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Availability of COVID-19 mRNA vaccine for patients with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with intravenous immunoglobulin (IVIg) raises the question of whether COVID-19 mRNA vaccine influences disease activity or IVIg-mediated immunomodulation in CIDP. In this exploratory study, blood samples of CIDP patients on IVIg treatment were longitudinally analyzed before and after vaccination with a COVID-19 mRNA vaccine. A total of 44 samples of eleven patients were characterized at four timepoints by ELISA and flow cytometry in terms of immunomarkers for disease activity and IVIg-immunomodulation. Apart from a significantly lower expression of CD32b on naïve B cells after vaccination, no significant alteration of immunomarkers for CIDP or IVIg-mediated immunomodulation was observed. Our exploratory study suggests that COVID-19 mRNA vaccine does not have a relevant impact on immune activity in CIDP. In addition, immunomodulatory effects of IVIg in CIDP are not altered by COVID-19 mRNA vaccine. This study was registered in the German clinical trial register (DRKS00025759). Graphical Abstract Overview over the study design. Blood samples of CIDP patients on recurrent IVIg treatment and vaccination with a COVID-19 mRNA vaccine were obtained at four timepoints for cytokine ELISA and flow cytometry, to assess key cytokines and cellular immunomarkers for disease activity and IVIg-immunomodulation in CIDP.

Background Magnetic resonance imaging (MRI) is currently explored as supplemental tool to monitor disease progression and treatment response in various neuromuscular disorders. We here assessed the utility of a multi-parametric magnetic resonance imaging (MRI) protocol including quantitative water T2 mapping, Dixon-based proton density fat fraction (PDFF) estimation and diffusion tensor imaging (DTI) to detect loss of spinal motor neurons and subsequent muscle damage in adult SMA patients. Methods Sixteen SMA patients and 13 age-matched controls were enrolled in this prospective, longitudinal study. All participants underwent MRI imaging including measurements of Dixon-based PDFF and DTI of the sciatic nerve. SMA patients furthermore underwent measurements of muscle water T2 (T2w) of the biceps femoris muscle (BFM) and quadriceps femoris muscle (QFM). Ten participants returned for a second scan six months later. MRI parameter were correlated with clinical data. All patients were on nusinersen treatment. Results There were significantly higher intramuscular fat fractions in the BFM and QFM of SMA patients compared to healthy controls at baseline and after 6 months. Furthermore, T2 values significantly correlated positively with intramuscular fat fractions. The Hammersmith functional motor scale significantly correlated with the QFM’s intramuscular fat fractions. DTI scans of the sciatic nerve were not significantly different between the two groups. Conclusion This study demonstrates that, water T2 mapping and Dixon-based PDFF estimation may distinguish between adult SMA patients and controls, due to massive intramuscular fat accumulation in SMA. More extensive long-term studies are warranted to further evaluate these two modalities as surrogate markers in SMA patients during treatment.

ObjectiveTo evaluate the utility of nerve magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and muscle MRI multi-echo Dixon for assessing lower motor neuron (LMN) degeneration in amyotrophic lateral sclerosis (ALS).MethodsIn this prospective observational cohort study, 14 patients with ALS and 13 healthy controls underwent a multiparametric MRI protocol, including DTI of the sciatic nerve and assessment of muscle proton density fat fraction of the biceps femoris and the quadriceps femoris muscles by a multi-echo Dixon sequence.ResultsIn ALS patients, mean fractional anisotropy values of the sciatic nerve were significantly lower than those of healthy controls. The quadriceps femoris, but not the biceps femoris muscle, showed significantly higher intramuscular fat fractions in ALS.InterpretationOur study provides evidence that multiparametric MRI protocols might help estimate structural nerve damage and neurogenic muscle changes in ALS.

Intravenous immunoglobulins (IVIg) are standard treatment for Guillain-Barré syndrome (GBS). Their exact mechanisms of action are versatile and not fully understood. One possible mechanism is neutralization of circulating autoantibodies via binding to anti- idiotypic antibodies forming idiotype-anti-idiotype dimeric IgG immune complexes. To examine the role of immune complex formation as mechanism of action for IVIg in GBS, 34 C57Bl/6 mice were either treated with anti-ganglioside antibodies and IVIg or IVIg and PBS alone, whereas eight additional mice were treated either with anti-ganglioside autoantibodies and IVIg or anti-ganglioside autoantibodies alone. Subsequently IgG dimer formation was assessed by high performance liquid chromatography (HPLC) and enzyme- linked immunosorbent assay (ELISA). In addition, IgG dimer formation was measured in sera of eight GBS patients who were treated with IVIg. In mice, a significant increase of dimeric IgG after administration of anti-ganglioside antibodies and IVIg could be observed. Re-monomerized IgG dimers showed immunoreactivity against gangliosides and serum immunoreactivity was significantly reduced after IVIg infusion. Likewise also in GBS patients, IgG dimer formation could be detected after IVIg treatment. Our data indicate that dimeric IgG immune complexes contain anti-idiotypic antibodies and provide proof of concept that IVIg treatment in GBS results in measurable amounts of IgG dimers. Larger patient cohorts are needed to evaluate serum IgG dimer increase as a possible marker for treatment response in GBS. Graphical Abstract Mechanism of action: Intravenous immunoglobulins (IVIg) and anti-ganglioside antibodies form dimeric IgG immune complexes, preventing axonal damage in Guillain-Barré Syndrome.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder causing inflammatory demyelination of peripheral nerves and consecutive disability. Diagnostic criteria and treatments are well established, but it is unknown how clinical practice may differ in different geographical regions. In this multicentre study, clinical management of CIDP was compared in 44 patients from Germany, India and Norway regarding diagnostic and therapeutic procedures. All centres used EFNS/PNS diagnostic criteria for CIDP but diagnostic workup varied regarding screening for infectious diseases, genetic testing and nerve biopsy. Intravenous immunoglobulin and prednisolone were the most common therapies in all centres with differences in indication and dosage. Patients from the Indian cohort were the most severely affected with less diverse therapeutic approaches, whereas psychological strain did not differ significantly from the two other cohorts. Our exploratory study discloses an unaddressed issue in management of CIDP that should be further investigated to optimise standard of care for CIDP worldwide.

