The role of mechanics during brain development

NASA Astrophysics Data System (ADS)

Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

2014-12-01

Convolutions are a classical hallmark of most mammalian brains. Brain surface morphology is often associated with intelligence and closely correlated with neurological dysfunction. Yet, we know surprisingly little about the underlying mechanisms of cortical folding. Here we identify the role of the key anatomic players during the folding process: cortical thickness, stiffness, and growth. To establish estimates for the critical time, pressure, and the wavelength at the onset of folding, we derive an analytical model using the Föppl-von Kármán theory. Analytical modeling provides a quick first insight into the critical conditions at the onset of folding, yet it fails to predict the evolution of complex instability patterns in the post-critical regime. To predict realistic surface morphologies, we establish a computational model using the continuum theory of finite growth. Computational modeling not only confirms our analytical estimates, but is also capable of predicting the formation of complex surface morphologies with asymmetric patterns and secondary folds. Taken together, our analytical and computational models explain why larger mammalian brains tend to be more convoluted than smaller brains. Both models provide mechanistic interpretations of the classical malformations of lissencephaly and polymicrogyria. Understanding the process of cortical folding in the mammalian brain has direct implications on the diagnostics of neurological disorders including severe retardation, epilepsy, schizophrenia, and autism.

The role of mechanics during brain development

PubMed Central

Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

2014-01-01

Convolutions are a classical hallmark of most mammalian brains. Brain surface morphology is often associated with intelligence and closely correlated to neurological dysfunction. Yet, we know surprisingly little about the underlying mechanisms of cortical folding. Here we identify the role of the key anatomic players during the folding process: cortical thickness, stiffness, and growth. To establish estimates for the critical time, pressure, and the wavelength at the onset of folding, we derive an analytical model using the Föppl-von-Kármán theory. Analytical modeling provides a quick first insight into the critical conditions at the onset of folding, yet it fails to predict the evolution of complex instability patterns in the post-critical regime. To predict realistic surface morphologies, we establish a computational model using the continuum theory of finite growth. Computational modeling not only confirms our analytical estimates, but is also capable of predicting the formation of complex surface morphologies with asymmetric patterns and secondary folds. Taken together, our analytical and computational models explain why larger mammalian brains tend to be more convoluted than smaller brains. Both models provide mechanistic interpretations of the classical malformations of lissencephaly and polymicrogyria. Understanding the process of cortical folding in the mammalian brain has direct implications on the diagnostics of neurological disorders including severe retardation, epilepsy, schizophrenia, and autism. PMID:25202162

Perceptions of self-efficacy and rehabilitation among neurologically disabled adults.

PubMed

Dixon, Guy; Thornton, Everard W; Young, Carolyn A

2007-03-01

To explore constructs relevant to self-efficacy in neurological rehabilitation. Qualitative methods using semi-structured interviews. Specialist neurological rehabilitation unit, Liverpool, UK. Twenty-four patients (12 male) with experience of inpatient rehabilitation, aged 17-59 (mean 38.1) years at onset, with diagnoses of stroke (n = 8), traumatic brain injury (n = 6) or other monophasic neurological impairment (n = 10). Eleven themes emerged from the data that reflect self-efficacy beliefs: self-reliance and independence were deemed important and many patients recognized the importance of determination, making time to take an active role and working in partnership with the multidisciplinary team. Patients had complex information needs but were able to use goal setting and the vicarious experiences of other inpatients to map out the stages of their own recovery. It was important for patients to be able to recognize for themselves that they were making progress and they valued external reassurance on this from other patients, staff and visitors. A number of difficulties were identified that interfered with their developing self-efficacy in rehabilitation, such as structuring their time. Two different models for rehabilitation emerged from the data, 'recovery' and 'adaptation'. Patients consistently identified 11 factors falling in the supraordinate themes of self, others and process, and these influenced their self-efficacy to participate in neurological rehabilitation. Patients consider rehabilitation in terms of either an 'adaptation' or 'recovery' model.

Toward modeling locomotion using electromyography-informed 3D models: application to cerebral palsy.

PubMed

Sartori, M; Fernandez, J W; Modenese, L; Carty, C P; Barber, L A; Oberhofer, K; Zhang, J; Handsfield, G G; Stott, N S; Besier, T F; Farina, D; Lloyd, D G

2017-03-01

This position paper proposes a modeling pipeline to develop clinically relevant neuromusculoskeletal models to understand and treat complex neurological disorders. Although applicable to a variety of neurological conditions, we provide direct pipeline applicative examples in the context of cerebral palsy (CP). This paper highlights technologies in: (1) patient-specific segmental rigid body models developed from magnetic resonance imaging for use in inverse kinematics and inverse dynamics pipelines; (2) efficient population-based approaches to derive skeletal models and muscle origins/insertions that are useful for population statistics and consistent creation of continuum models; (3) continuum muscle descriptions to account for complex muscle architecture including spatially varying material properties with muscle wrapping; (4) muscle and tendon properties specific to CP; and (5) neural-based electromyography-informed methods for muscle force prediction. This represents a novel modeling pipeline that couples for the first time electromyography extracted features of disrupted neuromuscular behavior with advanced numerical methods for modeling CP-specific musculoskeletal morphology and function. The translation of such pipeline to the clinical level will provide a new class of biomarkers that objectively describe the neuromusculoskeletal determinants of pathological locomotion and complement current clinical assessment techniques, which often rely on subjective judgment. WIREs Syst Biol Med 2017, 9:e1368. doi: 10.1002/wsbm.1368 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Unravelling the complex MRI pattern in glutaric aciduria type I using statistical models-a cohort study in 180 patients.

PubMed

Garbade, Sven F; Greenberg, Cheryl R; Demirkol, Mübeccel; Gökçay, Gülden; Ribes, Antonia; Campistol, Jaume; Burlina, Alberto B; Burgard, Peter; Kölker, Stefan

2014-09-01

Glutaric aciduria type I (GA-I) is a cerebral organic aciduria caused by inherited deficiency of glutaryl-CoA dehydrogenase and is characterized biochemically by an accumulation of putatively neurotoxic dicarboxylic metabolites. The majority of untreated patients develops a complex movement disorder with predominant dystonia during age 3-36 months. Magnetic resonance imaging (MRI) studies have demonstrated striatal and extrastriatal abnormalities. The major aim of this study was to elucidate the complex neuroradiological pattern of patients with GA-I and to associate the MRI findings with the severity of predominant neurological symptoms. In 180 patients, detailed information about the neurological presentation and brain region-specific MRI abnormalities were obtained via a standardized questionnaire. Patients with a movement disorder had more often MRI abnormalities in putamen, caudate, cortex, ventricles and external CSF spaces than patients without or with minor neurological symptoms. Putaminal MRI changes and strongly dilated ventricles were identified as the most reliable predictors of a movement disorder. In contrast, abnormalities in globus pallidus were not clearly associated with a movement disorder. Caudate and putamen as well as cortex, ventricles and external CSF spaces clearly collocalized on a two-dimensional map demonstrating statistical similarity and suggesting the same underlying pathomechanism. This study demonstrates that complex statistical methods are useful to decipher the age-dependent and region-specific MRI patterns of rare neurometabolic diseases and that these methods are helpful to elucidate the clinical relevance of specific MRI findings.

The use of regression tree analysis for predicting the functional outcome following traumatic spinal cord injury.

PubMed

Facchinello, Yann; Beauséjour, Marie; Richard-Denis, Andreane; Thompson, Cynthia; Mac-Thiong, Jean-Marc

2017-10-25

Predicting the long-term functional outcome following traumatic spinal cord injury is needed to adapt medical strategies and to plan an optimized rehabilitation. This study investigates the use of regression tree for the development of predictive models based on acute clinical and demographic predictors. This prospective study was performed on 172 patients hospitalized following traumatic spinal cord injury. Functional outcome was quantified using the Spinal Cord Independence Measure collected within the first-year post injury. Age, delay prior to surgery and Injury Severity Score were considered as continuous predictors while energy of injury, trauma mechanisms, neurological level of injury, injury severity, occurrence of early spasticity, urinary tract infection, pressure ulcer and pneumonia were coded as categorical inputs. A simplified model was built using only injury severity, neurological level, energy and age as predictor and was compared to a more complex model considering all 11 predictors mentioned above The models built using 4 and 11 predictors were found to explain 51.4% and 62.3% of the variance of the Spinal Cord Independence Measure total score after validation, respectively. The severity of the neurological deficit at admission was found to be the most important predictor. Other important predictors were the Injury Severity Score, age, neurological level and delay prior to surgery. Regression trees offer promising performances for predicting the functional outcome after a traumatic spinal cord injury. It could help to determine the number and type of predictors leading to a prediction model of the functional outcome that can be used clinically in the future.

Developing a 3-choice serial reaction time task for examining neural and cognitive function in an equine model.

PubMed

Roberts, Kirsty; Hemmings, Andrew J; McBride, Sebastian D; Parker, Matthew O

2017-12-01

Large animal models of human neurological disorders are advantageous compared to rodent models due to their neuroanatomical complexity, longevity and their ability to be maintained in naturalised environments. Some large animal models spontaneously develop behaviours that closely resemble the symptoms of neural and psychiatric disorders. The horse is an example of this; the domestic form of this species consistently develops spontaneous stereotypic behaviours akin to the compulsive and impulsive behaviours observed in human neurological disorders such as Tourette's syndrome. The ability to non-invasively probe normal and abnormal equine brain function through cognitive testing may provide an extremely useful methodological tool to assess brain changes associated with certain human neurological and psychiatric conditions. An automated operant system with the ability to present visual and auditory stimuli as well as dispense salient food reward was developed. To validate the system, ten horses were trained and tested using a standard cognitive task (three choice serial reaction time task (3-CSRTT)). All animals achieved total learning criterion and performed six probe sessions. Learning criterion was met within 16.30±0.79 sessions over a three day period. During six probe sessions, level of performance was maintained at 80.67±0.57% (mean±SEM) accuracy. This is the first mobile fully automated system developed to examine cognitive function in the horse. A fully-automated operant system for mobile cognitive function of a large animal model has been designed and validated. Horses pose an interesting complementary model to rodents for the examination of human neurological dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Neurological complications of human immunodeficiency virus infection.

PubMed Central

Kennedy, P. G.

1988-01-01

The protean neurological manifestations of human immunodeficiency virus (HIV) infection are reviewed. Both the central nervous system and peripheral nervous system may be affected and many of the complications may occur in individuals with acquired immunodeficiency syndrome (AIDS)-related complex, or who are seropositive for HIV alone as well as those with the established AIDS syndrome. Specific therapy is available for certain of these neurological conditions, but the clinical course in others is untreatable and progressive. Although it seems likely that the pathogenesis of some of these syndromes such as the AIDS-dementia complex are due to the direct effect of HIV on the nervous system, in others the neurological injury probably occurs as a consequence of the immunosuppression which HIV induces, or immune-mediated mechanisms. PMID:3050940

Abnormal Neural Progenitor Cells Differentiated from Induced Pluripotent Stem Cells Partially Mimicked Development of TSC2 Neurological Abnormalities.

PubMed

Li, Yaqin; Cao, Jiqing; Chen, Menglong; Li, Jing; Sun, Yiming; Zhang, Yu; Zhu, Yuling; Wang, Liang; Zhang, Cheng

2017-04-11

Tuberous sclerosis complex (TSC) is a disease featuring devastating and therapeutically challenging neurological abnormalities. However, there is a lack of specific neural progenitor cell models for TSC. Here, the pathology of TSC was studied using primitive neural stem cells (pNSCs) from a patient presenting a c.1444-2A>C mutation in TSC2. We found that TSC2 pNSCs had higher proliferative activity and increased PAX6 expression compared with those of control pNSCs. Neurons differentiated from TSC2 pNSCs showed enlargement of the soma, perturbed neurite outgrowth, and abnormal connections among cells. TSC2 astrocytes had increased saturation density and higher proliferative activity. Moreover, the activity of the mTOR pathway was enhanced in pNSCs and induced in neurons and astrocytes. Thus, our results suggested that TSC2 heterozygosity caused neurological malformations in pNSCs, indicating that its heterozygosity might be sufficient for the development of neurological abnormalities in patients. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Management of psychiatric and neurological comorbidities in epilepsy.

PubMed

Kanner, Andres M

2016-02-01

The treatment of epileptic seizure disorders is not restricted to the achievement of seizure-freedom, but must also include the management of comorbid medical, neurological, psychiatric and cognitive comorbidities. Psychiatric and neurological comorbidities are relatively common and often co-exist in people with epilepsy (PWE). For example, depression and anxiety disorders are the most common psychiatric comorbidities in PWE, and they are particularly common in PWE who also have a neurological comorbidity, such as migraine, stroke, traumatic brain injury or dementia. Moreover, psychiatric and neurological comorbodities often have a more severe impact on the quality of life in patients with treatment-resistant focal epilepsy than do the actual seizures. Epilepsy and psychiatric and neurological comorbidities have a complex relationship, which has a direct bearing on the management of both seizures and the comorbidities: the comorbidities have to be factored into the selection of antiepileptic drugs, and the susceptibility to seizures has to be considered when choosing the drugs to treat comorbidities. The aim of this Review is to highlight the complex relationship between epilepsy and common psychiatric and neurological comorbidities, and provide an overview of how treatment strategies for epilepsy can positively and negatively affect these comorbidities and vice versa.

Lungs in TSC

MedlinePlus

... Complex Consensus Group.* Tuberous Sclerosis Complex Surveillance and Management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. (2013) Pediatric Neurology, ...

Slow Perceptual Processing at the Core of Developmental Dyslexia: A Parameter-Based Assessment of Visual Attention

ERIC Educational Resources Information Center

Stenneken, Prisca; Egetemeir, Johanna; Schulte-Korne, Gerd; Muller, Hermann J.; Schneider, Werner X.; Finke, Kathrin

2011-01-01

The cognitive causes as well as the neurological and genetic basis of developmental dyslexia, a complex disorder of written language acquisition, are intensely discussed with regard to multiple-deficit models. Accumulating evidence has revealed dyslexics' impairments in a variety of tasks requiring visual attention. The heterogeneity of these…

A quantitative magnetic resonance histology atlas of postnatal rat brain development with regional estimates of growth and variability.

PubMed

Calabrese, Evan; Badea, Alexandra; Watson, Charles; Johnson, G Allan

2013-05-01

There has been growing interest in the role of postnatal brain development in the etiology of several neurologic diseases. The rat has long been recognized as a powerful model system for studying neuropathology and the safety of pharmacologic treatments. However, the complex spatiotemporal changes that occur during rat neurodevelopment remain to be elucidated. This work establishes the first magnetic resonance histology (MRH) atlas of the developing rat brain, with an emphasis on quantitation. The atlas comprises five specimens at each of nine time points, imaged with eight distinct MR contrasts and segmented into 26 developmentally defined brain regions. The atlas was used to establish a timeline of morphometric changes and variability throughout neurodevelopment and represents a quantitative database of rat neurodevelopment for characterizing rat models of human neurologic disease. Published by Elsevier Inc.

Peripheral neuropathy in complex inherited diseases: an approach to diagnosis.

PubMed

Rossor, Alexander M; Carr, Aisling S; Devine, Helen; Chandrashekar, Hoskote; Pelayo-Negro, Ana Lara; Pareyson, Davide; Shy, Michael E; Scherer, Steven S; Reilly, Mary M

2017-10-01

Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy, for example, spasticity, the type of neuropathy and the other neurological and non-neurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories: (1) ataxia, (2) spasticity and (3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy, for example, cardiomyopathy and neuropathy. We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain-Barré syndrome, as many will have a metabolic aetiology and be potentially treatable. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Formal faculty observation and assessment of bedside skills for 3rd-year neurology clerks.

PubMed

Thompson Stone, Robert; Mooney, Christopher; Wexler, Erika; Mink, Jonathan; Post, Jennifer; Jozefowicz, Ralph F

2016-11-22

To evaluate the feasibility and utility of instituting a formalized bedside skills evaluation (BSE) for 3rd-year medical students on the neurology clerkship. A neurologic BSE was developed for 3rd - year neurology clerks at the University of Rochester for the 2012-2014 academic years. Faculty directly observed 189 students completing a full history and neurologic examination on real inpatients. Mock grades were calculated utilizing the BSE in the final grade, and number of students with a grade difference was determined when compared to true grade. Correlation was explored between the BSE and clinical scores, National Board of Medical Examiners (NBME) scores, case complexity, and true final grades. A survey was administered to students to assess their clinical skills exposure and the usefulness of the BSE. Faculty completed and submitted a BSE form for 88.3% of students. There was a mock final grade change for 13.2% of students. Correlation coefficients between BSE score and clinical score/NBME score were 0.36 and 0.35, respectively. A statistically significant effect of BSE was found on final clerkship grade (F 2,186 = 31.9, p < 0.0001). There was no statistical difference between BSE score and differing case complexities. Incorporating a formal faculty-observed BSE into the 3rd year neurology clerkship was feasible. Low correlation between BSE score and other evaluations indicated a unique measurement to contribute to student grade. Using real patients with differing case complexity did not alter the grade. © 2016 American Academy of Neurology.

Challenges to neurology residency education in today's health care environment.

PubMed

Bega, Danny; Krainc, Dimitri

2016-09-01

Residency training has had to adapt to higher patient volumes, increased complexity of medical care, and the commercialized system of health care. These changes have led to a concerning culture shift in neurology. We review the relationship between the emerging health care delivery system and residency training, highlighting issues related to duty hours and work-life balance, the changing technological landscape, high patient volumes, and complex service obligations. We propose that the current challenges in health care delivery offer the opportunity to improve neurology residency through faculty development programs, bringing teaching back to the bedside, increasing resident autonomy, utilizing near-peer teaching, and rewarding educators who facilitate an environment of inquiry and scholarship, with the ultimate goal of better alignment between education and patient care. Ann Neurol 2016;80:315-320. © 2016 American Neurological Association.

The tissue-type plasminogen activator–plasminogen activator inhibitor 1 complex promotes neurovascular injury in brain trauma: evidence from mice and humans

PubMed Central

Sashindranath, Maithili; Sales, Eunice; Daglas, Maria; Freeman, Roxann; Samson, Andre L.; Cops, Elisa J.; Beckham, Simone; Galle, Adam; McLean, Catriona; Morganti-Kossmann, Cristina; Rosenfeld, Jeffrey V.; Madani, Rime; Vassalli, Jean-Dominique; Su, Enming J.; Lawrence, Daniel A.

2012-01-01

The neurovascular unit provides a dynamic interface between the circulation and central nervous system. Disruption of neurovascular integrity occurs in numerous brain pathologies including neurotrauma and ischaemic stroke. Tissue plasminogen activator is a serine protease that converts plasminogen to plasmin, a protease that dissolves blood clots. Besides its role in fibrinolysis, tissue plasminogen activator is abundantly expressed in the brain where it mediates extracellular proteolysis. However, proteolytically active tissue plasminogen activator also promotes neurovascular disruption after ischaemic stroke; the molecular mechanisms of this process are still unclear. Tissue plasminogen activator is naturally inhibited by serine protease inhibitors (serpins): plasminogen activator inhibitor-1, neuroserpin or protease nexin-1 that results in the formation of serpin:protease complexes. Proteases and serpin:protease complexes are cleared through high-affinity binding to low-density lipoprotein receptors, but their binding to these receptors can also transmit extracellular signals across the plasma membrane. The matrix metalloproteinases are the second major proteolytic system in the mammalian brain, and like tissue plasminogen activators are pivotal to neurological function but can also degrade structures of the neurovascular unit after injury. Herein, we show that tissue plasminogen activator potentiates neurovascular damage in a dose-dependent manner in a mouse model of neurotrauma. Surprisingly, inhibition of activity following administration of plasminogen activator inhibitor-1 significantly increased cerebrovascular permeability. This led to our finding that formation of complexes between tissue plasminogen activator and plasminogen activator inhibitor-1 in the brain parenchyma facilitates post-traumatic cerebrovascular damage. We demonstrate that following trauma, the complex binds to low-density lipoprotein receptors, triggering the induction of matrix metalloproteinase-3. Accordingly, pharmacological inhibition of matrix metalloproteinase-3 attenuates neurovascular permeability and improves neurological function in injured mice. Our results are clinically relevant, because concentrations of tissue plasminogen activator: plasminogen activator inhibitor-1 complex and matrix metalloproteinase-3 are significantly elevated in cerebrospinal fluid of trauma patients and correlate with neurological outcome. In a separate study, we found that matrix metalloproteinase-3 and albumin, a marker of cerebrovascular damage, were significantly increased in brain tissue of patients with neurotrauma. Perturbation of neurovascular homeostasis causing oedema, inflammation and cell death is an important cause of acute and long-term neurological dysfunction after trauma. A role for the tissue plasminogen activator–matrix metalloproteinase axis in promoting neurovascular disruption after neurotrauma has not been described thus far. Targeting tissue plasminogen activator: plasminogen activator inhibitor-1 complex signalling or downstream matrix metalloproteinase-3 induction may provide viable therapeutic strategies to reduce cerebrovascular permeability after neurotrauma. PMID:22822039

A health systems constraints analysis for neurologic diseases: the example of Timor-Leste.

PubMed

Mateen, Farrah J; Martins, Nelson

2014-04-08

Neurologic care exists within health systems and complex social, political, and economic environments. Identification of obstacles within health systems, defined as "constraints," is crucial to improving the delivery of neurologic care within its macroclimate. Here we use the World Health Organization's 6 building blocks of a health system to examine core services for priority interventions related to neurologic disease: (1) service delivery; (2) health workforce; (3) information; (4) medical products, vaccines, and technologies; (5) financing; and (6) leadership and governance. We demonstrate the use of a constraints analysis for neurologic disorders using the example of Timor-Leste, a newly sovereign and low-income country, which aims to improve neurologic care in the coming years.

Current Issues in the Neurology and Genetics of Learning-Related Traits and Disorders: Introduction to the Special Issue.

ERIC Educational Resources Information Center

Gilger, Jeffrey W.

2001-01-01

This introductory article briefly describes each of the following eight articles in this special issue on the neurology and genetics of learning related disorders. It notes the greater appreciation of learning disability as a set of complex disorders with broad and intricate neurological bases and of the large individual differences in how these…

A unique retinal epitheliopathy is associated with amyotrophic lateral sclerosis/Parkinsonism-Dementia complex of Guam.

PubMed

Steele, John C; Wresch, Robert; Hanlon, Samuel D; Keystone, Jay; Ben-Shlomo, Yoav

2015-08-01

The aim of this work was to examine whether a linear retinal pigment epitheliopathy is associated with the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. A total of 918 Guamanian Chamorros, with and without amyotrophic lateral sclerosis/parkinsonism-dementia complex, were examined cross-sectionally for linear retinal pigment epitheliopathy (LRPE). Overall, 239 Guamanians, who were neurologically asymptomatic, were followed for up to 20 years to determine the risk of developing amyotrophic lateral sclerosis/parkinsonism-dementia complex. The epitheliopathy was present in 59.7% (117 of 196) patients with amyotrophic lateral sclerosis/parkinsonism-dementia complex, but in only 24.7% (178 of 722) of subjects who were neurologically asymptomatic (age- and sex-adjusted risk difference: 35.0%; 95% confidence interval [CI]: 27.5-42.6; p < 0.0001). Prospectively, 15 of 50 cases with epitheliopathy developed amyotrophic lateral sclerosis/parkinsonism-dementia complex, compared to 4 of 189 cases without epitheliopathy (age- and sex-adjusted hazard ratio: 13.1; 95% CI: 4.0-43.1; P < 0.0001). Amyotrophic lateral sclerosis/parkinsonism-dementia complex is associated with an LRPE and predicts future neurological disease. Identifying the cause of this retinopathy could provide an understanding about the pathogenesis of amyotrophic lateral sclerosis/parkinsonism-dementia complex and related diseases. © 2015 International Parkinson and Movement Disorder Society.

Review on Graph Clustering and Subgraph Similarity Based Analysis of Neurological Disorders

PubMed Central

Thomas, Jaya; Seo, Dongmin; Sael, Lee

2016-01-01

How can complex relationships among molecular or clinico-pathological entities of neurological disorders be represented and analyzed? Graphs seem to be the current answer to the question no matter the type of information: molecular data, brain images or neural signals. We review a wide spectrum of graph representation and graph analysis methods and their application in the study of both the genomic level and the phenotypic level of the neurological disorder. We find numerous research works that create, process and analyze graphs formed from one or a few data types to gain an understanding of specific aspects of the neurological disorders. Furthermore, with the increasing number of data of various types becoming available for neurological disorders, we find that integrative analysis approaches that combine several types of data are being recognized as a way to gain a global understanding of the diseases. Although there are still not many integrative analyses of graphs due to the complexity in analysis, multi-layer graph analysis is a promising framework that can incorporate various data types. We describe and discuss the benefits of the multi-layer graph framework for studies of neurological disease. PMID:27258269

Review on Graph Clustering and Subgraph Similarity Based Analysis of Neurological Disorders.

PubMed

Thomas, Jaya; Seo, Dongmin; Sael, Lee

2016-06-01

How can complex relationships among molecular or clinico-pathological entities of neurological disorders be represented and analyzed? Graphs seem to be the current answer to the question no matter the type of information: molecular data, brain images or neural signals. We review a wide spectrum of graph representation and graph analysis methods and their application in the study of both the genomic level and the phenotypic level of the neurological disorder. We find numerous research works that create, process and analyze graphs formed from one or a few data types to gain an understanding of specific aspects of the neurological disorders. Furthermore, with the increasing number of data of various types becoming available for neurological disorders, we find that integrative analysis approaches that combine several types of data are being recognized as a way to gain a global understanding of the diseases. Although there are still not many integrative analyses of graphs due to the complexity in analysis, multi-layer graph analysis is a promising framework that can incorporate various data types. We describe and discuss the benefits of the multi-layer graph framework for studies of neurological disease.

Fused cerebral organoids model interactions between brain regions.

PubMed

Bagley, Joshua A; Reumann, Daniel; Bian, Shan; Lévi-Strauss, Julie; Knoblich, Juergen A

2017-07-01

Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.

Complex partial status epilepticus: a recurrent problem.

PubMed Central

Cockerell, O C; Walker, M C; Sander, J W; Shorvon, S D

1994-01-01

Twenty patients with complex partial status epilepticus were identified retrospectively from a specialist neurology hospital. Seventeen patients experienced recurrent episodes of complex partial status epilepticus, often occurring at regular intervals, usually over many years, and while being treated with effective anti-epileptic drugs. No unifying cause for the recurrences, and no common epilepsy aetiologies, were identified. In spite of the frequency of recurrence and length of history, none of the patients showed any marked evidence of cognitive or neurological deterioration. Complex partial status epilepticus is more common than is generally recognised, should be differentiated from other forms of non-convulsive status, and is often difficult to treat. PMID:8021671

Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping.

PubMed

Klein, Christopher J; Lennon, Vanda A; Aston, Paula A; McKeon, Andrew; O'Toole, Orna; Quek, Amy; Pittock, Sean J

2013-02-01

To determine, in patients identified as seropositive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuronal targets in the VGKC macromolecular complex. Retrospective cohort study. Clinical practice, Mayo Clinic Neuroimmunology Laboratory and Department of Neurology. A total of 54 853 patients were evaluated, of whom 1992 were found to be VGKC complex IgG positive. From June 1, 2008, to June 30, 2010, comprehensive service serologic evaluation performed on 54853 patients with unexplained neurologic symptoms identified 1992 patients (4%) who were positive for VGKC complex IgG (values ≥ 0.03 nmol/L). Among 316 seropositive patients evaluated clinically at our institution, 82 (26%) were seropositive for LGI1 IgG and/or CASPR2 IgG. Of these 82 patients, 27% had low (0.03-0.09 nmol/L), 51% had medium (0.10-0.99 nmol/L), and 22% had high (≥ 1.00 nmol/L) VGKC complex IgG values. Leucine-rich glioma-inactivated protein 1 IgG positivity was associated with higher VGKC complex IgG values (P< .001) and cortical presentations (P< .001); CASPR2 IgG was associated with peripheral motor excitability (P= .009). However, neither autoantibody was pathognomonic for a specific neurologic presentation or correlated significantly with cancer. Neurologic phenotypes were diverse. Cerebrocortical manifestations (including cognitive impairment and seizures) were recorded in 76% of patients with LGI1 IgG alone (n=46) and 29% with CASPR2 IgG alone (n=28). Peripheral motor hyperexcitability was found in 21% of patients with CASPR2 IgG alone and 6.5% of patients with LGI1 IgG alone. The study emphasizes diverse and overlapping neurologic phenotypes across a range of VGKC complex IgG values and varying LGI1 IgG and CASPR2 IgG specificities. The frequent occurrence of LGI1 IgG and CASPR2 IgG in serum samples with low and medium VGKC complex IgG values supports the clinical significance of low values in clinical evaluation. Additional antigenic components of VGKC macromolecular complexes remain to be defined.

Insights From LGI1 and CASPR2 Potassium Channel Complex Autoantibody Subtyping

PubMed Central

Klein, Christopher J.; Lennon, Vanda A.; Aston, Paula A.; McKeon, Andrew; O’Toole, Orna; Quek, Amy; Pittock, Sean J.

2014-01-01

Objective: To determine, in patients identified as sero-positive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuronal targets in the VGKC macromolecular complex. Design: Retrospective cohort study. Setting: Clinical practice, Mayo Clinic Neuroimmunology Laboratory and Department of Neurology. Patients: A total of 54853 patients were evaluated, of whom 1992 were found to be VGKC complex IgG positive. Results: From June 1, 2008, to June 30, 2010, comprehensive service serologic evaluation performed on 54 853 patients with unexplained neurologic symptoms identified 1992 patients (4%) who were positive for VGKC complex IgG (values ≥0.03 nmol/L). Among 316 seropositive patients evaluated clinically at our institution, 82 (26%) were seropositive for LGI1 IgG and/or CASPR2 IgG. Of these 82 patients, 27% had low (0.03-0.09 nmol/L), 51% had medium (0.10-0.99 nmol/L), and 22% had high (≥1.00 nmol/L) VGKC complex IgG values. Leucine-rich glioma-inactivated protein 1 IgG positivity was associated with higher VGKC complex IgG values (P<.001) and cortical presentations (P<.001); CASPR2 IgG was associated with peripheral motor excitability (P=.009). However, neither autoantibody was pathognomonic for a specific neurologic presentation or correlated significantly with cancer. Neurologic phenotypes were diverse. Cerebrocortical manifestations (including cognitive impairment and seizures) were recorded in 76% of patients with LGI1 IgG alone (n=46) and 29% with CASPR2 IgG alone (n=28). Peripheral motor hyperexcitability was found in 21% of patients with CASPR2 IgG alone and 6.5% of patients with LGI1 IgG alone. Conclusions: The study emphasizes diverse and overlapping neurologic phenotypes across a range of VGKC complex IgG values and varying LGI1 IgG and CASPR2 IgG specificities. The frequent occurrence of LGI1 IgG and CASPR2 IgG in serum samples with low and medium VGKC complex IgG values supports the clinical significance of low values in clinical evaluation. Additional antigenic components of VGKC macromolecular complexes remain to be defined. PMID:23407760

Formal faculty observation and assessment of bedside skills for 3rd-year neurology clerks

PubMed Central

Mooney, Christopher; Wexler, Erika; Mink, Jonathan; Post, Jennifer; Jozefowicz, Ralph F.

2016-01-01

Objective: To evaluate the feasibility and utility of instituting a formalized bedside skills evaluation (BSE) for 3rd-year medical students on the neurology clerkship. Methods: A neurologic BSE was developed for 3rd-year neurology clerks at the University of Rochester for the 2012–2014 academic years. Faculty directly observed 189 students completing a full history and neurologic examination on real inpatients. Mock grades were calculated utilizing the BSE in the final grade, and number of students with a grade difference was determined when compared to true grade. Correlation was explored between the BSE and clinical scores, National Board of Medical Examiners (NBME) scores, case complexity, and true final grades. A survey was administered to students to assess their clinical skills exposure and the usefulness of the BSE. Results: Faculty completed and submitted a BSE form for 88.3% of students. There was a mock final grade change for 13.2% of students. Correlation coefficients between BSE score and clinical score/NBME score were 0.36 and 0.35, respectively. A statistically significant effect of BSE was found on final clerkship grade (F2,186 = 31.9, p < 0.0001). There was no statistical difference between BSE score and differing case complexities. Conclusions: Incorporating a formal faculty-observed BSE into the 3rd year neurology clerkship was feasible. Low correlation between BSE score and other evaluations indicated a unique measurement to contribute to student grade. Using real patients with differing case complexity did not alter the grade. PMID:27770072

Studying the Brain in a Dish: 3D Cell Culture Models of Human Brain Development and Disease.

PubMed

Brown, Juliana; Quadrato, Giorgia; Arlotta, Paola

2018-01-01

The study of the cellular and molecular processes of the developing human brain has been hindered by access to suitable models of living human brain tissue. Recently developed 3D cell culture models offer the promise of studying fundamental brain processes in the context of human genetic background and species-specific developmental mechanisms. Here, we review the current state of 3D human brain organoid models and consider their potential to enable investigation of complex aspects of human brain development and the underpinning of human neurological disease. © 2018 Elsevier Inc. All rights reserved.

Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology.

PubMed

Wijdicks, Eelco F M; Varelas, Panayiotis N; Gronseth, Gary S; Greer, David M

2010-06-08

To provide an update of the 1995 American Academy of Neurology guideline with regard to the following questions: Are there patients who fulfill the clinical criteria of brain death who recover neurologic function? What is an adequate observation period to ensure that cessation of neurologic function is permanent? Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death? What is the comparative safety of techniques for determining apnea? Are there new ancillary tests that accurately identify patients with brain death? A systematic literature search was conducted and included a review of MEDLINE and EMBASE from January 1996 to May 2009. Studies were limited to adults. In adults, there are no published reports of recovery of neurologic function after a diagnosis of brain death using the criteria reviewed in the 1995 American Academy of Neurology practice parameter. Complex-spontaneous motor movements and false-positive triggering of the ventilator may occur in patients who are brain dead. There is insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly. Apneic oxygenation diffusion to determine apnea is safe, but there is insufficient evidence to determine the comparative safety of techniques used for apnea testing. There is insufficient evidence to determine if newer ancillary tests accurately confirm the cessation of function of the entire brain.

Need for palliative care for neurological diseases.

PubMed

Provinciali, Leandro; Carlini, Giulia; Tarquini, Daniela; Defanti, Carlo Alberto; Veronese, Simone; Pucci, Eugenio

2016-10-01

The new concept of palliative care supports the idea of palliation as an early approach to patients affected by disabling and life-limiting disease which focuses on the patient's quality of life along the entire course of disease. This model moves beyond the traditional concept of palliation as an approach restricted to the final stage of disease and widens the fields of intervention. There is a growing awareness of the importance of palliative care not only in oncological diseases but also in many other branches of medicine, and it appears particularly evident in the approach to many of the most frequent neurological diseases that are chronic, incurable and autonomy-impairing illnesses. The definition and implementation of palliative goals and procedures in neurology must take into account the specific features of these conditions in terms of the complexity and variability of symptoms, clinical course, disability and prognosis. The realization of an effective palliative approach to neurological diseases requires specific skills and expertise to adapt the concept of palliation to the peculiarities of these diseases; this approach should be realized through the cooperation of different services and the action of a multidisciplinary team in which the neurologist should play a central role to identify and face the patient's needs. In this view, it is paramount for the neurologist to be trained in these issues to promote the integration of palliative care in the care of neurological patients.

Neurological Disease in Lupus: Toward a Personalized Medicine Approach.

PubMed

McGlasson, Sarah; Wiseman, Stewart; Wardlaw, Joanna; Dhaun, Neeraj; Hunt, David P J

2018-01-01

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials.

The role of mTOR signalling in neurogenesis, insights from tuberous sclerosis complex.

PubMed

Tee, Andrew R; Sampson, Julian R; Pal, Deb K; Bateman, Joseph M

2016-04-01

Understanding the development and function of the nervous system is one of the foremost aims of current biomedical research. The nervous system is generated during a relatively short period of intense neurogenesis that is orchestrated by a number of key molecular signalling pathways. Even subtle defects in the activity of these molecules can have serious repercussions resulting in neurological, neurodevelopmental and neurocognitive problems including epilepsy, intellectual disability and autism. Tuberous sclerosis complex (TSC) is a monogenic disease characterised by these problems and by the formation of benign tumours in multiple organs, including the brain. TSC is caused by mutations in the TSC1 or TSC2 gene leading to activation of the mechanistic target of rapamycin (mTOR) signalling pathway. A desire to understand the neurological manifestations of TSC has stimulated research into the role of the mTOR pathway in neurogenesis. In this review we describe TSC neurobiology and how the use of animal model systems has provided insights into the roles of mTOR signalling in neuronal differentiation and migration. Recent progress in this field has identified novel mTOR pathway components regulating neuronal differentiation. The roles of mTOR signalling and aberrant neurogenesis in epilepsy are also discussed. Continuing efforts to understand mTOR neurobiology will help to identify new therapeutic targets for TSC and other neurological diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

The neurologic significance of celiac disease biomarkers

PubMed Central

Lennon, Vanda A.; Pittock, Sean J.; Kryzer, Thomas J.; Murray, Joseph

2014-01-01

Objective: To report neurologic phenotypes and their etiologies determined among 68 patients with either (1) celiac disease (CD) or (2) no CD, but gliadin antibody positivity (2002–2012). Methods: Neurologic patients included both those with the CD-prerequisite major histocompatibility complex class II human leukocyte antigen (HLA)-DQ2/DQ8 haplotype, and those without. The 3 groups were as follows: group 1 (n = 44), CD or transglutaminase (Tg)-2/deamidated gliadin immunoglobulin (Ig)A/IgG detected; group 2 (n = 15), HLA-DQ2/DQ8 noncarriers, and gliadin IgA/IgG detected; and group 3 (n = 9), HLA-DQ2/DQ8 carriers, and gliadin IgA/IgG detected. Neurologic patients and 21 nonneurologic CD patients were evaluated for neural and Tg6 antibodies. Results: In group 1, 42 of 44 patients had CD. Neurologic phenotypes (cerebellar ataxia, 13; neuropathy, 11; dementia, 8; myeloneuropathy, 5; other, 7) and causes (autoimmune, 9; deficiencies of vitamin E, folate, or copper, 6; genetic, 6; toxic or metabolic, 4; unknown, 19) were diverse. In groups 2 and 3, 21 of 24 patients had cerebellar ataxia; none had CD. Causes of neurologic disorders in groups 2 and 3 were diverse (autoimmune, 4; degenerative, 4; toxic, 3; nutritional deficiency, 1; other, 2; unknown, 10). One or more neural-reactive autoantibodies were detected in 10 of 68 patients, all with autoimmune neurologic diagnoses (glutamic acid decarboxylase 65 IgG, 4; voltage-gated potassium channel complex IgG, 3; others, 5). Tg6-IgA/IgG was detected in 7 of 68 patients (cerebellar ataxia, 3; myelopathy, 2; ataxia and parkinsonism, 1; neuropathy, 1); the 2 patients with myelopathy had neurologic disorders explained by malabsorption of copper, vitamin E, and folate rather than by neurologic autoimmunity. Conclusions: Our data support causes alternative to gluten exposure for neurologic dysfunction among most gliadin antibody–positive patients without CD. Nutritional deficiency and coexisting autoimmunity may cause neurologic dysfunction in CD. PMID:25261501

HEW and the neurologically handicapped

NASA Technical Reports Server (NTRS)

Huber, W. V.

1974-01-01

Some of the neurological disorders and therapeutic devices are considered with which the Department of Health, Education, and Welfare (HEW) is most concerned. The organization of the Department, because it is a rather complex one with many different agencies involved, is also described.

Predict the neurological recovery under hypothermia after cardiac arrest using C0 complexity measure of EEG signals.

PubMed

Lu, Yueli; Jiang, Dineng; Jia, Xiaofeng; Qiu, Yihong; Zhu, Yisheng; Thakor, Nitish; Tong, Shanbao

2008-01-01

Clinical trials have proven the efficacy of therapeutic hypothermia in improving the functional outcome after cardiac arrest (CA) compared with the normothermic controls. Experimental researches also demonstrated quantitative electroencephalogram (qEEG) analysis was associated with the long-term outcome of the therapeutic hypothermia in brain injury. Nevertheless, qEEG has not been able to provide a prediction earlier than 6h after the return of spontaneous circulation (ROSC). In this study, we use C0 complexity to analyze the nonlinear characteristic of EEG, which could predict the neurological recovery under therapeutic hypothermia during the early phase after asphyxial cardiac arrest in rats. Twelve Wistar rats were randomly assigned to 9-min asphyxia injury under hypothermia (33 degrees C, n=6) or normothermia (37 degrees C, n=6). Significantly greater C0 complexity was found in hypothermic group than that in normothermic group as early as 4h after the ROSC (P0.05). C0 complexity at 4h correlated well with the 72h neurodeficit score (NDS) (Pearson's correlation = 0.882). The results showed that the C0 complexity could be an early predictor of the long-term neurological recovery from cardiac arrest.

Neurological Disease in Lupus: Toward a Personalized Medicine Approach

PubMed Central

McGlasson, Sarah; Wiseman, Stewart; Wardlaw, Joanna; Dhaun, Neeraj; Hunt, David P. J.

2018-01-01

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials. PMID:29928273

Zebrafish neurobehavioral phenomics for aquatic neuropharmacology and toxicology research.

PubMed

Kalueff, Allan V; Echevarria, David J; Homechaudhuri, Sumit; Stewart, Adam Michael; Collier, Adam D; Kaluyeva, Aleksandra A; Li, Shaomin; Liu, Yingcong; Chen, Peirong; Wang, JiaJia; Yang, Lei; Mitra, Anisa; Pal, Subharthi; Chaudhuri, Adwitiya; Roy, Anwesha; Biswas, Missidona; Roy, Dola; Podder, Anupam; Poudel, Manoj K; Katare, Deepshikha P; Mani, Ruchi J; Kyzar, Evan J; Gaikwad, Siddharth; Nguyen, Michael; Song, Cai

2016-01-01

Zebrafish (Danio rerio) are rapidly emerging as an important model organism for aquatic neuropharmacology and toxicology research. The behavioral/phenotypic complexity of zebrafish allows for thorough dissection of complex human brain disorders and drug-evoked pathological states. As numerous zebrafish models become available with a wide spectrum of behavioral, genetic, and environmental methods to test novel drugs, here we discuss recent zebrafish phenomics methods to facilitate drug discovery, particularly in the field of biological psychiatry. Additionally, behavioral, neurological, and endocrine endpoints are becoming increasingly well-characterized in zebrafish, making them an inexpensive, robust and effective model for toxicology research and pharmacological screening. We also discuss zebrafish behavioral phenotypes, experimental considerations, pharmacological candidates and relevance of zebrafish neurophenomics to other 'omics' (e.g., genomic, proteomic) approaches. Finally, we critically evaluate the limitations of utilizing this model organism, and outline future strategies of research in the field of zebrafish phenomics. Copyright © 2015 Elsevier B.V. All rights reserved.

Simulation in neurology.

PubMed

Micieli, Giuseppe; Cavallini, Anna; Santalucia, Paola; Gensini, Gianfranco

2015-10-01

Simulation is a frontier for disseminating knowledge in almost all the fields of medicine and it is attracting growing interest because it offers a means of developing new teaching and training models, as well as of verifying what has been learned in a critical setting that simulates clinical practice. The role of simulation in neurology, until now limited by the obvious physical limitations of the dummies used to train students and learners, is now increasing since, today, it allows anamnestic data to be related to the instrumental evidence necessary for diagnosis and therapeutic decision-making, i.e., to the findings of neurophysiological investigations (EEG, carotid and vertebral echography and transcranial Doppler, for example) and neuroradiological investigations (CT, MRI imaging), as well as vital parameter monitoring (ECG, saturimetry, blood pressure, respiratory frequency, etc.). Simulation, by providing learners with opportunities to discuss, with experts, different profiles of biological parameters (both during the simulation itself and in the subsequent debriefing session), is becoming an increasingly important tool for training those involved in evaluation of critical neurological patients (stroke, Guillan Barrè syndrome, myasthenia, status epilepticus, headache, vertigo, confusional status, etc.) and complex cases. In this SIMMED (Italian Society for Simulation in Medicine) position paper, the applications (present and, possibly, future) of simulation in neurology are reported.

Artistic creativity and dementia.

PubMed

Miller, Zachary A; Miller, Bruce L

2013-01-01

Artistic ability and creativity are defining characteristics of human behavior. Behavioral neurology, as a specialty, believes that even the most complex behaviors can be modeled and understood as the summation of smaller cognitive functions. Literature from individuals with specific brain lesions has helped to map out these smaller regions of cognitive abilities. More recently, models based on neurodegenerative conditions, especially from the frontotemporal dementias, have allowed for greater nuanced investigations into the various functional anatomies necessary for artistic behavior and possibly the underlying networks that promote creativity. © 2013 Elsevier B.V. All rights reserved.

Interactive drama in complex neurological disability management.

