关键词： Complex V   Phenotype   MT-ATP6   Blue native PAGE   Respirometry  

摘要： Diagnosing complex V deficiencies caused by new variants in mitochondrial DNA is challenging due to the rarity, phenotypic diversity, and limited functional assessments. We describe a child with the m.9032T > C variant in MT-ATP6 encoding p.(Leu169Pro), with primary presentation of microcephaly, ataxia, hearing loss, and lactic acidosis. Functional studies reveal abnormal fragment F1 of complex V on blue native gel electrophoresis. Respirometry showed excessively tight coupling through complex V depressing oxygen consumption upon ADP stimulation and an excessive increase following uncoupling, in the presence of upregulation of mitochondrial biogenesis. These data add evidence about pathogenicity and functional impact of this variant.

关键词： Stroke   Basilar artery occlusion   Endovascular therapy   Outcomes  

摘要： Background and purpose: We hypothesized that the relationships between treatments and outcomes in acute basilar artery occlusion (BAO) are different, depending on the severity of initial neurological deficits. Methods: Of 2420 ischemic stroke patients with large vessel occlusion in a prospective, multicenter registry in Japan, patients with acute BAO were enrolled. Subjects were divided into two severity groups according to the baseline NIH Stroke Scale score: severe (>= 10) and mild (<10) groups. The primary effectiveness outcome was favorable outcome, defined as modified Rankin Scale score 0-3 at 3 months. Safety outcomes included any intracranial hemorrhage (ICH) within 72 h. Outcomes in each group were compared between patients who received endovascular therapy (EVT) and those with standard medical treatment (SMT). Results: In this study, 167 patients (52 female;median age 75 years) were analyzed. The favorable outcome was seen in 93 patients (56%) overall. In the severe group (n = 128), the proportion of favorable outcome was higher in patients who received EVT (60/111, 54%) than those with SMT (2/17, 12%, P < 0.01). In the mild group (n = 39), the rates of favorable outcome were comparable between the EVT (13/18, 72%) and SMT patients (18/21, 86%, P = 0.43). No significant differences in the rates of any ICH were seen among any groups. Conclusions: In acute BAO stroke with severe neurological deficit, independent ambulation was more frequently seen in patients who received EVT than those with SMT. Patients with mild neurological deficits showed similar rates of independent ambulation between the two treatment selections.

关键词： cerebral blood flow   cerebral ischemia   neuroinflammation   neuronal cell death   serum and glucocorticoid-regulated kinase  

摘要： Cardiopulmonary arrest (CA) is the leading cause of death and disability in the United States. CA-induced brain injury is influenced by multifactorial processes, including reduced cerebral blood flow (hypoperfusion) and neuroinflammation, which can lead to neuronal cell death and functional deficits. We have identified serum and glucocorticoid-regulated kinase-1 (SGK1) as a new target in brain ischemia previously described in the heart, liver, and kidneys (i.e., diabetes and hypertension). Our data suggest brain SGK1 mRNA and protein expression (i.e., hippocampus), presented with hypoperfusion (low cerebral blood flow) and neuroinflammation, leading to further studies of the potential role of SGK1 in CA-induced brain injury. We used a 6-min asphyxia cardiac arrest (ACA) rat model to induce global cerebral ischemia. Modulation of SGK1 was implemented via GSK650394, a SGK1-specific inhibitor (1.2 mu g/kg icv). Accordingly, treatment with GSK650394 attenuated cortical hypoperfusion and neuroinflammation (via Iba1 expression) after ACA, whereas neuronal survival was enhanced in the CA1 region of the hippocampus. Learning/memory deficits were observed 3 days after ACA but ameliorated with GSK650394. In conclusion, SGK1 is a major contributor to ACA-induced brain injury and neurological deficits, while inhibition of SGK1 with GSK650394 provided neuroprotection against CA-induced hypoperfusion, neuroinflammation, neuronal cell death, and learning/memory deficits. Our studies could lead to a novel, therapeutic target for alleviating brain injury following cerebral ischemia. NEW & NOTEWORTHY Upregulation of SGK1 exacerbates brain injury during cerebral ischemia. Inhibition of SGK1 affords neuroprotection against cardiac arrest-induced hypoperfusion, neuroinflammation, neuronal cell death, and neurological deficits.

