OBJECTIVE: Nerve enlargement has been described in autoimmune nodopathy and chronic inflammatory demyelinating polyneuropathy (CIDP). However, comparisons of the distribution of enlargement between autoimmune nodopathy and CIDP have not been well characterized. To fill this gap, we explored differences in the ultrasonographic and electrophysiological features between autoimmune nodopathy and CIDP.
METHODS: Between March 2015 and June 2023, patients fulfilling diagnostic criteria for CIDP were enrolled; among them, those with positive antibodies against nodal-paranodal cell-adhesion molecules were distinguished as autoimmune nodopathy. Nerve ultrasound and nerve conduction studies (NCS) were performed.
RESULTS: Overall, 114 CIDP patients and 13 patients with autoimmune nodopathy were recruited. Cross-sectional areas (CSA) at all sites were larger in patients with CIDP and autoimmune nodopathy than in healthy controls. CSAs at the roots and trunks of the brachial plexus were significantly larger in patients with anti-neurofascin-155 (NF155), anti-contactin-1 (CNTN1), and anti-contactin-associated protein 1 (CASPR1) antibodies than in CIDP patients. The patients with anti-NF186 antibody did not have enlargement in the brachial plexus. NCS showed more frequent probable conduction block at Erb\'s point in autoimmune nodopathy than in CIDP (61.9% vs. 36.6% for median nerve, 52.4% vs. 39.5% for ulnar nerve). Markedly prolonged distal motor latencies were also present in autoimmune nodopathy.
CONCLUSIONS: Patients with autoimmune nodopathies had distinct distributions of peripheral nerve enlargement revealed by ultrasound, as well as distinct NCS patterns, which were different from CIDP. This suggests the potential utility of nerve ultrasound and NCS to supplement clinical characteristics for distinguishing nodopathies from CIDP.

UNASSIGNED: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous but treatable immune-mediated neuropathy. Ofatumumab (OFA) is a fully human anti-CD20 monoclonal antibody that has shown promising efficacy in central demyelinating diseases, such as multiple sclerosis (MS). However, there is a lack of studies on the usage of OFA in peripheral demyelinating diseases, particularly CIDP. A case of relapsed and refractory CIDP with an ineffective response to conventional immunotherapy and intolerance to rituximab (RTX) but a positive response to subcutaneous injections of OFA is presented.
UNASSIGNED: The patient, a 46-year-old man diagnosed with CIDP, received high-dose intravenous methylprednisolone, intravenous immunoglobulin (IVIG), and plasma exchange(PE) during the acute phase of the disease, and long-term oral administration of prednisone, azathioprine (AZA), and mycophenolate mofetil (MMF) during the remission phase. However, the patient suffered six relapses over a five-year period, and because of these, along with an ineffective response to conventional immunotherapy, and intolerance to RTX, subcutaneous injections of OFA were selected as a prophylactic treatment against relapses. After a total of six injections of OFA, CD19+B cells were substantially depleted. The patient has been followed for more than 23 months without relapse.
UNASSIGNED: This case demonstrates the effectiveness and good tolerability of OFA in the treatment of relapsed and refractory CIDP. Further studies are needed to investigate the efficacy and safety of OFA in patients with relapsed and refractory CIDP, especially in those who have shown an ineffective response to conventional immunotherapy and are intolerant to RTX.

OBJECTIVE: Somatosensory evoked potentials (SSEPs) are described as a supportive tool to diagnose chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); however, there is a lack of studies determining the effectiveness of SSEPs in monitoring the clinical course of individuals with this condition. The aims of this study are to evaluate the utility of SSEPs in monitoring patients with CIDP and to assess their association with clinical outcomes following immunomodulatory therapy.
METHODS: This was a single-center retrospective observational study that included patients who met European Federation of Neurological Societies and Peripheral Nerve Society criteria for CIDP between 2018 and 2023. SSEPs were performed at diagnosis and during follow-up after the start of immunomodulatory treatment. Fisher\'s exact test was employed to assess the association between clinical improvement and SSEP improvement.
RESULTS: Eighteen patients were included in the study. Ten patients had a typical CIDP pattern and 11 were male. In 17, SSEPs were abnormal prior to the start of immunomodulatory treatment. In patients who showed clinical improvement with immunomodulatory therapy, we observed that 15/17 had partial or complete improvement in SSEPs. Patients who showed no clinical improvement with first-line treatment exhibited worsening SSEPs. There was a significant association between clinical and SSEPs improvement (p = 0.009).
CONCLUSIONS: We observed a positive association between improvement in SSEPs and clinical improvement in patients with CIDP. Our data suggest that SSEPs may be useful for monitoring the clinical course of patients with CIDP, but additional, larger studies are needed.

