Chronic Inflammatory Demyelinating Polyneuropathy Patients Research Articles

Whole-body magnetic resonance neurography in patients with chronic inflammatory demyelinating polyneuropathy.

Whole-body magnetic resonance neurography (MRN) is an imaging modality that shows peripheral nerve signal change in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We aimed to explore the diagnostic potential of whole-body MRN and its potential as a monitoring tool after immunotherapy in treatment-naïve CIDP patients. Whole-body MRN using coronal 3-dimensional short tau inversion recovery (STIR) sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) techniques was performed in patients being investigated for CIDP and in healthy controls. Baseline clinical neuropathy scales and electrophysiologic parameters were collected, and MRN findings were compared before and after CIDP treatment. We found highly concordant symmetrical thickening and increased T2 signal intensities in the brachial/lumbosacral plexus, femoral, or sciatic nerves in five of the eight patients with a final diagnosis of CIDP and none of the healthy controls. There were no treatment-related imaging changes in five patients with CIDP who completed a follow-up study. Diffuse, symmetrical thickening, and increased T2 signal in root, plexus, and peripheral nerves were found in two patients ultimately excluded due to a diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome in addition to signal changes in the muscles, bony lesions, organomegaly, and lymphadenopathy. Whole-body MRN imaging shows promise in detecting abnormalities in proximal nerve segments in patients with CIDP. Future studies evaluating the role of MRN in assessing treatment response should consider follow-up scans after treatment durations of more than 4 months.

Autoantibodies Against Dihydrolipoamide S-Acetyltransferase in Immune-Mediated Neuropathies.

This study aimed to identify disease-related autoantibodies in the serum of patients with immune-mediated neuropathies including chronic inflammatory demyelinating polyneuropathy (CIDP) and to investigate the clinical characteristics of patients with these antibodies. Proteins extracted from mouse brain tissue were used to react with sera from patients with CIDP by western blotting (WB) to determine the presence of common bands. Positive bands were then identified by mass spectrometry and confirmed for reactivity with patient sera using enzyme-linked immunosorbent assay (ELISA) and WB. Reactivity was further confirmed by cell-based and tissue-based indirect immunofluorescence assays. The clinical characteristics of patients with candidate autoantibody-positive CIDP were analyzed, and their association with other neurologic diseases was also investigated. Screening of 78 CIDP patient sera by WB revealed a positive band around 60-70 kDa identified as dihydrolipoamide S-acetyltransferase (DLAT) by immunoprecipitation and mass spectrometry. Serum immunoglobulin G (IgG) and IgM antibodies' reactivity to recombinant DLAT was confirmed using ELISA and WB. A relatively high reactivity was observed in 29 of 160 (18%) patients with CIDP, followed by patients with sensory neuropathy (6/58, 10%) and patients with MS (2/47, 4%), but not in patients with Guillain-Barré syndrome (0/27), patients with hereditary neuropathy (0/40), and healthy controls (0/26). Both the cell-based and tissue-based assays confirmed reactivity in 26 of 33 patients with CIDP. Comparing the clinical characteristics of patients with CIDP with anti-DLAT antibodies (n = 29) with those of negative cases (n = 131), a higher percentage of patients had comorbid sensory ataxia (69% vs 37%), cranial nerve disorders (24% vs 9%), and malignancy (20% vs 5%). A high DLAT expression was observed in human autopsy dorsal root ganglia, confirming the reactivity of patient serum with mouse dorsal root ganglion cells. Reactivity to DLAT was confirmed in patient sera, mainly in patients with CIDP. DLAT is highly expressed in the dorsal root ganglion cells, and anti-DLAT antibody may serve as a biomarker for sensory-dominant neuropathies.

Insights into refractory chronic inflammatory demyelinating polyneuropathy: a comprehensive real-world study.

