关键词： immunogenetics   neurological disease  

摘要： Genes encoding antigen-presenting molecules within the human major histocompatibility complex (MHC) account for the highest component of genetic risk for many neurological diseases, such as multiple sclerosis, neuromyelitis optica, Parkinson's disease, Alzheimer's disease, schizophrenia, myasthenia gravis and amyotrophic lateral sclerosis. Myriad genetic, immunological and environmental factors may contribute to an individual's susceptibility to neurological disease. Here, we review and discuss the decades long research on the influence of genetic variation at the MHC locus and the role of immunogenetic killer cell immunoglobulin-like receptor (KIR) loci in neurological diseases, including multiple sclerosis, neuromyelitis optica, Parkinson's disease, Alzheimer's disease, schizophrenia, myasthenia gravis and amyotrophic lateral sclerosis. The findings of immunogenetic association studies are consistent with a polygenic model of inheritance in the heterogeneous and multifactorial nature of complex traits in various neurological diseases. Future investigation is highly recommended to evaluate both coding and non-coding variation in immunogenetic loci using high-throughput high-resolution next-generation sequencing technologies in diverse ethnic groups to fully appreciate their role in neurological diseases.

关键词： Vasospasm   Hemorrhage   Microthrombi   Sensitivomotor deficits   Mice  

摘要： Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality and morbidity. Long-term cognitive and sensorimotor deficits are serious complications following SAH but still not well explained and described in mouse preclinical models. The aim of our study is to characterize a well-mastered SAH murine model and to establish developing pathological mechanisms leading to cognitive and motor deficits, allowing identification of specific targets involved in these long-term troubles. We hereby demonstrate that the double blood injection model of SAH induced long-lasting large cerebral artery vasospasm (CVS), microthrombosis formation and cerebral brain damage including defect in potential paravascular diffusion. These neurobiological alterations appear to be associated with sensorimotor and cognitive dysfunctions mainly detected 10 days after the bleeding episode. In conclusion, this characterized model of SAH in mice, stressing prolonged neurobiological pathological mechanisms and associated sensitivomotor deficits, will constitute a validated preclinical model to better decipher the link between CVS, long-term cerebral apoptosis and cognitive disorders occurring during SAH and to allow investigating novel therapeutic approaches in transgenic mice.

关键词： Tics   Tourette disorder   Obsessive-compulsive disorder   Repetitive behaviors   Differential diagnosis  

摘要： Repetitive movements are the hallmark of chronic tic disorders such as Tourette disorder (TD), whereas repetitive behaviors are characteristic of obsessive-compulsive disorder (OCD). Both disorders tend to frequently co-occur, as a substantial number of patients with TD also suffer from OCD and vice versa. While the clinical distinction between tics and OCD is usually easy, there are borderline forms, and correct symptom recognition is vital for choosing the appropriate treatment modalities for each disorder, be they pharmacological, psychotherapeutic (behavioral therapy) or brain stimulation (deep brain stimulation, repetitive transcranial magnetic stimulation). (C) 2018 Elsevier Masson SAS. All rights reserved.

关键词： Wilson's disease   Long-term outcome   Motor abnormalities   Non-motor abnormalities   Compliance   Comorbidity  

摘要： Introduction: Aim of the study was to characterize the clinical spectrum of long-term treated patients with Wilson's disease (WD) and to identify risk factors influencing long-term outcome. Methods: In a cross-sectional study 30 WD-patients being treated for at least 2.5 and up to 31 years underwent a detailed clinical investigation, scoring of clinical findings yielding 7 motor and 3 non-motor subscores as well as laboratory testing. A factor analysis of these subscores and laboratory parameters was performed to detect those items with the highest influence on outcome, an ANOVA and subgroup analysis tested the influence of age, age at onset of diagnosis and duration of treatment on outcome. A correlation analysis was performed between clinical subscores and laboratory findings. Results: Three factors (F1-F3) characterized the clinical outcome (F1: tremor and pathological reflexes;F2: dystonia and dysarthria;F3: cerebellar abnormalities and gait), and three factors the laboratory findings (LF1: serum level of ceruloplasmin;LF2: liver enzymes;LF3: INR). Mildly affected patients had an elevated 24 h urinary copper excretion, more affected patients presented with elevated liver enzymes. Six of the 7 motor subscores did not change with duration of treatment, whereas tremor (p < .04), the total score (p < .02) and especially the non-motor items (p < .001) significantly increased with duration of treatment. The outcome of patients with neuropsychiatric abnormalities was significantly worse (p < .01) compared to the rest of the patients. Conclusions: Long-term outcome in WD is influenced by patient's compliance and neurological comorbidity. (C) 2018 Elsevier Ltd. All rights reserved.

关键词： Biomedical ethics   clinical trials   neurological disorders  

摘要： Patients with progressive neurodegenerative diseases often pursue trial entry seeking to access cutting edge therapies. However, cutting edge therapies for neurodegenerative diseases tend to have higher adverse event rates and underperform placebo. This essay argues that patients seeking trial entry are probably better off, medically, by being assigned to the placebo arm. Because trials involve extra clinic visits and research procedures, patients may be still better off medically by skipping trial participation altogether. I close by arguing that the Neurology research community might better honor the contributions of research subjects by pressing sponsors to promptly publish the results of non-positive trials, minimizing the use of uneven randomization ratios that favor assignment to the investigational treatment, and by fostering systematic collection of data on the risk/benefit balance of trial participation.

