To define the clinical spectrum and treatment responses of anti-Kelch-like protein 11 (KLHL11) IgG-associated neurological syndromes by screening a large, expanded cohort of patients with suspected autoimmune cerebellar ataxia (ACA), autoimmune encephalitis (AE), and related neurological disorders. In this retrospective, observational study, serum samples from 930 patients collected from over 100 medical institutions across Japan between 2002 and 2025 were screened. The study population was categorized into five cohorts: cerebellar ataxia (CA) of unknown etiology (n = 778), AE (n = 49), brainstem encephalitis (n = 2), myelitis (n = 12), and multiple system atrophy (MSA) (n = 89). Anti-KLHL11 antibodies were detected using a fixed cell-based assay with HEK293T cells. Cerebrospinal fluid was analyzed in all serum-positive cases. Anti-KLHL11 antibodies were identified in four cases, three males and one female with a mean onset age > 60 years, all showing dual positivity in serum and cerebrospinal fluid. The clinical phenotypes consisted of predominantly CA (n = 2), combined limbic encephalitis (LE) and CA (n = 1), and isolated LE associated with small-cell lung cancer (n = 1). Notably, none of the cases were associated with testicular tumor. While typical paraneoplastic presentations were observed, one patient had no detectable malignancy and improved with immunotherapy alone, and another showed neurological recovery following treatment of a non-testicular tumor. Anti-KLHL11 antibodies were absent in all disease controls with MSA. Expanding our initial findings, this nationwide study indicates that anti-KLHL11 antibody-associated ACA and AE are rare but increasingly recognized in Japan and may be under-recognized globally. The clinical spectrum of anti-KLHL11 antibody-associated neurological diseases is broad, including females and individuals without a detectable testicular tumor. Importantly, patients presenting with AE may show more favorable responses to immunotherapy or tumor-directed treatment than those with isolated CA, highlighting the importance of early recognition and phenotype-specific management.

We conducted a study to determine the impact of body mass index (BMI) (underweight, normal weight, and overweight) on the severity of COVID-19 across different periods of variant predominance using a large-scale data registry of hospitalized COVID-19 patients in Japan (COVIREGI-JP), involving 46,291 Japanese patients aged 20-89 years. Severity was classified based on the most intensive treatment received throughout the hospitalization. Multiple logistic models were used to assess the risk of severe disease, and adjusted odds ratios (ORs) for BMI < 18.5, 18.5-20, and ≥ 25 relative to BMI of 20.1-24.9 were calculated by sex and age group. The risk of severe COVID-19 and death was high among those with BMI < 18.5 [OR (95% CI): 1.88 (1.52-2.33), 1.59 (1.22-2.07)] as well as those with BMI ≥ 25 [1.38 (1.20-1.60), 1.87 (1.50-2.34)] for both men and women, respectively. The risk was extremely high among those with BMI < 18.5 when the Omicron variant was predominant [2.41 (1.66-3.49) for men, 2.96 (1.77-4.97) for women]. An important point to note is that being underweight as well as obesity increased the risk of severe COVID-19 and death. More attention should be paid to underweight individuals when predicting COVID-19 risk.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a new spectrum of autoimmune inflammatory nervous system disorders associated with infection, neoplasm, or drug use. We present the first pediatric case of GFAP astrocytopathy caused by an influenza A infection. The patient manifested meningoencephalitis, central respiratory failure, quadriplegia, elimination disorders, and syndrome of inappropriate antidiuretic hormone secretion. Methylprednisolone pulse therapy led to a good prognosis. In cases of progressive atypical complications of influenza infection, immunotherapy-reactive GFAP astrocytopathy should be considered as a differential diagnosis for prompt treatment.

Serum anti-IgLON5 antibodies, which were tested in 223 patients meeting the diagnostic criteria for progressive supranuclear palsy/corticobasal syndrome (PSP/CBS), were negative in all patients. Our study suggests that the frequency of anti-IgLON5 disease is extremely rare in patients with typical presentation of PSP/CBS.

We report the clinical and neuroimaging findings of patients with glial fibrillary acidic protein (GFAP)-immunoglobulin G (IgG)-like anti-astrocytic antibodies in their cerebrospinal fluid. We identified 28 patients whose IgG reacted with astrocytes in a tissue-based assay but did not react with GFAPα in a cell-based assay. Many patients presented with fever and/or headache, followed by consciousness disturbance, meningeal irritation, hyperreflexia, and urinary disturbance. Three patients each showed perivascular radial gadolinium enhancement or longitudinally extensive spinal cord lesions on magnetic resonance imaging. Thirteen of 14 patients responded to the immunotherapies. We suggest that these patients exhibited immunotherapy-responsive inflammatory neurological disorders with cerebrospinal fluid GFAP-IgG-like anti-astrocytic antibodies.

