Chronic Inflammatory Demyelinating Polyneuropathy Patients Research Articles

International chronic inflammatory demyelinating polyneuropathy outcome study (ICOS): Protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous immune-mediated disorder with extensive variation in clinical presentation, electrophysiological phenotype, treatment response and long-term outcome. This heterogeneity may reflect the existence of distinct subtypes of CIDP with a different pathogenesis that require personalized treatment. The International CIDP Outcome Study (ICOS) is a prospective, observational, multicenter cohort study that aims to describe this variation and to define clinical and biological determinants and predictors of these subtypes, disease activity, treatment response and outcome. All patients fulfilling the European Federation of Neurological Societies/Peripheral Nerve Society 2010 diagnostic criteria for CIDP can participate, independent of age, duration and severity of the disease or treatment. We collect data on the clinical presentation, diagnostics, validated clinical outcome measures, (response to) treatment, and we collect biomaterials (DNA, cerebrospinal fluid and serial serum samples). We aim to include at least 1000 CIDP patients with a follow-up of at least 2 years. ICOS started in November 2015 in three academic medical centers in The Netherlands and by October 2018 169 patients are included: 69 new and 100 prevalent cases. ICOS is based on the format of the International Guillain-Barré syndrome (GBS) Outcome Study (IGOS). Dutch centers are invited to participate in ICOS that will continue as an independent national registry. International centers will be able to collect data and biomaterials according to the ICOS protocol by using the optional ICOS module within the INCbase infrastructure. ICOS will help to standardize the collection of data and biosamples for future research in CIDP.

Feasibility of switching from intravenous to subcutaneous immunoglobulin in CIDP: PATH trial and clinical experience

The PATH study showed efficacy of subcutaneous IgG administration (SCIG) in chronic inflammatory demyelinating polyneuropathy (CIDP). We evaluated the feasibility of switching from intravenous IgG (IVIG) to SCIG in CIDP patients according to PATH data and clinical experience. In PATH, CIDP patients were randomized to SCIG (0.2 or 0.4 g/kg/week) or placebo after IVIG restabilization. Observational studies of switching from IVIG to SCIG in CIDP and multifocal motor neuropathy are also considered. Forty-eight% of PATH subjects experienced ⩾ 1 adverse event (AE) with IVIG (rate: 0.175/infusion). Corresponding percentages for SCIG-0.2 and SCIG-0.4 were 58% and 52% (0.08 and 0.05/infusion). The most common AE was headache for IVIG (16%), and local infusion site reactions for SCIG (19% and 29%). Most subjects (88%) felt SCIG was easier to use versus IVIG. More subjects (p In observational studies, switching from IVIG to SCIG (1–5 infusion[s]/week) was associated with reduced incidence of AEs (22% vs. 1%, and 60% vs. 0%, IVIG vs. SCIG), improved QoL and higher patient preference for SCIG versus IVIG (69–90%). The PATH trial and observational studies document the feasibility, safety and efficacy of SCIG therapy in CIDP.

Subcutaneous immunoglobulin (SCIG) for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP), a multicenter randomized double-blind placebo-controlled trial: The PATH Study

Several CIDP patients need long-term corticosteroids or intravenous immunoglobulin (IVIG), with IVIG being associated with improved safety profile. SCIG is an alternative option for immunoglobulin delivery but it was not investigated in large-scale trials in CIDP. PATH was a randomized, double-blind trial investigating 0.2 and 0.4 g/kg weekly doses of SCIG IgPro20 (Hizentra®, CSL Behring) versus placebo for maintenance treatment in 172 CIDP patients. IVIG-dependent adults with definite or probable CIDP were eligible. The primary outcome was the percentage of subjects with a CIDP relapse (1-point deterioration on adjusted INCAT disability score) or who were withdrawn for any reason during the 24-week SCIg-treatment. Multiple secondary endpoints were assessed. Overall, 33% of patients on high-dose SCIG, 39% of those on low-dose SCIG and 63% of placebo recipients experienced CIDP relapse or were withdrawn from treatment (p < 0.05 for both SCIG doses vs placebo). INCAT score, MRC sum score, and grip strength remained stable with SCIG, while they deteriorated with placebo. High-dose SCIG prevented R-ODS decline. Adverse events occurred in 47 (27%) patients (18% placebo, 30% low-dose, and 35% high-dose). Both IgPro20 doses were effective and safe as maintenance treatment in patients with CIDP, compared with placebo.

