Anti-contactin 1 Antibody-associated Membranous Nephropathy in Chronic Inflammatory Demyelinating Polyneuropathy with Several Autoantibodies.

A 50-year-old man diagnosed with anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was referred to our department for the evaluation of proteinuria. A kidney biopsy revealed membranous nephropathy (MN). Immunohistochemistry for CNTN1 revealed positive granular staining along the glomerular basement membrane, confirming anti-CNTN1 antibody-associated MN. Immunofluorescence showed a full-house pattern, and several autoantibodies, such as anti-nuclear antibody, anti-double-strand DNA antibody, and anti-cardiolipin antibody, were detected in the patient's serum. Although limited autoantibodies have been investigated in some of the reported cases, a variety of autoantibodies might be produced in anti-CNTN1 antibody-associated CIDP, accompanied by MN.

Physician awareness and understanding of chronic inflammatory demyelinating polyradiculoneuropathy in Japan: a web-based study.

OBJECTIVES: To investigate potential knowledge gaps between neurologists and non-specialists and identify challenges in the current management of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), with a focus on 'early diagnosis' and 'appropriate treatment' for CIDP. DESIGN: A non-interventional, cross-sectional, web-based quantitative survey of physicians working in healthcare clinics or hospitals in Japan. SETTING: Participants were recruited from the Nikkei Business Publications panel from 18 August to 14 September 2022. PARTICIPANTS: Responses from 360 physicians (120 each of internists, orthopaedists and neurologists) were collected. OUTCOME MEASURES: Responses relating to a CIDP hypothetical case and current understanding were assessed to determine awareness, collaboration preferences and diagnosis and treatment decisions. RESULTS: Understanding of CIDP was 90.8% among neurologists, 10.8% among orthopaedists and 13.3% among internists; >80% of orthopaedists and internists answered that neurologists are preferable for treatment. Diagnostic assessment using a hypothetical case showed 95.0% of neurologists, 74.2% of orthopaedists and 72.5% of internists suspected CIDP. Among orthopaedists and internists suspecting CIDP, >70% considered referring to neurology, while ~10% considered continuing treatment without a referral. Among neurologists, 69.4% chose intravenous immunoglobulin (IVIg) as first-line treatment and determined effectiveness to be ≤3 months. CONCLUSIONS: Orthopaedists and internists had lower CIDP awareness compared with neurologists, which may lead to inadequate referrals to neurology. Evaluation of IVIg effectiveness for maintenance therapy occurred earlier than the guideline recommendations (6-12 months), risking premature discontinuation. Improving CIDP knowledge among orthopaedists and internists is critical for better diagnosis and collaboration with neurologists. Neurologists should consider slow and careful evaluation of IVIg maintenance therapy. TRIAL REGISTRATION NUMBER: UMIN000048516.

[Modern aspects of diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy in children]. / Sovremennye aspekty diagnostiki i lecheniya khronicheskoi vospalitel'noi demieliniziruyushchei polineiropatii u detei.

OBJECTIVE: Analysis of demographic, clinical, laboratory, electrophysiological and neuroimaging data and pathogenetic therapy of pediatric patients with chronic inflammatory demyelinating polyneuropathy (CIDP). MATERIAL AND METHODS: Patients (n=30) were observed in a separate structural unit of the Russian Children's Clinical Hospital of the Russian National Research Medical University named after. N.I. Pirogova Ministry of Health of the Russian Federation in the period from 2006 to 2023. The examination was carried out in accordance with the recommendations of the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society on the Management of CIDP (2021). All patients received immunotherapy, including intravenous immunoglobulin (IVIG) (n=1), IVIG and glucocorticosteroids (GCS) (n=17, 56.7%), IVIG+GCS+plasmapheresis (n=12, 40.0%). Alternative therapy included cyclophosphamide (n=1), cyclophosphamide followed by mycophenolate mofetil (n=1), rituximab (n=2, 6.6%), azathioprine (n=3), mycophenolate mofetil (n=2, 6.6%). RESULTS: In all patients, there was a significant difference between scores on the MRCss and INCAT functional scales before and after treatment. At the moment, 11/30 (36.6%) patients are in clinical remission and are not receiving pathogenetic therapy. The median duration of remission is 48 months (30-84). The longest remission (84 months) was observed in a patient with the onset of CIDP at the age of 1 year 7 months. CONCLUSION: Early diagnosis of CIDP is important, since the disease is potentially curable; early administration of pathogenetic therapy provides a long-term favorable prognosis.

