Objective Patients with myasthenia gravis without acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) antibodies detected by radioimmunoprecipitation assays (RIAs) are classified as seronegative myasthenia gravis (SNMG). Live cell-based assays (l-CBAs) can detect additional antibodies to clustered AChR, MuSK and low-density lipoprotein receptor-related protein 4 (LRP4), but positivity rates are variable and both clinical relevance and utility of CBA platforms remain unclear. Methods Sera from 82 patients with SNMG were tested by l-CBAs. Human embryonic kidney cells were transfected to individually express clustered AChR, MuSK or LRP4; or transfected to jointly express both clustered adult AChR and MuSK. Sera from 30 and 20 patients positive by RIA for AChR or MuSK antibodies were used as comparators. Results 53 of 82 (72%) patients with SNMG had generalised and 29 (28%) had ocular disease. The clustered AChR CBA detected antibodies in 16 of 82 patients (19.5%; including 4 patients with solely fetal AChR antibodies), while 7 of 82 (8.5%) patients had MuSK antibodies. A novel exploratory combined adult AChR-MuSK l-CBA efficiently detected all these antibodies in a subset of the SNMG cohort. No LRP4 antibodies were identified. Overall, patients with SNMG with clustered AChR antibodies, CBA-positive MuSK-MG or triple seronegative were younger, had less severe disease than patients with RIA-positive MG and had a better clinical outcome when immunotherapy was started soon after disease onset, although the time interval from onset to immunotherapy was not different when compared with patients with RIA-positive MG. Conclusion Around one-third of patients with SNMG had AChR or MuSK antibodies by l-CBAs, which were efficiently detected with a combined l-CBA. The results in this large and unselected cohort of patients with MG demonstrate the diagnostic usefulness of performing CBAs and the importance of making these tests more widely available.

Background and purpose: During the COVID‐19 pandemic, myasthenia gravis (MG) patients have been identified as subjects at high risk of developing severe COVID‐19, and thus were offered vaccination with priority. The lack of direct data on the safety and tolerability of SARS‐CoV‐2 vaccines in MG have contributed to vaccine hesitancy. To address this issue, the safety and tolerability of SARS‐CoV‐2 vaccines were assessed in a large cohort of MG patients from two referral centers.Methods: Patients with confirmed MG diagnosis, consecutively seen between October and December 2021 at two MG centers, were enrolled. Demographics, clinical characteristics, and information regarding SARS‐CoV‐2 infection/vaccination were extracted from medical reports and/or collected throughout telephonic or in‐person interviews.Results: Ninety‐eight (94.2%) of 104 patients included were administered at least two vaccine doses 4 weeks before the interview or earlier, and among them, 63 of 98 (64.2%) have already received the “booster” dose. The most frequently used vaccines were BNT162b2‐Pfizer‐BioNTech and mRNA‐1273‐Moderna. Overall, only minor side effects were reported, most commonly local pain and fever. MG worsening after vaccination was observed in eight of 104 (7.7%) cases. The frequency of worsening among muscle‐specific tyrosine kinase MG cases (3/9, 33.3%) was significantly higher compared to other serological subgroups. Spontaneous symptom regression was observed in six of eight cases. Twelve of 104 (11.5%) patients had SARS‐CoV‐2 infection, and none of the SARS‐CoV‐2‐infected MG patients worsened after vaccination.Conclusions: Our data support the safety and tolerability of mRNA COVID‐19 vaccines, which should be strongly recommended in MG patients, who could be at higher risk of complications if exposed to SARS‐CoV‐2 infection.

Background Rituximab (RTX) efficacy in patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorders (MOGADs) is still poorly understood, though it appears to be lower than in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSDs). The aim of this systematic review and meta-analysis is to assess the efficacy and safety profile of RTX in patients with MOGAD and to compare RTX efficacy between MOGAD and AQP4-IgG+NMOSD. Methods We searched original English-language articles published between 2012 and 2021 in MEDLINE, Cochrane, Central Register of Controlled Trials and clinicaltrials.gov, reporting data on RTX efficacy in patients with MOGAD. The main outcome measures were annualised relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score mean differences (MDs) after RTX. The meta-analysis was performed with a random effects model. Covariates associated with the outcome measures were analysed with a linear meta-regression. Results The systematic review included 315 patients (138 women, mean onset age 26.8 years) from 32 studies. Nineteen studies (282 patients) were included in the meta-analysis. After RTX, a significant decrease of ARR was found (MD: −0.92, 95% CI –1.24 to –0.60, p<0.001), markedly different from the AQP4-IgG+NMOSD (MD: −1.73 vs MOGAD −0.92, subgroup difference testing: Q=9.09, p=0.002). However, when controlling for the mean ARR pre-RTX, this difference was not significant. After RTX, the EDSS score decreased significantly (MD: −0.84, 95% CI −1.41 to –0.26, p=0.004). The frequency of RTX-related adverse events was 18.8% (36/192) and overall RTX-related mortality 0.5% (1/192). Conclusions RTX showed effective in MOGAD, although to a lesser extent than in AQP4-IgG+NMOSD, while the safety profile warrants some caution in its prescription. Randomised-controlled trials are needed to confirm these findings and provide robust evidence to improve treatment strategies in patients with MOGAD. PROSPERO registration number CRD42020175439.

Subacute sclerosing panencephalitis (SSPE) is a late complication of measles virus infection that occurs in previously healthy children. This disease has no specific cure and is associated with a high degree of disability and mortality. In recent years, there has been an increase in its incidence in relation to a reduction in vaccination adherence, accentuated by the COVID-19 pandemic. In this article, we take stock of the current evidence on SSPE and report our personal clinical experience. We emphasise that, to date, the only effective protection strategy against this disease is vaccination against the measles virus.

Multiple sclerosis (MS) is primarily a disease diagnosed in young and middle-aged adults. Although MS is a rare condition in pediatric age, an increasing rate of patients is diagnosed under the age of 18. The disabling nature of the disease cannot be reduced only to physical symptoms. Several additional symptoms such as cognitive impairment, fatigue, and psychological symptoms are common features of pediatric MS. The reviewed literature suggests that, despite the lower physical disability, children and adolescents diagnosed with MS are vulnerable to cognitive impairment even in the early stage of the disease. The neuropsychological profile of pediatric MS may resemble that of adult MS, including an impairment in attention/information processing speed, learning, verbal, and visuospatial memory. However, cognitive difficulties in children and adolescents are more likely to involve also general intelligence and linguistic abilities, presumably due to patients’ younger age and cognitive growth stage. Cognitive difficulties, beyond physical disability and relapses, may have a considerable impact on learning and school achievement. Depression and fatigue are other highly prevalent disturbances in pediatric MS and may contribute to patients’ low functional outcomes. Overall, these manifestations may cause considerable functional impairment on daily activities and quality of life that may require individualized rehabilitative treatment and extensive psychosocial care. Additional neuropsychological research evaluating larger samples, using more homogenous methods, and exploring the role of MS treatment on cognitive and psychological development is required.