Nerve echogenicity and intranerve CSA variability in high-resolution nerve ultrasound (HRUS) in chronic inflammatory demyelinating polyneuropathy (CIDP).

HRUS is increasingly being used in the diagnosis and evaluation of autoimmune neuropathies such as CIDP. Recently, studies focused not only on changes of nerves size, but also the fascicular structure and the echogenicity changes in CIDP. However, little is known about the alterations of echogenicity in the long-term course in CIDP. The aim of this study was to evaluate echogenicity in CIDP patients in a long-term follow-up period and to analyze the benefit of the evaluation of echogenicity compared to nerve size. 20 patients fulfilling the definite diagnostic criteria of CIDP received clinical examination, nerve conduction studies and HRUS every 6 months over a median follow-up time of 34 months. Patients were divided into clinically stable/regressive disease course or progressive disease course according to the development of the inflammatory neuropathy cause and treatment overall disability sum score. Echogenicity of peripheral nerves was measured semi-automated and quantitative. Echogenicity was divided into three classes by fraction of black: hypoechogenic, mixed hypo-/hyperechogenic, hyperechogenic. Patients with hyperechogenic arm nerves more frequently show clinical worsening, whereas patients with hypoechogenic arm nerves remain stable or even improved over time. In the long-term course of the disease, echogenicity mostly did not change, and if changes occured echogenicity did not correspond to ODSS changes. Echogenicity of the arm nerves in CIDP may be used as a prognostic marker, but not as a follow-up tool for evaluating clinical changes. Further studies in a larger cohort are needed to confirm these results.

Chronic Inflammatory Demyelinating Polyneuropathy With Concurrent Membranous Nephropathy: An Anti-paranode and Podocyte Protein Antibody Study and Literature Survey.

Background: Several case reports have described the concurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN). The presence of autoantibodies against podocyte antigens phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) in MN suggests an autoimmune mechanism. Some CIDP patients also harbor autoantibodies against paranodal proteins such as neurofascin 155 (NF155) and contactin-1 (CNTN1). We investigated the relationship between CIDP and MN by assaying autoantibodies against paranodal and podocyte antigens in a CIDP patient with MN, and by a literature survey on the clinical features of CIDP with MN.Methods: Anti-CNTN1 and NF155 antibodies were measured by flow cytometry using HEK293 cell lines stably expressing human CNTN1 or NF155. Binding capacity of antibodies was validated by immunostaining mouse teased sciatic nerve fibers. Anti-PLA2R antibodies were measured by enzyme-linked sorbent assay and anti-THSD7A antibodies by indirect immunofluorescence assay. Clinical features between 14 CIDP with MN cases including two with anti-CNTN1 antibodies and 20 anti-CNTN1 antibody-positive CIDP cases were compared.Results: A patient whose ages was in the late 70 s complained of progressive weakness and superficial and deep sensory impairment in four extremities over 6 months. Nerve conduction studies showed prominent demyelination patterns. The patient presented with nephrotic syndrome. Renal biopsy disclosed basement membrane thickening with local subepithelial projections and glomerular deposits of IgG4, compatible with MN. Autoantibody assays revealed the presence of IgG4 and IgG1 anti-CNTN1 antibodies, but an absence of anti-NF155, anti-PLA2R, and anti-THSD7A antibodies. The patient's serum stained paranodes of teased sciatic nerves. CIDP with MN and anti-CNTN1 antibody-positive CIDP commonly showed male preponderance, relatively higher age of onset, acute to subacute onset in 35–50% of cases, distal dominant sensorimotor neuropathy, proprioceptive impairment leading to sensory ataxia, and very high cerebrospinal fluid protein levels. However, 11 of 13 CIDP patients with MN had a favorable response to mono- or combined immunotherapies whereas anti-CNTN1 antibody-positive CIDP was frequently refractory to corticosteroids and intravenous immunoglobulin administration.Conclusion: CIDP with MN and anti-CNTN1 antibody-positive CIDP show considerable overlap but are not identical. CIDP with MN is probably heterogeneous and some cases harbor anti-CNTN1 antibodies.

