Characteristics and outcome of chronic inflammatory demyelinating polyradiculoneuropathy patients according to their diagnostic certainty based on the 2021 EAN/PNS criteria.

INTRODUCTION: To describe the clinical characteristics and long term outcome of CIDP patients according to 2021 EAN/PNS diagnostic certainty categories. METHODS: We reviewed clinical data, response to treatment, cerebrospinal fluid examination, and nerve conduction studies parameters of 39 adult "CIDP" and 24 "possible CIDP" patients. Data were collected at diagnosis and after one (T1), two (T2), three (T3) and five years (T5). RESULTS: At diagnosis, "possible CIDP" patients' phenotypes were more atypical (especially focal/multifocal, p < .01) and "CIDP" patients had a higher NIS and INCAT scores (p = .08 and 0.08). Compared to baseline: median NIS score decreased in "CIDP" and was stable in "possible CIDP" patients at T1 (p < .05), T2 (p < .05) and T3 (p < .01); median MRC score slightly increased in "CIDP" and was stable in "possible CIDP" patients at T2 (p < .05); and INCAT disability scale slightly decreased in "CIDP" and was stable in "possible CIDP" patients at T3 (p < .05). The proportion of moderate to severely disabled (mRS > 2) patients in "possible CIDP" group was higher than in "CIDP" group (not significant). "CIDP" patients had a better objective response to immunotherapy (59 % responders) than "possible CIDP" patients (29 % responders, p < .05), especially among typical CIDP patients (86 % of responders in "CIDP" versus 33 % of responders in "possible CIDP" patients, p < .05). CONCLUSION: "CIDP" patients had a more severe neuropathy, estimated with the NIS and INCAT scores, and "possible CIDP" patients had a more atypical phenotype at baseline. Our data suggest that long-term patient outcome and response to immunotherapy is better in "CIDP" than "possible CIDP".

Antibodies in immune-mediated peripheral neuropathies. Where are we in 2024?

Over the past 30 years, about 20 antibodies have been identified in immune-mediated neuropathies, recognizing membrane or intracellular proteins or glycolipids of neuron and Schwann cells. This article reviews the different methods used for their detection, what we know about their pathogenic role, how they have helped identify several disorders, and how they are essential for diagnosis. Despite sustained efforts, some immune-mediated disorders still lack identified autoantibodies, notably the classical form of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. The reasons for this are discussed. The article also tries to determine potential future developments in antibody research, particularly the use of omic approaches and the search for other types of biomarkers beyond diagnostic ones, such as those that can identify patients who will respond to a given treatment.

Charcot-Marie-Tooth type 2CC misdiagnosed as Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

BACKGROUND AND AIMS: Charcot-Marie-Tooth (CMT) is a heterogeneous group of genetic neuropathies and is typically characterized by distal muscle weakness, sensory loss, pes cavus and areflexia. Herein we describe a case of CMT2CC presenting with proximal muscle weakness and equivocal electrophysiological features, that was misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). CASE REPORT: A 30-year-old woman complained of proximal muscle weakness with difficulty climbing stairs. Neurological examination showed weakness in lower limb (LL) muscles, that was marked proximally and mild distally, and absence of deep tendon reflexes in the ankles. Nerve conduction studies (NCS) showed sensory-motor neuropathy with non-uniform NC velocity and a partial conduction block (CBs) in peroneal nerve and tibial nerves. Thus, a diagnosis of CIDP was entertained and the patient underwent ineffective treatment with intravenous immunoglobulins. At electrophysiological revaluation CB in peroneal nerve was undetectable as also distal CMAP had decreased whereas the CBs persisted in tibial nerves. Hypothesizing a hereditary neuropathy, we examined the proband's son, who presented mild weakness of distal and proximal muscles at lower limbs. Neurophysiological investigation showed findings consistent with an intermediate-axonal electrophysiological pattern. A targeted-NGS including 136 CMT genes showed the heterozygous frameshift mutation (c.3057dupG; p.K1020fs*43) in the NEFH gene, coding for the neurofilament heavy chain and causing CMT2CC. INTERPRETATION: Diagnosis of a genetic neuropathy may be challenging when clinical features are atypical and/or electrophysiological features are misleading. The most common misdiagnosis is CIDP. Our report suggests that also CMT2CC patients with proximal muscle weakness and equivocal electrophysiological features might be misdiagnosed as CIDP.

