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Background and Purpose: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease with humoral and cellular autoimmunity causing demyelination of peripheral nerves, commonly treated with intravenous immunoglobulins (IVIg). The neonatal Fc receptor (FcRn), encoded by the FCGRT gene, prevents the degradation of immunoglobulin G (IgG) by recycling circulating IgG. A variable number of tandem repeat (VNTR) polymorphism in the promoter region of the FCGRT gene is associated with different expression levels of mRNA and protein. Thus, patients with genotypes associated with relatively low FcRn expression may show a poorer treatment response to IVIg due to increased IVIg degradation., Methods: VNTR genotypes were analyzed in 144 patients with CIDP. Patients' clinical data, including neurological scores and treatment data, were collected as part of the Immune-Mediated Neuropathies Biobank registry., Results: Most patients (n = 124, 86%) were VNTR 3/3 homozygotes, and 20 patients (14%) were VNTR 2/3 heterozygotes. Both VNTR 3/3 and VNTR 2/3 genotype groups showed no difference in clinical disability and immunoglobulin dosage. However, patients with a VNTR 2 allele were more likely to receive subcutaneous immunoglobulins (SCIg) than patients homozygous for the VNTR 3 allele (25% vs. 9.7%, p = 0.02) and were more likely to receive second-line therapy (75% vs. 54%, p = 0.05)., Conclusions: The VNTR 2/3 genotype is associated with the administration of SCIg, possibly reflecting a greater benefit from SCIg due to more constant immunoglobulin levels without lower IVIg levels between the treatment circles. Also, the greater need for second-line treatment in VNTR 2/3 patients could be an indirect sign of a lower response to immunoglobulins., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: To evaluate magnetic resonance neurography (MRN) for the longitudinal assessment of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)., Methods: Prospective examination of twelve CIDP patients by neurological assessment, MRN, and nerve conduction studies in 2016 and 6 years later in 2022. Imaging parameters were compared with matched healthy controls and correlated with clinical and electrophysiological markers. The MRN protocol included T2-weighted imaging, diffusion tensor imaging (DTI), T2 relaxometry, and magnetization transfer imaging (MTI)., Results: Nerve cross-sectional area (CSA) was increased in CIDP patients compared to controls (plexus: p = 0.003; sciatic nerve: p < 0.001). Over 6 years, nerve CSA decreased in CIDP patients, most pronounced at the lumbosacral plexus (p = 0.015). Longitudinally, changes in CSA correlated with changes in the inflammatory neuropathy cause and treatment validated overall disability sum score (INCAT/ODSS) (p = 0.006). High initial nerve CSA was inversely correlated with changes in the INCAT/ODSS over 6 years (p < 0.05). The DTI parameter fractional anisotropy (FA) showed robust correlations with electrodiagnostic testing both cross-sectionally and longitudinally (p < 0.05). MTI as a newly added imaging technique revealed a significantly reduced magnetization transfer ratio (MTR) in CIDP patients (p < 0.01), suggesting underlying changes in macromolecular tissue composition, and correlated significantly with electrophysiological parameters of demyelination (p < 0.05)., Interpretation: This study provides evidence that changes in nerve CSA and FA reflect the clinical and electrophysiological course of CIDP patients. Initial nerve hypertrophy might predict a rather benign course or better therapy response., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

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., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: SARS-CoV-2 pandemic is especially compromising for patients with autoimmune diseases with or without immunomodulatory treatment. This study aimed to investigate the longitudinal changes in the health care of patients with immune-mediated neuropathies during the COVID-19 pandemic., Methods: We performed a longitudinal study using questionnaires in a prospective cohort of patients with immune-mediated neuropathies at two timepoints of the pandemic: May-July 2021 and May-July 2022., Results: The cohort consisted of 73 patients (55 male), mean age 62 years, 68 patients with CIDP, 5 with other immune neuropathies. In 2021, 19.2% of the patients reported a reduced number of physician-patient-contacts, while 13.7% reported this in 2022. Nevertheless, the overall health-care situation worsened from 2021 to 2022: 15.1% reported reduced overall healthcare in 2021, 26.0% in 2022. In 2021, 29.4% of patients reported absence of physio-/occupational therapy, while 34.4% reported this in 2022. Switching immunomodulatory treatment and stretching of treatment intervals occurred more often in 2022 (38.4%) than in 2021 (27.4%). 12 COVID-19-infections occurred overall, with typical only mild symptoms. The rate of fully vaccinated patients was 61.6% and 98.6% in May-July 2021 and 2022, respectively. Only minor side-effects after vaccination were reported., Conclusion: Despite mitigation of COVID-19 restrictions from 2021 to 2022, the health-care situation of patients worsened in this time. Reasons could be the international shortage of immunoglobulins during the pandemic and reduced physio/ergotherapy due to lingering regulatory restrictions. Vaccination rate was high in our cohort of patients compared to the general German population and CIDP did not seem to be a risk factor for severe SARS-CoV-2 infections., (© 2022. The Author(s).)

