Rituximab in juvenile myasthenia gravis-an international cohort study and literature review.

Juvenile myasthenia gravis (JMG) is a rare, antibody-mediated disorder of the neuromuscular junction. Treatment strategies in JMG are largely informed by adult MG treatments as the pathophysiology is similar. Rituximab is increasingly considered as a treatment option in refractory JMG but has not yet been systematically investigated in this patient group We conducted a retrospective study from five international centres with expertise in paediatric myasthenia. 10 JMG patients treated with rituximab were identified. Following rituximab treatment all patients had a reduction in JMG-related hospital admissions. At 24 month follow up, 6 patients (60%) had achieved complete stable remission or pharmacological remission and 7 patients were able to reduce immunomodulatory treatment(s). The main side-effect was infusion-related reactions (30%) which resolved in all patients with symptomatic treatment. We compared our cohort to previously reported JMG cases treated with rituximab and noted similar response rates but a slightly higher side-effect profile. Rituximab is a safe and effective treatment option in moderate to severe JMG and most patients have an improvement in MG symptoms post treatment.

Pregnancy outcomes in patients with congenital myasthenic syndromes.

INTRODUCTION/AIMS: The congenital myasthenic syndromes (CMS) are a heterogeneous group of inherited disorders that affect neuromuscular junction transmission. Data on pregnancy outcomes in women with CMS are limited due to their infrequency. In this study we explored pregnancy with CMS in a large cohort of women attending a national specialty clinic in England. METHODS: All women with CMS who had a documented pregnancy were invited to complete a questionnaire assessing clinical status during pregnancy and postpartum, pregnancy outcomes, fetal outcomes, and medication use during pregnancy. RESULTS: Among 16 women with CMS (acetylcholine receptor deficiency [CHRNE], slow channel syndrome [CHRNA1], DOK7, RAPSYN and glycosylation [DPAGT1 and GFPT1]), 27 pregnancies were recorded: 26 single pregnancies and 1 twin pregnancy. Symptom worsening was reported in 63% of pregnancies, but recovery to baseline function was seen in all but one patient. Miscarriage and cesarean section occurred in 31% and 33% of the women, respectively. Over half of the patients continued taking their medication during pregnancy, which included pyridostigmine (n = 10), 3,4-diaminopyridine (n = 9), ephedrine (n = 3), salbutamol (n = 3), and quinidine (n = 1). No fetal malformations were recorded. DISCUSSION: Our results show that clinical worsening during pregnancy was common but rarely persistent. The majority of women with CMS can safely plan pregnancy, but close follow-up is required from their neurology and obstetric teams. Although we identified no safety concerns, continued medication use should be reviewed on a case-by-case basis.

Reelin cells and sex-dependent synaptopathology in autism following postnatal immune activation.

BACKGROUND AND PURPOSE: Autism spectrum disorders (ASD) are heterogeneous neurodevelopmental disorders with considerably increased risk in male infants born preterm and with neonatal infection. Here, we investigated the role of postnatal immune activation on hippocampal synaptopathology by targeting Reelin+ cells in mice with ASD-like behaviours. EXPERIMENTAL APPROACH: C57/Bl6 mouse pups of both sexes received lipopolysaccharide (LPS, 1 mg·kg-1 ) on postnatal day (P) 5. At P45, animal behaviour was examined by marble burying and sociability test, followed by ex vivo brain MRI diffusion kurtosis imaging (DKI). Hippocampal synaptogenesis, number and morphology of Reelin+ cells, and mRNA expression of trans-synaptic genes, including neurexin-3, neuroligin-1, and cell-adhesion molecule nectin-1, were analysed at P12 and P45. KEY RESULTS: Social withdrawal and increased stereotypic activities in males were related to increased mean diffusivity on MRI-DKI and overgrowth in hippocampus together with retention of long-thin immature synapses on apical dendrites, decreased volume and number of Reelin+ cells as well as reduced expression of trans-synaptic and cell-adhesion molecules. CONCLUSION AND IMPLICATIONS: The study provides new insights into sex-dependent mechanisms that may underlie ASD-like behaviour in males following postnatal immune activation. We identify GABAergic interneurons as core components of dysmaturation of excitatory synapses in the hippocampus following postnatal infection and provide cellular and molecular substrates for the MRI findings with translational value.

Early versus late risk factors for deficit and nondeficit schizophrenia.