Clinical, Sonographic, and Electrophysiologic Longitudinal Features of Chronic Inflammatory Demyelinating Polyneuropathy.

Several studies have aimed to find potential biomarkers to simplify the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) and to monitor and predict the disease course. However, reliable markers are still lacking. We aimed to investigate whether high-resolution nerve ultrasound (HRUS) is suitable for monitoring the long-term clinical course of CIDP. Twenty patients fulfilling the definite diagnostic criteria of CIDP received clinical examination, evaluation of the INCAT (inflammatory neuropathy cause and treatment) overall disability sum score (ODSS) as well as nerve conduction studies, and HRUS every 6 months over a median follow-up time of 34 months. Patients were divided into clinically stable/regressive disease course or progressive disease course according to the development of the ODSS. The intranerve cross-sectional-area (CSA) variability of the nerves of the lower extremity increased with disease progression, whereas it remained unchanged in patients with a stable or remitting disease course. Nerve ultrasound can be used as a method to objectify the long-term disease course in CIDP patients. The intranerve CSA variability is suitable for monitoring the clinical course of patients with CIDP.

Simultaneous MR neurography and apparent T2 mapping in brachial plexus: Evaluation of patients with chronic inflammatory demyelinating polyradiculoneuropathy

PurposeMR neurography is known to be useful to evaluate nerve pathology. The purpose of this study was to evaluate the usefulness of simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement imaging (SHINKEI) to distinguish patients with chronic inflammatory demyelinating polyneuropathy (CIDP) from healthy subjects. Materials and methodsThis retrospective study included 13 patients with CIDP and five healthy subjects from 2015 to 2017. The T2 relaxation time and the size of the cervical ganglia and roots of the brachial plexus were measured. Statistical analyses were performed with the Mann-Whitney U test and receiver operating characteristics (ROC) analysis. ResultsThe T2 relaxation times of the ganglia and roots were longer in patients with CIDP (119.31 ± 35.53 msec and 111.15 ± 33.82 msec) than in healthy subjects (101.42 ± 26.42 msec and 85.29 ± 13.22 msec, P = 0.0007 and P < 0.0001, respectively). The sizes of the ganglia and the roots were larger in patients with CIDP (6.25 ± 1.56 mm and 4.37 ± 1.71 mm) than in healthy subjects (5.59 ± 1.08 mm and 3.50 ± 0.62 mm, P = 0.0114 and P = 0.0014, respectively). ROC analysis revealed that T2 relaxation time of the roots was best at distinguishing CIDP patients from healthy subjects (the area under the curve = 0.748). ConclusionPatients with CIDP could be distinguished from healthy subjects using simultaneous apparent T2 mapping and neurography with SHINKEI.

Lumbar plexus in patients with chronic inflammatory demyelinating polyradiculoneuropathy: evaluation with simultaneous T2 mapping and neurography method with SHINKEI.

