关键词： Activities of daily living   Cerebral performance category   Cohort study   Long-term survival   Short-term survival   Resuscitation  

摘要： Purpose: Investigate the relation between age, baseline neurological and functional status, and survival after out of-hospital cardiac arrest (OHCA). Methods: Data analysis from the Jerusalem District Resuscitation Study. Patients >80 years and those 18-80 years with OHCA from 4/2005-12/2010 were compared. Primary outcome: survival at four time points;secondary outcomes: neurological and functional status at hospital discharge, and relationship between survival, age and pre-arrest activities of daily living (ADL) and Cerebral Performance Category (CPC) scores (higher scores indicate worse function in both). Results: 3,211 patients (1,259 80 years, 1952 aged 18-80) with median follow-up 5.9 years (range 0.1-11.1 years) were included. Survival was better for younger patients at all four time points, including 7.8% versus 2.5% at hospital discharge, 4.6% versus 0.2% at late follow-up. Functional status at discharge was also better, 4.8 +/- 5.4 versus 9.0 +/- 4.7, p<0.001, and more young patients had CPC1/2, 60.7% versus 32.2%, p = 0.004. Older patients who survived to emergency department admission had increased mortality per year of age (2.6%, hazard ratio [HR] 1.026, 95% confidence interval [CI] 1.006-1.048 versus 1.7%, HR 1.017, 95% CI 1.010-1.025), per point in pre-arrest ADL (3.0%, HR 1.030, 95% CI 1.007-1.054 versus 5.8%, HR 1.058, 95% CI 1.036-1.080), and per point in pre-arrest CPC (24%, HR 1.242, 95% CI 1.097-1.406 versus 37%, HR 1.370 95% CI 1.232-1.524). Conclusion: Patient independence before arrest may be a more crucial determinant of resuscitation outcome than older age alone. Discussion of end-of-life preferences is particularly important for older individuals with functional and cognitive decline.

关键词： Coronavirus   COVID-19   Stroke   Cerebrovascular accident   Complication  

摘要： Introduction: COVID-19 is a multi-system infection which predominantly affects the respiratory system, but also causes systemic inflammation, endothelialitis and thrombosis. The consequences of this include renal dysfunction, hepatitis and stroke. In this systematic review, we aimed to evaluate the epidemiology, clinical course, and outcomes of patients who suffer from stroke as a complication of COVID-19. Methods: We conducted a systematic review of all studies published between November 1, 2019 and July 8, 2020 which reported on patients who suffered from stroke as a complication of COVID-19. Results: 326 studies were screened, and 30 studies reporting findings from 55,176 patients including 899 with stroke were included. The average age of patients who suffered from stroke as a complication of COVID-19 was 65.5 (Range: 40.4-76.4 years). The average incidence of stroke as a complication of COVID-19 was 1.74% (95% CI: 1.09% to 2.51%). The average mortality of stroke in COVID-19 patients was 31.76% (95% CI: 17.77% to 47.31%). These patients also had deranged clinical parameters including deranged coagulation profiles, liver function tests, and full blood counts. Conclusion: Although stroke is an uncommon complication of COVID-19, when present, it often results in significant morbidity and mortality. In COVID-19 patients, stroke was associated with older age, comorbidities, and severe illness.

关键词： Sleep   Neurological disorders   Orexinergic system   Paravascular transport   Brain   Cerebrospinal fluid   Alzheimer's disease   Traumatic brain injury   Epilepsy  

摘要： Until recently, both the purpose of the biological need for sleep and the mechanism by which the central nervous system eliminated metabolic waste products were unknown. The glymphatic system is the recently discovered macroscopic waste clearance system for the CNS, which predominantly functions during sleep states. Important implications for the glymphatic system exist for a significant proportion of neurological disorders, including traumatic brain injury, epilepsy, stroke, migraine, and Alzheimer's disease. Within the limited amount of research pertaining to this novel system there exists controversy regarding several of the key structural and functional aspects of the glymphatic system. In this review we address evidence from both standpoints regarding the prominent debates surrounding the glymphatic system, including the functional differences in wakefulness vs. sleep, the role of glial aquaporin-4 water channels, and whether it reflects a convective flow or a passive diffusion process. The answers that underlie these questions will have crucial and distinct outcomes for the future of the glymphatic system and the disorders it has been implicated in. However, this review also summarizes the potential role of the glymphatic system in the development and progression of the aforementioned neurological disorders. Furthermore, the possible contribution of the orexinergic system to this relationship between the glymphatic system, sleep, and these neurological disorders is also explored. Overall, in order to develop and utilize therapeutic interventions centred around the glymphatic system we must first dedicate further investigation to elucidating these discrepancies and unanswered questions.

关键词： basal ganglia cavitation   ECHS1   HIBCH   Leigh syndrome   methacrylate metabolites   paroxysmal dystonia   valine catabolism  

摘要： The neurological phenotype of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) and short-chain enoyl-CoA hydratase (SCEH) defects is expanding and natural history studies are necessary to improve clinical management. From 42 patients with Leigh syndrome studied by massive parallel sequencing, we identified five patients with SCEH and HIBCH deficiency. Fourteen additional patients were recruited through collaborations with other centres. In total, we analysed the neurological features and mutation spectrum in 19 new SCEH/HIBCH patients. For natural history studies and phenotype to genotype associations we also included 70 previously reported patients. The 19 newly identified cases presented with Leigh syndrome (SCEH, n = 11;HIBCH, n = 6) and paroxysmal dystonia (SCEH, n = 2). Basal ganglia lesions (18 patients) were associated with small cysts in the putamen/pallidum in half of the cases, a characteristic hallmark for diagnosis. Eighteen pathogenic variants were identified, 11 were novel. Among all 89 cases, we observed a longer survival in HIBCH compared to SCEH patients, and in HIBCH patients carrying homozygous mutations on the protein surface compared to those with variants inside/near the catalytic region. The SCEH p.(Ala173Val) change was associated with a milder form of paroxysmal dystonia triggered by increased energy demands. In a child harbouring SCEH p.(Ala173Val) and the novel p.(Leu123Phe) change, an 83.6% reduction of the protein was observed in fibroblasts. The SCEH and HIBCH defects in the catabolic valine pathway were a frequent cause of Leigh syndrome in our cohort. We identified phenotype and genotype associations that may help predict outcome and improve clinical management.

