关键词： Amyotrophic lateral sclerosis   Anatomy   Biology and life sciences   Bladder   Bladder and ureteric disorders   Cell biology   Cell signaling   Central nervous system   Cognitive neurology   Cognitive neuroscience   Cognitive science   Diagnostic medicine   HTLV-1   Lesions   Medical microbiology   Medicine and health sciences   Microbial pathogens   Microbiology   Motor neuron diseases   Nervous system   Neurodegenerative diseases   Neurological signaling   Neurology   Neuroscience   Organisms   Pathogens   Pathology and laboratory medicine   Renal system   Research Article   Retroviruses   RNA viruses   Signal transduction   Signs and symptoms   Urology   Viral pathogens   Viruses  

摘要： Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL). Methods: 175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases Emilio Ribas, SAo Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH). Results: After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS. Conclusions: We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome. Author summary At least 5-10 million people live with the Human T-Cell Lymphotropic Virus type 1 (HTLV-1) worldwide, and around 0.25-5% of them may develop HTLV-1-associated

关键词： Nephrotic syndrome   Children   Sinovenous thrombosis   Stroke   Posterior reversible encephalopathy  

摘要： Background and objective: Nephrotic syndrome (NS) in childhood can be accompanied by serious neurological complications increasing the morbidity of disease. The study aimed to assess the spectrum of neurological complications in children with in terms of clinical presentation, contributory risk factors, and outcome. Methods: In this systematic review, we searched for articles in PubMed, providing individual patient-level data for any neurological complication in children and adolescents with primary NS, between January 1, 1990 and April 30, 2018. Findings: The search yielded 63 articles, involving 103 patients. Events occurred more frequently during nephrotic state relapses;71.6% of cerebral thromboembolic (TE) events and 81.2% of posterior reversible encephalopathy (PRES) cases. Median duration of disease before a cerebral TE event was 3 months (IQR 0-27), and 18 months (IQR 1-37.5) for PRES. Among cases with TE, 73.1% presented with cerebral sinovenous thrombosis (CSVT), and 16.9% parenchymal lesions. 70% of patients had a risk factor for neurological complication including NS-associated thrombophilia, hypertension, and treatment with immunosuppressive agents. Outcome was favorable in 93.8% of the patients with PRES. In patients with cerebral TE outcome was favorable in 95.8% of the cases with CSVT only, and in 64.7% of the cases with parenchymal lesions. Conclusions: Neurological complications may occur in children with primary NS and risk factors during nephrotic state relapses. The outcome for PRES has been reported favorable. Outcome in cerebral TE events may differ by the presence of venous or artery infarct. Recognition of additional protrombotic state risk factors may help to lower the incidence of neurological complications. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

关键词： Pregnancy   Cerebral palsy   Outcome   Developmental delay   Intra-amniotic infection  

摘要： Background: Chorioamnionitis is a common and potentially devastating complication of pregnancy associated with maternal and perinatal adverse outcomes. Objective: To evaluate a possible association between maternal chorioamnionitis and long-term pediatric neurological morbidity. Study design: A population-based retrospective cohort analysis was performed comparing the risk of long-term neurological morbidity. Pediatric neurological morbidity evaluated included hospitalizations with neurological morbidity. Kaplan Meier survival curves were constructed to compare the cumulative neurological morbidity and a Cox regression model was used to control for confounders. Results: 238 622 newborns were included. Of them, 0.5% were born to mothers with chorioamnionitis. 3.1% offspring were hospitalized with a neurological condition. Total neurological morbidity was not significantly more common in the chorioamnionitis group (3.8% vs. 3.1% respectively, OR 1.23, 95% CI 0.9-1.6, p = 0.147). However, a significant and independent association was noted between maternal chorioamnionitis and cerebral palsy. (0.5% vs. 0.1%, OR 5.77, 95% CI 2.5-13.0, p = 0.001). In a Cox proportional hazards model, controlling for preterm delivery, birthweight, maternal factors and mode of delivery the association between chorioamnionitis and cerebral palsy remained significant (adjusted HR = 2.78, 95% CI 1.20-6.43, P = 0.016). Conclusion: Maternal chorioamnionitis is associated with cerebral palsy in the offspring, independently of other birth circumstances such as preterm delivery and birthweight. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

关键词： cerebral palsy   developmental disorders   long-term follow-up   neurological morbidity   offspring   placental abruption  