Outcome measures in pediatric chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION/AIMS: Objective outcome measures in children undergoing treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are lacking. The aim of the study was to record serial grip strength and motor nerve conduction studies to assess interval change. METHODS: This was a retrospective review of 16 children (8 females and 8 males; median age, 9.7 years; interquartile range, 6-13 years) with CIDP followed at a tertiary children's hospital from 2013 to 2021. Subjects were treated with intravenous immunoglobulin (IVIG). Right and left grip strength measurements were obtained at each clinic visit using a handheld dynamometer. Annual right median motor nerve conduction study data were recorded during the study period. RESULTS: Mean duration of follow-up was 2.9 years. Grip strength (right: 0.19 kg/month, p < 0.001; left 0.23 kg/month, p < 0.001) and median F-wave latencies (-0.23/month, p = 0.015) showed significant improvement over time. Akaike information criterion showed time + IVIG frequency <21 days as best fit for grip strength and distal compound muscle action potential amplitude. DISCUSSION: Our study results indicate serial grip strength measurements are a feasible and objective way to assess motor strength improvement in children with CIDP receiving immunotherapy.

Anti-MAG neuropathy: historical aspects, clinical-pathological correlations, and considerations for future therapeutical trials.

BACKGROUND: Patients with anti-MAG neuropathy present with distal demyelinating polyneuropathy, IgM monoclonal gammopathy, and elevated titers of anti-MAG antibodies. OBJECTIVE: This paper reviews what is known about the clinical presentation, course, pathophysiology, and treatment of anti-MAG neuropathy, with considerations for the design of therapeutic trials. METHODS: A literature review of the medical and scientific literature related to anti-MAG neuropathy, and the design of therapeutic clinical trials in peripheral neuropathy. RESULTS: Anti-MAG neuropathy can remain indolent for many years but then enter a progressive phase. Highly elevated antibody titers are diagnostic, but intermediate titers can also occur in chronic inflammatory demyelinating polyneuropathy (CIDP). The peripheral nerves can become inexcitable, thereby masking the demyelinating abnormalities. There is good evidence that the anti-MAG antibodies cause neuropathy. Reduction of the autoantibody concentration by agents that target B-cells was reported to result in clinical improvement in case series and uncontrolled trials, but not in controlled clinical trials, probably due to inadequate trial design. CONCLUSION: We propose that therapeutic trials for anti-MAG neuropathy include patients with the typical presentation, some degree of weakness, highly elevated anti-MAG antibody titers, and at least one nerve exhibiting demyelinating range abnormalities. Treatment with one or a combination of anti-B-cell agents would aim at reducing the autoantibody concentration by at least 60%. A trial duration of 2 years may be required to show efficacy. The neuropathy impairment score of the lower extremities (NIS-LL) plus the Lower Limb Function (LLF) score would be a suitable primary outcome measure.

ANTECEDENTES: Pacientes com neuropatia anti-MAG apresentam polineuropatia desmielinizante distal, gamopatia monoclonal IgM e títulos elevados de anticorpos anti-MAG. OBJETIVO: Este artigo revisa o que se sabe sobre a apresentação clínica, curso, fisiopatologia e tratamento da neuropatia anti-MAG, com considerações para o desenho de ensaios terapêuticos. MéTODOS: Revisão bibliográfica da literatura médica e científica relacionada à neuropatia anti-MAG e desenho de ensaios clínicos terapêuticos em neuropatia periférica. RESULTADOS: A neuropatia anti-MAG pode permanecer indolente durante muitos anos, mas depois entra numa fase progressiva. Títulos de anticorpos altamente elevados são diagnósticos, mas títulos intermediários também podem ocorrer na polineuropatia desmielinizante inflamatória crônica (CIDP). Os nervos periféricos podem tornar-se inexcitáveis, mascarando, assim, as anomalias desmielinizantes. Há boas evidências de que os anticorpos anti-MAG causam a neuropatia. Foi relatado que a redução da concentração de autoanticorpos por agentes direcionados às células B resultou em melhora clínica em séries de casos e ensaios não controlados, mas não em ensaios clínicos controlados, provavelmente devido ao desenho inadequado dos ensaios. CONCLUSãO: Propomos que os ensaios terapêuticos para neuropatia anti-MAG incluam pacientes com apresentação típica, algum grau de fraqueza, títulos de anticorpos anti-MAG altamente elevados e pelo menos um nervo exibindo anormalidades na faixa desmielinizante. O tratamento com um ou uma combinação de agentes anticélulas B teria como objetivo reduzir a concentração de autoanticorpos em pelo menos 60%. Pode ser necessária uma duração de ensaio de 2 anos para demonstrar eficácia. A pontuação de comprometimento da neuropatia das extremidades inferiores (NIS-LL) mais a pontuação da função dos membros inferiores (LLF) seria uma medida de resultado primário adequada.

