Clinicopathological characteristics of subtypes of chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To evaluate the clinical and pathological correlations characterising each clinical subtype of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: We assessed 106 consecutive patients who had CIDP fulfilling the European Federation of Neurological Societies and Peripheral Nerve Society criteria and had been referred for sural nerve biopsy. Patients with anti-neurofascin 155, anti-contactin 1 and anti-LM1 antibodies were excluded. RESULTS: 55 patients were classified as having typical CIDP. Regarding atypical CIDP, the multifocal acquired demyelinating sensory and motor (MADSAM) (n=15), distal acquired demyelinating symmetric (DADS) (n=16) and pure sensory (n=15) forms were major subtypes, while the pure motor (n=4) and focal (n=1) forms were rare. Nerve conduction studies revealed that distal motor latencies and F-wave latencies were markedly prolonged in the typical CIDP group but relatively preserved in the MADSAM group. Motor conduction velocity was conspicuously slowed in the DADS group, and distal motor latencies were markedly prolonged in the pure sensory group. Sural nerve biopsy specimens from patients with MADSAM, DADS and pure sensory type tended to show extreme variation in myelinated fibre density among fascicles due to focal myelinated fibre loss or onion-bulb formation, whereas patients with typical CIDP tended to show mild fascicular variation. Epineurial lymphocytic infiltration was conspicuous in cases with marked fascicular variation in myelinated fibre density. CONCLUSIONS: Preferential involvement of distal and proximal segments and uniform pathological features in typical CIDP indicate a role of humoral factors at sites where the blood-nerve barrier is deficient. By contrast, focal lesions in MADSAM, DADS and pure sensory forms may share neuropathic mechanisms primarily affecting the nerve trunk.

Differences in peripheral myelin antigen-specific T cell responses and T memory subsets in atypical versus typical CIDP.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is presented by a large heterogeneity of clinical phenotypes. Around 50% of patients suffer from typical CIDP and show better therapy response than atypical variants. The goal of our study was to search for cellular immunological differences in typical versus atypical CIDP in comparison to controls. METHODS: We evaluated 26 (9 typical, 17 atypical) patients with mainly active-unstable CIDP using clinical and immunological examinations (enzyme-linked immunospot assay ELISPOT, fluorescence-activated cell sorting FACS) in comparison to 28 healthy, age-matched controls (HC). Typical or atypical CIDP measurements were compared with HC using Kruskal-Wallis test. RESULTS: Atypical CIDP patients showed increased frequencies of T cell subsets, especially CD4+ effector memory T cells (TEM) and CD4+ central memory T cells (TCM) as well as a tendency of higher T cell responses against the peripheral myelin antigens of PMP-22, P2, P0 and MBP peptides compared to typical CIDP. Searching for novel auto-antigens, we found that T cell responses against P0 180-199 as well as MBP 82-100 were significantly elevated in atypical CIDP patients vs. HC. CONCLUSIONS: Our results indicate differences in underlying T cell responses between atypical and typical CIDP characterized by a higher peripheral myelin antigen-specific T cell responses as well as a specific altered CD4+ memory compartment in atypical CIDP. Larger multi-center studies study are warranted in order to characterize T cell auto-reactivity in atypical CIDP subgroups in order to establish immunological markers as a diagnostic tool.

Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased threshold change in threshold electrotonus in both hyperpolarizing and depolarizing directions [depolarizing threshold electrotonus (90-100 ms) P < 0.005, hyperpolarizing threshold electrotonus (10-20 ms), P < 0.01, hyperpolarizing threshold electrotonus (90-100 ms), P < 0.05], perhaps suggesting early hyperpolarization. In addition, using excitability parameters superexcitability, subexcitability and hyperpolarizing threshold electrotonus (10-20 ms), the patients with acute inflammatory demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to differentiate acute from acute-onset chronic inflammatory demyelinating polyneuropathy at an early stage. Characteristic nerve excitability parameter changes occur in early acute-onset chronic inflammatory demyelinating polyneuropathy, to match the clinical phenotype. Importantly, this pattern of change was strikingly different to that shown by patients with acute inflammatory demyelinating polyneuropathy, suggesting that nerve excitability techniques may be useful in distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy at the initial stage.

Does the chronic inflammatory demyelinating polyradiculoneuropathy due to secondary cause differ from primary?