Background: Diagnosis and treatment of patients with immune-mediated neuropathies is challenging due to the heterogeneity of the diseases., Objectives: To assess similarities and differences in the current care of patients with immune-mediated polyneuropathies in specialized centers in Germany within the German neuritis network "Neuritis Netz"., Material and Methods: We conducted a cross-sectional survey of nine neurological departments in Germany that specialize in the care of patients with immune-mediated neuropathies. We assessed the diagnosis, the approach to diagnostic work-up and follow-up, typical symptoms at manifestation and progression of the disease, and treatment data., Results: This report includes data from 1529 patients per year treated for immune-mediated neuropathies, of whom 1320 suffered from chronic inflammatory demyelinating polyneuropathy (CIDP). Diagnostic work-up almost always included nerve conduction studies, electromyography, and lumbar puncture in accordance with current guidelines. The use of ultrasound, biopsy, and MRI varied. The most important clinical parameter for therapy monitoring in all centers was motor function in the clinical follow-up examinations. A wide range of different immunosuppressants was used for maintenance therapy in about 15% of patients., Conclusions: These data provide important epidemiological insights into the care of patients with immune-mediated neuropathies in Germany. The further development of specific recommendations for treatment and follow-up examinations is necessary to ensure a uniform standard of patient care. This effort is greatly facilitated by a structured collaboration between expert centers such as Neuritis Netz., (© 2022. The Author(s).)

Background and Purpose: Pain, fatigue and depression in chronic inflammatory demyelinating polyneuropathy (CIDP) are often underestimated, as the focus lies on sensorimotor dysfunction and gait instability. The aim of this study was to investigate their prevalence, characteristics and contribution to disability in a prospective cohort of 84 patients with CIDP., Methods: Pain, fatigue, depression and quality of life were measured using the Pain Detect Questionnaire, Krupp's Fatigue Severity Scale, Beck Depression Inventory II and the German Short-Form 36 Health Survey. Sensorimotor deficits and disability were assessed using the Inflammatory Neuropathy Cause and Treatment overall disability score, the Rasch-built Overall Disability Scale, the Medical Research Council sum score and the Inflammatory Neuropathy Cause and Treatment sensory sum score. The interrelation between the five factors was assessed using analysis of variance and linear regression analysis., Results: Pain was reported in 62%, mostly of moderate and severe intensity, whereas pain characteristics indicated neuropathic pain (NP) in 29%. Sensory dysfunction was stronger in NP patients compared to pain-free patients (p = 0.001). Pain of any type, especially NP, was associated with more pronounced fatigue symptoms (p = 0.010). Depressive symptoms were more frequent in patients with pain compared to the pain-free patients (61% vs. 33%, p = 0.02) and were more severe and frequent in NP than in non-NP patients (p = 0.005). Patients with pain had a worse physical quality of life than pain-free patients (p = 0.001)., Conclusion: Pain, depression and fatigue are relevant disability factors in CIDP affecting quality of life. Sensory dysfunction is associated with NP. Therefore, evaluation of CIDP-related disability should include pain and sensory function for adequate monitoring of therapeutic interventions., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Monitoring of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is challenging in daily medical practice because the interrelationship between clinical disability, CIDP subtype, and neuronal degeneration is still elusive. The aim of this prospective cohort study was to investigate the role of different electrophysiological variables in CIDP monitoring., Methods: Comprehensive bilateral nerve conduction studies (NCS) and structured clinical examinations were performed in 95 patients with typical CIDP and CIDP variants (age at inclusion 58.6 ± 11.6 years; median [range] inflammatory neuropathy cause and treatment overall disability score (INCAT-ODSS) 3 [0-9]), at time of first diagnosis in 25 of these patients (based on data from the prospective Immune-mediated Neuropathies Biobank registry). After 12 months, 33 patients underwent follow-up examination. Typical CIDP patients and patients with CIDP variants were characterized electrophysiologically and each individual NCS variable