PubMed

Fenech, Anne

2009-01-01

To establish whether interactive drama has any effect on the responses of people with complex neurological disabilities resident in a long term care facility. This was a service evaluation using interviews with a group of 31 independently consenting long term care residents, and 27 staff, and observations of engagement of 74 residents involved in an Interactive Drama Project (92.4% of those who had the opportunity to participate). Twenty five (81%) of the 31 residents interviewed reported a new atmosphere of community spirit, 29 (93%) enjoyed the rehearsals, 28 (90.5%) reported a state of 'flow' and 17 (54.6%) a perception of achievement. Fifteen (55.7%) of the 27 staff who completed questionnaires felt that the project had had a positive effect on staff-resident relationship. Twenty (64.4%) residents and 14 (51.7%) staff reported learning something new about others. The majority of participants with complex neurological disabilities were able to engage with interactive drama for some of the time. Therefore interactive drama offered residents opportunities for enjoyment, achievement, challenge and experiencing meaningful occupations.

Drosophila and experimental neurology in the post-genomic era.

PubMed

Shulman, Joshua M

2015-12-01

For decades, the fruit fly, Drosophila melanogaster, has been among the premiere genetic model systems for probing fundamental neurobiology, including elucidation of mechanisms responsible for human neurologic disorders. Flies continue to offer virtually unparalleled versatility and speed for genetic manipulation, strong genomic conservation, and a nervous system that recapitulates a range of cellular and network properties relevant to human disease. I focus here on four critical challenges emerging from recent advances in our understanding of the genomic basis of human neurologic disorders where innovative experimental strategies are urgently needed: (1) pinpointing causal genes from associated genomic loci; (2) confirming the functional impact of allelic variants; (3) elucidating nervous system roles for novel or poorly studied genes; and (4) probing network interactions within implicated regulatory pathways. Drosophila genetic approaches are ideally suited to address each of these potential translational roadblocks, and will therefore contribute to mechanistic insights and potential breakthrough therapies for complex genetic disorders in the coming years. Strategic collaboration between neurologists, human geneticists, and the Drosophila research community holds great promise to accelerate progress in the post-genomic era. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel homozygous variants in ATCAY, MCOLN1, and SACS in complex neurological disorders.

PubMed

Manzoor, Humera; Brüggemann, Norbert; Hussain, Hafiz Muhammad Jafar; Bäumer, Tobias; Hinrichs, Frauke; Wajid, Muhammad; Münchau, Alexander; Naz, Sadaf; Lohmann, Katja

2018-06-01

Neurological disorders comprise a large group of clinically and genetically heterogeneous disorders, many of which have a genetic cause. In addition to a detailed neurological examination, exome sequencing is being increasingly used as a complementary diagnostic tool to identify the underlying genetic cause in patients with unclear, supposedly genetically determined disorders. To identify the genetic cause of a complex movement disorder in five consanguineous Pakistani families. We included five consanguineous Pakistani families with complex recessively inherited movement disorders. Clinical investigation including videotaping was carried out in a total of 59 family members (4-21 per family) and MRI in six patients. Exome sequencing was performed in 4-5 family members per pedigree to explore the underlying genetic cause. Patients presented a wide spectrum of neurological symptoms including ataxia and/or dystonia. We identified three novel homozygous, segregating variants in ATCAY (p.Pro200Profs*20), MCOLN1 (p.Ile184Thr), and SACS (p.Asn3040Lysfs*4) in three of the families. Thus, we were able to identify the likely cause of the disease in a considerable number of families (60%) with the relatively simple and nowadays widely available method of exome sequencing. Of note, close collaboration of neurologists and geneticists was instrumental for proper data interpretation. We expand the phenotypic, genotypic, and ethnical spectrum of mutations in these genes. Our findings alert neurologists that rare genetic causes should be considered in complex phenotypes regardless of ethnicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neurology and neurologic practice in China.

PubMed

Shi, Fu-Dong; Jia, Jian-Ping

2011-11-29

In the wake of dramatic economic success during the past 2 decades, the specialized field of neurology has undergone a significant transformation in China. With an increase in life expectancy, the problems of aging and cognition have grown. Lifestyle alterations have been associated with an epidemiologic transition both in the incidence and etiology of stroke. These changes, together with an array of social issues and institution of health care reform, are creating challenges for practicing neurologists throughout China. Notable problems include overcrowded, decrepit facilities, overloaded physician schedules, deteriorating physician-patient relationships, and an insufficient infrastructure to accommodate patients who need specialized neurologic care. Conversely, with the creation of large and sophisticated neurology centers in many cities across the country, tremendous opportunities exist. Developments in neurologic subspecialties enable delivery of high-quality care. Clinical and translational research based on large patient populations as well as highly sophisticated technologies are emerging in many neurologic centers and pharmaceutical companies. Child neurology and neurorehabilitation will be fast-developing subdisciplines. Given China's extensive population, the growth and progress of its neurology complex, and its ever-improving quality control, it is reasonable to anticipate that Chinese neurologists will contribute notably to unraveling the pathogenic factors causing neurologic diseases and to providing new therapeutic solutions.

Expanding medicines for neurologic disorders on the WHO Model List.

PubMed

Rimmer, Kathryn; Shah, Hiral; Thakur, Kiran

2017-03-07

The WHO Model List of Essential Medicines is a recommended formulary for high-priority diseases based on public health trends and epidemiology patterns. The biennial publication serves as a guide for countries, particularly low- and lower-middle-income countries, to develop their own national essential medicines list (EML), and many nongovernmental organizations base their medication supplies on the WHO EML. Over the last 40 years, WHO has expanded the EML in response to treatment gaps for infectious diseases, pediatrics, palliative care, and cancer. In contrast, neurotherapeutics are poorly represented on the Model List despite the global burden of neurologic disorders, which have continued to increase in the last decade. It is imperative that the neurology community advocate for more evidence-based neurologic medicines on the WHO EML. Equitable access to essential neurologic medicines is a crucial step toward reducing the treatment gap for high-burden neurologic disorders worldwide. © 2017 American Academy of Neurology.

Aquatic rehabilitation for the treatment of neurological disorders.

PubMed

Morris, D M

1994-01-01

Patients with neurological disorders present therapists with complex challenges for treatment, including weakness, hypertonicity, voluntary movement deficit, limited range of motion, sensory loss, incoordination, and postural instability. The presence of one or more of these impairments negatively influences these patients by contributing to problems in walking, transferring, and reaching. Aquatic rehabilitation offers a unique, versatile approach to the treatment of these disabilities. This article examines the problems encountered by patients with neurological disorders, general principles guiding neurotreatment, and aquatic neurorehabilitation approaches.

The practice of neurology: Looking ahead by looking back.

PubMed

Ringel, Steven P

2015-05-19

Over the last 50 years, there have been many improvements in therapy for individuals with neurologic disorders. Simultaneously, the complexity and cost of care have increased. The delivery of neurologic services is inefficient. The needs of both patients and neurologists are not being optimally addressed. Although greater attention is on the quality, safety, and value of the care, there remains a need for fundamental redesign in the way neurologic services are provided. The future practice of neurology will likely be interdisciplinary and provide both easy access and efficient coordination of services. No matter what changes in financing of health care are adopted, focus needs to be on reducing health care costs. Patients seeking neurologic care will expect seamless, innovative, and cost-effective services and to be active participants in their care. The proposed modifications address current demands and advocate for prospective innovative solutions. The changes proposed to improve care for patients will simultaneously make the careers of neurologists more gratifying and less stressful. © 2015 American Academy of Neurology.

The Health Care Financing Administration's new examination documentation criteria: minimum auditing standards for the neurologic examination to be used by Medicare and other payors. Report from the American Academy of Neurology Medical Economics and Management Subcommittee.

PubMed

Nuwer, M R; Sigsbee, B

1998-02-01

Medicare recently announced the adoption of minimum documentation criteria for the neurologic examination. These criteria are added to existing standards for the history and medical decision-making. These criteria will be used in compliance audits by Medicare and other payors. Given the current federal initiative to eliminate fraud in the Medicare program, all neurologists need to comply with these standards. These criteria are for documentation only. Neurologic standards of care require a more complex and diverse examination pertinent to the problem(s) under consideration. Further guidance as to the content of a neurologic evaluation is outlined in the article "Practice guidelines: Neurologic evaluation" (Neurology 1990; 40: 871). The level of history and examination required for specific services is defined in the American Medical Association current procedural terminology book. Documentation standards for examination of children are not yet defined.

Lesch Nyhan syndrome: a novel complex mutation in a Tunisian child.

PubMed

Rebai, Ibtihel; Kraoua, Ichraf; Benrhouma, Hanene; Rouissi, Aida; Turki, Ilhem; Ceballos-Picot, Irène; Gouider-Khouja, Neziha

2014-11-01

Lesch Nyhan syndrome (LNS) is an X-linked recessive disorder due to complete deficiency of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme. Defect of the enzymatic activity is related to mutations of the HPRT1 gene. The disorder severity is due to neurological features and renal complications. Up to now, more than 300 mutations have been reported. We report on a Tunisian child with a severe phenotype due to a novel identified complex mutation. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Increased time to pregnancy is associated with less optimal neurological condition in 4-year-old singletons, in vitro fertilization itself is not.

PubMed

Schendelaar, P; Van den Heuvel, E R; Heineman, M J; La Bastide-Van Gemert, S; Middelburg, K J; Seggers, J; Hadders-Algra, M

2014-12-01

Does ovarian hyperstimulation, the in vitro procedures required for in vitro fertilization (IVF)/ intracytoplasmic sperm injection or the combination of both, affect the neurological outcome of 4-year-old singletons? Ovarian hyperstimulation, the in vitro procedure and the combination of both, were not associated with the worse neurological outcome in 4-year-old singletons. Assisted reproduction techniques (ARTs) are not associated with neurological dysfunction during the first post-natal years; however, effects on the long-term neurological outcome are still inconclusive. An increased time to pregnancy (TTP, a proxy for the severity of subfertility) has been associated with a less optimal neurological condition at age 2. The present study focuses on the neurodevelopmental outcome of 4-year-old ART-offspring. Longitudinal, prospective follow-up study. Four-year-old singletons born to subfertile parents (subfertile group, n = 195), including singletons born after controlled ovarian hyperstimulation IVF (COH-IVF, n = 63), modified natural cycle IVF (MNC-IVF, n = 53) and natural conception (Sub-NC, n = 79). Data on underlying cause of subfertility and TTP were present. In addition, we assessed newly recruited 4-year-old singletons born to fertile parents after natural conception (reference group, n = 98). Neurological development was evaluated with the neurological examination according to Hempel, resulting in a neurological optimality score (NOS), a fluency score and the occurrence of the clinically relevant form of minor neurological dysfunction (complex MND). The primary outcome was the fluency score, as fluency of movements is easily reduced by subtle brain dysfunction. Data were analysed with univariable and multivariable regression analyses, in which special attention was paid to sex differences in the neurological outcome. The fluency score, NOS and the prevalence of complex MND were similar in COH-IVF, MNC-IVF and Sub-NC children. The neurological condition of children born to subfertile parents was similar to that of children of fertile parents and was independent of the underlying cause of subfertility. No statistically significant associations were found between TTP and the fluency score and NOS. However, a positive correlation was found between TTP and the prevalence of complex MND (TTP in years, adjusted odds ratio [OR] [95% confidence interval, CI]: 1.207 [1.038 to 1.404], P = 0.014); a correlation which could be attributed to girls, in whom an evident positive correlation was present (adjusted OR [95% CI]: 1.542 [1.161 to 2.047], P = 0.003). A similar association was absent in boys. The prospective design of our study and small post-natal attrition rate (9.3%) reduced potential selection bias based on the child's development or health. The assessors were blind to the mode of conception, except for the group of children born to fertile parents, which was newly recruited. The study lacks sufficient power to conclude firmly that increased TTP is associated with a higher prevalence of complex MND. Our study suggests that the severity of subfertility, rather than its simple presence or components of IVF treatment, affects the neurological outcome. Moreover, girls may be neurologically more vulnerable for the effect of severity of subfertility. The finding that the severity of subfertility may be the decisive factor rather than the presence of a history of subfertility per se corroborates previous reports. Our results cannot be generalized to multiples, as we studied singletons only. The study was financially supported by the University Medical Center Groningen, grant number: 754510, the Junior Scientific Masterclass, the Postgraduate School Behavioural and Cognitive Neurosciences and the Cornelia Foundation, Groningen, The Netherlands. The authors have no conflicts of interest to declare. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Predictability and Robustness in the Manipulation of Dynamically Complex Objects

PubMed Central

Hasson, Christopher J.

2017-01-01

Manipulation of complex objects and tools is a hallmark of many activities of daily living, but how the human neuromotor control system interacts with such objects is not well understood. Even the seemingly simple task of transporting a cup of coffee without spilling creates complex interaction forces that humans need to compensate for. Predicting the behavior of an underactuated object with nonlinear fluid dynamics based on an internal model appears daunting. Hence, this research tests the hypothesis that humans learn strategies that make interactions predictable and robust to inaccuracies in neural representations of object dynamics. The task of moving a cup of coffee is modeled with a cart-and-pendulum system that is rendered in a virtual environment, where subjects interact with a virtual cup with a rolling ball inside using a robotic manipulandum. To gain insight into human control strategies, we operationalize predictability and robustness to permit quantitative theory-based assessment. Predictability is quantified by the mutual information between the applied force and the object dynamics; robustness is quantified by the energy margin away from failure. Three studies are reviewed that show how with practice subjects develop movement strategies that are predictable and robust. Alternative criteria, common for free movement, such as maximization of smoothness and minimization of force, do not account for the observed data. As manual dexterity is compromised in many individuals with neurological disorders, the experimental paradigm and its analyses are a promising platform to gain insights into neurological diseases, such as dystonia and multiple sclerosis, as well as healthy aging. PMID:28035560

Successful nonoperative treatment of a three-column thoracic fracture in a patient with ankylosing spondylitis: existence and clinical significance of the fourth column of the spine.

PubMed

Shen, Francis H; Samartzis, Dino

2007-07-01

A case report. To report the successful nonoperative management of a patient with progressive ankylosing spondylitis who sustained a three-column flexion-distraction injury of the upper thoracic spine with an intact sternal-rib complex, thereby emphasizing the existence and clinical relevance of the fourth-column concept in such patients. Three-column injuries of the cervical and lumbar spine are typically unstable and require surgical stabilization. Patients with ankylosing spondylitis are at an increase risk to sustain three-column injuries of the spine due to their progressive inflammatory disease, a state that renders the spine brittle and alters its biomechanical function. A fourth-column model of the thoracic spine has been proposed and incorporates the sternal-rib complex; however, such a model has rarely been addressed in the literature and its role regarding three-column upper thoracic spine injury with an intact sternal-rib complex in patients with ankylosing spondylitis is unknown. METHODS.: A 68-year-old white man with ankylosing spondylitis and Pickwickian body habitus sustained a three-column flexion-distraction injury at T5 following a ground-level fall. The patient complained of midthoracic back pain; however, he was neurologically intact and ambulated without aids. Because of the patient's numerous active medical issues that substantially increased his perioperative risks combined with symptomatic improvement of his pain, the patient refused surgical stabilization. In addition, because of the patient's body habitus and pulmonary issues, external brace immobilization was not tolerated. At 17 months of follow-up, the patient remained neurologically intact, ambulated well, his midthoracic back pain had subsided, and no progressive kyphosis was noted. This case confirms the existence and clinical relevance of the fourth column of the thoracic spine and its role in providing added spinal stability in the patient with ankylosing spondylitis. As such, it is still possible to achieve a favorable clinical outcome in a select subpopulation of patients with ankylosing spondylitis that sustain three-column flexion-distraction injuries who are neurologically intact and are not candidates for surgical stabilization.

International issues: Obtaining an adult neurology residency position in the United States: an overview.

PubMed

Jordan, Justin T; Sellner, Johann; Struhal, Walter; Schneider, Logan; Mayans, David

2014-04-08

Around the world, there are marked differences in neurology training, including training duration and degree of specialization. In the United States, adult neurology residency is composed of 1 year of internal medicine training (preliminary year) and 3 years of neurology-specific training. Child neurology, which is not the focus of this article, is 2 years of pediatrics and 3 years of neurology training. The route to adult neurology residency training in the United States is standardized and is similar to most other US specialties. Whereas US medical graduates often receive stepwise guidance from their medical school regarding application for residency training, international graduates often enter this complex process with little or no such assistance. Despite this discrepancy, about 10%-15% of residency positions in the United States are filled by international medical graduates.(1,2) In adult neurology specifically, 35% of matched positions were filled by international graduates in 2013, 75% of whom were not US citizens.(1) In an effort to provide a preliminary understanding of the application process and related terminology (table 1) and thereby encourage international residency applicants, we describe the steps necessary to apply for neurology residency in the United States.

Pain Information Brochure

MedlinePlus

... National Institute of Neurological Disorders and Stroke Complex Regional Pain Syndrome Complex Regional Pain Syndrome Information Page ... ACTTION Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks. Date last modified: Contact Us ...

Tuberous Sclerosis Complex National Database

DTIC Science & Technology

2006-10-01

about conditions in the following areas (as applicable to the participant): academic, cardiac, cognitive, dental , dermatological, liver, neurological...Search Criteria Add To These Results With an Affected Area Academic Cardiac Dental Dermatological Liver Neurological...The Research Integrity Officer, with the assistance of counsel (if needed), will convene the first meeting of the investigation committee to review

Blood-brain barrier-on-a-chip: Microphysiological systems that capture the complexity of the blood-central nervous system interface.

PubMed

Phan, Duc Tt; Bender, R Hugh F; Andrejecsk, Jillian W; Sobrino, Agua; Hachey, Stephanie J; George, Steven C; Hughes, Christopher Cw

2017-11-01

The blood-brain barrier is a dynamic and highly organized structure that strictly regulates the molecules allowed to cross the brain vasculature into the central nervous system. The blood-brain barrier pathology has been associated with a number of central nervous system diseases, including vascular malformations, stroke/vascular dementia, Alzheimer's disease, multiple sclerosis, and various neurological tumors including glioblastoma multiforme. There is a compelling need for representative models of this critical interface. Current research relies heavily on animal models (mostly mice) or on two-dimensional (2D) in vitro models, neither of which fully capture the complexities of the human blood-brain barrier. Physiological differences between humans and mice make translation to the clinic problematic, while monolayer cultures cannot capture the inherently three-dimensional (3D) nature of the blood-brain barrier, which includes close association of the abluminal side of the endothelium with astrocyte foot-processes and pericytes. Here we discuss the central nervous system diseases associated with blood-brain barrier pathology, recent advances in the development of novel 3D blood-brain barrier -on-a-chip systems that better mimic the physiological complexity and structure of human blood-brain barrier, and provide an outlook on how these blood-brain barrier-on-a-chip systems can be used for central nervous system disease modeling. Impact statement The field of microphysiological systems is rapidly evolving as new technologies are introduced and our understanding of organ physiology develops. In this review, we focus on Blood-Brain Barrier (BBB) models, with a particular emphasis on how they relate to neurological disorders such as Alzheimer's disease, multiple sclerosis, stroke, cancer, and vascular malformations. We emphasize the importance of capturing the three-dimensional nature of the brain and the unique architecture of the BBB - something that until recently had not been well modeled by in vitro systems. Our hope is that this review will provide a launch pad for new ideas and methodologies that can provide us with truly physiological BBB models capable of yielding new insights into the function of this critical interface.

Neurology and neurologic practice in China

PubMed Central

2011-01-01

In the wake of dramatic economic success during the past 2 decades, the specialized field of neurology has undergone a significant transformation in China. With an increase in life expectancy, the problems of aging and cognition have grown. Lifestyle alterations have been associated with an epidemiologic transition both in the incidence and etiology of stroke. These changes, together with an array of social issues and institution of health care reform, are creating challenges for practicing neurologists throughout China. Notable problems include overcrowded, decrepit facilities, overloaded physician schedules, deteriorating physician-patient relationships, and an insufficient infrastructure to accommodate patients who need specialized neurologic care. Conversely, with the creation of large and sophisticated neurology centers in many cities across the country, tremendous opportunities exist. Developments in neurologic subspecialties enable delivery of high-quality care. Clinical and translational research based on large patient populations as well as highly sophisticated technologies are emerging in many neurologic centers and pharmaceutical companies. Child neurology and neurorehabilitation will be fast-developing subdisciplines. Given China's extensive population, the growth and progress of its neurology complex, and its ever-improving quality control, it is reasonable to anticipate that Chinese neurologists will contribute notably to unraveling the pathogenic factors causing neurologic diseases and to providing new therapeutic solutions. PMID:22123780

Impairment of executive function in Kenyan children exposed to severe falciparum malaria with neurological involvement.

PubMed

Kariuki, Symon M; Abubakar, Amina; Newton, Charles R J C; Kihara, Michael

2014-09-16

Persistent neurocognitive impairments occur in a fifth of children hospitalized with severe falciparum malaria. There is little data on the association between different neurological phenotypes of severe malaria (seizures, impaired consciousness and prostration) and impairments in executive function. Executive functioning of children exposed to severe malaria with different neurological phenotypes (N = 58) and in those unexposed (N = 56) was examined using neuropsychological tests such as vigilance test, test for everyday attention test for children (TEA-Ch), contingency naming test (CNT) and self-ordered pointing test (SOPT). Linear regression was used to determine the association between neurological phenotypes of severe malaria and executive function performance scores, accounting for potential confounders. Children with complex seizures in severe malaria performed more poorly than unexposed controls in the vigilance (median efficiency scores (interquartile range) = 4.84 (1.28-5.68) vs. 5.84 (4.71-6.42), P = 0.030) and SOPT (mean errors (standard deviation) = 29.50 (8.82) vs. 24.80 (6.50), P = 0.029) tests, but no differences were observed in TEA-Ch and CNT tests. Performance scores for other neurological phenotypes of severe malaria were similar with those of unexposed controls. After accounting for potential confounders, such as child's age, sex, schooling; maternal age, schooling and economic activity; perinatal factors and history of seizures, complex seizures remained associated with efficiency scores in the vigilance test (beta coefficient (β) (95% confidence interval (CI)) = -0.40 (-0.67, -0.13), P = 0.006) and everyday attention scores of the TEA-Ch test (β (95% CI) = -0.57 (-1.04, -0.10), P = 0.019); the association with SOPT error scores was weak (β (95% CI) = 4.57 (-0.73-9.89), P = 0.089). Combined neurological phenotypes were not significantly associated with executive function performance scores. Executive function impairment in children with severe malaria is associated with specific neurological phenotypes, particularly complex seizures. Effective prophylaxis and management of malaria-associated acute seizures may improve executive functioning performance scores of children.

Education requirements for nurses working with people with complex neurological conditions: nurses' perceptions.

PubMed

Baker, Mark

2012-01-01

Following a service evaluation methodology, this paper reports on registered nurses' (RNs) and healthcare assistants' (HCAs) perceptions about education and training requirements in order to work with people with complex neurological disabilities. A service evaluation was undertaken to meet the study aim using a non-probability, convenience method of sampling 368 nurses (n=110 RNs, n=258 HCAs) employed between October and November 2008 at one specialist hospital in south-west London in the U.K. The main results show that respondents were clear about the need to develop an education and training programme for RNs and HCAs working in this speciality area (91% of RNs and 94% of HCAs). A variety of topics were identified to be included within a work-based education and training programme, such as positively managing challenging behaviour, moving and handling, working with families. Adults with complex neurological needs have diverse needs and thus nurses working with this patient group require diverse education and training in order to deliver quality patient-focused nursing care. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Charles Miller Fisher: the grandmaster of neurological observation].

PubMed

Fukutake, Toshio

2014-11-01

Charles Miller Fisher is widely regarded as the father of modern stroke neurology. He discovered almost all pathomechanisms of cerebral infarction, including embolism from atrial fibrillation, carotid artery disease, and lacunar infarcts and their syndromes, by the most meticulous clinico-pathological observations. Moreover, his work provided the basis for treatments such as anticoagulation, antiplatelet therapy, and carotid endarterectomy. He also contributed greatly to several topics of General Neurology; for example, migraine, normal pressure hydrocephalus, and Miller Fisher syndrome. In his late years, he tried to expand the neurological field to the more complex disorders of human behavior, including hysteria, dementia, and ill-defined pain syndromes. He thus became known as the grandmaster of refined neurological observation. His lifelong detailed studies were crucially important in helping neurologists all over the world recognize disorders and syndromes that had not previously been understood.

Cannabis: old medicine with new promise for neurological disorders.

PubMed

Carter, Gregory T; Weydt, Patrick

2002-03-01

Marijuana is a complex substance containing over 60 different forms of cannabinoids, the active ingredients. Cannabinoids are now known to have the capacity for neuromodulation, via direct, receptor-based mechanisms at numerous levels within the nervous system. These have therapeutic properties that may be applicable to the treatment of neurological disorders; including anti-oxidative, neuroprotective, analgesic and anti-inflammatory actions; immunomodulation, modulation of glial cells and tumor growth regulation. This article reviews the emerging research on the physiological mechanisms of endogenous and exogenous cannabinoids in the context of neurological disease.

Disruptive technology disorder: A past, present, and future neurologic syndrome.

PubMed

Weaver, Donald F

2017-07-25

Based upon an analysis of 6 major historical technological advances over the last 150 years, a new syndrome, disruptive technology disorder (DTD), is introduced. DTD describes the human health ailments that accompany the implementation of disruptive technologies. Elevator sickness, railway spine, and bicycle face are representative examples. Though the underlying causative disruptive technologies may differ, many neurologic symptoms (headache, dizziness, weakness) are common to multiple DTDs. Born of technology-driven societal change, DTDs manifest as a complex interplay between biological and psychological symptoms. © 2017 American Academy of Neurology.

Development and Validation of an Empiric Tool to Predict Favorable Neurologic Outcomes Among PICU Patients.

PubMed

Gupta, Punkaj; Rettiganti, Mallikarjuna; Gossett, Jeffrey M; Daufeldt, Jennifer; Rice, Tom B; Wetzel, Randall C

2018-01-01

To create a novel tool to predict favorable neurologic outcomes during ICU stay among children with critical illness. Logistic regression models using adaptive lasso methodology were used to identify independent factors associated with favorable neurologic outcomes. A mixed effects logistic regression model was used to create the final prediction model including all predictors selected from the lasso model. Model validation was performed using a 10-fold internal cross-validation approach. Virtual Pediatric Systems (VPS, LLC, Los Angeles, CA) database. Patients less than 18 years old admitted to one of the participating ICUs in the Virtual Pediatric Systems database were included (2009-2015). None. A total of 160,570 patients from 90 hospitals qualified for inclusion. Of these, 1,675 patients (1.04%) were associated with a decline in Pediatric Cerebral Performance Category scale by at least 2 between ICU admission and ICU discharge (unfavorable neurologic outcome). The independent factors associated with unfavorable neurologic outcome included higher weight at ICU admission, higher Pediatric Index of Morality-2 score at ICU admission, cardiac arrest, stroke, seizures, head/nonhead trauma, use of conventional mechanical ventilation and high-frequency oscillatory ventilation, prolonged hospital length of ICU stay, and prolonged use of mechanical ventilation. The presence of chromosomal anomaly, cardiac surgery, and utilization of nitric oxide were associated with favorable neurologic outcome. The final online prediction tool can be accessed at https://soipredictiontool.shinyapps.io/GNOScore/. Our model predicted 139,688 patients with favorable neurologic outcomes in an internal validation sample when the observed number of patients with favorable neurologic outcomes was among 139,591 patients. The area under the receiver operating curve for the validation model was 0.90. This proposed prediction tool encompasses 20 risk factors into one probability to predict favorable neurologic outcome during ICU stay among children with critical illness. Future studies should seek external validation and improved discrimination of this prediction tool.

The neurotechnological revolution: unlocking the brain's secrets to develop innovative technologies as well as treatments for neurological diseases.

PubMed

Banks, Jim

2015-01-01

The brain contains all that makes us human, but its complexity is the source of both inspiration and frailty. Aging population is increasingly in need of effective care and therapies for brain diseases, including stroke, Parkinson's disease and Alzheimer's disease. The world's scientific community working hard to unravel the secrets of the brain's computing power and to devise technologies that can heal it when it fails and restore critical functions to patients with neurological conditions. Neurotechnology is the emerging field that brings together the development of technologies to study the brain and devices that improve and repair brain function. What is certain is the momentum behind neurotechnological research is building, and whether through implants, BCIs, or innovative computational systems inspired by the human brain, more light will be shed on our most complex and most precious organ, which will no doubt lead to effective treatment for many neurological conditions.

Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells.

PubMed

Xu, Xiao-hong; Zhong, Zhong

2013-06-01

With the general decline of pharmaceutical research productivity, there are concerns that many components of the drug discovery process need to be redesigned and optimized. For example, the human immortalized cell lines or animal primary cells commonly used in traditional drug screening may not faithfully recapitulate the pathological mechanisms of human diseases, leading to biases in assays, targets, or compounds that do not effectively address disease mechanisms. Recent advances in stem cell research, especially in the development of induced pluripotent stem cell (iPSC) technology, provide a new paradigm for drug screening by permitting the use of human cells with the same genetic makeup as the patients without the typical quantity constraints associated with patient primary cells. In this article, we will review the progress made to date on cellular disease models using human stem cells, with a focus on patient-specific iPSCs for neurological diseases. We will discuss the key challenges and the factors that associated with the success of using stem cell models for drug discovery through examples from monogenic diseases, diseases with various known genetic components, and complex diseases caused by a combination of genetic, environmental and other factors.

A category adjustment approach to memory for spatial location in natural scenes.

PubMed

Holden, Mark P; Curby, Kim M; Newcombe, Nora S; Shipley, Thomas F

2010-05-01

Memories for spatial locations often show systematic errors toward the central value of the surrounding region. This bias has been explained using a Bayesian model in which fine-grained and categorical information are combined (Huttenlocher, Hedges, & Duncan, 1991). However, experiments testing this model have largely used locations contained in simple geometric shapes. Use of this paradigm raises 2 issues. First, do results generalize to the complex natural world? Second, what types of information might be used to segment complex spaces into constituent categories? Experiment 1 addressed the 1st question by showing a bias toward prototypical values in memory for spatial locations in complex natural scenes. Experiment 2 addressed the 2nd question by manipulating the availability of basic visual cues (using color negatives) or of semantic information about the scene (using inverted images). Error patterns suggest that both perceptual and conceptual information are involved in segmentation. The possible neurological foundations of location memory of this kind are discussed. PsycINFO Database Record (c) 2010 APA, all rights reserved.

SNAP-25 IN NEUROPSYCHIATRIC DISORDERS

PubMed Central

Corradini, Irene; Verderio, Claudia; Sala, Mariaelvina; Wilson, Michael C.; Matteoli, Michela

2009-01-01

SNAP-25 is plasma membrane protein which, together with syntaxin and the synaptic vesicle protein VAMP/synaptobrevin, forms the SNARE docking complex for regulated exocytosis. SNAP-25 also modulates different voltage-gated calcium channels, representing therefore a multifunctional protein that plays essential roles in neurotransmitter release at different steps. Recent genetic studies of human populations and of some mouse models implicate that alterations in SNAP-25 gene structure, expression and/or function may contribute directly to these distinct neuropsychiatric and neurological disorders. PMID:19161380

A larval zebrafish model of bipolar disorder as a screening platform for neuro-therapeutics.

PubMed

Ellis, Lee David; Soanes, Kelly Howard

2012-08-01

Modelling neurological diseases has proven extraordinarily difficult due to the phenotypic complexity of each disorder. The zebrafish has become a useful model system with which to study abnormal neurological and behavioural activity and holds promise as a model of human disease. While most of the disease modelling using zebrafish has made use of adults, larvae hold tremendous promise for the high-throughput screening of potential therapeutics. The further development of larval disease models will strengthen their ability to contribute to the drug screening process. Here we have used zebrafish larvae to model the symptoms of bipolar disorder by treating larvae with sub-convulsive concentrations of the GABA antagonist pentylenetetrazol (PTZ). A number of therapeutics that act on different targets, in addition to those that have been used to treat bipolar disorder, were tested against this model to assess its predictive value. Carbamazepine, valproic acid, baclofen and honokiol, were found to oppose various aspects of the PTZ-induced changes in activity. Lidocaine and haloperidol exacerbated the PTZ-induced activity changes and sulpiride had no effect. By comparing the degree of phenotypic rescue with the mechanism of action of each therapeutic we have shown that the low-concentration PTZ model can produce a number of intermediate phenotypes that model symptoms of bipolar disorder, may be useful in modelling other disease states, and will help predict the efficacy of novel therapeutics. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

3D printed nervous system on a chip.

PubMed

Johnson, Blake N; Lancaster, Karen Z; Hogue, Ian B; Meng, Fanben; Kong, Yong Lin; Enquist, Lynn W; McAlpine, Michael C

2016-04-21

Bioinspired organ-level in vitro platforms are emerging as effective technologies for fundamental research, drug discovery, and personalized healthcare. In particular, models for nervous system research are especially important, due to the complexity of neurological phenomena and challenges associated with developing targeted treatment of neurological disorders. Here we introduce an additive manufacturing-based approach in the form of a bioinspired, customizable 3D printed nervous system on a chip (3DNSC) for the study of viral infection in the nervous system. Micro-extrusion 3D printing strategies enabled the assembly of biomimetic scaffold components (microchannels and compartmented chambers) for the alignment of axonal networks and spatial organization of cellular components. Physiologically relevant studies of nervous system infection using the multiscale biomimetic device demonstrated the functionality of the in vitro platform. We found that Schwann cells participate in axon-to-cell viral spread but appear refractory to infection, exhibiting a multiplicity of infection (MOI) of 1.4 genomes per cell. These results suggest that 3D printing is a valuable approach for the prototyping of a customized model nervous system on a chip technology.

Bridging the gap: large animal models in neurodegenerative research.

PubMed

Eaton, S L; Wishart, T M

2017-08-01

The world health organisation has declared neurological disorders as one of the greatest public health risks in the world today. Yet, despite this growing concern, the mechanisms underpinning many of these conditions are still poorly understood. This may in part be due to the seemingly diverse nature of the initiating insults ranging from genetic (such as the Ataxia's and Lysosomal storage disorders) through to protein misfolding and aggregation (i.e. Prions), and those of a predominantly unknown aetiology (i.e. Alzheimer's and Parkinson's disease). However, efforts to elucidate mechanistic regulation are also likely to be hampered because of the complexity of the human nervous system, the apparent selective regional vulnerability and differential degenerative progression. The key to elucidating these aetiologies is determining the regional molecular cascades, which are occurring from the early through to terminal stages of disease progression. Whilst much molecular data have been captured at the end stage of disease from post-mortem analysis in humans, the very early stages of disease are often conspicuously asymptomatic, and even if they were not, repeated sampling from multiple brain regions of "affected" patients and "controls" is neither ethical nor possible. Model systems therefore become fundamental for elucidating the mechanisms governing these complex neurodegenerative conditions. However, finding a model that precisely mimics the human condition can be challenging and expensive. Whilst cellular and invertebrate models are frequently used in neurodegenerative research and have undoubtedly yielded much useful data, the comparatively simplistic nature of these systems makes insights gained from such a stand alone model limited when it comes to translation. Given the recent advances in gene editing technology, the options for novel model generation in higher order species have opened up new and exciting possibilities for the field. In this review, we therefore explain some of the reasons why larger animal models often appear to give a more robust recapitulation of human neurological disorders and why they may be a critical stepping stone for effective therapeutic translation.

[Therapeutic update in tuberous sclerosis complex: the role of mTOR pathway inhibitors].

PubMed

Ruiz-Falcó Rojas, M Luz

2012-05-21

Tuberous sclerosis complex is an autosomal dominant disease, with variable expressivity and multisystemic involvement, which is characterised by the growth of benign tumours called hamartomas. The organs that are most commonly affected are the brain, skin, kidneys, eyes, heart and lungs. Of all the children with this disease, 85% present neurological manifestations that, due to their severity, are the main cause of morbidity and mortality. The most significant neurological manifestations are epilepsy, autism spectrum disorders and mental retardation. It has been shown that in tuberous sclerosis complex the genes TSC1 and TSC2 alter the mTOR enzyme cascade, which sets off inhibition of this pathway. The possibility of resorting to treatments applied at the origin, thus inhibiting this pathway, is currently being evaluated.

Focal status epilepticus and progressive dyskinesia: A novel phenotype for glycine receptor antibody-mediated neurological disease in children.

PubMed

Chan, D W S; Thomas, T; Lim, M; Ling, S; Woodhall, M; Vincent, A

2017-03-01

Antibody-associated disorders of the central nervous system are increasingly recognised in adults and children. Some are known to be paraneoplastic, whereas in others an infective trigger is postulated. They include disorders associated with antibodies to N-methyl-d-aspartate receptor (NMDAR), voltage-gated potassium channel-complexes (VGKC-complex), GABA B receptor or glycine receptor (GlyR). With antibodies to NMDAR or VGKC-complexes, distinct clinical patterns are well characterised, but as more antibodies are discovered, the spectra of associated disorders are evolving. GlyR antibodies have been detected in patients with progressive encephalopathy with rigidity and myoclonus (PERM), or stiff man syndrome, both rare but disabling conditions. We report a case of a young child with focal seizures and progressive dyskinesia in whom GlyR antibodies were detected. Anticonvulsants and immunotherapy were effective in treating both the seizures and movement disorder with good neurological outcome and with a decline in the patient's serum GlyR-Ab titres. Glycine receptor antibodies are associated with focal status epilepticus and seizures, encephalopathy and progressive dyskinesia and should be evaluated in autoimmune encephalitis. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Preventing "Neurophobia": Remodeling Neurology Education for 21st-Century Medical Students through Effective Pedagogical Strategies for "Neurophilia".

PubMed

Shelley, Bhaskara P; Chacko, Thomas V; Nair, Balakrishnan R

2018-01-01

Neurology has a reputation, particularly as a complex "head-to-toe" discipline for undergraduate medical students. Neurophobia syndrome, a global phenomenon, fundamentally stems from pedagogical deficiencies during the undergraduate curriculum, the lack of vertical integration between basic neurosciences and clinical bedside neurology, the lack of clinical reasoning exercises, cognitive heuristics, and clinical problem-solving, errors in diagnostic competence, and hyposkilia. This ultimately results in poor clinical competence and proficiency in clinical neurology and causes attrition in nurturing a passion for learning the neurology discipline. This article explores plausible factors that contribute to the genesis of neurophobia and multifaceted strategies to nurture interest in neurosciences and provide possible solutions to demystify neurology education, especially the need for evidence-based educational interventions. Remodeling neurology education through effective pedagogical strategies and remedial measures, and using the Miller's pyramid, would provide a framework for assessing clinical competence in clinical bedside neurology. Technology-enhanced education and digital classrooms would undoubtedly stamp out neurophobia in medical students of the 21 st century. It will not frighten off another generation of nonneurologist physicians to empower them to hone expertise in order to tackle the increasing burden of neurological disorders in India. Furthermore, promoting neurophilia would facilitate the next generation of medical students in pursuing career options in neurology which would be quintessential not only in closing India's looming neurologist workforce gap but also in fostering interest in research imperatives in the next generation of medical students.

Preventing “Neurophobia”: Remodeling Neurology Education for 21st-Century Medical Students through Effective Pedagogical Strategies for “Neurophilia”

PubMed Central

Shelley, Bhaskara P.; Chacko, Thomas V.; Nair, Balakrishnan R.

2018-01-01

Neurology has a reputation, particularly as a complex “head-to-toe” discipline for undergraduate medical students. Neurophobia syndrome, a global phenomenon, fundamentally stems from pedagogical deficiencies during the undergraduate curriculum, the lack of vertical integration between basic neurosciences and clinical bedside neurology, the lack of clinical reasoning exercises, cognitive heuristics, and clinical problem-solving, errors in diagnostic competence, and hyposkilia. This ultimately results in poor clinical competence and proficiency in clinical neurology and causes attrition in nurturing a passion for learning the neurology discipline. This article explores plausible factors that contribute to the genesis of neurophobia and multifaceted strategies to nurture interest in neurosciences and provide possible solutions to demystify neurology education, especially the need for evidence-based educational interventions. Remodeling neurology education through effective pedagogical strategies and remedial measures, and using the Miller's pyramid, would provide a framework for assessing clinical competence in clinical bedside neurology. Technology-enhanced education and digital classrooms would undoubtedly stamp out neurophobia in medical students of the 21st century. It will not frighten off another generation of nonneurologist physicians to empower them to hone expertise in order to tackle the increasing burden of neurological disorders in India. Furthermore, promoting neurophilia would facilitate the next generation of medical students in pursuing career options in neurology which would be quintessential not only in closing India's looming neurologist workforce gap but also in fostering interest in research imperatives in the next generation of medical students. PMID:29720792

A rare cause of late onset neurological deficit in post tuberculous kyphotic deformity—case report

PubMed Central

Shetty, Ajoy Prasad; Kanna, Rishi M.; Rajasekaran, Shanmuganathan

2017-01-01

Late onset neurological deficit is a rare complication of spinal tuberculosis. Reactivation of the disease and compression by internal gibbus are the common causes for late onset neurological deficit. We report a rare cause of late onset paraplegia in a patient with post tubercular kyphotic deformity. The late onset neurological deficit was due to the adjacent segment degeneration proximal to the kyphotic deformity. Posterior hypertrophied ligamentum flavum and anterior disc osteophyte complex caused the cord compression. The increased stress for prolonged period at the end of the deformity was the reason for the accelerated degeneration. Patient underwent posterior decompression, posterolateral and interbody fusion. Deformity correction was not done. To our best knowledge, this is only the second report of this unusual cause of late onset paraplegia. PMID:29354759

A rare cause of late onset neurological deficit in post tuberculous kyphotic deformity-case report.

PubMed

Subramani, Suresh; Shetty, Ajoy Prasad; Kanna, Rishi M; Rajasekaran, Shanmuganathan

2017-12-01

Late onset neurological deficit is a rare complication of spinal tuberculosis. Reactivation of the disease and compression by internal gibbus are the common causes for late onset neurological deficit. We report a rare cause of late onset paraplegia in a patient with post tubercular kyphotic deformity. The late onset neurological deficit was due to the adjacent segment degeneration proximal to the kyphotic deformity. Posterior hypertrophied ligamentum flavum and anterior disc osteophyte complex caused the cord compression. The increased stress for prolonged period at the end of the deformity was the reason for the accelerated degeneration. Patient underwent posterior decompression, posterolateral and interbody fusion. Deformity correction was not done. To our best knowledge, this is only the second report of this unusual cause of late onset paraplegia.

Neurology Didactic Curricula for Psychiatry Residents: A Review of the Literature and a Survey of Program Directors

ERIC Educational Resources Information Center

Reardon, Claudia L.; Walaszek, Art

2012-01-01

Objective: Minimal literature exists on neurology didactic instruction offered to psychiatry residents, and there is no model neurology didactic curriculum offered for psychiatry residency programs. The authors sought to describe the current state of neurology didactic training in psychiatry residencies. Methods: The authors electronically…

Children With Medical Complexity: An Emerging Population for Clinical and Research Initiatives

PubMed Central

Kuo, Dennis Z.; Agrawal, Rishi; Berry, Jay G.; Bhagat, Santi K. M.; Simon, Tamara D.; Srivastava, Rajendu

2011-01-01

Children with medical complexity (CMC) have medical fragility and intensive care needs that are not easily met by existing health care models. CMC may have a congenital or acquired multisystem disease, a severe neurologic condition with marked functional impairment, and/or technology dependence for activities of daily living. Although these children are at risk of poor health and family outcomes, there are few well-characterized clinical initiatives and research efforts devoted to improving their care. In this article, we present a definitional framework of CMC that consists of substantial family-identified service needs, characteristic chronic and severe conditions, functional limitations, and high health care use. We explore the diversity of existing care models and apply the principles of the chronic care model to address the clinical needs of CMC. Finally, we suggest a research agenda that uses a uniform definition to accurately describe the population and to evaluate outcomes from the perspectives of the child, the family, and the broader health care system. PMID:21339266

Atypical presentations of subacute sclerosing panencephalitis in two neurologically handicapped cases.

PubMed

Demir, E; Ozcelik, A; Arhan, E; Serdaroglu, A; Gucuyener, K

2009-08-01

Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disorder caused by persistent measles infection. Here, we report two neurologically handicapped cases presenting with atypical features of SSPE. Patient 1 who had mild mental retardation manifested acute encephalopathy with partial seizures and hemiplegia, mimicking encephalitis. He showed a fulminant course without myoclonia or a periodic electroencephalogram complex. Although SSPE is usually associated with an increased diffusion pattern, diffusion-weighted imaging of our patient showed decreased diffusion in the right hippocampus. Patient 2 with infantile hemiparesis presented with secondary generalized seizures, followed by asymettrical myoclonias involving the side contralateral to the hemiparesis. A periodic electroencephalogram complex was absent on the previously damaged brain regions. Our findings show that preexisting neurological disorders may modify the clinical or electrophysiological findings of SSPE, leading to atypical presentations. SSPE should be considered in the differential diagnosis of acute encephalopathy with lateralizing signs or unidentified seizures. Decreased diffusion resolution in diffusion-weighted-imaging may correlate with rapid clinical progression in SSPE. Georg Thieme Verlag KG Stuttgart New York.

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

PubMed Central

Torres, Viviana I.; Vallejo, Daniela

2017-01-01

Synapses are complex structures that allow communication between neurons in the central nervous system. Studies conducted in vertebrate and invertebrate models have contributed to the knowledge of the function of synaptic proteins. The functional synapse requires numerous protein complexes with specialized functions that are regulated in space and time to allow synaptic plasticity. However, their interplay during neuronal development, learning, and memory is poorly understood. Accumulating evidence links synapse proteins to neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. In this review, we describe the way in which several proteins that participate in cell adhesion, scaffolding, exocytosis, and neurotransmitter reception from presynaptic and postsynaptic compartments, mainly from excitatory synapses, have been associated with several synaptopathies, and we relate their functions to the disease phenotype. PMID:28331639

Parental quality of life in complex paediatric neurologic disorders of unknown aetiology.