Prevalence, Clinical Profiles, and Prognosis of CIDP in Japanese Nationwide Survey: Analyses of 1,257 Diagnosis-Confirmed Patients.

BACKGROUND AND OBJECTIVES: To investigate the current epidemiology, clinical profile, and treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) using a nationwide survey in Japan. METHODS: We conducted a nationwide survey using an epidemiologic method established in 2021. Questionnaire sheets were sent to the hospital departments of neurology and pediatric neurology throughout Japan. A primary questionnaire was used to determine the number of patients and their prevalence, and a second questionnaire was used to collect detailed clinical information. RESULTS: The primary survey showed that the estimated number of patients with CIDP was 4,180, with a prevalence of 3.3 per 100,000 persons. In the secondary survey, detailed clinical data were available for 1,257 patients. The male-to-female ratio was 1.5:1, and the median age at onset was 52 years. Typical CIDP was the most frequent subtype (52%), followed by distal (17%) and multifocal/focal CIDP (17%). Initial treatments included immunoglobulin therapy (72%), corticosteroids (15%), and others (13%). Among patients with CIDP, 78% had a progressive/relapsing course, 14% did not respond to first-line treatments, and 18% could not walk independently at the last visit. Among the subtypes, typical CIDP had the most severe disability before treatment (44% of patients could not walk independently). However, they showed a more favorable response to treatment than those with distal or multifocal CIDP. In the subgroup analyses, logistic regression analyses showed that younger age at onset, no muscle atrophy, and abnormal median-normal sural sensory nerve responses were associated with a higher probability of independent walking. DISCUSSION: Our study represents the largest cohort study on CIDP to demonstrate the current epidemiologic and clinical status of CIDP in Japan. Clinical subtypes seem to be associated with different treatment responses and outcomes; therefore, an appropriate treatment strategy according to the pathophysiology of each subtype is required to improve the prognosis of CIDP.

A study on the role of serum uric acid in differentiating acute inflammatory demyelinating polyneuropathy from acute-onset chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: Clinical symptoms and laboratory indices for acute inflammatory demyelinating polyneuropathy (AIDP), a variant of Guillain-Barré syndrome, and acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) were analyzed to identify factors that could contribute to early differential diagnosis. METHODS: A retrospective chart review was performed on 44 AIDP and 44 A-CIDP patients looking for any demographic characteristics, clinical manifestations or laboratory parameters that might differentiate AIDP from acutely presenting CIDP. RESULTS: In Guillain-Barré syndrome patients (N = 63), 69.84% (N = 44) were classified as having AIDP, 19.05% (N = 12) were found to have acute motor axonal neuropathy, 6.35% (N = 4) were found to have acute motor and sensory axonal neuropathy, and 4.76% (N = 3) were found to have Miller Fisher syndrome. Serum uric acid (UA) was higher in A-CIDP patients (329.55 ± 72.23 µmol/L) than in AIDP patients (221.08 ± 71.32 µmol/L) (p = 0.000). Receiver operating characteristic analyses indicated that the optimal UA cutoff was 283.50 µmol/L. Above this level, patients were more likely to present A-CIDP than AIDP (specificity 81.80%, sensitivity 81.80%). During the follow-up process, serum samples were effectively collected from 19 AIDP patients during the rehabilitation phase and 28 A-CIDP patients during the remission stage, and it was found that UA levels were significantly increased in A-CIDP (remission) (298.9 ± 90.39 µmol/L) compared with AIDP (rehabilitation) (220.1 ± 108.2 µmol/L, p = 0.009). CONCLUSION: These results suggest that serum UA level can help to differentiate AIDP from A-CIDP with high specificity and sensitivity, which is helpful for early diagnosis and guidance of treatment.

Impact of 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria on diagnosis and therapy of chronic inflammatory demyelinating polyradiculoneuropathy variants.

BACKGROUND AND PURPOSE: There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated. METHODS: We applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP. RESULTS: According to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did. CONCLUSIONS: The 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients.

Anti-pan-neurofascin nodopathy: cause of fulminant neuropathy.