and the overall sum score for axonal damage and demyelination were then correlated to clinical disability scores (INCAT-ODSS, modified Medical Research Council (MRS) sum score, and INCAT sensory score)., Results: As opposed to demyelination markers, the NCS axonal damage variable correlated strongly with disability at both first diagnosis and advanced disease stages in cross-sectional and longitudinal analyses. Distal compound muscle action potential amplitudes of the upper limbs were found to have the strongest correlation with overall clinical function. Typical and atypical CIDP variants had distinct electrophysiological characteristics but, in typical CIDP, axonal degeneration markers were more strongly associated with clinical disability., Conclusions: Total disability is largely determined by the degree of axonal damage, especially in typical CIDP. Although most patients have symptoms predominantly in the legs, NCS of the upper limbs are essential for the monitoring of patients with CIDP and CIDP variants., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The assessment of disease activity is fundamental in the management of chronic inflammatory demyelinating polyneuropathy (CIDP). Previous studies with small patient numbers found an increase of corneal immune cell infiltrates as a potential marker of inflammation in patients with CIDP. However, its clinical relevance remained unclear. The present study aimed to determine whether the amount of corneal inflammatory cells (CIC) measured by corneal confocal microscopy (CCM) detects disease activity in CIDP. CIC were measured in 142 CCM-investigations of 97 CIDP-patients. Data on clinical disease activity, disability (INCAT-ODSS) and need for therapy escalation at the timepoint of CCM, 3 and 6 months later were analyzed depending CIC-count. Pathological spontaneous activity during electromyography was examined as another possible biomarker for disease activity in comparison to CIC-count. An increased CIC-count at baseline was found in patients with clinical disease activity and disability progression in the following 3-6 months. An increase to more than 25 CIC/mm 2 had a sensitivity of 0.73 and a specificity of 0.71 to detect clinical disease activity and a sensitivity of 0.77 and a specificity of 0.64 to detect disability progression (increasing INCAT-ODSS) in the following 6 months. An increase to more than 50 CIC/mm 2 had a sensitivity of about 0.51 and a specificity of 0.91 to detect clinical disease activity and a sensitivity of 0.53 and a specificity of 0.80 to detect disability progression. CIC count is a non-invasive biomarker for the detection of disease activity in the following 6 months in CIDP., (© 2021. The Author(s).)

Objective: To evaluate the European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) in a cohort of patients diagnosed and treated for CIDP in a tertiary university hospital., Methods: In a monocentric retrospective study of 203 CIDP patients, diagnosed according to expert opinion, we evaluated the EFNS/PNS diagnostic criteria. Clinical course and nerve conduction studies (NCS) over 1 year from first referral were studied. Secondarily, we compared the clinical and paraclinical characteristics, including nerve ultrasound, of patients who failed with those who fulfilled the criteria in order to identify clinically relevant differences., Results: At 1 year, 182 (89.7%) patients fulfilled the criteria (156/76.9% definite, 22/10.8% probable, and 4/2% possible). Twenty-one (10.3%) patients did not because the electrodiagnostic criteria remained negative. These still showed signs of demyelination but did not reach the cut-off values. They also presented typical, albeit less pronounced, multifocal nerve enlargement in ultrasonography. Mean disability at presentation and 1 year after was significantly lower. Most importantly, a relevant proportion of these patients also responded to therapy (6/21 = 28.6% vs. 82/182 = 45.3% of those fulfilling the criteria)., Interpretation: CIDP diagnosis could be established for 89.7% of patients over the course of 1 year using EFNS/PNS criteria. The remaining patients (10.3%) presented with milder disability, less accentuated demyelination, but otherwise similar characteristics and still considerable probability of treatment response. Failure to fulfill diagnostic criteria should not automatically preclude treatment. Nerve ultrasound should be considered as a complementary diagnostic tool to detect signs of inflammation in CIDP., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Purpose: We evaluated muscle echointensity as a marker for secondary axonal damage