关键词： Functional neurological disorder   Conversion disorder   Psychogenic   Functional movement disorder   Functional deficit   Treatment  

摘要： Motor functional neurological disorders (FNDs) are motor symptoms not explained by a lesion or related to a known dysfunction of the central nervous system, yet functional imaging studies suggest the presence of a genuine brain dysfunction. With this common disabling condition, there is a particular need for collaboration between neurologists and psychiatrists. Neurologists can search for positive clinical signs to make the diagnosis, which can then be followed by an explanation of the disease, whereas psychiatrists can look for psychological factors and psychiatric comorbidities in order to deliver appropriate treatment. Such a multidisciplinary approach is important, particularly with the participation of neurologists, psychiatrists, physiotherapists and psychologists. If necessary, additional treatments such as transcranial magnetic stimulation (TMS), hypnosis and sedation may be proposed. (C) 2018 Elsevier Masson SAS. All rights reserved.

关键词： Transition   Tools   Barriers   Transfer   Models of care   Core elements  

摘要： Purpose of the Review The goal of the article is to describe a systematic approach through core principles and steps for the transition of the patient with a neurological disorder to the adult model of care, to provide steps and principles to help receiving providers successfully integrate the patient into their practice, and to discuss cultural, systemic, and discipline-based barriers to transition. Recent Finding The literature has expanded rapidly. The recent publications help define the barriers to the process and are currently exploring the best methods to evaluate readiness, needs, barriers, and develop solutions for best practices. There is a consensus that there is a need for a systematic approach to transition and integration of the patient with a neurological disorder. Summary The transition of the child and youth with special health care needs (CYSHCN) is complex with multiple barriers. An important concept is that these patients, their families, and medical care providers all benefit from a coordinated and collaborative methodology.

关键词： cerebral venous thrombosis   modified Rankin scale   neurological outcome   recanalization   stroke  

摘要： Background: Studies with limited sample size and with discordant results described the recanalization time-course of cerebral venous thrombosis (CVT). The neurological outcome after a first episode of CVT is good, but the role of recanalization on neurological dependence is still debated. Objectives: The aim of the study is to assess the recanalization rate after cerebral venous thrombosis (CVT) and its prognostic role in long-term neurological outcome. Patients/Methods: In a retrospective observational multicenter cohort study, patients with an acute first episode of CVT with at least one available imaging test during follow-up were enrolled. Patency status of the vessels was categorized as complete, partial or not recanalized. Neurological outcome was defined using the modified Rankin scale (mRS) as good (mRS = 0-1) or poor (mRS = 2-6). Results: Five-hundred and eight patients (median [IQR] age, 39 [28.5-49] years;26% male) were included. Complete or partial recanalization was not differently represented in patients undergoing scans at different periods of time (from 28-day to 3 month-period up to a 1-3 year-period). mRS at the time of follow-up imaging was available in 483 patients;92.8% of them had a mRS of 0-1. CVT recanalization (odds ratio [OR], 2.56;95% confidence interval [CI], 1.59-4.13) was positively associated, whereas cancer (OR, 0.29;95% CI, 0.09-0.88) and personal history of venous thromboembolism (VTE) (OR, 0.36;95% CI, 0.14-0.92) were negatively associated as independent predictors of favorable (mRS = 0-1) outcome at follow-up. Conclusions: Most patients with a first CVT had complete or partial recanalization at follow-up. Recanalization was independently associated with a favorable neurological outcome.

关键词： child   Injury Severity Score   nervous system   neurosurgery   skating   skull   trauma  

摘要： BackgroundSkateboarding is a popular recreation among children and adolescents. Injuries that result in presentation to emergency departments are varied including head injuries. The study aims to assess the type and severity of neurological damage to the brain and spine in children from injuries incurred while using a skateboard. MethodsAfter obtaining Ethics approval, a retrospective case review was performed of all admissions to all Brisbane, Australia public hospital neurosurgery departments of children 18 years and less who experienced injuries to the brain and spine for the years 2010-2014. ResultsThere were 51 skateboard-related admissions over the study period of which 94% were male. The mean age was 14.3 years. The Injury Severity Score (ISS) ranged from 1 to 38 with a mean of 11.4. A total of 70.5% of the ISS scores fell within the minor or moderate categories and 29.5% fell within the serious and severe categories. There were no ISS scores in the critical category. A total of 16 skull vault fractures and 14 skull base fractures were recorded. There were 13 extradural haematomas of which five were evacuated by craniotomy and one of whom experienced hemiplegia. There was a spinal cord injury with paraplegia. A range of other neurological complications occurred. There were no deaths. ConclusionUncommon but serious neurological morbidity accompanies skateboard use. Concerns remain about the level of helmet use and choice of unsafe locations for skateboarding.

关键词： human immunodeficiency virus   global health   HIV-associated neurocognitive disorders   peripheral neuropathy   cerebrovascular disease  

摘要： With the advent of combination antiretroviral therapies, the mortality rate from HIV has declined, while the prevalence of long-term HIV-related neurologic complications continues to rise. Thirty-six million individuals are living with HIV around the world, many of whom reside in resource-limited settings. The majority of studies have focused on individuals residing in the developed world, while the impact of HIV disproportionately affects people living in developing countries. This review focuses on recent domestic and international studies regarding neurologic complications related to HIV, including opportunistic infections, peripheral neuropathy, cerebrovascular disease, and HIV-associated neurocognitive disorders, in light of the growing population affected by these conditions.