摘要： Additionally, the study by Kong and colleagues3 cited by Li and colleagues' Correspondence did not report co-infection, but rather early cases of COVID-19 in Wuhan, China, that were detected through the national influenza surveillance programme; existing influenza surveillance networks have been used for sentinel testing and to look for potential signs of community transmission worldwide, as supported by the WHO Global Influenza Surveillance and Response System. Furthermore, influenza-like illness is a syndromic definition and does not imply influenza to be the causative illness; its description aligns closely with the “acute respiratory infection” definition used to prompt testing for COVID-19 in earlier WHO and national guidelines.4 Our group has shown previously that, in patients with new neurological disease and evidence of more than one infection, there are additional challenges in thinking about causality, particularly when the results are from specimens collected outside the CNS.5,6 TS was an advisor for the GlaxoSmithKline ebola vaccine programme, chaired the Siemens diagnostics clinical advisory board and healthineers clinical advisory board, and also has a pending patent test for bacterial meningitis based on a blood test (GB 1606537.7; April 14, 2016). BS reports non-financial support from UK National Institute for Health Research through its Global Health Research Group on Brain Infections, outside the submitted work.

关键词： Neurological complications   SARS-CoV-2   Pandemic  

摘要： Background In December 2019, unexplained cases of pneumonia emerged in Wuhan, China, which were found to be secondary to the novel coronavirus SARS-CoV-2. On March 11, 2020, the WHO declared the Coronavirus Disease 2019 (COVID-2019) outbreak, a pandemic. Objective To clarify the neurological complications of SARS-CoV-2 infection including the potential mechanisms and therapeutic options. Methods We conducted a systematic literature search from December 01, 2019 to May 14, 2020 using multiple combinations of keywords from PubMed and Ovid Medline databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included articles with cases of COVID-19 where neurological involvement was evident. Results We were able to identify 82 cases of COVID-19 with neurological complications. The mean age was 62.3 years. 37.8% of the patients were women (n = 31). 48.8% of the patients (n = 40) had cerebrovascular insults, 28% (n = 23) had neuromuscular disorders, and 23% of the patients (n = 19) had encephalitis or encephalopathy. Conclusions Neurological manifestations of COVID-19 are not rare, especially large vessel stroke, Guillain-Barre syndrome, and meningoencephalitis. Moving forward, further studies are needed to clarify the prevalence of the neurological complications of SARS-CoV-2 infection, investigate their biological backgrounds, and test treatment options. Physicians should be cautious not to overlook other neurological diagnoses that can mimic COVID-19 during the pandemic.

关键词： cardiac surgery   cardiopulmonary bypass   delirium   hyperoxia   postoperative pulmonary complications  

关键词： Continuous electroencephalography (CEEG)   EEG   Critical care   Nonconvulsive seizure   Intensive care  

摘要： Monitoring critically ill patients in NCCU requires multiple modalities including neurological examinations, measurement of metabolic parameters (partial pressure of brain oxygen or micro dialysis), and monitoring of physiological parameters (Intracranial pressure monitoring, transcranial Doppler, and continuous electroencephalography [CEEG]). CEEG is an efficient monitoring tool to characterize spells, assess degree of encephalopathy, complement neuroimaging for identifying cause of possible coma, assess level of sedation, detect ischemia or vasospasm, and to assist with prognostication [4]. A review of 208 patients admitted to a neurocritical care unit from the emergency department (ED) for acute transient neurological deficits, loss of consciousness, or unclear motor phenomena found variability with clinical suspicion [16]. NCSE was successfully terminated for five patients (63%), but only one experienced clinical improvement, which was transient; and all eight patients eventually died after a period of prolonged coma.” [...]it remains unclear if treating NCSE affects outcome in patients with SAH [46].

关键词： Iatrogenesis   Elderly   Neurological manifestations   Adverse drug events  

摘要： Older people are often exposed to polypharmacy in a multimorbidity context. Inappropriate polypharmacy is often harmful, increasing the risk of inappropriate prescriptions and therefore adverse drug events (ADEs). Five to 20% of all hospital admissions are related to ADE in older people, among which 40 to 70% could be prevented. However, identifying ADEs and drug-related admissions in the elderly is challenging because ADEs often present as common geriatric problems such as falls, delirium, which might be due to the aging process, underlying diseases, and/or medications. In the pharmacovigilance database of the World Health Organization, drug-related neurological manifestations are the third reported cause of ADEs in the elderly, and neurological drugs are the third leading class of medications involved in ADEs. We must therefore be particularly vigilant, both in our prescriptions but also in our diagnoses to avoid prescribing inappropriate treatments and detect ADEs. Even though multiple pharmacologic changes occur in the elderly (absorption, distribution, drug metabolism and excretion), most of medications are still often prescribed at the same daily dosage as in young adults. When prescribing any drug for old patients, we should remember that daily intake should be adapted to these specificities, keeping in mind the old well-known aphorism "start low, go slow". In this review, we describe the main drug-related neurological manifestations (drug-induced movement disorders, falls, seizures, delirium, hypoglycemia, stroke, hyponatremia, peripheral neuropathy and myopathy, and serotonin syndrome) and the main drugs associated with neurological manifestations (dopamine receptor blocking agents, antithrombotics, anti-cholinergics, beta-lactams, antidepressants, benzodiazepines, mood stabilizers). (C) 2020 Elsevier Masson SAS. All rights reserved.