PubMed

van Nimwegen, K J M; Kievit, W; van der Wilt, G J; Schieving, J H; Willemsen, M A A P; Donders, A R T; Verhaak, C M; Grutters, J P C

2016-09-01

Complex paediatric neurology (CPN) patients generally present with non-specific symptoms, such as developmental delay, impaired movement and epilepsy. The diagnostic trajectory in these disorders is usually complicated and long-lasting, and may be burdensome to the patients and their parents. Additionally, as caring for a chronically ill child can be stressful and demanding, parents of these patients may experience impaired health-related quality of life (HRQoL). This study aims to assess parental HRQoL and factors related to it in CPN. Physical and mental HRQoL of 120 parents was measured and compared to the general population using the SF-12 questionnaire. Parents also completed this questionnaire for the measurement of patient HRQoL. Additional questionnaires were used to measure parental uncertainty (Visual Analogue Scale) and worry phenomena (Penn State Worry Questionnaire), and to obtain socio-demographic data. A linear mixed model with random effect was used to investigate which of these variables were associated with parental HRQoL. As compared to the general population, HRQoL of these parents appeared diminished. Fathers showed both lowered physical (51.76, p < 0.05) and mental (49.41, p < 0.01) HRQoL, whereas mothers only showed diminished mental (46.46, p < 0.01) HRQoL. Patient HRQoL and parental worry phenomena were significantly correlated with overall and mental parental HRQoL. The reduction in parental mental HRQoL is alarming, also because children strongly rely on their parents and parental mental health is known to influence children's health. Awareness of these problems among clinicians, and supportive care if needed are important to prevent exacerbation of the problems. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

A neural network model for transference and repetition compulsion based on pattern completion.

PubMed

Javanbakht, Arash; Ragan, Charles L

2008-01-01

In recent years because of the fascinating growth of the body of neuroscientific knowledge, psychoanalytic scientists have worked on models for the neurological substrates of key psychoanalytic concepts. Transference is an important example. In this article, the psychological process of transference is described, employing the neurological function of pattern completion in hippocampal and thalamo-cortical pathways. Similarly, repetition compulsion is seen as another type of such neurological function; however, it is understood as an attempt for mastery of the unknown, rather than simply for mastery of past experiences and perceptions. Based on this suggested model of neurological function, the myth of the psychoanalyst as blank screen is seen as impossible and ineffective, based on neurofunctional understandings of neuropsychological process. The mutative effect of psychoanalytic therapy, correcting patterns of pathological relatedness, is described briefly from conscious and unconscious perspectives. While cognitive understanding (insight) helps to modify transferentially restored, maladaptive patterns of relatedness, the development of more adaptive patterns is also contingent upon an affective experience (working through), which alters the neurological substrates of unconscious, pathological affective patterns and their neurological functional correlates.

Evaluating team-based, lecture-based, and hybrid learning methods for neurology clerkship in China: a method-comparison study

PubMed Central

2014-01-01

Background Neurology is complex, abstract, and difficult for students to learn. However, a good learning method for neurology clerkship training is required to help students quickly develop strong clinical thinking as well as problem-solving skills. Both the traditional lecture-based learning (LBL) and the relatively new team-based learning (TBL) methods have inherent strengths and weaknesses when applied to neurology clerkship education. However, the strengths of each method may complement the weaknesses of the other. Combining TBL with LBL may produce better learning outcomes than TBL or LBL alone. We propose a hybrid method (TBL + LBL) and designed an experiment to compare the learning outcomes with those of pure LBL and pure TBL. Methods One hundred twenty-seven fourth-year medical students attended a two-week neurology clerkship program organized by the Department of Neurology, Sun Yat-Sen Memorial Hospital. All of the students were from Grade 2007, Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University. These students were assigned to one of three groups randomly: Group A (TBL + LBL, with 41 students), Group B (LBL, with 43 students), and Group C (TBL, with 43 students). The learning outcomes were evaluated by a questionnaire and two tests covering basic knowledge of neurology and clinical practice. Results The practice test scores of Group A were similar to those of Group B, but significantly higher than those of Group C. The theoretical test scores and the total scores of Group A were significantly higher than those of Groups B and C. In addition, 100% of the students in Group A were satisfied with the combination of TBL + LBL. Conclusions Our results support our proposal that the combination of TBL + LBL is acceptable to students and produces better learning outcomes than either method alone in neurology clerkships. In addition, the proposed hybrid method may also be suited for other medical clerkships that require students to absorb a large amount of abstract and complex course materials in a short period, such as pediatrics and internal medicine clerkships. PMID:24884854

Computational Medicine: Translating Models to Clinical Care

PubMed Central

Winslow, Raimond L.; Trayanova, Natalia; Geman, Donald; Miller, Michael I.

2013-01-01

Because of the inherent complexity of coupled nonlinear biological systems, the development of computational models is necessary for achieving a quantitative understanding of their structure and function in health and disease. Statistical learning is applied to high-dimensional biomolecular data to create models that describe relationships between molecules and networks. Multiscale modeling links networks to cells, organs, and organ systems. Computational approaches are used to characterize anatomic shape and its variations in health and disease. In each case, the purposes of modeling are to capture all that we know about disease and to develop improved therapies tailored to the needs of individuals. We discuss advances in computational medicine, with specific examples in the fields of cancer, diabetes, cardiology, and neurology. Advances in translating these computational methods to the clinic are described, as well as challenges in applying models for improving patient health. PMID:23115356

An initial physical mechanism in the treatment of neurologic disorders with externally applied pico Tesla magnetic fields.

PubMed

Jacobson, J I; Yamanashi, W S

1995-04-01

The recent clinical studies describing the treatment of some neurological disorders with an externally applied pico Tesla (10(-12) Tesla, or 10(-8) gauss) magnetic field are considered from a physical view point. An equation relating the intrinsic (or rest) energy of a charged particle of mass m with its energy of interaction in an externally applied magnetic field B is presented. The equation represents an initial basic physical interaction as a part of a more complex biological mechanism to explain the therapeutic effects of externally applied magnetic fields in these and other neurologic disorders.

A physical mechanism in the treatment of neurologic disorders with externally applied pico Tesla magnetic fields.

PubMed

Jacobson, J I; Yamanashi, W S

1995-06-01

The clinical studies describing the treatment of some neurological disorders with an externally applied pico Tesla (10R Tesla, or 10(-8) gauss) magnetic field are considered from a physical view point. An equation relating the intrinsic or "rest" energy of a charged particle of mass with its energy of interaction in an externally applied magnetic field B is presented. The equation is proposed to represent an initial basic physical interaction as a part of a more complex biological mechanism to explain the therapeutic effects of externally applied magnetic fields in these and other neurologic disorders.

Smart home technology for safety and functional independence: the UK experience.

PubMed

Dewsbury, Guy; Linskell, Jeremy

2011-01-01

This paper proposes that people with neurological conditions can be successfully supported by smart homes only when their needs and aspirations of the technological interventions are fully understood and integrated in the design. A neurological condition can and does provide a clue to the finished technological design but this alone fails to personalise the system and stands to be rejected by the person who requires the technology. This paper explores the underlying issues of the complexity of this design process when designing for people with neurological conditions, and advances a matrix to facilitate the assessment process to maintain a person-centred design of any system.

[The coma awakening unit, between intensive care and rehabilitation].

PubMed

Mimouni, Arnaud

2015-01-01

After intensive care and before classic neurological rehabilitation is possible, patients in an altered state of consciousness are cared for at early stages in so-called coma awakening units. The care involves, on the one hand, the complex support of the patient's awakening from coma as a neurological and existential process, and on the other, support for their families. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Fate of manganese associated with the inhalation of welding fumes: potential neurological effects.

PubMed

Antonini, James M; Santamaria, Annette B; Jenkins, Neil T; Albini, Elisa; Lucchini, Roberto

2006-05-01

Welding fumes are a complex mixture composed of different metals. Most welding fumes contain a small percentage of manganese. There is an emerging concern among occupational health officials about the potential neurological effects associated with the exposure to manganese in welding fumes. Little is known about the fate of manganese that is complexed with other metals in the welding particles after inhalation. Depending on the welding process and the composition of the welding electrode, manganese may be present in different oxidation states and have different solubility properties. These differences may affect the biological responses to manganese after the inhalation of welding fumes. Manganese intoxication and the associated neurological symptoms have been reported in individual cases of welders who have been exposed to high concentrations of manganese-containing welding fumes due to work in poorly ventilated areas. However, the question remains as to whether welders who are exposed to low levels of welding fumes over long periods of time are at risk for the development of neurological diseases. For the most part, questions remain unanswered. There is still paucity of adequate scientific reports on welders who suffered significant neurotoxicity, hence there is a need for well-designed epidemiology studies that combine complete information on the occupational exposure of welders with both behavioral and biochemical endpoints of neurotoxicity.

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.

PubMed

Vissers, Lisenka E L M; van Nimwegen, Kirsten J M; Schieving, Jolanda H; Kamsteeg, Erik-Jan; Kleefstra, Tjitske; Yntema, Helger G; Pfundt, Rolph; van der Wilt, Gert Jan; Krabbenborg, Lotte; Brunner, Han G; van der Burg, Simone; Grutters, Janneke; Veltman, Joris A; Willemsen, Michèl A A P

2017-09-01

Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation. We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene-based testing) and WES simultaneously. Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted. Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.Genet Med advance online publication 23 March 2017.

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

PubMed Central

Vissers, Lisenka E.L.M.; van Nimwegen, Kirsten J.M.; Schieving, Jolanda H.; Kamsteeg, Erik-Jan; Kleefstra, Tjitske; Yntema, Helger G.; Pfundt, Rolph; van der Wilt, Gert Jan; Krabbenborg, Lotte; Brunner, Han G.; van der Burg, Simone; Grutters, Janneke; Veltman, Joris A.; Willemsen, Michèl A.A.P.

2017-01-01

Purpose: Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation. Methods: We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene–based testing) and WES simultaneously. Results: Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted. Conclusion: Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin. Genet Med advance online publication 23 March 2017 PMID:28333917

[The hypothesis of infectious etiology for idiopathic nervous system diseases: from the postulates of Koch to the criteria of Hill].

PubMed

Bélec, L

1999-01-01

The evaluation of the hypothesis of an infectious etiology to some neurological diseases comprises four different situations. First, numerous neurological diseases have an obvious infectious etiology (encephilitis, meningoencephilitis). Second, some neurological disorders were primarily suspected to be have an infectious etiology, but the causative microorganism was discovered either longtime after the princeps description of the disease (neurologic Whipple disease, due to Tropheryma whippelii), or at the same time (tropical spastic para-paresis secondary to HTLV-I infection). Third, for other neurological diseases, an infectious etiology that was not suspected at time of their anatomoclinic descriptions, was further demonstrated in the context of a generally complex physiopathology (Guillain-Barré syndrome and infection by Campylobacter jejuni). Finally, some idiopathic neurological diseases could be related to well known or yet unknown microorganisms, in association with some environmental factors, and with a particular genetic or acquired susceptibility of the host. The evaluation of an infectious etiology to these idiopathic neurological disorders must be envisioned according to 3 possibilities: 1) generally, the neurological disease is well defined, but its etiology remains unknown and an infectious hypothesis could be relevant (multiple sclerosis, post-polio syndrome, amyotrophic lateral sclerosis); 2) sometimes, a microorganism that is not associated with a known disease, and then qualified as "orphelin", could be associated with neurological disorders (spumaretrovirus); 3) finally, a new neurological disease could be associated with a known or yet unknown microorganism, directly or indirectly. In conclusion, some idiopathic neurological diseases could have an infectious etiology, with physiopathologic, diagnostic, prophylactic (vaccination) and therapeutic (use of anti-infectious drugs) consequences.

Coexistence and chaos in complex ecologies [rapid communication

NASA Astrophysics Data System (ADS)

Sprott, J. C.; Vano, J. A.; Wildenberg, J. C.; Anderson, M. B.; Noel, J. K.

2005-02-01

Many complex dynamical systems in ecology, economics, neurology, and elsewhere, in which agents compete for limited resources, exhibit apparently chaotic fluctuations. This Letter proposes a purely deterministic mechanism for evolving robustly but weakly chaotic systems that exhibit adaptation, self-organization, sporadic volatility, and punctuated equilibria.

Neurology didactic curricula for psychiatry residents: a review of the literature and a survey of program directors.

PubMed

Reardon, Claudia L; Walaszek, Art

2012-03-01

Minimal literature exists on neurology didactic instruction offered to psychiatry residents, and there is no model neurology didactic curriculum offered for psychiatry residency programs. The authors sought to describe the current state of neurology didactic training in psychiatry residencies. The authors electronically surveyed 172 directors of U.S. psychiatric residency training programs to examine the types and extent of neurology didactic instruction offered to their residents. Fifty-seven program directors (33%) responded. The majority of these psychiatry residency programs offer neurology didactic instruction to their residents, as provided by both neurology and psychiatry faculty, in a number of different settings and covering many topics. However, room for improvement likely remains. The authors hope this report will guide psychiatry residencies in optimizing their neurology didactic curricula. Further research should explore tools for assessing resident knowledge in neurology and measure the effectiveness of neurology curricula in increasing knowledge and improving clinical outcomes.

Pyruvate dehydrogenase deficiency and epilepsy.

PubMed

Prasad, Chitra; Rupar, Tony; Prasad, Asuri N

2011-11-01

The pyruvate dehydrogenase complex (PDHc) is a mitochondrial matrix multienzyme complex that provides the link between glycolysis and the tricarboxylic acid (TCA) cycle by catalyzing the conversion of pyruvate into acetyl-CoA. PDHc deficiency is one of the commoner metabolic disorders of lactic acidosis presenting with neurological phenotypes that vary with age and gender. In this mini-review, we postulate mechanisms of epilepsy in the setting of PDHc deficiency using two illustrative cases (one with pyruvate dehydrogenase complex E1-alpha polypeptide (PDHA1) deficiency and the second one with pyruvate dehydrogenase complex E1-beta subunit (PDHB) deficiency (a rare subtype of PDHc deficiency)) and a selected review of published case series. PDHc plays a critical role in the pathway of carbohydrate metabolism and energy production. In severe deficiency states the resulting energy deficit impacts on brain development in utero resulting in structural brain anomalies and epilepsy. Milder deficiency states present with variable manifestations that include cognitive delay, ataxia, and seizures. Epileptogenesis in PDHc deficiency is linked to energy failure, development of structural brain anomalies and abnormal neurotransmitter metabolism. The use of the ketogenic diet bypasses the metabolic block, by providing a direct source of acetyl-CoA, leading to amelioration of some symptoms. Genetic counseling is essential as PDHA1 deficiency (commonest defect) is X-linked although females can be affected due to unfavorable lyonization, while PDHB and PDH phosphatase (PDP) deficiencies (much rarer defects) are of autosomal recessive inheritance. Research is in progress for looking into animal models to better understand pathogenesis and management of this challenging disorder. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

A Profile of Patients With Traumatic Brain Injury Within Home Care, Long-Term Care, Complex Continuing Care, and Institutional Mental Health Settings in a Publicly Insured Population.

PubMed

Colantonio, Angela; Hsueh, Jayden; Petgrave, Josian; Hirdes, John P; Berg, Katherine

2015-01-01

To describe the sociodemographic and clinical profile of people with traumatic brain injury (TBI) in home care, nursing homes, and complex continuing care settings in a national sample. Cross-sectional study using available Resident Assessment Instrument (RAI 2.0 and RAI Home Care [HC]) national databases in Canada from 1996 to 2011. The profile of people with TBI was compared with patients with and without prespecified neurological conditions within each setting. Adults 18 years and older identified with TBI (n = 10 878) and adult patients with other neurological (n = 422 300) and non-neurological (n = 571 567) conditions. Demographic and clinical characteristics, functional characteristics, mood and behavior, and treatment and medication variables. Data from Canadian home care (RAI-HC), mental health (RAI-MH), nursing home, and complex continuing care facilities (RAI Minimum Data Set 2.0). Patients with TBI were significantly different on almost all items. They were among the youngest in care settings, and psychotropic drug use by this population was among the highest in at least 2 settings. These data can inform the planning for appropriate care and resources for patients with TBI in a range of settings.

Neurocutaneous melanosis and the Dandy-Walker complex: an uncommon but not so insignificant association.

PubMed

Marnet, Dominique; Vinchon, Matthieu; Mostofi, Keyvan; Catteau, Benoit; Kerdraon, Olivier; Dhellemmes, Patrick

2009-12-01

Neurocutaneous melanosis represents a rare congenital but nonheritable phakomatosis defined as the association of giant or multiple congenital nonmalignant melanocytic nevi with leptomeningeal melanosis or melanoma of the central nervous system. We describe the case of an adolescent with a giant congenital bathing trunk melanocytic nevus who developed progressive intracranial hypertension due to leptomeningeal melanosis confirmed by surgical biopsy. Brain and spine magnetic resonance images showed posterior fossa malformation compatible with the Dandy-Walker complex, hydrocephalus, and extensive enhancement of posterior fossa then spine. Shunt placement, corticotherapy, and chemotherapy were attempted leading to transient relief but the boy died 12 months after the onset of primary neurological symptoms. We discuss diagnosis, pathogenesis, management, and prognosis in the light of data from the recent literature. Neurocutaneous melanosis is considered to follow from neurulation disorders which could account for associated developmental malformations as the so-called Dandy-Walker complex. Cutaneous lesions are usually recognized at birth whereas neurological manifestations develop later. Numerous neurological symptoms have been reported according to extent of leptomeningeal and parenchymal infiltration. Whether magnetic resonance imaging of the neuroaxis represents the choice radiological exam, definite diagnosis relies upon the histological data obtained by mean of biopsy. Once symptomatic, surgical and medical measures remain palliative since death occurs within 3 years.

Cerebrovascular diseases at the C. Mondino National Institute of Neurology: from Ottorino Rossi to the present day

PubMed Central

Micieli, Giuseppe; Martignoni, Emilia; Sandrini, Giorgio; Bono, Giorgio; Nappi, Giuseppe

Summary This paper traces the development of research and healthcare models in the field of cerebrovascular disorders at the C. Mondino National Institute of Neurology in Pavia, Italy. It starts with a description of the original experiences of Ottorino Rossi and his thesis on atherosclerosis which date back to the beginning of the last century; it then illustrates the connections between his seminal essay and the future directions followed by research in this institute, through to the development of one of the first stroke units in Italy. In this context, we examine a large range of scientific approaches, many related to cerebrovascular diseases (such as headaches) and autonomic disorders, and some of their biological and physiological markers. The originality of an approach also based on tools of advanced technology, including information technology, is emphasised, as is the importance of passion and perseverance in the pursuit of extraordinary results in what is an extremely complex and difficult field. PMID:21729590

Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

PubMed Central

Hu, Heng; Doll, Danielle N.; Sun, Jiahong; Lewis, Sara E.; Wimsatt, Jeffrey H.; Kessler, Matthew J.; Simpkins, James W.; Ren, Xuefang

2016-01-01

Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for stroke severity in experimental stroke animal models and may have translational significance for clinical stroke patients - targeting endothelial mitochondria may be a clinically useful approach for stroke therapy. PMID:26816660

Spontaneous hypothermia ameliorated inflammation and neurologic deficit in rat cardiac arrest models following resuscitation

PubMed Central

Zhou, Minggen; Wang, Peng; Yang, Zhengfei; Wu, Haidong; Huang, Zitong

2018-01-01

Cardiac arrest (CA) is a leading cause of mortality worldwide. The majority of the associated mortalities are caused by post-CA syndrome, which includes symptoms, such as neurologic damage, myocardial dysfunction and systemic inflammation. Following CA, return of spontaneous circulation (ROSC) leads to a brain reperfusion injury, which subsequently causes adverse neurologic outcomes or mortality. Therefore, investigating the underlying mechanisms of ROSC-induced neurologic deficits and establishing potential treatments is critical to prevent and treat post-CA syndrome. In the current study, CA rat models were established by asphyxia. Following ROSC, the temperature was controlled to achieve hypothermia. The general neurologic status was assessed using the neurologic deficit scale. Changes in the concentrations of interleukin (IL)-18 and IL-1β were measured with ELISA and the dynamic change in NACHT, LRR and PYD domains-containing protein 3 inflammasome components was determined by western blot analysis and immunohistochemistry. Neuronal death and apoptosis were measured via TUNEL assays. In the CA rat models, increasing the duration of CA before cardiopulmonary resuscitation was found to aggravate the neural deficit and increase the incidence of inflammation. Following ROSC, the expression level of the inflammasome components was observed to increase in CA rat models, which was accompanied by increased secretion of IL-18 and IL-1β, indicating the promotion of inflammation. In addition, the study identified the beneficial role of spontaneous hypothermia in ameliorating the ROSC-induced inflammation and neurologic deficit in CA rat models, including the downregulation of inflammasome components and attenuating neuronal apoptosis. The present study contributes to the understanding of underlying mechanisms in CA-evoked inflammation and the subsequent neurologic damage following ROSC. A novel potential therapeutic strategy that may increase survival times and the quality of life for patients suffering from post-CA syndrome is proposed in the present study. PMID:29207113

On viewer motivation, unit of analysis, and the VIMAP. Comment on "Move me, astonish me ... delight my eyes and brain: The Vienna Integrated Model of top-down and bottom-up processes in Art Perception (VIMAP) and corresponding affective, evaluative, and neurophysiological correlates" by Matthew Pelowski et al.

NASA Astrophysics Data System (ADS)

Tinio, Pablo P. L.

2017-07-01

The Vienna Integrated Model of Art Perception (VIMAP; [5]) is the most comprehensive model of the art experience today. The model incorporates bottom-up and top-down cognitive processes and accounts for different outcomes of the art experience, such as aesthetic evaluations, emotions, and physiological and neurological responses to art. In their presentation of the model, Pelowski et al. also present hypotheses that are amenable to empirical testing. These features make the VIMAP an ambitious model that attempts to explain how meaningful, complex, and profound aspects of the art experience come about, which is a significant extension of previous models of the art experience (e.g., [1-3,10]), and which gives the VIMAP good explanatory power.

Patient-Specific Pluripotent Stem Cells in Neurological Diseases

PubMed Central

Durnaoglu, Serpen; Genc, Sermin; Genc, Kursad

2011-01-01

Many human neurological diseases are not currently curable and result in devastating neurologic sequelae. The increasing availability of induced pluripotent stem cells (iPSCs) derived from adult human somatic cells provides new prospects for cellreplacement strategies and disease-related basic research in a broad spectrum of human neurologic diseases. Patient-specific iPSC-based modeling of neurogenetic and neurodegenerative diseases is an emerging efficient tool for in vitro modeling to understand disease and to screen for genes and drugs that modify the disease process. With the exponential increase in iPSC research in recent years, human iPSCs have been successfully derived with different technologies and from various cell types. Although there remain a great deal to learn about patient-specific iPSC safety, the reprogramming mechanisms, better ways to direct a specific reprogramming, ideal cell source for cellular grafts, and the mechanisms by which transplanted stem cells lead to an enhanced functional recovery and structural reorganization, the discovery of the therapeutic potential of iPSCs offers new opportunities for the treatment of incurable neurologic diseases. However, iPSC-based therapeutic strategies need to be thoroughly evaluated in preclinical animal models of neurological diseases before they can be applied in a clinical setting. PMID:21776279

Human neuronal coenzyme Q10 deficiency results in global loss of mitochondrial respiratory chain activity, increased mitochondrial oxidative stress and reversal of ATP synthase activity: implications for pathogenesis and treatment.

PubMed

Duberley, Kate E C; Abramov, Andrey Y; Chalasani, Annapurna; Heales, Simon J; Rahman, Shamima; Hargreaves, Iain P

2013-01-01

Disorders of coenzyme Q(10) (CoQ(10)) biosynthesis represent the most treatable subgroup of mitochondrial diseases. Neurological involvement is frequently observed in CoQ(10) deficiency, typically presenting as cerebellar ataxia and/or seizures. The aetiology of the neurological presentation of CoQ(10) deficiency has yet to be fully elucidated and therefore in order to investigate these phenomena we have established a neuronal cell model of CoQ(10) deficiency by treatment of neuronal SH-SY5Y cell line with para-aminobenzoic acid (PABA). PABA is a competitive inhibitor of the CoQ(10) biosynthetic pathway enzyme, COQ2. PABA treatment (1 mM) resulted in a 54 % decrease (46 % residual CoQ(10)) decrease in neuronal CoQ(10) status (p < 0.01). Reduction of neuronal CoQ(10) status was accompanied by a progressive decrease in mitochondrial respiratory chain enzyme activities, with a 67.5 % decrease in cellular ATP production at 46 % residual CoQ(10). Mitochondrial oxidative stress increased four-fold at 77 % and 46 % residual CoQ(10). A 40 % increase in mitochondrial membrane potential was detected at 46 % residual CoQ(10) with depolarisation following oligomycin treatment suggesting a reversal of complex V activity. This neuronal cell model provides insights into the effects of CoQ(10) deficiency on neuronal mitochondrial function and oxidative stress, and will be an important tool to evaluate candidate therapies for neurological conditions associated with CoQ(10) deficiency.

Therapists' experiences and perceptions of teamwork in neurological rehabilitation: critical happenings in effective and ineffective teamwork.

PubMed

Suddick, Kitty M; De Souza, Lorraine H

2007-12-01

This paper reports the second part of an exploratory study into occupational therapists' and physiotherapists' perceptions and experiences of teamwork in neurological rehabilitation: the factors that were thought to influence effective and ineffective teamwork, and the meaning behind effective and ineffective teamwork in neurological rehabilitation. The study was undertaken through semi-structured interviews of 10 therapists from three different neurological rehabilitation teams based in the United Kingdom, and used the critical incident technique. Through analysis of the data, several main themes emerged regarding the perceived critical happenings in effective and ineffective teamwork. These were: team events and characteristics, team members' characteristics, shared and collaborative working practices, communication, specific organizational structures, environmental, external, and patient and family-related factors. Effective and ineffective team-work was perceived to impact on a number of levels: having implications for the team, the patient, individual team members, and the neurological rehabilitation service. The study supported the perceived value of team work within neurological rehabilitation. It also indicated the extensive and variable factors that may influence the team-working process as well as the complex and diverse nature of the process.

Predicting long-term neurological outcomes after severe traumatic brain injury requiring decompressive craniectomy: A comparison of the CRASH and IMPACT prognostic models.

PubMed

Honeybul, Stephen; Ho, Kwok M

2016-09-01

Predicting long-term neurological outcomes after severe traumatic brain (TBI) is important, but which prognostic model in the context of decompressive craniectomy has the best performance remains uncertain. This prospective observational cohort study included all patients who had severe TBI requiring decompressive craniectomy between 2004 and 2014, in the two neurosurgical centres in Perth, Western Australia. Severe disability, vegetative state, or death were defined as unfavourable neurological outcomes. Area under the receiver-operating-characteristic curve (AUROC) and slope and intercept of the calibration curve were used to assess discrimination and calibration of the CRASH (Corticosteroid-Randomisation-After-Significant-Head injury) and IMPACT (International-Mission-For-Prognosis-And-Clinical-Trial) models, respectively. Of the 319 patients included in the study, 119 (37%) had unfavourable neurological outcomes at 18-month after decompressive craniectomy for severe TBI. Both CRASH (AUROC 0.86, 95% confidence interval 0.81-0.90) and IMPACT full-model (AUROC 0.85, 95% CI 0.80-0.89) were similar in discriminating between favourable and unfavourable neurological outcome at 18-month after surgery (p=0.690 for the difference in AUROC derived from the two models). Although both models tended to over-predict the risks of long-term unfavourable outcome, the IMPACT model had a slightly better calibration than the CRASH model (intercept of the calibration curve=-4.1 vs. -5.7, and log likelihoods -159 vs. -360, respectively), especially when the predicted risks of unfavourable outcome were <80%. Both CRASH and IMPACT prognostic models were good in discriminating between favourable and unfavourable long-term neurological outcome for patients with severe TBI requiring decompressive craniectomy, but the calibration of the IMPACT full-model was better than the CRASH model. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

A Complex Contraception Registry

ClinicalTrials.gov

2018-03-13

Diabetes; Cardiovascular Disease; Epilepsy; Migraine; Neurological Disorders; Cancer; Bariatric Surgery Candidate; Organ or Tissue Transplant; Complications; Lupus Erythematosus, Systemic; Other Hematologic Conditions; Other Venous Embolism and Thrombosis

[Leigh syndrome and leukodystrophy due to partial succinate dehydrogenase deficiency: regression with riboflavin].

PubMed

Pinard, J M; Marsac, C; Barkaoui, E; Desguerre, I; Birch-Machin, M; Reinert, P; Ponsot, G

1999-04-01

Succinate dehydrogenase (SDH) deficiency is rare. Clinical manifestations can appear in infancy with a marked impairment of psychomotor development with pyramidal signs and extrapyramidal rigidity. A 10-month-old boy developed severe neurological features, evoking a Leigh syndrome; magnetic resonance imaging showed features of leukodystrophy. A deficiency in the complex II respiratory chain (succinate dehydrogenase [SDH]) was shown. The course was remarkable by the regression of neurological impairment under treatment by riboflavin. The delay of psychomotor development, mainly involving language, was moderate at the age of 5 years. The relatively good prognosis of this patient, despite severe initial neurological impairment, may be due to the partial enzyme deficiency and/or riboflavin administration.

Complexity and multifractality of neuronal noise in mouse and human hippocampal epileptiform dynamics.

PubMed

Serletis, Demitre; Bardakjian, Berj L; Valiante, Taufik A; Carlen, Peter L

2012-10-01

Fractal methods offer an invaluable means of investigating turbulent nonlinearity in non-stationary biomedical recordings from the brain. Here, we investigate properties of complexity (i.e. the correlation dimension, maximum Lyapunov exponent, 1/f(γ) noise and approximate entropy) and multifractality in background neuronal noise-like activity underlying epileptiform transitions recorded at the intracellular and local network scales from two in vitro models: the whole-intact mouse hippocampus and lesional human hippocampal slices. Our results show evidence for reduced dynamical complexity and multifractal signal features following transition to the ictal epileptiform state. These findings suggest that pathological breakdown in multifractal complexity coincides with loss of signal variability or heterogeneity, consistent with an unhealthy ictal state that is far from the equilibrium of turbulent yet healthy fractal dynamics in the brain. Thus, it appears that background noise-like activity successfully captures complex and multifractal signal features that may, at least in part, be used to classify and identify brain state transitions in the healthy and epileptic brain, offering potential promise for therapeutic neuromodulatory strategies for afflicted patients suffering from epilepsy and other related neurological disorders.

Development of intelligent model to determine favorable wheelchair tilt and recline angles for people with spinal cord injury.

PubMed

Fu, Jicheng; Jan, Yih-Kuen; Jones, Maria

2011-01-01

Machine-learning techniques have found widespread applications in bioinformatics. Such techniques provide invaluable insight on understanding the complex biomedical mechanisms and predicting the optimal individualized intervention for patients. In our case, we are particularly interested in developing an individualized clinical guideline on wheelchair tilt and recline usage for people with spinal cord injury (SCI). The current clinical practice suggests uniform settings to all patients. However, our previous study revealed that the response of skin blood flow to wheelchair tilt and recline settings varied largely among patients. Our finding suggests that an individualized setting is needed for people with SCI to maximally utilize the residual neurological function to reduce pressure ulcer risk. In order to achieve this goal, we intend to develop an intelligent model to determine the favorable wheelchair usage to reduce pressure ulcers risk for wheelchair users with SCI. In this study, we use artificial neural networks (ANNs) to construct an intelligent model that can predict whether a given tilt and recline setting will be favorable to people with SCI based on neurological functions and SCI injury history. Our results indicate that the intelligent model significantly outperforms the traditional statistical approach in accurately classifying favorable wheelchair tilt and recline settings. To the best of our knowledge, this is the first study using intelligent models to predict the favorable wheelchair tilt and recline angles. Our methods demonstrate the feasibility of using ANN to develop individualized wheelchair tilt and recline guidance for people with SCI.

Speech Perception in MRI Scanner Noise by Persons with Aphasia

ERIC Educational Resources Information Center

Healy, Eric W.; Moser, Dana C.; Morrow-Odom, K. Leigh; Hall, Deborah A.; Fridriksson, Julius

2007-01-01

Purpose: To examine reductions in performance on auditory tasks by aphasic and neurologically intact individuals as a result of concomitant magnetic resonance imaging (MRI) scanner noise. Method: Four tasks together forming a continuum of linguistic complexity were developed. They included complex-tone pitch discrimination, same-different…

A Neurology of the Conservative-Liberal Dimension of Political Ideology.

PubMed

Mendez, Mario F

2017-01-01

Differences in political ideology are a major source of human disagreement and conflict. There is increasing evidence that neurobiological mechanisms mediate individual differences in political ideology through effects on a conservative-liberal axis. This review summarizes personality, evolutionary and genetic, cognitive, neuroimaging, and neurological studies of conservatism-liberalism and discusses how they might affect political ideology. What emerges from this highly variable literature is evidence for a normal right-sided "conservative-complex" involving structures sensitive to negativity bias, threat, disgust, and avoidance. This conservative-complex may be damaged with brain disease, sometimes leading to a pathological "liberal shift" or a reduced tendency to conservatism in political ideology. Although not deterministic, these findings recommend further research on politics and the brain.

Using deep learning to investigate the neuroimaging correlates of psychiatric and neurological disorders: Methods and applications.

PubMed

Vieira, Sandra; Pinaya, Walter H L; Mechelli, Andrea

2017-03-01

Deep learning (DL) is a family of machine learning methods that has gained considerable attention in the scientific community, breaking benchmark records in areas such as speech and visual recognition. DL differs from conventional machine learning methods by virtue of its ability to learn the optimal representation from the raw data through consecutive nonlinear transformations, achieving increasingly higher levels of abstraction and complexity. Given its ability to detect abstract and complex patterns, DL has been applied in neuroimaging studies of psychiatric and neurological disorders, which are characterised by subtle and diffuse alterations. Here we introduce the underlying concepts of DL and review studies that have used this approach to classify brain-based disorders. The results of these studies indicate that DL could be a powerful tool in the current search for biomarkers of psychiatric and neurologic disease. We conclude our review by discussing the main promises and challenges of using DL to elucidate brain-based disorders, as well as possible directions for future research. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Education research: neurology residency training in the new millennium.

PubMed

Schuh, L A; Adair, J C; Drogan, O; Kissela, B M; Morgenlander, J C; Corboy, J R

2009-01-27

To survey adult neurology program directors (ANPD) to identify their most pressing needs at a time of dramatic change in neurology resident education. All US ANPD were surveyed in 2007 using an instrument adjusted from a 1999 survey instrument. The goal was to characterize current program content, the institution and evaluation of the core competencies, program director characteristics, program director support, the institution of work duty hour requirements, resident support, and the curriculum needs of program directors and programs. A response rate of 82.9% was obtained. There is a significant disconnect between administration time spent by ANPD and departmental/institutional support of this, with ANPD spending approximately 35% of a 50-hour week on administration with only 16.7% salary support. Rearrangement of rotations or services has been the most common mode for ANPD to deal with work duty hour requirements, with few programs employing mid level providers. Most ANPD do not feel work duty hour reform has improved resident education. More residents are entering fellowships following graduation than documented in the past. Curriculum deficiencies still exist for ANPD to meet all Neurology Program Requirements, especially for nontraditional neurology topics outside the conventional bounds of clinical neurology (e.g., practice management). Nearly one quarter of neurology residency programs do not have a meeting or book fund for every resident in the program. Adult neurology program directors (ANPDs) face multiple important financial and organizational hurdles. At a time of increasing complexity in medical education, ANPDs need more institutional support.

Manipulations of MeCP2 in glutamatergic neurons highlight their contributions to Rett and other neurological disorders

USDA-ARS?s Scientific Manuscript database

Many postnatal onset neurological disorders such as autism spectrum disorders (ASDs) and intellectual disability are thought to arise largely from disruption of excitatory/inhibitory homeostasis. Although mouse models of Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-functi...

International Issues: Teleneurology in humanitarian crises: Lessons from the Médecins Sans Frontières experience.

PubMed

Saadi, Altaf; Mateen, Farrah J

2017-07-18

Humanitarian emergencies defined by armed conflict, political strife, famine, or natural disaster can devastate populations rapidly. Neurologic disorders accompany these complex humanitarian emergencies but often go unheeded, exacerbated by a scarcity of neurologists. Teleneurology offers the promise of neurologic care remotely in the face of this inadequate local clinician supply. We describe our experiences as voluntary neurology teleconsultants with Médecins Sans Frontières in order to highlight both the promises and challenges of teleneurology in humanitarian contexts. We identified the major advantages of this service as (1) minimal resources and incurred costs while (2) changing a patient's clinical course favorably, and (3) creating a community for the field referrer and neurology specialist. Current challenges include (1) limited diagnostic resources and difficult diagnostic and therapeutic decision-making, (2) need for greater continuity and familiarity between the field site and neurologist, (3) gaps in the US neurology curriculum to provide expertise for all sites, (4) lack of follow-up and feedback from the field to advise future cases, and (5) low frequency of consultations. Growth opportunities include eventual expansion to the development of a community of neurologists who can provide context-specific care and maximize use of multimedia at low Internet bandwidth. Lessons from our experience may help optimize teleneurology's effect and reduce disparities in neurologic care, particularly in humanitarian crises. © 2017 American Academy of Neurology.

HMGB1 a-Box Reverses Brain Edema and Deterioration of Neurological Function in a Traumatic Brain Injury Mouse Model.

PubMed

Yang, Lijun; Wang, Feng; Yang, Liang; Yuan, Yunchao; Chen, Yan; Zhang, Gengshen; Fan, Zhenzeng

2018-01-01

Traumatic brain injury (TBI) is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB), subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1) has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI. TBI was induced by controlled cortical impact (CCI) in adult male mice. HMGB1 A-box fragment was given intravenously at 2 mg/kg/day for 3 days after CCI. HMGB1 A-box-treated CCI mice were compared with saline-treated CCI mice and sham mice in terms of BBB disruption evaluated by Evan's blue extravasation, brain edema by brain water content, cell death by propidium iodide staining, inflammation by Western blot and ELISA assay for cytokine productions, as well as neurological functions by the modified Neurological Severity Score, wire grip and beam walking tests. HMGB1 A-box reversed brain damages in the mice following TBI. It significantly reduced brain edema by protecting integrity of the BBB, ameliorated cell degeneration, and decreased expression of pro-inflammatory cytokines released in injured brain after TBI. These cellular and molecular effects were accompanied by improved behavioral performance in TBI mice. Notably, HMGB1 A-box blocked IL-1β-induced HMGB1 release, and preferentially attenuated TLR4, Myd88 and P65 in astrocyte cultures. Our data suggest that HMGB1 is involved in CCI-induced TBI, which can be inhibited by HMGB1 A-box fragment. Therefore, HMGB1 A-box fragment may have therapeutic potential for the secondary brain damages in TBI. © 2018 The Author(s). Published by S. Karger AG, Basel.

Some thoughts about consciousness: from a quantum mechanics perspective.

PubMed

Gargiulo, Gerald J

2013-08-01

The article explores some of the basic findings of quantum physics and information theory and their possible usefulness in offering new vistas for understanding psychoanalysis and the patient-analyst interchange. Technical terms are explained and placed in context, and examples of applying quantum models to clinical experience are offered. Given the complexity of the findings of quantum mechanics and information theory, the article aims only to introduce some of the major concepts from these disciplines. Within this framework the article also briefly addresses the question of mind as well as the problematic of reducing the experience of consciousness to neurological brain functioning.

Module modified acute physiology and chronic health evaluation II: predicting the mortality of neuro-critical disease.

PubMed

Su, Yingying; Wang, Miao; Liu, Yifei; Ye, Hong; Gao, Daiquan; Chen, Weibi; Zhang, Yunzhou; Zhang, Yan

2014-12-01

This study aimed to conduct and assess a module modified acute physiology and chronic health evaluation (MM-APACHE) II model, based on disease categories modified-acute physiology and chronic health evaluation (DCM-APACHE) II model, in predicting mortality more accurately in neuro-intensive care units (N-ICUs). In total, 1686 patients entered into this prospective study. Acute physiology and chronic health evaluation (APACHE) II scores of all patients on admission and worst 24-, 48-, 72-hour scores were obtained. Neurological diagnosis on admission was classified into five categories: cerebral infarction, intracranial hemorrhage, neurological infection, spinal neuromuscular (SNM) disease, and other neurological diseases. The APACHE II scores of cerebral infarction, intracranial hemorrhage, and neurological infection patients were used for building the MM-APACHE II model. There were 1386 cases for cerebral infarction disease, intracranial hemorrhage disease, and neurological infection disease. The logistic linear regression showed that 72-hour APACHE II score (Wals  =  173.04, P < 0.001) and disease classification (Wals  =  12.51, P  =  0.02) were of importance in forecasting hospital mortality. Module modified acute physiology and chronic health evaluation II model, built on the variables of the 72-hour APACHE II score and disease category, had good discrimination (area under the receiver operating characteristic curve (AU-ROC  =  0.830)) and calibration (χ2  =  12.518, P  =  0.20), and was better than the Knaus APACHE II model (AU-ROC  =  0.778). The APACHE II severity of disease classification system cannot provide accurate prognosis for all kinds of the diseases. A MM-APACHE II model can accurately predict hospital mortality for cerebral infarction, intracranial hemorrhage, and neurologic infection patients in N-ICU.

A hyperacute neurology team - transforming emergency neurological care.

PubMed

Nitkunan, Arani; MacDonald, Bridget K; Boodhoo, Ajay; Tomkins, Andrew; Smyth, Caitlin; Southam, Medina; Schon, Fred

2017-07-01

We present the results of an 18-month study of a new model of how to care for emergency neurological admissions. We have established a hyperacute neurology team at a single district general hospital. Key features are a senior acute neurology nurse coordinator, an exclusively consultant-delivered service, acute epilepsy nurses, an acute neurophysiology service supported by neuroradiology and acute physicians and based within the acute medical admissions unit. Key improvements are a major increase in the number of patients seen, the speed with which they are seen and the percentage seen on acute medical unit before going to the general wards. We have shown a reduced length of stay and readmission rates for patients with epilepsy. Epilepsy accounted for 30% of all referrals. The cost implications of running this service are modest. We feel that this model is worthy of widespread consideration. © Royal College of Physicians 2017. All rights reserved.

Strategies for the Integration of Cough and Swallow to Maintain Airway Protection in Humans.

PubMed

Huff, Alyssa; Reed, Mitchell D; Smith, Barbara K; Brown, Edward H; Ovechkin, Alexander V; Pitts, Teresa

2018-06-20

Airway protective behaviors, like cough and swallow, deteriorate in many populations suffering from neurologic disorders. While coordination of these behaviors has been investigated in an animal model, it has not been tested in humans. We used a novel protocol, adapted from previous work in the cat, to assess cough and swallow independently and their coordination strategies in seven healthy males (26 ± 6 years). Surface electromyograms of the submental complex and external oblique complex, spirometry, and thoracic and abdominal wall kinematics, were used to evaluate the timing of swallow, cough, and breathing as well as lung volume (LV) during these behaviors. Unlike the cat, there was significant variability in the cough-swallow phase preference; however, there was a targeted LV range in which swallow occurred. These results give insight into the differences between the cat and human models in airway protective strategies related to the coordination of cough and swallow behaviors, allowing for better understanding of dystussia and dysphagia.

John Hughlings Jackson's evolutionary neurology: a unifying framework for cognitive neuroscience.

PubMed

Franz, Elizabeth A; Gillett, Grant

2011-10-01

John Hughlings Jackson was a pioneer in neurology who thought deeply about the structure of the brain and how that manifested itself in the various syndromes that he saw in the clinic. He enunciated a theory of the evolution and dissolution of neural function based on the idea that basic sensorimotor processes become embedded in networks of connections that relate them in successively more complex ways to allow for performance of more and more nuanced and adaptive functions. Hughlings Jackson noted the curious link between human thought, action and speech. He further recognized that disinhibition or release from control and direction marked neurological damage. His integrative framework remains deeply relevant to the plethora of results being produced by the careful and diverse experimentation currently undertaken with the aid of brain imaging techniques of which he could only dream. In celebration of the memory of John Hughlings Jackson, we revisit his concept of neural evolution and development, which led to what eventually became a leading model of brain organization, whereby a new order of behavioural control--the conscious mind--is created out of simpler elements, in a manner similar to Herbert Spencer's evolutionary theory. By this Hughlings Jackson did not mean anything dualistic but merely that the highest layer of evolution of nervous arrangements was 'highly complicated' and that dissolution of that higher level leaves 'a lower consciousness and a shallower nervous system'.