To evaluate the usefulness of simultaneous T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement imaging (SHINKEI) in the lumbar plexus to distinguish patients with chronic inflammatory demyelinating polyneuropathy (CIDP) from healthy controls. Our institutional review boards approved this retrospective study, and written informed consent was waived. 10 patients with CIDP from 2015 to 2017 were studied along with 5 healthy controls on a 3 T scanner. The T2 relaxation time and the size of the dorsal root ganglia and nerves of the lumbar plexus at L3-S1 were measured. Statistical analyses were performed with the Mann-Whitney U test and a receiver operating characteristics analysis. The T2 relaxation times of the dorsal root ganglia and the nerves of the lumbar plexus were longer in the CIDP patients (133.34 ± 41.36 and 130.40 ± 47.78 ms) compared to the healthy controls (114.69 ± 24.90 and 83.72 ± 17.51 ms, p = 0.0265 and p < 0.0001, respectively). The sizes of the nerves were larger in the CIDP patients (6.19 ± 2.28 mm) compared to the controls (4.54 ± 0.86 mm, p < 0.0001). However, there was no significant difference between the sizes of the ganglia in the CIDP patients and the controls. The receiver operating characteristics analysis revealed that the T2 relaxation time of the nerves was best at distinguishing the CIDP patients from the controls (Az = 0.848). Patients with CIDP could be distinguished from healthy controls using simultaneous T2 mapping and neurography with SHINKEI in the lumbar plexus. Patients with CIDP could be distinguished from healthy controls using simultaneous T2 mapping and neurography with SHINKEI in the lumbar plexus.

Reductions in muscle quality and quantity in chronic inflammatory demyelinating polyneuropathy patients assessed by magnetic resonance imaging.

Weakness in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) may be caused by decreases in muscle quantity and quality, but this has not been explored. Twelve patients with CIDP (mean age 61 years) and 10 age-matched (mean age 59 years) control subjects were assessed for ankle dorsiflexion strength, and two different MRI scans (T1 and T2) of leg musculature. Isometric strength was 36% lower in CIDP patients compared with controls. Tibialis anterior muscle volumes of CIDP patients were smaller by ∼17% compared with controls, and non-contractile tissue volume was ∼58% greater in CIDP patients. When normalized to total muscle or corrected contractile volume, strength was ∼29% and ∼18% lower, respectively, in CIDP patients. These results provide insight into the structural integrity of muscle contractile proteins and pathologic changes to whole-muscle tissue composition that contribute to impaired muscle function in CIDP. Muscle Nerve 58: 396-401, 2018.

Nerve ultrasound can distinguish chronic inflammatory demyelinating polyneuropathy from demyelinating diabetic sensorimotor polyneuropathy

Diabetic patients with poor glycaemic control can demonstrate demyelinating distal sensorimotor polyneuropathy (D-DSP) on electrophysiology. Distinguishing D-DSP from chronic inflammatory demyelinating polyneuropathy (CIDP) can be challenging. In this study, we investigated the role of nerve ultrasound in differentiating the two neuropathies. Nerve ultrasound findings of D-DSP patients (fulfilling the electrophysiological but not clinical criteria for CIDP) were compared with non-diabetic CIDP patients (fulfilling both criteria). We studied 108 and 95 nerves from 9 D-DSP and 10 CIDP patients respectively. CIDP patients had significantly larger cross-sectional areas of the median nerve at the mid-arm (17.0 ± 12.5 vs 8.7 ± 2.6; p = 0.005), ulnar nerve at the wrist (7.3 ± 3.1 vs 4.1 ± 1.0; p = 0.001), mid forearm (8.8 ± 5.3 vs 5.5 ± 1.5; p = 0.002) and mid-arm (14.5 ± 14.1 vs 7.5 ± 1.9; p = 0.013), and radial nerve at mid forearm (4.1 ± 2.4 vs 1.2 ± 0.4; p < 0.001). In comparison to D-DSP, CIDP patients had markedly larger nerves at the proximal and non-entrapment sites of the upper limbs, suggesting that nerve ultrasound is useful in differentiating the two neuropathies.

Conventional and unconventional therapies in typical and atypical chronic inflammatory demyelinating polyneuropathy with different clinical course of progression.

