INTRODUCTION:Pathological α-synuclein (α-Syn) propagation may cause Parkinson's disease progression. We aimed to verify whether single-dose intranasal administration of α-Syn preformed fibrils (PFFs) induces α-Syn pathology in the olfactory bulb (OB). METHODS:A single dose of α-Syn PFFs was administered to the left nasal cavity of wild-type mice. The untreated right side served as a control. The α-Syn pathology of the OBs was examined up to 12 months after the injection. RESULTS:Lewy neurite-like aggregates were observed in the OB 6 and 12 months after the treatment. CONCLUSIONS:These findings suggest that pathological α-Syn can propagate from the olfactory mucosa to the OB and reveal the potential dangers of α-Syn PFFs inhalation.

Introduction: Immune-related adverse events (ir-AEs) are increasingly becoming a concern, as immune checkpoint inhibitors (ICIs) are used more frequently. Herein, we present a case of fulminant cytokine release syndrome (CRS) complicated by dermatomyositis after the combination therapy with ICIs. Patient concerns: A 70-year-old male developed dermatomyositis during the course of treatment with two ICIs, nivolumab and ipilimumab. He was treated by steroid pulse therapy, but the effect was limited. Afterwards, he had acute-onset high fever, hypotension, respiratory failure, impaired consciousness, renal failure, and coagulation abnormality at the same time. C reactive protein (CRP), creatinine kinase (CK), D-dimer, and ferritin levels were considerably elevated: CRP, 24mg/dL; CK, 40,500U/L; D-dimer, 290mg/mL; ferritin, 329,000ng/mL. Diagnosis: CRS induced by ICI combination therapy. Interventions: Given that high fever and elevated CRP level indicated potential sepsis, an antibiotic was used until the confirmation of negative blood cultures. All the simultaneous acute symptoms were supposed to be CRS. He was admitted to the intensive care unit (ICU), and temporary intubation and hemodialysis were needed. Immunosuppressive therapy was reinforced by mycophenolate mofetil together with steroid, and plasma exchange was performed for the elimination of abnormal proteins. Outcomes: The patient's clinical symptoms and laboratory parameters gradually improved and he was discharged from the ICU in a month. Conclusion: Fulminant CRS can be induced by ICI combination therapy. As the initial symptoms of CRS resemble sepsis, it is important to consider CRS as a differential diagnosis and to initiate immunosuppressive therapy early when needed. In steroidresistant cases, early introduction of other immunosuppressive therapy and plasma exchange can be effective.

Abstract Penicillium marneffei (Talaromyces marneffei) infection sometimes occurs in HIV‐infected patients in South‐East Asia. However, reports on asymptomatic cases are rare. Herein, we report a case of a 27‐year‐old Burmese HIV‐positive woman with pulmonary penicilliosis. Chest radiography showed a lung mass; however, the patient did not have any respiratory symptoms. Cultures of bronchoalveolar lavage and lung tissue grew P marneffei. The patient was diagnosed with penicilliosis and successfully treated with amphotericin B and itraconazole. Our findings suggest that P marneffei infection should be considered in the differential diagnosis of a lung mass in HIV‐infected patients, even when asymptomatic for respiratory symptoms.

Background Diffusion-weighted imaging (DWI) on magnetic resonance imaging (MRI) shows limited sensitivity in the acute-phase brainstem infarctions, including lateral medullary infarction (LMI), and the detailed characteristics of acute LMI patients with initially negative DWI-MRI findings have not been reported previously. Therefore, we aimed to investigate the differences in the backgrounds or symptoms of acute LMI patients with initially negative findings in standard axial DWI-MRI and those with positive findings. Methods In this retrospective cohort study, we collected the data for 35 consecutive acute LMI patients who were hospitalized in our hospital from January 2011 to December 2018. Initial standard axial DWI-MRI was assessed, and the patients were divided into positive and negative groups. The characteristics of the two groups were compared, and the usefulness of additional thin-slice coronal DWI-MRI was also investigated. Results Nine (26%) acute LMI patients were initially negative on standard axial DWI-MRI. The patients were independently associated with smoking history (78% vs. 23%,p = 0.021) and headache (78% vs. 31%,p = 0.046). Thin-slice coronal DWI-MRI showed positive findings in 50% of the patients with negative findings in standard axial DWI-MRI. All four patients with negative findings in both standard axial and thin-slice coronal DWI-MRI had smoking history and headache. Conclusion Smoking history and headache were associated with initial negative results in standard axial DWI-MRI in acute LMI. Additional thin-slice coronal DWI-MRI was sometimes useful in detecting acute LMI. Follow-up MRI is important for patients showing negative findings in initial DWI-MRI.