BACKGROUND: The clinical presentation, neurophysiological findings, and outcome may vary between primary and secondary chronic inflammatory demyelinating polyradiculopathy (CIDP). OBJECTIVE: To compare clinical and electrodiagnostic features of primary and secondary CIDP. SETTING: Tertiary care teaching referral hospital. MATERIALS AND METHODS: The CIDP patients who were diagnosed as per European Federation of Neurological Societies/Peripheral Nerve Society criteria were included and subjected to detailed history and examinations. The clinical disability was graded on a 0-10 scale. Neurophysiology included motor and sensory nerve conductions and F wave studies of all four limbs. Based on investigations for underlying diseases, the patients were categorized into primary or secondary CIDP. Prednisolone was prescribed in all and azathioprine added in resistant cases. The secondary CIDP group received specific treatment in addition. The outcome was assessed at 3 months, 6 months, and last follow-up. RESULTS: A total of 65 patients aged 17 to 72 years were included and 20 were females. Twenty-five patients had secondary CIDP and include diabetes mellitus (16), POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) (4), monoclonal gammopathy of undetermined significance (2), myeloma (1), lymphoma (1), and malignancy (1). The secondary CIDP patients were older (48.35 vs 41.0 years), had less relapsing remitting (0 vs 6) and more frequent dysautonomia (7 vs 1). The demyelinating features were more marked in primary CIDP group and had better outcome compared with secondary CIDP. CONCLUSIONS: Of the total patients with CIDP, 38.5% of patients had secondary CIDP which was associated with progressive course, less demyelinating features, and worse prognosis.

Chronic inflammatory demyelinating polyneuropathy disease activity status: recommendations for clinical research standards and use in clinical practice.

Defining long-term outcomes in chronic inflammatory demyelinating polyneuropathy (CIDP) has been complicated by varying definitions of treatment response and differing scales measuring impairment or disability. An expert panel was convened to devise a CIDP Disease Activity Status (CDAS) and to classify long-term outcome by applying it to 106 patients with a consensus diagnosis of CIDP. Sixty of these cases were graded blindly by three independent reviewers to assess inter-rater reliability. The mean duration of follow-up was 6.4 years (range, 3 months-23 years). Eleven percent of patients were classified as cured (stable examination and off treatment for ≥5 years), 20% were in remission (stable and off treatment for <5 years), 44% had stable active disease but required ongoing therapy for at least 1 year, 7% were improving after recent initiation of therapy, and 18% had unstable active disease (treatment naïve or treatment refractory). Excellent inter-rater reliability was observed (kappa scores: 0.93-0.97; p < 0.0001). The CDAS is considered a simple and reproducible tool to classify patients with CIDP according to disease activity and treatment status that can be applied easily in practice and potentially to select patients for clinical trials.

Distal acquired demyelinating symmetric neuropathy associated with anti-GM1 antibodies: is this a CIDP variant?

Distal acquired demyelinating symmetric (DADS) neuropathy is clinically characterised by distal motor and sensory disturbances. Typically DADS does not respond or responds poorly to intravenous immunoglobulins (IVIg). We report the case of a 58-year-old patient who developed distal paraparesis. Serum electrophoresis demonstrated monoclonal IgM paraproteinemia having an anti-GM1 but no anti-MAG activity. Conduction velocities showed demyelinating pattern. Work-up excluded a lymphoproliferative disorder After IVIg treatment we observed a clinical and neurophysiological improvement. Regarding these peculiar findings, we suggest that DADS needs to be splitted in several forms determined among others by clinical, neurophysiological and antiganglioside profile and therapeutic response. We advocate to perform systematic antiganglioside antibodies assay additionnaly to anti-MAG when DADS is suspected in order to improve dysimmune neuropathies classification.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Its Variants.

PURPOSE OF REVIEW: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and its variants comprise a group of immune-mediated neuropathies with distinctive clinical presentations and electrodiagnostic features. Prompt recognition of these treatable disorders is mandatory as delays result in significant disability and morbidity. This article highlights the clinical presentation, pathophysiology, diagnostic evaluation, and treatment approach of these polyneuropathies. RECENT FINDINGS: The spectrum of CIDP is expanding with the recent characterization of neuropathies associated with nodal and paranodal antibodies. These neuropathies are distinguished by their unique presentations and are often refractory to IV immunoglobulin (IVIg) therapy. Subcutaneous immunoglobulins have recently been approved as a treatment option for CIDP and join corticosteroids, IVIg, and plasma exchange as first-line treatment. SUMMARY: CIDP is characterized by progressive symmetric proximal and distal weakness, large fiber sensory loss, and areflexia, with clinical nadir reached more than 8 weeks after symptom onset. Autoimmune demyelinating neuropathies fall on a continuum, with differences in the type of nerve fibers affected and pattern of deficits. Distinguishing between typical CIDP and its variants allows for selection of the most appropriate treatment.

