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1.  Comparative efficacy of different acute reperfusion therapies for acute ischemic stroke: a comprehensive benefit–risk analysis of clinical trials 
Brain and Behavior  2014;4(6):789-797.
Background
Numerous acute reperfusion therapies (RPT) are currently investigated as potential new therapeutic targets in acute ischemic stroke (AIS). We conducted a comprehensive benefit–risk analysis of available clinical studies assessing different acute RPT, and investigated the utility of each intervention in comparison to standard intravenous thrombolysis (IVT) and in relation to the onset-to-treatment time (OTT).
Methods
A comprehensive literature search was conducted to identify all available published, peer-reviewed clinical studies that evaluated the efficacy of different RPT in AIS. Benefit-to-risk ratio (BRR), adjusted for baseline stroke severity, was estimated as the percentage of patients achieving favorable functional outcome (BRR1, mRS score: 0–1) or functional independence (BRR2, mRS score: 0–2) at 3 months divided by the percentage of patients who died during the same period.
Results
A total of 18 randomized (n = 13) and nonrandomized (n = 5) clinical studies fulfilled our inclusion criteria. IV therapy with tenecteplase (TNK) was found to have the highest BRRs (BRR1 = 5.76 and BRR2 = 6.82 for low-dose TNK; BRR1 = 5.80 and BRR2 = 6.87 for high-dose TNK), followed by sonothrombolysis (BRR1 = 2.75 and BRR2 = 3.38), while endovascular thrombectomy with MERCI retriever was found to have the lowest BRRs (BRR1 range, 0.31–0.65; BRR2 range, 0.52–1.18). A second degree negative polynomial correlation was detected between favorable functional outcome and OTT (R2 value: 0.6419; P < 0.00001) indicating the time dependency of clinical efficacy of all reperfusion therapies.
Conclusion
Intravenous thrombolysis (IVT) with TNK and sonothrombolysis have the higher BRR among investigational reperfusion therapies. The combination of sonothrombolysis with IV administration of TNK appears a potentially promising therapeutic option deserving further investigation.
doi:10.1002/brb3.279
PMCID: PMC4178251  PMID: 25365799
Acute stroke; analysis; benefit-to-risk ratio; reperfusion therapies
2.  Issue Information 
Brain and Behavior  2014;4(6):i-iii.
doi:10.1002/brb3.169
PMCID: PMC4257765
3.  N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities 
Brain and Behavior  2014;4(2):108-122.
Background
There is an expanding field of research investigating the benefits of medicines with multiple mechanisms of action across neurological disorders. N-acetylcysteine (NAC), widely known as an antidote to acetaminophen overdose, is now emerging as treatment of vascular and nonvascular neurological disorders. NAC as a precursor to the antioxidant glutathione modulates glutamatergic, neurotrophic, and inflammatory pathways.
Aim and discussion
Most NAC studies up to date have been carried out in animal models of various neurological disorders with only a few studies completed in humans. In psychiatry, NAC has been tested in over 20 clinical trials as an adjunctive treatment; however, this topic is beyond the scope of this review. Herein, we discuss NAC molecular, intracellular, and systemic effects, focusing on its potential applications in neurodegenerative diseases including spinocerebellar ataxia, Parkinson's disease, tardive dyskinesia, myoclonus epilepsy of the Unverricht–Lundbor type as well as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease.
Conclusion
Finally, we review the potential applications of NAC to facilitate recovery after traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular vasospasm after subarachnoid hemorrhage.
doi:10.1002/brb3.208
PMCID: PMC3967529  PMID: 24683506
N-acetylcysteine; neurological disorder; treatment
4.  Issue Information 
Brain and Behavior  2014;4(1):i-ii.
doi:10.1002/brb3.164
PMCID: PMC3937701  PMID: 24653960

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