Effects of oral steroid sparing immunosuppressive drugs in long term maintenance treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

Background and objectives: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired treatable autoimmune disorder. Due to limited availability and affordability of IV immunoglobulins and therapeutic plasma exchange in Pakistan, oral immunosuppressive drugs (ISDs) are used despite limited role in literature. The study aimed to determine the response to ISDs in CIDP patients by assessing the frequency of remission, reduction of disability using a neuropathy related disability score called Inflammatory Neuropathy Cause and Treatment score (or INCAT score), as well as reduction in steroid maintenance dose. Methods: The retrospective observational study of six months duration (May to October, 2020) was carried out in Aga Khan University Hospital, Karachi, Pakistan. Medical record of all the patients with idiopathic CIDP taking oral ISDs in last five years was selected which included bio-data, clinical signs and symptoms, medication details, and INCAT scores. Descriptive statistics were described i.e. frequency, percentages, mean/standard deviation using Microsoft Excel v.2021. Results: Out of thirteen patients, Azathioprine was used in nine, Mycophenolate mofetil in two and Cyclosporine in two, with remission (INCAT score improvement ≥ 1) achieved in eight, one and zero patients respectively. Duration of ISDs ranged from three to twenty-four months (average 15.8 months). Patients with monoclonal paraproteinemia and prior exposure to ISDs had a poor response to the introduction of subsequent ISDs. Conclusion: The study describes preliminary experience of the potential role of relatively cheaper and more convenient oral ISDs (especially Azathioprine) as an alternative or sparing agent to first line agents for CIDP and sets the stage for larger scale studies and randomized controlled trials.

Hematopoietic stem cell transplantation (HSCT) for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): Is it CIDP?

Autologous hematopoietic stem cell transplantation (HSCT) is associated with 5-year treatment-free remissions in approximately 80% of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who failed or were dependent on intravenous immunoglobulin and or plasmapheresis. Autologous HSCT was associated with significant improvement in strength, independent ambulation, quality of life, nerve conduction velocity, and compound muscle action potential amplitude. The results of HSCT are dependent on proper patient selection, i.e., the right diagnosis and the right stage of the disease. An important caveat is that a significant number of patients with a CIDP diagnostic label are found upon further workup have a peripheral neuropathy of another etiology. Patients undergoing HSCT for CIDP should be reevaluated before HSCT to confirm the diagnosis and those who fail HSCT should be reevaluated for a diagnosis other than CIDP.

Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single-dose riliprubart, an anti-C1s humanized monoclonal antibody in East-Asian adults: results from a Phase 1, randomized, open-label trial.

OBJECTIVES: This Phase 1 trial was planned to investigate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of a single dose of riliprubart in healthy East-Asian adult participants. METHODS: A single-center, parallel-group, randomized, open-label, single-dose study was performed to evaluate the PK, PD, safety, and tolerability of riliprubart (50 mg/kg intravenous [IV] or 600 mg subcutaneous [SC]) in 37 healthy East-Asian (Chinese, Japanese, and Korean) participants. RESULTS: Riliprubart was slowly absorbed after SC administration (median tmax: 7.01-10.48 days) and showed a long half-life after IV or SC administration (mean: 9.52-11.0 weeks), with a bioavailability of 74.6% after SC administration. The PD profiles, which are evaluated by classical complement pathway activity or CH50, were similar and largely overlapped across East-Asian participants after a single IV or SC dose. Riliprubart was safe and well tolerated in participants following a single IV or SC dose. CONCLUSIONS: Riliprubart was safe and well tolerated and demonstrated favorable PK and PD profiles in healthy East-Asian participants following a single IV or SC dose. These results are comparable to first-in-human study results from non-East-Asian participants and support the same dosing regimen of riliprubart for global simultaneous clinical development. CLINICAL TRIAL REGISTRATION: This trial is registered at https://cris.nih.go.kr (identifier: KCT0006571).

Serological indication of chronic inflammatory demyelinating polyneuropathy as an extrahepatic manifestation of hepatitis E virus infection.

