关键词： deep hypothermic circulatory arrest   permanent neurological dysfunction   prognostic factors   regional cerebral oxygen saturation monitoring   total aortic arch replacement  

摘要： Objective To explore the prognostic factors for permanent neurological dysfunction (PND) after total aortic arch replacement with regional cerebral oxygen saturation (rSO(2)) monitoring. Methods This retrospective study enrolled 98 type A aortic dissection aneurysm patients who underwent emergency total aortic arch replacement combined with deep hypothermic circulatory arrest and right axillary artery selective antegrade cerebral perfusion (SACP). Data such as age, gender, body mass index, preoperative coexisting disease, laboratory test results, intraoperative critical operation duration, and intraoperative rSO(2) were collected, and the neurological prognoses in the hospital were recorded and grouped by severity. Multiple logistic regression analysis was performed on the statistically significant differences between the groups to screen the predictors of postoperative neurological complications in these patients. Results Forty-two patients had postoperative neurological complications, among which there were 29 cases (29.6%) of transient neurological dysfunction, and 13 cases (13.3%) of PND. Multiple logistic regression results showed that advanced age, preoperative low platelet count, prolonged hemostasis time and lowest relative rSO(2) to baseline (Delta rSO(2)min) in each time period were risk factors for postoperative PND. The ROC curve measurement showed that the optimal cut-off value of Delta rSO(2)min was 79.7%, and the area under the curve was 0.708 (95% confidence interval = 0.557-0.858), p = 0.016;the optimal cut-off value of Delta rSO(2)min in SACP was 81.6%, and the area under the curve was 0.720 (95% confidence interval = 0.570-0.870), p = 0.011;the optimal cut-off value of Delta rSO(2)min in cardiopulmonary bypass (CPB) was 80.8%, and the area under the curve was 0.697 (95% confidence interval = 0.554-0.840), p = 0.023. Conclusion Intraoperative Delta rSO(2)min that is lower than the basal level of about 80%, advanced age, preoperative low platelet co

关键词： Quinone oxidoreductase   Multiple sclerosis   Alzheimer's disease   Protein misfolding   Antioxidant enzyme   Pharmacological chaperone  

摘要： NAD(P)H quinone oxidoreductase 1 (NQO1) is a multi-functional protein that catalyses the reduction of quinones (and other molecules), thus playing roles in xenobiotic detoxification and redox balance, and also has roles in stabilising apoptosis regulators such as p53. The structure and enzymology of NQO1 is well-characterised, showing a substituted enzyme mechanism in which NAD(P)H binds first and reduces an FAD cofactor in the active site, assisted by a charge relay system involving Tyr-155 and His-161. Protein dynamics play important role in physio-pathological aspects of this protein. NQO1 is a good target to treat cancer due to its overexpression in cancer cells. A polymorphic form of NQO1 (p.P187S) is associated with increased cancer risk and certain neurological disorders (such as multiple sclerosis and Alzheimer's disease), possibly due to its roles in the antioxidant defence. p.P187S has greatly reduced FAD affinity and stability, due to destabilization of the flavin binding site and the C-terminal domain, which leading to reduced activity and enhanced degradation. Suppressor mutations partially restore the activity of p.P187S by local stabilization of these regions, and showing long-range allosteric communication within the protein. Consequently, the correction of NQO1 misfolding by pharmacological chaperones is a viable strategy, which may be useful to treat cancer and some neurological conditions, targeting structural spots linked to specific disease-mechanisms. Thus, NQO1 emerges as a good model to investigate loss of function mechanisms in genetic diseases as well as to improve strategies to discriminate between neutral and pathogenic variants in genome-wide sequencing studies.

关键词： Stiff-person syndrome   Cerebellar ataxia   Epilepsy   Autoimmune   GAD antibodies  

摘要： A number of neurological syndromes have been described in patients with positive serum antibodies (Abs) against the enzyme glutamic acid decarboxylase (GAD), the rate limiting step in the synthesis of GABA (gamma-aminobutyric acid). These disorders include: classical stiff-person syndrome and variants, cerebellar ataxia, limbic and extra-limbic encephalitis, nystagmus/oculomotor dysfunction, drug-resistant epilepsy, paraneoplastic stiff-person syndrome and progressive encephalopathy with rigidity and myoclonus (PERM), the latter two are mainly related to amphiphysin and the glycine receptor Abs respectively;but patients may also have positive GAD-Abs. Although observations are consistent with an autoimmune response in these patients and there is evidence of GABAergic dysfunction in some cases;the pathogenic role of GAD-Abs in the nervous system has not been clarified and it is a matter of debate. The diagnosis of these syndromes is based on clinical grounds plus the presence of GAD-Abs in serum and CSF with demonstration of intrathecal secretion. Although some presentations may be negative for GAD-Abs, such as stiff-person syndrome;positive GAD-Abs are required for the diagnosis in patients with cerebellar ataxia, encephalitis, and epilepsy. Immunotherapy is required for most patients. Intravenous immunoglobulins, oral or IV steroids and plasma exchange are considered the first line options, aimed to induce remission, but chronic immunosuppression is usually required. Symptomatic therapy should also be provided, aimed to control muscle spasms, seizures, delirium, etc. Prognosis varies among patients;but it is considered intermediate between that of patients with neurological syndromes associated with neural Abs against membrane antigens and those with onconeural Abs.