Autoimmune nodopathies are inflammatory diseases of the peripheral nervous system with clinical and neurophysiological peculiar characteristics. In this nosological category, we find patients with autoantibodies against Neurofascin 140/186 and 155, Contactin1, and Caspr1 directed precisely towards nodal and paranodal structures. These antibodies are extremely rare and cause severe clinical symptoms. We describe the clinical case of a patient with autoimmune nodopathy caused by the coexistence of anti-neurofascin (NF) 186/140 and 155, characterized by progressive weakness in all limbs leading to tetraplegia, involving cranial nerves, and respiratory insufficiency. Response to first-line treatments was good followed by rapid dramatic clinical relapse. There are few reported cases of anti-pan NF neuropathy in the literature, and they present a clinical phenotype similar to our patient. In these cases, early recognition of clinical red flags of nodopathies and serial neurophysiological studies can facilitate the diagnosis. However, the severe clinical relapse suggests a possible early use of immunosuppressive therapies for this rare category of patients.

Serum Neurofilament and Free Light Chain Levels in Patients Undergoing Treatment for Chronic Inflammatory Demyelinating Polyneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder affecting the peripheral nervous system. Despite the established diagnostic criteria, monitoring disease activity and treatment remains challenging. To address this limitation, we investigated serum neurofilament light chain (sNfL) and serum free light chains (sFLCs) as potential biomarkers. A total of 32 CIDP patients undergoing immunoglobulin therapy and 32 healthy controls enrolled in the present study, and agreed to have their blood plasma sNfL and sFLCs analyzed, while CIDP severity was assessed through the modified Rankin Scale (mRS) and the Overall Neuropathy Limitations Scale (ONLS). In line with the immunoglobulin treatment aimed at limiting neuronal damage administered to the majority of patients, sNfL levels did not exhibit significant differences between the two groups. However, CIDP patients showed significantly elevated sFLC and sFLC ratios, while the marker levels did not correlate with the clinical scores. The study confirms the potential of sFLCs as a sensitive biomarker of inflammatory processes in CIDP. Additionally, the present study results regarding neurofilaments strengthen the role of sNfL in monitoring CIDP treatments, confirming the effectiveness of immunoglobulin therapy. Overall, our results demonstrate how combining these markers can lead to better patient characterization for improved treatment.

Anti-neurofascin 155 Antibody-positive Neuropathy in a Human Immunodeficiency Virus-infected Patient.

Human immunodeficiency virus (HIV)-associated neuropathy is a common complication of HIV infection and has several clinical subtypes. HIV-associated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating neuropathy whose clinical features are known to differ from those of CIDP in the HIV-uninfected population. We herein report a case of CIDP in an HIV-infected patient who was finally diagnosed with anti-neurofascin 155 (NF155) antibody-positive neuropathy. The clinical features, including clinical findings and therapeutic responses, were typical of paranodal antibody-mediated neuropathy. To our knowledge, this is the first case of anti-NF155 antibody-associated neuropathy in an HIV-infected patient.

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.

Tendon-Sparing Extraocular Muscle Enlargement Associated With Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory, sensorimotor polyneuropathy. It has presented with a variety of orbital and neuro-ophthalmic manifestations, including cranial nerve hypertrophy and a single case of extraocular muscle enlargement. The authors present a second case of tendon-sparing, extraocular muscle enlargement, resulting in new-onset diplopia and strabismus in a teenager with CIDP. The workup ruled out alternative causes of extraocular muscle enlargement, such as hyperthyroidism, inflammation, or malignancy. As with other cases of CIDP, management involved a combination of immunoglobulin therapy and anti-inflammatory medications. The patient experienced resolution of his symptoms, and radiologic improvement was noted in the muscle enlargement. As many CIDP patients have a favorable treatment response and long-term prognosis, awareness of this rare disease with an early and accurate diagnosis is important.

Repeated Acute Exacerbations of Chronic Inflammatory Demyelinating Polyradiculoneuropathy Accompanied by Pain and Swelling in Distal Extremities.

An 81-year-old man experienced acute progression of weakness in the extremities accompanied by a fever, tenderness, and swelling in distal parts of the extremities. He had flaccid tetraparesis with fasciculations and general hyporeflexia. Nerve conduction studies indicated demyelinating sensorimotor neuropathy. A cerebrospinal fluid examination revealed elevated proteins without pleocytosis. Immunological treatments were effective, but his symptoms exhibited repeated relapse and remission phases. He was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with an acute onset. The highlight of this case is pain with inflammatory reaction recognized as red flags of CIDP, with the clinical course and electrophysiological findings compatible with CIDP.

Prognostic value of neurofilament light in blood in patients with polyneuropathy: A systematic review.