A 72-year-old woman with a seven-year history of Parkinson's disease, characterized by gait instability, rigidity, and postural instability, was admitted to our department for evaluation of recurrent episodes of hypoxemia and altered consciousness. During hospitalization, she experienced recurrent episodes of respiratory failure, prompting the measurement of anti-IgLON5 antibodies, which were found to be positive, leading to a diagnosis of anti-IgLON5 disease. The respiratory failure could not be attributed to vocal cord paralysis or respiratory muscle weakness, leading to the hypothesis that subglottic laryngeal spasm was the cause. Treatment with steroid pulse therapy resulted in improved ventilation. While several cases of anti-IgLON5 disease presenting with respiratory failure due to respiratory muscle weakness have been reported, this case suggests that subglottic laryngeal spasm may also be an underlying cause of respiratory failure in anti-IgLON5 disease.

Autoimmune encephalitis can cause various sleep disorders. Anti-NMDAR encephalitis often presents with insomnia in the acute phase, which may transition into hypersomnia or confusional arousal during recovery. Anti-LGI1 and anti-CASPR2 encephalitis can also cause Morvan's syndrome. This syndrome is characterized by blurred distinctions between sleep stages, leading to status dissociatus and agrypnia excitata. Anti-IgLON5 disease is associated with parasomnia, sleep apnea, and stridor, all of which can lead to sudden death. NMOSD and anti-Ma2 encephalitis may present as narcolepsy accompanied by hypothalamic lesions, likely due to orexin deficiency.

Background We present a pediatric case of longitudinally extensive transverse myelitis, brainstem encephalitis, and peripheral neuropathy, double positive for anti-glial fibrillary acidic protein (GFAP)α and anti-lactosylceramide (LacCer) antibodies, presenting GFAP-astrocytopathy (GFAP-A) and encephalo-myelo-radiculo-neuropathy (EMRN). Case presentation A 12-year-old boy presented with headaches and fever for 10 days. Initial clinical evaluation revealed hyponatremia, urinary retention, and altered consciousness with confusion. Brain magnetic resonance imaging (MRI) demonstrated a hyperintense abnormality in the splenium of the corpus callosum on T2- and diffusion-weighted images, consistent with reversible splenial lesion syndrome. The patient progressively experienced decreased consciousness and brainstem dysfunction (hypoventilation and brainstem reflex loss), was admitted to the intensive care unit, and treated for severe cardiac dysfunction and acute respiratory distress. Methylprednisolone, immunoglobulin, and plasma exchange were intravenously administered. A second MRI scan on day 31 showed multiple long T2 lesions in the brainstem and its surface, basal ganglia, thalamus, claustrum, white matter, and cerebellum. Spinal MRI revealed a longitudinally extensive spinal cord lesion extending into the central gray matter and enhanced nerve roots. Neural conductivity examination revealed motor axonopathy and loss of F-waves. Anti-GFAPα antibodies in the cerebrospinal fluid (CSF) and anti-LacCer antibodies in the serum and CSF were present. Gradually, the patient recovered from cardiac dysfunction and regained respiration and brainstem reflexes. Severe lower-limb-dominant flaccid paralysis and bladder and bowel dysfunctions remained. Discussion/Conclusion This severe case of overlapping anti-GFAPα and anti-LacCer antibodies highlights the importance of careful autoantibody examination in cases with EMRN and/or GFAP-A.

Autoimmune encephalitis presenting with predominant psychiatric symptoms is termed autoimmune psychosis. Identifying clinical features indicative of autoimmune psychosis-referred to as red flags-facilitates early diagnosis. These red flags encompass an infectious prodrome, rapid progression, tumors (currently or recently diagnosed), coexisting autoimmune disorders, severe headache, fluctuating catatonia, involuntary movements, focal neurologic deficits, reduced consciousness, cognitive impairment, autonomic dysfunction, speech impairment, seizures, hyponatremia (unrelated to medication side effects), and malignant syndromes triggered by antipsychotic medications.

A 26-year-old woman receiving immunosuppressive therapy for polymyositis was infected with COVID-19 (an omicron mutant strain) and presented with fever. On the second day after the onset, she was admitted to our hospital and developed status epilepticus. Brain magnetic resonance imaging on admission revealed abnormal symmetric hyperintensities in the bilateral putamen and around the dorsal horns of the lateral ventricle. Three days after admission, brain computed tomography revealed marked cerebral edema and herniation. The cerebrospinal fluid (CSF) cell count was normal, and the reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 was negative. Interleukin (IL)-2, 6, and 10 levels were within the normal range in both serum and CSF, whereas IL-8 levels in the CSF were markedly higher compared to serum levels. She had fulminant acute encephalopathy, suspected to be in the early stages of acute necrotizing encephalopathy (ANE). Steroid pulse therapy and intravenous infusions of remdesivir were ineffective, and the patient died of sepsis on the 26th day after admission. We demonstrated that ANE may occur even in patients infected with Omicron strains and speculated that the pathogenesis in this case might be associated with intrathecal IL-8 production by microglial activation.

Spinocerebellar ataxia 27 B (SCA27B) is caused by the expansion of GAA repeats in the intron of the fibroblast growth factor 14 (FGF14) on chromosome 13 and is inherited dominantly. An 80-year-old male visited the hospital complaining of ataxic gait and harboring 229 pure GAA repeat units in the FGF14. Almost all the clinical features were similar to that of SCA27B. However, the patient initially presented with episodic grip myotonia, which has not been previously reported.