Brain repair after stroke—a novel neurological model

PubMed Central

Small, Steven L.; Buccino, Giovanni; Solodkin, Ana

2017-01-01

Following stroke, patients are commonly left with debilitating motor and speech impairments. This article reviews the state of the art in neurological repair for stroke and proposes a new model for the future. We suggest that stroke treatment—from the time of the ictus itself to living with the consequences—must be fundamentally neurological, from limiting the extent of injury at the outset, to repairing the consequent damage. Our model links brain and behaviour by targeting brain circuits, and we illustrate the model though action observation treatment, which aims to enhance brain network connectivity. The model is based on the assumptions that the mechanisms of neural repair inherently involve cellular and circuit plasticity, that brain plasticity is a synaptic phenomenon that is largely stimulus-dependent, and that brain repair required both physical and behavioural interventions that are tailored to reorganize specific brain circuits. We review current approaches to brain repair after stroke and present our new model, and discuss the biological foundations, rationales, and data to support our novel approach to upper-extremity and language rehabilitation. We believe that by enhancing plasticity at the level of brain network interactions, this neurological model for brain repair could ultimately lead to a cure for stroke. PMID:24217509

Teaching Neurophysiology, Neuropharmacology, and Experimental Design Using Animal Models of Psychiatric and Neurological Disorders

ERIC Educational Resources Information Center

Morsink, Maarten C.; Dukers, Danny F.

2009-01-01

Animal models have been widely used for studying the physiology and pharmacology of psychiatric and neurological diseases. The concepts of face, construct, and predictive validity are used as indicators to estimate the extent to which the animal model mimics the disease. Currently, we used these three concepts to design a theoretical assignment to…

Implementation issues relevant to outpatient neurology palliative care.

PubMed

Kluger, Benzi M; Persenaire, Michael J; Holden, Samantha K; Palmer, Laura T; Redwine, Hannah; Berk, Julie; Anderson, C Alan; Filley, Christopher M; Kutner, Jean; Miyasaki, Janis; Carter, Julie

2017-11-29

There is growing interest in the application of palliative care principles to improve care for patients and families affected by neurologic diseases. We developed an interdisciplinary outpatient clinic for patients and families affected by neurologic disorders to better address the problems faced by our highest need patients. We have developed and improved this program over the past three years and share several of our most important lessons as well as ongoing challenges and areas where we see our clinic evolving in the future. We provide a description of our clinic logistics, including key steps in the initiation of the clinic, and provide descriptions from similar clinics at other institutions to demonstrate some of the variability in this growing field. We also provide results from a formal one-year quality improvement project and a one-year retrospective study of patients attending this clinic. Our clinic has grown steadily since its inception and maintains high satisfaction ratings from patients, caregivers, and referring providers. To maintain standardized and efficient care we have developed materials for patients and referring physicians as well as checklists and other processes used by our interdisciplinary team. Feedback from our quality improvement project helped define optimal visit duration and refine communication among team members and with patients and families. Results from our chart review suggest our clinic influences advance care planning and place of death. Common referral reasons include psychosocial support, complex symptom management, and advance care planning. Current challenges for our clinic include developing a strategy for continued growth, creating a sustainable financial model for interdisciplinary care, integrating our services with disease-specific sections, improving primary palliative care knowledge and skills within our referral base, and building effective alliances with community neurologists, geriatrics, primary care, nursing homes, and hospices. Specialized outpatient palliative care for neurologic disorders fills several important gaps in care for this patient population, provides important educational opportunities for trainees, and creates opportunities for patient and caregiver-centered research. Educational initiatives are needed to train general neurologists in primary palliative care, to train neurologists in specialist palliative care, and to train palliative medicine specialists in neurology. Research is needed to build an evidence base to identify patient and caregiver needs, support specific interventions, and to build more efficient models of care in both academic and community settings.

Unravelling functional neurology: a scoping review of theories and clinical applications in a context of chiropractic manual therapy.

PubMed

Meyer, Anne-Laure; Meyer, Amanda; Etherington, Sarah; Leboeuf-Yde, Charlotte

2017-01-01

Functional Neurology (FN), a seemingly attractive treatment approach used by some chiropractors, proposes to have an effect on a multitude of conditions but some of its concepts are controversial. A scoping review was performed to describe, in the context of chiropractic manual therapy, 1) the FN theories, and 2) its clinical applications (i.e. its indications, examination procedures, treatment modalities, treatment plans, and clinical outcomes) using four sources: i) one key textbook, ii) the scientific peer-reviewed literature, iii) websites from chiropractors using FN, and iv) semi-structured interviews of chiropractors using FN. The scientific literature was searched in PubMed, PsycINFO, and SPORTDiscus, completed by a hand search in the journal Functional Neurology, Rehabilitation and Ergonomics (November 2016 and March 2017, respectively). The only textbook on the topic we found was included and articles were chosen if they had an element of manual therapy. There was no restriction for study design but discussion papers were excluded. Websites were found in Google using the search term "Functional Neurology". Chiropractors, known to use FN, were invited based on their geographical location. Theories were mainly uncovered in the textbook as were all aspects of the clinical applications except treatment plans. The other three sources were used for the five aspects of clinical applications. Results were summarized and reported extensively in tables. Eleven articles were included, five websites scrutinized, and four semi-structured interviews performed. FN is based on the belief that reversible lesions in the nervous system are the cause of a multitude of conditions and that specific clusters of neurons can be positively affected by manipulative therapy, but also by many other stimuli. Diagnostic procedures include both conventional and unusual tests, with an interpretation specific to FN. Initial treatment is intense and clinical outcomes reported as positive. FN gives the impression to be a complex alternative to the old variant of the chiropractic subluxation model, in which the vertebral subluxation is replaced by "physiological lesions" of the brain, and the treatment, spinal adjustments, are complemented by various neurological stimuli. Both models purport to treat not the symptoms but the cause. We conclude there is a need for more scientific documentation on the validity of FN.

Time-driven activity-based costing to estimate cost of care at multidisciplinary aerodigestive centers.

PubMed

Garcia, Jordan A; Mistry, Bipin; Hardy, Stephen; Fracchia, Mary Shannon; Hersh, Cheryl; Wentland, Carissa; Vadakekalam, Joseph; Kaplan, Robert; Hartnick, Christopher J

2017-09-01

Providing high-value healthcare to patients is increasingly becoming an objective for providers including those at multidisciplinary aerodigestive centers. Measuring value has two components: 1) identify relevant health outcomes and 2) determine relevant treatment costs. Via their inherent structure, multidisciplinary care units consolidate care for complex patients. However, their potential impact on decreasing healthcare costs is less clear. The goal of this study was to estimate the potential cost savings of treating patients with laryngeal clefts at multidisciplinary aerodigestive centers. Retrospective chart review. Time-driven activity-based costing was used to estimate the cost of care for patients with laryngeal cleft seen between 2008 and 2013 at the Massachusetts Eye and Ear Infirmary Pediatric Aerodigestive Center. Retrospective chart review was performed to identify clinic utilization by patients as well as patient diet outcomes after treatment. Patients were stratified into neurologically complex and neurologically noncomplex groups. The cost of care for patients requiring surgical intervention was five and three times as expensive of the cost of care for patients not requiring surgery for neurologically noncomplex and complex patients, respectively. Following treatment, 50% and 55% of complex and noncomplex patients returned to normal diet, whereas 83% and 87% of patients experienced improved diets, respectively. Additionally, multidisciplinary team-based care for children with laryngeal clefts potentially achieves 20% to 40% cost savings. These findings demonstrate how time-driven activity-based costing can be used to estimate and compare patient costs in multidisciplinary aerodigestive centers. 2c. Laryngoscope, 127:2152-2158, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Neurological Complications of Cardiac Disease.

PubMed

Madan, Nandini; Carvalho, Karen S

2017-02-01

This article focuses on the complex interactions between the cardiovascular and neurologic systems. Initially, we focus on neurological complications in children with congenital heart disease both secondary to the underlying cardiac disease and complications of interventions. We later discuss diagnosis and management of common syncope syndromes with emphasis on vasovagal syncope. We also review the diagnosis, classification, and management of children and adolescents with postural orthostatic tachycardia syndrome. Lastly, we discuss long QT syndrome and sudden unexpected death in epilepsy (SUDEP), reviewing advances in genetics and current knowledge of pathophysiology of these conditions. This article attempts to provide an overview of these disorders with focus on pathophysiology, advances in molecular genetics, and current medical interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk factors for neurological worsening and symptomatic watershed infarction in internal carotid artery aneurysm treated by extracranial-intracranial bypass using radial artery graft.

PubMed

Matsukawa, Hidetoshi; Tanikawa, Rokuya; Kamiyama, Hiroyasu; Tsuboi, Toshiyuki; Noda, Kosumo; Ota, Nakao; Miyata, Shiro; Oda, Jumpei; Takeda, Rihee; Tokuda, Sadahisa; Kamada, Kyousuke

2016-08-01

OBJECT The revascularization technique, including bypass created using the external carotid artery (ECA), radial artery (RA), and M2 portion of middle cerebral artery (MCA), has remained indispensable for treatment of complex aneurysms. To date, it remains unknown whether diameters of the RA, superficial temporal artery (STA), and C2 portion of the internal carotid artery (ICA) and intraoperative MCA blood pressure have influences on the outcome and the symptomatic watershed infarction (WI). The aim of the present study was to evaluate the factors for the symptomatic WI and neurological worsening in patients treated by ECA-RA-M2 bypass for complex ICA aneurysm with therapeutic ICA occlusion. METHODS The authors measured the sizes of vessels (RA, C2, M2, and STA) and intraoperative MCA blood pressure (initial, after ICA occlusion, and after releasing the RA graft bypass) in 37 patients. Symptomatic WI was defined as presence of the following: postoperative new neurological deficits, WI on postoperative diffusion-weighted imaging, and ipsilateral cerebral blood flow reduction on SPECT. Neurological worsening was defined as the increase in 1 or more modified Rankin Scale scores. First, the authors performed receiver operating characteristic curve analysis for continuous variables and the binary end point of the symptomatic WI. The clinical, radiological, and physiological characteristics of patients with and without the symptomatic WI were compared using the log-rank test. Then, the authors compared the variables between patients with and without neurological worsening at discharge and at the 12-month follow-up examination or last hospital visit. RESULTS Symptomatic WI was observed in 2 (5.4%) patients. The mean MCA pressure after releasing the RA graft (< 55 mm Hg; p = 0.017), mean (MCA pressure after releasing the RA graft)/(initial MCA pressure) (< 0.70 mm Hg; p = 0.032), and mean cross-sectional area ratio ([RA/C2 diameter](2) < 0.40 mm [p < 0.0001] and [STA/C2 diameter](2) < 0.044 mm [p < 0.0001]) were related to the symptomatic WI. All preoperatively independent patients remained independent (modified Rankin Scale score < 3). After adjusting for age and sex, left operative side (p = 0.0090 and 0.038) and perforating artery ischemia (p = 0.0050 and 0.022) were related to neurological worsening at discharge (11 [29%] patients) and at the 12-month follow-up or last hospital visit (8 [22%] patients). CONCLUSIONS Results of the present study showed that the vessel diameter and intraoperative MCA pressure had impacts on the symptomatic WI and that operative side and perforating artery ischemia were related to neurological worsening in patients with complex ICA aneurysms treated by ECA-RA-M2 bypass.

Curriculum in Psychiatry and Neurology for Pharmacy Programs

PubMed Central

Bostwick, Jolene R.; Goldstone, Lisa W; Thomas, Kelan; Nemire, Ruth; Gable, Kelly N.; Cates, Marshall; Caballero, Joshua; Smith, Tawny; Bainbridge, Jacquelyn

2017-01-01

Objective. To describe pharmacy curricula in psychiatry and neurology and to report on neuropsychiatric pharmacy specialists’ views on optimal curriculum. Methods. Design and administer one electronic survey to accredited pharmacy programs asking them to report information on curricula in psychiatry and neurology for the 2014-2015 academic year. Design and administer a separate electronic survey to board certified pharmacists with an academic affiliation who are members of the College of Psychiatric and Neurologic Pharmacists (CPNP) asking about their teaching activities and their opinion on optimal curricula. Results. Fifty-six percent of pharmacy programs and 65% of CPNP members responded to the surveys. The program survey revealed greater than 80% of topics were taught by full-time faculty. Didactic lecturing, team-based learning, and case studies were the most common teaching methods. Programs dedicated the most didactics (3 to 5+ hours) to epilepsy, depression, schizophrenia, substance use disorders, and pain. Autism, traumatic brain injury, personality, and eating disorders were either not taught or given ≤ 1 hour of didactics in most programs. Inpatient psychiatry had the most APPE placements with a mean of 19.6, range 0-83. APPE electives in psychiatry outnumbered those in neurology 5 to 1. CPNP member survey results showed 2 out of 3 members agreed that curriculum could be improved with additional APPEs in psychiatry and neurology. Conclusion. Didactic hour distribution in psychiatry and neurology could be improved to better align with board certification in psychiatric pharmacy (BCPP) recommendations and disorder prevalence and complexity. Specialists recommend an experiential component in neurology and psychiatry to combat stigma and improve pharmacist knowledge and skills. PMID:29109559

Cost-efficiency of specialist hyperacute in-patient rehabilitation services for medically unstable patients with complex rehabilitation needs: a prospective cohort analysis.

PubMed

Turner-Stokes, Lynne; Bavikatte, Ganesh; Williams, Heather; Bill, Alan; Sephton, Keith

2016-09-08

To evaluate functional outcomes, care needs and cost-efficiency of hyperacute (HA) rehabilitation for a cohort of in-patients with complex neurological disability and unstable medical/surgical conditions. A multicentre cohort analysis of prospectively collected clinical data from the UK Rehabilitation Outcomes Collaborative (UKROC) national clinical database, 2012-2015. Two HA specialist rehabilitation services in England, providing different service models for HA rehabilitation. All patients admitted to each of the units with an admission rehabilitation complexity M score of ≥3 (N=190; mean age 46 (SD16) years; males:females 63:37%). Diagnoses were acquired brain injury (n=166; 87%), spinal cord injury (n=9; 5%), peripheral neurological conditions (n=9; 5%) and other (n=6; 3%). Specialist in-patient multidisciplinary rehabilitation combined with management and stabilisation of intercurrent medical and surgical problems. Rehabilitation complexity and medical acuity: Rehabilitation Complexity Scale-version 13. Dependency and care costs: Northwick Park Dependency Scale/Care Needs Assessment (NPDS/NPCNA). Functional independence: UK Functional Assessment Measure (UK FIM+FAM). (1) reduction in dependency and (2) cost-efficiency, measured as the time taken to offset rehabilitation costs by savings in NPCNA-estimated costs of on-going care in the community. The mean length of stay was 103 (SD66) days. Some differences were observed between the two units, which were in keeping with the different service models. However, both units showed a significant reduction in dependency and acuity between admission and discharge on all measures (Wilcoxon: p<0.001). For the 180 (95%) patients with complete NPCNA data, the mean episode cost was £77 119 (bootstrapped 95% CI £70 614 to £83 894) and the mean reduction in 'weekly care costs' was £462/week (95% CI 349 to 582). The mean time to offset the cost of rehabilitation was 27.6 months (95% CI 13.2 to 43.8). Despite its relatively high initial cost, specialist HA rehabilitation can be highly cost-efficient, producing substantial savings in on-going care costs, and relieving pressure in the acute care services. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Cost-efficiency of specialist hyperacute in-patient rehabilitation services for medically unstable patients with complex rehabilitation needs: a prospective cohort analysis

PubMed Central

Turner-Stokes, Lynne; Bavikatte, Ganesh; Williams, Heather; Bill, Alan; Sephton, Keith

2016-01-01

Objectives To evaluate functional outcomes, care needs and cost-efficiency of hyperacute (HA) rehabilitation for a cohort of in-patients with complex neurological disability and unstable medical/surgical conditions. Design A multicentre cohort analysis of prospectively collected clinical data from the UK Rehabilitation Outcomes Collaborative (UKROC) national clinical database, 2012–2015. Setting Two HA specialist rehabilitation services in England, providing different service models for HA rehabilitation. Participants All patients admitted to each of the units with an admission rehabilitation complexity M score of ≥3 (N=190; mean age 46 (SD16) years; males:females 63:37%). Diagnoses were acquired brain injury (n=166; 87%), spinal cord injury (n=9; 5%), peripheral neurological conditions (n=9; 5%) and other (n=6; 3%). Intervention Specialist in-patient multidisciplinary rehabilitation combined with management and stabilisation of intercurrent medical and surgical problems. Outcome measures Rehabilitation complexity and medical acuity: Rehabilitation Complexity Scale—version 13. Dependency and care costs: Northwick Park Dependency Scale/Care Needs Assessment (NPDS/NPCNA). Functional independence: UK Functional Assessment Measure (UK FIM+FAM). Primary outcomes: (1) reduction in dependency and (2) cost-efficiency, measured as the time taken to offset rehabilitation costs by savings in NPCNA-estimated costs of on-going care in the community. Results The mean length of stay was 103 (SD66) days. Some differences were observed between the two units, which were in keeping with the different service models. However, both units showed a significant reduction in dependency and acuity between admission and discharge on all measures (Wilcoxon: p<0.001). For the 180 (95%) patients with complete NPCNA data, the mean episode cost was £77 119 (bootstrapped 95% CI £70 614 to £83 894) and the mean reduction in ‘weekly care costs’ was £462/week (95% CI 349 to 582). The mean time to offset the cost of rehabilitation was 27.6 months (95% CI 13.2 to 43.8). Conclusions Despite its relatively high initial cost, specialist HA rehabilitation can be highly cost-efficient, producing substantial savings in on-going care costs, and relieving pressure in the acute care services. PMID:27609852

Complex and differential glial responses in Alzheimer's disease and ageing.

PubMed

Rodríguez, José J; Butt, Arthur M; Gardenal, Emanuela; Parpura, Vladimir; Verkhratsky, Alexei

2016-01-01

Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.

FROM REINFORCEMENT LEARNING MODELS OF THE BASAL GANGLIA TO THE PATHOPHYSIOLOGY OF PSYCHIATRIC AND NEUROLOGICAL DISORDERS

PubMed Central

Maia, Tiago V.; Frank, Michael J.

2013-01-01

Over the last decade and a half, reinforcement learning models have fostered an increasingly sophisticated understanding of the functions of dopamine and cortico-basal ganglia-thalamo-cortical (CBGTC) circuits. More recently, these models, and the insights that they afford, have started to be used to understand key aspects of several psychiatric and neurological disorders that involve disturbances of the dopaminergic system and CBGTC circuits. We review this approach and its existing and potential applications to Parkinson’s disease, Tourette’s syndrome, attention-deficit/hyperactivity disorder, addiction, schizophrenia, and preclinical animal models used to screen novel antipsychotic drugs. The approach’s proven explanatory and predictive power bodes well for the continued growth of computational psychiatry and computational neurology. PMID:21270784

Multi-compartment microscopic diffusion imaging

PubMed Central

Kaden, Enrico; Kelm, Nathaniel D.; Carson, Robert P.; Does, Mark D.; Alexander, Daniel C.

2017-01-01

This paper introduces a multi-compartment model for microscopic diffusion anisotropy imaging. The aim is to estimate microscopic features specific to the intra- and extra-neurite compartments in nervous tissue unconfounded by the effects of fibre crossings and orientation dispersion, which are ubiquitous in the brain. The proposed MRI method is based on the Spherical Mean Technique (SMT), which factors out the neurite orientation distribution and thus provides direct estimates of the microscopic tissue structure. This technique can be immediately used in the clinic for the assessment of various neurological conditions, as it requires only a widely available off-the-shelf sequence with two b-shells and high-angular gradient resolution achievable within clinically feasible scan times. To demonstrate the developed method, we use high-quality diffusion data acquired with a bespoke scanner system from the Human Connectome Project. This study establishes the normative values of the new biomarkers for a large cohort of healthy young adults, which may then support clinical diagnostics in patients. Moreover, we show that the microscopic diffusion indices offer direct sensitivity to pathological tissue alterations, exemplified in a preclinical animal model of Tuberous Sclerosis Complex (TSC), a genetic multi-organ disorder which impacts brain microstructure and hence may lead to neurological manifestations such as autism, epilepsy and developmental delay. PMID:27282476

CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation

PubMed Central

De Rubeis, Silvia; Pasciuto, Emanuela; Li, Ka Wan; Fernández, Esperanza; Di Marino, Daniele; Buzzi, Andrea; Ostroff, Linnaea E.; Klann, Eric; Zwartkruis, Fried J.T.; Komiyama, Noboru H.; Grant, Seth G.N.; Poujol, Christel; Choquet, Daniel; Achsel, Tilmann; Posthuma, Danielle; Smit, August B.; Bagni, Claudia

2013-01-01

Summary The CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia. CYFIP1 plays a dual role in two apparently unrelated processes, inhibiting local protein synthesis and favoring actin remodeling. Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases CYFIP1 from the translational inhibitory complex, triggering translation of target mRNAs and shifting CYFIP1 into the WAVE regulatory complex. Active Rac1 alters the CYFIP1 conformation, as demonstrated by intramolecular FRET, and is key in changing the equilibrium of the two complexes. CYFIP1 thus orchestrates the two molecular cascades, protein translation and actin polymerization, each of which is necessary for correct spine morphology in neurons. The CYFIP1 interactome reveals many interactors associated with brain disorders, opening new perspectives to define regulatory pathways shared by neurological disabilities characterized by spine dysmorphogenesis. PMID:24050404

Household food insecurity and symptoms of neurologic disorder in Ethiopia: an observational analysis.

PubMed

El-Sayed, Abdulrahman M; Hadley, Craig; Tessema, Fasil; Tegegn, Ayelew; Cowan, John A; Galea, Sandro

2010-12-31

Food insecurity (FI) has been shown to be associated with poor health both in developing and developed countries. Little is known about the relation between FI and neurological disorder. We assessed the relation between FI and risk for neurologic symptoms in southwest Ethiopia. Data about food security, gender, age, household assets, and self-reported neurologic symptoms were collected from a representative, community-based sample of adults (N = 900) in Jimma Zone, Ethiopia. We calculated univariate statistics and used bivariate chi-square tests and multivariate logistic regression models to assess the relation between FI and risk of neurologic symptoms including seizures, extremity weakness, extremity numbness, tremors/ataxia, aphasia, carpal tunnel syndrome, vision dysfunction, and spinal pain. In separate multivariate models by outcome and gender, adjusting for age and household socioeconomic status, severe FI was associated with higher odds of seizures, movement abnormalities, carpal tunnel, vision dysfunction, spinal pain, and comorbid disorders among women. Severe FI was associated with higher odds of seizures, extremity numbness, movement abnormalities, difficulty speaking, carpal tunnel, vision dysfunction, and comorbid disorders among men. We found that FI was associated with symptoms of neurologic disorder. Given the cross-sectional nature of our study, the directionality of these associations is unclear. Future research should assess causal mechanisms relating FI to neurologic symptoms in sub-Saharan Africa.

Targeting Human Central Nervous System Protein Kinases: An Isoform Selective p38αMAPK Inhibitor That Attenuates Disease Progression in Alzheimer’s Disease Mouse Models

PubMed Central

2015-01-01

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, pursuit of the neurotherapeutic hypothesis requires kinase isoform selective inhibitors with appropriate neuropharmacology features. Synaptic dysfunction disorders offer a potential for enhanced pharmacological efficacy due to stress-induced activation of p38αMAPK in both neurons and glia, the interacting cellular components of the synaptic pathophysiological axis, to be modulated. We report a novel isoform selective p38αMAPK inhibitor, MW01-18-150SRM (=MW150), that is efficacious in suppression of hippocampal-dependent associative and spatial memory deficits in two distinct synaptic dysfunction mouse models. A synthetic scheme for biocompatible product and positive outcomes from pharmacological screens are presented. The high-resolution crystallographic structure of the p38αMAPK/MW150 complex documents active site binding, reveals a potential low energy conformation of the bound inhibitor, and suggests a structural explanation for MW150’s exquisite target selectivity. As far as we are aware, MW150 is without precedent as an isoform selective p38MAPK inhibitor or as a kinase inhibitor capable of modulating in vivo stress related behavior. PMID:25676389

Risk factors for hydrocephalus and neurological deficit in children born with an encephalocele.

PubMed

Da Silva, Stephanie L; Jeelani, Yasser; Dang, Ha; Krieger, Mark D; McComb, J Gordon

2015-04-01

There is a known association of hydrocephalus with encephaloceles. Risk factors for hydrocephalus and neurological deficit were ascertained in a series of patients born with an encephalocele. A retrospective analysis was undertaken of patients treated for encephaloceles at Children's Hospital Los Angeles between 1994 and 2012. The following factors were evaluated for their prognostic value: age at presentation, sex, location of encephalocele, size, contents, microcephaly, presence of hydrocephalus, CSF leak, associated cranial anomalies, and neurological outcome. Seventy children were identified, including 38 girls and 32 boys. The median age at presentation was 2 months. The mean follow-up duration was 3.7 years. Encephalocele location was classified as anterior (n = 14) or posterior (n = 56) to the coronal suture. The average maximum encephalocele diameter was 4 cm (range 0.5-23 cm). Forty-seven encephaloceles contained neural tissue. Eight infants presented at birth with CSF leaking from the encephalocele, with 1 being infected. Six patients presented with hydrocephalus, while 11 developed progressive hydrocephalus postoperatively. On univariate analysis, the presence of neural tissue, cranial anomalies, encephalocele size of at least 2 cm, seizure disorder, and microcephaly were each positively associated with hydrocephalus. On multivariate logistic regression modeling, the single prognostic factor for hydrocephalus of borderline statistical significance was the presence of neural tissue (odds ratio [OR] = 5.8, 95% confidence interval [CI] = 0.8-74.0). Fourteen patients had severe developmental delay, 28 had mild/moderate delay, and 28 were neurologically normal. On univariate analysis, the presence of cranial anomalies, larger size of encephalocele, hydrocephalus, and microcephaly were positively associated with neurological deficit. In the multivariable model, the only statistically significant prognostic factor for neurological deficit was presence of hydrocephalus (OR 17.2, 95% CI 1.7-infinity). In multivariate models, the presence of neural tissue was borderline significantly associated with hydrocephalus and the presence of hydrocephalus was significantly associated with neurological deficit. The location of the encephalocele did not have a statistically significant association with incidence of hydrocephalus or neurological deficit. In contrast to modestly good/fair neurological outcome in children with an encephalocele without hydrocephalus, the presence of hydrocephalus resulted in a far worse neurological outcome.

Management of thoracolumbar spine trauma: An overview

PubMed Central

Rajasekaran, S; Kanna, Rishi Mugesh; Shetty, Ajoy Prasad

2015-01-01

Thoracolumbar spine fractures are common injuries that can result in significant disability, deformity and neurological deficit. Controversies exist regarding the appropriate radiological investigations, the indications for surgical management and the timing, approach and type of surgery. This review provides an overview of the epidemiology, biomechanical principles, radiological and clinical evaluation, classification and management principles. Literature review of all relevant articles published in PubMed covering thoracolumbar spine fractures with or without neurologic deficit was performed. The search terms used were thoracolumbar, thoracic, lumbar, fracture, trauma and management. All relevant articles and abstracts covering thoracolumbar spine fractures with and without neurologic deficit were reviewed. Biomechanically the thoracolumbar spine is predisposed to a higher incidence of spinal injuries. Computed tomography provides adequate bony detail for assessing spinal stability while magnetic resonance imaging shows injuries to soft tissues (posterior ligamentous complex [PLC]) and neurological structures. Different classification systems exist and the most recent is the AO spine knowledge forum classification of thoracolumbar trauma. Treatment includes both nonoperative and operative methods and selected based on the degree of bony injury, neurological involvement, presence of associated injuries and the integrity of the PLC. Significant advances in imaging have helped in the better understanding of thoracolumbar fractures, including information on canal morphology and injury to soft tissue structures. The ideal classification that is simple, comprehensive and guides management is still elusive. Involvement of three columns, progressive neurological deficit, significant kyphosis and canal compromise with neurological deficit are accepted indications for surgical stabilization through anterior, posterior or combined approaches. PMID:25593358

Fuxianhuiid ventral nerve cord and early nervous system evolution in Panarthropoda

PubMed Central

Yang, Jie; Ortega-Hernández, Javier; Butterfield, Nicholas J.; Liu, Yu; Boyan, George S.; Hou, Jin-bo; Lan, Tian; Zhang, Xi-guang

2016-01-01

Panarthropods are typified by disparate grades of neurological organization reflecting a complex evolutionary history. The fossil record offers a unique opportunity to reconstruct early character evolution of the nervous system via exceptional preservation in extinct representatives. Here we describe the neurological architecture of the ventral nerve cord (VNC) in the upper-stem group euarthropod Chengjiangocaris kunmingensis from the early Cambrian Xiaoshiba Lagerstätte (South China). The VNC of C. kunmingensis comprises a homonymous series of condensed ganglia that extend throughout the body, each associated with a pair of biramous limbs. Submillimetric preservation reveals numerous segmental and intersegmental nerve roots emerging from both sides of the VNC, which correspond topologically to the peripheral nerves of extant Priapulida and Onychophora. The fuxianhuiid VNC indicates that ancestral neurological features of Ecdysozoa persisted into derived members of stem-group Euarthropoda but were later lost in crown-group representatives. These findings illuminate the VNC ground pattern in Panarthropoda and suggest the independent secondary loss of cycloneuralian-like neurological characters in Tardigrada and Euarthropoda. PMID:26933218

Survey of the Child Neurology Program Coordinator Association: Workforce Issues and Readiness for the Next Accreditation System.

PubMed

Feist, Terri B; Campbell, Julia L; LaBare, Julie A; Gilbert, Donald L

2016-03-01

In preparation for the implementation of the Next Accreditation System in Child Neurology, the authors organized the first meeting of child neurology program coordinators in October 2014. A workforce and program-readiness survey was conducted initially. Coordinator job titles varied widely. Most respondents (65%) managed 1 or more fellowships plus child neurology residency. Most had worked in graduate medical education less than 5 years (53%), with no career path (88%), supervised by someone without graduate medical education experience (85%), in divisions where faculty knowledge was judged inadequate (72%). A small proportion of programs had established clinical competency committee policies (28%) and was ready to implement milestone-based evaluations (56%). A post-conference survey demonstrated substantial improvements in relevant skills. The complexity of residency program management in the Next Accreditation System era supports substantive modifications to the program coordinator role. Such changes should include defined career pathway, managerial classification, administrative support, and continuing education. © The Author(s) 2015.

Fuxianhuiid ventral nerve cord and early nervous system evolution in Panarthropoda.

PubMed

Yang, Jie; Ortega-Hernández, Javier; Butterfield, Nicholas J; Liu, Yu; Boyan, George S; Hou, Jin-Bo; Lan, Tian; Zhang, Xi-Guang

2016-03-15

Panarthropods are typified by disparate grades of neurological organization reflecting a complex evolutionary history. The fossil record offers a unique opportunity to reconstruct early character evolution of the nervous system via exceptional preservation in extinct representatives. Here we describe the neurological architecture of the ventral nerve cord (VNC) in the upper-stem group euarthropod Chengjiangocaris kunmingensis from the early Cambrian Xiaoshiba Lagerstätte (South China). The VNC of C. kunmingensis comprises a homonymous series of condensed ganglia that extend throughout the body, each associated with a pair of biramous limbs. Submillimetric preservation reveals numerous segmental and intersegmental nerve roots emerging from both sides of the VNC, which correspond topologically to the peripheral nerves of extant Priapulida and Onychophora. The fuxianhuiid VNC indicates that ancestral neurological features of Ecdysozoa persisted into derived members of stem-group Euarthropoda but were later lost in crown-group representatives. These findings illuminate the VNC ground pattern in Panarthropoda and suggest the independent secondary loss of cycloneuralian-like neurological characters in Tardigrada and Euarthropoda.

Conservative management of idiopathic anterior atlantoaxial subluxation without neurological deficits in an 83-year-old female: A case report.

PubMed

Marchand, Andrée-Anne; Wong, Jessica J

2014-03-01

Atlantoaxial subluxation that is not related to traumatic, congenital, or rheumatological conditions is rare and can be a diagnostic challenge. This case report details a case of anterior atlantoaxial subluxation in an 83-year-old female without history of trauma, congenital, or rheumatological conditions. She presented to the chiropractor with insidious neck pain and headaches, without neurological deficits. Radiographs revealed a widened atlantodental space (measuring 6 mm) indicating anterior atlantoaxial subluxation and potential sagittal atlantoaxial instability. Prompt detection and appropriate conservative management resulted in favourable long-term outcome at 13-months follow-up. Conservative management included education, mobilizations, soft tissue therapy, monitoring for neurological progression, and co-management with the family physician. The purpose of this case report is to heighten awareness of the clinical presentation of idiopathic anterior atlantoaxial subluxation without neurological deficits. Discussion will focus on the incidence, mechanism, clinical presentation, and conservative management of a complex case of anterior atlantoaxial subluxation.

Drosophila melanogaster: a fly through its history and current use.

PubMed

Stephenson, R; Metcalfe, N H

2013-01-01

Drosophila melanogaster, the common fruit fly, has been used as a model organism in both medical and scientific research for over a century. Work by Thomas Hunt Morgan (1866-1945) and his students at Columbia University at the beginning of the twentieth century led to great discoveries such as sex-linked inheritance and that ionising radiation causes mutations in genes. However, the use of Drosophila was not limited to genetic research. Experimentation with this model organism has also led to discoveries in neuroscience and neurodevelopment, including the basis of circadian rhythms. Its complex nervous system, conserved neurological function, and human disease-related loci allow Drosophila to be an ideal model organism for the study of neurodegenerative disease, for which it is used today, aiding research into diseases such as Alzheimer's and Parkinson's, which are becoming more prevalent in today's ageing population.

Modeling Disease Severity in Multiple Sclerosis Using Electronic Health Records

PubMed Central

Xia, Zongqi; Secor, Elizabeth; Chibnik, Lori B.; Bove, Riley M.; Cheng, Suchun; Chitnis, Tanuja; Cagan, Andrew; Gainer, Vivian S.; Chen, Pei J.; Liao, Katherine P.; Shaw, Stanley Y.; Ananthakrishnan, Ashwin N.; Szolovits, Peter; Weiner, Howard L.; Karlson, Elizabeth W.; Murphy, Shawn N.; Savova, Guergana K.; Cai, Tianxi; Churchill, Susanne E.; Plenge, Robert M.; Kohane, Isaac S.; De Jager, Philip L.

2013-01-01

Objective To optimally leverage the scalability and unique features of the electronic health records (EHR) for research that would ultimately improve patient care, we need to accurately identify patients and extract clinically meaningful measures. Using multiple sclerosis (MS) as a proof of principle, we showcased how to leverage routinely collected EHR data to identify patients with a complex neurological disorder and derive an important surrogate measure of disease severity heretofore only available in research settings. Methods In a cross-sectional observational study, 5,495 MS patients were identified from the EHR systems of two major referral hospitals using an algorithm that includes codified and narrative information extracted using natural language processing. In the subset of patients who receive neurological care at a MS Center where disease measures have been collected, we used routinely collected EHR data to extract two aggregate indicators of MS severity of clinical relevance multiple sclerosis severity score (MSSS) and brain parenchymal fraction (BPF, a measure of whole brain volume). Results The EHR algorithm that identifies MS patients has an area under the curve of 0.958, 83% sensitivity, 92% positive predictive value, and 89% negative predictive value when a 95% specificity threshold is used. The correlation between EHR-derived and true MSSS has a mean R2 = 0.38±0.05, and that between EHR-derived and true BPF has a mean R2 = 0.22±0.08. To illustrate its clinical relevance, derived MSSS captures the expected difference in disease severity between relapsing-remitting and progressive MS patients after adjusting for sex, age of symptom onset and disease duration (p = 1.56×10−12). Conclusion Incorporation of sophisticated codified and narrative EHR data accurately identifies MS patients and provides estimation of a well-accepted indicator of MS severity that is widely used in research settings but not part of the routine medical records. Similar approaches could be applied to other complex neurological disorders. PMID:24244385

Neurological soft signs in antisocial men and relation with psychopathy.

PubMed

Demirel, Omer Faruk; Demirel, Aysegul; Kadak, Muhammed Tayyib; Emül, Murat; Duran, Alaattin

2016-06-30

Neurological soft signs (NSS) were studied in some axis-I disorders like schizophrenia, obsessive compulsive disorder, bipolar disorder, alcohol and substance abuse disorder. Aim of this study is detection of neurological soft signs in antisocial personality disorder and relation of these signs with psychopathy. The study was included 41 antisocial men and 41 healthy control subjects. Sociodemographic form, neurological evaluation scale and Hare psychopathy checklist was applied to the antisocial subjects, whereas sociodemographic form and neurological evaluation scale were applied to the controls. Antisocial men exhibited significiantly more NSS in total score and subgroups scales (p<0.05). It was shown that there was a significant association with psychopathy scores and NSS sequencing complex motor tasks (r=0.309; p=0.049) and NSS other tests subgroup scores (r=0.328; p=0.037). Similar relation was also observed in comparison between psychopathy subgroups. NSS accepted as being endophenotypes in schizophrenia, were also detected in antisocial group significantly more than controls in our study. Significant relationship between psychopathy and NSS may also hint the role of genetic mechanisms in personality development, though new extended studies with larger sample size are needed for clarification of this relationship. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

From Molecular Circuit Dysfunction to Disease: Case Studies in Epilepsy, Traumatic Brain Injury, and Alzheimer’s Disease

PubMed Central

Dulla, Chris G.; Coulter, Douglas A.; Ziburkus, Jokubas

2015-01-01

Complex circuitry with feed-forward and feed-back systems regulate neuronal activity throughout the brain. Cell biological, electrical, and neurotransmitter systems enable neural networks to process and drive the entire spectrum of cognitive, behavioral, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits relies on hundreds, if not thousands, of unique molecular interactions. Even single molecule dysfunctions can be disrupting to neural circuit activity, leading to neurological pathology. Here, we sample our current understanding of how molecular aberrations lead to disruptions in networks using three neurological pathologies as exemplars: epilepsy, traumatic brain injury (TBI), and Alzheimer’s disease (AD). Epilepsy provides a window into how total destabilization of network balance can occur. TBI is an abrupt physical disruption that manifests in both acute and chronic neurological deficits. Last, in AD progressive cell loss leads to devastating cognitive consequences. Interestingly, all three of these neurological diseases are interrelated. The goal of this review, therefore, is to identify molecular changes that may lead to network dysfunction, elaborate on how altered network activity and circuit structure can contribute to neurological disease, and suggest common threads that may lie at the heart of molecular circuit dysfunction. PMID:25948650

Norman Geschwind and the use of history in the (re)birth of behavioral neurology.

PubMed

Kushner, Howard I

2015-01-01

When Norman Geschwind (1926-1984) attended medical school in the 1940s, his psychiatry professors taught as if behavior were unrelated to neuropathology. The focus of neurology remained the diagnosis and treatment of aphasias and epilepsies, while cognitive impairments and developmental disorders were classified as functional (psychological) disorders. Geschwind was troubled by the fact that many of the patients he saw with neurological deficits also presented with behavioral (developmental) disorders. Geschwind's generation also had been taught that aphasias resulted from global rather than localized or focal neurological lesions. These holists, including the prepsychoanalytic Sigmund Freud, targeted the work of aphasiologist Carl Wernicke as an exemplar of the flaws of the localizationist hypothesis. Reading Wernicke in the original, Geschwind discovered a complex and multilayered explanation for aphasias that implicated lesions located in association pathways that, when extensive, resulted in behavioral disorders. Geschwind also reread the works of the holists, discovering that, while their rhetoric rejected Wernicke, their explanations of aphasias actually reinforced Wernicke's hypothesis. Building on his reading of these historical documents and his clinical experiences, Geschwind urged the resurrection of Wernicke's disconnection syndromes that Geschwind labeled as Behavioral Neurology.

From Molecular Circuit Dysfunction to Disease: Case Studies in Epilepsy, Traumatic Brain Injury, and Alzheimer's Disease.

PubMed

Dulla, Chris G; Coulter, Douglas A; Ziburkus, Jokubas

2016-06-01

Complex circuitry with feed-forward and feed-back systems regulate neuronal activity throughout the brain. Cell biological, electrical, and neurotransmitter systems enable neural networks to process and drive the entire spectrum of cognitive, behavioral, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits relies on hundreds, if not thousands, of unique molecular interactions. Even single molecule dysfunctions can be disrupting to neural circuit activity, leading to neurological pathology. Here, we sample our current understanding of how molecular aberrations lead to disruptions in networks using three neurological pathologies as exemplars: epilepsy, traumatic brain injury (TBI), and Alzheimer's disease (AD). Epilepsy provides a window into how total destabilization of network balance can occur. TBI is an abrupt physical disruption that manifests in both acute and chronic neurological deficits. Last, in AD progressive cell loss leads to devastating cognitive consequences. Interestingly, all three of these neurological diseases are interrelated. The goal of this review, therefore, is to identify molecular changes that may lead to network dysfunction, elaborate on how altered network activity and circuit structure can contribute to neurological disease, and suggest common threads that may lie at the heart of molecular circuit dysfunction. © The Author(s) 2015.

Survey of Neurological Disorders in Children Aged 9-15 Years in Northern India.

PubMed

Kumar, Rashmi; Bhave, Anupama; Bhargava, Roli; Agarwal, G G

2016-04-01

The prevalence of neurological disorders in resource-poor settings, although likely to be high, is largely unexplored. The prevalence and risk factors for neurological disorders, including epilepsy and intellectual, motor, vision, and hearing deficits, in children aged 9 to 15 years in the community were investigated. A new instrument was developed, validated, and used in a 2-stage community survey for neurological disorders in Lucknow, India. Screen-positives and random proportion of screen-negatives were validated using predefined criteria. Prevalence of different neurological disorders was calculated by weighted proportions. Of 6431 children screened, 221 were positive. A total of 214 screen-positives and 251 screen-negatives were validated. Prevalence of neurological disorders was 31.3 per 1000 children of this age group (weighted 95% confidence interval = 16.5, 46.4). The final model for risk factors included age, mud house, delayed cry at birth, and previous head injury. The prevalence of neurological disorders is high in this region. Predictors of neurological disorders are largely modifiable. © The Author(s) 2015.

Building-associated neurological damage modeled in human cells: a mechanism of neurotoxic effects by exposure to mycotoxins in the indoor environment.

PubMed

Karunasena, Enusha; Larrañaga, Michael D; Simoni, Jan S; Douglas, David R; Straus, David C

2010-12-01

Damage to human neurological system cells resulting from exposure to mycotoxins confirms a previously controversial public health threat for occupants of water-damaged buildings. Leading scientific organizations disagree about the ability of inhaled mycotoxins in the indoor environment to cause adverse human health effects. Damage to the neurological system can result from exposure to trichothecene mycotoxins in the indoor environment. This study demonstrates that neurological system cell damage can occur from satratoxin H exposure to neurological cells at exposure levels that can be found in water-damaged buildings contaminated with fungal growth. The constant activation of inflammatory and apoptotic pathways at low levels of exposure in human brain capillary endothelial cells, astrocytes, and neural progenitor cells may amplify devastation to neurological tissues and lead to neurological system cell damage from indirect events triggered by the presence of trichothecenes.

Implementation of the Hammersmith Infant Neurological Examination in a High-Risk Infant Follow-Up Program.

PubMed

Maitre, Nathalie L; Chorna, Olena; Romeo, Domenico M; Guzzetta, Andrea

2016-12-01

High-risk infant follow-up programs provide early identification and referral for treatment of neurodevelopmental delays and impairments. In these programs, a standardized neurological examination is a critical component of evaluation for clinical and research purposes. To address primary challenges of provider educational diversity and standardized documentation, we designed an approach to training and implementation of the Hammersmith Infant Neurological Examination with precourse materials, a workshop model, and adaptation of the electronic medical record. Provider completion and documentation of a neurological examination were evaluated before and after Hammersmith Infant Neurological Examination training. Standardized training and implementation of the Hammersmith Infant Neurological Examination in a large high-risk infant follow-up is feasible and effective and allows for quantitative evaluation of neurological findings and developmental trajectories. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Case Study on the Effect of Word Repetition Method Supported by Neurological Affecting Model on Fluent Reading

ERIC Educational Resources Information Center

Duran, Erol

2013-01-01

This research is a case study which is a qualitative study model and named as example event as well. The purpose of this research is determining the effect of word repetitive reading method supported with neurological affecting model on fluent reading. In this study, False Analysis Inventory was used in order to determine the student's oral…

Mice with experimental antiphospholipid syndrome display hippocampal dysfunction and a reduction of dendritic complexity in hippocampal CA1 neurones.

PubMed

Frauenknecht, Katrin; Katzav, Aviva; Weiss Lavi, Ronen; Sabag, Avishag; Otten, Susanne; Chapman, Joab; Sommer, Clemens J

2015-08-01

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by high titres of auto-antibodies (aPL) leading to thrombosis and consequent infarcts. However, many affected patients develop neurological symptoms in the absence of stroke. Similarly, in a mouse model of this disease (eAPS), animals consistently develop behavioural abnormalities despite lack of ischemic brain injury. Therefore, the present study was designed to identify structural alterations of hippocampal neurones underlying the neurological symptoms in eAPS. Adult female Balb/C mice were subjected to either induction of eAPS by immunization with β2-Glycoprotein 1 or to a control group. After sixteen weeks animals underwent behavioural and cognitive testing using Staircase test (experiment 1 and 2) and Y-maze alternation test (experiment 1) and were tested for serum aPL levels (both experiments). Animals of experiment 1 (n = 7/group) were used for hippocampal neurone analysis using Golgi-Cox staining. Animals of experiment 2 (n = 7/group) were used to analyse molecular markers of total dendritic integrity (MAP2), presynaptic plasticity (synaptobrevin 2/VAMP2) and dendritic spines (synaptopodin) using immunohistochemistry. eAPS mice developed increased aPL titres and presented with abnormal behaviour and impaired short term memory. Further, they revealed a reduction of dendritic complexity of hippocampal CA1 neurones as reflected by decreased dendritic length, arborization and spine density, respectively. Additional decrease of the spine-associated protein expression of Synaptopodin points to dendritic spines as major targets in the pathological process. Reduction of hippocampal dendritic complexity may represent the structural basis for the behavioural and cognitive abnormalities of eAPS mice. © 2014 British Neuropathological Society.