Different distribution of demyelination in chronic inflammatory demyelinating polyneuropathy subtypes.

In demyelinating polyneuropathies, distribution patterns of demyelination reflect underlying pathogenesis. Median and ulnar nerve conduction studies were reviewed in 85 typical chronic inflammatory demyelinating polyneuropathy (CIDP) patients and 29 multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). Distal latencies were prolonged in typical CIDP and near normal in MADSAM. Abnormal amplitude reductions in the nerve trunks were more frequent in MADSAM than typical CIDP. Presumably because the blood-nerve barrier is anatomically deficient at the distal nerve terminals, antibody-mediated demyelination is a major pathophysiology in typical CIDP. In contrast, blood-nerve barrier breakdown is likely to be predominant in MADSAM.

A comparison of clinically atypical with typical chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: There is a paucity of prospective studies evaluating the atypical features of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). AIMS: To compare clinical and electrodiagnostic features of clinically typical and atypical CIDP patients. METHODS: The patients with typical and atypical CIDP diagnosed according to the European Federation of Neurological Societies/Peripheral Nerve Society were included. The disability was graded on a 0-10 scale. Neurophysiological study included motor and sensory nerve conduction and F wave studies of both upper and lower limbs. The patients were treated with prednisolone with or without azathioprine. The outcome was evaluated at 6 months and improvement was defined as at least 2 grades improvement. RESULTS: Eight out of 37 CIDP patients had atypical features, which included asymmetry in 2, dysautonomia in 3 and pure motor weakness, amyotrophic-lateral-sclerosis-like syndrome and distal weakness in 1 patient each. Tendon reflexes were retained in 3 patients. The mean duration of symptoms was 43 weeks in the typical and 30 weeks in the atypical group. The age, sex, disability, therapeutic response and neurophysiological features were similar in the 2 groups. CONCLUSION: About one fifth of CIDP patients may have atypical clinical features; however, their electrodiagnostic features and response to treatment are no different from typical CIDP.

Getting closer to patients: the INCAT Overall Disability Sum Score relates better to patients' own clinical judgement in immune-mediated polyneuropathies.

OBJECTIVE: To determine which widely used disability measure in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) shows the strongest association with patients' rating scores. METHODS: Five disability scales and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) were assessed serially in 20 patients with newly diagnosed GBS (n = 7) or CIDP (n = 13). Also at each visit, the patient's condition was self-assessed as being worse, unchanged or better. Longitudinal regressions were carried out to determine the association between disability scales (independent variables) and SF-36 and patients' rating scores (dependent variables). RESULTS: Higher associations with the SF-36 were found in the Overall Disability Sum Score (ODSS) than other disability measures. A higher correlation with ODSS changes was also found in the rating scores of the patients. CONCLUSION: In addition to literature findings, higher associations were found between Inflammatory Neuropathy Cause and Treatment Group ODSS and outcome assessed from patients' perceptions in immune-related polyneuropathies than in other commonly used disability scales.

Disease activity in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: Evaluation of disease status in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is often done by a combination of clinical evaluation and electrodiagnostic studies. A CIDP disease activity status (CDAS) was developed to standardize outcomes in CIDP patients. We aimed to determine if the CDAS was concordant with classical evaluation and whether CDAS enables benchmarking of CIDP. METHODS: We performed a retrospective chart review of 305 CIDP patients and identified 206 patients with >1 visit and applied the CDAS to this cohort. We examined relationships between the CDAS and classical evaluation as to outcomes and compared our cohort to other CIDP cohorts who had CDAS. RESULTS: We found that the CDAS mirrored disease severity as measured by electrophysiology and vibration perception thresholds in that CDAS class 5 had more severe neuropathy. Our results are similar to other cohorts in the middle CDAS strata with the exception of fewer subjects in CDAS 1 and more in CDAS 5. The only demographic factor predicting CDAS 5 in our cohort was age, and the overall treatment response rate using the CDAS classification was 79.3%. CONCLUSIONS: CDAS appears to have sufficient face-validity as a grading system to assess disease activity in relation to treatment status. The use of CDAS appears to allow benchmarking of patients with CIDP that may be useful in subject selection for clinical trials and also to highlight differences in practice.

