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An 84‐year‐old man presented with somnolence, dysphagia, and right hemiplegia, all occurring within a month, approximately one year after initial admission due to subacute, transient cognitive decline suggestive of acute disseminated encephalomyelitis involving the cerebral white matter. Serial magnetic resonance imaging (MRI) studies over that period revealed three high‐intensity signal lesions on fluid‐attenuated inversion recovery images, appearing in chronological order in the left upper and left lower medulla oblongata and left pontine base. Despite some clinical improvement following methylprednisolone pulse therapy, the patient died of respiratory failure. Autopsy revealed four fresh, well‐defined lesions in the brainstem, three of which corresponded to the lesions detected radiologically. The remaining lesion was located in the dorsal medulla oblongata and involved the right solitary nucleus. This might have appeared at a later disease stage, eventually causing respiratory failure. Histologically, all four lesions showed loss of myelin, preservation of axons, and infiltration of lymphocytes, predominantly CD8‐positive T cells, consistent with the histological features of autoimmune demyelinating diseases, particularly the confluent demyelination observed in the early and acute phases of multiple sclerosis (MS). In the cerebral white matter, autoimmune demyelination appeared superimposed on ischemic changes, consistent with the cerebrospinal fluid (CSF) and MRI findings on initial admission. No anti‐AQP4 or MOG antibodies or those potentially causing autoimmune encephalitis/demyelination were detected in either the serum or CSF. Despite several similarities to MS, such as the relapsing–remitting disease course and lesion histology, the entire clinicopathological picture in the present patient, especially the advanced age at onset and development of brainstem lesions in close proximity within a short time frame, did not fit those of MS or other autoimmune diseases that are currently established. The present results suggest that exceptionally older individuals can be affected by an as yet unknown inflammatory demyelinating disease of the CNS. [ABSTRACT FROM AUTHOR]

The article presents a study that investigates the incidence rates of dropped head syndrome (DHS) on patients with amyotrophic lateral sclerosis (ALS) in Okinawa, Japan. Researchers studied 105 ALS patients with DHS, where they obtained the age of DHS onset, muscular weakness distribution, initial symptoms and neurological finds. Moreover, they found that incidence rates in three patients with ALS was 2.9% and they were 56, 63 and 53 years old when ALS occurred.

We started a registry for cases of immunoglobulin (Ig)G4-related disease (IgG4-RD) in December 2019 to clarify the clinical profile of IgG4-RD. In this study, clinical information from 854 cases registered by February 16, 2024 was analyzed from multiple perspectives. Diagnosis of IgG4-RD was made in 808 cases, comprising 638 definite, 38 probable, and 132 possible. The mean ± SD age at time of enrollment of the 808 cases was 67.9 ± 11.3 years, with 68.8% being male. The pancreas was the most frequently affected organ (49.8%), followed by the submandibular glands (46.2%) and lacrimal glands (30.6%). This study reconfirmed the pancreas and head-and-neck region as major affected areas in IgG4-RD. Clinically, submandibular adenitis and autoimmune pancreatitis often occur together in the same patient, but no association between the two organs was observed in our analysis. Regarding diagnosis, the comprehensive diagnostic criteria were most commonly used (63.6%). Storiform fibrosis and phlebitis obliterans were detected at different frequencies in different organs. In summary, this registry study identified clinical, imaging, hematologic, and pathologic findings in 808 Japanese patients with IgG4-RD. The frequency of affected organs and their characteristic pathological findings will be particularly useful for future practice.

