cells, and would involve a non-classical class I-related molecule MR1. Although their preferential distribution in the gut mucosa indicates their role in the host response at the site of pathogen entry, it remains unknown whether they play an alternative role at different sites or in immunological disorders. Using single-strand conformation polymorphism clonotype analysis, we investigated the presence of the human AV19-AJ33 T cells (V(alpha)7.2-J(alpha)33 T cells) in autopsy samples from multiple sclerosis (MS) patients as well as in nerve biopsy samples from chronic inflammatory demyelinating polyneuropathy (CIDP) patients. Here we report that the V(alpha)7.2-J(alpha)33 T cells are accumulated in some of the central nervous system lesions of MS and in the majority of the peripheral nerve samples from CIDP. We have previously revealed that CD1d-restricted, V(alpha)24-J(alpha)Q NKT cells are remarkably reduced in the peripheral blood from MS. However, V(alpha)7.2-J(alpha)33 T cells are not reduced in the peripheral blood from MS and could be detected in a large majority of the cerebrospinal fluid samples obtained during relapse of MS. The present results indicate that the V(alpha)7.2-J(alpha)33 T cells are involved in the autoimmune inflammatory lesions.

Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 87

Inflammatory vasculopathy is observed in 20 to 66% of nerve biopsies in diabetic neuropathy, especially in patients with proximal diabetic neuropathy (diabetic amyotrophy) or with other patterns of multifocal neuropathy. Moreover there is growing evidence that diabetic patients have an increased predisposition to Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Many authors suggest that there is a more pervasive contribution of inflammatory and immuno‐mediated damage to the pathogenesis of diabetic neuropathy than had previously been imagined. In these patients, immunosuppressive therapy is indicated. However differentiating CIDP in diabetic patients from diabetic neuropathy (DNP) may be difficult. We tried to differentiate immuno‐mediated and inflammatory neuropathies in diabetic patients with polyneuropathy revealing the presence of matrix metalloproteinases (MMPs) in the endoneurium. MMPs are calcium‐dependent zinc endopeptidases which are able to degrade the basement membrane and thus contribute to tissue destruction and cell invasion. Sural nerve biopsies were taken from 10 diabetic patients with CIDP and 5 patients with DNP. Immunohistochemistry was performed for T‐cells, macrophages, von Willebrand factor and MMP‐9. Endoneurial and epineurial immunoreactivity was evaluated and quantified separately. Small epineurial T‐cells infiltrates were present in 5 out of 10 CIDP patients and in none of DNP patients. In CIDP patients 53% of endoneurial vessels were immunoreactive for MMP‐9 against only 12% in DNP patients and this difference reached a statistical significance. In conclusion we demonstrated that immunoreactivity of MMP‐9 is strongly enhanced in diabetic patients with CIDP but not in patients with DNP. The pattern of immunoreactivity may help to select patients for a trial with immunosuppressant drugs.

Autoimmunoreactivity to Schwann cells in patients with inflammatory neuropathies.

Inflammatory demyelinating neuropathies are characterized by a loss of peripheral nerve myelin. Myelin breakdown is thought to result from an autoimmune reaction towards nerve components. Schwann cells play a crucial role in the synthesis and maintenance of peripheral nerve myelin. An immune attack targeting Schwann cells could therefore affect myelin integrity, leading to disease. We studied the reactivity of sera from patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) towards Schwann cells using immunofluorescence microscopy. We found 24% of the GBS (56 out of 233) and 26% of the CIDP (12 out of 46) patients to have circulating immunoglobulin G autoantibodies against proliferating, non-myelinating human Schwann cells. In contrast, healthy donors showed positive staining in only two out of 34 sera. No reaction was found with sera from patients with non-inflammatory neurological disorders. Immunofluorescence was localized at the distal tips (leading lamella) of the Schwann cell processes. Distal tips of neurites (nerve-growth-cones) of in vitro differentiated non-myelinated hNT2 neurons also stained strongly. GBS and CIDP serum immunoreactivity was also observed in teased nerve fibre preparations. These data suggest that, at least part of the immunoreactivity is not directed against myelin, but towards non-myelin proteins and epitopes possibly involved in Schwann cell-axon interaction.

