Hideo Handa

Aim: Several studies have reported a higher prevalence of migraine in patients with multiple sclerosis (MS) than in healthy controls (HCs). The aim of this study was to elucidate the headache prevalence in patients with MS or other neuroimmunological disorders, as well as to investigate the associations between headache characteristics and disease activity. Methods: In this multicenter study in Japan, a headache questionnaire was distributed to patients with MS (n = 338), aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder (NMOSD; n = 106), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD; n = 51) or acetylcholine receptor antibody-positive myasthenia gravis (MG; n = 104), and healthy controls (HCs; n = 407). We included only participants aged 18–65 years in this study. The questionnaire responses were classified according to the International Classification of Headache Disorders, 3rd edition. The questionnaire was designed to systematically capture headache characteristics based on established diagnostic criteria. Results: In total, any type of headache was found for 54.1% in MS, 63.2% in NMOSD, 43.1% in MOGAD, 43.3% in MG and 43.5% in HCs. After Holm–Bonferroni correction for comparisons among the five groups, the MS ( p = 0.015) and NMOSD ( p < 0.001) groups had significantly higher odds of any headache compared to the HC group. No difference was observed for migraine (MS 16.0%, NMOSD 16.0%, MOGAD 9.8%, MG 12.5%, HCs 17.0%). In contrast, patients with MS (24.0%) and NMOSD (37.7%) showed a significantly higher frequency of tension-type headache (TTH) than HCs (16.7%) even after adjusting for age and sex. Neither disease activity nor disease-modifying therapy displayed any association with headache severity in patients with MS, NMOSD, or MOGAD. Conclusions: Our study showed no increased prevalence of migraine in MS and other neuroimmunological disorders, whereas TTH comorbidity was higher in MS and NMOSD than in controls.

Background: The pathogenic mechanisms underlying autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A), a central nervous system disorder associated with GFAP autoimmunity, remain controversial. The present study aimed to investigate the potential role of the intrathecal reactivation of Epstein–Barr virus (EBV) in patients with GFAP-A. Methods: EBV-DNA levels were measured in the cerebrospinal fluid (CSF) and blood samples of 14 patients with GFAP-A and 28 patients with other disorders. IgM and IgG antibodies against EBV viral capsid antigen (VCA) and IgG antibodies against early antigen (EA) were also measured in serum samples. Results: EBV-DNA was detected in the CSF samples in 10 of the 14 patients with GFAP-A and in 1 of the 28 patients in the disease control group, with a significant difference between the two groups (71.4% vs 3.6%; ps =0.6143, p=0.0194). Serum antibody profiling revealed evidence of past EBV infection, with VCA-IgG positivity and VCA-IgM and/or EA-IgG negativity observed in 92.9% of the patients with GFAP-A. Conclusion: The study findings suggest that GFAP autoimmunity is associated with intrathecal EBV reactivation.

Efgartigimod, which has been well tolerated and efficacious in individuals with generalized myasthenia gravis (MG), is available in Japan not only for the treatment of anti–acetylcholine receptor–positive (AChR+) but also anti–muscle-specific receptor tyrosine kinase (MuSK+) and seronegative generalized MG. We report details of the use of efgartigimod for generalized MG in clinical practice in Japan. We included patients with generalized MG in the 2021 survey of Japan Myasthenia Gravis Registry (JAMG-R) study group who received an initial cycle of efgartigimod between May and September 2022. We defined “responders” as patients who achieved a score ≥2 points for MG activities of daily living (MG-ADL) in the first treatment cycle. The MG composite and the Revised scale of the 15-item Myasthenia Gravis–Quality of Life scale (MG-QOL15-r) were also evaluated. Of 1,343 JAMG-R patients, 36 (2.7%) started efgartigimod (female 68%, age 53 years). Their serologic profiles were as follows: AChR+, n = 19 (53%); MuSK+, n = 6 (17%); and seronegative, n = 11 (31%). Twenty-six patients (72%) had refractory MG. There were 81 cycles of efgartigimod during the 26-week observation in 34 patients (average, 2.4 cycles). The mean interval between cycles was 5.9 weeks. A continuous 4-weekly infusion of efgartigimod was performed in 65 (80%) of 81 cycles. In the first cycle, the MG-ADL score of the 34 patients decreased significantly from 10.5 ± 4.3 to 6.9 ± 5.1 (p = 0.003). Similarly, the mean MG composite and MG-QOL15-r decreased from 18.4 ± 13.6 to 11.8 ± 9.6 (p = 0.004) and from 19.2 ± 6.3 to 14.2 ± 8.3 (p = 0.007), respectively. Twenty-one (62%) patients were responders. Therapeutic responses were observed in the subsequent cycles. The duration of effectiveness of efgartigimod was varied among the responders; 4 responders had only a single effective cycle. Significant improvement was observed in the MuSK+ patients. Prednisolone dose of 7 patients was reduced. Our examination of the patients' postintervention status revealed that 6 patients achieved minimal manifestations. COVID-19 occurred in 5 patients. We failed to detect clinical or laboratory findings associated with responders. Efgartigimod can be considered for the treatment of patients with generalized MG who do not achieve minimal manifestations, with a broad flexibility of patient selection and treatment schedules.

Kawasaki disease is an acute febrile illness prevalent in early childhood that is characterized by systemic vasculitis and associated with various multisystemic imaging manifestations. Kawasaki disease (KD) is a common pediatric vasculitis syndrome involving medium- and small-sized arteries that is especially prevalent in early childhood (ie, age 6 months to 5 years). The diagnos...