AIM: We examined whether timing of known risk factors for schizophrenia may influence the development of schizophrenia with primary negative symptoms. METHOD: This cross-sectional single-centre study in England used a clinical cohort of 167 clozapine-treated schizophrenia patients. Deficit and nondeficit schizophrenia models were used as clinical proxies of patients with and without primary negative symptoms respectively. Patients were assessed using the Schedule for the Deficit Syndrome. We examined previously replicated risk factors (family history of psychosis, advanced paternal age, male gender, birth weight <3000g, summer birth, cannabis use, exposure to physical or sexual abuse and/or bullying) as well as other traumatic events for deficit and nondeficit schizophrenia. RESULTS: We found a distinct risk factor pattern for the two groups. Compared to the nondeficit group, patients with deficit schizophrenia reported a significantly lower prevalence of cannabis use (p=0.005) at the time of first-episode psychosis (FEP), physical or sexual abuse (p=0.033) prior to FEP, less exposure to crime-related traumatic events (p=0.012) and significantly associated with summer birth (p=0.017). The groups did not differ in terms of family history of psychosis, advanced paternal age, male gender, or low birth weight. To account for multiple comparisons, a confirmatory analysis was performed using logistic regression which yielded similar results except that summer birth no longer reached statistical significance. CONCLUSION: Our results suggest the timing of the insult may influence the symptom presentation, with insults later in life (cannabis or traumatic events) being associated with psychotic presentation and less with primary negative symptoms.

COVID-19 in a Cohort of Patients with Congenital Myasthenic Syndrome.

Congenital Myasthenic Syndromes (CMS) are a rare group of genetic disorders of neuromuscular transmission. Some subtypes of CMS can be associated with respiratory and bulbar weakness and these patients may therefore be at high risk of developing a severe disease from COVID-19. We screened 73 patients with genetically confirmed CMS who were attending the UK national referral centre for evidence of previous Severe Acute Respiratory Syndrome Corona Virus 2 infection and their clinical outcome. Of 73 patients, seven had history of confirmed COVID-19. None of the infected patients developed a severe disease, and there were no signals that CMS alone carries a high risk of severe disease from COVID-19.

Early versus late risk factors for deficit and nondeficit schizophrenia.

AIM: We examined whether timing of known risk factors for schizophrenia may influence the development of schizophrenia with primary negative symptoms. METHOD: This cross-sectional single-centre study in England used a clinical cohort of 167 clozapine-treated schizophrenia patients. Deficit and nondeficit schizophrenia models were used as clinical proxies of patients with and without primary negative symptoms respectively. Patients were assessed using the Schedule for the Deficit Syndrome. We examined previously replicated risk factors (family history of psychosis, advanced paternal age, male gender, birth weight <3000g, summer birth, cannabis use, exposure to physical or sexual abuse and/or bullying) as well as other traumatic events for deficit and nondeficit schizophrenia. RESULTS: We found a distinct risk factor pattern for the two groups. Compared to the nondeficit group, patients with deficit schizophrenia reported a significantly lower prevalence of cannabis use (p=0.005) at the time of first-episode psychosis (FEP), physical or sexual abuse (p=0.033) prior to FEP, less exposure to crime-related traumatic events (p=0.012) and significantly associated with summer birth (p=0.017). The groups did not differ in terms of family history of psychosis, advanced paternal age, male gender, or low birth weight. To account for multiple comparisons, a confirmatory analysis was performed using logistic regression which yielded similar results except that summer birth no longer reached statistical significance. CONCLUSION: Our results suggest the timing of the insult may influence the symptom presentation, with insults later in life (cannabis or traumatic events) being associated with psychotic presentation and less with primary negative symptoms.

Correction to: Physical health in children with neurodevelopmental disorders.

The original version of this article unfortunately contained a mistake in Fig. 2 part labels, the label "d" was incorrectly labelled as "c" and the subsequent labels should be corrected as d, e, and f. The corrected Fig. 2 is given below.

Physical health in children with neurodevelopmental disorders.

With increasing numbers of children being diagnosed with neurodevelopmental disorders (NDDs) attention has been drawn to these children's physical health. We aimed to identify the prevalence of defined physical problems (epilepsy, migraine, asthma, cancer, diabetes, psoriasis, lactose intolerance, celiac disease, diarrhea, constipation, daytime enuresis, encopresis) in a nationwide population of 9- and 12-year-old twins subdivided into those with and without indications of NDDs. Parents of 28,058 twins participated in a well-validated telephone interview regarding their children's mental health and answered questions about their physical problems. The results indicate a high rate of physical problems in children with NDDs, particularly in those with indications of the presence of combinations of several NDDs.