Refractory chronic inflammatory demyelinating polyneuropathy (CIDP) is a challenging subset of CIDP. It does not respond well to immune therapy and causes substantial disability. A comprehensive understanding of its clinical profile, electrophysiological characteristics and potential risk factors associated with refractoriness remains to be further elucidated. Data in this cross-sectional study was collected and reviewed from the Huashan Peripheral Neuropathy Database (HSPN). Included patients were categorized into refractory CIDP and non-refractory CIDP groups based on treatment response. The clinical and electrophysiological characteristics were compared between refractory and non-refractory CIDP groups. Potential risk factors associated with refractory CIDP were explored with a multivariate logistic regression model. Fifty-eight patients with CIDP were included. Four disease course patterns of refractory CIDP are described: a relapsing-remitting form, a stable form, a secondary progressive form and a primary progressive form. Compared to non-refractory CIDP patients, refractory CIDP exhibited a longer disease duration (48.96 ± 33.72 vs. 28.33 ± 13.72 months, p = 0.038) and worse functional impairment (MRC sum score, 46.08 ± 12.69 vs. 52.81 ± 7.34, p = 0.018; mRS, 2.76 ± 0.93 vs. 2.33 ± 0.99, p = 0.082; INCAT, 3.68 ± 1.76 vs. 3.03 ± 2.28, p = 0.056, respectively). Electrophysiological studies further revealed greater axonal impairment (4.15 ± 2.0 vs. 5.94 ± 2.77 mv, p = 0.011, ulnar CMAP) and more severe demyelination (5.56 ± 2.86 vs. 4.18 ± 3.71 ms, p = 0.008, ulnar distal latency, 7.94 ± 5.62 vs. 6.52 ± 6.64 ms, p = 0.035, median distal latency; 30.21 ± 12.59 vs. 37.48 ± 12.44 m/s, p = 0.035, median conduction velocity; 58.66 ± 25.73 vs. 42.30 ± 13.77 ms, p = 0.033, median F-wave latency), compared to non-refractory CIDP. Disease duration was shown to be an independent risk factor for refractory CIDP (p < 0.05, 95%CI [0.007, 0.076]). This study provided a comprehensive description of refractory CIDP, addressing its clinical features, classification of clinical course, electrophysiological characteristics, and prognostic factors, effectively elucidating its various aspects. These findings contribute to a better understanding of this challenging subset of CIDP and might be informative for management and treatment strategies.

Chronic Inflammatory Demyelinating Polyneuropathy and Evaluation of the Visual Evoked Potentials: A Review of the Literature.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disorder characterised by the progressive demyelination of peripheral nerves, resulting in motor and sensory deficits. While much research has focused on clinical and electrophysiological aspects of CIDP, there is an emerging interest in exploring its impact on the visual system through visual evoked potentials (VEPs). This comprehensive review synthesises existing literature on VEP findings in CIDP patients, shedding light on their potential diagnostic and prognostic value. The review thoroughly examines studies spanning the last two decades, exploring VEP abnormalities in CIDP patients. Notably, VEP studies have consistently revealed prolonged latencies and reduced amplitudes in CIDP patients compared to healthy controls. These alterations in VEP parameters suggest that the demyelinating process extends beyond the peripheral nervous system to affect the central nervous system, particularly the optic nerve and its connections. The correlation between VEP abnormalities and clinical manifestations of CIDP, such as visual impairment and sensory deficits, underscores the clinical relevance of VEP assessment in CIDP management. Furthermore, this review addresses the potential utility of VEPs in aiding CIDP diagnosis and monitoring disease progression. VEP abnormalities may serve as valuable biomarkers for disease activity, helping clinicians make timely therapeutic decisions. Moreover, this review discusses the limitations and challenges associated with VEP assessment in CIDP, including variability in recording techniques and the need for standardised protocols. In conclusion, this review highlights the evolving role of VEPs as a non-invasive tool in CIDP evaluation. The consistent VEP abnormalities observed in CIDP patients suggest the involvement of the central nervous system in this demyelinating disorder. As our understanding of CIDP and its pathophysiology continues to evolve, further research in this area may lead to improved diagnostic accuracy and monitoring strategies, ultimately enhancing the clinical management of CIDP patients.

Symptom and Treatment Satisfaction in Members of the US and Canadian GBS/CIDP Foundations with a Diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy.

Current guidelines for defining good outcomes in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) are predominately defined by experts. At present, we do not have a patient-anchored definition of what constitutes a "good" outcome. Our study aimed to assess the symptom burden of people living with CIDP, as well as satisfaction with treatments and clinical outcomes. We conducted an online-survey in CIDP patients registered with the US and Canadian GBS/CIDP foundations. Respondents answered general demographic and clinical questions, as well as satisfaction with current symptom burden and treatments, plus validated outcome measures. A total of 318 individuals with self-reported CIDP completed the online survey, of whom 128 (40%) considered their current disease burden as satisfactory while 190 (60%) did not. Of 305 patients who answered the treatment satisfaction question, 222(74%) were satisfied with their treatments. Patients who were satisfied with their current symptoms had, on average, better scores in quality of life and disease severity scales, although regression modeling showed that only ability to walk, stable symptoms, and health utility scores were associated with symptom satisfaction. Treatment satisfaction was associated with stable symptoms, use of IVIG, and use of one versus no medication. A high proportion of members of the US and Canadian GBS/CIDP Foundations reporting a diagnosis of CIDP were unsatisfied with current symptoms, despite a high level of overall satisfaction with treatments. There is an unmet need for improving long-term outcomes in people with a diagnosis of CIDP, and for studying patient-centered long-term treatment goals.

