Efficacy and economic evaluation of delivery of care with tele-continuous EEG in critically ill patients: a multicentre, randomised controlled trial (Tele-cRCT) study protocol.

INTRODUCTION: Some critically ill patients are confirmed by continuous electroencephalography (cEEG) monitoring that non-convulsive seizure (NCS) and/or non-convulsive status epilepticus (NCSE) are causes of their depressed level of consciousness. Shortage of epilepsy specialists, especially in developing countries, is a major limiting factor in implementing cEEG in general practice. Delivery of care with tele-continous EEG (tele-cEEG) may be a potential solution as this allows specialists from a central facility to remotely assist local neurologists from distant areas in interpreting EEG findings and suggest proper treatment. No tele-cEEG programme has been implemented to help improve quality of care. Therefore, this study is conducted to assess the efficacy and cost utility of implementing tele-cEEG in critical care. METHODS AND ANALYSIS: The Tele-cRCT study is a 3-year prospective, randomised, controlled, parallel, multicentre, superiority trial comparing delivery of care through 'Tele-cEEG' intervention with 'Tele-routine EEG (Tele-rEEG)' in patients with clinical suspicion of NCS/NCSE. A group of EEG specialists and a tele-EEG system were set up to remotely interpret EEG findings in six regional government hospitals across Thailand. The primary outcomes are functional neurological outcome (modified Rankin Scale, mRS), mortality rate and incidence of seizures. The secondary outcomes are cost utility, length of stay, emergency visit/readmission, impact on changing medical decisions and health professionals' perceptions about tele-cEEG implementation. Functional outcome (mRS) will be assessed at 3 and 7 days after recruitment, and again at time of hospital discharge, and at 90 days, 6 months, 9 months and 1 year. Costs and health-related quality of life will be assessed using the Thai version of the EuroQol-five dimensions-five levels (EQ-5D-5L) at hospital discharge, and at 90 days, 6 months, 9 months and 1 year. ETHICS AND DISSEMINATION: This study has been approved by the ethics committees of the Faculty of Medicine, Chulalongkorn University, and of Ramathibodi Hospital, Mahidol University, and registered on Thai Clinical Trials Registry. The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: TCTR20181022002; preresults.

Diagnostic Performance of the Electroencephalogram in the Elderly Manifesting With Episodes of Unresponsiveness.

This study aimed to determine diagnostic performance of the EEG in diagnosing seizures and to ascertain risk factors associated with seizures in the elderly presenting with episodes of unresponsiveness compared with younger patients. This is a cross-sectional study. Only EEGs requested with indication of transient unresponsiveness (TUR) were included. Patients were divided into 2 groups, younger (aged 18-49 years) and elderly (aged >60 years). The EEG was an index test. Reference standard, independently verified by 2 board-certified neurologists, was a clinical diagnosis of presence or absence of epilepsy/probable seizures. Univariate and multivariate analyses were performed to ascertain associated risk factors for epilepsy/probable seizures. Among 2187 total EEG recordings, 244 (11.16%) recordings were requested with indication of TUR. A total of 156 patients (50 younger and 106 elderly) were recruited for analysis. Prevalence of epilepsy/probable seizures in patients with TUR was 26.9%. Prevalence of interictal epileptiform discharges was 16% in the younger and 12.3% in the elderly. Overall diagnostic performance was poorer in the elderly. Associated risk factors for having seizures were presence of intermittent slow waves in the younger and presence of positive motor signs as well as presence of nonepileptiform abnormalities in the elderly. Prevalence of seizures and interictal epileptiform discharges was low in the elderly who manifests with TUR. Overall diagnostic performance of the EEG in diagnosing seizures was poorer in the elderly mainly due to low sensitivity. When we encounter patients with TUR, thorough and detailed history is still a mainstay of a diagnosis of seizures, not the EEG results.

SHP-1 promoter 2 methylation in cerebrospinal fluid for diagnosis of leptomeningeal epithelial-derived malignancy (carcinomatous meningitis).

Current diagnostic methods for leptomeningeal metastasis (LM) from epithelial-derived malignancy (EDM) have limited sensitivity. Here, we explored SHP-1 promoter 2 methylation (SHP1P2)-an epithelial-specific methylation marker previously proven as risk stratification and potential diagnostic marker in non-small cell lung cancer-for EDM with LM. We prospectively recruited 136 patients who were diagnosed EDM with LM (n = 25), EDM without LM (n = 14), non-EDM with LM (n = 8), and benign meningeal diseases (n = 89). The primary cancer sites for EDM with LM were lung (n = 17), breast (n = 5), and colon (n = 3). We performed quantitative analyses of cell-free (cfSHP1P2) and whole fraction (wSHP1P2) from cerebrospinal fluid (CSF); results were correlated with the clinicopathological data, including CSF cytology. Median cfSHP1P2 and wSHP1P2 were 3.08 [range: 0-163.5] and 9.35 [0.69-91.63] ng/ml, respectively, in EDM with LM; 0 [0-0.08] and 0.23 [0-7.84] ng/ml in EDM without LM; and were undetectable in most cases of benign meningeal diseases and non-EDM with LM. The cut-off values of 0.22 ng/ml for methylated cfSHP1P2 and 0.59 ng/ml for wSHP1P2 were the best to discriminate EDM with LM from EDM without LM (sensitivity: 79-100 %; specificity: 83-100 %), as well as from other benign conditions (sensitivity: 85-100 % specificity: 78-100 %). CSF cytology yielded 76 % sensitivity for diagnosing EDM with LM. Further validation of CSF SHP1P2 methylation detection as a role of adjunctive tool for LM from EDM should be interested based on our study.

Peripheral neuropathy associated with ipilimumab: a report of 2 cases.

Ipilimumab, a monoclonal antibody targeting human cytotoxic T-lymphocyte-associated antigen 4, was approved by the FDA and European Medicines Agency for the treatment of metastatic melanoma. Immune-related adverse effects can occur with the use of this agent, but peripheral nervous system problems are rare. We report 2 cases of ipilimumab-induced polyneuropathy.