摘要： Background Placental abruption is a major determinant of maternal and perinatal morbidity and mortality, often related to asphyxia and preterm birth. However, the impact of abruption on the long-term morbidity of the offspring is less investigated. Methods We designed a hospital-based cohort study, in which the incidence of long-term neurology-related hospitalisations of offspring to women with and without placental abruption was assessed. All singleton deliveries between 1991 and 2014 were included in the study. Congenital anomalies, perinatal mortality, and multifetal pregnancies were excluded from the analyses. We compared cumulative morbidity incidence using Kaplan-Meier survival curves and estimated the risk for long-term neurological hospitalisations from Cox proportional hazards models after adjustment for putative including maternal age, parity, hypertensive disorders, pre-gestational and gestational diabetes, gender, ethnicity, and year of birth. Results Over the 22-year period, 2 202 269 person-years of follow-up, there were 217 910 deliveries of which 0.5% (n = 1003) were complicated with placental abruption. The median (interquartile range) follow-up of children in the abruption and non-abruption groups was 10.3 (4.6, 15.9) and 12.0 (6.3, 16.5) years, respectively. The cumulative incidence of total neurological hospitalisations was comparable between abruption (3.32 per 1000 person-years) and non-abruption (3.16 per 1000 person-years). Abruption was associated with increased rates of cerebral palsy (hazard ratio [HR] 6.71, 95% CI 3.32, 13.58) and developmental disorders (HR 3.36, 95% CI 1.38, 8.13), but not for total neurology-related hospitalisations (HR 1.08, 95% CI 0.78, 1.49). Conclusion Placental abruption is associated with increased rate of cerebral palsy and developmental disorders in the offspring later in life. This study may define risk factors for childhood neuropsychiatric disorders, enabling early diagnosis and intervention in children with

关键词： Agenesis of the corpus callosum   Interhemispheric cysts   Malformations of cortical development   Epilepsy   Outcome   Brain MRI   Children  

摘要： Objectives To describe the neurological phenotype of children with prenatal diagnosis of agenesis of corpus callosum (ACC) and interhemispheric cysts associated with malformations of cortical development (MCD). Methods We reviewed the neuroimaging, neurologic, EEG, and genetic data of 36 patients (21 males, mean age 7 years) with ACC and interhemispheric cysts. Associations were tested with Chi-squared and Fisher exact tests. Results According to the 2001 Barkovich classification, we found 4 type 1c (11.1%), 6 type 2a (16.6%), 18 type 2b (50%, 6/18 girls with Aicardi syndrome), and 9 type 2c cysts (22.2%). EEG showed specific epileptic activity in 27/36 patients (75%). Epilepsy was diagnosed in 16 subjects (16/36, 44.4%), including all Aicardi patients, and was associated with cognitive impairment (p=0.032). Severe intellectual disability and epilepsy were associated with type 2b cysts, always due to Aicardi patients (p<0.05). After excluding Aicardi patients, all subjects with type 2b cysts had mild neurological phenotype. Patients with 2a and 2c cysts more frequently had normal cognition (83.3% and 62.5% of cases, respectively). Patients with type 1c cyst mostly had mild/moderate cognitive impairment. Severe neurologic deficits were associated with 1c cysts and 2b cysts with Aicardi syndrome (p<0.05). Multilobar and/or bilateral MCD were associated with severe neurological and epileptic phenotypes (p<0.05). Conclusion Once excluded Aicardi syndrome, most patients with ACC and interhemispheric cysts have a mild clinical phenotype characterized by borderline/normal cognition and minor neurological signs. Despite the high prevalence of EEG epileptic abnormalities, epilepsy in these cases is infrequent and usually responsive to antiepileptic drugs.

关键词： neurotoxicity   CAR T cells   immunotherapy  

摘要： Chimeric antigen receptor T cell therapy has become an important tool in the treatment of relapsed and refractory malignancy;however, it is associated with significant neurological toxicity. We characterized the neurological toxicity associated with chimeric antigen receptor T-cell therapy in a consecutive series of 100 patients up to 2 months post transfusion, 28 of whom were obtained from chart review and the others by prospective observation. The underlying neoplasms were lymphoma (74%), myeloma (14%), leukaemia (10%), and sarcoma (2%). The median age of the cohort was 64.5 years old and 39% of patients were female. The most commonly occurring neurological symptoms were encephalopathy (57%), headache (42%), tremor (38%), aphasia (35%) and focal weakness (11%). Focal neurological deficits are frequently observed after chimeric antigen receptor T-cell therapy and are associated with regional EEG abnormalities, FDG-PET hypometabolism, and elevated velocities on transcranial Doppler ultrasound. In contrast, structural imaging was typically normal. As this form of treatment is more widely adopted, recognition of the frequently encountered symptoms will be of increasing importance for the neurologists and oncologists caring for this growing patient population.