Efficacy and Safety of Intravenous Immunoglobulin Treatment in Selected Neurological Diseases-One Centre's Experience Based on the Therapy of 141 Patients.

Intravenous immunoglobulins (IVIg) are the first-choice drugs for the treatment of certain neuroimmune diseases. The aim of this study was to evaluate the efficacy and safety of IVIg in patients with selected nervous system diseases. The study enrolled patients who received IVIg in programmes financed by the National Health Fund in Poland. The status of patients upon inclusion and during treatment was assessed using scales dedicated to specific neurological diseases. The study enrolled 141 patients aged 56.28 ± 14.72 (51.77% female): 21 patients with myasthenia gravis (MG), 65 with chronic inflammatory demyelinating polyneuropathy (CIDP), 30 with Guillain-Barré syndrome (GBS), 12 with neuromyelitis optica spectrum disorder (NMOSD) and 13 patients with autoimmune encephalitis (AE). Neurological improvement was found in 14 (66.66%) MG patients (with a reduction of at least three points on the Quantitative Myasthenia Gravis Score (QMGS) within 14 days from the completion of the cycle), and in 34 (52.3%) GBS patients (with a reduction of at least one point on the Medical Research Council Scale within 14 days from the completion of the cycle). The parameters with the strongest effect on clinical improvement in MG patients were age [OR 1.033, CI 95% [0.09-1.09], p = 0.049] and baseline QMGS [OR 0.505; CI 95% [0.24-0.87], p = 0.038]. In the majority of CIDP patients (27, 97%) and NMOSD patients (6, 50%), neurological stabilisation was observed (without clinical improvement, defined for CIDP patients as an increase of at least two points on the Lovett Scale after three courses of IVIg were administered, and for NMOSD patients as an increase of at least one point on the Medical Research Council Scale and/or a shift of at least 0.3 logMAR after three courses of treatment). Deep-vein thrombosis was only one serious adverse event in the total group of patients treated with IVIg. The use of IVIg in patients with MG and GBS mostly results in neurological improvement, while in patients with NMOSD and CIDP, it mostly results in disease stabilisation. This could indicate the predominant anti-idiotypic antibody activity of IVIg in acute neuroimmune diseases or during exacerbations in chronic autoimmune diseases. The therapy of AE in comorbid neoplastic disease is burdened with an elevated risk of failure for IVIg. The results of our study confirm the improved safety of IVIg for selected neurological diseases.

Standardized tapering off subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy.

Attempting discontinuation of treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is recommended. However, there is no evidence based regimen for tapering off subcutaneous immunoglobulin (SCIG). This trial investigated stepwise tapering off SCIG to detect remission and the lowest effective dosage. During tapering off, frequent vs less frequent clinical evaluation was compared. Patients with CIDP receiving a stable SCIG dosage followed a standardized tapering off regimen: 90%, 75%, 50%, 25% and 0% of the initial dose every 12th week, pending no deterioration occurred. In case of relapse during tapering off, the lowest effective dose was identified. Treatment with SCIG was registered for two years after participation. Disability score and grip strength were primary parameters. Participants were randomized to clinical evaluation every 6th week (frequent) or 12th week (less frequent). Fifty-five patients were included of which thirty-five relapsed. Twenty patients (36%) were able to discontinue treatment without relapse. In relapsing patients, median dosage could be reduced by 10% (range, 0-75). After two years, 18 of 20 patients were still in remission without treatment. Frequent clinical evaluation did not detect deterioration more frequently than less frequent evaluation; RR 0.5 (95% CI, 0.2-1.2) (p = 0.17). In stable CIDP patients, SCIG could be completely tapered off in 36% of the patients and only in 10% of these patients relapse occurred during the following two years. More frequent evaluation was not superior to detect deterioration.

Disease activity in chronic inflammatory demyelinating polyneuropathy: association between circulating B-cell subsets, cytokine levels, and clinical outcomes.