Childhood CIDP: Study of 31 patients and comparison between slow and rapid-onset groups.

OBJECTIVES: To describe 31 children presenting a CIDP; to compare patients with rapid-onset disease vs. patients with slow-onset disease, a rapid-onset disease being defined by a time to peak impairment of less than 8 weeks. STUDY DESIGN: A retrospective chart review identified 31 patients completing criteria for childhood CIDP, with 24 "confirmed CIDP" and 7 "possible CIDP". Data collected were time to peak impairment, clinical presentation, cerebrospinal fluid analysis, nerve conduction study, nerve biopsy, treatments. Evaluation at the end of follow-up was reported according to modified Rankin scale. RESULTS: Thirteen patients (42%) exhibited symptoms in less than 2 months with more often cranial nerve abnormalities (38% vs. 6%, p = 0.059), and sensitive symptoms (62% vs. 11%, p = 0.0057). They evolved predominantly in a relapsing way (69% vs. 22%, p = 0.0047). Length of the disease was also longer in the rapid-onset group (5.5 years vs. 3.83 years) but without statistical difference. The slow-onset group exhibited more frequently ataxia at onset (28% vs. 8%, p > 0.05), and evolved predominantly in a progressive manner (61% vs. 15%, p > 0.05). Outcome was similar and good in the two groups. At least 3 out of the 4 major electrophysiological criteria were positive for 27/31 children (87%). Axonal involvement could be present very early. Immunoglobulins were given in 29 cases and corticosteroids in 22. A partial or complete recovery 1 month after first treatment was reported in 30 cases. Among second-line treatments, only azathioprine seemed effective in two out of three intractable children. CONCLUSIONS: The differences noted between the two groups should be tested in wider populations. Electrophysiological criteria are restrictive and axonal involvement should be studied. Prospective trials are required to find out the best first and second line treatments.

Chronic inflammatory demyelinating polyradiculoneuropathy: a study of proposed electrodiagnostic and histologic criteria.

OBJECTIVE: To examine the sensitivity of the 3 proposed electrodiagnostic (EDX) criteria for demyelination, the sensitivity and specificity of the proposed Ad Hoc Subcommittee of the American Academy of Neurology AIDS [Acquired Immunodeficiency Syndrome] Task Force histologic criteria (AAN criteria), the degree of agreement among these criteria, and the diagnostic value of sural nerve histologic criteria in patients with idiopathic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). DESIGN AND METHODS: A retrospective analysis of 24 patients with idiopathic CIDP and 12 patients with diabetic polyneuropathy (DP) who underwent comparable testing of clinical, histologic, and EDX features. RESULTS: We found 42%, 50%, and 79% sensitivity of the proposed EDX, AAN teased fiber, and AAN electron microscopic (EM) criteria, respectively, for demyelination in CIDP. The specificity of the proposed AAN teased fiber and EM criteria for demyelination was greater than 80% when tested against patients with DP. There was lack of agreement between the EDX and histologic criteria. Almost two thirds of patients with CIDP who met the EM criteria but none of the EDX criteria for demyelination showed a favorable response to immunomodulatory therapy. CONCLUSIONS: Sural nerve histologic criteria offer unique sensitivity and acceptable specificity toward the diagnosis of CIDP. Sural nerve biopsy should be considered when a clinical suspicion of CIDP remains in patients who do not meet the proposed EDX criteria for demyelination.

Chronic acquired demyelinating symmetric polyneuropathy classified by pattern of weakness.

