关键词： dopamine   SPECT   transporter   presynaptic   degeneration   parkinsonism  

摘要： Background and Purpose: The dopamine transporter scan or DaT scan is abnormal in presynaptic parkinsonism but normal in nondegenerative or postsynaptic parkinsonism. In this study, we tried to ascertain the impact of DaT scan on the diagnosis and clinical management and if the semiquantitative analysis of the DaT scans has any correlation with the clinical symptoms. Methods: The electronic and nonelectronic records of patients of Plymouth Hospital NHS Trust, United Kingdom, from 2011 to 2015 were studied to find the indication, outcome, and the impact of the scan on the management of patients. The DaT scan results were assessed visually and semiquantitatively by the Department of Nuclear Medicine. The available data were statistically analyzed with the help of Microsoft XL2010 and GraphPad software. Results: A total of 258 people had DaT scan. The scan results suggested an alternate diagnosis in 50.5% of clinically diagnosed patients with Parkinson disease. Similarly, DaT scan changed the diagnosis of 40% of patients with clinical diagnosis of vascular parkinsonism, 25% of clinically diagnosed drug-induced parkinsonism, and 54% of patients with possible Lewy body dementia. Visual assessment of the DaT scan revealed that more than 60% had grade 2 abnormalities. The distribution volume ratio, a semiquantitative tool for tracer uptake, was significantly less in the patients with akinetic-rigid subtype of Parkinson disease in comparison to a tremor predominant subtype. Conclusions: Dopamine transporter scan had a significant impact in diagnosis and management.

关键词： Orofacial pain   misdiagnosis   post traumatic neuropathic pain   temporomandibular disorder   idiopathic facial pain   headache   neurovascular  

摘要： This study assessed the impact of collaborative working with a headache neurologist on diagnoses of patients attending orofacial pain (OFP) clinic. Patient diagnostic data was collected from adult patients attending an Orofacial Pain Service from January 2013 to January 2017. A liaison headache neurologist was appointed late 2015;OFP clinics were co-run with the neurologist specialist thereafter. Overall, 639 patients attended the service;315 in 2013-2015 and 324 in 2016-2017. Compared to 2013-2015, there were increased rates of diagnoses related to neurovascular (27.5% vs. 19.0%;P = .012) and musculoskeletal pain (36.9% vs. 26.0%;P = .003) in the 2016-2017 cohort and decreased rates of neuropathic (55.6% vs. 70.2%;P < .001) and atypical/idiopathic pain (1.3% vs. 5.4%;P = .003) diagnoses. There was a trend towards an increased rate of comorbid diagnoses (26.3% vs. 20.3%;P = .077), especially those relating to headache conditions. The findings suggest that introduction of a specialist headache neurologist into the OFP clinic widened its remit of assessment, increasing recognition of (co-morbid) neurovascular-related pain and decreasing atypical/idiopathic pain diagnoses in patients with complex OFP. The increase rate of musculoskeletal pain diagnosis in the later cohort is likely attributable to service expansion and normalisation of diagnostics reportedly seen in other OFP services. Statement of clinical relevance: Orofacial pain is a complex diagnosis, it requires a multidisciplinary approach that includes neurological input.

关键词： Gaucher disease type 2   Dysphagia   Aspiration   Neurodegeneration   Modified barium swallow  

摘要： Background: Gaucher disease type 2 (GD2) is defined by acute neurological decline, failure to thrive, and early demise. Currently, there is no clear standard for evaluating, staging, and counseling regarding neurological decline in GD2. Due to the high prevalence of progressive dysphagia secondary to acute neurological involvement, we aimed to identify key components of swallow function which could serve as markers of disease progression in GD2. Methods: A post-hoc analysis of modified barium swallow studies was performed. Six parameters of swallowing were scored in a retrospective chart review of eleven infants with GD2. Mixed effects regression, principal component analysis (PCA), and a transition analysis were used to evaluate swallow function and model disease progression. Results: All patients exhibited impaired swallow function. There was no association between any of the swallow parameters and age, indicating non-linear disease progression. PCA and transition analysis identified five parameters capturing multiple dimensions of swallowing which defined two distinct disease states. Conclusion: A five-parameter swallow evaluation was sufficient to identify distinct states of GD2 and model prospective outcomes. This multi-dimensional evaluation could be a useful efficacy parameter for future therapeutic trials in GD2 and other neurodegenerative disorders of infancy.