Materials for Neural Differentiation, Trans-Differentiation, and Modeling of Neurological Disease.

PubMed

Gong, Lulu; Cao, Lining; Shen, Zhenmin; Shao, Li; Gao, Shaorong; Zhang, Chao; Lu, Jianfeng; Li, Weida

2018-04-01

Neuron regeneration from pluripotent stem cells (PSCs) differentiation or somatic cells trans-differentiation is a promising approach for cell replacement in neurodegenerative diseases and provides a powerful tool for investigating neural development, modeling neurological diseases, and uncovering the mechanisms that underlie diseases. Advancing the materials that are applied in neural differentiation and trans-differentiation promotes the safety, efficiency, and efficacy of neuron regeneration. In the neural differentiation process, matrix materials, either natural or synthetic, not only provide a structural and biochemical support for the monolayer or three-dimensional (3D) cultured cells but also assist in cell adhesion and cell-to-cell communication. They play important roles in directing the differentiation of PSCs into neural cells and modeling neurological diseases. For the trans-differentiation of neural cells, several materials have been used to make the conversion feasible for future therapy. Here, the most current applications of materials for neural differentiation for PSCs, neuronal trans-differentiation, and neurological disease modeling is summarized and discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

CRISPR-engineered genome editing for the next generation neurological disease modeling.

PubMed

Feng, Weijun; Liu, Hai-Kun; Kawauchi, Daisuke

2018-02-02

Neurological disorders often occur because of failure of proper brain development and/or appropriate maintenance of neuronal circuits. In order to understand roles of causative factors (e.g. genes, cell types) in disease development, generation of solid animal models has been one of straight-forward approaches. Recent next generation sequencing studies on human patient-derived clinical samples have identified various types of recurrent mutations in individual neurological diseases. While these discoveries have prompted us to evaluate impact of mutated genes on these neurological diseases, a feasible but flexible genome editing tool had remained to be developed. An advance of genome editing technology using the clustered regularly interspaced short palindromic repeats (CRISPR) with the CRISPR-associated protein (Cas) offers us a tremendous potential to create a variety of mutations in the cell, leading to "next generation" disease models carrying disease-associated mutations. We will here review recent progress of CRISPR-based brain disease modeling studies and discuss future requirement to tackle current difficulties in usage of these technologies. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurologic Phenotypes Associated With Mutations in RTN4IP1 (OPA10) in Children and Young Adults.

PubMed

Charif, Majida; Nasca, Alessia; Thompson, Kyle; Gerber, Sylvie; Makowski, Christine; Mazaheri, Neda; Bris, Céline; Goudenège, David; Legati, Andrea; Maroofian, Reza; Shariati, Gholamreza; Lamantea, Eleonora; Hopton, Sila; Ardissone, Anna; Moroni, Isabella; Giannotta, Melania; Siegel, Corinna; Strom, Tim M; Prokisch, Holger; Vignal-Clermont, Catherine; Derrien, Sabine; Zanlonghi, Xavier; Kaplan, Josseline; Hamel, Christian P; Leruez, Stephanie; Procaccio, Vincent; Bonneau, Dominique; Reynier, Pascal; White, Frances E; Hardy, Steven A; Barbosa, Inês A; Simpson, Michael A; Vara, Roshni; Perdomo Trujillo, Yaumara; Galehdari, Hamind; Deshpande, Charu; Haack, Tobias B; Rozet, Jean-Michel; Taylor, Robert W; Ghezzi, Daniele; Amati-Bonneau, Patrizia; Lenaers, Guy

2018-01-01

Neurologic disorders with isolated symptoms or complex syndromes are relatively frequent among mitochondrial inherited diseases. Recessive RTN4IP1 gene mutations have been shown to cause isolated and syndromic optic neuropathies. To define the spectrum of clinical phenotypes associated with mutations in RTN4IP1 encoding a mitochondrial quinone oxidoreductase. This study involved 12 individuals from 11 families with severe central nervous system diseases and optic atrophy. Targeted and whole-exome sequencing were performed-at Hospital Angers (France), Institute of Neurology Milan (Italy), Imagine Institute Paris (France), Helmoltz Zentrum of Munich (Germany), and Beijing Genomics Institute (China)-to clarify the molecular diagnosis of patients. Each patient's neurologic, ophthalmologic, magnetic resonance imaging, and biochemical features were investigated. This study was conducted from May 1, 2014, to June 30, 2016. Recessive mutations in RTN4IP1 were identified. Clinical presentations ranged from isolated optic atrophy to severe encephalopathies. Of the 12 individuals in the study, 6 (50%) were male and 6 (50%) were female. They ranged in age from 5 months to 32 years. Of the 11 families, 6 (5 of whom were consanguineous) had a member or members who presented isolated optic atrophy with the already reported p.Arg103His or the novel p.Ile362Phe, p.Met43Ile, and p.Tyr51Cys amino acid changes. The 5 other families had a member or members who presented severe neurologic syndromes with a common core of symptoms, including optic atrophy, seizure, intellectual disability, growth retardation, and elevated lactate levels. Additional clinical features of those affected were deafness, abnormalities on magnetic resonance images of the brain, stridor, and abnormal electroencephalographic patterns, all of which eventually led to death before age 3 years. In these patients, novel and very rare homozygous and compound heterozygous mutations were identified that led to the absence of the protein and complex I disassembly as well as mild mitochondrial network fragmentation. A broad clinical spectrum of neurologic features, ranging from isolated optic atrophy to severe early-onset encephalopathies, is associated with RTN4IP1 biallelic mutations and should prompt RTN4IP1 screening in both syndromic neurologic presentations and nonsyndromic recessive optic neuropathies.

Use of the interRAI CHESS scale to predict mortality among persons with neurological conditions in three care settings.

PubMed

Hirdes, John P; Poss, Jeffrey W; Mitchell, Lori; Korngut, Lawrence; Heckman, George

2014-01-01

Persons with certain neurological conditions have higher mortality rates than the population without neurological conditions, but the risk factors for increased mortality within diagnostic groups are less well understood. The interRAI CHESS scale has been shown to be a strong predictor of mortality in the overall population of persons receiving health care in community and institutional settings. This study examines the performance of CHESS as a predictor of mortality among persons with 11 different neurological conditions. Survival analyses were done with interRAI assessments linked to mortality data among persons in home care (n = 359,940), complex continuing care hospitals/units (n = 88,721), and nursing homes (n = 185,309) in seven Canadian provinces/territories. CHESS was a significant predictor of mortality in all 3 care settings for the 11 neurological diagnostic groups considered after adjusting for age and sex. The distribution of CHESS scores varied between diagnostic groups and within diagnostic groups in different care settings. CHESS is a valid predictor of mortality in neurological populations in community and institutional care. It may prove useful for several clinical, administrative, policy-development, evaluation and research purposes. Because it is routinely gathered as part of normal clinical practice in jurisdictions (like Canada) that have implemented interRAI assessment instruments, CHESS can be derived without additional need for data collection.

The Infant Motor Profile: a standardized and qualitative method to assess motor behaviour in infancy.

PubMed

Heineman, Kirsten R; Bos, Arend F; Hadders-Algra, Mijna

2008-04-01

A reliable and valid instrument to assess neuromotor condition in infancy is a prerequisite for early detection of developmental motor disorders. We developed a video-based assessment of motor behaviour, the Infant Motor Profile (IMP), to evaluate motor abilities, movement variability, ability to select motor strategies, movement symmetry, and fluency. The IMP consists of 80 items and is applicable in children from 3 to 18 months. The present study aimed to test intra- and interobserver reliability and concurrent validity of the IMP with the Alberta Infant Motor Scale (AIMS) and Touwen neurological examination. The study group consisted of 40 low-risk term (median gestational age [GA] 40 wks, range 38-42 wks) and 40 high-risk preterm infants (median GA 29.6 wks, range 26-33 wks) with corrected ages 4 to 18 months (31 females, 49 males). Intra- and interobserver agreement of the IMP were satisfactory (Spearman's rho=0.9). Concurrent validity of IMP and AIMS was good (Spearman's rho=0.8, p<0.005). The IMP was able to differentiate between infants with normal neurological condition, simple minor neurological dysfunction (MND), complex MND, and abnormal neurological condition (p<0.005). This means that the IMP may be a promising tool to evaluate neurological integrity during infancy, a suggestion that needs confirmation by means of assessment of larger groups of infants with heterogeneous neurological conditions.

The history of neurocritical care.

PubMed

Wijdicks, E F M

2017-01-01

Critical care medicine came into sharp focus in the second part of the 20th century. The care of acutely ill neurologic patients in the USA may have originated in postoperative neurosurgical units, but for many years patients with neurocritical illness were admitted to intensive care units next to patients with general medical or surgical conditions. Neurologists may have had their first exposure to the complexity of neurocritical care during the poliomyelitis epidemics, but few were interested. Much later, the development of neurocritical care as a legitimate subspecialty was possible as a result of a new cadre of neurologists, with support by departments of neurosurgery and anesthesia, who appreciated their added knowledge and expertise in care of acute neurologic illness. Fellowship programs have matured in the US and training programs in certain European countries. Certification in the USA is possible through the American Academy of Neurology United Council of Neurologic Specialties. Most neurointensivists had a formal neurology training. This chapter is a brief analysis of the development of the specialty critical care neurology and how it gained strength, what it is to be a neurointensivist, what the future of care of these patients may hold, and what it takes for neurointensivists to stay exemplary. This chapter revisits some of the earlier known and previously unknown landmarks in the history of neurocritical care. © 2017 Elsevier B.V. All rights reserved.

Impaired growth and neurological abnormalities in branched-chain α-keto acid dehydrogenase kinase-deficient mice

PubMed Central

Joshi, Mandar A.; Jeoung, Nam Ho; Obayashi, Mariko; Hattab, Eyas M.; Brocken, Eric G.; Liechty, Edward A.; Kubek, Michael J.; Vattem, Krishna M.; Wek, Ronald C.; Harris, Robert A.

2006-01-01

The BCKDH (branched-chain α-keto acid dehydrogenase complex) catalyses the rate-limiting step in the oxidation of BCAAs (branched-chain amino acids). Activity of the complex is regulated by a specific kinase, BDK (BCKDH kinase), which causes inactivation, and a phosphatase, BDP (BCKDH phosphatase), which causes activation. In the present study, the effect of the disruption of the BDK gene on growth and development of mice was investigated. BCKDH activity was much greater in most tissues of BDK−/− mice. This occurred in part because the E1 component of the complex cannot be phosphorylated due to the absence of BDK and also because greater than normal amounts of the E1 component were present in tissues of BDK−/− mice. Lack of control of BCKDH activity resulted in markedly lower blood and tissue levels of the BCAAs in BDK−/− mice. At 12 weeks of age, BDK−/− mice were 15% smaller than wild-type mice and their fur lacked normal lustre. Brain, muscle and adipose tissue weights were reduced, whereas weights of the liver and kidney were greater. Neurological abnormalities were apparent by hind limb flexion throughout life and epileptic seizures after 6–7 months of age. Inhibition of protein synthesis in the brain due to hyperphosphorylation of eIF2α (eukaryotic translation initiation factor 2α) might contribute to the neurological abnormalities seen in BDK−/− mice. BDK−/− mice show significant improvement in growth and appearance when fed a high protein diet, suggesting that higher amounts of dietary BCAA can partially compensate for increased oxidation in BDK−/− mice. Disruption of the BDK gene establishes that regulation of BCKDH by phosphorylation is critically important for the regulation of oxidative disposal of BCAAs. The phenotype of the BDK−/− mice demonstrates the importance of tight regulation of oxidative disposal of BCAAs for normal growth and neurological function. PMID:16875466

Pain is the Greatest Preoperative Concern for Patients and Parents Before Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

PubMed

Chan, Priscella; Skaggs, David L; Sanders, Austin E; Villamor, Gabriela A; Choi, Paul D; Tolo, Vernon T; Andras, Lindsay M

2017-11-01

Prospective cross-sectional study. To evaluate patients' and parents' concerns so they can be addressed with appropriate preoperative counseling. Despite much research on outcomes for posterior spinal fusion (PSF) in adolescent idiopathic scoliosis (AIS), little is available about preoperative fears or concerns. Patients with AIS undergoing PSF, their parents, and surgeons were prospectively enrolled and asked to complete a survey on their fears and concerns about surgery at their preoperative appointment. Forty-eight patients and parents completed surveys. Four attending pediatric spine surgeons participated and submitted 48 responses. Mean age of patients was 14.2 years. On a scale of 0 to 10, mean level of concern reported by parents (6.9) was higher than that reported by patients (4.6). Surgeons rated the procedure's complexity on a scale of 0 to 10 and reported a mean of 5.2. Neither patients' nor parents' level of concern correlated with the surgeons' assessment of the procedure's complexity level (R = 0.19 and 0.12, P = 0.20 and P = 0.42, respectively). Top three concerns for patients were pain (25%), ability to return to activities (21%), and neurologic injury (17%). Top three concerns for parents were pain (35%), neurologic injury (21%), and amount of correction (17%). Top three concerns for surgeons were postoperative shoulder balance (44%), neurologic injury (27%), and lowest instrumented vertebrae selection (27%). Patients reported the same concerns 23% of the time as parents, and 17% of the time as surgeons. Parents and surgeons reported the same concerns 21% of the time. Pain was the greatest concern for both patients and parents but was rarely listed as a concern by surgeons. Parent and patient level of concern did not correlate to the surgeon's assessment of the procedure's complexity. Neurologic injury was a top concern for all groups, but otherwise there was little overlap between physician, patient, and parent concerns. 3.

Pattern and predictors of neurological morbidities among childhood cerebral malaria survivors in central Sudan.

PubMed

Mergani, Adil; Khamis, Ammar H; Fatih Hashim, E L; Gumma, Mohamed; Awadelseed, Bella; Elwali, Nasr Eldin M A; Haboor, Ali Babikir

2015-09-01

Cerebral malaria is considered a leading cause of neuro-disability in sub-Saharan Africa among children and about 25% of survivors have long-term neurological and cognitive deficits or epilepsy. Their development was reported to be associated with protracted seizures, deep and prolonged coma. The study was aimed to determine the discharge pattern and to identify potential and informative predictors of neurological sequelae at discharge, complicating childhood cerebral malaria in central Sudan. A cross-sectional prospective study was carried out during malaria transmission seasons from 2000 to 2004 in Wad Medani, Sinnar and Singa hospitals, central Sudan. Children suspected of having cerebral malaria were examined and diagnosed by a Pediatrician for clinical, laboratory findings and any neurological complications. Univariate and multiple regression model analysis were performed to evaluate the association of clinical and laboratory findings with occurrence of neurological complications using the SPSS. Out of 940 examined children, only 409 were diagnosed with cerebral malaria with a mean age of 6.1 ± 3.3 yr. The mortality rate associated with the study was 14.2% (58) and 18.2% (64) of survivors (351) had neurological sequelae. Abnormal posture, either decerebration or decortication, focal convulsion and coma duration of >48 h were significant predictors for surviving from cerebral malaria with a neurological sequelae in children from central Sudan by Univariate analysis. Multiple logistic regression model fitting these variables, revealed 39.6% sensitivity for prediction of childhood cerebral malaria survivors with neurological sequelae (R² = 0.396; p=0.001). Neurological sequelae are common due to childhood cerebral malaria in central Sudan. Their prediction at admission, clinical presentation and laboratory findings may guide clinical intervention and proper management that may decrease morbidity and improve CM consequences.

Medical students' experience of emotions and success in neurological studies - What do they tell us?

PubMed

Ansakorpi, Hanna; Sumelahti, Marja-Liisa; Kaasila, Raimo

2017-04-04

There is a need to develop effective educational experience in neurology to improve the students' skills in diagnosing and managing patients with neurological symptoms or disease. The aim of this study was to investigate the medical students' attitudes and emotions towards neurology before and after the four week clinical course at two Finnish Universities in order to find elements to improve effective learning by decreasing the emotional stress in medical studies. In this two-stage study, 58 medical students participated in an internet survey with open-ended questions after completing a clinical neurology course. In the content analysis of this survey 20 students (35%) were identified with negative anticipation towards neurology before undertaking the clinical neurology course. In the second phase of the study, the narrative analysis method was used to analyse the face-to-face interviews. Two of these interviews are described in this paper and represent cases who expressed negative emotions in both online survey and narrative interview. According to the content analysis, the principal emotions that were experienced at the beginning of the clinical neurology course were insecurity about personal performance (n = 19, 95%) anxiety (n = 9, 45%) and fear (n = 6, 30%). During the course the combined negative emotions (insecurity, anxiety, and fear) decreased in 80% of students (16/20 cases), remained unchanged in 15% (3/20) and could not be evaluated in 1 (5%) case. The main reasons for the observed negative anticipation were the complexity of neurology and challenges in the interpretation of clinical findings. Based on content analysis and narratives, elements that were evaluated as the most significant contributors in reducing this included small group teaching with real patients, teachers' expertise and the increase in self-confidence. Teaching with appropriate didactic methodology and feedback, and plenty of practical training can improve effective learning in neurology. We suggest that the pedagogic competence of the clinical teacher influences a student's motivation and proficiency and reduce stress in neurology-related learning tasks.

Follow the Reader: An Effective Strategy to Support Students Reading More Complex Text

ERIC Educational Resources Information Center

Klvacek, Michelle L.; Monroe, Eula Ewing; Wilcox, Brad; Hall-Kenyon, Kendra M.; Morrison, Timothy G.

2017-01-01

This article describes how one second-grade teacher implemented Follow the Reader, her term for dyad reading. Common Core expects students to read increasingly complex texts. Teachers can implement dyad reading with this end in mind. It is a modified version of the neurological impress method in which a lead reader and an assisted reader sit side…

Time-based partitioning model for predicting neurologically favorable outcome among adults with witnessed bystander out-of-hospital CPA.

PubMed

Abe, Toshikazu; Tokuda, Yasuharu; Cook, E Francis

2011-01-01

Optimal acceptable time intervals from collapse to bystander cardiopulmonary resuscitation (CPR) for neurologically favorable outcome among adults with witnessed out-of-hospital cardiopulmonary arrest (CPA) have been unclear. Our aim was to assess the optimal acceptable thresholds of the time intervals of CPR for neurologically favorable outcome and survival using a recursive partitioning model. From January 1, 2005 through December 31, 2009, we conducted a prospective population-based observational study across Japan involving consecutive out-of-hospital CPA patients (N = 69,648) who received a witnessed bystander CPR. Of 69,648 patients, 34,605 were assigned to the derivation data set and 35,043 to the validation data set. Time factors associated with better outcomes: the better outcomes were survival and neurologically favorable outcome at one month, defined as category one (good cerebral performance) or two (moderate cerebral disability) of the cerebral performance categories. Based on the recursive partitioning model from the derivation dataset (n = 34,605) to predict the neurologically favorable outcome at one month, 5 min threshold was the acceptable time interval from collapse to CPR initiation; 11 min from collapse to ambulance arrival; 18 min from collapse to return of spontaneous circulation (ROSC); and 19 min from collapse to hospital arrival. Among the validation dataset (n = 35,043), 209/2,292 (9.1%) in all patients with the acceptable time intervals and 1,388/2,706 (52.1%) in the subgroup with the acceptable time intervals and pre-hospital ROSC showed neurologically favorable outcome. Initiation of CPR should be within 5 min for obtaining neurologically favorable outcome among adults with witnessed out-of-hospital CPA. Patients with the acceptable time intervals of bystander CPR and pre-hospital ROSC within 18 min could have 50% chance of neurologically favorable outcome.

Could Sirtuin Activities Modify ALS Onset and Progression?

PubMed

Tang, Bor Luen

2017-10-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a complex etiology. Sirtuins have been implicated as disease-modifying factors in several neurological disorders, and in the past decade, attempts have been made to check if manipulating Sirtuin activities and levels could confer benefit in terms of neuroprotection and survival in ALS models. The efforts have largely focused on mutant SOD1, and while limited in scope, the results were largely positive. Here, the body of work linking Sirtuins with ALS is reviewed, with discussions on how Sirtuins and their activities may impact on the major etiological mechanisms of ALS. Moving forward, it is important that the potentially beneficial effect of Sirtuins in ALS disease onset and progression are assessed in ALS models with TDP-43, FUS, and C9orf72 mutations.

Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations from the 2015 Strategic Planning Conference

PubMed Central

Sahin, Mustafa; Henske, Elizabeth P.; Manning, Brendan D.; Ess, Kevin C.; Bissler, John J.; Klann, Eric; Kwiatkowski, David J.; Roberds, Steven L.; Silva, Alcino J.; Hillaire-Clarke, Coryse St.; Young, Lisa R.; Zervas, Mark; Mamounas, Laura A.

2016-01-01

On March 10–12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland to assess progress and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis (http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm). In addition to the National Institute of Neurological Disorders and Stroke and Tuberous Sclerosis Alliance, participants in the strategic planning effort and workshop included representatives from six other Institutes of the National Institutes of Health, the Department of Defense Tuberous Sclerosis Complex Research Program and a broad cross-section of basic scientists and clinicians with expertise in tuberous sclerosis complex along with representatives from the pharmaceutical industry. This review summarizes outcomes from the extensive pre-meeting deliberations and final workshop recommendations, and includes: 1) progress in the field since publication of the initial 2003 research plan for tuberous sclerosis complex; 2) the key gaps, needs and challenges that hinder progress in tuberous sclerosis complex research; and 3) a new set of research priorities along with specific recommendations for addressing the major challenges in each priority area. The new research plan is organized around both short-term and long-term goals with the expectation that progress toward specific objectives can be achieved within a five- to ten-year timeframe. PMID:27267556

The Influence of Acute Hyperglycemia in an Animal Model of Lacunar Stroke That Is Induced by Artificial Particle Embolization

PubMed Central

Tsai, Ming-Jun; Lin, Ming-Wei; Huang, Yaw-Bin; Kuo, Yu-Min; Tsai, Yi-Hung

2016-01-01

Animal and clinical studies have revealed that hyperglycemia during ischemic stroke increases the stroke's severity and the infarct size in clinical and animal studies. However, no conclusive evidence demonstrates that acute hyperglycemia worsens post-stroke outcomes and increases infarct size in lacunar stroke. In this study, we developed a rat model of lacunar stroke that was induced via the injection of artificial embolic particles during full consciousness. We then used this model to compare the acute influence of hyperglycemia in lacunar stroke and diffuse infarction, by evaluating neurologic behavior and the rate, size, and location of the infarction. The time course of the neurologic deficits was clearly recorded from immediately after induction to 24 h post-stroke in both types of stroke. We found that acute hyperglycemia aggravated the neurologic deficit in diffuse infarction at 24 h after stroke, and also aggravated the cerebral infarct. Furthermore, the infarct volumes of the basal ganglion, thalamus, hippocampus, and cerebellum but not the cortex were positively correlated with serum glucose levels. In contrast, acute hyperglycemia reduced the infarct volume and neurologic symptoms in lacunar stroke within 4 min after stroke induction, and this effect persisted for up to 24 h post-stroke. In conclusion, acute hyperglycemia aggravated the neurologic outcomes in diffuse infarction, although it significantly reduced the size of the cerebral infarct and improved the neurologic deficits in lacunar stroke. PMID:27226775

Pilot of integrated, colocated neurology in a primary care medical home.

PubMed

Young, Nathan P; Elrashidi, Muhamad Y; Crane, Sarah J; Ebbert, Jon O

2017-06-01

Novel health care delivery models are needed to reduce health care use while delivering effective and safe care. We developed a model of a neurologist integrated and colocated in primary care leveraging "curbside," electronic, and traditional consultations. Our objective was to examine the impact on health care resource use of diagnostic testing and referrals for face-to-face neurological consultation and adverse outcomes associated with electronic and curbside consultations. Consecutive patients from December 1, 2014, to March 13, 2015, were included in the analysis about whom contact was made between a primary care clinician and a colocated neurologist. Over 3.5 months of the pilot, 359 unique patients generated 429 consultations (179 curbsides, 68 electronic consultations, and 182 face-to-face visits). The integrated model resulted in avoidance of 78 face-to-face tertiary neurology consultations, 39 brain magnetic resonance imaging, 50 electromyograms, and 53 other advanced imaging studies. Earlier curbside consultation may have prevented unnecessary testing or face-to-face tertiary neurology consultations in 40 (22%) patients. Earlier face-to-face consultation may have avoided expensive testing in 31 (17%) patients. No cases met criteria for an adverse outcome. The number of referrals to tertiary neurology declined by 64%, and the total number of face-to-face visits per month declined by 25%. Colocated neurology in a primary care medical home offers a promising intervention to deliver high-value care. © 2016 John Wiley & Sons, Ltd.

Determining the Roles of Inositol Trisphosphate Receptors in Neurodegeneration: Interdisciplinary Perspectives on a Complex Topic.

PubMed

Takada, Silvia Honda; Ikebara, Juliane Midori; de Sousa, Erica; Cardoso, Débora Sterzeck; Resende, Rodrigo Ribeiro; Ulrich, Henning; Rückl, Martin; Rüdiger, Sten; Kihara, Alexandre Hiroaki

2017-11-01

It is well known that calcium (Ca 2+ ) is involved in the triggering of neuronal death. Ca 2+ cytosolic levels are regulated by Ca 2+ release from internal stores located in organelles, such as the endoplasmic reticulum. Indeed, Ca 2+ transit from distinct cell compartments follows complex dynamics that are mediated by specific receptors, notably inositol trisphosphate receptors (IP3Rs). Ca 2+ release by IP3Rs plays essential roles in several neurological disorders; however, details of these processes are poorly understood. Moreover, recent studies have shown that subcellular location, molecular identity, and density of IP3Rs profoundly affect Ca 2+ transit in neurons. Therefore, regulation of IP3R gene products in specific cellular vicinities seems to be crucial in a wide range of cellular processes from neuroprotection to neurodegeneration. In this regard, microRNAs seem to govern not only IP3Rs translation levels but also subcellular accumulation. Combining new data from molecular cell biology with mathematical modelling, we were able to summarize the state of the art on this topic. In addition to presenting how Ca 2+ dynamics mediated by IP3R activation follow a stochastic regimen, we integrated a theoretical approach in an easy-to-apply, cell biology-coherent fashion. Following the presented premises and in contrast to previously tested hypotheses, Ca 2+ released by IP3Rs may play different roles in specific neurological diseases, including Alzheimer's disease and Parkinson's disease.

Coping, adapting or self-managing - what is the difference? A concept review based on the neurological literature.

PubMed

Audulv, Åsa; Packer, Tanya; Hutchinson, Susan; Roger, Kerstin S; Kephart, George

2016-11-01

The aim of this study was to report: (1) an analysis of the concepts of coping, adaptation and self-management in the context of managing a neurological condition; and (2) the overlap between the concepts. The three concepts are often confused or used interchangeably. Understanding similarities and differences between concepts will avoid misunderstandings in care. The varied and often unpredictable symptoms and degenerative nature of neurological conditions make this an ideal population in which to examine the concepts. Concept analysis. Articles were extracted from a large literature review about living with a neurological condition. The original searches were conducted using SCOPUS, EMBASE, CINAHL and Psych INFO. Seventy-seven articles met the inclusion criteria of: (1) original article concerning coping, adaptation or self-management of a neurological condition; (2) written in English; and (3) published between 1999-2011. The concepts were examined according to Morse's concept analysis method; structural elements were then compared. Coping and adaptation to a neurological condition showed statistically significant overlap with a common focus on internal management. In contrast, self-management appears to focus on disease-controlling and health-related management strategies. Coping appears to be the most mature concept, whereas self-management is least coherent in definition and application. All three concepts are relevant for people with neurological conditions. Healthcare teams need to be cautious when using these terms to avoid miscommunication and to ensure clients have access to all needed interventions. Viewing the three concepts as a complex whole may be more aligned with client experience. © 2016 John Wiley & Sons Ltd.

Complex bilobular, bisaccular, and broad-neck microsurgical aneurysm formation in the rabbit bifurcation model for the study of upcoming endovascular techniques.

PubMed

Marbacher, S; Erhardt, S; Schläppi, J-A; Coluccia, D; Remonda, L; Fandino, J; Sherif, C

2011-04-01

Despite rapid advances in the development of materials and techniques for endovascular intracranial aneurysm treatment, occlusion of large broad-neck aneurysms remains a challenge. Animal models featuring complex aneurysm architecture are needed to test endovascular innovations and train interventionalists. Eleven adult female New Zealand rabbits were assigned to 3 experimental groups. Complex bilobular, bisaccular, and broad-neck venous pouch aneurysms were surgically formed at an artificially created bifurcation of both CCAs. Three and 5 weeks postoperatively, the rabbits underwent 2D-DSA and CE-3D-MRA, respectively. Mortality was 0%. We observed no neurologic, respiratory, or gastrointestinal complications. The aneurysm patency rate was 91% (1 aneurysm thrombosis). There was 1 postoperative aneurysm hemorrhage (9% morbidity). The mean aneurysm volumes were 176.9 ± 63.6 mm(3), 298.6 ± 75.2 mm(3), and 183.4 ± 72.4 mm(3) in bilobular, bisaccular, and broad-neck aneurysms, respectively. The mean operation time was 245 minutes (range, 175-290 minutes). An average of 27 ± 4 interrupted sutures (range, 21-32) were needed to create the aneurysms. This study demonstrates the feasibility of creating complex venous pouch bifurcation aneurysms in the rabbit with low morbidity, mortality, and high short-term aneurysm patency. The necks, domes, and volumes of the bilobular, bisaccular, and broad-neck aneurysms created are larger than those previously described. These new complex aneurysm formations are a promising tool for in vivo animal testing of new endovascular devices.

The beneficial role of Naringin- a citrus bioflavonoid, against oxidative stress-induced neurobehavioral disorders and cognitive dysfunction in rodents: A systematic review and meta-analysis.

PubMed

Viswanatha, Gollapalle Lakshminarayanashastry; Shylaja, H; Moolemath, Yogananda

2017-10-01

Naringin is a bioflavonoid, very abundantly found in citrus species. In literature, naringin has been scientifically well documented for its beneficial effects in various neurological disorders. In this systematic review and meta-analysis, we have made an attempt to correlate the protective role of naringin against oxidative stress-induced neurological disorders in rodents. The systematic search was performed using electronic databases; the search was mainly focused on the role of naringin in oxidative stress-induced neuropathological conditions in rodents. While, the meta-analysis was performed on the effect of naringin on oxidative stress markers [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH), lipid peroxidation (LPO)], nitrite, mitochondrial complexes (I to IV) and enzymes (acetylcholinesterase, Na + -K + -ATPase, Ca 2+ -ATPase, and Mg 2+ -ATPase) in the rodent brain. The data was analyzed using Review Manager Software. Based on the inclusion and exclusion criteria, twenty studies were selected. The meta-analysis revealed that, naringin could significantly inhibit various physical and chemical stimuli- induced neurological perturbances in the rodent brain, mediated through oxidative stress. Further, naringin also significantly restored the levels of all the oxidative stress markers (oxidative, nitrosative, enzymes, and mitochondrial complexes) in different parts of the rodent brain. This systematic review and meta-analysis supports the available scientific evidence on the beneficial role of naringin in the management of various neurological ailments. However, further studies involving human subjects is recommended to establish the safety and therapeutic efficacy in humans. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Reelin Regulates the Maturation of Dendritic Spines, Synaptogenesis and Glial Ensheathment of Newborn Granule Cells.

PubMed

Bosch, Carles; Masachs, Nuria; Exposito-Alonso, David; Martínez, Albert; Teixeira, Cátia M; Fernaud, Isabel; Pujadas, Lluís; Ulloa, Fausto; Comella, Joan X; DeFelipe, Javier; Merchán-Pérez, Angel; Soriano, Eduardo

2016-10-17

The extracellular protein Reelin has an important role in neurological diseases, including epilepsy, Alzheimer's disease and psychiatric diseases, targeting hippocampal circuits. Here we address the role of Reelin in the development of synaptic contacts in adult-generated granule cells (GCs), a neuronal population that is crucial for learning and memory and implicated in neurological and psychiatric diseases. We found that the Reelin pathway controls the shapes, sizes, and types of dendritic spines, the complexity of multisynaptic innervations and the degree of the perisynaptic astroglial ensheathment that controls synaptic homeostasis. These findings show a pivotal role of Reelin in GC synaptogenesis and provide a foundation for structural circuit alterations caused by Reelin deregulation that may occur in neurological and psychiatric disorders. © The Author 2016. Published by Oxford University Press.

Neurological and neurocognitive functions from intrauterine methylmercury exposure.

PubMed

Yorifuji, Takashi; Kado, Yoko; Diez, Midory Higa; Kishikawa, Toshihiro; Sanada, Satoshi

2016-05-03

In the 1950s, large-scale food poisoning caused by methylmercury was identified in Minamata, Japan. Although severe intrauterine exposure cases (ie, congenital Minamata disease patients) are well known, possible impacts of methylmercury exposure in utero among residents, which is likely at lower levels than in congenital Minamata disease patients, are rarely explored. In 2014, the authors examined neurological and neurocognitive functions among 18 exposed participants in Minamata, focusing on fine motor, visuospatial construction, and executive functions. More than half of the participants had some fine motor and coordination difficulties. In addition, several participants had lower performance for neurocognitive function tests (the Rey-Osterrieth Complex Figure test and Keio version of the Wisconsin card sorting test). These deficits imply diffuse brain damage. This study suggests possible neurological and neurocognitive impacts of prenatal exposure to methylmercury among exposed residents of Minamata.

Is it possible to revive the flagging interest in thermography for neurology?

NASA Astrophysics Data System (ADS)

Stulin, Igor D.

1993-11-01

The paper describes the results of twenty-years of experience in applying thermography (thermal imaging) in routine and urgent neurology, based on the study of more than ten thousand patients. Stress is laid on the fact that thermography is of great significance for diagnosing dextrocerebral hemorrhagic insult with a manifestation of pronounced hemihypothermia in the paralyzed limbs, identifying paraorbital hyperthermia on the side of rhinogenous cerebral abscess, for instrumental registration of transitory heat-up of the nasolabial region in the case of patients suffering from hypertensive nasal bleeding. Much attention is given to diagnosis of intra- and extracerebral phlebopathy in urgent neurology -- early diagnosis of iatrogenic catheterization phlebitis, interference with the venous return in the paralyzed lower limb. The novelty here is the employment of telethermography for complex diagnosis of cerebral death.

Neurological function, information-motivation-behavioral skills factors, and risk behaviors among HIV-positive alcohol users.

PubMed

Malow, Robert M; Dévieux, Jessy G; Stein, Judith A; Rosenberg, Rhonda; Lerner, Brenda G; Attonito, Jennifer; Villalba, Karina

2012-11-01

The purpose of this study was to examine neurological impairment in combination with information-motivation-behavioral skills (IMB) variables. The study tests the role of IMB variables as mediators of antecedent variables of demographics, life stress, social support, and neurological impairment with outcome measures of HIV preventive and risk behaviors in a sample of HIV-positive, alcohol-using adults (n = 250) with a history of alcohol abuse/dependence. Neurological impairment was measured with the Color Trails Test (CTT). Average performance on the CTT by the sample was substantially worse than established norms. In a directional latent variable model, neurological impairment directly predicted lower transmission knowledge scores and poorer performance on an observational condom skills assessment. Greater neurological impairment was significantly associated with greater age. Future interventions geared toward HIV+ adults who use alcohol should take into consideration HIV-related and age-related neurological functioning which may impede the facilitation of safe sex behaviors.

Latent Growth Modeling of nursing care dependency of acute neurological inpatients.

PubMed

Piredda, M; Ghezzi, V; De Marinis, M G; Palese, A

2015-01-01

Longitudinal three-time point study, addressing how neurological adult patient care dependency varies from the admission time to the 3rd day of acute hospitalization. Nursing care dependency was measured with the Care Dependency Scale (CDS) and a Latent Growth Modeling approach was used to analyse the CDS trend in 124 neurosurgical and stroke inpatients. Care dependence followed a decreasing linear trend. Results can help nurse-managers planning an appropriate amount of nursing care for acute neurological patients during their initial stage of hospitalization. Further studies are needed aimed at investigating the determinants of nursing care dependence during the entire in-hospital stay.

Viral infection leading to brain dysfunction: more prevalent than appreciated?

PubMed Central

van den Pol, Anthony N.

2009-01-01

Virus infections of the brain can lead to transient or permanent neurologic or psychiatric dysfunction. Some of the complexities in establishing the causal role of viruses in brain disease are explored here. PMID:19840542

Adult Hip Flexion Contracture due to Neurological Disease: A New Treatment Protocol—Surgical Treatment of Neurological Hip Flexion Contracture

PubMed Central

Nicodemo, Alberto; Arrigoni, Chiara; Bersano, Andrea; Massè, Alessandro

2014-01-01

Congenital, traumatic, or extrinsic causes can lead people to paraplegia; some of these are potentially; reversible and others are not. Paraplegia can couse hip flexion contracture and, consequently, pressure sores, scoliosis, and hyperlordosis; lumbar and groin pain are strictly correlated. Scientific literature contains many studies about children hip flexion related to neurological diseases, mainly caused by cerebral palsy; only few papers focus on this complication in adults. In this study we report our experience on surgical treatment of adult hip flexion contracture due to neurological diseases; we have tried to outline an algorithm to choose the best treatment avoiding useless or too aggressive therapies. We present 5 cases of adult hips flexion due to neurological conditions treated following our algorithm. At 1-year-follow-up all patients had a good clinical outcome in terms of hip range of motion, pain and recovery of walking if possible. In conclusion we think that this algorithm could be a good guideline to treat these complex cases even if we need to treat more patients to confirm this theory. We believe also that postoperation physiotherapy it is useful in hip motility preservation, improvement of muscular function, and walking ability recovery when possible. PMID:24707293

Adult Hip Flexion Contracture due to Neurological Disease: A New Treatment Protocol-Surgical Treatment of Neurological Hip Flexion Contracture.

PubMed

Nicodemo, Alberto; Arrigoni, Chiara; Bersano, Andrea; Massè, Alessandro

2014-01-01

Congenital, traumatic, or extrinsic causes can lead people to paraplegia; some of these are potentially; reversible and others are not. Paraplegia can couse hip flexion contracture and, consequently, pressure sores, scoliosis, and hyperlordosis; lumbar and groin pain are strictly correlated. Scientific literature contains many studies about children hip flexion related to neurological diseases, mainly caused by cerebral palsy; only few papers focus on this complication in adults. In this study we report our experience on surgical treatment of adult hip flexion contracture due to neurological diseases; we have tried to outline an algorithm to choose the best treatment avoiding useless or too aggressive therapies. We present 5 cases of adult hips flexion due to neurological conditions treated following our algorithm. At 1-year-follow-up all patients had a good clinical outcome in terms of hip range of motion, pain and recovery of walking if possible. In conclusion we think that this algorithm could be a good guideline to treat these complex cases even if we need to treat more patients to confirm this theory. We believe also that postoperation physiotherapy it is useful in hip motility preservation, improvement of muscular function, and walking ability recovery when possible.

Brain Dynamics: Methodological Issues and Applications in Psychiatric and Neurologic Diseases

NASA Astrophysics Data System (ADS)

Pezard, Laurent

The human brain is a complex dynamical system generating the EEG signal. Numerical methods developed to study complex physical dynamics have been used to characterize EEG since the mid-eighties. This endeavor raised several issues related to the specificity of EEG. Firstly, theoretical and methodological studies should address the major differences between the dynamics of the human brain and physical systems. Secondly, this approach of EEG signal should prove to be relevant for dealing with physiological or clinical problems. A set of studies performed in our group is presented here within the context of these two problematic aspects. After the discussion of methodological drawbacks, we review numerical simulations related to the high dimension and spatial extension of brain dynamics. Experimental studies in neurologic and psychiatric disease are then presented. We conclude that if it is now clear that brain dynamics changes in relation with clinical situations, methodological problems remain largely unsolved.

Xenon Blocks Neuronal Injury Associated with Decompression

PubMed Central

Blatteau, Jean-Eric; David, Hélène N.; Vallée, Nicolas; Meckler, Cedric; Demaistre, Sebastien; Lambrechts, Kate; Risso, Jean-Jacques; Abraini, Jacques H.

2015-01-01

Despite state-of-the-art hyperbaric oxygen (HBO) treatment, about 30% of patients suffering neurologic decompression sickness (DCS) exhibit incomplete recovery. Since the mechanisms of neurologic DCS involve ischemic processes which result in excitotoxicity, it is likely that HBO in combination with an anti-excitotoxic treatment would improve the outcome in patients being treated for DCS. Therefore, in the present study, we investigated the effect of the noble gas xenon in an ex vivo model of neurologic DCS. Xenon has been shown to provide neuroprotection in multiple models of acute ischemic insults. Fast decompression compared to slow decompression induced an increase in lactate dehydrogenase (LDH), a well-known marker of sub-lethal cell injury. Post-decompression administration of xenon blocked the increase in LDH release induced by fast decompression. These data suggest that xenon could be an efficient additional treatment to HBO for the treatment of neurologic DCS. PMID:26469983

Xenon Blocks Neuronal Injury Associated with Decompression.

PubMed

Blatteau, Jean-Eric; David, Hélène N; Vallée, Nicolas; Meckler, Cedric; Demaistre, Sebastien; Lambrechts, Kate; Risso, Jean-Jacques; Abraini, Jacques H

2015-10-15

Despite state-of-the-art hyperbaric oxygen (HBO) treatment, about 30% of patients suffering neurologic decompression sickness (DCS) exhibit incomplete recovery. Since the mechanisms of neurologic DCS involve ischemic processes which result in excitotoxicity, it is likely that HBO in combination with an anti-excitotoxic treatment would improve the outcome in patients being treated for DCS. Therefore, in the present study, we investigated the effect of the noble gas xenon in an ex vivo model of neurologic DCS. Xenon has been shown to provide neuroprotection in multiple models of acute ischemic insults. Fast decompression compared to slow decompression induced an increase in lactate dehydrogenase (LDH), a well-known marker of sub-lethal cell injury. Post-decompression administration of xenon blocked the increase in LDH release induced by fast decompression. These data suggest that xenon could be an efficient additional treatment to HBO for the treatment of neurologic DCS.

Interview: the National Institute of Neurological Diseases and Stroke/American Epilepsy Society benchmarks and research priorities for epilepsy research.

PubMed

Lowenstein, Daniel H

2011-10-01

Daniel H Lowenstein, MD, is the Robert B and Ellinor Aird Professor and Vice-Chairman of Neurology, Director of the Epilepsy Center, and Director of Physician-Scientist Education and Training at the University of California, San Francisco (UCSF). He received his BA in Mathematics from the University of Colorado and MD from Harvard Medical School. He completed his neurology residency training at UCSF. Dr Lowenstein is a clinician-scientist who has studied both basic science and clinical aspects of epilepsy. In recent years, he has been an organizer of a large-scale, international effort to study the complex genetics of epilepsy, known as the Epilepsy Phenome/Genome Project. He has been actively involved in advancing the cause of epilepsy at the national and international level. Dr Lowenstein served as President of the American Epilepsy Society from 2003 to 2004 and the National Institute of Neurological Diseases and Stroke (NINDS) Advisory Council from 2000 to 2004, and has overseen the development of the NINDS Epilepsy Research Benchmarks since their inception in 2000.

Diagnostic tools of early brain disturbances in an asymptomatic neonate with maple syrup urine disease.

PubMed

Terek, Demet; Koroglu, Ozge; Yalaz, Mehmet; Gokben, Sarenur; Calli, Cem; Coker, Mahmut; Kultursay, Nilgun

2013-08-01

Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder resulting from the defective activity of branched-chain 2-ketoacid dehydrogenase complex. Routine screening of newborn with tandem mass spectroscopy on the third day of life may detect elevated branched-chain amino acids in blood before the appearance of encephalopathic symptoms in MSUD cases. If undiagnosed by such a routine screening test, patients often present with encephalopathy and seizures. Clinical neurologic examination is supplemented by electroencephalography and imaging. Here, we report abnormal amplitude-integrated electroencephalography, electroencephalography, magnetic resonance imaging, and magnetic resonance imaging spectroscopy findings in a neurologically asymptomatic male newborn who was diagnosed with MSUD at the third week of life. These neurologic disturbances disappeared at the fourth month of life with appropriate special diet. Therefore, even in already asymptomatic cases, early neurologic deterioration of brain metabolism and structure can be detected with these early laboratory findings, indicating the importance of early diagnosis and management. Patients may also benefit from these investigations during the follow-up period. Georg Thieme Verlag KG Stuttgart · New York.

Translational neurophysiology in sheep: measuring sleep and neurological dysfunction in CLN5 Batten disease affected sheep

PubMed Central

Perentos, Nicholas; Martins, Amadeu Q.; Watson, Thomas C.; Bartsch, Ullrich; Mitchell, Nadia L.; Palmer, David N.; Jones, Matthew W.