Anti-IgLON5 disease shows various neurological manifestations, of which dysautonomia is one of the major symptoms and is rarely improved by immunotherapy. We herein report a patient with anti-IgLON5 disease who showed several autonomic failures, including vocal cord palsy for four months. The patient presented with cognitive impairments, bulbar symptoms accompanied by myorhythmia in the pharynx and tongue, cerebellar ataxia with tremor, motor neuron symptoms in the limbs, gastrointestinal dysfunction, orthostatic hypotension, non-rapid eye movement sleep disorder on polysomnography, and severe vocal cord palsy. Combined immunotherapy improved his symptoms, including vocal cord palsy, suggesting that combined immunotherapy might improve dysautonomia in anti-IgLON5 disease.

IntroductionAnti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a rare autoimmune encephalitis that can mimic progressive supranuclear palsy or corticobasal syndrome. Moreover, anti-IgLON5 disease can present with symptoms characteristic of multiple system atrophy (MSA), such as cerebellar ataxia and autonomic dysfunction. However, the clinical features of anti-IgLON5 disease resembling MSA have not been well established.MethodsWe enrolled 35 patients with suspected MSA for whom anti-IgLON5 antibody tests were requested. We evaluated immunoglobulin G (IgG) against IgLON5 using cell-based assays. We also summarized the clinical characteristics of patients who were positive for anti-IgLON5 antibodies.ResultsWe identified serum and cerebrospinal fluid anti-IgLON5 antibodies in three patients. These patients had many clinical features characteristic of MSA, including parkinsonism, cerebellar ataxia, severe orthostatic hypotension, acute respiratory failure, sleep parasomnia, vocal cord paralysis, and pyramidal tract signs. Clinical features atypical for MSA were myorhythmia, horizontal eye movement restriction, fasciculations, and painful muscle cramps.ConclusionAnti-IgLON5 disease may be an important differential diagnosis of MSA. A comprehensive physical examination, including assessments of eye movement, lower motor neuron signs, and atypical involuntary movements, is important to avoid misdiagnosis.

Owing to the miniaturization of diagnostic ultrasound scanners and their spread of their bedside use, ultrasonography has been actively utilized in emergency situations. Ultrasonography performed by medical personnel with focused approaches at the bedside for clinical decision‐making and improving the quality of invasive procedures is now called point‐of‐care ultrasonography (POCUS). The concept of POCUS has spread worldwide; however, in Japan, formal clinical guidance concerning POCUS is lacking, except for the application of focused assessment with sonography for trauma (FAST) and ultrasound‐guided central venous cannulation. The Committee for the Promotion of POCUS in the Japanese Association for Acute Medicine (JAAM) has often discussed improving the quality of acute care using POCUS, and the “Clinical Guidance for Emergency and Point‐of‐Care Ultrasonography” was finally established with the endorsement of JAAM. The background, targets for acute care physicians, rationale based on published articles, and integrated application were mentioned in this guidance. The core points include the fundamental principles of ultrasound, airway, chest, cardiac, abdominal, and deep venous ultrasound, ultrasound‐guided procedures, and the usage of ultrasound based on symptoms. Additional points, which are currently being considered as potential core points in the future, have also been widely mentioned. This guidance describes the overview and future direction of ultrasonography for acute care physicians and can be utilized for emergency ultrasound education. We hope this guidance will contribute to the effective use of ultrasonography in acute care settings in Japan.

•We herein present a case of chronic progressive autoimmune GFAP astrocytopathy.•Symmetrical high-intensity signals on FLAIR were observed in the white matter of the temporal and occipital lobes, lateral cerebral ventricle walls, hippocampus, amygdala, and occipital cortex, with extensive Gd enhancement in radial perivascular lesions and the ependyma in the choroid plexus.•Improvements were achieved by 4 courses of IVMP and one of IVIg.

Aim: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH. Methods: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality. Results: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeuticdose UFH was 9.2%. Logistic regression analysis showed that age >= 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P<.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P <.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test). Conclusions: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

A 59-year-old man had developed visual abnormality, nausea, headache, and weight loss since three months before. The ophthalmologist found severe optic disc edema in both eyes, and referred him to our hospital. The patient had mild cerebellar ataxia. Increased cerebrospinal fluid pressure, increased protein and cell counts, positive oligoclonal band, and contrast-enhanced head MRI showed multiple linear perivascular radial gadolinium enhancement around bilateral lateral ventricles. His subjective and objective findings significantly improved with steroid treatment. The cerebrospinal fluid was found to be positive for glial fibrillary acidic protein (GFAP) antibodies, and a diagnosis of GFAP astrocytopathy was obtained. When optic edema or radial contrast effects was observed on contrast-enhanced MRI, GFAP astrocytopathy should be considerd. Prompt immunotherapy is required to circumvent the development of permanent visual impairment.