ObjectiveSingle cases and small series of Guillain-Barré syndrome (GBS) have been reported during the SARS-CoV-2 outbreak worldwide. We evaluated incidence and clinical features of GBS in a cohort of patients from two regions of northern Italy with the highest number of patients with COVID-19.MethodsGBS cases diagnosed in 12 referral hospitals from Lombardy and Veneto in March and April 2020 were retrospectively collected. As a control population, GBS diagnosed in March and April 2019 in the same hospitals were considered.ResultsIncidence of GBS in March and April 2020 was 0.202/100 000/month (estimated rate 2.43/100 000/year) vs 0.077/100 000/month (estimated rate 0.93/100 000/year) in the same months of 2019 with a 2.6-fold increase. Estimated incidence of GBS in COVID-19-positive patients was 47.9/100 000 and in the COVID-19-positive hospitalised patients was 236/100 000. COVID-19-positive patients with GBS, when compared with COVID-19-negative subjects, showed lower MRC sum score (26.3±18.3 vs 41.4±14.8, p=0.006), higher frequency of demyelinating subtype (76.6% vs 35.3%, p=0.011), more frequent low blood pressure (50% vs 11.8%, p=0.017) and higher rate of admission to intensive care unit (66.6% vs 17.6%, p=0.002).ConclusionsThis study shows an increased incidence of GBS during the COVID-19 outbreak in northern Italy, supporting a pathogenic link. COVID-19-associated GBS is predominantly demyelinating and seems to be more severe than non-COVID-19 GBS, although it is likely that in some patients the systemic impairment due to COVID-19 might have contributed to the severity of the whole clinical picture.

ObjectiveTo assess the prevalence and isotypes of anti-nodal/paranodal antibodies to nodal/paranodal proteins in a large chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cohort, compare clinical features in seronegative vs seropositive patients, and gather evidence of their isotype-specific pathogenic role.MethodsAntibodies to neurofascin-155 (Nfasc155), neurofascin-140/186 (Nfasc140/186), contactin-1 (CNTN1), and contactin-associated protein 1 (Caspr1) were detected with ELISA and/or cell-based assay. Antibody pathogenicity was tested by immunohistochemistry on skin biopsy, intraneural injection, and cell aggregation assay.ResultsOf 342 patients with CIDP, 19 (5.5%) had antibodies against Nfasc155 (n = 9), Nfasc140/186 and Nfasc155 (n = 1), CNTN1 (n = 3), and Caspr1 (n = 6). Antibodies were absent from healthy and disease controls, including neuropathies of different causes, and were mostly detected in patients with European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite CIDP (n = 18). Predominant antibody isotypes were immunoglobulin G (IgG)4 (n = 13), IgG3 (n = 2), IgG1 (n = 2), or undetectable (n = 2). IgG4 antibody-associated phenotypes included onset before 30 years, severe neuropathy, subacute onset, tremor, sensory ataxia, and poor response to intravenous immunoglobulin (IVIG). Immunosuppressive treatments, including rituximab, cyclophosphamide, and methotrexate, proved effective if started early in IVIG-resistant IgG4-seropositive cases. Five patients with an IgG1, IgG3, or undetectable isotype showed clinical features indistinguishable from seronegative patients, including good response to IVIG. IgG4 autoantibodies were associated with morphological changes at paranodes in patients' skin biopsies. We also provided preliminary evidence from a single patient about the pathogenicity of anti-Caspr1 IgG4, showing their ability to penetrate paranodal regions and disrupt the integrity of the Nfasc155/CNTN1/Caspr1 complex.ConclusionsOur findings confirm previous data on the tight clinico-serological correlation between antibodies to nodal/paranodal proteins and CIDP. Despite the low prevalence, testing for their presence and isotype could ultimately be part of the diagnostic workup in suspected inflammatory demyelinating neuropathy to improve diagnostic accuracy and guide treatment.Classification of evidenceThis study provides Class III evidence that antibodies to nodal/paranodal proteins identify patients with CIDP (sensitivity 6%, specificity 100%).

ObjectivesA few variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been described, but their frequency and evolution to typical CIDP remain unclear. To determine the frequency and characteristics of the CIDP variants, their possible evolution to typical CIDP, and treatment response.MethodsWe applied a set of diagnostic criteria to 460 patients included in a database of Italian patients with CIDP. Clinical characteristics and treatment response were reviewed for each patient. The Kaplan-Meier curve was used to estimate the progression rate from atypical to typical CIDP.ResultsAt the time of inclusion, 376 (82%) patients had a diagnosis of typical CIDP while 84 (18%) had atypical CIDP, including 34 (7%) with distal acquired demyelinating symmetric neuropathy (DADS), 17 (4%) with purely motor, 17 (4%) with Lewis-Sumner syndrome (LSS) and 16 (3.5%) with purely sensory CIDP. Based on retrospective review of the symptoms and signs present at onset and for at least 1 year, 180 (39%) patients had an initial diagnosis compatible with atypical CIDP that in 96 (53%) patients evolved to typical CIDP. Mean disease duration was longer in patients evolving to typical CIDP than in those not evolving (p=0.0016). Patients with DADS and LSS had a less frequent response to immunoglobulin than those with typical CIDP, while patients with purely motor and sensory CIDP had a similar treatment response.ConclusionsThe proportion of patients with atypical CIDP varies during the disease course. DADS and LSS have a less frequent response to intravenous immunoglobulin compared with typical CIDP, raising the possibility of a different underlying pathogenetic mechanism.

Guillain-Barr e syndrome (GBS) incidence can increase during outbreaks of infectious illnesses. A few cases of GBS associated with coronavirus disease 2019 (COVID-19) infection have been reported. The aim was to identify specific clinical features of GBS associated with COVID-19. PubMed, Embase and Cochrane were searched from 1 November 2019 to 17 May 2020 and included all papers with full text in English, Spanish, French or Italian, reporting original data of patients with GBS and COVID-19. Data were extracted according to a predefined protocol. A total of 18 patients reported in 14 papers were included in this review. All the patients were symptomatic for COVID-19, with cough and fever as the most frequently reported symptoms. The interval between the onset of symptoms of COVID-19 and the first symptoms of GBS ranged from À8 to 24 days (mean 9 days; median 10 days). Most of the patients had a typical GBS clinical form predominantly with a demyelinating electrophysiological subtype. Mechanical ventilation was necessary in eight (44%) patients. Two (11%) patients died. Published cases of GBS associated with COVID-19 report a sensorimotor, predominantly demyelinating GBS with a typical clinical presentation. Clinical features and disease course seem similar to those observed in GBS related to other etiologies. These results should be interpreted with caution since only 18 cases have been heterogeneously reported so far.