关键词： Infection   Pneumonia   Brain injury   Neurotrauma   Inflammation   Immune response   Immunosuppression  

摘要： Traumatic brain injury (TBI) is a serious global health issue, being the leading cause of death and disability for individuals under the age of 45, and one of the largest causes of global neurological disability. In addition to the brain injury itself, it is increasingly appreciated that a TBI may also alter the systemic immune response in a way that renders TBI patients more vulnerable to infections in the acute post-injury period. Such infections pose an additional challenge to the patient, increasing rates of mortality and morbidity, and worsening neurological outcomes. Hospitalization, surgical interventions, and a state of immunosuppression induced by injury to the central nervous system (CNS), may all contribute to the high rate of infections seen in the population with TBI. Ongoing research to better understand the immunomodulators that underlie TBI-induced immunosuppression may aid in the development of effective therapeutic strategies to improve the recovery trajectory for patients. This review first describes the clinical scenario, posing the question of whether TBI patients are more susceptible to infections such as pneumonia, and if so, why? We then consider how cross-talk between the injured brain and the systemic immune system occurs, and further, how the additional immune challenge of an acquired infection can contribute to ongoing neuroinflammation and neurodegeneration after a TBI. Experimental models combining TBI with infection are discussed, as well as current treatment options available for this double-barreled insult. The aims of this review are to summarize current understanding of the bidirectional relationship between the CNS and the immune system when faced with a mechanical trauma combined with a concomitant infection, and to highlight key outstanding questions that remain in the field.

关键词： Preterm   White matter injury   Cranial ultrasound   Magnetic resonance imaging   Neurodevelopmental outcome   Echogenicity  

摘要： This study aimed to investigate the accuracy of different grades of brain injuries on serial and term equivalent age (TEA)-cranial ultrasound imaging (cUS) as compared to TEA magnetic resonance imaging (MRI) in extremely preterm infants <28weeks, and determine the predictive value of imaging abnormalities on neurodevelopmental outcome at 1 and 3years. Seventy-five infants were included in the study. Severe TEA-cUS injury had high positive predictive value-PPV (100%) for predicting severe MRI injury compared to mild to moderate TEA-cUS injury or severe injury on worst cranial ultrasound scan. Absence of moderate to severe injury on TEA cUS or worst serial cUS was a good predictor of a normal MRI (negative predictive values >93%). Severe grade 3 injuries on TEA-US had high predictive values in predicting abnormal neurodevelopment at both 1 and 3years of age (PPV 100%). All grades of MRI and worst serial cUS injuries poorly predicted abnormal neurodevelopment at 1 and 3years. Absence of an injury either on a cranial ultrasound or an MRI did not predict a normal outcome. Multiple logistic regression did not show a significant correlation between imaging injury and neurodevelopmental ***: This study demonstrates that TEA cUS can reliably identify severe brain abnormalities that would be seen on MRI imaging and positively predict abnormal neurodevelopment at both 1 and 3years. Although MRI can pick up more subtle abnormalities that may be missed on cUS, their predictive value on neurodevelopmental impairment is poor. Normal cUS and MRI scan may not exclude abnormal neurodevelopment. Routine TEA-MRI scan provides limited benefit in predicting abnormal neurodevelopment in extremely preterm infants.

关键词： Autism spectrum disorder   Cerebral cortex   DYRK1A mutations   Epilepsy   Neurodevelopment   Transcriptome  

摘要： Autism spectrum disorders are early onset neurodevelopmental disorders characterized by deficits in social communication and restricted repetitive behaviors, yet they are quite heterogeneous in terms of their genetic basis and phenotypic manifestations. Recently, de novo pathogenic mutations in DYRK1A, a chromosome 21 gene associated to neuropathological traits of Down syndrome, have been identified in patients presenting a recognizable syndrome included in the autism spectrum. These mutations produce DYRK1A kinases with partial or complete absence of the catalytic domain, or they represent missense mutations located within this domain. Here, we undertook an extensive biochemical characterization of the DYRK1A missense mutations reported to date and show that most of them, but not all, result in enzymatically dead DYRK1A proteins. We also show that haploinsufficientDyrkla(+/-) mutant mice mirror the neurological traits associated with the human pathology, such as defective social interactions, stereotypic behaviors and epileptic activity. These mutant mice present altered proportions of excitatory and inhibitory neocortical neurons and synapses. Moreover, we provide evidence that alterations in the production of cortical excitatory neurons are contributing to these defects. Indeed, by the end of the neurogenic period, the expression of developmental regulated genes involved in neuron differentiation and/or activity is altered. Therefore, our data indicate that altered neocortical neurogenesis could critically affect the formation of cortical circuits, thereby contributing to the neuropathological changes in DYRK1A haploinsufficiency syndrome.

关键词： Prognosis   Specificity  

摘要： Objective Outcome prediction in patients after cardiac arrest (CA) is challenging. Electroencephalographic reactivity (EEG-R) might be a reliable predictor. We aimed to determine the prognostic value of EEG-R using a standardized assessment. Methods In a prospective cohort study, a strictly defined EEG-R assessment protocol was executed twice per day in adult patients after CA. EEG-R was classified as present or absent by 3 EEG readers, blinded to patient characteristics. Uncertain reactivity was classified as present. Primary outcome was best Cerebral Performance Category score (CPC) in 6 months after CA, dichotomized as good (CPC = 1-2) or poor (CPC = 3-5). EEG-R was considered reliable for predicting poor outcome if specificity was >= 95%. For good outcome prediction, a specificity of >= 80% was used. Added value of EEG-R was the increase in specificity when combined with EEG background, neurological examination, and somatosensory evoked potentials (SSEPs). Results Of 160 patients enrolled, 149 were available for analyses. Absence of EEG-R for poor outcome prediction had a specificity of 82% and a sensitivity of 73%. For good outcome prediction, specificity was 73% and sensitivity 82%. Specificity for poor outcome prediction increased from 98% to 99% when EEG-R was added to a multimodal model. For good outcome prediction, specificity increased from 70% to 89%. Interpretation EEG-R testing in itself is not sufficiently reliable for outcome prediction in patients after CA. For poor outcome prediction, it has no substantial added value to EEG background, neurological examination, and SSEPs. For prediction of good outcome, EEG-R seems to have added value. ANN NEUROL 2019