OBJECTIVES: To study a representative group of patients with chronic acquired symmetric demyelinating polyneuropathies, and to evaluate classification by pattern of weakness and by presence of immunoglobulin monoclonal protein (M protein). METHODS: In Vest-Agder County, Norway, an unselected population of patients with chronic symmetric polyneuropathies who fulfill electrodiagnostic criteria for demyelination are registered in a database and followed up prospectively. Data were taken from the database on April 2, 2001. Patients with proximal as well as distal weakness were classified as having chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and patients with only distal symptoms as having distal acquired demyelinating symmetric polyneuropathy (DADS). RESULTS: A total of 29 patients had chronic acquired symmetric demyelinating polyneuropathy; 15 had CIDP and 14 had DADS. The 2 categories differed regarding spinal protein level (mean +/- SD, 0.102 +/- 0.060 g/dL in CIDP vs 0.065 +/- 0.029 g/dL in DADS; P =.05); clinical course (remitting in 6 of 13 patients with CIDP vs 0 of 14 with DADS; P =.02); disability score at diagnosis (mean +/- SD, 3.3 +/- 1.0 in CIDP vs 1.9 +/- 0.6 in DADS; P<.001) and at peak of symptoms (mean +/- SD, 3.6 +/- 1.1 in CIDP vs 2.3 +/- 0.6 in DADS; P<.001); and response to immunosuppressive treatment (11 of 12 patients with CIDP vs 2 of 7 with DADS; P =.01). An M protein was detected in 8 patients (3 with CIDP and 5 with DADS). Patients with polyneuropathy with and without M protein were similar in clinical features, course, disability, and treatment response. CONCLUSION: Classification by presence or absence of proximal weakness separates patients with chronic acquired symmetric demyelinating polyneuropathy into groups that are different in clinical course, disability, and treatment response.

Chronic inflammatory demyelinating polyneuropathy presenting with features of GBS.

The authors report five patients with inflammatory demyelinating polyneuropathy with a Guillain-Barré syndrome (GBS)-like onset and initial clinical features, but with persistent symptoms similar to chronic inflammatory demyelinating polyneuropathy (CIDP). Patients in the chronic phase improved with corticosteroid or IV immunoglobulin therapy. Patients with apparent GBS who show persistent symptoms may benefit from corticosteroids or other treatment that is beneficial in the management of CIDP.

Patients with chronic inflammatory demyelinating polyneuropathy initially diagnosed as Guillain-Barré syndrome.

Progression periods for Guillain-Barré syndrome (GBS) differ from those of chronic inflammatory demyelinating polyneuropathy (CIDP), but physicians could classify patients with CIDP within 4 weeks of onset as GBS. We studied and report the frequency of GBS patients who were later diagnosed as CIDP (11/663, 2%). Plasmapheresis or intravenous immunoglobulin transiently improved all the 11 patients, who 11 progressed slowly or had a relapse beyond the 8 weeks, and the other 2 suffered a relapse between 4 and 8 weeks from the onset. Three patients had had an antecedent infectious illness. CSF albumino-cytological dissociation was detected in 6 patients within 2 weeks of onset. Recognition of the existence of such patients is important for the early diagnosis and treatment of those patients with CIDP for whom GBS has been diagnosed at onset.

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%. CONCLUSIONS: 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.

Severity and patterns of blood-nerve barrier breakdown in patients with chronic inflammatory demyelinating polyradiculoneuropathy: correlations with clinical subtypes.

OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is currently classified into clinical subtypes, including typical and atypical forms (multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) and distal acquired demyelinating symmetric neuropathy (DADS)). The aim of this study was to elucidate the patterns and severity of breakdown of the blood-nerve barrier (BNB) in each CIDP subtype. METHODS: We evaluated the effects of sera obtained from patients with typical CIDP, MADSAM and DADS and control subjects on the expression levels of tight junction proteins and transendothelial electrical resistance (TEER) value in human peripheral nerve microvascular endothelial cells (PnMECs). RESULTS: The sera obtained from the patients with the three clinical phenotypes of CIDP decreased the amount of claudin-5 protein levels and TEER values in the PnMECs. In addition, the sera obtained from typical CIDP patients more prominently reduced claudin-5 protein levels and TEER values in the PnMECs than did that obtained from the MADSAM and DADS patients. Furthermore, the severity of BNB disruption after exposure to the sera was associated with higher Hughes grade, lower MRC score, more pronounced slowing of motor nerve conduction in the median nerve and higher frequency of abnormal temporal dispersion. CONCLUSIONS: Sera derived from typical CIDP patients destroy the BNB more severely than those from MADSAM or DADS patients. The extent of BNB disruption in the setting of CIDP is associated with clinical disability and demyelination in the nerve trunk. These observations may explain the phenotypical differences between CIDP subtypes.