关键词： PARP-1   Neuroinflammation   Neurological disorders   PARP1 inhibitors  

摘要： Poly (ADP-ribose) polymerases (PARPs) constitute a family of enzymes associated with divergent cellular processes that are not limited to DNA repair, chromatin organization, genome integrity, and apoptosis but also found to play a crucial role in inflammation. PARPs mediate poly (ADP-ribosylation) of DNA binding proteins that is often responsible for chromatin remodeling thereby ensure effective repairing of DNA stand breaks although during the conditions of severe genotoxic stress PARPs direct the cell fate towards apoptotic events. Recent discoveries have pushed PARPs into the spotlight as targets for treating cancer, metabolic, inflammatory and neurological disorders. Of note, PARP-1 is the most abundant isoform of PARPs (18 member super family) which executes more than 90% of PARPs functions. Since oxidative/nitrosative stress actuated PARP-1 is linked to vigorous DNA damage and wide spread provocative inflammatory response that underlie the aetiopathogenesis of different neurological disorders, possibility of developing PARP-1 inhibitors as plausible neurotherapeutic agents attracts considerable research interest. This review outlines the recent advances in PARP-1 biology and examines the capability of PARP-1 inhibitors as treatment modalities in intense and interminable diseases of neuronal origin.

摘要： This commentary is on the original article by Verity et al. on pages 287–294 of this issue.

关键词： Interpregnancy interval   Long-term   Offspring   Neurological morbidity   Neurological disease  

摘要： Purpose The purpose of our study was to evaluate the effect of IPI on long-term neurological morbidity of the offspring. Methods In this retrospective cohort study, 144,397 singleton infants born to multiparous mothers, between the years 1991 and 2014 in a tertiary medical center, were evaluated for different perinatal outcomes and were followed until 18 years of age for long-term neurological morbidity according to three IPI groups: Short IPI (< 6 months), long IPI (> 60 months) and intermediate IPI (6-60 months). We used a Kaplan-Meier survival curve to compare cumulative incidence of long-term neurological morbidity, and a Cox regression analysis to control for confounders such as gestational age, birth weight and maternal age. Results Offspring born to mothers with long IPI had higher rates of neurological morbidity (3.62% among offspring born after long IPI vs. 3.18% and 3.19% among offspring born after short and intermediate IPI, respectively,p = 0.041). The cumulative incidence of long-term neurological morbidity was significantly higher in the long IPI group (Kaplan-Meier log-rank testp < 0.001). Being born after a long IPI was found to be an independent risk factor for long-term neurological morbidity of the offspring (adjusted hazard ratio 1.2;95% confidence interval 1.1-1.4;p < 0.001). Conclusion Long IPI is independently associated with an increased risk of long-term neurological morbidity of the offspring.

关键词： Coenzyme Q   Mitochondria   Neurological diseases   Secondary coenzyme Q deficiency   Brain   Muscle  

摘要： Coenzyme Q (CoQ) is a ubiquitous lipid serving essential cellular functions. It is the only component of the mitochondrial respiratory chain that can be exogenously absorbed. Here, we provide an overview of current knowledge, controversies, and open questions about CoQ intracellular and tissue distribution, in particular in brain and skeletal muscle. We discuss human neurological diseases and mouse models associated with secondary CoQ deficiency in these tissues and highlight pharmacokinetic and anatomical challenges in exogenous CoQ biodistribution, recent improvements in CoQ formulations and imaging, as well as alternative therapeutical strategies to CoQ supplementation. The last section proposes possible mechanisms underlying secondary CoQ deficiency in human diseases with emphasis on neurological and neuromuscular disorders.

关键词： Escin   Intracerebral hemorrhage   Blood brain barrier   Systemic inflammation  

摘要： This study aims to investigate whether escin ameliorates the impairments of neurological function by ameliorating systemic inflammation instead of targeting the brain directly in intracerebral hemorrhage (ICH) mice. It showed that escin did not cross the blood brain barrier (BBB). Compared with the ICH group, the Garcia test scores in the escin groups were significantly increased. Brain water contents and Evans blue extravasation of the right basal ganglia in the ICH group were augmented, and significantly reduced by escin. Escin abated the increases of monocyte counts and serum IL-1 beta levels induced by ICH. IL-1 beta administration reversed the effect of escin on Garcia test scores, the brain water contents, and the Evans blue extravasation. Escin ameliorated the increasing levels of RhoA, ROCK1, nuclear NF-kappa B and the decreasing expression of I kappa B alpha, cytosolic NF-kappa B, occludin, claudin-5 in the ICH group. IL-1 beta administration blocked not only escin-mediated increases of I kappa B alpha, cytosolic NF-kappa B, occludin, and claudin-5, but also escin-caused decreases of RhoA, ROCK1, and nuclear NF-kappa B. The results indicate that escin improves neurological outcomes and the BBB function in ICH mice, which is associated with attenuating ICH-induced peripheral system inflammation, and therefore, inhibiting IL-1 beta/RhoA/NF-kappa B signaling pathway in BBB, at least in part. These findings suggest that it may be useful to ameliorate brain injury by inhibiting systemic inflammation instead of aiming to target the brain directly after ICH.