Factors associated with drug retention of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: A multicentre REVEAL cohort study.

OBJECTIVES: To determine the current retention rate of mepolizumab (MPZ) and identify factors associated with drug retention in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in the Kansai multicentre cohort (REVEAL cohort). METHODS: Sixty patients diagnosed with EGPA and treated with MPZ between December 2016 and June 2023 were enrolled. The clinical characteristics, including laboratory data, treatments administered, and disease course outcomes were collected retrospectively. The patients were stratified into MPZ continuation (n=53) and discontinuation (n=7) groups, and drug retention was statistically compared using the log-rank test. RESULTS: The median age of patients was 54.5 years, with 55% females, and 33% antineutrophil cytoplasmic antibody-positive at disease onset. MPZ exhibited a retention rate of 78.7% after five years. The reasons for discontinuation included treatment of coexisting diseases, inadequate response, and remission. Patient characteristics at disease onset were comparable between the groups. Patients receiving immunosuppressants (IS) before MPZ introduction demonstrated significantly higher retention rates (P = 0.038). During the final observation, the MPZ continuation group had a lower vasculitis damage index score (P = 0.027). CONCLUSIONS: MPZ exhibited a high 5-year retention rate, particularly in patients requiring IS. This study implies that long-term use of MPZ may mitigate irreversible organ damage.

An autopsy case of progressive multifocal leukoencephalopathy with massive iron deposition in juxtacortical lesions.

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by JC virus infection of oligodendrocytes. Little has been reported on iron deposits in patients with PML. Herein, we report a case of PML with massive iron deposition in the juxtacortical regions attaching white matter lesions in a 71-year-old woman who developed bilateral visual disturbance and progressive aphasia after 16 months of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone treatment for follicular lymphoma. Magnetic resonance imaging revealed white matter lesions in the left parietal and other lobes with massive iron deposition in the juxtacortical lesions. A PCR test for JC virus was positive, confirming the diagnosis of PML. Despite treatment with mefloquine and mirtazapine, the patient died six months later. At autopsy, demyelination was found dominantly in the left parietal lobe. Moreover, hemosiderin-laden macrophages and reactive astrocytes containing ferritin were abundant in the juxtacortical regions adjacent to the white matter lesions. This is a previously unreported case of PML after lymphoma, in which iron deposition was confirmed both radiologically and pathologically.

Multiple Cerebral Infarctions Accompanied by Subcortical and Subarachnoid Hemorrhaging in Bilateral Border Zone Areas in a Patient with Eosinophilic Granulomatosis with Polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with peripheral neuropathy, but reports of central nervous system involvement are quite rare. We herein report a patient with EGPA first identified as having hypereosinophilia who later developed asthma, eosinophilic otitis media, sinusitis, and hemorrhagic colitis. She subsequently developed hemiparesis. Head magnetic resonance imaging revealed multiple cerebral infarctions with subcortical and subarachnoid hemorrhaging colocalized at the bilateral border zone areas. She was diagnosed with EGPA-induced stroke and successfully treated with oral prednisolone. Inflammation in the small cerebral arteries in EGPA may induce bilateral border zone infarction with colocalizing subcortical and subarachnoid hemorrhaging.

Liver injury after methylprednisolone pulse therapy in multiple sclerosis is usually due to idiosyncratic drug-induced toxicity rather than autoimmune hepatitis.

BACKGROUND: In patients with multiple sclerosis (MS), development of hepatic injury has been sporadically reported after methylprednisolone (MP) pulse therapy. Some studies suggest autoimmune hepatitis, while other studies reported direct hepatotoxicity as a cause for hepatic injury. Here, we studied the pathological mechanism of such liver injury in patients with MS. METHODS: From 2005 to 2016, eight patients with MS developed liver injury after MP pulse therapy. Their average age was 38 years (range: 28-49 years, all female). Autoimmune antibodies were measured and a liver biopsy was performed in seven patients. RESULTS: Liver injury developed within two weeks in two patients and later (30-90 days after MP) in six patients. No hepatitis-related autoantibody or hepatitis virus were found. All cases were classified as hepatocellular injury and none as cholestatic or mixed. A liver biopsy in five cases revealed centrilobular necrosis with lobular infiltrates of inflammatory cells, suggesting drug-induced acute hepatitis. The biopsy findings in another case suggested a residual stage of acute hepatitis. Only one patient showed portal expansion with periportal fibrosis, suggesting autoimmune hepatitis. All patients recovered spontaneously or with only hepatoprotective drugs, although one patient with possible autoimmune hepatitis recovered slowly. CONCLUSION: Liver injury develops usually later than two weeks after MP treatment. The prognosis is good in most cases and rarely autoimmune hepatitis may be involved.

An autopsy case of globular glial tauopathy presenting with clinical features of motor neuron disease with dementia and iron deposition in the motor cortex.