Immune-mediated demyelinating polyneuropathies (IMDPs) are rare disorders in which dysregulated adaptive immune responses cause peripheral nerve demyelinating inflammation and axonal injury in susceptible individuals. Despite significant advances in understanding IMDP pathogenesis guided by patient data and representative mammalian models, specific therapies are lacking. Significant knowledge gaps in IMDP pathogenesis still exist, e.g. precise antigen(s) and mechanisms that initially trigger immune system activation and identification of large population disease susceptibility factors. The initial directional cues for antigen-specific effector or autoreactive leukocyte trafficking into peripheral nerves are also unknown. An overview of current animal models, with emphasis on the experimental autoimmune neuritis and spontaneous autoimmune peripheral polyneuropathy models, is provided. Insights on the initial directional cues for peripheral nerve tissue specific autoimmunity using a novel Major Histocompatibility Complex class II conditional knockout mouse strain are also discussed, suggesting an essential research tool to study cell- and time-dependent adaptive immunity in autoimmune diseases.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare immune-mediated neuropathy for which there is no clearly identified risk factor. The present study identified rare variants in the FBXO38 gene in three familial cases of CIDP with response to corticosteroids in three generations with incomplete penetrance, and in an unrelated fourth case with diffuse nerve hypertrophy. FBXO38 may be involved in the regulation of the immunity mediated by CD8 T cells, which have an important role in CIDP pathophysiology, through PD1 degradation. Considering these findings, FBXO38 should be investigated as a potential genetic factor in larger cohorts of patients with CIDP.

BACKGROUND: To investigate Ranvier\'s autoantibodies prevalence and isotypes in various peripheral neuropathy variants, compare clinical features between seronegative and seropositive patients, and elucidate immune mechanisms underlying antibody generation.
METHODS: Antibodies against anti-neurofascin-155 (NF155), NF186, contactin-1 (CNTN1), CNTN2, contactin-associated protein 1 (CASPR1), and CASPR2 were identified through cell-based assays. Plasma cytokines were analyzed in anti-NF155 antibody-positive chronic inflammatory demyelinating polyneuropathy (NF155+ CIDP) and Ranvier\'s antibodies-negative CIDP (Ab- CIDP) patients using a multiplexed fluorescent immunoassay, validated in vitro in a cell culture model.
RESULTS: In 368 plasma samples, 50 Ranvier\'s autoantibodies were found in 45 individuals, primarily in CIDP cases (25 out of 69 patients) and in 10 out of 122 Guillain-Barré syndrome patients. Anti-NF155 and CNTN1-IgG were exclusive to CIDP. Fourteen samples were NF155-IgG, primarily IgG4 subclass, linked to CIDP features including early onset, tremor, sensory disturbance, elevated CSF protein, prolonged motor latency, conduction block, and poor treatment response. NF155-IgG had low sensitivity (20.28%) but high specificity (100%) for CIDP, rising to 88.88% with tremor and prolonged motor latency. Cytokine profiling in NF155+ CIDP revealed distinct immune responses involving helper T cells, toll-like receptor pathways. Some NF155+ CIDP patients had circulating NF155-specific B cells producing NF155-IgG without antigen presence, suggesting therapeutic potential.
CONCLUSIONS: The study emphasizes the high specificity and sensitivity of NF155-IgG for diagnosing CIDP characterized by distinctive features. Further investigation into circulating NF155-specific B cell phenotypes may pave the way for B cell directed therapy.

There is increasing evidence of neurological involvement in patients with coronavirus disease. Reports of neurological manifestations include altered mental status, Guillain-Barré syndrome (GBS) and its forms, encephalopathy, psychosis, neurocognitive (dementia) syndrome, ischemic strokes, intracerebral hemorrhage, and acute transverse myelitis. We present three patients with rare neurological manifestations of the COVID-19 disease, with a special focus on rehabilitation in a health resort setting. Outcomes were evaluated based on neurological examination and the modified Barthel index. We highlight the importance of an interdisciplinary approach to reduce disability and improve functionality and quality of life.