Guillain-Barré syndrome and neuralgic amyotrophy have been associated with hepatitis E virus (HEV) genotype 3 infections, while myasthenia gravis (MG) has been associated with HEV genotype 4 infections. However, whether chronic inflammatory demyelinating polyneuropathy (CIDP) is associated with HEV infections has not been conclusively clarified yet. 102 CIDP patients, 102 age- and sex-matched blood donors, 61 peripheral neuropathy patients (non-CIDP patients), and 26 MG patients were tested for HEV and anti-HEV IgM and IgG. Sixty-five of the 102 (64%) CIDP patients tested positive for anti-HEV IgG and one (1%) for anti-HEV IgM. No other patient tested positive for ati-HEV IgM. In the subgroup of CIDP patients with initial diagnosis (without previous IVIG treatment), 30/54 (56%) tested positive for anti-HEV IgG. Anti-HEV rates were significantly lower in blood donors (28%), non-CIDP peripheral neuropathy patients (20%), and MG patients (12%). No subject tested positive for HEV viremia. CSF tested negative for in 61 CIDP patients (54 patients with primary diagnosis). The development of CIDP but not non-CIDP polyneuropathy may be triggered by HEV exposure in an HEV genotype 3 endemic region. The increased anti-HEV seroprevalence in CIDP patients is not a consequence of IVIG therapy.

Efficacy and Safety of Rescue Treatment with Plasma Exchange in Patients with Acute Inflammatory Neurological Disorders: A Single Center Experience.

BACKGROUND: Therapeutic plasma exchange (TPE) is a highly effective rescue treatment for patients with acute exacerbation of neuroimmunological disease that removes circulating autoantibodies and inflammatory components from the bloodstream. The aims of this study are to explore the safety and the effectiveness of TPE in patients with autoimmune neurological disorders. METHODS: We retrospectively evaluated the frequency of adverse events (AEs) and the effectiveness of TPE using the modified Ranking Scale (mRS) in patients with acute neurological flares who underwent TPE at the University Hospital of Palermo. RESULTS: Of 59 patients, the majority underwent TPE due to multiple sclerosis (MS) relapse. In 23.7% of cases, TPE was performed before obtaining a definite diagnosis due to the severity of the clinical presentation. After TPE, the mRS score was globally reduced (p < 0.0001), and this effect was marked in patients with MS, Guillain-Barré syndrome, and myasthenia gravis crisis but not in those with paraneoplastic syndromes. Circulating pathogenetic antibodies, younger age, and the early use of TPE were factors strongly associated with TPE effectiveness. The overall safety profile of TPE was satisfactory with an AE frequency of 15%. CONCLUSIONS: These results highlight the early use of TPE in patients with circulating pathogenetic antibodies as well as its favorable safety profile.

Preventing long-term disability in CIDP: the role of timely diagnosis and treatment monitoring in a multicenter CIDP cohort.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory disease affecting the peripheral nerves and the most frequent autoimmune polyneuropathy. Given the lack of established biomarkers or risk factors for the development of CIDP and patients' treatment response, this research effort seeks to identify potential clinical factors that may influence disease progression and overall treatment efficacy. METHODS: In this multicenter, retrospective analysis, we have screened 197 CIDP patients who presented to the University Hospitals in Düsseldorf, Berlin, Cologne, Essen, Magdeburg and Munich between 2018 and 2022. We utilized the respective hospital information system and examined baseline data with clinical examination, medical letters, laboratory results, antibody status, nerve conduction studies, imaging and biopsy findings. Aside from clinical baseline data, we analyzed treatment outcomes using the Standard of Care (SOC) definition, as well as a comparison of an early (within the first 12 months after manifestation) versus late (more than 12 months after manifestation) onset of therapy. RESULTS: In terms of treatment, most patients received intravenous immunoglobulin (56%) or prednisolone (39%) as their first therapy. Patients who started their initial treatment later experienced a worsening disease course, as reflected by a significant deterioration in their Inflammatory Neuropathy Cause and Treatment (INCAT) leg disability score. SOC-refractory patients had worse clinical outcomes than SOC-responders. Associated factors for SOC-refractory status included the presence of fatigue as a symptom and alcohol dependence. CONCLUSION: Timely diagnosis, prompt initiation of treatment and careful monitoring of treatment response are essential for the prevention of long-term disability in CIDP and suggest a "hit hard and early" treatment paradigm.

Subacute Cutaneous Lupus Erythematosus Secondary to Intravenous Immunoglobulin Infusions.

Subacute cutaneous lupus erythematosus (SCLE) is a variant of cutaneous lupus erythematosus (CLE) characterized by distinct skin lesions. Clinical manifestations typically include annular or psoriasiform skin lesions, often localized in sun-exposed areas such as the chest and back. The pathogenesis of SCLE is largely unknown, and contributing factors include genetics, environmental exposures, and immunological dysregulation. SCLE may be idiopathic or drug-induced, with common triggers being calcium channel blockers, thiazide diuretics, and terbinafine. Intravenous immunoglobulin (IVIG) treatment, frequently used in various autoimmune conditions, has a rare association with SCLE. We report a case in which this condition arose during IVIG treatment for chronic inflammatory demyelinating polyneuropathy (CIDP). Knowledge of this rare effect is beneficial to all providers who prescribe IVIG, including neurology, rheumatology, and dermatology.