Changes in serum macrophage-related factors in patients with chronic inflammatory demyelinating polyneuropathy caused by intravenous immunoglobulin therapy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a slowly progressive or recurrent neuropathy accompanied by infiltration of macrophages in the peripheral nerves. Macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein-1 (MCP-1) are a macrophage-related cytokine and chemokine, respectively. Although, intravenous immunoglobulin (IVIg) infusion therapy has been used for treating CIDP patients, not all CIDP patients have responded to IVIg infusion therapy. To determine the mechanisms of the action of IVIg, we examined serum M-CSF and MCP-1 levels during and after IVIg infusion therapy in 19 CIDP patients treated with IVIg (0.4 g/kg/day for 5 days). Ten of the 19 patients (52.6%) responded to IVIg therapy. Both M-CSF and MCP-1 concentrations in IVIg responders were significantly higher on day 1 postinfusion than those in nonresponders, but decreased to their pretreatment values on day 5 postinfusion. The results suggest that immunomodulation through M-CSF and MCP-1 is involved in the mechanisms underlying the effect of IVIg infusion therapy in CIDP patients.

Individual attributes versus composite scores of nerve conduction abnormality: sensitivity, reproducibility, and concordance with impairment.

Composite scores may be more sensitive and reproducible than single attributes of nerve conduction for detection of peripheral neuropathy, but this requires validation in large patient cohorts. Also, the concordance of individual attributes versus composite scores with clinical measures of severity has not been tested. Here, we study these issues in prospectively studied cohorts: diabetic patients from Rochester, Minnesota (RDNS; n = 396); chronic inflammatory demyelinating polyneuropathy (CIDP) patients (n = 55); and multifocal motor neuropathy (MMN) patients (n = 18). With specificity fixed at the 97.5 percentile, we found that, in generalized polyneuropathies (diabetic and CIDP), composite scores (especially ones including conduction velocity, distal latencies, and F-waves) of individual or multiple nerves tended to be more sensitive than individual attributes. By contrast, for multiple mononeuropathies, some individual attributes or composite scores of individual nerves were more sensitive than composite scores. In diabetic polyneuropathy, composite scores tended to be more reproducible than individual attributes of nerve conduction. Highly significant correlations were found between individual attributes or composite scores and neurologic impairment in diabetic polyneuropathy and in CIDP; in general, correlation coefficients were higher for composite scores. These correlations were higher for amplitudes than for conduction velocities or distal latencies. We conclude that, with the availability of microprocessors and normative databases, electromyographers may increasingly seek to express nerve conduction abnormality also as composite scores of individual or several nerves.

The First Chronic Inflammatory Demyelinating Polyneuropathy Patient to be Treated with Intravenous Immunoglobulin

After completing my neurological training my main field of interest was in cerebrovascular disorders. However, my practice changed in several ways in 1982 after I gave intravenous immunoglobulin (IVIg) to...

CAN ELECTROPHYSIOLOGY DIFFERENTIATE POLYNEUROPATHY WITH ANTI‐MAG/SGPG ANTIBODIES FROM CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY?

Objectives: Patients with polyneuropathy and antibodies to myelin‐associated glycoprotein (MAG) and sulphated glucuronyl paragloboside (SGPG) differ from chronic inflammatory demyelinating polyneuropathy (CIDP) because of a slower, progressive course, symmetrical and predominantly sensory involvement of legs, predominantly distal slowing of motor conductions, and poorer response to therapy. We studied whether a wide set of electrophysiologic parameters may differentiate these two neuropathies. Methods: We reviewed the electrophysiological studies of 10 patients with anti‐MAG/SGPG antibodies and 22 with CIDP examining: (1) motor conduction velocity and distal compound muscle action potential amplitude; (2) conduction block (CB) and temporal dispersion; (3) distal motor latency and terminal latency index (TLI); (4) F wave and proximal conduction time; and (5) sensory conduction and occurrence of abnormal median with normal sural sensory potential. Results: Anti‐MAG/SGPG neuropathies showed: (1) more severe involvement of peroneal nerves; (2) more frequent disproportionate distal slowing of motor conductions (TLI less than or equal to 0.25) and absent sural potential; and (3) no CB. However 3/22 CIDP patients also had at least two nerves with TLI 0.25 and no CB. Conclusions: Electrophysiologic findings suggest in anti‐MAG/SGPG neuropathy a length‐dependent process with a likely centripetal evolution. A disproportionate slowing of conduction in distal segments of motor nerves suggests the diagnosis of anti‐MAG/SGPG neuropathy, although it is not pathognomonic.