关键词： Mitochondrial DNA   Genetic variants   Neurological disorders   Neurodevelopmental syndromes   Neurodegenerative diseases   Neuropsychiatric disorders   Systematic literature review  

摘要： Mitochondria are small cytosolic organelles and the main source of energy production for the cells, especially in the brain. This organelle has its own genome, the mitochondrial DNA (mtDNA), and genetic variants in this molecule can alter the normal energy metabolism in the brain, contributing to the development of a wide assortment of Neurological Disorders (ND), including neurodevelopmental syndromes, neurodegenerative diseases and neuropsychiatric disorders. These ND are comprised by a heterogeneous group of syndromes and diseases that encompass different cognitive phenotypes and behavioral disorders, such as autism, Asperger's syndrome, pervasive developmental disorder, attention deficit hyperactivity disorder, Huntington disease, Leigh Syndrome and bipolar disorder. In this work we carried out a Systematic Literature Review (SLR) to identify and describe the mitochondrial genetic variants associated with the occurrence of ND. Most of genetic variants found in mtDNA were associated with Single Nucleotide Polimorphisms (SNPs), similar to 79%, with similar to 15% corresponding to deletions, similar to 3% to Copy Number Variations (CNVs), similar to 2% to insertions and another 1% included mtDNA replication problems and genetic rearrangements. We also found that most of the variants were associated with coding regions of mitochondrial proteins but were also found in regulatory transcripts (tRNA and rRNA) and in the D-Loop replication region of the mtDNA. After analysis of mtDNA deletions and CNV, none of them occur in the D-Loop region. This SLR shows that all transcribed mtDNA molecules have mutations correlated with ND. Finally, we describe that all mtDNA variants found were associated with deterioration of cognitive (dementia) and intellectual functions, learning disabilities, developmental delays, and personality and behavior problems.

关键词： Neurogenic heterotopic ossification   Spinal cord injury   Botulinum toxin type a   Osteogenesis  

关键词： rehabilitation   sleep   CPAP   stroke   transcranial direct current stimulation   transcranial magnetic stimulation   targeted memory reactivation   rhythmic auditory stimulation   neuromodulation   occupational therapy   physical therapy   motor learning   memory   consolidation   memory consolidation  

摘要： Objective. Conduct a systematic review of nonpharmacological interventions applied during sleep to enhance physical rehabilitation outcomes of individuals with a neurological diagnosis. Data Sources. Three online databases were searched for original research. Study Selection. Intervention studies were included that used outcome measures of impairment, activity, and/or participation. Data Extraction. Two reviewers independently screened 2287 titles and abstracts, reviewed 101 full texts, extracted data, and assessed study quality and risk of bias for 9 included studies. Data Synthesis. All included studies were randomized controlled trials involving continuous positive airway pressure (CPAP) with inpatient individuals with stroke and sleep apnea. Several studies also included long-term outpatient follow-ups. Results in terms of outcomes based on impairment, activity, and participation were mixed. However, several studies found that the use of CPAP following stroke and sleep apnea during early stroke recovery had benefits relative to no CPAP. Conclusions. The only nonpharmacological intervention to be administered during sleep in a neurological population to improve physical rehabilitation outcomes was found to be CPAP. This review was complicated by the variety of outcome measures used, lack of physical rehabilitation description, and CPAP compliance. In general, participants who had acceptable to good CPAP compliance saw the largest improvements in physical rehabilitation outcomes. Several other promising methods of brain stimulation during sleep are discussed.

关键词： Down syndrome   Intellectual disability   Cognitive deficits   Cannabinoid receptor type-1   Endocannabinoid system   Hippocampus  

摘要： Intellectual disability is the most limiting hallmark of Down syndrome, for which there is no gold-standard clinical treatment yet. The endocannabinoid system is a widespread neuromodulatory system involved in multiple functions including learning and memory processes. Alterations of this system contribute to the pathogenesis of several neurological and neurodevelopmental disorders. However, the involvement of the endocannabinoid system in the pathogenesis of Down syndrome has not been explored before. We used the best characterized preclinical model of Down syndrome, the segmentally trisomic Ts65Dn model. In male Ts65Dn mice, cannabinoid type-1 receptor (CB1R) expression was enhanced and its function increased in hippocampal excitatory terminals. Knockdown of CB1R in the hippocampus of male Ts65Dn mice restored hippocampal-dependent memory. Concomitant with this result, pharmacological inhibition of CB1R restored memory deficits, hippocampal synaptic plasticity and adult neurogenesis in the subgranular zone of the dentate gyrus. Notably, the blockade of CB1R also normalized hippocampal-dependent memory in female Ts65Dn mice. To further investigate the mechanisms involved, we used a second transgenic mouse model overexpressing a single gene candidate for Down syndrome cognitive phenotypes, the dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A). CB1R pharmacological blockade similarly improved cognitive performance, synaptic plasticity and neurogenesis in transgenic male Dyrk1A mice. Our results identify CB1R as a novel druggable target potentially relevant for the improvement of cognitive deficits associated with Down syndrome.