Report of a fulminant anti-pan-neurofascin-associated neuropathy responsive to rituximab and bortezomib.

Inflammatory neuropathies with pathogenic involvement of the nodes of Ranvier through autoantibodies have been increasingly characterized in the past years. The so-called anti-pan-NF-associated neuropathies caused by the simultaneous existence of anti-Neurofascin-186/-140 and -155-antibodies are extremely rare and cause life-threatening symptoms. Therapeutic strategies are needed as symptoms may be life-threatening and may not respond to standard first-line CIDP treatment. We report a case of a 52-year-old male with a rare anti-pan-neurofascin (NF) (-155, -186/-140)-associated neuropathy. The initial presentation was subacute with mild paresthesia leading to a fulminant "locked-in"-like syndrome requiring mechanical ventilation within the first eight weeks despite treatment with intravenous immunoglobulins. Nerve conduction studies revealed non-excitable nerves with acute spontaneous activity in electromyography. High titers of anti-Neurofascin-155, -186/-140-antibodies were detected in serum and cerebrospinal fluid. A combination of aggressive immunotherapy consisting of intravenous immunoglobulins, plasma exchange, rituximab and bortezomib resulted in clinical improvement with ambulation and non-detectable anti-neurofascin-antibodies within the following 3 months. The follow-up nerve conduction studies showed normalized amplitudes of the peripheral nerves with signs of reinnervation in electromyography. We conclude that an early aggressive immunotherapy consisting of a combination of rituximab and bortezomib could be considered as a therapeutic option for anti-pan-NF-associated neuropathies.

Morphological Differentiation of Corneal Inflammatory Cells: Proposal of Pragmatic Protocol.

PURPOSE: Corneal confocal microscopy is a noninvasive imaging technique to analyze corneal nerve fibers and corneal inflammatory cells (CICs). The amount of CICs is a potential biomarker of disease activity in chronic autoinflammatory diseases. To date, there are no standardized criteria for the morphological characterization of CICs. The aim was to establish a protocol for a standardized morphological classification of CICs based on a literature search and to test this protocol for applicability and reliability. METHODS: A systematic review of the literature about definitions of CICs was conducted. Existing morphological descriptions were translated into a structured algorithm and applied by raters. Subsequently, the protocol was optimized by reducing and defining the criteria of the cell types. The optimized algorithm was applied by 4 raters. The interrater reliability was calculated using Fleiss kappa (K). RESULTS: A systematic review of the literature revealed no uniform morphological criteria for the differentiation of the individual cell types in CICs. Our first protocol achieved only a low level of agreement between 3 raters (K = 0.09; 1062 rated cells). Our revised protocol was able to achieve a higher interrater reliability with 3 (K = 0.64; 471 rated cells) and 4 (K = 0.61; 628 rated cells) raters. CONCLUSIONS: The indirect use of criteria from the literature leads to a high error rate. By clearly defining the individual cell types and standardizing the protocol, reproducible results were obtained, allowing the introduction of this protocol for the future evaluation of CICs in the corneal confocal microscopy.

The impact of the SARS-CoV-2-pandemic on patients with chronic inflammatory neuropathies: results from the German INHIBIT register.

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.