Intravenous immunoglobulin (IVIG), corticosteroids and therapeutic plasma exchange (TPE) are evidence-based conventional treatments for chronic inflammatory demyelinating polyneuropathy (CIDP). In many centres, unconventional treatments are frequently used as alternatives. We evaluated the outcome of conventional and unconventional therapies in 31 CIDP patients. Overall response rate with conventional first-line immunotherapies was 77% (20/26), comparable between IVIG and corticosteroids (80% vs 70%). Use of TPE was limited. Treatment response among typical and atypical CIDP were comparable (76 vs 80%). Non-responders were patients with progressive form of typical CIDP and DADS. Majority (21/26, 81%) of patients with persistent neurological deficits received maintenance therapy. Two subgroups of patients frequently treated with maintenance immunosuppressants were those with improving or stable disease following first-line treatment (12, 57%) and those with progressive form of CIDP (2, 10%). Primary indications for immunosuppressant use were corticosteroids-sparing and additional immunosuppression effects. Nine (64%) patients with improving or stable disease given azathioprine were taken off corticosteroids after a median duration of 14 months (range 12-108). Two (14%) eventually achieved cure or clinical remission without treatment. Maintenance IVIg was given to 6 (29%) relapsing CIDP patients; none of achieved cure or remission after similar median duration of treatment. Less potent immunosuppressant drugs (azathioprine, mycophenolate mofetil, and methotrexate) were frequently used, with moderate adverse effect profiles. In resource limited setting, unconventional treatments were commonly used among CIDP patients with different clinical course of progression. In most cases, careful risk-benefit re-assessment is required to justify its further use.

Multifocal visual evoked potentials in chronic inflammatory demyelinating polyneuropathy.

ObjectiveStudies using conventional full‐field visual evoked potentials (ffVEP) have reported subtle abnormalities in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We hypothesize that these abnormalities can be detected in the majority of CIDP patients using enhanced methods.MethodsWe performed a cross‐sectional noninterventional study comparing 18 CIDP patients and 18 matched healthy controls using multifocal VEP (mfVEP) as a technique with enhanced sensitivity to detect conduction abnormalities across the spectrum of optic nerve fibers. Patients with confounding diseases (ophthalmologic, diabetes mellitus) were excluded.ResultsThe mean amplitude and latency, as well as the low‐contrast visual acuity, did not differ between CIDP patients and controls. Subanalyses revealed latency differences concerning the superior sector of the visual field. Severity markers of CIDP (ODSS, motor nerve conduction velocity) were associated with mfVEP latency delay.InterpretationWe could not adduce evidence for clinically or diagnostically relevant visual pathway involvement in CIDP. The latency differences identified were very subtle and restricted to the superior visual field which cannot be readily explained biologically, anatomically, or pathologically. In summary, we conclude that our study revealed no relevant differences in mfVEP parameters between CIDP patients and controls.

Quantifying the changes in activity level of neuromuscular patients using the ACTIVLIM questionnaire: A 5-years study