Background and Objectives: All 4 previous nationwide surveys of multiple sclerosis (MS) in Japan were conducted before the discovery of anti-aquaporin-4 (AQP4) antibodies; thus, neuromyelitis optica spectrum disorder (NMOSD) was included in MS, as optic-spinal MS. We aimed to clarify the epidemiologic features and trends of MS and NMOSD in Japan separately using a fifth nationwide survey., Methods: The primary survey, in which a questionnaire was sent to 3,799 selected departments (including neurology/internal medicine, pediatrics, and ophthalmology), explored the estimated number and prevalence of patients with MS or NMOSD in 2017, and the secondary survey collected detailed characteristics of the patients using a second questionnaire., Results: The response rates for the primary and secondary surveys were 60.1% and 53.9%, respectively. The estimated total number of patients with MS or NMOSD was 24,800, 2.5-fold higher than that in the fourth survey in 2003. The crude prevalence was 19.6 per 100,000 patients (14.2 for MS and 5.4 for NMOSD), compared with 7.7 per 100,000 patients in the fourth survey. Patients with MS showed milder disability (median Expanded Disability Status Scale [EDSS] score: 2.0 [interquartile range 1.0-4.5] vs 2.5 [1.0-6.0]), decreased secondary progression (8.5% vs 15.2%), and increased usage of disease-modifying drugs (63.7% vs 37.2%) compared with those with conventional MS in the fourth survey. The proportions of oligoclonal bands and Barkhof criteria fulfillment on MRI, which are features of classical MS, increased with advancing year of birth. Patients with NMOSD also showed less disability and shorter disease duration than patients with optic-spinal MS in the fourth survey (EDSS score: 3.5 [2.0-5.5] vs 3.8 [2.0-6.0]; disease duration: 8.0 [3.9-14.8] vs 10.0 [5.0-16.0]). Among patients with NMOSD, disability was exacerbated by a history of longitudinally extensive spinal cord lesions and anti-AQP4 antibody positivity, which both decreased with advancing year of birth., Discussion: The prevalences of MS (particularly with classical features) and NMOSD have been increasing in Japan, suggesting the contribution of environmental factors. However, disabilities in patients with MS and NMOSD have been mitigated. Extensive usage of various disease-modifying drugs could be a factor contributing to this disability mitigation in MS.

IgG4-related disease is a unique fibroinflammatory disorder with organ system involvement, which was first described in Japan. It is characterized by high serum IgG4 levels and infiltration of IgG4-positive plasma cells in several organs. IgG4-related disease can involve the central and peripheral nervous systems, resulting in hypertrophic pachymeningitis, orbital diseases, hypophysitis, and peripheral nerve disease. Sufficient pathological findings are important for diagnosing IgG4-related disease and distinguishing it from mimics. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria and the 2020 Revised Comprehensive Diagnostic Criteria have recently been published. Herein, we describe a current update of the clinicopathological features, approach to diagnosis, and management of IgG4-related neurological diseases.

Tumefactive demyelinating lesion(TDL)is defined as a large lesion, size >2 cm, mass effect, perilesional edema and/or ring enhancement. TDL could occur in multiple sclerosis(MS), neuromyelitis optica spectrum disorder(NMOSD), acute disseminated encephalomyelitis(ADEM)or other immunological diseases. Non-invasive methods including MR imaging and assay of several autoantibodies(e.g. aquaporin-4 autoantibodies)are recommended when each TDL is identified. The radiological findings on MRI are characterized by size >2 cm, mass effect, perilesional edema, T2 weighted hypointense rim, peripheral diffusion restriction, open ring enhancement, vascular enhancement, and central vein sign. When atypical clinical and radiological presentations are present in patients with TDL, diagnosis may necessitate brain biopsy due to exclude alternative pathology(e.g. primary central nervous system lymphoma). Because treatments and outcomes for patients with TDL are dependent on each disease etiology including MS, NMOSD, ADEM or others, we should always clarify the entire picture behind the disease.

Paraneoplastic neurological syndromes (PNS) are caused by immune responses against neuronal antigens expressed by the tumor. Based on the immunological pathomechanisms and responsiveness of treatments, onconeuronal antibodies are divided into two categories: 1) antibodies against neural intracellular antigens and 2) antibodies against neuronal surface or synaptic antigens. The recent discovery of onconeuronal antibodies have radically changed concepts of CNS autoimmunity, including PNS. The recognition of PNS provides a foundation for the early detection of underlying tumors and initiations of prompt treatments, which can result in substantial improvement. We here review the characteristic onconeuronal antibodies, including anti-Hu, anti-Ma2, and anti-N-methyl-D-aspartate receptor, and discuss the algorithm for the diagnosis of PNS.