in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) using ultrasonography. Findings were correlated with clinical disability and muscular strength., Methods: Eighty patients with CIDP (40 with typical and 40 with atypical CIDP) were examined clinically, including assessment of Medical Research Council (MRC) sum score and Inflammatory Neuropathy Cause and Treatment Overall Disability Sum Score (INCAT-ODSS). Echointensity in eight proximal and distal muscles of the arms and legs was evaluated by muscle ultrasonography using the Heckmatt scale., Results: Alterations of echointensity occurred most frequently in the distal leg muscles, with a median (range) Heckmatt score of 1.5 (1-4). There were no differences between typical and atypical CIDP patients with regard to Heckmatt score. Alterations of echointensity correlated to disability and muscle strength. The arm score of the INCAT-ODSS correlated to Heckmatt score for the distal arm muscles (r = 0.23, p = 0.046) and the leg score of the INCAT-ODSS correlated to Heckmatt scores for the proximal (r = 0.34, p = 0.002) and distal leg muscles (r = 0.33, p = 0.004). MRC sum score, as well as individual MRC scores for arm and leg muscles, correlated to Heckmatt scores of the corresponding muscle groups (r = -0.25, p = 0.02 for MRC sum score)., Conclusion: Increased muscle echointensity, reflecting fibrosis and fatty infiltration due to secondary axonal damage, correlated to muscular strength and disability in a large cohort of CIDP patients. Alterations of echointensity occur in both typical and atypical CIDP patients and are pronounced in the distal leg muscles., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Monitoring of the disease course of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) remains challenging because nerve conduction studies do not adequately correlate with functional disability. The prognostic value of pathological spontaneous activity (PSA) in needle electromyography (EMG) in different CIDP subgroups in a longitudinal context has, to date, not been analysed. We aimed to determine whether PSA was a prognostic marker or a marker of disease activity in a cohort of patients with CIDP., Methods: A total of 127 patients with CIDP spectrum disorder were retrospectively analysed over 57 ± 47 months regarding the occurrence of PSA (fibrillations and positive sharp waves). The presence of PSA at diagnosis, newly occurring PSA, and continuously present PSA were longitudinally correlated with clinical disability using the Inflammatory Neuropathy Cause and Treatment Overall Disability Sum Score (INCAT-ODSS) and CIDP subtype., Results: Pathological spontaneous activity occurred in 49.6% of all CIDP patients at first diagnosis. More frequent evidence of PSA was significantly associated with a higher INCAT-ODSS at the last follow-up. Continuous and new occurrence of PSA were associated with higher degree of disability at the last follow-up. The majority of patients with sustained evidence of PSA were characterized by an atypical phenotype, higher degree of disability, and the need for escalation of treatment., Conclusions: Pathological spontaneous activity was associated with a higher degree of disability and occurred more frequently in atypical CIDP variants according to the longitudinal data of a large cohort of patients with CIDP. Our results showed that EMG examination was an adequate marker for disease progression and should be evaluated during the disease course., (© 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired, chronic progressive or relapsing immune mediated disorder of the peripheral nervous system. Thickening of cranial nerves as a sign of central nerve involvement is increasingly reported in the last years. Our aim was to assess systematically for the first time the frequency of optic nerve hypertrophy in patients with CIDP by means of transorbital sonography (TOS). Thirty-four optic nerves of 17 patients with CIDP (age=60.8±13.3y, range=39-82y; 7 female) were examined by TOS. The diameter of Optic nerve (OND) as well as the intern and extern diameters of the sheath (ONDSi, ONSDe) was measured 3mm behind the optic disc. Findings were compared to the data of 15 healthy controls. CIDP-patients showed a mean OND of 2.8±0.4mm, an ONSDi of 4.7±0.7mm, and an ONSDe of 6.3±0.9mm. No papilledema was detectable. There was no significant difference to the healthy control group. Our study revealed no evidence for a frequent optic nerve involvement in CIDP. Reported cases seem to represent exceptions. Transorbital sonography could be a useful tool in these rare cases with optic nerve hypertrophy., (Copyright © 2016. Published by Elsevier B.V.)