Uncommon Presentation of IgM Monoclonal Gammopathy of Undetermined Significance (MGUS) and Anti-Myelin-Associated Glycoprotein (MAG)-Associated Demyelinating Peripheral Neuropathy as Respiratory Failure: A Case Report.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal plasma cell disorder characterized by monoclonal immunoglobulins and/or an abnormal free immunoglobulin light chain ratio. MGUS can be associated with immune-mediated neuropathies, including chronic inflammatory demyelinating neuropathy and its variants. Here, we report the case of a 76-year-old male who presented with progressive weakness, initially in the lower extremities and later including the upper extremities. Serum protein electrophoresis and immunofixation identified an IgM kappa monoclonal protein and further testing confirmed high titers of anti-myelin-associated glycoprotein (MAG) antibodies, leading to a diagnosis of anti-MAG-associated demyelinating peripheral neuropathy. The coexistence of MGUS and anti-MAG antibodies requires meticulous diagnosis and management, especially in patients who present with atypical symptoms of the disease.

Recurrent CNTN1 antibody-positive nodopathy: a case report and literature review.

Background: Contactin-1 (CNTN1) antibody-positive nodopathy is rare and exhibits distinct clinical symptoms such as tremors and ataxia. However, the mechanisms of these symptoms and the characteristics of the cerebral spinal fluid (CSF) remain unknown. Case presentation: Here, we report a case of recurrent CNTN1 antibody-positive nodopathy. Initially, a 45-year-old woman experiencing numbness in the upper limbs and weakness in the lower limbs was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Eleven years later, her symptoms worsened, and she began to experience tremors and ataxia. Tests for serum CNTN1, GT1a, and GQ1b antibodies returned positive. Subsequently, she was diagnosed with CNTN1 antibody-positive nodopathy and underwent plasmapheresis therapy, although the treatment's efficacy was limited. To gain a deeper understanding of the disease, we conducted a comprehensive literature review, identifying 52 cases of CNTN1 antibody-positive nodopathy to date, with a tremor prevalence of 26.9%. Additionally, we found that the average CSF protein level in CNTN1 antibody-positive nodopathy was 2.57 g/L, with 87% of patients exhibiting a CSF protein level above 1.5 g/L. Conclusion: We present a rare case of recurrent CNTN1 antibody-positive nodopathy. Our findings indicate a high prevalence of tremor (26.9%) and elevated CSF protein levels among patients with CNTN1 antibody-positive nodopathy.

An immuno-DOT diagnostic assay for autoimmune nodopathy.

OBJECTIVES: Autoimmune nodopathy (AN) is a life-threatening peripheral neuropathy mediated by four autoantibodies targeting axoglial cell adhesion molecules at the nodes of Ranvier: Neurofascin-155 (Nfasc155), PanNeurofascin (PanNfasc), Contactin-1 (CNTN1), and Contactin-associated protein 1 (CASPR1). Antibody detection is a strong biomarker for AN diagnosis and treatment monitoring. The aim of this study was to develop an immuno-dot assay (immuno-DOT) compatible with routine implementation in medical laboratories. METHODS: This new approach was compared to standard techniques: indirect immunofluorescence assay, cell-based assay, and ELISA. Sensitivities (Se) and specificities (Sp) were calculated on a cohort composed of 58 patients diagnosed with AN, 50 seronegative patients with chronic inflammatory demyelinating polyradiculoneuropathy, 20 healthy controls, 30 patients with Guillain-Barré syndrome, 20 with monoclonal gammopathy and 20 with Charcot-Marie-Tooth disease. The patients were diagnosed with AN based on compatible electro-clinical arguments and at least two positive standard techniques. RESULTS: Immuno-DOT sensitivities and specificities were Se=91 %, Sp=97 % for anti-Nfasc155; Se=80 %, Sp=94 % for anti-PanNfasc; Se=93 %, Sp=98 % for anti-CNTN1; and Se=87 %, Sp=94 % for anti-CASPR1. Immuno-DOT allowed the diagnosis within 3 h and the accurate follow-up of the immune reactivity and isotype, and dot intensity correlated with antibody titers following treatments. A longitudinal study indicated that immuno-DOT yielded reliable results even after six months of storage at -20 °C. CONCLUSIONS: The diagnostic performance of immuno-DOT was satisfactory and compatible with routine implementation in medical laboratories.