Chronic inflammatory demyelinating polyneuropathy (CIDP), a common and treatable autoimmune neuropathy, is frequently misdiagnosed. The aim of this study is to evaluate the relationship between immunological markers and clinical outcome measures in a mixed cohort of patients with typical CIDP and CIDP variants at different disease stages. Twenty-three typical, 16 multifocal and five distal CIDP patients were included. Twenty-five sex and age-matched healthy controls and 12 patients with Charcot-Marie-Tooth type 1A (CMT1A) disease served as controls. Peripheral B-cell populations were analyzed by flow cytometry. IL6, IL10, TNFA mRNA and mir-21, mir-146a, and mir-155-5p expression levels were evaluated by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMC) and/or skin biopsy specimens. Results were then assessed for a possible association with clinical disability scores and intraepidermal nerve fiber densities (IENFD) in the distal leg. We detected a significant reduction in naive B cells (P ≤ 0.001), plasma cells (P ≤ 0.001) and regulatory B cells (P < 0.05), and an elevation in switched memory B cells (P ≤ 0.001) in CIDP compared to healthy controls. CMT1A and CIDP patients had comparable B-cell subset distribution. CIDP cases had significantly higher TNFA and IL10 gene expression levels in PBMC compared to healthy controls (P < 0.05 and P ≤ 0.01, respectively). IENFDs in the distal leg showed a moderate negative correlation with switched memory B-cell ratios (r = -0.51, P < 0.05) and a moderate positive correlation with plasma cell ratios (r = 0.46, P < 0.05). INCAT sum scores showed a moderate positive correlation with IL6 gene expression levels in PBMC (r = 0.54, P < 0.05). Altered B-cell homeostasis and IL10 and TNFA gene expression levels imply chronic antigen exposure and overactivity in the humoral immune system, and seem to be a common pathological pathway in both typical CIDP and CIDP variants.

Electrodiagnostic profile of conduction slowing in amyotrophic lateral sclerosis

ObjectiveSince motor nerve conduction slowing can occur due to loss of large axons, we investigate the conduction slowing profile in amyotrophic lateral sclerosis (ALS) and identify the limits beyond which the diagnosis of exclusive axonal loss is unlikely. MethodsFirst, using linear regression analysis, we established the range of motor conduction slowing in 76 chronic inflammatory demyelinating polyneuropathy (CIDP) patients. Demyelinating range confidence intervals were defined by assessing conduction velocity (CV), distal latency (DML), and F-wave latency (F) in relation to distal compound muscle action potential (CMAP) amplitude of median, ulnar, fibular, and tibial nerves. Results were subsequently validated in 38 additional CIDP patients. Then, the newly established demyelination confidence intervals were used to investigate the profile of conduction slowing in 95 ALS patients. ResultsCV slowing, prolonged DML, and abnormal F were observed in 22.2%, 19.6%, and 47.1% of the studied nerves respectively in ALS patients. When slowing occurred, it affected more than one segment of the motor nerve, suggesting that CMAP amplitude dependent conduction slowing caused by an exclusive loss of large axons is the main mechanism of slowing. No ALS patient had more than 2 nerves with CV slowing in the confidence interval defined by the regression equations or the American Academy of Neurology (AAN) research criteria for CIDP diagnosis. ConclusionsThe presence of more than two motor nerves with CV slowing in the demyelinating range defined by the regression analysis or AAN criteria in ALS patients suggests the contribution of acquired demyelination or other additional mechanisms exist in the electrodiagnostic profile of ALS.

Pathology explains various mechanisms of auto-immune inflammatory peripheral neuropathies.

Autoimmune neuropathies are a heterogeneous group of rare and disabling diseases in which the immune system is thought to target antigens in the peripheral nervous system: they usually respond to immune therapies. Guillain-Barré syndrome is divided into several subtypes including "acute inflammatory demyelinating polyradiculoneuropathy," "acute motor axonal neuropathy," "acute motor sensory neuropathy," and other variants. Chronic forms such as chronic inflammatory demyelinating polyneuropathy (CIDP) and other subtypes and polyneuropathy associated with IgM monoclonal gammopathy; autoimmune nodopathies also belong to this group of auto-immune neuropathies. It has been shown that immunoglobulin G from the serum of about 30% of CIDP patients immunolabels nodes of Ranvier or paranodes of myelinated axons. Whatever the cause of myelin damage of the peripheral nervous system, the initial attack on myelin by a dysimmune process may begin either at the internodal area or in the paranodal and nodal regions. The term "nodoparanodopathy" was first applied to some "axonal Guillain-Barré syndrome" subtypes, then extended to cases classified as CIDP bearing IgG4 antibodies against paranodal axoglial proteins. In these cases, paranodal dissection develops in the absence of macrophage-induced demyelination. In contrast, the mechanisms of demyelination of other dysimmune neuropathies induced by macrophages are unexplained, as no antibodies have been identified in such cases. The main objective of this presentation is to show that the pathology illustrates, confirms, and may explain such mechanisms.

