Normobaric Oxygen Therapy in Acute Stroke: A Systematic Review and Meta-Analysis.

PURPOSE: Normobaric oxygen (NBO) is potentially a readily accessible neuroprotective therapy. We undertook a systematic review to assess NBO in acute stroke. METHODS: MEDLINE, EMBASE, and CENTRAL databases were searched to December 2020. Randomized controlled trials of NBO administered <7 days after stroke to normoxic patients with no other indication for oxygen were identified. Data on early neurological recovery; functional outcome; mortality; oxygen saturation, and imaging markers were collected. FINDINGS: Fifteen publications involving 12 cohorts and 9,255 participants were identified. One study with 8,003 participants had low risk of bias, but the designs of smaller trials had limitations. Ninety-seven per cent of participants were in studies of low-flow oxygen (≤4 L/min). 82.8% had ischaemic stroke. Median time to treatment was 19.3 h. Meta-analysis demonstrated no significant effect on: reduction in National Institutes of Health Stroke Scale at 7 days in all stroke or ischaemic stroke only (mean difference -0.16 [-1.11 to 0.80] and -0.73 [-3.54 to 2.08], respectively); modified Rankin scale at 3-6 months of follow-up (combined standardized mean difference [SMD] -0.08 [-0.38 to 0.22]; 3 months SMD -0.01 [-0.03 to 0.029]; 6-month SMD -0.20 [-1.49 to 1.09]), or mortality (odds ratio 1.15 [0.87-1.53]). DISCUSSION: The majority of patients were administered low-flow oxygen in the sub-acute phase. Intervention strategies targeted at modification of early tissue survival (higher oxygen delivery and administration at early time points when significant volumes of viable tissue persist) have not been tested adequately. CONCLUSION: Studies of NBO have shown no significant effect on early neurological recovery, functional outcome, or mortality in acute stroke. Oxygen has been predominantly low-flow and commenced in the sub-acute phase.

Working memory updating training promotes plasticity & behavioural gains: A systematic review & meta-analysis.

AIMS: Recent reviews yield contradictory findings regarding the efficacy of working memory training and transfer to untrained tasks. We reviewed working memory updating (WMU) training studies and examined cognitive and neural outcomes on training and transfer tasks. METHODS: Database searches for adult brain imaging studies of WMU training were conducted. Training-induced neural changes were assessed qualitatively, and meta-analyses were performed on behavioural training and transfer effects. RESULTS: A large behavioural training effect was found for WMU training groups compared to control groups. There was a moderate near transfer effect on tasks in the same cognitive domain, and a non-significant effect for far transfer to other cognitive domains. Functional neuroimaging changes for WMU training tasks revealed consistent frontoparietal activity decreases while both decreases and increases were found for subcortical regions. CONCLUSIONS: WMU training promotes plasticity and has potential applications in optimizing interventions for neurological populations. Future research should focus on the mechanisms and factors underlying plasticity and generalisation of training gains.

Glutamic acid decarboxylase (GAD) antibodies in epilepsy: diagnostic yield and therapeutic implications.

PURPOSE: The aetiology of adult onset epilepsy remains unascertained in a significant proportion of patients. Antibodies directed against neuronal antigens have been suggested to have a potential pathogenic role in some cases of epilepsy. We describe a series of patients with adult onset epilepsy in whom antibodies to glutamic acid decarboxylase (GAD Abs) have been identified. METHODS: All patients attending a regional epilepsy service with unexplained adult onset epilepsy' were tested for the presence of GAD Abs. Those with high serum titres underwent CSF analysis, and were offered additional treatment with immunotherapy. Those who underwent immunotherapy were monitored by monthly review. Clinical details and response to treatment was collated by review of notes. RESULTS: Of 112 patients tested, high serum titres were found in 6 (5.4%) patients. These patients had clinical and electroencephalographic evidence of focal epilepsy. CSF analysis revealed oligoclonal bands and intrathecal GAD Abs in all patients. Five patients received immunotherapy. No improvement in seizures was observed in any. One patient with equivocal MRI evidence of hippocampal sclerosis and concordant video EEG and PET scan, achieved 12 months seizure freedom following temporal lobectomy. CONCLUSIONS: The relevance of GAD Abs to epilepsy remains uncertain. Our experience does not support the routine use of immunotherapy in patients with epilepsy and GAD Abs. Larger studies enrolling greater numbers of patients are required to identify sufficient numbers of patients for controlled treatment trials.