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Background/objective: Patients with poor-grade subarachnoid bleed (World Federation of Neurosurgical Societies grades 4-5) often improve their neurocognitive function months after their ictus. However, it is essential to explore the timing of intervention and its impact on long-term outcome. We compared the long-term outcomes between immediate management within 24 h and delayed management after 24 h in patients following poor-grade subarachnoid bleed., Methods: This was a retrospective population-based study, including patients with poor-grade subarachnoid bleed who received definitive management between 1 January 2011 and 31 December 2016 in a large tertiary neurocritical care unit. The primary outcome was adjusted odds ratio of favourable outcome (Glasgow Outcome Scale 4-5) for survivors at 12 months following discharge, as measured by the Glasgow Outcome Scale. The secondary outcomes included adjusted odds ratio of a favourable outcome at discharge, 3 months and 6 months following discharge and survival rate at 28 days, 3 months, 6 months and 12 months following haemorrhage., Results: A total of 111 patients were included in this study: 53 (48%) received immediate management and 58 (52%) received delayed management. The mean time delay from referral to intervention was 14.9 ± 5.8 h in immediate management patients, compared to 79.6 ± 106.1 h in delayed management patients. At 12 months following discharge, the adjusted odds ratio for favourable outcome in immediate management versus delayed management patients was 0.96 (confidence interval (CI) = 0.17, 5.39; p  = 0.961). At hospital discharge, 3 months and 6 months, the adjusted odds ratio for favourable outcome was 3.85 (CI = 1.38, 10.73; p  = 0.010), 1.04 (CI = 0.22, 5.00; p  = 0.956) and 0.98 (CI = 0.21, 4.58; p  = 0.982), respectively. There were no differences in survival rate between the groups at 28 days, 3 months, 6 months and 12 months (71.7% in immediate management group vs. 82.8% in delayed management group at 12 months, p  = 0.163)., Conclusions: Immediate management and delayed management after poor-grade subarachnoid bleed are associated with similar morbidity and mortality at 12 months. Therefore, delaying intervention in poor-grade patients may be a reasonable approach, especially if time is needed to plan the procedure or stabilise the patient adequately., (© The Intensive Care Society 2020.)

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) where the communication ability of nerve cells in the brain and spinal cord with each other gets impaired. Some current findings suggest the role of glutamate excitotoxicity in the development and progression of MS. An excess release of glutamate leads to the activation of ionotropic and metabotropic receptors, thus resulting in accumulation of toxic cytoplasmic Ca(2+) and cell death. However, it has been observed that gamma-aminobutyric acid-A (GABAA) receptors located in the nerve terminals activate presynaptic Ca(2+)/calmodulin-dependent signaling to inhibit depolarization-evoked Ca(2+) influx and glutamate release from isolated nerve terminals, which suggest a potential implication of GABAA receptor in management of MS. With this proof of concept, we tried to explore the potential of selective GABAA receptor agonists or positive allosteric modulators (diazepam and phenobarbitone sodium) and GABAA level enhancer (sodium valproate) for management of MS by screening them for their activity in experimental autoimmune encephalomyelitis (EAE) model in rats and cuprizone-induced demyelination model in mice. In this study, sodium valproate was found to show the best activity in the animal models whereas phenobarbitone sodium showed moderate activity. However, diazepam was found to be ineffective.