Clinical features and prognostic factors of patients with cancer-associated stroke.

BACKGROUND: Cerebrovascular diseases in cancer patients significantly aggravate their condition and prognosis; therefore, prompt and accurate diagnosis and treatment are important. The purpose of this study was to investigate patient demographics, laboratory data, brain magnetic resonance imaging (MRI) findings, and prognosis among patients with stroke and cancer, especially cancer-associated ischemic stroke (CAIS). METHODS: We performed a retrospective, single-center study. We enrolled consecutive patients who had acute stroke and were admitted to our hospital between January 2011 and December 2021. We collected general demographic characteristics, cancer histopathological type, laboratory data, brain MRI findings, and prognosis data. RESULTS: Among 2040 patients with acute stroke, a total of 160 patients (7.8%) had active cancer. The types of strokes were cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, and transient ischemic attack in 124, 25, 5, and 6 patients, respectively. Among the patients with ischemic stroke, there were 69 cases of CAIS. Pancreas and adenocarcinoma were the most frequent types of primary tumor and histopathology. Patients with adenocarcinoma and those with cerebral infarctions in both bilateral anterior and posterior cerebral circulation areas showed higher D-dimer levels. Pancreatic cancer and high plasma D-dimer levels were associated with poor survival rate. CONCLUSION: CAIS was seen more frequently in patients with pancreatic cancer and adenocarcinoma. Pancreatic cancer and high plasma D-dimer levels were potential factors of poor prognosis in patients with CAIS.

Neuromyelitis optica spectrum disorder secondary to treatment with anti-PD-1 antibody nivolumab: the first report.

BACKGROUND: Immune checkpoint blockade is developed as standard treatment for non-small cell lung cancer. However immune-related adverse events (irAE) have still unknown complications. Here, we report a patient with lung squamous cell carcinoma who developed neuromyelitis optica spectrum disorder with nivolumab. CASE PRESENTATION: A 75-year-old Japanese man with lung squamous cell carcinoma was administered nivolumab as second-line treatment. Two months after treatment with nivolumab, he presented acute paralysis in the bilateral lower limbs, sensory loss. Spinal magnetic resonance imaging showed T2 hyperintense lesions between C5-6 and Th12-L1. He was diagnosed with neuromyelitis optica spectrum disorder (NMOSD) by anti-aquaporin-4 antibody-positive in the serum and other examinations. After treatment, steroid reactivity was poor. CONCLUSION: This is the first patient who developed anti-AQP4 antibody-positive NMOSD as a nivolumab-induced irAE. Clinicians should be aware of this kind of potential neurological complication by using immune check point inhibitor and start the treatment of this irAE as soon as possible.

Biopsy-proven case of Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system.

A 75-year-old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7-year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2-weighted MRI showed diffuse high-intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein-Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV-encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system. High-dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy-proven EBV-positive/HIV-negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV-associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis.

Cerebrospinal fluid levels of alpha-synuclein, amyloid ß, tau, phosphorylated tau, and neuron-specific enolase in patients with Parkinson's disease, dementia with Lewy bodies or other neurological disorders: Their relationships with cognition and nuclear medicine imaging findings.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are common neurodegenerative disorders, but no established biochemical markers for these diseases have been identified. We enrolled 78 subjects (27 patients with PD/DLB, 34 patients with non-PD/DLB neurodegenerative disorders [non-PD/DLB], and 17 controls). Cerebrospinal fluid (CSF) was collected via the standard lumbar puncture technique. The CSF levels of alpha-synuclein, amyloid ß40, amyloid ß42, tau, phosphorylated tau (p-tau), neuron-specific enolase (NSE), and hemoglobin were measured with enzyme-linked immunosorbent assays. Dopamine transporter imaging with 123I-ioflupane was also performed. The PD/DLB patients exhibited significantly lower CSF alpha-synuclein levels than non-PD/DLB group. Significantly elevated CSF levels of tau, p-tau, and NSE were detected in the non-PD/DLB group. Multivariate analysis revealed that the mini-mental state examination score was correlated with the CSF amyloid ß42 level. The specific binding ratio on 123I-ioflupane imaging was decreased in the PD/DLB group, but it was not correlated with the CSF alpha-synuclein level. These results indicate that (1) the CSF alpha-synuclein level is a useful biomarker of PD/DLB; (2) the CSF levels of tau, p-tau, and NSE can be used to discriminate PD/DLB from non-PD/DLB; and (3) the CSF amyloid ß42 level is an independent predictor of cognitive decline in neurological disorders.