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.

INTRAMYELINIC EDEMA: AN ELEMENTARY PATHOLOGICAL LESION IN CIDP

Pathological abnormalities of sural nerve biopsies from patients affected by chronic inflammatory demyelinating polyneuropathy (CIDP) include segmental demyelination, inflammatory infiltrates, axonal degeneration, subperineurial edema and Schwann cell proliferation.There are few reports in the literature (Waddy '89, Sabatelli '96) describing edema of the myelin sheath as an additional pathological feature of CIDP. This peculiar abnormality is a prominent finding in several experimental toxic and compression neuropathies. In 1993 Tatum described Intramyelinic Edema in experimental allergic neuritis induced by systemic passive transfer of human IgM anti‐myelin‐associated glycoprotein, and suggested that this change may play a role in the pathogenesis of demyelination.In order to establish whether intramyelinic edema may represent an elementary pathological lesion in human peripheral neuropathies, we reviewed morphological data of sural nerve biopsies from 46 CIDP patients admitted to our Institute from 1988 to 2001 and we compared them with findings from patients affected by other neuropathies.IE was observed in 6 patients with CIDP, but in none of the 500 patients affected by neuropathies of different etiology. In two out of the six patients the neuropathy was associated with IgM‐paraprotein, without anti‐MAG activity. IE was a prominent feature in only one patient while in the remaining patients it was confined to sporadic fibers. In one patient with a mild form of CIDP, IE was the only pathological finding. In the remaining patients it was associated with segmental demyelination and axonal loss.Our findings show that although IE is observed in only a minority of CIDP patients (13% of our series), this pathological finding may be considered a specific abnormality of inflammatory demyelinating neuropathies. We suggest that axonal shrinkage, which is invariably associated with IE, may represent a mechanism of loss of function in CIDP, in addition to segmental demyelination and axonal loss.

Can electrophysiology differentiate polyneuropathy with anti-MAG/SGPG antibodies from chronic inflammatory demyelinating polyneuropathy?

Objectives: Patients with polyneuropathy and antibodies to myelin-associated glycoprotein (MAG) and sulphated glucuronyl paragloboside (SGPG) differ from chronic inflammatory demyelinating polyneuropathy (CIDP) because of a slower, progressive course, symmetrical and predominantly sensory involvement of legs, predominantly distal slowing of motor conductions, and poorer response to therapy. We studied whether a wide set of electrophysiologic parameters may differentiate these two neuropathies. Methods: We reviewed the electrophysiological studies of 10 patients with anti-MAG/SGPG antibodies and 22 with CIDP examining: (1) motor conduction velocity and distal compound muscle action potential amplitude; (2) conduction block (CB) and temporal dispersion; (3) distal motor latency and terminal latency index (TLI); (4) F wave and proximal conduction time; and (5) sensory conduction and occurrence of abnormal median with normal sural sensory potential. Results: Anti-MAG/SGPG neuropathies showed: (1) more severe involvement of peroneal nerves; (2) more frequent disproportionate distal slowing of motor conductions (TLI≤0.25) and absent sural potential, and (3) no CB. However 3/22 CIDP patients also had at least two nerves with TLI≤0.25 and no CB. Conclusions: Electrophysiologic findings suggest in anti-MAG/SGPG neuropathy a length-dependent process with a likely centripetal evolution. A disproportionate slowing of conduction in distal segments of motor nerves suggests the diagnosis of anti-MAG/SGPG neuropathy, although it is not pathognomonic.

Diagnostic value of sural nerve demyelination in chronic inflammatory demyelinating polyneuropathy.