关键词： Aging   Brain injury   Ischemia   Migraine   Spreading depolarization   Spreading depression  

摘要： Secondary injury following acute brain insults significantly contributes to poorer neurological outcome. The spontaneous, recurrent occurrence of spreading depolarization events (SD) has been recognized as a potent secondary injury mechanism in subarachnoid hemorrhage, malignant ischemic stroke and traumatic brain injury. In addition, SD is the underlying mechanism of the aura symptoms of migraineurs. The susceptibility of the nervous tissue to SD is subject to the metabolic status of the tissue, the ionic composition of the extracellular space, and the functional status of ion pumps, voltage-gated and other cation channels, glutamate receptors and excitatory amino acid transporters. All these mechanisms tune the excitability of the nervous tissue. Aging has also been found to alter SD susceptibility, which appears to be highest at young adulthood, and decline over the aging process. The lower susceptibility of the cerebral gray matter to SD in the old brain may be caused by the age-related impairment of mechanisms implicated in ion translocations between the intra- and extracellular compartments, glutamate signaling and surplus potassium and glutamate clearance. Even though the aging nervous tissue is thus less able to sustain SD, the consequences of SD recurrence in the old brain have proven to be graver, possibly leading to accelerated lesion maturation. Taken that recurrent SDs may pose an increased burden in the aging injured brain, the benefit of therapeutic approaches to restrict SD generation and propagation may be particularly relevant for elderly patients.

关键词： Stroke   Exercise   Community program  

摘要： Background: Many survivors of stroke face chronic disability and increased risk for recurrent stroke. Regular physical activity can reduce these risk factors and improve cardiovascular fitness. Most survivors of stroke face barriers to exercise, including lack of access to programs;as a result, most are sedentary. Objective: Pilot the Neurological Exercise Training (NExT) program or survivors of stroke for attendance, safety, and effectiveness. Methods: The NExT program was designed to promote self-directed exercise in a safe, accessible environment. Six participants attended as desired during open gym hours over two exercise periods per week totalling 19 weeks. After, participants were encouraged to continue exercise away from the gym for 20 weeks. Practicability of the program was assessed through safety, attendance, exercise intensity, and perception of the program. Pilot effectiveness measures were performed at five time points and effect sizes were generated. Results: Attendance averaged 76% (SD12%) of possible sessions with an average duration of 62 (SD 11.3) minutes. Effectiveness measures had positive effect sizes after 19 weeks of the NExT program, but these benefits were lost after 20-weeks (cohen's d, mobility = 0.67 to -0.22, balance = 0.57 to -1.22, strength = 0.41 to -0.30, endurance = 0.09 to -0.19 and fatigue = 1.02 to -0.57). Conclusion: Results demonstrate that a community-based gym that is accessible for survivors of stroke will be well attended and perceived as beneficial. Pilot data suggests positive changes in multiple health domains regardless of the type of exercise self-selected by participants. Offering the gym on a continual basis may maintain gains. (C) 2019 Elsevier Inc. All rights reserved.

关键词： Childhood epilepsy   Civil rights   Children with disability   Disability evaluation  

摘要： Epilepsy is a chronic neurological disorder which affects not only the health of the affected child, but also has an economic, psychological and emotional impact on the family as a whole. In the transition from Person with Disability (PWD) act (1995) to Rights of Persons with Disabilities act (RPWD act) (2016), which covers all aspects of life of a person with any disability, epilepsy has been excluded from the list of disorders, resulting in a loss of many of the benefits that were earlier available to persons with epilepsy, causing concern to all caregivers of persons with epilepsy. Additionally, physicians/ pediatricians/ neurologists are not really aware of the benefits that are available to persons with epilepsy, especially children. To address these issues, an expert group meeting of pediatric neurologists and epileptologists in India along with social workers/epilepsy educators legal experts, parents, and teachers was held. The implication of epilepsy being dropped as a disability, was discussed, and most of the experts concurred that epilepsy should be considered as a disability, depending of the type of seizures or the epilepsy syndrome. Also, the current status of income tax benefits, child care benefits, travel concession, schooling and health insurance for children with epilepsy in India were also discussed. The importance of creating awareness on these issues was stressed on. Here authors present the group consensus statement on these legal and social aspects about the care of children with epilepsy.