The ACTIVLIM questionnaire was developed to measure global activity performance of neuromuscular patients (NMPs). It also has the potential to assess real life improvement resulting from new coming therapies. For this purpose, long term follow-up data are mandatory. Such data are currently absent from the literature. The aim of the present study is to compare ACTIVLIM measures of NMPs from the Belgian Neuromuscular Disease Registry (BNMDR) between years 2011 and 2015. Data from 1064 NMPs who completed the ACTIVLIM questionnaire in 2011 and 2015 were extracted from the BNMDR. RUMM 2030™ was used to obtain their global activity performance level on a unidimensional and linear measurement scale. The Wilcoxon signed rank tests and paired t-tests were used to compare ACTIVLIM measures obtained in 2011 and 2015 for the whole sample and for the 9 most prevalent diseases in BNMDR. In the whole sample, 64% of NMPs showed a deterioration of their activity (P ≤ 0.012; effect size (ES) = −0.32). The magnitude of deterioration was the most important for Duchenne muscular dystrophy (74% of them deteriorated; P < 0.001; ES = −0.46), limb-girdle muscular dystrophy (74% deteriorated; P < 0.001; ES = −0.44), hereditary spastic paraplegia (66% deteriorated; P < 0.001, ES = −0.41), and amyotrophic lateral sclerosis (69% deteriorated; P < 0.001; ES = −0.40). Deterioration was significant but less important for myotonic dystrophy type 1 (63% deteriorated; P < 0.001; ES = −0.32), spinocerebellar ataxias (67% deteriorated; P < 0.001; ES = −0.31), facioscapulohumeral dystrophy (59% deteriorated; P = 0.016; ES = −0.23), and hereditary motor and sensory neuropathy (60% deteriorated; P < 0.001; ES = −0.22). For patients with chronic inflammatory demyelinating polyneuropathy (CIDP), no deterioration was observed (P = 0.939; ES = −0.01). This is the first study focusing on activity level of NMPs using ACTIVLIM across a 5-year period. As expected, most patients showed deterioration in their activity. Among the most prevalent neuromuscular diseases, CIDP patients showed a different evolution of their global activity performance.

Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance.

Discovery of disease-associated autoantibodies has transformed the clinical management of a variety of neurological disorders. Detection of autoantibodies aids diagnosis and allows patient stratification resulting in treatment optimization. In the last years, a set of autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies target neurofascin, contactin1, or contactin-associated protein 1, and we propose to name CIDP patients with these antibodies collectively as seropositive. They have unique clinical characteristics that differ from seronegative CIDP. Moreover, there is compelling evidence that autoantibodies are relevant for the pathogenesis. In this article, we review the current knowledge on the characteristics of autoantibodies against the node of Ranvier proteins and their clinical relevance in CIDP. We start with a description of the structure of the node of Ranvier followed by a summary of assays used to identify seropositive patients; and then, we describe clinical features and characteristics linked to seropositivity. We review knowledge on the role of these autoantibodies for the pathogenesis with relevance for the emerging concept of nodopathy/paranodopathy and summarize the treatment implications.

S139. A retrospective study of patients with chronic inflammatory demyelinating polyneuropathy (CIDP): Identifying ultrasonographic features for diagnosis and prognosis

CIDP often requires continued treatment over years to control the disease, with treatment decisions often made on global impression of benefit or failure rather than more formalized measures. High frequency ultrasound of peripheral nerves has the potential to provide information about nerve function and structure, and response to treatment. These parameters can be obtained non-invasively, relatively quickly, and with minimal patient discomfort, and thus are good candidates for repeatable testing. Recent studies have confirmed that NMUS is beneficial in diagnosis of CIDP, but further research is needed to determine any role in prognosis, and whether serial assessment of CIDP patients is of benefit. We aimed to determine if parameters found on neuromuscular ultrasound (NMUS) correlate with diagnosis and clinical features in patients with CIDP. We conducted a retrospective chart review to identify patients with CIDP studied with ultrasound at Wake Forest Baptist Medical Center from January 2000 to August 2017. We extracted a standardized dataset of clinical (duration of disease, current clinical state, and treatment history), electrodiagnostic and ultrasound findings (in particular nerve size as measured by cross sectional area (CSA)) from various upper and lower limb nerves. 148 patients coded with a diagnosis of CIDP (ICD-10 G61.8 and ICD-9 357.81) who attended the WFBMC diagnostic neurology laboratory were identified and the charts reviewed. Of the 148 patients, 50 adult patients had been studied with ultrasound at least once. After chart review it was determined that 21 of these patients had definite CIDP, 22 an alternate diagnosis, and 7 patients had possible CIDP but had insufficient follow up to confirm. Abnormalities on ultrasound (in particular focal nerve enlargement) were common in our CIDP cohort, with 20 of 21 subjects having at least one abnormal finding. We analyzed our data in line with previously published diagnostic scores and protocols, and differences between CIDP and not CIDP patients were clearly evident, despite the often-incomplete data acquisition in this real-world retrospective cohort (sensitivity and specificity will be presented). The findings in different clinical subtypes and distribution patterns will also be presented and discussed. In this real-world study of ultrasound in patients with possible CIDP, there are clear differences in ultrasound parameters between those who have CIDP compared with those who have an alternate neuropathy.