The objective of the study was to determine the diagnostic value of features of demyelination and inflammation in sural nerve biopsy specimens of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The features of (i) demyelination, (ii) axonal de- and regeneration and (iii) inflammation were investigated by measuring the number of onion bulbs, g ratio (axon diameter/total nerve fibre diameter), myelinated nerve fibre density, number of clusters and endoneurial area in 21 patients with CIDP, as well as in 13 patients with chronic idiopathic axonal polyneuropathy (CIAP) and six autopsy controls. In addition, teased fibres were classified and lengths of internodes measured. We found no difference in demyelinating features between patients with CIDP and CIAP, as the percentage of fibres with segmental de- and remyelination and the number of onion bulbs were similar in both polyneuropathy groups. The g ratio, expected to be higher in a demyelinating disease due to thinner myelin sheaths, was significantly lower in CIDP than CIAP. Evidence for axonal degeneration was found in both CIDP and CIAP, as both showed a decrease in myelinated nerve fibre density. There was no evidence of endoneurial oedema in CIDP, as the endoneurial area did not differ between CIDP, CIAP and the autopsy controls. Although significant differences of features of demyelination, axonal degeneration and inflammation were found in sural nerve biopsy specimens, there was a considerable overlap between abnormalities in CIDP and CIAP patients. In the majority of patients, quantitative analysis of light microscopical abnormalities in sural nerves was similar in CIDP and CIAP. Therefore, a sural nerve biopsy is of limited diagnostic value in CIDP.

Investigation of serum response to PMP22, connexin 32 and P 0 in inflammatory neuropathies

We investigated serological immune responses against three major peripheral nerve myelin constituents in patients with immune-mediated neuropathies. Connexin 32 (Cx32), myelin protein zero (MPZ, P 0) and peripheral myelin protein 22 (PMP22) were produced in Chinese hamster ovary (CHO)-K1 cells. From a panel of 25 Guillain-Barré syndrome (GBS) and 24 chronic inflammatory demyelinating polyneuropathy (CIDP) patients, only two patients showed reactivity towards Cx32 and P 0.

Serum levels of tumor necrosis factor-alpha in chronic inflammatory demyelinating polyneuropathy.

Activated macrophages and T lymphocytes may play a role in the pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP). Both cell types secrete tumor necrosis factor-alpha (TNFalpha), which has toxic effects on myelin and endothelial cells. The serum concentration of TNFalpha was measured by ELISA and compared with clinical and electrophysiological profiles in 20 patients with CIDP. An increased serum level of TNFalpha was detected in 5 (25%) patients and was associated with subacute progression, severe neurologic disabilities, and symmetric weakness involving proximal as well as distal muscles. TNFalpha levels increased during the active phase in this subgroup of patients. The levels of TNFalpha correlated with the severity of demyelinating conduction abnormalities in the intermediate as well as distal nerve segments, suggesting demyelination diffusely distributed along the nerves. Circulating TNFalpha increases during the active phase in a subgroup of CIDP patients and may play a role in the pathogenesis of demyelination and the breakdown of the blood-nerve barrier in CIDP.

Oncostatin M (oncM) Spontaneous Production By Peripheral Blood Mononuclear Cells (PBMC) Is Increased In Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Pro‐inflammatory cytokines provide key signals necessary for antigen stimulation of T‐cells, inflammatory cell recruitment in the nerve, activation of cell‐mediated effector mechanisms and directly alter neuroglial and neuronal cell survival and function. The involvement of oncM, a novel pleiotropic pro‐inflammatory cytokine acting on cells of neural, vascular, hematopoietic and lymphoid origin, has not been investigated, to our knowledge, in CIDP. We have assessed oncM production by PBMC in 9 CIDP pts (5 M, 4 F; mean age: 64.4, range: 35–80), compared to 6 healthy controls (2 M, 4 F; mean age: 42.0, range: 31–54). We found that although mean spontaneous production of oncM in 72‐hr PBMC cultures was not significantly different in CIDP compared to HC (HC 251.7 ± 34.5 pg/ml vs CIDP 331.5 ± 67.4 pg/ml; 2‐tailed Student's t‐test, p = 0.08), PBMC from active pts produced higher levels of oncM. Our results, although based on very small numbers, suggest that PBMC from CIDP patients spontaneously produce high levels of oncM during the active phases (relapse or progression). The evidence that CIDP PBMC are primed in vivo to produce and release high levels of inflammatory cytokines, such as oncM suggests the presence of a basal activation of the immune system which in turn may play an important role in the physiopathology of the disease. In addition to enhancing immune‐mediated inflammatory processes, oncM might directly exert damaging effects on the blood‐nerve barrier and on neural cell survival as well as on PNS plasticity, similar to what is hypothesized in multiple sclerosis. Thus, the increased production of oncM by immune cells may play a role in maintaining the complex circuitry of molecular and cellular interactions responsible of neurologic damage in CIDP.

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.