Epidemiology and Clinical Course of Chronic Autoimmune Neuropathies During the SARS-CoV-2 Pandemic in Latvia

Background: Chronic autoimmune neuropathies are a group of rare neurological disorders caused by the immune response to autoantigens in the peripheral nervous system. Objective: This study aimed to report epidemiological data in Latvia on the most common chronic autoimmune neuropathies and evaluate SARS-CoV-2 infections or vaccinations’ impact on our patient’s clinical course of the disease. Methods: A single-center observational study was performed, which included all patients diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) in Latvia since 2015. Prevalence and incidence were calculated by using population data from the corresponding time of the Central Statistics Bureau of Latvia. Detailed clinical evaluation and re-assessment of diagnostic criteria were performed in the whole study group. All patients underwent telephone interviews regarding their SARS-CoV-2 vaccination or infection status. Results: This study included 23 CIDP and 8 MMN patients. The point prevalence and incidence of CIDP were 1.21 per 100 000 people and 1.16 per 100 000 people, respectively. The point prevalence and incidence of MMN were 0.42 per 100 000 individuals and 0.40 per 100 000 individuals, respectively. Most of the patients involved in this study (90%, n=28) with CIDP or MMN were vaccinated against SARS-CoV-2 infection, and none of the patients experienced fluctuations or relapse regarding autoimmune polyneuropathy. Conclusion: The incidence and prevalence of CIDP and MMN in Latvia are similar to previously reported European studies. In our study group, vaccination against SARS-CoV-2 was safe and did not negatively affect the clinical course of CIDP and MMN patients.

Efficacy of hematopoietic stem cell transplantation treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta-analysis.

Treatment options for chronic inflammatory demyelinating polyneuropathy (CIDP) are intravenous immunoglobulin, plasmapheresis, corticosteroids and immunosuppressive drugs. However, a substantial proportion of patients with CIDP remain refractory to treatment and develop severe functional disability. A systematic review and a meta-analysis of the efficacy of hematopoietic stem cell transplantation (HSCT) treatment in refractory CIDP patients was performed. The study is based on queries in the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science and clinicaltrials.gov databases on 4 December 2022. Articles that met our eligibility criteria were included after screening. Patients' characteristics, treatment regime and outcome measures were extracted. Eighty-nine patients in 11 studies were included. The pooled estimate of responsiveness amongst the four included studies was 87.04% (95% confidence interval 66.7%-99.5%) and the pooled estimate of freedom of all immune modulating or suppressive drugs was 80.75% (95% confidence interval 71.2%-90.2%). This meta-analysis and systematic review suggested that HSCT can be effective in the treatment of refractory CIDP. Whilst there are risks involved, HSCT may be a beneficial and viable therapy for refractory CIDP when carefully evaluated.

Nerve Ultrasound of Peripheral Nerves in Patients Treated with Immune Checkpoint Inhibitors.

Background and Objectives: Immune checkpoint inhibitors (ICIs) have enriched tumor therapy, improving overall survival. Immunotherapy adverse events (irAEs) occur in up to 50% of patients and also affect the peripheral nervous system. The exact pathomechanism is unclear; however, an autoimmune process is implicated. Thus, the clinical evaluation of irAEs in the peripheral nervous system is still demanding. We retrospectively analyzed nerve ultrasound (NU) data of polyneuropathies (PNPs) secondary to checkpoint inhibitors. Materials and Methods: NU data of patients with PNP symptoms secondary to ICI therapy were retrospectively analyzed using the Ultrasound Pattern Sum Score (UPSS) as a quantitative marker. Our findings were compared with a propensity score match analysis (1:1 ratio) to NU findings in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and chemotherapy-associated PNP patients. Results: In total, 10 patients were included (4 female, mean age 66 ± 10.5, IQR 60-77), where NU was performed in 80%. The UPSS obtained ranged from 0 to 5 (mean 2 ± 1.6, IQR 1-2.5). The morphological changes seen in the NUs resembled sonographic changes seen in chemotherapy-associated PNP (n = 10, mean UPSS 1 ± 1, IQR 0-2) with little to no nerve swelling. In contrast, CIDP patients had a significantly higher UPSS (n = 10, mean UPSS 11 ± 4, IQR 8-13, p < 0.0001). Conclusions: Although an autoimmune process is hypothesized to cause peripheral neurological irAEs, NU showed no increased swelling as seen in CIDP. The nerve swelling observed was mild and comparable to ultrasound findings seen in chemotherapy-associated PNP.