关键词： Breastfeeding   Maternal smoking   Neurobehavioural profile   Newborn infants   Pregnancy  

摘要： Aim We examined associations between neurological alterations in infants born to smoking mothers and breastfeeding success at discharge and three months of age. Methods This 2016 study compared 35 normal weight infants born to smoking mothers at 37-41 weeks and 35 matched controls born to non-smoking mothers at the Maternity Hospital of Careggi University, Florence, Italy. Neonatal behaviour was evaluated using the neurological soft signs (NSS) component of the Graham-Rosenblith Scale. Breastfeeding variables were measured using the LATCH score that covers: breast latching, audible swallowing, type of nipple, mother's comfort and help they needed to hold their baby to their breast. A questionnaire on excessive crying and feeding was distributed at discharge, and further data were collected during a three-month telephone interview. Results At discharge, the infants born to smoking mothers had a significantly lower LATCH score and significantly poorer performance on several items of the NSS component than the controls. The LATCH score and number of NSS were inversely proportional. At the three-month follow-up only 57.1% of the smoking group infants were breastfeeding compared with 87.5% of the control infants (p < 0.01). Conclusion Infants with smoking mothers displayed altered neurobehavioural profiles and had a difficult start to breastfeeding.

关键词： Parkinson's disease   Impulse control disorders   Capacity   Control   Responsibility  

摘要： Dopamine replacement therapy can induce impulse control disorders (ICDs) (e.g., hypersexuality) in susceptible Parkinson's disease patients. ICDs can sometimes result in criminal offending. In a number of past Commonwealth cases, it appears offending ICD patients have been considered to be suffering from 'irresistible impulses' such that their decision-making capacity, behavioural control and responsibility were totally compromised. This contrasts with courts' general scepticism of drug-induced 'compulsion' in cases of addiction-related offending. In one case of explicit ICD-related offending, testimony was limited to three experts and not contested by the prosecution. We explored whether the testimony offered in this particular case, and another similar case, reflects the views of the neurological and psychiatric communities at large. Thematic analysis revealed that neurologists, geriatricians and psychiatrists (n = 11): (a) attributed ICDs to a variety of causes;(b) considered ICD patients' decision-making capacities and behavioural control to be partially, but not totally, compromised;(c) were divided or ambivalent about ICD patients' responsibility;and (d) astutely noted the difficulties inherent in assessing complex constructs such as 'control' and 'responsibility'. We suggest that there is sufficient divergence between our findings and expert testimony from past cases for prosecution teams to engage their own experts in future cases of ICD-related offending. (C) 2018 Elsevier Ltd. All rights reserved.

关键词： mHealth  

关键词： riluzole   spinal cord injury   neurological function   meta-analysis  

摘要： Spinal cord injury (SCI) is a devastating condition that has few treatment options. Riluzole, a sodium channel blocker used to treat amyotrophic lateral sclerosis, has been initially trialed in human SCI. We performed a systematic review to critically assess the efficacy of riluzole in locomotor recovery and damage extension in SCI rat models, and the potential for clinical translation. PubMed, Embase, Cochrane Library, and Chinese databases were searched from their inception date to March 2018. Two reviewers independently selected animal studies that evaluated neurological recovery and lesion area following riluzole treatment in SCI rat models, extracted data and assessed methodological quality. Pairwise meta-analysis, subgroup analysis, and network meta-analysis were performed to assess the effects of riluzole on SCI. Ten eligible studies were included. Two studies had high methodological quality. Overall, the Basso, Beattie, and Bresnahan scores were increased in riluzole-treated animals versus controls, and effect sizes showed a gradual increase from the 1st (five studies, n = 104, mean difference = 1.24, 95% CI = 0.11 to 2.37, p = 0.03) to 6th week after treatment (five studies, n = 120, mean difference = 2.34, 95% CI = 1.26 to 3.42, p < 0.0001). Riluzole was associated with improved outcomes in the inclined plane test and the tissue preservation area. Subgroup analyses suggested an association of locomotor recovery with riluzole dose. Network meta-analysis showed that 5 mg/kg riluzole exhibited greater protection than 2.5 and 8 mg/kg riluzole. Collectively, this review suggests that riluzole has a protective effect on SCI, with good safety and a clear mechanism of action and may be suitable for future clinical trials or applications. However, animal results should be interpreted with caution given the known limitations in animal experimental design and methodological quality.