关键词： Mixed effect models   Model based drug development   Disease progression modeling   Pharmacometrics   Neuroscience  

摘要： Intracerebral hemorrhage (ICH) is a form of stroke characterized by uncontrolled bleeding into the parenchyma of the brain. There is no approved therapy for ICH and it is associated with very poor neurological outcomes with around half of subjects dying within 1 month and most subjects showing complete or partial disability. A key challenge is to identify subjects who could benefit from intervention using characteristics such as baseline hemorrhage volume and the increase in hemorrhage volume in the first few hours, which have been correlated with final outcomes in ICH. Combined longitudinal models were developed to describe stroke scales using categorical data (Modified Rankin Scale, mRS), continuous bounded data (National Institutes of Health Stroke Scale, NIHSS), and time to death. Covariate effects for baseline hematoma volume and maximum increase in hematoma volume were incorporated to assess the improvement in outcome when hematoma volume increase would be reduced by a potential treatment. The combined model provided an adequate description of stroke scales, with patients split into a Non-survival and a High-survival sub-population, and dropout due to death was well described by a constant hazard survival model. Models were compared indicating that the combined mRS/NIHSS model provided the most information, followed by the NIHSS-only model, and the mRS-only model, and finally the traditional statistical analysis on dichotomized response at 90 days. Simulations showed that substantial reductions in hematoma volume increase were required to increase the probability of a favorable outcome.

摘要： Study objective: Although most transient ischemic attack and minor stroke patients in US emergency departments (EDs) are admitted, experience in other countries suggests that timely outpatient evaluation of transient ischemic attack and minor stroke can be safe. We assess the feasibility and safety of a rapid outpatient stroke clinic for transient ischemic attack and minor stroke: Rapid Access Vascular Evaluation-Neurology (RAVEN). Methods: Transient ischemic attack and minor stroke patients presenting to the ED with a National Institutes of Health Stroke Scale score of 5 or less and nondisabling deficit were assessed for potential discharge to RAVEN with a protocol incorporating social and medical criteria. Outpatient evaluation by a vascular neurologist, including vessel imaging, was performed within 24 hours at the RAVEN clinic. Participants were evaluated for compliance with clinic attendance and 90-day recurrent transient ischemic attack and minor stroke and hospitalization rates. Results: Between December 2016 and June 2018, 162 transient ischemic attack and minor stroke patients were discharged to RAVEN. One hundred fifty-four patients (95.1%) appeared as scheduled and 101 (66%) had a final diagnosis of transient ischemic attack and minor stroke. Two patients (1.3%) required hospitalization (one for worsening symptoms and another for intracranial arterial stenosis caused by zoster) at RAVEN evaluation. Among the 101 patients with confirmed transient ischemic attack and minor stroke, 18 (19.1%) had returned to an ED or been admitted at 90 days. Five were noted to have had recurrent neurologic symptoms diagnosed as transient ischemic attack (4.9%), whereas one had a recurrent stroke (0.9%). No individuals with transient ischemic attack and minor stroke died, and none received thrombolytics or thrombectomy, during the interval period. These 90-day outcomes were similar to historical published data on transient ischemic attack and minor stroke. Conclusion: Rapid

关键词： Fall Prevention   Exercise Intervention   Neurological Disorder   Systematic Review  

摘要： Fall prevention requires a multifaceted approach that should include individual risk assessment and intervention strategies. Exercise interventions may mitigate most risk factors for falls (eg, balance impairment, gait impairment, and muscle weakness). Numerous systematic reviews or meta-analyses have assessed the effectiveness of exercise interventions among people with various types of neurological disorders;however, the evidence obtained has not been synthesized into an overview. Therefore, the present systematic review assessed systematic reviews of exercise intervention for fall prevention among people with neurological disorders. The research sources were the Cochrane Database of Systematic Reviews, PubMed, and Embase. Eligible studies were selected, and data were extracted independently by two reviewers. A total of 15 studies (six systematic reviews and nine meta-analyses) were included. These systematic reviews examined in this study have demonstrated that exercise interventions reduced the number, frequency, and rate of falls among people with neurological disorders, including cognitive impairment, dementia, and Parkinson disease. Furthermore, the current study presented insufficient evidence regarding the effectiveness of exercise interventions for fall prevention among people with stroke, multiple sclerosis, and diabetes mellitus with polyneuropathy. Therefore, additional investigations are necessary to evaluate the effectiveness of exercise for fall prevention among people with multiple sclerosis, stroke, and diabetes mellitus with polyneuropathy.