Chronic inflammatory demyelinating polyneuropathy: evaluation of the vestibular system with cervical and ocular vestibular evoked myogenic potentials.

To investigate the possibility of vestibular damage in a group of patients suffering from chronic inflammatory demyelinating polyneuropathy (CIDP) using a diagnostic protocol including the caloric test, C-VEMPs and O-VEMPs. Twenty patients suffering from CIDP (mean age 58.5 years, range 33-80 years; 4 women and 16 men) were investigated. To assess any eventual audio-vestibular involvement, all patients of the study underwent pure tone audiometry, Fitzgerald-Hallpike caloric vestibular test, C-VEMPs and O-VEMPs. In 11 patients with CIDP values of both O-VEMPs and C-VEMPs were either absent or abnormal. An absent trace at O-VEMPs testing occurred in 36% of these pathological patients, whereas an increase of n10 latency and amplitude was present in the other 64% . A specific diagnostic protocol including the caloric test, C-VEMPS, O-VEMPS, could be useful when employed for identifying vestibular damage in CIDP patients.

Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes.

The objective of this study is to investigate whether chronic inflammatory demyelinating polyneuropathy (CIDP) and its subtypes differ in their type 1 T-helper (TH1) cell response against nodal/paranodal neurofascin (NF186, NF155) as well as myelin protein zero (P0 180-199) and myelin basic protein (MBP 82-100). Interferon-gamma (IFN-γ) enzyme-linked immunospot assay was used to detect antigen-specific T cell responses in 48 patients suffering typical CIDP (n = 18), distal acquired demyelinating polyneuropathy (n = 8), multifocal acquired demyelinating sensory and motor polyneuropathy (MADSAM; n = 9), and sensory CIDP (n = 13) compared to other non-immune polyneuropathy (ON; n = 19) and healthy controls (n = 9). Compared to controls, MADSAM and sensory CIDP patients showed broadest IFN-γ T cell responses to all four antigens. Positive IFN-γ responses against two or more antigens were highly predictive for CIDP (positive predictive value = 0.95) and were found in 77% of CIDP patients. Patients with limited antigen-specific response were females, more severely affected with neuropathic pain and proximal paresis. The area under the receiver operating characteristics curve (AUC) of NF186 in MADSAM was 0.94 [95% confidential interval (CI) 0.82-1.00] compared to ON. For sensory CIDP, AUC of P0 180-199 was 0.94 (95% CI 0.86-1.00) and for MBP 82-100 0.95 (95% CI 0.88-1.00) compared to ON. Cell-mediated immune responses to (para)nodal and myelin-derived antigens are common in CIDP. TH1 response against NF186 may be used as a biomarker for MADSAM and TH1 responses against P0 180-199 and MBP 82-100 as biomarkers for sensory CIDP. Larger multicenter studies study are warranted in order to establish these immunological markers as a diagnostic tools.