2015-01-01

Creating valid mouse models of slowly progressing human neurological diseases is challenging, not least because the short lifespan of rodents confounds realistic modelling of disease time course. With their large brains and long lives, sheep offer significant advantages for translational studies of human disease. Here we used normal and CLN5 Batten disease affected sheep to demonstrate the use of the species for studying neurological function in a model of human disease. We show that electroencephalography can be used in sheep, and that longitudinal recordings spanning many months are possible. This is the first time such an electroencephalography study has been performed in sheep. We characterized sleep in sheep, quantifying characteristic vigilance states and neurophysiological hallmarks such as sleep spindles. Mild sleep abnormalities and abnormal epileptiform waveforms were found in the electroencephalographies of Batten disease affected sheep. These abnormalities resemble the epileptiform activity seen in children with Batten disease and demonstrate the translational relevance of both the technique and the model. Given that both spontaneous and engineered sheep models of human neurodegenerative diseases already exist, sheep constitute a powerful species in which longitudinal in vivo studies can be conducted. This will advance our understanding of normal brain function and improve our capacity for translational research into neurological disorders. PMID:25724202

Microphysiological Human Brain and Neural Systems-on-a-Chip: Potential Alternatives to Small Animal Models and Emerging Platforms for Drug Discovery and Personalized Medicine.

PubMed

Haring, Alexander P; Sontheimer, Harald; Johnson, Blake N

2017-06-01

Translational challenges associated with reductionist modeling approaches, as well as ethical concerns and economic implications of small animal testing, drive the need for developing microphysiological neural systems for modeling human neurological diseases, disorders, and injuries. Here, we provide a comprehensive review of microphysiological brain and neural systems-on-a-chip (NSCs) for modeling higher order trajectories in the human nervous system. Societal, economic, and national security impacts of neurological diseases, disorders, and injuries are highlighted to identify critical NSC application spaces. Hierarchical design and manufacturing of NSCs are discussed with distinction for surface- and bulk-based systems. Three broad NSC classes are identified and reviewed: microfluidic NSCs, compartmentalized NSCs, and hydrogel NSCs. Emerging areas and future directions are highlighted, including the application of 3D printing to design and manufacturing of next-generation NSCs, the use of stem cells for constructing patient-specific NSCs, and the application of human NSCs to 'personalized neurology'. Technical hurdles and remaining challenges are discussed. This review identifies the state-of-the-art design methodologies, manufacturing approaches, and performance capabilities of NSCs. This work suggests NSCs appear poised to revolutionize the modeling of human neurological diseases, disorders, and injuries.

Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells

PubMed Central

Mungenast, Alison E.; Siegert, Sandra; Tsai, Li-Huei

2018-01-01

In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer’s disease (AD) have been often failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells. In this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD. PMID:26657644

Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells.

PubMed

Mungenast, Alison E; Siegert, Sandra; Tsai, Li-Huei

2016-06-01

In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer's disease (AD) have been failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells. In this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas9 will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

NASA Astrophysics Data System (ADS)

Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

2015-11-01

Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.

Mass Spectrometry Strategies for Clinical Metabolomics and Lipidomics in Psychiatry, Neurology, and Neuro-Oncology

PubMed Central

Wood, Paul L

2014-01-01

Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites. Conceptual and financial factors contribute to the generation of statistically under-powered clinical studies, whereas bioinformatics issues result in the publication of a large number of unidentified metabolites. The path forward in this field involves targeted metabolomics analyses of large control and patient populations to define both the normal range of a defined metabolite and the potential heterogeneity (eg, bimodal) in complex patient populations. This approach requires that metabolomics research groups, in addition to developing a number of analytical platforms, build sufficient chemistry resources to supply the analytical standards required for absolute metabolite quantitation. Examples of metabolomics evaluations of sulfur amino-acid metabolism in psychiatry, neurology, and neuro-oncology and of lipidomics in neurology will be reviewed. PMID:23842599

Mass spectrometry strategies for clinical metabolomics and lipidomics in psychiatry, neurology, and neuro-oncology.

PubMed

Wood, Paul L

2014-01-01

Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites. Conceptual and financial factors contribute to the generation of statistically under-powered clinical studies, whereas bioinformatics issues result in the publication of a large number of unidentified metabolites. The path forward in this field involves targeted metabolomics analyses of large control and patient populations to define both the normal range of a defined metabolite and the potential heterogeneity (eg, bimodal) in complex patient populations. This approach requires that metabolomics research groups, in addition to developing a number of analytical platforms, build sufficient chemistry resources to supply the analytical standards required for absolute metabolite quantitation. Examples of metabolomics evaluations of sulfur amino-acid metabolism in psychiatry, neurology, and neuro-oncology and of lipidomics in neurology will be reviewed.

Integrative cortical dysfunction and pervasive motion perception deficit in fragile X syndrome.

PubMed

Kogan, C S; Bertone, A; Cornish, K; Boutet, I; Der Kaloustian, V M; Andermann, E; Faubert, J; Chaudhuri, A

2004-11-09

Fragile X syndrome (FXS) is associated with neurologic deficits recently attributed to the magnocellular pathway of the lateral geniculate nucleus. To test the hypotheses that FXS individuals 1) have a pervasive visual motion perception impairment affecting neocortical circuits in the parietal lobe and 2) have deficits in integrative neocortical mechanisms necessary for perception of complex stimuli. Psychophysical tests of visual motion and form perception defined by either first-order (luminance) or second-order (texture) attributes were used to probe early and later occipito-temporal and occipito-parietal functioning. When compared to developmental- and age-matched controls, FXS individuals displayed severe impairments in first- and second-order motion perception. This deficit was accompanied by near normal perception for first-order form stimuli but not second-order form stimuli. Impaired visual motion processing for first- and second-order stimuli suggests that both early- and later-level neurologic function of the parietal lobe are affected in Fragile X syndrome (FXS). Furthermore, this deficit likely stems from abnormal input from the magnocellular compartment of the lateral geniculate nucleus. Impaired visual form and motion processing for complex visual stimuli with normal processing for simple (i.e., first-order) form stimuli suggests that FXS individuals have normal early form processing accompanied by a generalized impairment in neurologic mechanisms necessary for integrating all early visual input.

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

PubMed Central

Li, Ying C.

2017-01-01

Presynaptic nerve terminals are highly specialized vesicle-trafficking machines. Neurotransmitter release from these terminals is sustained by constant local recycling of synaptic vesicles independent from the neuronal cell body. This independence places significant constraints on maintenance of synaptic protein complexes and scaffolds. Key events during the synaptic vesicle cycle—such as exocytosis and endocytosis—require formation and disassembly of protein complexes. This extremely dynamic environment poses unique challenges for proteostasis at synaptic terminals. Therefore, it is not surprising that subtle alterations in synaptic vesicle cycle-associated proteins directly or indirectly contribute to pathophysiology seen in several neurologic and psychiatric diseases. In contrast to the increasing number of examples in which presynaptic dysfunction causes neurologic symptoms or cognitive deficits associated with multiple brain disorders, synaptic vesicle-recycling machinery remains an underexplored drug target. In addition, irrespective of the involvement of presynaptic function in the disease process, presynaptic machinery may also prove to be a viable therapeutic target because subtle alterations in the neurotransmitter release may counter disease mechanisms, correct, or compensate for synaptic communication deficits without the need to interfere with postsynaptic receptor signaling. In this article, we will overview critical properties of presynaptic release machinery to help elucidate novel presynaptic avenues for the development of therapeutic strategies against neurologic and neuropsychiatric disorders. PMID:28265000

The child neurology clinical workforce in 2015: Report of the AAP/CNS Joint Taskforce.

PubMed

Kang, Peter B; Bale, James F; Mintz, Mark; Joshi, Sucheta M; Gilbert, Donald L; Radabaugh, Carrie; Ruch-Ross, Holly

2016-09-27

More than a decade has passed since the last major workforce survey of child neurologists in the United States; thus, a reassessment of the child neurology workforce is needed, along with an inaugural assessment of a new related field, neurodevelopmental disabilities. The American Academy of Pediatrics and the Child Neurology Society conducted an electronic survey in 2015 of child neurologists and neurodevelopmental disabilities specialists. The majority of respondents participate in maintenance of certification, practice in academic medical centers, and offer subspecialty care. EEG reading and epilepsy care are common subspecialty practice areas, although many child neurologists have not had formal training in this field. In keeping with broader trends, medical school debts are substantially higher than in the past and will often take many years to pay off. Although a broad majority would choose these fields again, there are widespread dissatisfactions with compensation and benefits given the length of training and the complexity of care provided, and frustrations with mounting regulatory and administrative stresses that interfere with clinical practice. Although not unique to child neurology and neurodevelopmental disabilities, such issues may present barriers for the recruitment of trainees into these fields. Creative approaches to enhance the recruitment of the next generation of child neurologists and neurodevelopmental disabilities specialists will benefit society, especially in light of all the exciting new treatments under development for an array of chronic childhood neurologic disorders. © 2016 American Academy of Neurology.

Psychophysical and perceptual performance in a simulated-scotoma model of human eye injury

NASA Astrophysics Data System (ADS)

Brandeis, R.; Egoz, I.; Peri, D.; Sapiens, N.; Turetz, J.

2008-02-01

Macular scotomas, affecting visual functioning, characterize many eye and neurological diseases like AMD, diabetes mellitus, multiple sclerosis, and macular hole. In this work, foveal visual field defects were modeled, and their effects were evaluated on spatial contrast sensitivity and a task of stimulus detection and aiming. The modeled occluding scotomas, of different size, were superimposed on the stimuli presented on the computer display, and were stabilized on the retina using a mono Purkinje Eye-Tracker. Spatial contrast sensitivity was evaluated using square-wave grating stimuli, whose contrast thresholds were measured using the method of constant stimuli with "catch trials". The detection task consisted of a triple conjunctive visual search display of: size (in visual angle), contrast and background (simple, low-level features vs. complex, high-level features). Search/aiming accuracy as well as R.T. measures used for performance evaluation. Artificially generated scotomas suppressed spatial contrast sensitivity in a size dependent manner, similar to previous studies. Deprivation effect was dependent on spatial frequency, consistent with retinal inhomogeneity models. Stimulus detection time was slowed in complex background search situation more than in simple background. Detection speed was dependent on scotoma size and size of stimulus. In contrast, visually guided aiming was more sensitive to scotoma effect in simple background search situation than in complex background. Both stimulus aiming R.T. and accuracy (precision targeting) were impaired, as a function of scotoma size and size of stimulus. The data can be explained by models distinguishing between saliency-based, parallel and serial search processes, guiding visual attention, which are supported by underlying retinal as well as neural mechanisms.

Respiratory chain complex II as general sensor for apoptosis.

PubMed

Grimm, Stefan

2013-05-01

I review here the evidence that complex II of the respiratory chain (RC) constitutes a general sensor for apoptosis induction. This concept emerged from work on neurodegenerative diseases and from recent data on metabolic alterations in cancer cells affecting the RC and in particular on mutations of complex II subunits. It is also supported by experiments with many anticancer compounds that compared the apoptosis sensitivities of complex II-deficient versus WT cells. These results are explained by the mechanistic understanding of how complex II mediates the diverse range of apoptosis signals. This protein aggregate is specifically activated for apoptosis by pH change as a common and early feature of dying cells. This leads to the dissociation of its SDHA and SDHB subunits from the remaining membrane-anchored subunits and the consequent block of it enzymatic SQR activity, while its SDH activity, which is contained in the SDHA/SDHB subcomplex, remains intact. The uncontrolled SDH activity then generates excessive amounts of reactive oxygen species for the demise of the cell. Future studies on these mitochondrial processes will help refine this model, unravel the contribution of mutations in complex II subunits as the cause of degenerative neurological diseases and tumorigenesis, and aid in discovering novel interference options. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease. Copyright © 2012 Elsevier B.V. All rights reserved.

Development and validation of the Good Outcome Following Attempted Resuscitation (GO-FAR) score to predict neurologically intact survival after in-hospital cardiopulmonary resuscitation.

PubMed

Ebell, Mark H; Jang, Woncheol; Shen, Ye; Geocadin, Romergryko G

2013-11-11

Informing patients and providers of the likelihood of survival after in-hospital cardiac arrest (IHCA), neurologically intact or with minimal deficits, may be useful when discussing do-not-attempt-resuscitation orders. To develop a simple prearrest point score that can identify patients unlikely to survive IHCA, neurologically intact or with minimal deficits. The study included 51,240 inpatients experiencing an index episode of IHCA between January 1, 2007, and December 31, 2009, in 366 hospitals participating in the Get With the Guidelines-Resuscitation registry. Dividing data into training (44.4%), test (22.2%), and validation (33.4%) data sets, we used multivariate methods to select the best independent predictors of good neurologic outcome, created a series of candidate decision models, and used the test data set to select the model that best classified patients as having a very low (<1%), low (1%-3%), average (>3%-15%), or higher than average (>15%) likelihood of survival after in-hospital cardiopulmonary resuscitation for IHCA with good neurologic status. The final model was evaluated using the validation data set. Survival to discharge after in-hospital cardiopulmonary resuscitation for IHCA with good neurologic status (neurologically intact or with minimal deficits) based on a Cerebral Performance Category score of 1. The best performing model was a simple point score based on 13 prearrest variables. The C statistic was 0.78 when applied to the validation set. It identified the likelihood of a good outcome as very low in 9.4% of patients (good outcome in 0.9%), low in 18.9% (good outcome in 1.7%), average in 54.0% (good outcome in 9.4%), and above average in 17.7% (good outcome in 27.5%). Overall, the score can identify more than one-quarter of patients as having a low or very low likelihood of survival to discharge, neurologically intact or with minimal deficits after IHCA (good outcome in 1.4%). The Good Outcome Following Attempted Resuscitation (GO-FAR) scoring system identifies patients who are unlikely to benefit from a resuscitation attempt should they experience IHCA. This information can be used as part of a shared decision regarding do-not-attempt-resuscitation orders.

Teleneurology applications: Report of the Telemedicine Work Group of the American Academy of Neurology.

PubMed

Wechsler, Lawrence R; Tsao, Jack W; Levine, Steven R; Swain-Eng, Rebecca J; Adams, Robert J; Demaerschalk, Bart M; Hess, David C; Moro, Elena; Schwamm, Lee H; Steffensen, Steve; Stern, Barney J; Zuckerman, Steven J; Bhattacharya, Pratik; Davis, Larry E; Yurkiewicz, Ilana R; Alphonso, Aimee L

2013-02-12

To review current literature on neurology telemedicine and to discuss its application to patient care, neurology practice, military medicine, and current federal policy. Review of practice models and published literature on primary studies of the efficacy of neurology telemedicine. Teleneurology is of greatest benefit to populations with restricted access to general and subspecialty neurologic care in rural areas, those with limited mobility, and those deployed by the military. Through the use of real-time audio-visual interaction, imaging, and store-and-forward systems, a greater proportion of neurologists are able to meet the demand for specialty care in underserved communities, decrease the response time for acute stroke assessment, and expand the collaboration between primary care physicians, neurologists, and other disciplines. The American Stroke Association has developed a defined policy on teleneurology, and the American Academy of Neurology and federal health care policy are beginning to follow suit. Teleneurology is an effective tool for the rapid evaluation of patients in remote locations requiring neurologic care. These underserved locations include geographically isolated rural areas as well as urban cores with insufficient available neurology specialists. With this technology, neurologists will be better able to meet the burgeoning demand for access to neurologic care in an era of declining availability. An increase in physician awareness and support at the federal and state level is necessary to facilitate expansion of telemedicine into further areas of neurology.

Brain Vulnerability to Repeated Blast Overpressure and Polytrauma

DTIC Science & Technology

2015-10-01

characterization of the mouse model of repeated blast also found no cumula- tive effect of repeated blast on cortical levels of reactive oxygen species [39]. C...overpressure in rats to investigate the cumulative effects of multiple blast exposures on neurologic status, neurobehavioral function, and brain...preclinical model of blast overpressure in rats to investigate the cumulative effects of multiple blast exposures using neurological, neurochemical

How music training enhances working memory: a cerebrocerebellar blending mechanism that can lead equally to scientific discovery and therapeutic efficacy in neurological disorders.

PubMed

Vandervert, Larry

2015-01-01

Following in the vein of studies that concluded that music training resulted in plastic changes in Einstein's cerebral cortex, controlled research has shown that music training (1) enhances central executive attentional processes in working memory, and (2) has also been shown to be of significant therapeutic value in neurological disorders. Within this framework of music training-induced enhancement of central executive attentional processes, the purpose of this article is to argue that: (1) The foundational basis of the central executive begins in infancy as attentional control during the establishment of working memory, (2) In accordance with Akshoomoff, Courchesne and Townsend's and Leggio and Molinari's cerebellar sequence detection and prediction models, the rigors of volitional control demands of music training can enhance voluntary manipulation of information in thought and movement, (3) The music training-enhanced blending of cerebellar internal models in working memory as can be experienced as intuition in scientific discovery (as Einstein often indicated) or, equally, as moments of therapeutic advancement toward goals in the development of voluntary control in neurological disorders, and (4) The blending of internal models as in (3) thus provides a mechanism by which music training enhances central executive processes in working memory that can lead to scientific discovery and improved therapeutic outcomes in neurological disorders. Within the framework of Leggio and Molinari's cerebellar sequence detection model, it is determined that intuitive steps forward that occur in both scientific discovery and during therapy in those with neurological disorders operate according to the same mechanism of adaptive error-driven blending of cerebellar internal models. It is concluded that the entire framework of the central executive structure of working memory is a product of the cerebrocerebellar system which can, through the learning of internal models, incorporate the multi-dimensional rigor and volitional-control demands of music training and, thereby, enhance voluntary control. It is further concluded that this cerebrocerebellar view of the music training-induced enhancement of central executive control in working memory provides a needed mechanism to explain both the highest level of scientific discovery and the efficacy of music training in the remediation of neurological impairments.

[Early prediction of the neurological result at 12 months in newborns at neurological risk].

PubMed

Herbón, F; Garibotti, G; Moguilevsky, J

2015-08-01

The aim of this study was to evaluate the Amiel-Tison neurological examination (AT) and cranial ultrasound at term for predicting the neurological result at 12 months in newborns with neurological risk. The study included 89 newborns with high risk of neurological damage, who were discharged from the Neonatal Intensive Care of the Hospital Zonal Bariloche, Argentina. The assessment consisted of a neurological examination and cranial ultrasound at term, and neurological examination and evaluation of development at 12 months. The sensitivity, specificity, positive and negative predictor value was calculated. The relationship between perinatal factors and neurodevelopment at 12 month of age was also calculated using logistic regression models. Seventy children completed the follow-up. At 12 months of age, 14% had an abnormal neurological examination, and 17% abnormal development. The neurological examination and the cranial ultrasound at term had low sensitivity to predict abnormal neurodevelopment. At 12 months, 93% of newborns with normal AT showed normal neurological results, and 86% normal development. Among newborns with normal cranial ultrasound the percentages were 90 and 81%, respectively. Among children with three or more perinatal risk factors, the frequency of abnormalities in the neurological response was 5.4 times higher than among those with fewer risk factors, and abnormal development was 3.5 times more frequent. The neurological examination and cranial ultrasound at term had low sensitivity but high negative predictive value for the neurodevelopment at 12 months. Three or more perinatal risk factors were associated with neurodevelopment abnormalities at 12 months of age. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Implementation of the Hammersmith Infant Neurological Exam in a High-Risk Infant Follow-Up Program

PubMed Central

Maitre, Nathalie L; Chorna, Olena; Romeo, Domenico M; Guzzetta, Andrea

2017-01-01

Background High-Risk Infant Follow-Up (HRIF) programs provide early identification and referral for treatment of neurodevelopmental delays and impairments. In these programs, a standardized neurological exam is a critical component of evaluation for clinical and research purposes. Implementation To address primary challenges of provider educational diversity and standardized documentation, we designed an approach to training and implementation of the Hammersmith Infant Neurological Exam (HINE) with pre-course materials, a workshop model and adaptation of the electronic medical record. Conclusions Provider completion and documentation of a neurologic exam were evaluated before and after HINE training. Standardized training and implementation of the HINE in a large HRIF is feasible and effective and allows for quantitative evaluation of neurological findings and developmental trajectories. PMID:27765470

Chronic pain as a manifestation of potassium channel-complex autoimmunity

PubMed Central

Lennon, Vanda A.; Aston, Paula A.; McKeon, Andrew; Pittock, Sean J.

2012-01-01

Objective: Autoantibodies targeting voltage-gated potassium channel (VGKC) complexes cause a spectrum of neuronal hyperexcitability disorders. We investigated pain as a manifestation of VGKC-complex autoimmunity. Methods: We reviewed the prevalence and characteristics of pain in VGKC-complex-immunoglobulin G (IgG)–seropositive patients in 25 months of comprehensive service testing for neural autoantibodies, subtyped positive sera for LGI1-IgG and CASPR2-IgG specificities, and reviewed pain prevalence in autoimmune control patients. Results: VGKC-complex-IgG was identified in 1,992 patients of 54,853 tested (4%). Of 316 evaluated neurologically at Mayo Clinic, 159 (50%) had pain, in isolation (28%) or with accompanying neurologic manifestations (72%), and not attributable to alternative cause. Pain was subacute in onset, chronic in course, neuropathic, nociceptive, regional, or diffuse and sometimes attributed to fibromyalgia (6%) or psychogenic cause (13%). Most patients had normal peripheral nervous system function, measured by neuropathy impairment scores and nerve conduction. Evidence of neuronal hyperexcitability (hyperhidrosis, quantitative heat-pain hyperalgesia, or electromyographic excitability) was 25-fold more common in pain patients. Pain management required multiple medications in 70% (narcotics, 30%); 13 of 16 patients reported pain relief with immunotherapy. Pain was significantly associated with CASPR2-IgG-positivity (16% positive with pain, 7% without pain; p = 0.014) but not with LGI1-IgG. Less than 10% of 167 patients with neural autoantibodies other than VGKC-complex-IgG reported pain. Conclusions: Chronic idiopathic pain is a syndromic manifestation of VGKC-complex autoimmunity. Hyperexcitability of nociceptive pathways is implicated. CASPR2-IgG significantly associates with pain, but in most patients the antigenic VGKC-complex molecule remains to be determined. VGKC-complex autoimmunity represents an important new direction for pain research and therapy. PMID:22895588

Clinical utility of seropositive voltage-gated potassium channel-complex antibody.

PubMed

Jammoul, Adham; Shayya, Luay; Mente, Karin; Li, Jianbo; Rae-Grant, Alexander; Li, Yuebing

2016-10-01

Antibodies against voltage-gated potassium channel (VGKC)-complex are implicated in the pathogenesis of acquired neuromyotonia, limbic encephalitis, faciobrachial dystonic seizure, and Morvan syndrome. Outside these entities, the clinical value of VGKC-complex antibodies remains unclear. We conducted a single-center review of patients positive for VGKC-complex antibodies over an 8-year period. Among 114 patients positive for VGKC-complex antibody, 11 (9.6%) carrying the diagnosis of limbic encephalitis (n = 9) or neuromyotonia (n = 2) constituted the classic group, and the remaining 103 cases of various neurologic and non-neurologic disorders comprised the nonclassic group. The median titer for the classic group was higher than the nonclassic group ( p < 0.0001). A total of 90.9% of the patients in the classic and 21.4% in the nonclassic group possessed high (>0.25 nM) VGKC-complex antibody levels ( p < 0.0001). A total of 75.0% of the patients in the high-level group had definite or probable autoimmune basis, while nonautoimmune disorders were seen in 75.6% of patients from the low-level group ( p < 0.0001). A total of 26.3% of patients were found with active or remote solid organ or hematologic malignancy, but no antibody titer difference was observed among subgroups of absent, active, or remote malignancy. Compared to age-matched US national census, rates of active cancer in our cohort were higher in patients older than 45 years. High VGKC-complex antibody titers are more likely found in patients with classically associated syndromes and other autoimmune conditions. Low-level VGKC-complex antibodies can be detected in nonspecific and mostly nonautoimmune disorders. The presence of VGKC-complex antibody, rather than its level, may serve as a marker of malignancy.

VGKC complex antibodies in pediatric severe acute encephalitis: a study and literature review.

PubMed

Lin, Jainn-Jim; Lin, Kuang-Lin; Hsia, Shao-Hsuan; Wang, Huei-Shyong; Chiu, Cheng-Hsun; CHEESE Study Group

2013-08-01

Antibodies to surface proteins like voltage-gated potassium channel (VGKC) complexes are increasingly found in different neurologic diseases and encephalitis in adults and recently, in children. Detecting such antibodies can help identify forms of encephalitis that may respond to immuno-therapies. However, there are few reports on VGKC complex antibodies in pediatric severe acute encephalitis. This study retrospectively reviewed antibodies to VGKC, leucine-rich glioma-inactivated 1 (Lgi1), and contactin-associated protein-like 2 (Caspr2) in 46 children with severe acute encephalitis. Published cases of VGKC complex antibodies in pediatric encephalitis in the period of 2000-2012 were also reviewed. Elevated VGKC complex antibodies (>100pM) were detected in one of the 46 children with severe acute encephalitis. The 4-year and 6-month-old girl presented with seizure and disturbed consciousness. Viral PCR/culture and serologic evidence of influenza A infection was noted. She also had complications of epilepsy, impaired cognition, and altered behavior and psychology. Antibodies to Lgi1 and Caspr2 were not detected. Ten previously published reports revealed that VGKC complex antibodies can occur in children with limbic encephalitis and acute or sub-acute encephalitis. The incidence of VGKC complex antibodies in pediatric severe acute encephalitis is not high with only one (2.2%) of 46 children in this study. And, this is the first report on the association of VGKC complex antibodies and patients with influenza A-related severe acute encephalitis. The mechanism of VGKC complex antibodies in pediatric severe acute encephalitis warrants further study. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Chronic pain as a manifestation of potassium channel-complex autoimmunity.

PubMed

Klein, Christopher J; Lennon, Vanda A; Aston, Paula A; McKeon, Andrew; Pittock, Sean J

2012-09-11

Autoantibodies targeting voltage-gated potassium channel (VGKC) complexes cause a spectrum of neuronal hyperexcitability disorders. We investigated pain as a manifestation of VGKC-complex autoimmunity. We reviewed the prevalence and characteristics of pain in VGKC-complex-immunoglobulin G (IgG)-seropositive patients in 25 months of comprehensive service testing for neural autoantibodies, subtyped positive sera for LGI1-IgG and CASPR2-IgG specificities, and reviewed pain prevalence in autoimmune control patients. VGKC-complex-IgG was identified in 1,992 patients of 54,853 tested (4%). Of 316 evaluated neurologically at Mayo Clinic, 159 (50%) had pain, in isolation (28%) or with accompanying neurologic manifestations (72%), and not attributable to alternative cause. Pain was subacute in onset, chronic in course, neuropathic, nociceptive, regional, or diffuse and sometimes attributed to fibromyalgia (6%) or psychogenic cause (13%). Most patients had normal peripheral nervous system function, measured by neuropathy impairment scores and nerve conduction. Evidence of neuronal hyperexcitability (hyperhidrosis, quantitative heat-pain hyperalgesia, or electromyographic excitability) was 25-fold more common in pain patients. Pain management required multiple medications in 70% (narcotics, 30%); 13 of 16 patients reported pain relief with immunotherapy. Pain was significantly associated with CASPR2-IgG-positivity (16% positive with pain, 7% without pain; p = 0.014) but not with LGI1-IgG. Less than 10% of 167 patients with neural autoantibodies other than VGKC-complex-IgG reported pain. Chronic idiopathic pain is a syndromic manifestation of VGKC-complex autoimmunity. Hyperexcitability of nociceptive pathways is implicated. CASPR2-IgG significantly associates with pain, but in most patients the antigenic VGKC-complex molecule remains to be determined. VGKC-complex autoimmunity represents an important new direction for pain research and therapy.

Clinical utility of seropositive voltage-gated potassium channel–complex antibody

PubMed Central

Jammoul, Adham; Shayya, Luay; Mente, Karin; Li, Jianbo; Rae-Grant, Alexander

2016-01-01

Abstract Background: Antibodies against voltage-gated potassium channel (VGKC)–complex are implicated in the pathogenesis of acquired neuromyotonia, limbic encephalitis, faciobrachial dystonic seizure, and Morvan syndrome. Outside these entities, the clinical value of VGKC-complex antibodies remains unclear. Methods: We conducted a single-center review of patients positive for VGKC-complex antibodies over an 8-year period. Results: Among 114 patients positive for VGKC-complex antibody, 11 (9.6%) carrying the diagnosis of limbic encephalitis (n = 9) or neuromyotonia (n = 2) constituted the classic group, and the remaining 103 cases of various neurologic and non-neurologic disorders comprised the nonclassic group. The median titer for the classic group was higher than the nonclassic group (p < 0.0001). A total of 90.9% of the patients in the classic and 21.4% in the nonclassic group possessed high (>0.25 nM) VGKC-complex antibody levels (p < 0.0001). A total of 75.0% of the patients in the high-level group had definite or probable autoimmune basis, while nonautoimmune disorders were seen in 75.6% of patients from the low-level group (p < 0.0001). A total of 26.3% of patients were found with active or remote solid organ or hematologic malignancy, but no antibody titer difference was observed among subgroups of absent, active, or remote malignancy. Compared to age-matched US national census, rates of active cancer in our cohort were higher in patients older than 45 years. Conclusions: High VGKC-complex antibody titers are more likely found in patients with classically associated syndromes and other autoimmune conditions. Low-level VGKC-complex antibodies can be detected in nonspecific and mostly nonautoimmune disorders. The presence of VGKC-complex antibody, rather than its level, may serve as a marker of malignancy. PMID:27847683

RNA structures as mediators of neurological diseases and as drug targets

PubMed Central

Bernat, Viachaslau; Disney, Matthew D.

2015-01-01

RNAs adopt diverse folded structures that are essential for function and thus play critical roles in cellular biology. A striking example of this is the ribosome, a complex, three-dimensionally folded macromolecular machine that orchestrates protein synthesis. Advances in RNA biochemistry, structural and molecular biology, and bioinformatics have revealed other non-coding RNAs whose functions are dictated by their structure. It is not surprising that aberrantly folded RNA structures contribute to disease. In this review, we provide a brief introduction into RNA structural biology and then describe how RNA structures function in cells and cause or contribute to neurological disease. Finally, we highlight successful applications of rational design principles to provide chemical probes and lead compounds targeting structured RNAs. Based on several examples of well-characterized RNA-driven neurological disorders, we demonstrate how designed small molecules can facilitate study of RNA dysfunction, elucidating previously unknown roles for RNA in disease, and provide lead therapeutics. PMID:26139368

Neurology or rehabilitation medicine?

PubMed Central

McLellan, D L

1992-01-01

Rehabilitation is a process of active change by which a person who is disabled acquires and uses the knowledge and skills necessary for optimal physical, psychological and social function. Rehabilitation medicine is now established in Britain as a specialty concerned primarily with three groups: 1) those with multiple disability; 2) disabled people undergoing personal or social transitions, for example, school leavers; and 3) those with disabilities requiring complex technical or medical solutions. Rehabilitation medicine is distinguished from traditional clinical neurology by its emphasis on teamwork and on the analysis and reduction of disability rather than the diagnosis and treatment of impairment. Both neurology and rehabilitation medicine are dwarfed by the size of the problems they are expected to overcome and there is no justification for competition between the two specialties. The training of neurologists requires fundamental changes if they are to be equipped to assist rehabilitation effectively and contribute to the scientific development of the subject. PMID:1532980

Hereditary spastic paraplegia.

PubMed

Blackstone, Craig

2018-01-01

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurologic disorders with the common feature of prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. The HSPs exist not only in "pure" forms but also in "complex" forms that are associated with additional neurologic and extraneurologic features. The HSPs are among the most genetically diverse neurologic disorders, with well over 70 distinct genetic loci, for which about 60 mutated genes have already been identified. Numerous studies elucidating the molecular pathogenesis underlying HSPs have highlighted the importance of basic cellular functions - especially membrane trafficking, mitochondrial function, organelle shaping and biogenesis, axon transport, and lipid/cholesterol metabolism - in axon development and maintenance. An encouragingly small number of converging cellular pathogenic themes have been identified for the most common HSPs, and some of these pathways present compelling targets for future therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

[In-patient (early) rehabilitation].

PubMed

Wallesch, Claus-W; Lautenschläger, Sindy

2017-04-01

It is difficult to develop the financing and hospital provision of interventions for early rehabilitation within the diagnosis-related group (DRG) system. In addition to a range of partially rehabilitative complex interventions, the system recognizes three main forms of early rehabilitative interventions: geriatric, neurological/neurosurgical, and interdisciplinary and others. In this article, the appropriate definitions and cost-effectiveness of these procedures are analyzed and compared. The early rehabilitative interventions are characterized by constant cooperation in the therapeutic team, especially neurological early rehabilitation through the incorporation of nursing as a therapeutic profession. Whereas geriatric and neurological early rehabilitation are reflected in the DRG system, the former provided in many general hospitals and the latter mainly in specialized institutions, interdisciplinary early rehabilitation has only occasionally been represented in the DRG system so far. If all acute in-patients who require early rehabilitation should receive such an intervention, an additional fee must be implemented for this this interdisciplinary service.

Generation of Xeroderma Pigmentosum-A Patient-Derived Induced Pluripotent Stem Cell Line for Use As Future Disease Model.

PubMed

Ohnishi, Hiroe; Kawasaki, Takashi; Deguchi, Tomonori; Yuba, Shunsuke

2015-08-01

Xeroderma pigmentosum group A (XP-A) is a genetic disorder in which there is an abnormality in nucleotide excision repair that causes hypersensitivity to sunlight and multiple skin cancers. The development of central and peripheral neurological disorders not correlated to ultraviolet light exposure is associated with XP-A. The genes responsible for XP-A have been identified and a XPA knockout mouse has been generated. These knockout mice exhibit cutaneous symptoms, but they do not show neurological disorders. The mechanism of pathogenesis of neurological disorders is still unclear and therapeutic methods have not been established. Therefore, we generated XP-A patient-derived human induced pluripotent stem cells (XPA-iPSCs) to produce in vitro models of neurological disorders. We obtained iPSC lines from fibroblasts of two patients carrying different mutations. Drugs screened using XPA-iPSC lines can be helpful for treating XP-A patients in Japan. Additionally, we revealed that these iPSCs have the potential to differentiate into neural lineage cells, including dopaminergic neurons, which decrease in XP-A patients. Our results indicate that expression of the normal XPA gene without mutations is not required for generation of iPSCs and differentiation of iPSCs into neural lineage cells. XPA-iPSCs may become useful models that clarify our understanding of neurological pathogenesis and help to establish therapeutic methods.

Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference.

PubMed

Sahin, Mustafa; Henske, Elizabeth P; Manning, Brendan D; Ess, Kevin C; Bissler, John J; Klann, Eric; Kwiatkowski, David J; Roberds, Steven L; Silva, Alcino J; Hillaire-Clarke, Coryse St; Young, Lisa R; Zervas, Mark; Mamounas, Laura A

2016-07-01

On March 10 to March 12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland, to assess progress and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis (http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm). In addition to the National Institute of Neurological Disorders and Stroke and Tuberous Sclerosis Alliance, participants in the strategic planning effort and workshop included representatives from six other Institutes of the National Institutes of Health, the Department of Defense Tuberous Sclerosis Complex Research Program, and a broad cross-section of basic scientists and clinicians with expertise in tuberous sclerosis complex along with representatives from the pharmaceutical industry. Here we summarize the outcomes from the extensive premeeting deliberations and final workshop recommendations, including (1) progress in the field since publication of the initial 2003 research plan for tuberous sclerosis complex, (2) the key gaps, needs, and challenges that hinder progress in tuberous sclerosis complex research, and (3) a new set of research priorities along with specific recommendations for addressing the major challenges in each priority area. The new research plan is organized around both short-term and long-term goals with the expectation that progress toward specific objectives can be achieved within a five to ten year time frame. Copyright © 2016 Elsevier Inc. All rights reserved.

Complexity and multifractality of neuronal noise in mouse and human hippocampal epileptiform dynamics

NASA Astrophysics Data System (ADS)

Serletis, Demitre; Bardakjian, Berj L.; Valiante, Taufik A.; Carlen, Peter L.

2012-10-01

Fractal methods offer an invaluable means of investigating turbulent nonlinearity in non-stationary biomedical recordings from the brain. Here, we investigate properties of complexity (i.e. the correlation dimension, maximum Lyapunov exponent, 1/fγ noise and approximate entropy) and multifractality in background neuronal noise-like activity underlying epileptiform transitions recorded at the intracellular and local network scales from two in vitro models: the whole-intact mouse hippocampus and lesional human hippocampal slices. Our results show evidence for reduced dynamical complexity and multifractal signal features following transition to the ictal epileptiform state. These findings suggest that pathological breakdown in multifractal complexity coincides with loss of signal variability or heterogeneity, consistent with an unhealthy ictal state that is far from the equilibrium of turbulent yet healthy fractal dynamics in the brain. Thus, it appears that background noise-like activity successfully captures complex and multifractal signal features that may, at least in part, be used to classify and identify brain state transitions in the healthy and epileptic brain, offering potential promise for therapeutic neuromodulatory strategies for afflicted patients suffering from epilepsy and other related neurological disorders. This paper is based on chapter 5 of Serletis (2010 PhD Dissertation Department of Physiology, Institute of Biomaterials and Biomedical Engineering, University of Toronto).

A cellular star atlas: using astrocytes from human pluripotent stem cells for disease studies

PubMed Central

Krencik, Robert; Ullian, Erik M.

2013-01-01

What roles do astrocytes play in human disease?This question remains unanswered for nearly every human neurological disorder. Yet, because of their abundance and complexity astrocytes can impact neurological function in many ways. The differentiation of human pluripotent stem cells (hPSCs) into neuronal and glial subtypes, including astrocytes, is becoming routine, thus their use as tools for modeling neurodevelopment and disease will provide one important approach to answer this question. When designing experiments, careful consideration must be given to choosing paradigms for differentiation, maturation, and functional analysis of these temporally asynchronous cellular populations in culture. In the case of astrocytes, they display heterogeneous characteristics depending upon species of origin, brain region, developmental stage, environmental factors, and disease states, all of which may render experimental results highly variable. In this review, challenges and future directions are discussed for using hPSC-derived astroglial progenitors and mature astrocytes for neurodevelopmental studies with a focus on exploring human astrocyte effects upon neuronal function. As new technologies emerge to measure the functions of astrocytes in vitro and in vivo, there is also a need for a standardized source of human astrocytes that are most relevant to the diseases of interest. PMID:23503583

Female children with incarcerated adult family members at risk for lifelong neurological decline.

PubMed

Brewer-Smyth, Kathleen; Pohlig, Ryan T; Bucurescu, Gabriel

2016-07-01

A secondary analysis of data from adult female prison inmates in the mid-Atlantic United States defined relationships between having incarcerated adult family members during childhood and neurological outcomes. Of 135 inmates, 99 (60%) had one or more incarcerated adult family members during childhood. Regression analyses revealed that having incarcerated adult family members was related to greater frequency and severity of childhood abuse and higher incidence of neurological deficits in adulthood, especially related to traumatic brain injuries, compared to those without incarcerated adult family members. Along with being role models, adult family members impact the neurological health of children throughout their life-span.

Female children with incarcerated adult family members at risk for life-long neurological decline

PubMed Central

Brewer-Smyth, Kathleen; Pohlig, Ryan T.; Bucurescu, Gabriel

2016-01-01

A secondary analysis of data from adult female prison inmates in the mid-Atlantic United States defined relationships between having incarcerated adult family members during childhood and neurological outcomes. Of 135 inmates, 99(73%) had one or more incarcerated adult family members during childhood. Regression analyses revealed that having incarcerated adult family members was related to greater frequency and severity of childhood abuse and higher incidence of neurological deficits in adulthood, especially related to traumatic brain injuries, compared to those without incarcerated adult family members. Along with being role models, adult family members impact the neurological health of children throughout their lifespan. PMID:26788781

A 3D human neural cell culture system for modeling Alzheimer’s disease

PubMed Central

Kim, Young Hye; Choi, Se Hoon; D’Avanzo, Carla; Hebisch, Matthias; Sliwinski, Christopher; Bylykbashi, Enjana; Washicosky, Kevin J.; Klee, Justin B.; Brüstle, Oliver; Tanzi, Rudolph E.; Kim, Doo Yeon

2015-01-01

Stem cell technologies have facilitated the development of human cellular disease models that can be used to study pathogenesis and test therapeutic candidates. These models hold promise for complex neurological diseases such as Alzheimer’s disease (AD) because existing animal models have been unable to fully recapitulate all aspects of pathology. We recently reported the characterization of a novel three-dimensional (3D) culture system that exhibits key events in AD pathogenesis, including extracellular aggregation of β-amyloid and accumulation of hyperphosphorylated tau. Here we provide instructions for the generation and analysis of 3D human neural cell cultures, including the production of genetically modified human neural progenitor cells (hNPCs) with familial AD mutations, the differentiation of the hNPCs in a 3D matrix, and the analysis of AD pathogenesis. The 3D culture generation takes 1–2 days. The aggregation of β-amyloid is observed after 6-weeks of differentiation followed by robust tau pathology after 10–14 weeks. PMID:26068894

Nucleotide excision repair deficient mouse models and neurological disease

PubMed Central

Niedernhofer, Laura J.

2008-01-01

Nucleotide excision repair (NER) is a highly conserved mechanism to remove helix-distorting DNA base damage. A major substrate for NER is DNA damage caused by environmental genotoxins, most notably ultraviolet radiation. Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy are three human diseases caused by inherited defects in NER. The symptoms and severity of these diseases vary dramatically, ranging from profound developmental delay to cancer predisposition and accelerated aging. All three syndromes include neurological disease, indicating an important role for NER in protecting against spontaneous DNA damage as well. To study the pathophysiology caused by DNA damage, numerous mouse models of NER deficiency were generated by knocking-out genes required for NER or knocking-in disease-causing human mutations. This review explores the utility of these mouse models to study neurological disease caused by NER deficiency. PMID:18272436

Pediatric neurocritical care: a neurology consultation model and implication for education and training.

PubMed

LaRovere, Kerri L; Graham, Robert J; Tasker, Robert C

2013-03-01

Pediatric neurocritical care is developing specialization within pediatric intensive care and pediatric neurology practice, and the evolving clinical expertise has relevance to training and education in both fields. We describe a model of service using a Neurology Consulting Team in the intensive care unit setting. Medical records were reviewed from a 32-month cohort of Neurology Consulting Team referrals. Six hundred eighty-nine (19%) of 3719 patients admitted to the intensive care unit were assessed by the team. The most common diagnostic categories were seizures, neurosurgical, cerebrovascular, or central nervous system infection. Fifty-seven percent (350 of 615 patients) required mechanical ventilation. Cohort mortality was 7% vs 2% for the general intensive care population (P < 0.01). The team provided 4592 initial and subsequent consultations; on average there were five to six new consultations per week. Each patient had a median of two (interquartile range, 1 to 6) consultations during admission. Three quarters of the cohort required neurodiagnostic investigation (1625 tests), with each patient undergoing a median of two (range, 0 to 3) studies. Taken together, the subset of pediatric intensive care unit patients undergoing neurology consultation, investigation, and management represents a significant practice experience for trainees, which has implications for future curriculum development in both pediatric critical care medicine and pediatric neurology. Copyright © 2013 Elsevier Inc. All rights reserved.

Duration of Untreated Cardiac Arrest and Clinical Relevance of Animal Experiments: The Relationship Between the "No-Flow" Duration and the Severity of Post-Cardiac Arrest Syndrome in a Porcine Model.

PubMed

Babini, Giovanni; Grassi, Luigi; Russo, Ilaria; Novelli, Deborah; Boccardo, Antonio; Luciani, Anita; Fumagalli, Francesca; Staszewsky, Lidia; Fiordaliso, Fabio; De Maglie, Marcella; Salio, Monica; Zani, Davide D; Letizia, Teresa; Masson, Serge; Luini, Mario V; Pravettoni, Davide; Scanziani, Eugenio; Latini, Roberto; Ristagno, Giuseppe

2018-02-01

The study investigated the effect of untreated cardiac arrest (CA), that is, "no-flow" time, on postresuscitation myocardial and neurological injury, and survival in a pig model to identify an optimal duration that adequately reflects the most frequent clinical scenario. An established model of myocardial infarction followed by CA and cardiopulmonary resuscitation was used. Twenty-two pigs were subjected to three no-flow durations: short (8-10 min), intermediate (12-13 min), and long (14-15 min). Left ventricular ejection fraction (LVEF) was assessed together with thermodilution cardiac output (CO) and high sensitivity cardiac troponin T (hs-cTnT). Neurological impairment was evaluated by neurological scores, serum neuron specific enolase (NSE), and histopathology. More than 60% of animals survived when the duration of CA was ≤13 min, compared to only 20% for a duration ≥14 min. Neuronal degeneration and neurological scores showed a trend toward a worse recovery for longer no-flow durations. No animals achieved a good neurological recovery for a no-flow ≥14 min, in comparison to a 56% for a duration ≤13 min (P = 0.043). Serum NSE levels significantly correlated with the no-flow duration (r = 0.892). Longer durations of CA were characterized by lower LVEF and CO compared to shorter durations (P < 0.05). The longer was the no-flow time, the higher was the number of defibrillations delivered (P = 0.043). The defibrillations delivered significantly correlated with LVEF and plasma hs-cTnT. Longer no-flow durations caused greater postresuscitation myocardial and neurological dysfunction and reduced survival. An untreated CA of 12-13 min may be an optimal choice for a clinically relevant model.