UNASSIGNED: According to the latest guidelines on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), patients with CIDP with anti-neurofascin 155 (NF155) antibodies are referred to as autoimmune nodopathy (AN), an autoimmune disorder distinct from CIDP. We aimed to compare the clinical data of patients with AN with anti-NF155 antibodies with those of anti-NF155 antibodies-negative patients with CIDP, and to summarize the clinical characteristics of patients with AN with anti-NF155 antibodies.
UNASSIGNED: Nine patients with AN with anti-NF155 antibodies and 28 serologically negative patients with CIDP were included in this study. Diagnosis was made according to the diagnostic criteria in the European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) guidelines on CIDP published in 2021. Demographics, clinical manifestations, electrophysiological examination, cerebrospinal fluid (CSF) tests, and response to treatment were retrospectively analyzed.
UNASSIGNED: Compared with serologically negative patients with CIDP, those patients with AN with anti-NF155 antibodies were younger (p=0.007), had a younger onset age (p=0.009), more frequent ataxia (p=0.019), higher CSF protein levels (p=0.001), and more frequent axon damage in electrophysiology (p=0.025). The main characteristics of patients with AN with anti-NF155 antibodies include younger age and onset age, limb weakness, sensory disturbance, ataxia, multiple motor-sensory peripheral neuropathies with demyelination and axonal damage on electrophysiological examination, markedly elevated CSF protein levels, and varying degrees of response to immunotherapy.
UNASSIGNED: Patients with AN with anti-NF155 antibodies differed from serologically negative patients with CIDP in terms of clinical characteristics. When AN is suspected, testing for antibodies associated with the nodes of Ranvier is essential for early diagnosis and to guide treatment.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a most common chronic immune-mediated demyelinating neuropathy, and includes a number of clinical subtypes. The major phenotype is \"typical CIDP\", which is characterized by symmetric polyneuropathy and \"proximal and distal\" muscle weakness. During the historical changes in the concept of CIDP, multifocal motor neuropathy, anti-myelin-associated glycoprotein (MAG) neuropathy, and autoimmune nodopathy have been excluded. Currently CIDP is considered as a syndrome including typical CIDP and CIDP variant such as distal CIDP and multifocal CIDP. In 2021, the international guideline of diagnosis and treatment for CIDP, European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) Guideline, was published. This review article introduces the putline of the guideline with medical-social situation in Japan. The diagnosis of CIDP is based on (1) phenotype of typical CIDP or variant, (2) electrophysiologic evidence of peripheral nerve demyelination, and (3) exclusion criteria. The first-line treatments are corticosteroids or immunoglobulin therapy, and plasma exchange should be considered if the 2 treatments were not effective sufficiently. This guideline recommends intravenous or subcutaneous immunoglobulin as a maintenance therapy, and suggests other immune-suppressive agents. In the near future, new treatment with biologics, such as monoclonal antibodies against neonatal Fc receptors, complements, and CD19/20 will be approved.

Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid arthritis. We conducted a systematic literature review on the role of cytokines and chemokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Ovid Medline, EMBASE and Web of Science were searched until August 31, 2022 for human studies investigating cytokines levels in CIDP or MMN. Fifty-five articles on 1061 CIDP patients and 86 MMN patients were included, with a median of 18 patients per study (range 3-71). Studies differed in the inclusion criteria, type of assay, manufacturer, control subjects, and tested biological material. Only a minority of studies reported data on disease activity. Interleukin (IL)-6, IL-17, CXCL10, and tumor necrosis factor alpha (TNF-α), were elevated in CIDP compared to controls in most of the studies. IL-6 and TNF-α levels are also correlated with disability. In MMN patients, IL-1Ra was elevated in the majority of the reports. While acknowledging the challenges in comparing studies and the various limitations of the studies, including small patient numbers, particularly in MMN, our review suggests that IL-6, IL-17, CXCL10, and TNF-α might play a role in CIDP pathogenesis. Larger studies are needed in MMN.