关键词： Grey-white matter ratio   Cardiac arrest   Neurological outcome   Targeted temperature management   Post-cardiac arrest syndrome   Prognostic factor  

摘要： Aim: This study evaluated whether the grey-white matter ratio (GWR) assessed via early brain computed tomography (CT) within 2 h after the return of spontaneous circulation (ROSC) following cardiac arrest is associated with poor neurological outcomes after 6 months in post-cardiac arrest patients treated with targeted temperature management (TTM). Methods: This study used data from the Korean Hypothermia Network prospective registry obtained from November 2015 to October 2017 to assess patients with out-of-hospital cardiac arrest (OHCA) who underwent brain CT within 2 h following the ROSC. The primary endpoint was the neurological outcome 6 months post-cardiac arrest (cerebral performance category;CPC). The GWR was measured using early brain CT images. The subgroup analysis examined the difference in GWRs obtained from early and repeated brain CT. Results: Five-hundred-twelve patients were enrolled. Good (CPC 1-2) and poor (CPC 3-5) neurological outcomes were observed in 162 (31.6%, 4 and 350 (68.4%, 4 patients, respectively. The multivariate logistic regression analysis revealed that the GWR measured using early brain CT was a statistically nonsignificant predictor of poor neurologic outcomes (p = 0.727). In patients with poor outcomes, the mean GWR obtained from early and repeated CT images were 1.171 +/- 0.058 and 1.091 +/- 0.133, respectively (p 0.001);there was no statistically significant difference between the GWRs in patients with good outcomes. Conclusion: The GWR assessed via early brain CT alone is not an independent factor predictive of poor neurologic outcomes but could be useful when used with repeated CT data.

关键词： global health   education   curriculum development  

摘要： Objectives: To describe the current landscape of opportunities and education in global health among child neurology and neurodevelopmental disabilities training programs and provide a framework for future development of global health education. Methods: Authors surveyed Trainee and Program Director groups, obtaining information regarding global health interest, participation and obstacles (trainees);and collaborations in global health, academic yield and obstacles, and global health educational development within the training program (program directors). Results: Of identified trainees and program directors, 35% and 48% responded, respectively. Among trainees, 82% reported interest in global health, with 25% reporting influence in program selection. Among program directors, 34% reported global health collaborations, most frequently clinical. Academic yield (conference participation or publications) was described by 46% of programs. Major obstacles described by both groups included administrative issues and funding;however, the latter was most important for program directors but not for trainees. Among program directors, 16% reported global health curricula, with lectures (100%), orientation courses (50%), and pre/post-travel sessions (50%) being commonest elements. The main content included education in public health, resourcefulness, and epidemiology. Half of responding programs offered a formal global health training track, including opportunities in language education (67%) and advanced degrees (33%). Conclusions: Similar to other specialties, growing interest in global health among trainees corresponds to growing availability of said opportunities;however, most display significant logistic obstacles and lack curricular development. Potential areas for intervention, including an interdisciplinary approach, and potential benefits to stakeholders are identified for programs wishing to expand in global health education.

关键词： Alzheimer's disease   Antioxidant   Dietary supplement   Ginkgo biloba extract   Herbal compounds   Neurodegenerative disease  

摘要： Alzheimer's disease (AD) is the most common progressive human neurodegenerative disorder affecting elderly population worldwide. Hence, prevention of AD has been a priority of AD research worldwide. Based on understanding of disease mechanism, different therapeutic strategies involving synthetic and herbal approaches are being used against AD. Among the herbal extract, Ginkgo biloba extract (GBE) is one of the most investigated herbal remedy for cognitive disorders and Alzheimer's disease (AD). Standardized extract of Ginkgo biloba is a popular dietary supplement taken by the elderly population to improve memory and age-related loss of cognitive function. Nevertheless, its efficacy in the prevention and treatment of dementia remains controversial. Specifically, the added effects of GBE in subjects already receiving "conventional" anti-dementia treatments have been to date very scarcely investigated. This review summarizes recent advancements in our understanding of the potential use of Ginkgo biloba extract in the prevention of AD including its antioxidant property. A better understanding of the mechanisms of action of GBE against AD will be important for designing therapeutic strategies, for basic understanding of the underlying neurodegenerative processes, and for a better understanding of the effectiveness and complexity of this herbal medicine.