Effect of Treatments on All-Cause of Mortality in Chronic Inflammatory Demyelinating Polyneuropathy (S19.008)

<h3>Objective:</h3> To investigate the effect on mortality of different treatments of chronic inflammatory demyelinating polyneuropathy (CIDP). <h3>Background:</h3> Treatment options, which include plasmapheresis, IVIg, steroids, immunosuppressants, or a combination of these and their effectiveness in reducing overall mortality remain a question of high interest in studying the outcomes of CIDP. <h3>Design/Methods:</h3> We used the New York State Planning and Research Cooperation (SPARCS) database to retrospectively collect all patients with CIDP from 1998–2018. ICD 9 and 10 codes were used to identify comorbidities. Mortality data was collected using discharge status as either expired or sent to hospice. Multivariate analysis with binary logistic regression adjusted for comorbidities, gender, and age. Comorbidities included type 2 diabetes, hypertension, heart failure, COPD, Parkinson’s disease, multiple sclerosis, autoimmune hypothyroidism, pneumonia, and a multitude of cardiovascular diseases were assessed from the date of diagnosis. Pearson Chi Squared test was used to test for significance. <h3>Results:</h3> 8,096 patients with CIDP were identified from 1998–2018.169 patients were treated with only plasmapheresis (2.0%), 602 patients were treated with only steroids (7.4%), 27 were treated with only immunosuppressants (0.3%), 1,802 were treated with only IVIg (22.2%), and 538 were treated with a combination therapy (6.6%). There was no significant difference in gender (p=0.119) or age (p=0.585) between those who were treated and those who were not treated. Multivariable binary logistic regression there was no significant difference in the likelihood of death whether a patient was ever treated or not treated (OR: 1.011; 95% CL: 0830–1.232; p=0.912). <h3>Conclusions:</h3> CIDP patients with a history of treatment with plasmapheresis, steroids, immunosuppressants, IVIg or a combination at any time, when confounding for all comorbid conditions, gender and age did not significantly affect mortality when compared to patients who did not. Work is in progress for subgroup analysis and identifying other risk factors for mortality including hospital admission and socioeconomic status. <b>Disclosure:</b> Miss Shaikh has nothing to disclose. Mr. Choudhry has nothing to disclose. Mr. Choudhry has nothing to disclose. Mr. Jaffry has nothing to disclose. Mr. Trivedi has nothing to disclose. Mr. Mandava has nothing to disclose. Mr. Jaffry has nothing to disclose. Mr. Ors has nothing to disclose. Ms. Faiz has nothing to disclose. Dr. Souayah has received publishing royalties from a publication relating to health care.

Motor Nerve Conduction Slowing in Amyotrophic Lateral Sclerosis (P10-8.006)

<h3>Objective:</h3> To determine the range of conduction values for motor nerve conduction slowing and further characterize the distribution of conduction slowing in ALS and characterize the limits of conduction slowing beyond which the diagnosis of ALS is uncertain. <h3>Background:</h3> Abnormal motor nerve conduction studies in ALS are attributed to loss of large axons and distal axonopathy, however conduction slowing can be the result of superimposed demyelinating polyneuropathy or an alternate diagnosis. <h3>Design/Methods:</h3> The electrodiagnostic data of 76 chronic inflammatory demyelinating polyneuropathy (CIDP) patients, identified using AAN research criteria was used to create 12 novel equations using regression analysis that determine a range of the expected slowing of a primary demyelinating polyneuropathy. Demyelinating range confidence intervals were defined by assessing conduction velocity (CV), distal latency (DL), and F latency in relation to distal compound muscle action potential (CMAP) amplitude of median, ulnar, fibular, and tibial nerves. Results were then validated in 38 additional CIDP patients. These developed equations were then used to evaluate conduction slowing in 95 patients with ALS. Transformed CMAP amplitude was used as an independent variable whereas transformed DL, CV, and F were used as dependent variables. <h3>Results:</h3> CV slowing, prolonged DL, and abnormal F latency were observed respectively in 22.2%, 19.6%, and 46.7% of the studied nerves. When slowing occurred, it affected more than one segment of the motor nerve, suggesting that loss of large axons is the main mechanism of slowing. No ALS patient had more than 2 nerves with CV slowing in the confidence interval defined by the regression equations or the American Academy of Neurology (AAN) research criteria for CIDP diagnosis. <h3>Conclusions:</h3> The presence of more than two motor nerves with CV slowing in the demyelinating range defined by the regression analysis or AAN criteria in ALS patients suggests an alternative diagnosis or superimposed demyelination. <b>Disclosure:</b> Mr. Mandava has nothing to disclose. Miss Shaikh has nothing to disclose. Mr. Jaffry has nothing to disclose. Mr. Jaffry has nothing to disclose. Mr. Ors has nothing to disclose. Mr. Trivedi has nothing to disclose. Ms. Faiz has nothing to disclose. Mr. Gandhi has nothing to disclose. Dr. Patel has nothing to disclose. Abu Nasar, MD has nothing to disclose. Ankit Pahwa has nothing to disclose. Dr. Sander has received personal compensation for serving as an employee of Grifols. Dr. Sander has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Sander has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Law firm. Dr. Souayah has received publishing royalties from a publication relating to health care.