Nerve conduction studies (NCS) are essential to assess peripheral nerve fiber function in research models of immune-mediated neuritis. However, the current lack of standard protocols and reference values impedes data comparability across models and studies. We performed a systematic review and subsequent meta-analysis of the last 30 years of NCS of immune-mediated neuritis in Lewis-rats. Twenty-six papers met the inclusion criteria for meta-analysis. Extracted data showed considerable heterogeneity of recorded nerve conduction velocity (NCV) and compound muscle action potential (CMAP). Studies also significantly differed in terms of technical, methodical, and data reporting issues. The heterogeneity of the underlying studies emphasizes the need for standardization when conducting and reporting NCS in rats. We provide normative values for NCS of the sciatic nerve of Lewis rats and propose seven items that should be addressed when NCS are performed when studying immune paradigms in Lewis rats.

Diagnosis and disease monitoring of non-systemic vasculitic neuropathy (NSVN) are based on electrophysiological and clinical measures. However, these methods are insensitive to detect subtle differences of axonal injury. We here assessed the utility of a multiparametric MRI protocol to quantify axonal injury and neurogenic muscle damage in NSVN. Ten NSVN patients and ten age-matched controls were investigated in this single-center prospective study. All participants were assessed by diffusion tensor imaging (DTI) of the tibial nerve and multiecho Dixon MRI of soleus and gastrocnemius muscles. These data were correlated with clinical and electrophysiological data. DTI scans of the tibial nerves of patients with NSVN showed significantly lower mean fractional anisotropy (FA) values (0.32 ± 0.02) compared to healthy controls (0.42 ± 0.01). FA values of NSVN patients correlated negatively with clinical measures of pain. Multiecho Dixon MRI scans revealed significantly higher intramuscular fat fractions in the soleus muscle (19.86 ± 6.18% vs. 5.86 ± 0.74%, p = 0.0015) and gastrocnemius muscle (26.09 ± 6.21% vs. 3.59 ± 0.82%, p = 0.0002) in NSVN patients compared to healthy controls. Our data provide a proof of concept that MRI can render information about nerve integrity and muscle pathology in NSVN. Further studies are warranted to evaluate DTI and multiecho Dixon MRI as surrogate markers in NSVN.

Data are sparse about mitochondrial damage in GBS and in its most frequently employed animal model, experimental autoimmune neuritis (EAN). We here characterized changes in mitochondrial content and morphology at different time points during EAN by use of ultrastructural imaging and immunofluorescent labelling. Histological examination revealed that demyelinated axons and their adjacent Schwann cells showed reduced mitochondrial content and remaining mitochondria appeared swollen with greater diameter in Schwann cells and unmyelinated axons. Our findings indicate that in EAN, particularly mitochondria in Schwann cells are damaged. Further studies are warranted to address whether these changes are amenable to novel, mitoprotective treatments.

Objective To evaluate the utility of nerve diffusion tensor imaging (DTI), nerve cross‐sectional area, and muscle magnetic resonance imaging (MRI) multiecho Dixon for assessing proximal nerve injury in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods In this prospective observational cohort study, 11 patients with CIDP and 11 healthy controls underwent a multiparametric MRI protocol with DTI of the sciatic nerve and assessment of muscle proton‐density fat fraction of the biceps femoris and the quadriceps femoris muscles by multiecho Dixon MRI. Patients were longitudinally evaluated by MRI, clinical examination, and nerve conduction studies at baseline and after 6 months. Results In sciatic nerves of CIDP patients, mean cross‐sectional area was significantly higher and fractional anisotropy value was significantly lower, compared to controls. In contrast, muscle proton‐density fat fraction was significantly higher in thigh muscles of patients with CIDP, compared to controls. MRI parameters showed high reproducibility at baseline and 6 months. Interpretation Advanced MRI parameters demonstrate subclinical proximal nerve damage and intramuscular fat accumulation in CIDP. Data suggest DTI and multiecho Dixon MRI might be useful in estimating axonal damage and neurogenic muscle changes in CIDP.