Neurofilament light protein (NfL) is a part of the neuronal skeleton, primarily expressed in axons, and is released when nerves are damaged. NfL has been found to be a potential diagnostic biomarker in different types of polyneuropathies. However, whether NfL levels can be used as a predictor for the risk of disease progression is currently less understood. We searched MEDLINE (PubMed), Embase, Cochrane Library, and Web of Science Searches and included longitudinal studies with a baseline and follow-up examination of adult patients with polyneuropathy and NfL measured in blood. Twenty studies investigating NfL as a predictor of disease progression were identified, examining eight polyneuropathy subtypes. The results from studies in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) patients were divergent, with two out of five studies finding a significant association between NfL levels and clinical outcomes. Meta-analysis of the three Guillian-Barré Syndrome (GBS) studies found higher odds for the inability to run after 1 year in patients with high levels of NfL (odds ratio 2.18, 95% confidence interval 1.04-4.56). Results from studies examining other subacute or chronic polyneuropathies like Charcot-Marie-Tooth (CMT) varied in study design and results. Our findings suggest NfL can be used as a predictor of disease progression, particularly in polyneuropathies such as CIDP and GBS. However, NfL may not serve as a reliable and cost-effective biomarker for slowly progressive polyneuropathies like CMT. Future standardized studies considering NfL as a prognostic blood biomarker in patients with different types of polyneuropathies are warranted.

Serum neurofilament light chain does not detect self-reported treatment-related fluctuations in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: Serum neurofilament light chain (sNfL) is a marker for axonal degeneration. Patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) often report a fluctuation of symptoms throughout one treatment cycle with intravenous immunoglobulins (IVIG). The aim of this study was to determine whether sNfL is suitable to quantify patient-reported symptom fluctuations. METHODS: Twenty-nine patients with the diagnosis of CIDP or a CIDP-variant under treatment with IVIG were recruited in this study and underwent examination before IVIG infusion, in the middle of the treatment interval, and before their next IVIG infusion. Patients were surveyed regarding symptom fluctuations at the last visit and divided into two groups: those with and without fluctuations of symptoms. At the first visit, sociodemographic and disease-specific data were collected. Clinical scores were assessed at every examination. sNfL values were compared between both groups at the different time points after conversion into Z-scores-adjusted for age and body mass index. RESULTS: Patients with CIDP show elevated sNfL Z-scores (median at baseline: 2.14, IQR: 1.0). There was no significant change in sNfL Z-scores or questionnaire scores within the treatment cycle in either group. There was no significant difference in sNfL levels between the patients with and without symptom fluctuations. CONCLUSIONS: CIDP patients show elevated sNfL levels. However, sNfL is not suitable to reflect patient-reported fluctuations of symptoms. This indicates that symptom fluctuations during treatment with IVIG in patients with CIDP are not caused by a neuroaxonal injury. Furthermore, repeated sNfL measurements within one treatment cycle with IVIG seem to have no benefit for symptom monitoring.

Validation of elevated levels of interleukin-8 in the cerebrospinal fluid, and discovery of new biomarkers in patients with GBS and CIDP using a proximity extension assay.

Background: Biomarkers for diagnosis of inflammatory neuropathies, assessment of prognosis, and treatment response are lacking. Methods: CSF and EDTA plasma from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), healthy controls (HC) and disease controls were analyzed with Olink multiplex proximity extension assay (PEA) from two independent cohorts. Levels of interleukin-8 (IL8) were further analyzed with ELISA in patients with GBS, CIDP, paraproteinemia-related demyelinating polyneuropathy (PDN), multifocal motor neuropathy (MMN), HC and disease controls. ROC analysis was performed. Outcome was measured with the GBS-disability score (GBS-ds) or Inflammatory Neuropathy Cause and Treatment (INCAT) score. Results: In CSF, multiplex PEA analysis revealed up-regulation of IL8 in GBS compared to CIDP and HC respectively, and CIDP compared to HC. In addition, levels of IL2RA were upregulated in GBS compared to both HC and CIDP, SELE in GBS compared to HC, and ITGAM, IL6, and NRP1 in GBS compared to CIDP. In plasma, levels of MMP3, THBD and ITGAM were upregulated in CIDP compared to HC. Validation of multiplex IL8 results using ELISA, revealed increased levels of IL8 in CSF in patients with GBS and CIDP versus HC and non-inflammatory polyneuropathies (NIP) respectively, as well as in PDN versus NIP and HC. Levels of IL8 in CSF correlated with impairment in the acute phase of GBS as well as outcome at 6-months follow up. Conclusion: IL8 in CSF is validated as a diagnostic biomarker in GBS and CIDP, and a prognostic biomarker in GBS. Multiplex PEA hereby identifies several potential biomarkers in GBS and CIDP.

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.