Immune checkpoint inhibitors can induce immune-related adverse events (irAEs) in different organs. Dermatomyositis is a rare form of systemic irAE. Although dermatomyositis-specific antibodies, especially anti-transcriptional intermediary factor 1-γ (anti-TIF1-γ) antibodies, have been detected in a few cases of immune checkpoint inhibitor-associated dermatomyositis, their titers before immunotherapy have not been examined. We hereby report the first irAE case of dermatomyositis accompanied by seroconversion of anti-TIF1-γ antibody following nivolumab treatment for advanced lung adenocarcinoma. A 64-year-old Japanese male with an advanced lung adenocarcinoma (cT4N2M1a stage IVA) received nivolumab as third-line therapy. Skin rashes appeared two days later, and were treated with a topical steroid as just drug eruptions. 7 weeks later, he was emergently admitted because of high serum creatine kinase level. Clinical examination showed deteriorated rashes along with slightly weakened proximal muscles. Muscle biopsy revealed myopathic changes consistent with dermatomyositis. Anti-TIF1-γ antibody was positive, which was found to be within normal range before nivolumab administration. He was diagnosed with dermatomyositis and treated with systemic corticosteroids, tacrolimus, and intravenous immunoglobulin. However, these drugs showed limited effectiveness against the progression of muscle weakness. He died of respiratory failure due to lung cancer and muscle weakness progression 6 months after the admission. In conclusion, our case demonstrates that the development of dermatomyositis was causally related to immune activation by nivolumab. Given the potential exacerbation of autoimmune paraneoplastic disorders in cancer patients receiving immunotherapy, clinicians should be aware of early manifestations of systemic irAEs that require prompt diagnosis and intervention.

Purpose: Few studies have assessed the duration of the postictal state after a generalized convulsion (GC) in adults. This study aimed to investigate the postictal duration after a GC and the factors associated with it. Methods: Patients aged >= 16 years who presented to the emergency department of a community general hospital with an unprovoked GC from January 2015 through December 2016 were evaluated retrospectively. A GC was defined as a bilateral convulsion with apparent impaired consciousness including a generalized tonic-clonic seizure. Results: We evaluated 209 consecutive GCs (median age, 42 years) with the median postictal duration of 0.75 h. The univariate analyses indicated that the median duration of the postictal state was significantly longer: in elderly patients (aged >= 65 years) than in younger patients (aged < 65 years) (2 h vs. 0.7 h, p = 0.0005); in patients with higher modified Rankin scale (mRS) scores (>= 3) at baseline than in those with lower scores (<= 2) (2.5 h vs. 0.7 h, p < 0.0001); in patients with longer seizure duration (>= 30 min) than in those with shorter duration (55 h vs. 0.7 h, p < 0.0001); in patients who were given emergency antiepileptic drugs than in those who were not (16 h vs. 0.6 h, p < 0.0001); and in patients who were intubated than in those who were not (63.5 h vs. 0.75 h, p = 0.0009). Multiple linear regression analyses indicated that older age, higher mRS scores at baseline, longer seizure duration, and administration of emergency antiepileptic drugs were independently associated with longer postictal duration. Conclusion: Age, baseline functional disability, and seizure duration were factors associated with the duration of the postictal state after a GC.

We herein report the successful management of a condition mimicking acquired laryngomalacia using conservative methods in an elderly man with a progressive neurological disorder. The patient developed stridor and was transferred to the intensive-care unit. Flexible laryngoscopy revealed a collapsed epiglottis during inspiration, as seen in acquired laryngomalacia, with mucinous material firmly adhered to the epiglottis. The stridor resolved after the removal of this material. Pathology revealed keratinized material, suggesting a collection of sputum or epithelial tissue. Thus, flexible laryngoscopy can differentiate the cause of airway obstruction and avoid unnecessary endotracheal intubation in patients with neurological disorders.

A 42‐year‐old woman without any past medical history was admitted to our hospital with a 1‐year history of a gradual decrease in the vi‐ sual acuity of her right eye. Her remained neurological examination, laboratory tests, and cerebrospinal fluid tests were normal. Contrast T1 magnetic resonance imaging revealed thickening and contrast enhancement of the dura around the cavernous sinus (Figure 1A,B). Fluorodeoxyglucose positron emission tomography revealed no sig‐ nificant uptake including in the lesion. The differential diagnosis was hypertrophic pachymeningitis because thickening of the dura around the cavernous sinus was noted. Since infectious or inflammatory causes were not proved, we performed a resection of the lesion around the cavernous sinus and the pathological findings revealed meningothelial meningioma (Figure 1C). The surgery revealed that most of the tumor was at‐ tached at the wall of the cavernous sinus, therefore, we diagnosed it as cavernous sinus meningioma and the tumor was supposed to be infiltrating into the sphenoid wing from the wall of the cavernous sinus. Cavernous sinus meningiomas represent approximately 1% of all meningiomas,1 although the frequent clinical symptom of cavern‐ ous sinus meningioma is optic nerve dysfunction (43%).2 Cavernous sinus meningiomas can represent the thickening and enhancement

Background: Immune checkpoint inhibitors (ICIs) are promising drugs for use in specific types of cancers, but sometimes immune-related adverse events (irAEs) occur. Autoimmune encephalitis is a rare irAE, and its clinical and laboratory features remain unknown.

Background: There are few studies on postictal duration after generalized tonic clonic seizure (GTCS) and its associated factors.

Background: Although the incidence of status epilepticus (SE) is higher in elderly people, its clinical characteristics are not thoroughly documented in this population.

Posterior reversible encephalopathy syndrome (PRES) typically affects the posterior subcortical white matter. We report the case of a 55-year-old man with atypical PRES, who had malignant hypertension and renal dysfunction. Magnetic resonance imaging of the brain revealed extensive vasogenic edema in the deep white matter including the temporal pole, as well as in the brainstem and cerebellum. Antihypertensive therapy and hemodialysis contributed to both clinical and radiological improvement. Involvement of the deep white matter including the temporal pole, which is rarely affected in an ischemic stroke, should be recognized as a potential sign of PRES.