Recurrent Cerebral Infarction Due to Moyamoya Disease Complicated With Systemic Lupus Erythematosus: A Case Report and Literature Review.

INTRODUCTION: We report a rare case of moyamoya disease caused by an RNF213 mutation, complicated with systemic lupus erythematosus. CASE REPORT: A 32-year-old woman experienced 4 cerebral ischemia stroke events within 6 months. The main symptom was left limb weakness with blurred vision in the right eye. Results of digital subtraction angiography conducted at another hospital were consistent with moyamoya disease. On genetic testing, we found that the patient carried 2 mutations in the moyamoya disease-related gene RNF213 (p.R4810K, p.T1727M). On the basis of the laboratory immunologic indicators, such as positive antibodies and abnormal immunoglobulin levels and imaging examinations, the patient was finally diagnosed as moyamoya disease complicated with systemic lupus erythematosus. She was treated with aspirin, butylphthalide, urinary kallidinogenase, and sodium methylprednisolone. CONCLUSIONS: This was a 32-year-old young patient diagnosed with moyamoya disease carrying RNF213 gene mutation and accompanied by lupus with cerebral ischemic event as the first occurrence. The patient's condition was complex; therefore, comprehensive analysis and in-depth consideration were needed to avoid a missed diagnosis and misdiagnosis. When the primary disease cannot be identified, genetic testing can help to clarify the diagnosis of moyamoya disease.

Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis.

BACKGROUND: Meningeal carcinomatosis (MC) is the most severe form of brain metastasis and causes significant morbidity and mortality. Currently, the diagnosis of MC is routinely confirmed on the basis of clinical manifestation, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging features. However, negative rate of CSF cytology and neuroimaging findings often result in a failure to diagnose MC from the patients who actually have the disease. Here we evaluate the CSF circulating tumor DNA (ctDNA) in the diagnosis of MC. METHODS: A total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF ctDNA extraction and cancer-associated gene mutations detection by next-generation sequencing (NGS) at the same time. RESULTS: The most frequent primary tumor in this study was lung cancer (26/35, 74%), followed by gastric cancer (2/35, 6%), breast cancer (2/35, 6%), prostatic cancer (1/35, 3%), parotid gland carcinoma (1/35, 3%) and lymphoma (1/35, 3%) while no primary tumor could be found in the remaining 2 patients in spite of using various inspection methods. Twenty-five CSF samples (25/35; 71%) were found neoplastic cells in CSF cytology examination while all of the 35 CSF samples (35/35; 100%) were revealed having detectable ctDNA in which cancer-associated gene mutations were detected. All of 35 patients with MC in the study underwent contrast-enhanced brain MRI and/or CT and 22 neuroimaging features (22/35; 63%) were consistent with MC. The sensitivity of the neuroimaging was 88% (95% confidence intervals [95% CI], 75 to 100) (p = 22/25) and 63% (95% CI, 47 to 79) (p = 22/35) compared to those of CSF cytology and CSF ctDNA, respectively. The sensitivity of the CSF cytology was 71% (95% CI, 56 to 86) (n = 25/35) compared to that of CSF ctDNA. CONCLUSIONS: This study suggests a higher sensitivity of CSF ctDNA than those of CSF cytology and neuroimaging findings. We find cancer-associated gene mutations in ctDNA from CSF of patients with MC at 100% of our cohort, and utilizing CSF ctDNA as liquid biopsy technology based on the detection of cancer-associated gene mutations may give additional information to diagnose MC with negative CSF cytology and/or negative neuroimaging findings.

The therapeutic value of cerebrospinal fluid ctDNA detection by next-generation sequencing for meningeal carcinomatosis: a case report.

BACKGROUND: It is usually very complicated to treat meningeal carcinomatosis, and it is important to treat it as soon as possible. CASE PRESENTATION: The 19-Del mutation was found in the exon for the epidermal growth factor receptor gene in the pleural effusion of a patient on March 11th, 2015. He took 250 mg of oral gefitinib once a day for 11 months beginning in December of 2015. On the 3rd of November 2016, he arrived at the hospital and presented with dizziness, headache and transient blurred vision. At this time, he began to take 4 mg of oral zoledronic acid once a month to prevent bone metastases. The result of a cytology exam of the cerebrospinal fluid showed that the man had meningeal carcinomatosis. The 19-Del mutation and the 20-T790 M mutation in the exon of the epidermal growth factor receptor gene was found by the next generation sequencing of the CSF. Then, he discontinued taking gefitinib and began to take 90-100 mg of oral AZD9291 once a day in November 2016. After adjusting the medication dose based on the NGS, his headache was noticeably reduced, and his condition gradually stabilized. CONCLUSIONS: Cerebrospinal fluid ctDNA detection by next generation sequencing may become a suitable biomarker to monitor clinical treatment response in meningeal carcinomatosis.

The gamma-aminobutyric acid-B receptor (GABAB) encephalitis: clinical manifestations and response to immunotherapy.

PURPOSE: We report 11 patients diagnosed with GABAB receptor (GABABR) antibodies encephalitis in China and aim to analyze the clinical characteristics, laboratory and imaging findings, therapeutic modalities and outcomes. METHODS: Clinical data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital of Hebei Medical University from February 2016 to October 2016 January were retrospectively collected and evaluated. RESULTS: Of the 11 patients, seven were males, and a mean age at presentation of 63 years (range: 47-79 years). The major clinical features include cognitive decline (9/11), epilepsy (10/11), mental and behavioral disorders (6/11), involuntary movement (4/11), sleep disorders (2/11), hearing loss (1/11), disturbance of consciousness (4/11) and fever (3/11). GABA-B receptor antibody was positive in serum and/or cerebrospinal fluid in 11 patients. Small-cell lung cancer was detected in five patients. Electroencephalogram monitoring demonstrated abnormal discharge in 10 cases. Epileptiform activities were found in five patients. Four patients showed abnormality in hippocampal region, parahippocampal gyrus, temporal and occipital lobe on magnetic resonance imaging. Ten patients accepted first-line immune therapy. Five patients with small-cell lung cancer received oncologic treatment. During a median follow-up of 11 months, eight patients showed a good outcome, two patients (cases 8 and 9) with tumors had a poor one and one patient (case 10) died of status epilepticus. CONCLUSION: Anti-GABAB receptor encephalitis is an uncommon autoimmune disease, which has been known to be often associated with cancer. Generally, patients associated with GABABR GABA-B receptor antibody encephalitis respond well to immunotherapy, especially if started early.