Chronic inflammatory demyelinating polyradiculoneuropathy associated with neuromyelitis optica spectrum disorder: A rare case report.

Introduction: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease that targets the myelin sheath, while neuromyelitis optica spectrum disorder (NMOSD) with anti-aquaporin-4 antibodies (AQP4-Ab) affects astrocytes. We report a unique case of CIDP associated with NMOSD. Case presentation: A 49-year-old woman presented to the emergency department with recurrent episodes of vertigo and blurred vision. Brain magnetic resonance imaging (MRI) with contrast eight months before admission showed Dawson's finger, and follow-up brain MRI showed a new hyperintense lesion. Visual evoked potential showed bilateral pre-chiasma lesions, and somatosensory evoked potential indicated lesions between the medulla and cerebral cortex. The patient tested positive for AQP4-Ab, and had ascending lower motor neuron weakness for the past 10 weeks. Electromyography revealed multiple demyelinating lesions suggestive of CIDP. The patient was intravenously administered corticosteroids, methotrexate, and azathioprine, resulting in clinical improvement. Conclusion: CIDP associated with NMOSD is a rare occurrence. In our patient, a combination of corticosteroids and immunosuppressants was effective. The mechanism of combined demyelination of the central and peripheral nervous systems is still not fully understood, and further immunological and pathological studies are needed.

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

INTRODUCTION/AIMS: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Focal inflammatory neuropathies.

This chapter focuses on neuropathies that present with focal involvement of nerve roots, plexus, and/or peripheral nerves associated with autoimmune and inflammatory mechanisms that present with focal involvement of nerve roots, plexus and/or peripheral nerves. The clinical presentation, diagnosis, and treatment of focal autoimmune demyelinating neuropathies, focal nonsystemic vasculitic disorders (diabetic and nondiabetic radiculoplexus neuropathies, postsurgical inflammatory neuropathy, and neuralgic amyotrophy), and focal neuropathies associated with sarcoidosis and bacterial and viral infections are reviewed.

Immune dysregulation in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder of the peripheral nerves with an incompletely understood underlying pathophysiology. This investigation focused on defining B and T cell frequencies, T cell functional capacity and innate immune system analysis in patients with CIDP. METHODS: By using multi-parameter flow cytometry, we examined the phenotype and function of PBMCs in 25 CIDP patients who were relatively clinically stable on treatment who met EFNS/PNS criteria, 21 patients with genetically confirmed hereditary neuropathy and 25 healthy controls. We also evaluated the regulatory T cell (Treg) inhibitory capacity by co-culturing Treg and effector T cells. RESULTS: Proinflammatory CD4 T cells, especially type 1 helper T cell (Th1) and CD8 T cells in patients with CIDP were found to have an enhanced capacity to produce inflammatory cytokines. There was no difference in frequency of Th17 regulatory cells in CIDP patients versus healthy controls, however, Treg function was impaired in CIDP patients. There was no remarkable difference in innate immune system measures. Within B cell subsets, transitional cell frequency was decreased in CIDP patients. INTERPRETATION: Patients with CIDP clinically stable on treatment continued to show evidence of a proinflammatory state with impaired Treg function. This potentially implies an inadequate suppression of ongoing inflammation not addressed by standard of care therapies as well as persistent activity of disease while on treatment. Targeting T cells, especially inhibiting Th1 and polyfunctional CD8 T cells or improving Treg cell function could be potential targets for future therapeutic research.

The multiple roles of nerve biopsy in the diagnosis and prognosis of suspected immune neuropathies.

INTRODUCTION: The value of a sural nerve biopsy for the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is controversial. Evidence-based recommendations for its implementation are lacking. We investigated factors leading to biopsy and analyzed biopsy outcomes and consequences, assessed the predictability of biopsy outcomes through clinical parameters to avoid unnecessary biopsies, and compared results with electrophysiological and clinical severity to determine their prognostic value. METHODS: 190 sural nerve biopsies were analyzed in two cohorts. One consisted of 163 biopsies and the second of 72 biopsies from the prospective Immune-mediated Neuropathies Biomaterial and Data registry (INHIBIT). Both have an intersection of 45 patients. 75 data sets from patients without biopsy were used. Analysis of nerve conduction studies, treatment, overall disability sum score (ODSS), biopsy outcomes, and diagnosis was performed. RESULTS: 51% of biopsied patients received the diagnosis CIDP (77% fulfilled EFNS/PNS criteria), 21% were not CIDP typical, and 27% were unspecific. Biopsied patients responded less frequently to immunotherapies at time of biopsy than non-biopsied patients (p = 0.003). Immunotherapy was initiated more frequently after biopsy (p < 0.001) and more often with intravenous immunoglobulins (p < 0.0001). 76% of all biopsied patients met the electrophysiological criteria for CIDP. Sensory nerve action potential amplitudes of 0 µV still provide 73% of histological diagnostic value. Histologic signs of degeneration predicted ODSS worsening after 1 year (p = 0.028) but disease severity did not correlate with histological damage severity. DISCUSSION: The main indication for nerve biopsy was the treatment of refractory cases of autoimmune neuropathies with the therapeutic consequence of treatment initiation or escalation. Sural biopsy also provided prognostic information. Even with extinguished sural SNAP, the biopsy can still have diagnostic value.