Philadelphia Infirmary for Nervous Diseases: America's original model of institutional neurology.

PubMed

Pappert, E J

1998-06-01

The role and contributions of the Philadelphia Orthopedic Hospital and Infirmary for Nervous Diseases in the development of neurology in 19th-century America are described. American neurology was largely born during the Civil War through the work of S.W. Mitchell at Turner's Lane Hospital. With the closing of this military facility, the United States was left without an institution dedicated to neurologic research and the treatment of nervous system diseases. Nineteenth century archival data, including original Trustees' minutes, annual board of managers reports, patient case books, and published research from the Philadelphia Orthopedic Hospital and Infirmary for Nervous Diseases were studied. The Philadelphia Orthopedic Hospital and Infirmary for Nervous Diseases promoted the development of neurology in the United States through three main activities. First, it offered patients with primary nervous system diseases, arthritis, and orthopedic disorders specialized care that was unavailable at medical universities. Second, its medical staff, especially Mitchell, provided opportunities for advanced neurologic education. Postgraduate physicians interested in neurologic disease attended formal lectures and directly participated in the operation of outpatient clinics and inpatient rounds. Finally, its formalized record system in the form of case books facilitated neurologic research. These records formed the basis of landmark publications by Mitchell, Sinkler, Osler, and others on rest therapy, spastic palsies, chorea, and other topics. As America's first and comprehensive peacetime neurologic facility, the Philadelphia Orthopedic Hospital and Infirmary for Nervous Diseases fostered the evolution of neurology as a separate, viable specialty in the post-Civil War period and provided a particular focus for the study of interactions among orthopedic, nutritional, and neurologic disorders.

The child neurology clinical workforce in 2015

PubMed Central

Bale, James F.; Mintz, Mark; Joshi, Sucheta M.; Gilbert, Donald L.; Radabaugh, Carrie; Ruch-Ross, Holly

2016-01-01

Objectives: More than a decade has passed since the last major workforce survey of child neurologists in the United States; thus, a reassessment of the child neurology workforce is needed, along with an inaugural assessment of a new related field, neurodevelopmental disabilities. Methods: The American Academy of Pediatrics and the Child Neurology Society conducted an electronic survey in 2015 of child neurologists and neurodevelopmental disabilities specialists. Results: The majority of respondents participate in maintenance of certification, practice in academic medical centers, and offer subspecialty care. EEG reading and epilepsy care are common subspecialty practice areas, although many child neurologists have not had formal training in this field. In keeping with broader trends, medical school debts are substantially higher than in the past and will often take many years to pay off. Although a broad majority would choose these fields again, there are widespread dissatisfactions with compensation and benefits given the length of training and the complexity of care provided, and frustrations with mounting regulatory and administrative stresses that interfere with clinical practice. Conclusions: Although not unique to child neurology and neurodevelopmental disabilities, such issues may present barriers for the recruitment of trainees into these fields. Creative approaches to enhance the recruitment of the next generation of child neurologists and neurodevelopmental disabilities specialists will benefit society, especially in light of all the exciting new treatments under development for an array of chronic childhood neurologic disorders. PMID:27566740

Teaching neurology to medical students with a simplified version of team-based learning.

PubMed

Brich, Jochen; Jost, Meike; Brüstle, Peter; Giesler, Marianne; Rijntjes, Michel

2017-08-08

To compare the effect of a simplified version of team-based learning (sTBL), an active learning/small group instructional strategy, with that of the traditionally used small group interactive seminars on the acquisition of knowledge and clinical reasoning (CR) skills. Third- and fourth-year medical students (n = 122) were randomly distributed into 2 groups. A crossover design was used in which 2 neurologic topics were taught by sTBL and 2 by small group interactive seminars. Knowledge was assessed with a multiple-choice question examination (MCQE), CR skills with a key feature problem examination (KFPE). Questionnaires were used for further methodologic evaluation. No group differences were found in the MCQE results. sTBL instruction of the topic "acute altered mental status" was associated with a significantly better student performance in the KFPE ( p = 0.008), with no differences in the other 3 topics covered. Although both teaching methods were highly rated by the students, a clear majority voted for sTBL as their preferred future teaching method. sTBL served as an equivalent alternative to small group interactive seminars for imparting knowledge and teaching CR skills, and was particularly advantageous for teaching CR in the setting of a complex neurologic topic. Furthermore, students reported a strong preference for the sTBL approach, making it a promising tool for effectively teaching neurology. © 2017 American Academy of Neurology.

Neuropharmacological Potential and Delivery Prospects of Thymoquinone for Neurological Disorders

PubMed Central

Cho, Duk-Yeon; Ezazul Haque, Md.; Kim, In-Su; Ganesan, Palanivel

2018-01-01

Thymoquinone (TQ) is an active ingredient isolated from Nigella sativa and has various pharmacological activities, such as protection against oxidative stress, inflammation, and infections. In addition, it might be a potential neuropharmacological agent because it exhibits versatile potential for attenuating neurological impairments. It features greater beneficial effects in toxin-induced neuroinflammation and neurotoxicity. In various models of neurological disorders, it demonstrates emergent functions, including safeguarding various neurodegenerative diseases and other neurological diseases, such as stroke, schizophrenia, and epilepsy. TQ also has potential effects in trauma mediating and chemical-, radiation-, and drug-induced central nervous system injuries. Considering the pharmacokinetic limitations, research has concentrated on different TQ novel formulations and delivery systems. Here, we visualize the neuropharmacological potential, challenges, and delivery prospects of TQ, specifically focusing on neurological disorders along with its chemistry, pharmacokinetics, and toxicity. PMID:29743967

Establishing an academic neurology specialty program: experiences over a five-year period.

PubMed

Packer, Rebecca A; Lambrechts, Nicolaas E; Bentley, R Timothy

2012-01-01

Veterinary neurology is an expanding specialty field. At the time of this writing, 13 out of 33 (40%) US and Canadian veterinary colleges, and many more veterinary colleges outside of North America, had no active clinical neurology service. New academic programs will likely be established to fill this need, often starting with a single neurologist. Establishing a neurology service with one founding faculty member can be accomplished by developing the program in phases and creating a support network that optimizes faculty strengths and interests. Such an approach allows for the gradual expansion of services and staffing in a manageable way to ultimately provide a full-service program. A description of this development process at Purdue University School of Veterinary Medicine is presented as a case study and model for the establishment of other neurology or specialty services.

The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders

PubMed Central

Stafstrom, Carl E.; Rho, Jong M.

2012-01-01

Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more “natural” treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component. PMID:22509165

Detection of LGI1 and CASPR2 antibodies with a commercial cell-based assay in patients with very high VGKC-complex antibody levels.

PubMed

Yeo, T; Chen, Z; Chai, J Y H; Tan, K

2017-07-15

The presence of VGKC-complex antibodies, without LGI1/CASPR2 antibodies, as a standalone marker for neurological autoimmunity remains controversial. Additionally, the lack of an unequivocal VGKC-complex antibody cut-off level defining neurological autoimmunity makes it important to test for monospecific antibodies. We aim to determine the performance characteristics of a commercial assay (Euroimmun, Lübeck, Germany) for LGI1/CASPR2 antibody detection in patients with very high VGKC-complex antibody levels and report their clinico-serological associations. We identified 8 patients in our cohort with the highest VGKC-complex antibody levels (median 2663.5pM, range 933-6730pM) with VGKC-complex antibody related syndromes (Group A). Two other groups were identified; 1 group with suspected neuronal surface antibody syndromes and negative for VGKC-complex antibodies (Group B, n=8), and another group with cerebellar ataxia and negative for onconeuronal antibodies (Group C, n=8). Seven out of 8 patients (87.5%) in Group A had LGI1 and/or CASPR2 antibodies. One Group B patient had LGI1 antibodies but was negative on re-testing with a live cell assay. No Group C patients had monospecific antibodies. Inter-rater reliability was high; combining Groups A and B patients, the kappa statistic was 0.87 and 1.0 for LGI1 and CASPR2 antibodies respectively. We demonstrated that a high proportion of patients with very high VGKC-complex antibody levels and relevant clinical syndromes have LGI1 and/or CASPR2 antibodies detected by the commercial assay. Our findings lend support to the use of the assay for rapid and reliable detection of LGI1 and CASPR2 antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

Prenatal Antecedents of Newborn Neurological Maturation

ERIC Educational Resources Information Center

DiPietro, Janet A.; Kivlighan, Katie T.; Costigan, Kathleen A.; Rubin, Suzanne E.; Shiffler, Dorothy E.; Henderson, Janice L.; Pillion, Joseph P.

2010-01-01

Fetal neurobehavioral development was modeled longitudinally using data collected at weekly intervals from 24 to 38 weeks gestation in a sample of 112 healthy pregnancies. Predictive associations between 3 measures of fetal neurobehavioral functioning and their developmental trajectories to neurological maturation in the first weeks after birth…

Risk factors for early post-operative neurological deterioration in dogs undergoing a cervical dorsal laminectomy or hemilaminectomy: 100 cases (2002-2014).

PubMed

Taylor-Brown, F E; Cardy, T J A; Liebel, F X; Garosi, L; Kenny, P J; Volk, H A; De Decker, S

2015-12-01

Early post-operative neurological deterioration is a well-known complication following dorsal cervical laminectomies and hemilaminectomies in dogs. This study aimed to evaluate potential risk factors for early post-operative neurological deterioration following these surgical procedures. Medical records of 100 dogs that had undergone a cervical dorsal laminectomy or hemilaminectomy between 2002 and 2014 were assessed retrospectively. Assessed variables included signalment, bodyweight, duration of clinical signs, neurological status before surgery, diagnosis, surgical site, type and extent of surgery and duration of procedure. Outcome measures were neurological status immediately following surgery and duration of hospitalisation. Univariate statistical analysis was performed to identify variables to be included in a multivariate model. Diagnoses included osseous associated cervical spondylomyelopathy (OACSM; n = 41), acute intervertebral disk extrusion (IVDE; 31), meningioma (11), spinal arachnoid diverticulum (10) and vertebral arch anomalies (7). Overall 54% (95% CI 45.25-64.75) of dogs were neurologically worse 48 h post-operatively. Multivariate statistical analysis identified four factors significantly related to early post-operative neurological outcome. Diagnoses of OACSM or meningioma were considered the strongest variables to predict early post-operative neurological deterioration, followed by higher (more severely affected) neurological grade before surgery and longer surgery time. This information can aid in the management of expectations of clinical staff and owners with dogs undergoing these surgical procedures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Teleneurology applications

PubMed Central

Wechsler, Lawrence R.; Tsao, Jack W.; Levine, Steven R.; Swain-Eng, Rebecca J.; Adams, Robert J.; Demaerschalk, Bart M.; Hess, David C.; Moro, Elena; Schwamm, Lee H.; Steffensen, Steve; Stern, Barney J.; Zuckerman, Steven J.; Bhattacharya, Pratik; Davis, Larry E.; Yurkiewicz, Ilana R.; Alphonso, Aimee L.

2013-01-01

Objective: To review current literature on neurology telemedicine and to discuss its application to patient care, neurology practice, military medicine, and current federal policy. Methods: Review of practice models and published literature on primary studies of the efficacy of neurology telemedicine. Results: Teleneurology is of greatest benefit to populations with restricted access to general and subspecialty neurologic care in rural areas, those with limited mobility, and those deployed by the military. Through the use of real-time audio-visual interaction, imaging, and store-and-forward systems, a greater proportion of neurologists are able to meet the demand for specialty care in underserved communities, decrease the response time for acute stroke assessment, and expand the collaboration between primary care physicians, neurologists, and other disciplines. The American Stroke Association has developed a defined policy on teleneurology, and the American Academy of Neurology and federal health care policy are beginning to follow suit. Conclusions: Teleneurology is an effective tool for the rapid evaluation of patients in remote locations requiring neurologic care. These underserved locations include geographically isolated rural areas as well as urban cores with insufficient available neurology specialists. With this technology, neurologists will be better able to meet the burgeoning demand for access to neurologic care in an era of declining availability. An increase in physician awareness and support at the federal and state level is necessary to facilitate expansion of telemedicine into further areas of neurology. PMID:23400317

Remote care of a patient with stroke in rural Trinidad: use of telemedicine to optimise global neurological care.

PubMed

Reyes, Antonio Jose; Ramcharan, Kanterpersad

2016-08-02

We report a patient driven home care system that successfully assisted 24/7 with the management of a 68-year-old woman after a stroke-a global illness. The patient's caregiver and physician used computer devices, smartphones and internet access for information exchange. Patient, caregiver, family and physician satisfaction, coupled with outcome and cost were indictors of quality of care. The novelty of this basic model of teleneurology is characterised by implementing a patient/caregiver driven system designed to improve access to cost-efficient neurological care, which has potential for use in primary, secondary and tertiary levels of healthcare in rural and underserved regions of the world. We suggest involvement of healthcare stakeholders in teleneurology to address this global problem of limited access to neurological care. This model can facilitate the management of neurological diseases, impact on outcome, reduce frequency of consultations and hospitalisations, facilitate teaching of healthcare workers and promote research. 2016 BMJ Publishing Group Ltd.

Peripheral Blood Biomarkers of Disease Outcome in a Monkey Model of Rift Valley Fever Encephalitis.

PubMed

Wonderlich, Elizabeth R; Caroline, Amy L; McMillen, Cynthia M; Walters, Aaron W; Reed, Douglas S; Barratt-Boyes, Simon M; Hartman, Amy L

2018-02-01

Rift Valley Fever (RVF) is an emerging arboviral disease of livestock and humans. Although the disease is caused by a mosquito-borne virus, humans are infected through contact with, or inhalation of, virus-laden particles from contaminated animal carcasses. Some individuals infected with RVF virus (RVFV) develop meningoencephalitis, resulting in morbidity and mortality. Little is known about the pathogenic mechanisms that lead to neurologic sequelae, and thus, animal models that represent human disease are needed. African green monkeys (AGM) exposed to aerosols containing RVFV develop a reproducibly lethal neurological disease that resembles human illness. To understand the disease process and identify biomarkers of lethality, two groups of 5 AGM were infected by inhalation with either a lethal or a sublethal dose of RVFV. Divergence between lethal and sublethal infections occurred as early as 2 days postinfection (dpi), at which point CD8 + T cells from lethally infected AGM expressed activated caspase-3 and simultaneously failed to increase levels of major histocompatibility complex (MHC) class II molecules, in contrast to surviving animals. At 4 dpi, lethally infected animals failed to demonstrate proliferation of total CD4 + and CD8 + T cells, in contrast to survivors. These marked changes in peripheral blood cells occur much earlier than more-established indicators of severe RVF disease, such as granulocytosis and fever. In addition, an early proinflammatory (gamma interferon [IFN-γ], interleukin 6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1]) and antiviral (IFN-α) response was seen in survivors, while very late cytokine expression was found in animals with lethal infections. By characterizing immunological markers of lethal disease, this study furthers our understanding of RVF pathogenesis and will allow the testing of therapeutics and vaccines in the AGM model. IMPORTANCE Rift Valley Fever (RVF) is an important emerging viral disease for which we lack both an effective human vaccine and treatment. Encephalitis and neurological disease resulting from RVF lead to death or significant long-term disability for infected people. African green monkeys (AGM) develop lethal neurological disease when infected with RVF virus by inhalation. Here we report the similarities in disease course between infected AGM and humans. For the first time, we examine the peripheral immune response during the course of infection in AGM and show that there are very early differences in the immune response between animals that survive infection and those that succumb. We conclude that AGM are a novel and suitable monkey model for studying the neuropathogenesis of RVF and for testing vaccines and therapeutics against this emerging viral pathogen. Copyright © 2018 American Society for Microbiology.

Child neurology residency: system implications of new training models.

PubMed

Heiser, Karen

2012-02-01

From limitations on residents' duty hours, to ways in which outcomes are measured, changes to graduate medical education are sweeping the nation. In this issue of the journal, Gilbert and Greenwood present thoughtful, if somewhat disparate, opinions on ways to improve the educational experience of child neurology trainees. As the Designated Institutional Officer of a large children's hospital, I have focused my commentary on "the big picture." That is, what systemwide impact can changes in child neurology trainees' education have.

Development of a Sensitive DNA Assay for the AIDS Virus, HTLV-III/LAV

DTIC Science & Technology

1989-11-19

lylphadenopathy syndrome, acquired immuno- deficiency disease syndrome (AIDS)-related complex (ARC) (including night sweats, fever, diarrhea, weight loss, oral ... candidiasis ), or AIDS (including neurological disease, opportunistic infections, or malignancies) (1). A signifi- cant number of infected individuals

Cost-efficiency of specialist inpatient rehabilitation for working-aged adults with complex neurological disabilities: a multicentre cohort analysis of a national clinical data set.

PubMed

Turner-Stokes, Lynne; Williams, Heather; Bill, Alan; Bassett, Paul; Sephton, Keith

2016-02-24

To evaluate functional outcomes, care needs and cost-efficiency of specialist rehabilitation for a multicentre cohort of inpatients with complex neurological disability, comparing different diagnostic groups across 3 levels of dependency. A multicentre cohort analysis of prospectively collected clinical data from the UK Rehabilitation Outcomes Collaborative (UKROC) national clinical database, 2010-2015. All 62 specialist (levels 1 and 2) rehabilitation services in England. Working-aged adults (16-65 years) with complex neurological disability. all episodes with length of stay (LOS) 8-400 days and complete outcome measures recorded on admission and discharge. Total N=5739: acquired brain injury n=4182 (73%); spinal cord injury n=506 (9%); peripheral neurological conditions n=282 (5%); progressive conditions n=769 (13%). Specialist inpatient multidisciplinary rehabilitation. Dependency and care costs: Northwick Park Dependency Scale/Care Needs Assessment (NPDS/NPCNA). Functional independence: UK Functional Assessment Measure (UK Functional Independence Measure (FIM)+FAM). Cost-efficiency: (1) time taken to offset rehabilitation costs by savings in NPCNA-estimated costs of ongoing care, (2) FIM efficiency (FIM gain/LOS days), (3) FIM+FAM efficiency (FIM+FAM gain/LOS days). Patients were analysed in 3 groups of dependency. Mean LOS 90.1 (SD 66) days. All groups showed significant reduction in dependency between admission and discharge on all measures (paired t tests: p<0.001). Mean reduction in 'weekly care costs' was greatest in the high-dependency group at £760/week (95% CI 726 to 794)), compared with the medium-dependency (£408/week (95% CI 370 to 445)), and low-dependency (£130/week (95% CI 82 to 178)), groups. Despite longer LOS, time taken to offset the cost of rehabilitation was 14.2 (95% CI 9.9 to 18.8) months in the high-dependency group, compared with 22.3 (95% CI 16.9 to 29.2) months (medium dependency), and 27.7 (95% CI 15.9 to 39.7) months (low dependency). FIM efficiency appeared greatest in medium-dependency patients (0.54), compared with the low-dependency (0.37) and high-dependency (0.38) groups. Broadly similar patterns were seen across all 4 diagnostic groups. Specialist rehabilitation can be highly cost-efficient for all neurological conditions, producing substantial savings in ongoing care costs, especially in high-dependency patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Neurocognitive and Neuroplastic Mechanisms of Novel Clinical Signs in CRPS.

PubMed

Kuttikat, Anoop; Noreika, Valdas; Shenker, Nicholas; Chennu, Srivas; Bekinschtein, Tristan; Brown, Christopher Andrew

2016-01-01

Complex regional pain syndrome (CRPS) is a chronic, debilitating pain condition that usually arises after trauma to a limb, but its precise etiology remains elusive. Novel clinical signs based on body perceptual disturbances have been reported, but their pathophysiological mechanisms remain poorly understood. Investigators have used functional neuroimaging techniques (including MEG, EEG, fMRI, and PET) to study changes mainly within the somatosensory and motor cortices. Here, we provide a focused review of the neuroimaging research findings that have generated insights into the potential neurocognitive and neuroplastic mechanisms underlying perceptual disturbances in CRPS. Neuroimaging findings, particularly with regard to somatosensory processing, have been promising but limited by a number of technique-specific factors (such as the complexity of neuroimaging investigations, poor spatial resolution of EEG/MEG, and use of modeling procedures that do not draw causal inferences) and more general factors including small samples sizes and poorly characterized patients. These factors have led to an underappreciation of the potential heterogeneity of pathophysiology that may underlie variable clinical presentation in CRPS. Also, until now, neurological deficits have been predominantly investigated separately from perceptual and cognitive disturbances. Here, we highlight the need to identify neurocognitive phenotypes of patients with CRPS that are underpinned by causal explanations for perceptual disturbances. We suggest that a combination of larger cohorts, patient phenotyping, the use of both high temporal, and spatial resolution neuroimaging methods, and the identification of simplified biomarkers is likely to be the most fruitful approach to identifying neurocognitive phenotypes in CRPS. Based on our review, we explain how such phenotypes could be characterized in terms of hierarchical models of perception and corresponding disturbances in recurrent processing involving the somatosensory, salience and executive brain networks. We also draw attention to complementary neurological factors that may explain some CRPS symptoms, including the possibility of central neuroinflammation and neuronal atrophy, and how these phenomena may overlap but be partially separable from neurocognitive deficits.

Neurocognitive and Neuroplastic Mechanisms of Novel Clinical Signs in CRPS

PubMed Central

Kuttikat, Anoop; Noreika, Valdas; Shenker, Nicholas; Chennu, Srivas; Bekinschtein, Tristan; Brown, Christopher Andrew

2016-01-01

Complex regional pain syndrome (CRPS) is a chronic, debilitating pain condition that usually arises after trauma to a limb, but its precise etiology remains elusive. Novel clinical signs based on body perceptual disturbances have been reported, but their pathophysiological mechanisms remain poorly understood. Investigators have used functional neuroimaging techniques (including MEG, EEG, fMRI, and PET) to study changes mainly within the somatosensory and motor cortices. Here, we provide a focused review of the neuroimaging research findings that have generated insights into the potential neurocognitive and neuroplastic mechanisms underlying perceptual disturbances in CRPS. Neuroimaging findings, particularly with regard to somatosensory processing, have been promising but limited by a number of technique-specific factors (such as the complexity of neuroimaging investigations, poor spatial resolution of EEG/MEG, and use of modeling procedures that do not draw causal inferences) and more general factors including small samples sizes and poorly characterized patients. These factors have led to an underappreciation of the potential heterogeneity of pathophysiology that may underlie variable clinical presentation in CRPS. Also, until now, neurological deficits have been predominantly investigated separately from perceptual and cognitive disturbances. Here, we highlight the need to identify neurocognitive phenotypes of patients with CRPS that are underpinned by causal explanations for perceptual disturbances. We suggest that a combination of larger cohorts, patient phenotyping, the use of both high temporal, and spatial resolution neuroimaging methods, and the identification of simplified biomarkers is likely to be the most fruitful approach to identifying neurocognitive phenotypes in CRPS. Based on our review, we explain how such phenotypes could be characterized in terms of hierarchical models of perception and corresponding disturbances in recurrent processing involving the somatosensory, salience and executive brain networks. We also draw attention to complementary neurological factors that may explain some CRPS symptoms, including the possibility of central neuroinflammation and neuronal atrophy, and how these phenomena may overlap but be partially separable from neurocognitive deficits. PMID:26858626

Severe impulsiveness as the primary manifestation of multiple sclerosis in a young female.

PubMed

Lopez-Meza, Elmer; Corona-Vazquez, Teresa; Ruano-Calderon, Luis A; Ramirez-Bermudez, Jesus

2005-12-01

Severe impulsiveness in the absence of apparent neurological signs has rarely been reported as a clinical presentation of multiple sclerosis (MS). An 11-year-old female developed progressive and sustained personality disturbances including disinhibition, hypersexuality, drug abuse, aggressiveness and suicide attempts, without neurological signs. She was given several unsuccessful psychopharmacological and psychotherapeutic interventions. At age 21, a diagnosis of MS was made, confirmed by imaging, laboratory and neurophysiological studies. Although unusual, MS may produce pure neurobehavioral disturbances. In the present case, widespread demyelinization produced a complex behavioral disorder, with features compatible with orbitofrontal and Klüver-Bucy syndromes.

Spinal motor neuron involvement in a patient with homozygous PRUNE mutation.

PubMed

Iacomino, Michele; Fiorillo, Chiara; Torella, Annalaura; Severino, Mariasavina; Broda, Paolo; Romano, Catia; Falsaperla, Raffaele; Pozzolini, Giulia; Minetti, Carlo; Striano, Pasquale; Nigro, Vincenzo; Zara, Federico

2018-05-01

In the last few years, whole exome sequencing (WES) allowed the identification of PRUNE mutations in patients featuring a complex neurological phenotype characterized by severe neurodevelopmental delay, microcephaly, epilepsy, optic atrophy, and brain or cerebellar atrophy. We describe an additional patient with homozygous PRUNE mutation who presented with spinal muscular atrophy phenotype, in addition to the already known brain developmental disorder. This novel feature expands the clinical consequences of PRUNE mutations and allow to converge PRUNE syndrome with previous descriptions of neurodevelopmental/neurodegenerative disorders linked to altered microtubule dynamics. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Grid-wide neuroimaging data federation in the context of the NeuroLOG project

PubMed Central

Michel, Franck; Gaignard, Alban; Ahmad, Farooq; Barillot, Christian; Batrancourt, Bénédicte; Dojat, Michel; Gibaud, Bernard; Girard, Pascal; Godard, David; Kassel, Gilles; Lingrand, Diane; Malandain, Grégoire; Montagnat, Johan; Pélégrini-Issac, Mélanie; Pennec, Xavier; Rojas Balderrama, Javier; Wali, Bacem

2010-01-01

Grid technologies are appealing to deal with the challenges raised by computational neurosciences and support multi-centric brain studies. However, core grids middleware hardly cope with the complex neuroimaging data representation and multi-layer data federation needs. Moreover, legacy neuroscience environments need to be preserved and cannot be simply superseded by grid services. This paper describes the NeuroLOG platform design and implementation, shedding light on its Data Management Layer. It addresses the integration of brain image files, associated relational metadata and neuroscience semantic data in a heterogeneous distributed environment, integrating legacy data managers through a mediation layer. PMID:20543431

Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome.

PubMed

Lee, Jin Sook; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Chae, Jong Hee

2016-04-01

Few studies have analyzed the clinical course and functional outcome in Leigh syndrome (LS). The aim of this study was to determine the clinical, radiological, biochemical, and genetic features of patients with LS, and identify prognostic indicators of the disease progression and neurological outcome. Thirty-nine patients who had been diagnosed with LS at the Seoul National University Children's Hospital were included. Their medical records, neuroimaging findings, and histological/biochemical findings of skeletal muscle specimens were reviewed. Targeted sequencing of mitochondrial DNA was performed based on mitochondrial respiratory chain (MRC) enzyme defects. Isolated complex I deficiency was the most frequently observed MRC defect (in 42% of 38 investigated patients). Mitochondrial DNA mutations were identified in 11 patients, of which 81.8% were MT-ND genes. The clinical outcome varied widely, from independent daily activity to severe disability. Poor functional outcomes and neurological deterioration were significantly associated with early onset (before an age of 1 year) and the presence of other lesions additional to basal ganglia involvement in the initial neuroimaging. The neurological severity and outcome of LS may vary widely and be better than those predicted based on previous studies. We suggest that age at onset and initial neuroimaging findings are prognostic indicators in LS.

Preterm birth and developmental problems in the preschool age. Part I: minor motor problems.

PubMed

Ferrari, Fabrizio; Gallo, Claudio; Pugliese, Marisa; Guidotti, Isotta; Gavioli, Sara; Coccolini, Elena; Zagni, Paola; Della Casa, Elisa; Rossi, Cecilia; Lugli, Licia; Todeschini, Alessandra; Ori, Luca; Bertoncelli, Natascia

2012-11-01

Nearly half of very preterm (VP) and extremely preterm (EP) infants suffers from minor disabilities. The paper overviews the literature dealing with motor problems other than cerebral palsy (CP) during infancy and preschool age. The term "minor motor problems" indicates a wide spectrum of motor disorders other than CP; "minor" does not mean "minimal", as a relevant proportion of the preterm infants will develop academic and behavioural problems at school age. Early onset disorders consist of abnormal general movements (GMs), transient dystonia and postural instability; these conditions usually fade during the first months. They were underestimated in the past; recently, qualitative assessment of GMs using Prechtl's method has become a major item of the neurological examination. Late onset disorders include developmental coordination disorder (DCD) and/or minor neurological dysfunction (MND): both terms cover partly overlapping problems. Simple MND (MND-1) and complex MND (MND-2) can be identified and MND-2 gives a higher risk for learning and behavioural disorders. A relationship between the quality of GMs and MND in childhood has been recently described. The Touwen infant neurological examination (TINE) can reliably detect neurological signs of MND even in infancy. However, the prognostic value of these disorders requires further investigations.

An exploratory study of the relationship between neurological soft signs and theory of mind deficits in schizophrenia.

PubMed

Romeo, Stefano; Chiandetti, Alessio; Siracusano, Alberto; Troisi, Alfonso

2014-08-15

Indirect evidence suggests partially common pathogenetic mechanisms for Neurological Soft Signs (NSS), neurocognition, and social cognition in schizophrenia. However, the possible association between NSS and mentalizing impairments has not yet been examined. In the present study, we assessed the ability to attribute mental states to others in patients with schizophrenia and predicted that the presence of theory of mind deficits would be significantly related to NSS. Participants were 90 clinically stable patients with a DSM-IV diagnosis of schizophrenia. NSS were assessed using the Neurological Evaluation Scale (NES). Theory of mind deficits were assessed using short verbal stories designed to measure false belief understanding. The findings of the study confirmed our hypothesis. Impaired sequencing of complex motor acts was the only neurological abnormality correlated with theory of mind deficits. By contrast, sensory integration, motor coordination and the NES Others subscale had no association with patients׳ ability to pass first- or second-order false belief tasks. If confirmed by future studies, the current findings provide the first preliminary evidence for the claim that specific NSS and theory of mind deficits may reflect overlapping neural substrates. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies.

PubMed

Chapman, J; Rand, J H; Brey, R L; Levine, S R; Blatt, I; Khamashta, M A; Shoenfeld, Y

2003-01-01

Although many types of neurological disorders and events have been described in association with antiphospholipid antibodies (aPL) and the antiphospholipid syndrome (APS), only ischaemic stroke is reasonably well established and accepted as a diagnostic criterion for the syndrome. We propose to evaluate, classify and rank the association of other neurological manifestations as possible, probable, or definite according to the data available from clinical studies and animal models. By these criteria, none of the neurological disorders or events such as epilepsy, psychiatric disease, dementia, transverse myelitis, multiple sclerosis-like disease, chorea, migraine, Guillian-Barrè syndrome, and sensory-neural hearing loss, can be definitely associated with aPL or APS.

Neurological sequelae of the operation "baby lift" airplane disaster.

PubMed

Cohen, M; Conners, C K; Brook, I; Feldman, S; Mason, J K; Dugas, M; Collis, L; Copeland, B; Lewis, O; Denhoff, E

1994-01-01

The aircraft disaster of the first flight of Operation "Baby Lift", which departed from Saigon, Vietnam, April 4, 1975, was survived by 149 orphaned children on their way to adoptive homes in the West. It had 157 passenger fatalities. The aircraft disaster exposed the surviving children to a complex disaster environment in which subatmospheric decompression, hypoxia, and deceleration were experienced, many children suffered a transient unconsciousness. We examined 135 surviving children between 1978 and 1985. The U.S. resident children were examined in the years 1979 to 1982 at an average age of 8 years and 6 months. They displayed the following symptomatology: attention deficit (> 75%), hyperactivity (> 65%), impulse disorder (> 55%), learning disabilities (> 35%), speech and language pathology (> 70%), and soft neurological signs (> 75%). The European children were examined in the years 1983 to 1985. On arrival at the adoptive home, 2 weeks after the accident they displayed the following symptomatology: muscle hypotonia (26%), seizures (2.5%), and regressed developmental milestones (33%). At the time of the diagnostic evaluations (1983 to 1985) the average age was 11 years and 8 months. They displayed the following symptomatology: attention deficit (59%), hyperactivity (52%), impulse disorder (48%), learning disabilities (43%), soft neurological signs (43%), epilepsy (16%), and speech and language pathology (34%). We conclude that a complex disaster environment can cause brain damage in children without prolonged unconsciousness, and that victims of disasters require a thorough evaluation from a multidisciplinary team.

Role of fractalkine/CX3CR1 signaling pathway in the recovery of neurological function after early ischemic stroke in a rat model.

PubMed

Liu, Yan-Zhi; Wang, Chun; Wang, Qian; Lin, Yong-Zhong; Ge, Yu-Song; Li, Dong-Mei; Mao, Geng-Sheng

2017-09-01

This study aims to explore the role of fractalkine/CX3C chemokine receptor 1 (CX3CR1) signaling pathway in the recovery of neurological functioning after an early ischemic stroke in rats. After establishment of permanent middle cerebral artery occlusion (pMCAO) models, 50 rats were divided into blank, sham, model, positive control and CX3CR1 inhibitor groups. Neurological impairment, walking and grip abilities, and cortical and hippocampal infarctions were evaluated by Zea Longa scoring criterion, beam-walking assay and grip strength test, and diffusion-weighted magnetic resonance imaging. qRT-PCR and Western blotting were performed to detect mRNA and protein expressions. ELISA was conducted to measure concentration of sFractalkine (sFkn), interleukin-1β (IL-1β) and TNF-α. The recovery rate of neurological functioning impairment and reduced walking and grip abilities was faster in the positive control and CX3CR1 inhibitor groups than the model group. The model, positive control and CX3CR1 inhibitor groups showed increased mRNA and protein expression of chemokine C-X3-C motif ligand 1 (CX3CL1) and CX3CR1, concentration of sFkn, IL-1β and TNF-α, and size of cortical and cerebral infarctions while decreased expression of NGF and BDNF compared with the blank and sham groups. Compared with the model group, the mRNA and protein expression of CX3CL1 and CX3CR1, concentration of sFkn, IL-1β and TNF-α, and size of cortical and cerebral infarctions decreased while expression of NGF and BDNF increased in the positive control and CX3CR1 inhibitor groups. Thus, the study suggests that inhibition of fractalkine/CX3CR1 signaling pathway promotes the recovery of neurological functioning after the occurrence of an early ischemic stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictive value of general movements' quality in low-risk infants for minor neurological dysfunction and behavioural problems at preschool age.

PubMed

Bennema, Anne N; Schendelaar, Pamela; Seggers, Jorien; Haadsma, Maaike L; Heineman, Maas Jan; Hadders-Algra, Mijna

2016-03-01

General movement (GM) assessment is a well-established tool to predict cerebral palsy in high-risk infants. Little is known on the predictive value of GM assessment in low-risk populations. To assess the predictive value of GM quality in early infancy for the development of the clinically relevant form of minor neurological dysfunction (complex MND) and behavioral problems at preschool age. Prospective cohort study. A total of 216 members of the prospective Groningen Assisted Reproductive Techniques (ART) cohort study were included in this study. ART did not affect neurodevelopmental outcome of these relatively low-risk infants born to subfertile parents. GM quality was determined at 2 weeks and 3 months. At 18 months and 4 years, the Hempel neurological examination was used to assess MND. At 4 years, parents completed the Child Behavior Checklist; this resulted in the total problem score (TPS), internalizing problem score (IPS), and externalizing problem score (EPS). Predictive values of definitely (DA) and mildly (MA) abnormal GMs were calculated. DA GMs at 2 weeks were associated with complex MND at 18 months and atypical TPS and IPS at 4 years (all p<0.05). Sensitivity and positive predictive value of DA GMs at 2 weeks were rather low (13%-60%); specificity and negative predictive value were excellent (92%-99%). DA GMs at 3 months occurred too infrequently to calculate prediction. MA GMs were not associated with outcome. GM quality as a single predictor for complex MND and behavioral problems at preschool age has limited clinical value in children at low risk for developmental disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clinical management departments for the neurosciences.

PubMed

Matías-Guiu, J; García-Ramos, R; Ramos, M; Soto, J

2016-01-01

Neuroscience-related clinical management departments (UGC in Spanish) represent a means of organising hospitals to deliver patient-centred care as well as specific clinical and administrative management models. The authors review the different UGC models in Spain and their implementation processes as well as any functional problems. We pay special attention to departments treating neurological patients. Neuroscience-related specialties may offer a good framework for the units that they contain. This may be due to the inherent variability and costs associated with neurological patients, the vital level of coordination that must be present between units providing care, and probably to the dynamic nature of the neurosciences as well. Difficulties associated with implementing and gaining acceptance for the new model have limited such UGCs until now. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

A new epileptic seizure classification based exclusively on ictal semiology.

PubMed

Lüders, H; Acharya, J; Baumgartner, C; Benbadis, S; Bleasel, A; Burgess, R; Dinner, D S; Ebner, A; Foldvary, N; Geller, E; Hamer, H; Holthausen, H; Kotagal, P; Morris, H; Meencke, H J; Noachtar, S; Rosenow, F; Sakamoto, A; Steinhoff, B J; Tuxhorn, I; Wyllie, E

1999-03-01

Historically, seizure semiology was the main feature in the differential diagnosis of epileptic syndromes. With the development of clinical EEG, the definition of electroclinical complexes became an essential tool to define epileptic syndromes, particularly focal epileptic syndromes. Modern advances in diagnostic technology, particularly in neuroimaging and molecular biology, now permit better definitions of epileptic syndromes. At the same time detailed studies showed that there does not necessarily exist a one-to-one relationship between epileptic seizures or electroclinical complexes and epileptic syndromes. These developments call for the reintroduction of an epileptic seizure classification based exclusively on clinical semiology, similar to the seizure classifications which were used by neurologists before the introduction of the modern diagnostic methods. This classification of epileptic seizures should always be complemented by an epileptic syndrome classification based on all the available clinical information (clinical history, neurological exam, ictal semiology, EEG, anatomical and functional neuroimaging, etc.). Such an approach is more consistent with mainstream clinical neurology and would avoid the current confusion between the classification of epileptic seizures (which in the International Seizure Classification is actually a classification of electroclinical complexes) and the classification of epileptic syndromes.

Complex I deficiency related to T10158C mutation ND3 gene: A further definition of the clinical spectrum.

PubMed

Grosso, Salvatore; Carluccio, Maria Alessandra; Cardaioli, Elena; Cerase, Alfonso; Malandrini, Alessandro; Romano, Chiara; Federico, Antonio; Dotti, Maria Teresa

2017-03-01

Complex I deficiency is the most common energy generation disorder which may clinically present at any age with a wide spectrum of symptoms and signs. The T10158C mutation ND3 gene is rare and occurs in patients showing an early rapid neurological deterioration invariably leading to death after a few months. We report a 9year-old boy with a mtDNA T10158C mutation showing a mild MELAS-like phenotype and brain MRI features congruent with both MELAS and Leigh syndrome. Epilepsia partialis continua also occurred in the clinical course and related to a mild cortical atrophy of the left perisylvian area. The present case confirms that the clinical spectrum of Complex I deficiency related to T10158C mutation ND3 gene is wider than previously described. Our observation further suggests that testing mutation in the MT-ND3 gene should be included in the diagnostic work-up of patients presenting with epilepsia partialis continua accompanied by suspicion of mitochondrial disorder. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Coma and Stroke Following Surgical Treatment of Unruptured Intracranial Aneurysm: An American College of Surgeons National Surgical Quality Improvement Program Study.

PubMed

McCutcheon, Brandon A; Kerezoudis, Panagiotis; Porter, Amanda L; Rinaldo, Lorenzo; Murphy, Meghan; Maloney, Patrick; Shepherd, Daniel; Hirshman, Brian R; Carter, Bob S; Lanzino, Giuseppe; Bydon, Mohamad; Meyer, Fredric

2016-07-01

A large national surgical registry was used to establish national benchmarks and associated predictors of major neurologic complications (i.e., coma and stroke) after surgical clipping of unruptured intracranial aneurysms. The American College of Surgeons National Surgical Quality Improvement Program data set between 2007 and 2013 was used for this retrospective cohort analysis. Demographic, comorbidity, and operative characteristics associated with the development of a major neurologic complication (i.e., coma or stroke) were elucidated using a backward selection stepwise logistic regression analysis. This model was subsequently used to fit a predictive score for major neurologic complications. Inclusion criteria were met by 662 patients. Of these patients, 57 (8.61%) developed a major neurologic complication (i.e., coma or stroke) within the 30-day postoperative period. On multivariable analysis, operative time (log odds 0.004 per minute; 95% confidence interval [CI], 0.002-0.007), age (log odds 0.05 per year; 95% CI, 0.02-0.08), history of chronic obstructive pulmonary disease (log odds 1.26; 95% CI, 0.43-2.08), and diabetes (log odds 1.15; 95% CI, 0.38-1.91) were associated with an increased odds of major neurologic complications. When patients were categorized according to quartile of a predictive score generated from the multivariable analysis, rates of major neurologic complications were 1.8%, 4.3%, 6.7%, and 21.2%. Using a large, national multi-institutional cohort, this study established representative national benchmarks and a predictive scoring system for major neurologic complications following operative management of unruptured intracranial aneurysms. The model may assist with risk stratification and tailoring of decision making in surgical candidates. Copyright © 2016 Elsevier Inc. All rights reserved.

Rapid evidence assessment of approaches to community neurological nursing care for people with neurological conditions post-discharge from acute care hospital.

PubMed

Pugh, Judith Dianne; McCoy, Kathleen; Williams, Anne M; Bentley, Brenda; Monterosso, Leanne

2018-04-16

Neurological conditions represent leading causes of non-fatal burden of disease that will consume a large proportion of projected healthcare expenditure. Inconsistent access to integrated healthcare and other services for people with long-term neurological conditions stresses acute care services. The purpose of this rapid evidence assessment, conducted February-June 2016, was to review the evidence supporting community neurological nursing approaches for patients with neurological conditions post-discharge from acute care hospitals. CINAHL Plus with Full Text and MEDLINE were searched for English-language studies published January 2000 to June 2016. Data were extracted using a purpose-designed protocol. Studies describing community neurological nursing care services post-discharge for adults with stroke, dementia, Alzheimer's disease, Parkinson's disease, multiple sclerosis or motor neurone disease were included and their quality was assessed. Two qualitative and three quantitative studies were reviewed. Two themes were identified in the narrative summary of findings: (i) continuity of care and self-management and (ii) variable impact on clinical or impairment outcomes. There was low quality evidence of patient satisfaction, improved patient social activity, depression scores, stroke knowledge and lifestyle modification associated with post-discharge care by neurological nurses as an intervention. There were few studies and weak evidence supporting the use of neurology-generalist nurses to promote continuity of care for people with long-term or progressive, long-term neurological conditions post-discharge from acute care hospital. Further research is needed to provide role clarity to facilitate comparative studies and evaluations of the effectiveness of community neurological nursing models of care. © 2018 John Wiley & Sons Ltd.

Nutrition and Mental Development.

ERIC Educational Resources Information Center

Crnic, Linda S.

1984-01-01

Studies on the effects of malnutrition on mental development are reviewed and the complexity of factors (such as alternatives in maternal behavior) surrounding malnutrition in animal studies is noted. Findings are cited which suggest that environmental stimulation may in part reverse the neurological effects and remediate some behavioral effects…

Altered Neuronal and Circuit Excitability in Fragile X Syndrome.

PubMed

Contractor, Anis; Klyachko, Vitaly A; Portera-Cailliau, Carlos

2015-08-19

Fragile X syndrome (FXS) results from a genetic mutation in a single gene yet produces a phenotypically complex disorder with a range of neurological and psychiatric problems. Efforts to decipher how perturbations in signaling pathways lead to the myriad alterations in synaptic and cellular functions have provided insights into the molecular underpinnings of this disorder. From this large body of data, the theme of circuit hyperexcitability has emerged as a potential explanation for many of the neurological and psychiatric symptoms in FXS. The mechanisms for hyperexcitability range from alterations in the expression or activity of ion channels to changes in neurotransmitters and receptors. Contributions of these processes are often brain region and cell type specific, resulting in complex effects on circuit function that manifest as altered excitability. Here, we review the current state of knowledge of the molecular, synaptic, and circuit-level mechanisms underlying hyperexcitability and their contributions to the FXS phenotypes. Copyright © 2015 Elsevier Inc. All rights reserved.

Resuscitation with Lyophilized Plasma Is Safe and Improves Neurological Recovery in a Long-Term Survival Model of Swine Subjected to Traumatic Brain Injury, Hemorrhagic Shock, and Polytrauma.