关键词： Bone marrow   microglia   phagocytosis   stroke   triggering receptor expressed on myeloid cells-2  

摘要： Triggering receptor expressed on myeloid cells-2 (TREM2) is an innate immune receptor that promotes phagocytosis by myeloid cells such as microglia and macrophages. We previously showed that TREM2 deficiency worsened outcomes from experimental stroke and impeded phagocytosis. However, myeloid cells participating in stroke pathology include both brain resident microglia and circulating macrophages. We now clarify whether TREM2 on brain microglia or circulating macrophages contribute to its beneficial role in ischemic stroke by generating bone marrow (BM) chimeric mice. BM chimera mice from TREM2 knockout (KO) or wild type (Wt) mice were used as donor and recipient mice. Mice were subjected to experimental stroke, and neurological function and infarct volume were assessed. Mice with intact TREM2 in brain microglia showed better neurological recovery and reduced infarct volumes, compared with mice lacking microglial TREM2. Myeloid cell activation and numbers of phagocytes were decreased in mice lacking brain TREM2, compared with mice with intact brain TREM2. These results suggest that TREM2 expression is important for post-stroke recovery, and that TREM2 expression on brain resident microglia is more essential to this recovery, than that of circulating macrophages. These findings might suggest a new therapeutic target for cerebrovascular diseases.

摘要： Background: One of the most critical phases of carotid endarterectomy (CEA) is the carotid cross-clamping test, which is a concrete evaluation of efficacy of collateral cerebral perfusion. Some studies revealed a strong correlation between tolerance to carotid cross-clamping and postoperative transient ischemic attack (TIA)/stroke complications. The aim of the study is to make a global analysis of supra-aortic trunks (SAT) and circle of Willis (CoW) patency to predict the tolerance to carotid cross-clamping preoperatively. Methods: We observed retrospectively 503 patients who underwent CEA under local anesthesia between January 2012 and 2017. We analyzed single preoperative risk factors, drug therapy, and vessels patency of the group of patients who did or did not present neurological symptoms at carotid cross-clamping. Afterward, we created a cerebral perfusion score (PTOT) to estimate the efficacy of collateral cerebral perfusion and we compared the results from both groups. The score ranges from 0 (hypothetical total occlusion of the SAT and CoW) to 0.65 in case of patency of all arterial districts. Moreover, we evaluated postoperative complication rates. Results: Patients with previous neurological symptoms, female gender, and diabetes correlate with a lower tolerance to carotid cross-clamping (odds ratio: 2.57, 2.78, and 2.57, respectively;P value < 0.05). The SAT and CoW score revealed that patients with score <0.2 more frequently did not tolerate carotid cross-clamping (P value 0.01). Patients who required an intra-operative shunt presented a higher risk of TIA/stroke within 30 days from surgery than those with a better neurological compensation (P value 0.03). Conclusions: The efficacy of cerebral mechanisms of compensation during carotid cross-clamping reflects the capability of the brain to adapt to ischemic insults, and this also correlates with the postoperative risk of TIA/stroke. It is possible to identify preoperatively patients with a higher risk of

关键词： GNDS   Multiple sclerosis   Cognitive impairment   PASAT   SDMT  

摘要： Objectives: Cognitive impairment is a common symptom affecting daily activities of the patients with multiple sclerosis (MS). Various cognitive evaluation tests are available, yet most of them are complex and time-consuming to perform in outpatient clinics. In this study, we aimed to validate a Japanese version of the Guys Neurological Disability Scale (GNDS) as a user-friendly tool to evaluate comprehensive disabilities in MS including cognitive function. Methods: Questions of the GNDS were translated into Japanese and named GNDS-J. Forty-four patients were examined by the Expanded Disability Status Scale (EDSS), the Paced Auditory Serial Addition Test (PASAT), the Symbol Digit Modalities Test (SDMT), the vitality scale, and the GNDS-J in the same time at remission state. Results: The GNDS-J scores correlated with the EDSS scores(r = 0.61), and inversely correlated with the PASAT2/1(r = -0.56/-0.49) scores and the SDMT scores (r = -0.68), whereas the GNDS-J did not show any correlation with the vitality scale. Furthermore, eleven patients were evaluated over 5 years for changes in these scores. Eight out of 11 patients had exacerbated GNDS, and all of these patients experienced clinical relapse during this period. Conclusion: The GNDS-J is a valid tool to perform in outpatient clinics, which could provide a comprehensive scale for evaluating symptoms of MS, thus the disease activity by repeated measure.