Globular glial tauopathy (GGT) is a 4-repeat (4R) tauopathy in which 4R tau accumulates to form globular glial inclusions (GGIs), predominantly in oligodendroglia. To date, little has been reported on iron deposits in patients with GGT. We report a case of GGT with iron deposits in a 78-year-old woman presenting with an 8-year history of slowly progressing limb weakness and cognitive decline. Susceptibility-weighted imaging revealed a low signal intensity in the right precentral gyrus, suggesting iron deposition. A clinical diagnosis of motor neuron disease with dementia was made 4 years after onset. At autopsy, gross pathological findings showed atrophy of the frontal and temporal lobes. A localized area of the precentral gyrus corresponding to the most severely affected limb showed the strongest atrophy, macroscopically, and displayed 4R tau-immunoreactive GGIs and microscopically many ferritin-immunoreactive neurons. We diagnosed this patient as having GGT. This is the first GGT case with iron deposition confirmed both radiologically and pathologically.

A novel treatment-responsive encephalitis with frequent opsoclonus and teratoma.

Among 249 patients with teratoma-associated encephalitis, 211 had N-methyl-D-aspartate receptor antibodies and 38 were negative for these antibodies. Whereas antibody-positive patients rarely developed prominent brainstem-cerebellar symptoms, 22 (58%) antibody-negative patients developed a brainstem-cerebellar syndrome, which in 45% occurred with opsoclonus. The median age of these patients was 28.5 years (range = 12-41), 91% were women, and 74% had full recovery after therapy and tumor resection. These findings uncover a novel phenotype of paraneoplastic opsoclonus that until recently was likely considered idiopathic or postinfectious. The triad of young age (teenager to young adult), systemic teratoma, and high response to treatment characterize this novel brainstem-cerebellar syndrome.

A case of anti-N-methyl-d-aspartate receptor encephalitis with multiple sclerosis-like demyelinated lesions.

OBJECTIVE: To describe an unusual case of a male patient with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis who presented with multiple white matter lesions. Brain biopsy of the patient was performed, and follow-up evaluation of the cerebrospinal fluid (CSF) NMDAR antibody titer was implemented. DESIGN: Case report. SETTING: University hospital. PATIENT: A 35-year-old man with anti-NMDAR encephalitis initially presented with fever and psychiatric symptoms. After an initial attack of anti-NMDAR encephalitis, 2 atypical relapses occurred, which presented with myelitis and multifocal white matter lesions; the lesions were open-ring-shaped and partially enhanced. INTERVENTION: Analysis of the brain biopsy specimen revealed the presence of demyelinated lesions with discrete borders. Subsequent intravenous methylprednisolone therapy resulted in improvement in the brain lesions. Prednisolone and cyclophosphamide were orally administered thereafter. Clinical progression of the disease paralleled observed changes in the CSF NMDAR antibody titer. CONCLUSION: The demyelinated lesions observed in this case were similar to lesions found in multiple sclerosis. On the basis of our finding that the clinical progression of the disease and the associated symptoms paralleled changes in the CSF NMDAR antibody titer, we speculate that the lesions formed as a result of anti-NMDAR encephalitis.

[Carcinomatous meningitis in a post-operative patient with lung adenocarcinoma for which erlotinib was effective - a case report].

A 53-year-old female was admitted to our hospital complaining of disturbance of consciousness and hallucinations. About one year and 5 months ago she had adenocarcinoma of the lung, which was treated with surgery and chemotherapy. Computed tomography and magnetic resonance imaging revealed that her lung cancer had relapsed as caricinomatous meningitis and multiple lung metastases. She was treated with erlotinib, which rapidly resulted in disappearance of her symptoms. She still continues to receive erlotinib therapy without suffering from evident relapse 7 months after the initiation of the treatment.

[Granulomatous angiitis of the CNS associated with cerebral amyloid angiopathy--an autopsied case with widespread involvement].

The patient was a 69-year-old woman without history of dementia who developed meningoencephalitis with initial signs of headache and disturbance of consciousness. In this time any abnormal lesions were admitted. Five weeks later, she developed bleeding from the right parietal lobe and underwent surgical removal of hematoma and brain biopsy at another hospital. The pathological specimen revealed beta-amyloid (Abeta) deposition in the pial vascular wall, perivascular invasion of multinucleated giant cells and lymphocytes, and the presence of numerous microinfarcts in the brain parenchyma. In response to pulsed steroid therapy, transient and slight improvement of level of consciousness was noted, but she died of pneumonia 12 weeks after disease onset. On post-mortem examination, widespread multinucleated giant cell granulomatous angiitis accompanied by Abeta deposition was found extensively even in the sacral cord. In addition, groups of tau-positive degenerated nerve processes without Abeta deposition were found scattered in the cerebral cortex.