A Case Report of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes (POEMS) Syndrome: A Diagnostic Iceberg.

POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, Skin changes) refers to a rare paraneoplastic entity linked to a plasma cell disorder, characterized by multiple systemic manifestations that must be studied together to establish a timely diagnosis. We report a case of a 60-year-old female who had been initially classified to have Guillain Barré syndrome for one year and seven months, receiving three cycles of immunoglobulin without a positive response. The clinical picture was characterized by painful paresthesias in four limbs and paraparesis, with the patient also developing distal cutaneous hyperpigmentation and multiple adenopathies. Neuroconduction studies revealed chronic sensorimotor axonal polyneuropathy and albumin-cytological dissociation was evidenced in the study of cerebrospinal fluid (CSF). In the subsequent evaluation, Lambda light chains and a lymph node biopsy compatible with Castleman's disease were found, and hence it was determined that the patient met the criteria for POEMS syndrome. This case report highlights the importance of incorporating other diagnostic perspectives when encountering patients with polyneuropathy of immunological origin who fail to respond to conventional therapies.

Semiquantitative assessment of preganglionic nerves for chronic immune-mediated neuropathies using brachial plexus magnetic resonance imaging.

Background: Brachial plexus magnetic resonance imaging (MRI) is an important noninvasive supplementary diagnostic method of chronic immune peripheral neuropathies, but few MRI studies on the preganglionic nerves have been conducted. This retrospective cross-sectional study aimed to establish a reliable assessment for brachial plexus preganglionic nerve thickness and to use this method to assess and compare nerve characteristics in various types of peripheral neuropathies. Methods: Hospitalized patients diagnosed as positive for anti-neurofascin-155 (NF155)-positive autoimmune nodopathy (AN) (NF155+), chronic inflammatory demyelinating polyneuropathy (CIDP), or multifocal motor neuropathy (MMN) at Huashan Hospital of Fudan University in Shanghai, China, who underwent brachial plexus MRI between October 2011 and August 2023 were consecutively recruited for this study. We also recruited participants who underwent brachial plexus MRI during this period with no history of trauma, inflammation, tumors, compression, or degenerative conditions as healthy controls. According to our self-developed semiquantitative assessment of preganglionic nerves, we assessed the bilateral preganglionic C5-C8 nerves individually and scored the enlargement degree from 0 to 4 points. Furthermore, a sum score ≥20 was defined as definite enlargement. Results: A total of 122 participants were enrolled, including 28 with NF155+, 40 with CIDP, 15 with MMN, and 39 healthy controls. In the comparison of the single-nerve scores, we found that there was a significant difference distribution among the four groups (χ2 test; P<0.001), with the patients with NF155+ exhibiting the highest scores in each of the bilateral C5-C8 nerves. In the comparison of the sum scores, a descending tendency was observed in patients NF155+, CIDP, and MMN, with median scores of 11, 4, and 0 points, respectively (Kruskal-Wallis test; P=0.003, P<0.001, and P=0.005, respectively for NF155+ vs. CIDP, NF155+ vs. MMN, and CIDP vs. MMN). The proportion of definite enlargement in those with NF155+ was greater than that in healthy controls (21% vs. 0%; χ2 test; P=0.004), and the sum score at 0 points was lower in the NF155+ group than in CIDP, MMN, and healthy control groups (7% vs. 37%, 87%, and 41%, respectively; χ2 test; P<0.001). Conclusions: This semiquantitative assessment can be a valuable tool for measuring preganglionic nerve enlargement, which was found to be decreased, respectively, in those with NF155+, CIDP, and MMN. Presence of definite enlargement could be a strong indicator of NF155+ in clinic.