Outcome in chronic inflammatory demyelinating polyneuropathy from a Malaysian centre over sixteen years

Long-term outcome in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is very limited, especially from Asian countries. We aimed to determine the outcome of our cohort of CIDP patients and to define the relevant clinical, electrophysiological and laboratory determinants of disease activity, progression and treatment response. We retrospectively reviewed records of 23 CIDP patients attending our Neurology service at Kuala Lumpur Hospital, Malaysia between January 2000 and December 2016. We analysed data on neurological deficits, electrophysiological and laboratory parameters to determine diagnostic characteristics, correlation with disease activity and clinical outcomes following treatment. Included were 15 (65%) males and 8 (35%) females with a mean age of 42.7 years (SD 14.4). Mean duration of follow-up visit was 66 months (range 6–134 months). The cohort consists of 19 classical (sensory-motor) CIDP and 4 MADSAM. Large majority of patients (66%) had either stable active disease (CDAS 3, 44%) or were in remission (CDAS class 2, 22%) following treatment with standard immunotherapies (Intravenous Immunoglobulins, steroids or immunosuppressants). The proportion of CIDP patients in each CDAS class was comparable to published cohorts from North America and Europe. Medical Research Council (MRC) sum score was the only clinical score that differed across CDAS classes (p = .010) with significant inverse correlation (Spearman’s rho −0.664, p = .001). In conclusion, treatment outcomes of our CIDP cohort was comparable to those of published series. Further studies with larger cohort of patients from other parts of Asia are important to determine the long-term outcome of this heterogenous disease in this region.

Mechanism and spectrum of anti‐glycolipid antibody‐mediated chronic inflammatory demyelinating polyneuropathy

AbstractThe pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP) is composed of cellular and humoral immunities. Macrophages might play a crucial role in cellular immunity. In addition, autoantibodies participate in the pathogenesis of CIDP. To date, various autoantibodies have been reported to affect peripheral nerve myelin. Although antibodies to glycolipids are frequently identified in Guillain‐Barré syndrome and closely related to the development of neuropathies, these are detected in only a small percentage of CIDP instances. Among glycolipids, sialosylneolactotetraosylceramide (LM1) is predominantly localized in human peripheral nerve myelin. LM1‐related antibodies (e.g. anti‐LM1, GM1/LM1 and GD1b/LM1 antibodies) are detected in some patients with CIDP and Guillain‐Barré syndrome. CIDP patients with those antibodies frequently present ataxia, but rarely have cranial nerve deficits; these features are associated with the localization of LM1, which is more abundant in the dorsal root than the cranial nerves. In immunoglobulin M paraproteinemic neuropathies, except for the anti‐myelin‐associated glycoprotein neuropathies, antibodies to glycolipids with disialosyl residues, such as GD1b and GQ1b, are also detected on occasion. Notably, this feature is clinically characterized by chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M paraprotein, cold agglutinins and disialosyl antibodies. Such clinical features are related to the localization of GD1b or GQ1b in human peripheral nerves. Overall, these correlations suggest a direct involvement of the antibodies in the pathogenesis of those aforementioned neuropathies.

Intraoral Sensory Abnormalities Caused by Tooth Extraction in a Patient with Chronic Inflammatory Demyelinating Polyneuropathy

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is considered to be an immunemediated, acquired disease of the peripheral nerves. CIDP patients infrequently develop neuropathy with various clinical forms, such as blink reflex and trigeminal neuropathy. However, to our knowledge, there is no information about intraoral somatosensory changes associated with CIDP. Here, we report the case of a patient with CIDP who exhibited somatosensory changes investigated by quantitative sensory testing (QST). Case Report: A 77-year-old Japanese man was referred to our institution with symptoms of intraoral pain and swollen gingiva. The patient had been diagnosed with CIDP 8 years earlier. The second premolar of the right mandible was diagnosed with apical periodontitis, and tooth extraction was performed to control his pain and inflammation. Following the tooth extraction, local inflammation and pain subsided, however, the patient reported spontaneous dysesthesia on the adjacent gingiva of the extracted tooth. Intraoral qualitative sensory testing of the gingiva showed gingival mechanical allodynia and cold hypoalgesia at the extraction site. We diagnosed the patient with painful post-traumatic trigeminal neuropathy related to tooth extraction. Conclusion: Because of the lack of evidence for peripheral, organic changes in the oral mucosa, the sensory changes may be best explained by peripheral disturbance, an association may exist between these reported somatosensory changes and CIDP.