Global Mortality of Chronic Inflammatory Demyelinating Polyneuropathy Patients Treated with Intravenous Immunoglobulin versus Steroid Therapies (P10-5.006)

<h3>Objective:</h3> To investigate whether there is a significant difference in global mortality of CIDP patients who were either administered intravenous immunoglobulin (IVIg) versus steroids. <h3>Background:</h3> Treatment modalities for CIDP remain a frontier field and relative differences between treatments still require investigation. <h3>Design/Methods:</h3> We enacted a retrospective analysis using the New York Statewide Planning and Research Cooperative System (SPARCS) database to isolate patients with CIDP who also expired. Mortality was considered if the patient died or had a final state of hospice care. Age was limited to 18 years or older. Patients who received both IVIg and steroid treatment were excluded from analysis. <h3>Results:</h3> We identified 8,096 patients who were diagnosed with CIDP from 1998–2018. 496 patients in this period expired. 640 CIDP patients received steroid treatment and 47 of these patients died (7.3%). 1,868 CIDP patients received IVIG treatment and 87 of them died (3.6%). There is no significant difference between average age between patients receiving IVIG or steroids (70.79±12.86 vs 72.44±12.74; p=0.497) or gender (p=0.890) in the death cohort. Multivariate regression analysis performed on all patients has shown the likelihood of death is not significantly different between steroid use compared to patients not treated with steroids or IVIG (OR: 1.052; 95% CL: 0.743–1.488; p=0.777). However, the likelihood of death was significantly reduced in the group treated with IVIG compared to the patients who did not receive IVIG or steroids (OR: 0.593; 95% CL: 0.449–0.782; p&lt;0.001). <h3>Conclusions:</h3> Our preliminary data suggest a significant reduction in all cause of death in CIDP patients treated with IVIG. Work in progress to identify the contributions of other demographic and socioeconomic factors along with severity of associated comorbid conditions in CIDP mortality. <b>Disclosure:</b> Mr. Jaffry has nothing to disclose. Mr. Jaffry has nothing to disclose. Mr. Trivedi has nothing to disclose. Mr. Ors has nothing to disclose. Mr. Mostafa has nothing to disclose. Miss Shaikh has nothing to disclose. Mr. Mandava has nothing to disclose. Ms. Faiz has nothing to disclose. Dr. Khan has nothing to disclose. Dr. Souayah has received publishing royalties from a publication relating to health care.

Chronic inflammatory neuropathies and their impact on activities and participation.

Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are inflammatory neuropathies that can lead to considerable limitations in daily activities and in social participation. However, systematic evaluation of these self-reported limitations is lacking in the currently available studies. Understanding the impact of these diagnoses on patients' life is important to optimize management strategies. To systematically assess the self-reported limitations in activities and participation and determine associated factors. A survey study was conducted in 2021 in a cohort of patients with CIDP (n = 257) and MMN (n = 148) from a university hospital. The survey included the Rasch-built Overall Disability Scale and the Utrecht Scale for Evaluation of Rehabilitation-Participation, questions addressing personal and disease-related factors and treatment. Multivariate linear regression analysis was used to determine associations with disease-related and personal factors. A total of 147 CIDP and 103 MMN patients responded. Limitations in activities were reported by 70.7% CIDP and 52.2% MMN patients with moderate to severe limitations in 22.4% and 5.9% patients, respectively. Participation restrictions were reported by 50% of CIDP and 40% of MMN patients, nevertheless satisfaction with participation was high. Fatigue, pain and resilience were independently associated with limitations in activities and satisfaction with participation in CIDP patients. Activity limitations and restrictions in participation are common in CIDP patients and to a lesser extent in MMN patients. Fatigue, pain and resilience independently contributed to perceived limitations in CIDP patients. Referral to a rehabilitation physician is warranted to address these limitations appropriately.