关键词： Diseases  

摘要： In the last 25 years C-13 MRS has been established as the only noninvasive method for measuring glutamate neurotransmission and cell specific neuroenergetics. Although technically and experimentally challenging C-13 MRS has already provided important new information on the relationship between neuroenergetics and neuronal function, the high energy cost of brain function in the resting state and the role of altered neuroenergetics and neurotransmitter cycling in disease. In this paper we review the metabolic and neurotransmitter pathways that can be measured by C-13 MRS and key findings on the linkage between neuroenergetics, neurotransmitter cycling, and brain function. Applications of C-13 MRS to neurological and psychiatric disease as well as brain cancer are reviewed. Recent technological developments that may help to overcome spatial resolution and brain coverage limitations of C-13 MRS are discussed.

摘要： Earlier this year, NICE published a new guideline on the recognition and referral of patients with suspected neurological conditions (NG127), to help non‐specialist healthcare professionals identify people who should be offered further specialist investigation. This article provides a brief summary of the guidance. [ABSTRACT FROM AUTHOR]

关键词： autoimmune disease   autonomic neuropathy   chronic nausea and vomiting   paraneoplastic  

摘要： Background The identification of autoantibodies directed against neuronal antigens has led to the recognition of a wide spectrum of neurological autoimmune disorders (NAD). With timely recognition and treatment, many patients with NAD see rapid improvement. Symptoms associated with NAD can be diverse and are determined by the regions of the nervous system affected. In addition to neurological symptoms, a number of these disorders present with prominent gastrointestinal (GI) manifestations such as nausea, diarrhea, weight loss, and gastroparesis prompting an initial evaluation by gastroenterologists. Purpose This review provides a general overview of autoantibodies within the nervous system, focusing on three scenarios in which nervous system autoimmunity may initially present with gut symptoms. A general approach to evaluation and treatment, including antibody testing, will be reviewed.

关键词： Oil spill   Deepwater Horizon   Coast Guard   Crude oil   Neurological symptoms   Exposure  

摘要： Introduction: The Deepwater Horizon (DWH) oil spill was the largest marine oil spill in U.S. history, involving the response of tens of thousands clean-up workers. Over 8500 United States Coast Guard personnel were deployed in response to the spill. Little is understood about the acute neurological effects of oil spill clean-uprelated exposures. Given the large number of people involved in large oil spill clean-ups, study of these effects is warranted. Methods: We utilized exposure, health, and lifestyle data from a post-deployment survey administered to Coast Guard responders to the DWH oil spill. Crude oil exposure was assessed via self-reported inhalation and skin contact metrics, categorized by frequency of self-reported exposure to crude oil during deployment (never, rarely, sometimes, most/all of the time). Combined exposure to crude oil and oil dispersant was also evaluated. Adjusted log binomial regressions were used to calculate prevalence ratios (PRs) and 95% confidence intervals (CI), investigating the associations between oil spill exposures and neurological symptoms during deployment. Stratified analyses investigated potential effect modification by sex, exhaust fume exposure, personal protective equipment (PPE) use, and deployment duration and timing. Results: Increasing frequency of crude oil exposure via inhalation was associated with increased likelihood of headaches (PRmost/all (vs.) (never) = 1.80), lightheadedness (PRmost/all vs. never = 3.36), difficulty concentrating (PRmost/all vs. never = 1.72), numbness/tingling sensation (PRmost/all vs. never = 3.32), blurred vision (PRmost/all vs. (never) = 2.87), and memory loss/confusion (PRmost/all vs. never = 2.03), with significant tests for trend. Similar results were found for crude oil exposure via skin contact. Exposure to both oil and oil dispersants yielded associations that were appreciably greater in magnitude than for oil alone for all neurological symptoms. Sensitivity analyses excluding res