Outcome in chronic inflammatory demyelinating polyneuropathy: A systematic review and meta-analysis.

The outcome in chronic inflammatory demyelinating polyneuropathy (CIDP) has been reported in longitudinal and cross-sectional studies. A considerable variation of long-term disease outcome appears in the reports. To overcome this uncertainty, a systematic review and meta-analyses of CIDP outcome including the parameters case fatality rate, ambulation, physical ability and remission was conducted. In accordance with the PRISMA guidelines, a systematic search in PubMed and EMBASE (OVID) for reports exceeding 2 years of follow-up on patients with active or previously active CIDP published until May 12th , 2022 was conducted. Studies were quality appraised using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for studies reporting prevalence data. Pooled analyses were conducted and the results were visualized using forest plots. The study protocol was prospectively registered on PROSPERO (CRD42021266903). A total of 1,290 titles were identified. Sixty-nine full-text articles were screened and 21 studies with 1,199 patients were selected for the data analysis. The pooled case fatality rate was 3.3% (95% CI: 1.9% - 5.7%). The pooled fraction of non-ambulatory patients was 8.2% (95% CI: 5.7% - 11.6%) and overall, 47.1% (95% CI: 39.5% - 54.9%) of CIDP patients had a good outcome without disability. In addition, the pooled rate of remission was 40.8% (95% CI: 30.6% - 51.8%). Future research is warranted on how to prevent long-term impairment in CIDP. In addition, care should be taken to develop clinical strategies to avoid immune modulating therapy in the many patients in remission. This article is protected by copyright. All rights reserved.

CIDP: Analysis of Immunomarkers During COVID-19 mRNA-Vaccination and IVIg-Immunomodulation: An Exploratory Study

Availability of COVID-19 mRNA vaccine for patients with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with intravenous immunoglobulin (IVIg) raises the question of whether COVID-19 mRNA vaccine influences disease activity or IVIg-mediated immunomodulation in CIDP. In this exploratory study, blood samples of CIDP patients on IVIg treatment were longitudinally analyzed before and after vaccination with a COVID-19 mRNA vaccine. A total of 44 samples of eleven patients were characterized at four timepoints by ELISA and flow cytometry in terms of immunomarkers for disease activity and IVIg-immunomodulation. Apart from a significantly lower expression of CD32b on naïve B cells after vaccination, no significant alteration of immunomarkers for CIDP or IVIg-mediated immunomodulation was observed. Our exploratory study suggests that COVID-19 mRNA vaccine does not have a relevant impact on immune activity in CIDP. In addition, immunomodulatory effects of IVIg in CIDP are not altered by COVID-19 mRNA vaccine. This study was registered in the German clinical trial register (DRKS00025759).Graphical Overview over the study design. Blood samples of CIDP patients on recurrent IVIg treatment and vaccination with a COVID-19 mRNA vaccine were obtained at four timepoints for cytokine ELISA and flow cytometry, to assess key cytokines and cellular immunomarkers for disease activity and IVIg-immunomodulation in CIDP.

Corneal nerve fiber involvement in chronic inflammatory demyelinating polyneuropathy.

Despite the primary myelin-related pathophysiology, small fiber neuropathy (SFN) and axonal degeneration are also considered to be involved and associated with disabling symptoms and impaired quality of life in chronic inflammatory demyelinating polyneuropathy (CIDP). Demonstration of SFN usually requires complex or invasive investigations. In vivo corneal confocal microscopy (IVCCM) has evolved as a non-invasive, easily applied method for quantification of small fiber involvement in peripheral nerve disorders. We aimed to investigate the potential role of IVCCM in CIDP. In this cross-sectional study, 15 patients with CIDP underwent assessment with clinical disability scales, neuropathic pain (NP) and autonomic symptom questionnaires, nerve conduction studies, and IVCCM. IVCCM parameters were analyzed and compared to those from 32 healthy controls. Corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) were significantly decreased in the CIDP group, compared to those in controls (p = 0.03 and p = 0.024, respectively). Langerhans cells and fiber tortuosity were increased in CIDP patients (p = 0.005 and p = 0.001, respectively). IVCCM parameters were significantly lower in patients with NP compared to those in patients without NP. IVCCM shows promise as a non-invasive complementary biomarker in the assessment of demyelinating polyneuropathies, providing insights into the potential pathophysiology of these non-length-dependent neuropathies.