PubMed

Georgoff, Patrick E; Nikolian, Vahagn C; Halaweish, Ihab; Chtraklin, Kiril; Bruhn, Peter J; Eidy, Hassan; Rasmussen, Monica; Li, Yongqing; Srinivasan, Ashok; Alam, Hasan B

2017-07-01

We have shown previously that fresh frozen plasma (FFP) and lyophilized plasma (LP) decrease brain lesion size and improve neurological recovery in a swine model of traumatic brain injury (TBI) and hemorrhagic shock (HS). In this study, we examine whether these findings can be validated in a clinically relevant model of severe TBI, HS, and polytrauma. Female Yorkshire swine were subjected to TBI (controlled cortical impact), hemorrhage (40% volume), grade III liver and splenic injuries, rib fracture, and rectus abdominis crush. The animals were maintained in a state of shock (mean arterial pressure 30-35 mm Hg) for 2 h, and then randomized to resuscitation with normal saline (NS), FFP, or LP (n = 5 swine/group). Animals were recovered and monitored for 30 d, during which time neurological recovery was assessed. Brain lesion sizes were measured via magnetic resonance imaging (MRI) on post-injury days (PID) three and 10. Animals were euthanized on PID 30. The severity of shock and response to resuscitation was similar in all groups. When compared with NS-treated animals, plasma-treated animals (FFP and LP) had significantly lower neurologic severity scores (PID 1-7) and a faster return to baseline neurological function. There was no significant difference in brain lesion sizes between groups. LP treatment was well tolerated and similar to FFP. In this clinically relevant large animal model of severe TBI, HS, and polytrauma, we have shown that plasma-based resuscitation strategies are safe and result in neurocognitive recovery that is faster than recovery after NS-based resuscitation.

Pyruvate dehydrogenase complex deficiency and its relationship with epilepsy frequency--An overview.

PubMed

Bhandary, Suman; Aguan, Kripamoy

2015-10-01

The pyruvate dehydrogenase complex (PDHc) is a member of a family of multienzyme complexes that provides the link between glycolysis and the tricarboxylic acid (TCA) cycle by catalyzing the physiologically irreversible decarboxylation of various 2-oxoacid substrates to their corresponding acyl-CoA derivatives, NADH and CO2. PDHc deficiency is a metabolic disorder commonly associated with lactic acidosis, progressive neurological and neuromuscular degeneration that vary with age and gender. In this review, we aim to discuss the relationship between occurrence of epilepsy and PDHc deficiency associated with the pyruvate dehydrogenase complex (E1α subunit (PDHA1) and E1β subunit (PDHB)) and PDH phosphatase (PDP) deficiency. PDHc plays a crucial role in the aerobic carbohydrate metabolism and regulates the use of carbohydrate as the source of oxidative energy. In severe PDHc deficiency, the energy deficit impairs brain development in utero resulting in physiological and structural changes in the brain that contributes to the subsequent onset of epileptogenesis. Epileptogenesis in PDHc deficiency is linked to energy failure and abnormal neurotransmitter metabolism that progressively alters neuronal excitability. This metabolic blockage might be restricted via inclusion of ketogenic diet that is broken up by β-oxidation and directly converting it to acetyl-CoA, and thereby improving the patient's health condition. Genetic counseling is essential as PDHA1 deficiency is X-linked. The demonstration of the X-chromosome localization of PDHA1 resolved a number of questions concerning the variable phenotype displayed by patients with E1 deficiency. Most patients show a broad range of neurological abnormalities, with the severity showing some dependence on the nature of the mutation in the Elα gene, while PDHB and PDH phosphatase (PDP) deficiencies are of autosomal recessive inheritance. However, in females, the disorder is further complicated by the pattern of X-chromosome inactivation, i.e., unfavorable lyonization. Furthermore research should focus on epileptogenic animal models; this might pave a new way toward identification of the pathophysiology of this challenging disorder. Copyright © 2015 Elsevier B.V. All rights reserved.

Systems Biology Approaches for Discovering Biomarkers for Traumatic Brain Injury

PubMed Central

Feala, Jacob D.; AbdulHameed, Mohamed Diwan M.; Yu, Chenggang; Dutta, Bhaskar; Yu, Xueping; Schmid, Kara; Dave, Jitendra; Tortella, Frank

2013-01-01

Abstract The rate of traumatic brain injury (TBI) in service members with wartime injuries has risen rapidly in recent years, and complex, variable links have emerged between TBI and long-term neurological disorders. The multifactorial nature of TBI secondary cellular response has confounded attempts to find cellular biomarkers for its diagnosis and prognosis or for guiding therapy for brain injury. One possibility is to apply emerging systems biology strategies to holistically probe and analyze the complex interweaving molecular pathways and networks that mediate the secondary cellular response through computational models that integrate these diverse data sets. Here, we review available systems biology strategies, databases, and tools. In addition, we describe opportunities for applying this methodology to existing TBI data sets to identify new biomarker candidates and gain insights about the underlying molecular mechanisms of TBI response. As an exemplar, we apply network and pathway analysis to a manually compiled list of 32 protein biomarker candidates from the literature, recover known TBI-related mechanisms, and generate hypothetical new biomarker candidates. PMID:23510232

Effect of cation type and concentration of nitrates on neurological disorders during experimental cerebral ischemia.

PubMed

Kuzenkov, V S; Krushinskii, A L; Reutov, V P

2013-10-01

Experiments were performed on the model of ischemic stroke due to bilateral occlusion of the carotid arteries. Nitrates had various effects on the dynamics of neurological disorders and mortality rate of Wistar rats, which depended on the cation type and concentration.

Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets

PubMed Central

Satterfield, Benjamin A.; Cross, Robert W.; Fenton, Karla A.; Borisevich, Viktoriya; Agans, Krystle N.; Deer, Daniel J.; Graber, Jessica; Basler, Christopher F.; Mire, Chad E.

2016-01-01

ABSTRACT Nipah virus (NiV) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severe respiratory disease in humans. The ferret model has emerged as the preferred small-animal model with which to study NiV disease, but much is still unknown about the viral determinants of NiV pathogenesis, including the contribution of the C protein in ferrets. Additionally, studies have yet to examine the synergistic effects of the various P gene products on pathogenesis in animal models. Using recombinant NiVs (rNiVs), we examine the sole contribution of the NiV C protein and the combined contributions of the C and W proteins in the ferret model of NiV pathogenesis. We show that an rNiV void of C expression resulted in 100% mortality, though with limited respiratory disease, like our previously reported rNiV void of W expression; this finding is in stark contrast to the attenuated phenotype observed in previous hamster studies utilizing rNiVs void of C expression. We also observed that an rNiV void of both C and W expression resulted in limited respiratory disease; however, there was severe neurological disease leading to 60% mortality, and the surviving ferrets demonstrated sequelae similar to those for human survivors of NiV encephalitis. IMPORTANCE Nipah virus (NiV) is a human pathogen capable of causing lethal respiratory and neurological disease. Many human survivors have long-lasting neurological impairment. Using a ferret model, this study demonstrated the roles of the NiV C and W proteins in pathogenesis, where lack of either the C or the W protein independently decreased the severity of clinical respiratory disease but did not decrease lethality. Abolishing both C and W expression, however, dramatically decreased the severity of respiratory disease and the level of destruction of splenic germinal centers. These ferrets still suffered severe neurological disease: 60% succumbed to disease, and the survivors experienced long-term neurological impairment, such as that seen in human survivors. This new ferret NiV C and W knockout model may allow, for the first time, the examination of interventions to prevent or mitigate the neurological damage and sequelae experienced by human survivors. PMID:27147733

Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets.

PubMed

Satterfield, Benjamin A; Cross, Robert W; Fenton, Karla A; Borisevich, Viktoriya; Agans, Krystle N; Deer, Daniel J; Graber, Jessica; Basler, Christopher F; Geisbert, Thomas W; Mire, Chad E

2016-07-15

Nipah virus (NiV) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severe respiratory disease in humans. The ferret model has emerged as the preferred small-animal model with which to study NiV disease, but much is still unknown about the viral determinants of NiV pathogenesis, including the contribution of the C protein in ferrets. Additionally, studies have yet to examine the synergistic effects of the various P gene products on pathogenesis in animal models. Using recombinant NiVs (rNiVs), we examine the sole contribution of the NiV C protein and the combined contributions of the C and W proteins in the ferret model of NiV pathogenesis. We show that an rNiV void of C expression resulted in 100% mortality, though with limited respiratory disease, like our previously reported rNiV void of W expression; this finding is in stark contrast to the attenuated phenotype observed in previous hamster studies utilizing rNiVs void of C expression. We also observed that an rNiV void of both C and W expression resulted in limited respiratory disease; however, there was severe neurological disease leading to 60% mortality, and the surviving ferrets demonstrated sequelae similar to those for human survivors of NiV encephalitis. Nipah virus (NiV) is a human pathogen capable of causing lethal respiratory and neurological disease. Many human survivors have long-lasting neurological impairment. Using a ferret model, this study demonstrated the roles of the NiV C and W proteins in pathogenesis, where lack of either the C or the W protein independently decreased the severity of clinical respiratory disease but did not decrease lethality. Abolishing both C and W expression, however, dramatically decreased the severity of respiratory disease and the level of destruction of splenic germinal centers. These ferrets still suffered severe neurological disease: 60% succumbed to disease, and the survivors experienced long-term neurological impairment, such as that seen in human survivors. This new ferret NiV C and W knockout model may allow, for the first time, the examination of interventions to prevent or mitigate the neurological damage and sequelae experienced by human survivors. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Optimal management of complications associated with achondroplasia

PubMed Central

Ireland, Penny J; Pacey, Verity; Zankl, Andreas; Edwards, Priya; Johnston, Leanne M; Savarirayan, Ravi

2014-01-01

Achondroplasia is the most common form of skeletal dysplasia, resulting in disproportionate short stature, and affects over 250,000 people worldwide. Individuals with achondroplasia demonstrate a number of well-recognized anatomical features that impact on growth and development, with a complex array of medical issues that are best managed through a multidisciplinary team approach. The complexity of this presentation, whereby individual impairments may impact upon multiple activity and participation areas, requires consideration and discussion under a broad framework to gain a more thorough understanding of the experience of this condition for individuals with achondroplasia. This paper examines the general literature and research evidence on the medical and health aspects of individuals with achondroplasia and presents a pictorial model of achondroplasia based on The International Classification of Functioning, Disability, and Health (ICF). An expanded model of the ICF will be used to review and present the current literature pertaining to the musculoskeletal, neurological, cardiorespiratory, and ear, nose, and throat impairments and complications across the lifespan, with discussion on the impact of these impairments upon activity and participation performance. Further research is required to fully identify factors influencing participation and to help develop strategies to address these factors. PMID:25053890

Magnetite-Amyloid-β deteriorates activity and functional organization in an in vitro model for Alzheimer’s disease

NASA Astrophysics Data System (ADS)

Teller, Sara; Tahirbegi, Islam Bogachan; Mir, Mònica; Samitier, Josep; Soriano, Jordi

2015-11-01

The understanding of the key mechanisms behind human brain deterioration in Alzheimer’ disease (AD) is a highly active field of research. The most widespread hypothesis considers a cascade of events initiated by amyloid-β peptide fibrils that ultimately lead to the formation of the lethal amyloid plaques. Recent studies have shown that other agents, in particular magnetite, can also play a pivotal role. To shed light on the action of magnetite and amyloid-β in the deterioration of neuronal circuits, we investigated their capacity to alter spontaneous activity patterns in cultured neuronal networks. Using a versatile experimental platform that allows the parallel monitoring of several cultures, the activity in controls was compared with the one in cultures dosed with magnetite, amyloid-β and magnetite-amyloid-β complex. A prominent degradation in spontaneous activity was observed solely when amyloid-β and magnetite acted together. Our work suggests that magnetite nanoparticles have a more prominent role in AD than previously thought, and may bring new insights in the understanding of the damaging action of magnetite-amyloid-β complex. Our experimental system also offers new interesting perspectives to explore key biochemical players in neurological disorders through a controlled, model system manner.

Integrating palliative care into neurology services: what do the professionals say?

PubMed Central

Gao, Wei; Evans, Catherine J; Jackson, Diana; van Vliet, Liesbeth M; Byrne, Anthony; Crosby, Vincent; Groves, Karen E; Lindsay, Fiona; Higginson, Irene J

2018-01-01

Objectives Evaluations of new services for palliative care in non-cancer conditions are few. OPTCARE Neuro is a multicentre trial evaluating the effectiveness of short-term integrated palliative care (SIPC) for progressive long-term neurological conditions. Here, we present survey results describing the current levels of collaboration between neurology and palliative care services and exploring the views of professionals towards the new SIPC service. Methods Neurology and palliative care teams from six UK trial sites (London, Nottingham, Liverpool, Cardiff, Brighton and Chertsey) were approached via email to complete an online survey. The survey was launched in July 2015 and consisted of multiple choice or open comment questions with responses collected using online forms. Results 33 neurology and 26 palliative care professionals responded. Collaborations between the two specialties were reported as being ‘good/excellent’ by 36% of neurology and by 58% of palliative care professionals. However, nearly half (45%) of neurology compared with only 12% of palliative care professionals rated current levels as being ‘poor/none’. Both professional groups felt that the new SIPC service would influence future collaborations for the better. However, they identified a number of barriers for the new SIPC service such as resources and clinician awareness. Conclusions Our results demonstrate the opportunity to increase collaboration between neurology and palliative care services for people with progressive neurological conditions, and the acceptability of SIPC as a model to support this. Trial registration number ISRCTN18337380; Pre-results. PMID:28774963

Efficacy of therapeutic hypothermia for neurological salvage in patients with cardiogenic sudden cardiac arrest: the importance of prehospital return of spontaneous circulation.

PubMed

Shinada, Takuro; Hata, Noritake; Kobayashi, Nobuaki; Tomita, Kazunori; Shirakabe, Akihiro; Tsurumi, Masafumi; Matsushita, Masato; Okazaki, Hirotake; Yamamoto, Yoshiya; Yokoyama, Shinya

2013-01-01

Cardiopulmonary resuscitation and mild therapeutic hypothermia (MTH) have improved neurological outcomes after sudden cardiac arrest, but the factors affecting favorable neurological outcome remain unclear. The aim of this study was to clarify these factors in patients in cardiac arrest treated with MTH. Forty-six consecutive patients (mean age, 59.4 ± 14.3 years; 37 men and 9 women) who had had cardiogenic cardiac arrest from January 2008 through December 2011, including cases that were and were not shockable, were enrolled in this study, and the factors affecting favorable neurological outcome were retrospectively investigated. The interval from cardiac arrest to cardiopulmonary resuscitation, the return of spontaneous circulation (ROSC), the start of MTH, and the attaining of the target temperature were retrieved from the medical records. The relationship between the neurological outcome and clinical findings, including the causes of cardiac arrest and vital signs before MTH, were also investigated. Blood pressure and body temperature before MTH were higher, the interval from cardiac arrest to ROSC was shorter, and MTH was started earlier in patients with favorable neurological outcomes than in those with unfavorable outcomes. A multivariate logistic regression model revealed that the presence of prehospital ROSC was predictive of a favorable neurological outcome. In addition, renal failure during MTH occurred more frequently in patients with unfavorable neurological outcomes. MTH is associated with favorable neurological outcomes after sudden cardiac arrest, including those with non-shockable rhythms, especially in patients with prehospital ROSC.

The inverse problem of brain energetics: ketone bodies as alternative substrates

NASA Astrophysics Data System (ADS)

Calvetti, D.; Occhipinti, R.; Somersalo, E.

2008-07-01

Little is known about brain energy metabolism under ketosis, although there is evidence that ketone bodies have a neuroprotective role in several neurological disorders. We investigate the inverse problem of estimating reaction fluxes and transport rates in the different cellular compartments of the brain, when the data amounts to a few measured arterial venous concentration differences. By using a recently developed methodology to perform Bayesian Flux Balance Analysis and a new five compartment model of the astrocyte-glutamatergic neuron cellular complex, we are able to identify the preferred biochemical pathways during shortage of glucose and in the presence of ketone bodies in the arterial blood. The analysis is performed in a minimally biased way, therefore revealing the potential of this methodology for hypothesis testing.

Astaxanthin as a Potential Neuroprotective Agent for Neurological Diseases

PubMed Central

Wu, Haijian; Niu, Huanjiang; Shao, Anwen; Wu, Cheng; Dixon, Brandon J.; Zhang, Jianmin; Yang, Shuxu; Wang, Yirong

2015-01-01

Neurological diseases, which consist of acute injuries and chronic neurodegeneration, are the leading causes of human death and disability. However, the pathophysiology of these diseases have not been fully elucidated, and effective treatments are still lacking. Astaxanthin, a member of the xanthophyll group, is a red-orange carotenoid with unique cell membrane actions and diverse biological activities. More importantly, there is evidence demonstrating that astaxanthin confers neuroprotective effects in experimental models of acute injuries, chronic neurodegenerative disorders, and neurological diseases. The beneficial effects of astaxanthin are linked to its oxidative, anti-inflammatory, and anti-apoptotic characteristics. In this review, we will focus on the neuroprotective properties of astaxanthin and explore the underlying mechanisms in the setting of neurological diseases. PMID:26378548

Prenatal Antecedents of Newborn Neurological Maturation

PubMed Central

DiPietro, Janet A.; Kivlighan, Katie T.; Costigan, Kathleen A.; Rubin, Suzanne E.; Shiffler, Dorothy E.; Henderson, Janice L.; Pillion, Joseph P.

2009-01-01

Fetal neurobehavioral development was modeled longitudinally using data collected at weekly intervals from 24- to -38 weeks gestation in a sample of 112 healthy pregnancies. Predictive associations between 3 measures of fetal neurobehavioral functioning and their developmental trajectories to neurological maturation in the 1st weeks after birth were examined. Prenatal measures included fetal heart rate variability, fetal movement, and coupling between fetal motor activity and heart rate patterning; neonatal outcomes include a standard neurologic examination (n = 97) and brainstem auditory evoked potential (BAEP; n = 47). Optimality in newborn motor activity and reflexes was predicted by fetal motor activity; fetal heart rate variability and somatic-cardiac coupling predicted BAEP parameters. Maternal pregnancy-specific psychological stress was associated with accelerated neurologic maturation. PMID:20331657

Zebrafish as a model for monocarboxyl transporter 8-deficiency.

PubMed

Vatine, Gad David; Zada, David; Lerer-Goldshtein, Tali; Tovin, Adi; Malkinson, Guy; Yaniv, Karina; Appelbaum, Lior

2013-01-04

Allan-Herndon-Dudley syndrome (AHDS) is a severe psychomotor retardation characterized by neurological impairment and abnormal thyroid hormone (TH) levels. Mutations in the TH transporter, monocarboxylate transporter 8 (MCT8), are associated with AHDS. MCT8 knock-out mice exhibit impaired TH levels; however, they lack neurological defects. Here, the zebrafish mct8 gene and promoter were isolated, and mct8 promoter-driven transgenic lines were used to show that, similar to humans, mct8 is primarily expressed in the nervous and vascular systems. Morpholino-based knockdown and rescue experiments revealed that MCT8 is strictly required for neural development in the brain and spinal cord. This study shows that MCT8 is a crucial regulator during embryonic development and establishes the first vertebrate model for MCT8 deficiency that exhibits a neurological phenotype.

Acute encephalitis, a poliomyelitis-like syndrome and neurological sequelae in a hamster model for flavivirus infections.

PubMed

Leyssen, Pieter; Croes, Romaric; Rau, Philipp; Heiland, Sabine; Verbeken, Erik; Sciot, Raphael; Paeshuyse, Jan; Charlier, Nathalie; De Clercq, Erik; Meyding-Lamadé, Uta; Neyts, Johan

2003-07-01

Infection of hamsters with the murine flavivirus Modoc results in (meningo)encephalitis, which is, during the acute phase, frequently associated with flaccid paralysis, as also observed in patients with West Nile virus encephalitis. Twenty percent of the hamsters that recover from the acute encephalitis develop life-long neurological sequelae, reminiscent of those observed, for example, in survivors of Japanese encephalitis. Magnetic resonance imaging and histology revealed severe lesions predominantly located in the olfactory-limbic system, both in hamsters with acute encephalitis as in survivors. Prominent pathology was also detected in the spinal cord of hamsters with paralysis. Modoc virus infections in hamsters provide a unique model for the study of encephalitis, a poliomyelitis-like syndrome and neurological sequelae following flavivirus infection.

Cell Signaling and Neurotoxicity: 3H-Arachidonic acid release (Phospholipase A2) in cerebellar granule neurons

EPA Science Inventory

Cell signaling is a complex process which controls basic cellular activities and coordinates actions to maintain normal cellular homeostasis. Alterations in signaling processes have been associated with neurological diseases such as Alzheimer's and cerebellar ataxia, as well as, ...

Minor neurological dysfunction in children with autism spectrum disorder.

PubMed

De Jong, Marianne; Punt, Marja; De Groot, Erik; Minderaa, Ruud B; Hadders-Algra, Mijna

2011-07-01

The aim of this study was to improve the understanding of brain function in children with autism spectrum disorder (ASD) in relation to minor neurological dysfunctions (MNDs). We studied MNDs in 122 children (93 males, 29 females; mean age 8 y 1 mo, SD 2 y 6 mo) who, among a total cohort of 705 children (513 males, 192 females; mean age 9 y, SD 2 y 0.5 mo) referred to a regional outpatient non-academic psychiatric centre in the Netherlands, were diagnosed with ASD after an extensive multidisciplinary psychiatric assessment. Children with clear neurological abnormalities (e.g. cerebral palsy or spina bifida) were excluded from the study. MNDs were assessed in all 705 children using the Touwen examination method. Special attention was paid to the severity and type of MND. Data of the children with ASD were compared with neurological morbidity data of children with other psychiatric disorders and with children in the general population, who were born at Groningen University Hospital between 1975 and 1978. Seventy-four percent of the children with ASD showed complex MNDs compared with 52% of the children with other psychiatric disorders and 6% of the reference group (χ(2) =18.0, p<0.001; χ(2) =937.5, p<0.001 respectively). Specific dysfunctions frequently encountered in ASD were dysfunctional posture and muscle tone, fine manipulative disability, dyscoordination, and excessive associated movements. These findings suggest a contribution of dysfunctional supraspinal networks involving multiple parts of the brain in the pathogenesis of ASD. This is consistent with findings from neuroimaging studies, and highlights the importance of neurological examinations in paediatric psychiatric assessments. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

RNA Structures as Mediators of Neurological Diseases and as Drug Targets.

PubMed

Bernat, Viachaslau; Disney, Matthew D

2015-07-01

RNAs adopt diverse folded structures that are essential for function and thus play critical roles in cellular biology. A striking example of this is the ribosome, a complex, three-dimensionally folded macromolecular machine that orchestrates protein synthesis. Advances in RNA biochemistry, structural and molecular biology, and bioinformatics have revealed other non-coding RNAs whose functions are dictated by their structure. It is not surprising that aberrantly folded RNA structures contribute to disease. In this Review, we provide a brief introduction into RNA structural biology and then describe how RNA structures function in cells and cause or contribute to neurological disease. Finally, we highlight successful applications of rational design principles to provide chemical probes and lead compounds targeting structured RNAs. Based on several examples of well-characterized RNA-driven neurological disorders, we demonstrate how designed small molecules can facilitate the study of RNA dysfunction, elucidating previously unknown roles for RNA in disease, and provide lead therapeutics. Copyright © 2015 Elsevier Inc. All rights reserved.

Dietary Intakes and Nutritional Issues in Neurologically Impaired Children.

PubMed

Penagini, Francesca; Mameli, Chiara; Fabiano, Valentina; Brunetti, Domenica; Dilillo, Dario; Zuccotti, Gian Vincenzo

2015-11-13

Neurologically impaired (NI) children are at increased risk of malnutrition due to several nutritional and non-nutritional factors. Among the nutritional factors, insufficient dietary intake as a consequence of feeding difficulties is one of the main issues. Feeding problems are frequently secondary to oropharyngeal dysphagia, which usually correlates with the severity of motor impairment and presents in around 90% of preschool children with cerebral palsy (CP) during the first year of life. Other nutritional factors are represented by excessive nutrient losses, often subsequent to gastroesophageal reflux and altered energy metabolism. Among the non-nutritional factors, the type and severity of neurological impairment, ambulatory status, the degree of cognitive impairment, and use of entiepileptic medication altogether concur to determination of nutritional status. With the present review, the current literature is discussed and a practical approach for nutritional assessment in NI children is proposed. Early identification and intervention of nutritional issues of NI children with a multidisciplinary approach is crucial to improve the overall health and quality of life of these complex children.

Consensus statement on the treatment of multiple sclerosis by the Spanish Society of Neurology in 2016.

PubMed

García Merino, A; Ramón Ara Callizo, J; Fernández Fernández, O; Landete Pascual, L; Moral Torres, E; Rodríguez-Antigüedad Zarrantz, A

2017-03-01

With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease. The present study lists the medications currently approved for multiple sclerosis and their official indications, and analyses such treatment-related aspects as activity, early treatment, maintenance, follow-up, treatment failure, changes in medication, and special therapeutic situations. This consensus statement includes treatment recommendations for a wide range of demyelinating diseases, from isolated demyelinating syndromes to the different forms of multiple sclerosis, as well as recommendations for initial therapy and changes in drug medication, and additional comments on induction and combined therapy and practical aspects of the use of these drugs. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Dietary Intakes and Nutritional Issues in Neurologically Impaired Children

PubMed Central

Penagini, Francesca; Mameli, Chiara; Fabiano, Valentina; Brunetti, Domenica; Dilillo, Dario; Zuccotti, Gian Vincenzo

2015-01-01

Neurologically impaired (NI) children are at increased risk of malnutrition due to several nutritional and non-nutritional factors. Among the nutritional factors, insufficient dietary intake as a consequence of feeding difficulties is one of the main issues. Feeding problems are frequently secondary to oropharyngeal dysphagia, which usually correlates with the severity of motor impairment and presents in around 90% of preschool children with cerebral palsy (CP) during the first year of life. Other nutritional factors are represented by excessive nutrient losses, often subsequent to gastroesophageal reflux and altered energy metabolism. Among the non-nutritional factors, the type and severity of neurological impairment, ambulatory status, the degree of cognitive impairment, and use of entiepileptic medication altogether concur to determination of nutritional status. With the present review, the current literature is discussed and a practical approach for nutritional assessment in NI children is proposed. Early identification and intervention of nutritional issues of NI children with a multidisciplinary approach is crucial to improve the overall health and quality of life of these complex children. PMID:26580646

Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

PubMed

Peluso, Michael J; Spudich, Serena

2014-09-01

The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

Neurological consequences of systemic inflammation in the premature neonate.

PubMed

Patra, Aparna; Huang, Hong; Bauer, John A; Giannone, Peter J

2017-06-01

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

Risk factors of neurological complications in cardiac surgery.

PubMed

Baranowska, Katarzyna; Juszczyk, Grzegorz; Dmitruk, Iwona; Knapp, Małgorzata; Tycińska, Agnieszka; Jakubów, Piotr; Adamczuk, Anna; Stankiewicz, Adrian; Hirnle, Tomasz

2012-01-01

Postoperative complications are integral to cardiac surgery. The most serious ones are stroke, which develops in about 7.5% of the patients, and postoperative encephalopathy, which affects 10-30% of the patients. According to bibliographical data, the number of complications is increasing. To analyse the risk factors and the types of neurological complications in patients undergoing heart surgery. We assessed retrospectively 323 consecutive patients undergoing surgery at the Department of Cardiac Surgery, University Teaching Hospital, Medical University of Bialystok, Poland, between July 2007 and June 2008. Group 1 comprised patients without neurological complications (n = 287; 89%) and Group 2 consisted of patients with neurological complications (n = 36; 11%). Our analysis included the following: preoperative status (age, sex, co-morbidities), intraoperative course (surgery type, duration of cardiopulmonary bypass [CPB], duration of aortic cross-clamping, types of medications administered, necessity of reinfusion from the cardiotomy reservoir and the necessity of tranexamic acid infusion) and the postoperative course (time to regaining consciousness, duration of mechanical ventilation, development of complications, types of complications). The results were then analysed statistically: arithmetic means and standard deviations were calculated for quantitative variables and the quantitative and percentage distributions were calculated for qualitative variables. The between- group comparisons of the quantitative variables were carried out using the t-Student test, while the qualitative variables were compared using the χ(2) test. The variables that proved significant in the univariate comparisons were included in the multivariate model. Regression analysis was the final step of the analysis of the risk factors for neurological complications. Based on the analysis of the ROC curve we calculated the cutoff values for the continuous variables. We calculated odds ratios with their 95% confidence intervals. P values of less than 0.05 were considered statistically significant. Among the 36 patients in Group 2, postoperative encephalopathy developed in 22 patients, transient ischaemic attacks in 7 patients, ischaemic stroke in 6 patients (associated with right hemisphere damage in 3 patients and with left hemisphere damage in 3 patients) and haemorrhagic stroke in 1 patient (right hemisphere). Early mortality was 5% with 2 (0.69%) patients dying in Group 1 and 14 (38.9%) in Group 2. Univariate analysis revealed that the preoperative risk factors of neurological complications were: age >68 years (with a cutoff value of 58.5 years), a history of stroke with paresis, atrial fibrillation (AF) and a euroSCORE of >6 (with a cutoff value of 4.5). The peri- and postoperative risk factors included: surgery type (complex coronary and valvular surgeries aortic valve surgeries), duration of CPB of >142 min, duration of aortic crossclamping of >88 min, mean perfusion pressure during CPB of <70 mm Hg, haemodilution manifested by a haematocrit (HCT) of <28%, perfusate supply, time to regaining consciousness of >14.5 h and duration of artificial ventilation of >30.5 h. Multivariate analysis revealed the following factors to increase the risk of neurological complications: long duration of ventilation, a history of stroke with paresis, AF, low HCT values and long duration of aortic cross-clamping. The Nagelkerke R2 coefficient of determination was 0.636, the sensitivity was 74.36%, the specificity was 97.545% and the accuracy was 94.74%. In patients undergoing heart surgery, the independent risk factors of neurological complications in the first 30 days include: long duration of ventilation, a history of stroke with paresis, AF, haemodilution manifested by an HCT of <28% and long duration of aortic cross-clamping. Neurological complications are associated with high postoperative mortality.

Inverse Modelling to Obtain Head Movement Controller Signal

NASA Technical Reports Server (NTRS)

Kim, W. S.; Lee, S. H.; Hannaford, B.; Stark, L.

1984-01-01

Experimentally obtained dynamics of time-optimal, horizontal head rotations have previously been simulated by a sixth order, nonlinear model driven by rectangular control signals. Electromyography (EMG) recordings have spects which differ in detail from the theoretical rectangular pulsed control signal. Control signals for time-optimal as well as sub-optimal horizontal head rotations were obtained by means of an inverse modelling procedures. With experimentally measured dynamical data serving as the input, this procedure inverts the model to produce the neurological control signals driving muscles and plant. The relationships between these controller signals, and EMG records should contribute to the understanding of the neurological control of movements.

Birth asphyxia: pathophysiologic events and fetal adaptive changes.

PubMed

Woods, J R

1983-06-01

We have made significant advances toward understanding birth asphyxia and its effects upon neurologic development in the newborn and infant. The fetus is well adapted to compensate for moderate alterations in oxygen delivery. However, near lethal hypoxemia, prolonged exposure, and survival result in cell death and permanent neurologic sequelae. Neuroelectrical measurements such as the EEG and visual evoked potential provide insight into the acute alterations in nerve transmission during asphyxia, and in the recovery phase may ultimately provide information for long-term prognosis. These measurements are limited, however, by their inability once lost to distinguish cell inactivity from cell death. Permanent neurologic damage from asphyxia appears now to be a complex process in which severe hypoxemia precipitates a cascade of events leading to glycolysis, glycogenolysis, hypotension, and ultimately the accumulation of high concentrations of lactate at the cell level. As a consequence, cellular and extracellular fluid shifts produce cerebral edema, further impairment of cerebral circulation, and ultimately cell death. Clinical studies have helped to identify the newborn at high risk for neurologic impairment, but a cause-effect relationship remains unclear. That birth asphyxia can produce severe neurologic damage and death is generally accepted. Moreover, improper resuscitation of a severely depressed newborn increases the chance of permanent sequelae. The important clinical question is: Can one alter the natural course of asphyxia as has been alluded to through pharmacologic and ventilator manipulation? Answers to this question will depend upon continued study of the mechanisms of asphyctic damage in the central nervous system.

[Neurological and psychomotor development of foetuses and children with congenital heart disease--causes and prevalence of disorders and long-term prognosis].

PubMed

Herberg, U; Hövels-Gürich, H

2012-06-01

Children with severe congenital heart defects (CHD) requiring open heart surgery in the first year of life are at high risk for developing neurological and psychomotor abnormalities. Depending on the type and severity of the CHD, between 15 and over 50% of these children have deficits, which are usually confined to distinct domains of development, although formal intelligence tends to be normal. Children with mild CHD, who comprise the majority of congenital heart defects, have a far better developmental prognosis than those with complex CHD. This review concentrates on the impact of severe CHD on the developing brain of the foetus and infant. It also provides a summary of recent clinical and neuroimaging studies, and an overview of the long-term neurological prognosis. Advanced neuroimaging modalities indicate that, related to altered cerebral blood flow and oxygenation, foetuses with severe CHD show delayed third trimester brain maturation and increased vulnerability for hypoxic injury. Morphological and neurological abnormalities are present before surgery, commonly affecting the white matter. In the long-term, impaired neurological and developmental outcomes are related to the combination of prenatal, perinatal and additional perioperative risk factors. Therefore, new therapeutic approaches aim to optimise the intra- and perinatal management of foetuses and newborns with congenital heart defects. Identification and avoidance of risk factors, early neurodevelopmental assessment and therapy may optimise the long-term outcome in this high-risk population. © Georg Thieme Verlag KG Stuttgart · New York.

Implementation and evaluation of Parkinson disease management in an outpatient clinical pharmacist-run neurology telephone clinic.

PubMed

Stefan, Teodora Cristina; Elharar, Nicole; Garcia, Guadalupe

2018-05-01

Parkinson disease (PD) is a progressive, debilitating neurodegenerative disease that often requires complex pharmacologic treatment regimens. Prior to this clinic, there was no involvement of a clinical pharmacy specialist (CPS) in the outpatient neurology clinic at the West Palm Beach Veterans Affairs Medical Center. This was a prospective, quality-improvement project to develop a clinical pharmacist-run neurology telephone clinic and evaluate pharmacologic and nonpharmacologic interventions in an effort to improve the quality of care for patients with PD. Additionally, the CPS conducted medication education groups to 24 patients with PD and their caregivers, if applicable, at this medical center with the purpose of promoting patient knowledge and medication awareness. Medication management was performed via telephone rather than face to face. Only patients with a concomitant mental health diagnosis for which they were receiving at least one psychotropic medication were included for individual visits due to the established scope of practice of the CPS being limited to mental health and primary care medications. Data collection included patient and clinic demographics as well as pharmacologic and nonpharmacologic interventions made for patients enrolled from January 6, 2017, through March 31, 2017. A total of 49 pharmacologic and nonpharmacologic interventions were made for 10 patients. We successfully implemented and evaluated a clinical pharmacist-run neurology telephone clinic for patients with PD. Expansion of this clinic to patients with various neurological disorders may improve access to care using an innovative method of medication management expertise by a CPS.

Epilepsy as a Network Disorder (1): What can we learn from other network disorders such as autistic spectrum disorder and mood disorders?

PubMed

Kanner, Andres M; Scharfman, Helen; Jette, Nathalie; Anagnostou, Evdokia; Bernard, Christophe; Camfield, Carol; Camfield, Peter; Legg, Karen; Dinstein, Ilan; Giacobbe, Peter; Friedman, Alon; Pohlmann-Eden, Bernd

2017-12-01

Epilepsy is a neurologic condition which often occurs with other neurologic and psychiatric disorders. The relation between epilepsy and these conditions is complex. Some population-based studies have identified a bidirectional relation, whereby not only patients with epilepsy are at increased risk of suffering from some of these neurologic and psychiatric disorders (migraine, stroke, dementia, autism, depression, anxiety disorders, Attention deficit hyperactivity disorder (ADHD), and psychosis), but also patients with these conditions are at increased risk of suffering from epilepsy. The existence of common pathogenic mechanisms has been postulated as a potential explanation of this phenomenon. To reassess the relationships between neurological and psychiatric conditions in general, and specifically autism, depression, Alzheimer's disease, schizophrenia, and epilepsy, a recent meeting brought together basic researchers and clinician scientists entitled "Epilepsy as a Network Disorder." This was the fourth in a series of conferences, the "Fourth International Halifax Conference and Retreat". This manuscript summarizes the proceedings on potential relations between Epilepsy on the one hand and autism and depression on the other. A companion manuscript provides a summary of the proceedings about the relation between epilepsy and Alzheimer's disease and schizophrenia, closed by the role of translational research in clarifying these relationships. The review of the topics in these two manuscripts will provide a better understanding of the mechanisms operant in some of the common neurologic and psychiatric comorbidities of epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Deformity Angular Ratio Describes the Severity of Spinal Deformity and Predicts the Risk of Neurologic Deficit in Posterior Vertebral Column Resection Surgery.

PubMed

Wang, Xiao-Bin; Lenke, Lawrence G; Thuet, Earl; Blanke, Kathy; Koester, Linda A; Roth, Michael

2016-09-15

Retrospective review of prospectively collected data. To assess the value of the deformity angular ratio (DAR, maximum Cobb measurement divided by number of vertebrae involved) in evaluating the severity of spinal deformity, and predicting the risk of neurologic deficit in posterior vertebral column resection (PVCR). Although the literature has demonstrated that PVCR in spinal deformity patients has achieved excellent outcomes, it is still high risk neurologically. This study, to our knowledge, is the largest series of PVCR patients from a single center, evaluating deformity severity, and potential neurologic deficit risk. A total of 202 consecutive pediatric and adult patients undergoing PVCRs from November 2002 to September 2014 were reviewed. The DAR (coronal DAR, sagittal DAR, and total DAR) was used to evaluate the complexity of the deformity. The incidence of spinal cord monitoring (SCM) events was 20.5%. Eight patients (4.0%) had new neurologic deficits. Patients with a high total DAR (≥25) were significantly younger (20.3 vs. 29.0 yr, P = 0.001), had more severe coronal and sagittal deformities, were more myelopathic (33.3% vs. 11.7%, P = 0.000), needed larger vertebral resections (1.8 vs. 1.3, P = 0.000), and had a significantly higher rate of SCM events than seen in the low total DAR (<25) patients (41.1% vs. 10.8%; P = 0.000). Patients with a high sagittal DAR (≥15) also had a significantly higher rate of SCM events (34.0% vs. 15.1%, P = 0.005) and a greater chance of neurologic deficits postoperatively (12.5% vs. 0, P = 0.000). For patients undergoing a PVCR, the DAR can be used to quantify the angularity of the spinal deformity, which is strongly correlated to the risk of neurologic deficits. Patients with a total DAR greater than or equal to 25 or sagittal DAR greater than or equal to 15 are at much higher risk for intraoperative SCM events and new neurologic deficits. 3.

The Trail Making test: a study of its ability to predict falls in the acute neurological in-patient population.

PubMed

Mateen, Bilal Akhter; Bussas, Matthias; Doogan, Catherine; Waller, Denise; Saverino, Alessia; Király, Franz J; Playford, E Diane

2018-05-01

To determine whether tests of cognitive function and patient-reported outcome measures of motor function can be used to create a machine learning-based predictive tool for falls. Prospective cohort study. Tertiary neurological and neurosurgical center. In all, 337 in-patients receiving neurosurgical, neurological, or neurorehabilitation-based care. Binary (Y/N) for falling during the in-patient episode, the Trail Making Test (a measure of attention and executive function) and the Walk-12 (a patient-reported measure of physical function). The principal outcome was a fall during the in-patient stay ( n = 54). The Trail test was identified as the best predictor of falls. Moreover, addition of other variables, did not improve the prediction (Wilcoxon signed-rank P < 0.001). Classical linear statistical modeling methods were then compared with more recent machine learning based strategies, for example, random forests, neural networks, support vector machines. The random forest was the best modeling strategy when utilizing just the Trail Making Test data (Wilcoxon signed-rank P < 0.001) with 68% (± 7.7) sensitivity, and 90% (± 2.3) specificity. This study identifies a simple yet powerful machine learning (Random Forest) based predictive model for an in-patient neurological population, utilizing a single neuropsychological test of cognitive function, the Trail Making test.

The Deformity Angular Ratio: Does It Correlate With High-Risk Cases for Potential Spinal Cord Monitoring Alerts in Pediatric 3-Column Thoracic Spinal Deformity Corrective Surgery?

PubMed

Lewis, Noah D H; Keshen, Sam G N; Lenke, Lawrence G; Zywiel, Michael G; Skaggs, David L; Dear, Taylor E; Strantzas, Samuel; Lewis, Stephen J

2015-08-01

A retrospective analysis. The purpose of this study was to determine whether the deformity angular ratio (DAR) can reliably assess the neurological risks of patients undergoing deformity correction. Identifying high-risk patients and procedures can help ensure that appropriate measures are taken to minimize neurological complications during spinal deformity corrections. Subjectively, surgeons look at radiographs and evaluate the riskiness of the procedure. However, 2 curves of similar magnitude and location can have significantly different risks of neurological deficit during surgery. Whether the curve spans many levels or just a few can significantly influence surgical strategies. Lenke et al have proposed the DAR, which is a measure of curve magnitude per level of deformity. The data from 35 pediatric spinal deformity correction procedures with thoracic 3-column osteotomies were reviewed. Measurements from preoperative radiographs were used to calculate the DAR. Binary logistic regression was used to model the relationship between DARs (independent variables) and presence or absence of an intraoperative alert (dependent variable). In patients undergoing 3-column osteotomies, sagittal curve magnitude and total curve magnitude were associated with increased incidence of transcranial motor evoked potential changes. Total DAR greater than 45° per level and sagittal DAR greater than 22° per level were associated with a 75% incidence of a motor evoked potential alert, with the incidence increasing to 90% with sagittal DAR of 28° per level. In patients undergoing 3-column osteotomies for severe spinal deformities, the DAR was predictive of patients developing intraoperative motor evoked potential alerts. Identifying accurate radiographical, patient, and procedural risk factors in the correction of severe deformities can help prepare the surgical team to improve safety and outcomes when carrying out complex spinal corrections. 3.

The Intersection between Ocular and Manual Motor Control: Eye–Hand Coordination in Acquired Brain Injury

PubMed Central

Rizzo, John-Ross; Hosseini, Maryam; Wong, Eric A.; Mackey, Wayne E.; Fung, James K.; Ahdoot, Edmond; Rucker, Janet C.; Raghavan, Preeti; Landy, Michael S.; Hudson, Todd E.

2017-01-01

Acute and chronic disease processes that lead to cerebral injury can often be clinically challenging diagnostically, prognostically, and therapeutically. Neurodegenerative processes are one such elusive diagnostic group, given their often diffuse and indolent nature, creating difficulties in pinpointing specific structural abnormalities that relate to functional limitations. A number of studies in recent years have focused on eye–hand coordination (EHC) in the setting of acquired brain injury (ABI), highlighting the important set of interconnected functions of the eye and hand and their relevance in neurological conditions. These experiments, which have concentrated on focal lesion-based models, have significantly improved our understanding of neurophysiology and underscored the sensitivity of biomarkers in acute and chronic neurological disease processes, especially when such biomarkers are combined synergistically. To better understand EHC and its connection with ABI, there is a need to clarify its definition and to delineate its neuroanatomical and computational underpinnings. Successful EHC relies on the complex feedback- and prediction-mediated relationship between the visual, ocular motor, and manual motor systems and takes advantage of finely orchestrated synergies between these systems in both the spatial and temporal domains. Interactions of this type are representative of functional sensorimotor control, and their disruption constitutes one of the most frequent deficits secondary to brain injury. The present review describes the visually mediated planning and control of eye movements, hand movements, and their coordination, with a particular focus on deficits that occur following neurovascular, neurotraumatic, and neurodegenerative conditions. Following this review, we also discuss potential future research directions, highlighting objective EHC as a sensitive biomarker complement within acute and chronic neurological disease processes. PMID:28620341

Child neurology: autism as a model: considerations for advanced training in behavioral child neurology.

PubMed

Jeste, Shafali S; Friedman, Sandra L; Urion, David K

2009-09-01

In this article, we advocate for advanced training for child neurologists in behavior and development in order to facilitate the investigation of childhood behavioral and neurodevelopmental disabilities, with autism serving as a model disorder. We explore the current training options and then propose alternative subspecialty training options that focus on behavior and development, with appreciation that most developmental disabilities are not static encephalopathies but, rather, dynamic processes representing the influence of genetics and environment on neural circuitry.

Neurologic manifestations of chronic methamphetamine abuse

PubMed Central

Rusyniak, Daniel E.

2011-01-01

Summary Chronic methamphetamine abuse has devastating effects on the central nervous system. The degree to which addicts will tolerate the dysfunction in the way they think, feel, move, and even look, is a powerful testimony to the addictive properties of this drug. While the mechanisms behind these disorders are complex, at their heart they involve the recurring increase in the concentrations of central monoamines with subsequent dysfunction in dopaminergic neurotransmission. The mainstay of treatment for the problems associated with chronic methamphetamine abuse is abstinence. However, by recognizing the manifestations of chronic abuse, clinicians will be better able to help their patients get treatment for their addiction and to deal with the neurologic complications related to chronic abuse. PMID:21803215

[Applications of botulinum toxin in Neurology].

PubMed

Garcia-Ruiz, Pedro J

2013-07-07

At present, botulinum toxin (BT) is one of the most fundamental available drugs in Neurology, only comparable with levodopa. BT is currently used in those entities characterized by excessive muscle contraction, including dystonia and spasticity. In addition, BT has been used to control pain associated with increased muscle contraction in dystonia and spasticity, but also is useful to control chronic pain not associated with muscle contraction, such as chronic daily headache. Finally, BT is useful in sialorrhoea and bruxism. The mechanism of action is complex, mainly acting on terminal neuromuscular junction, but also exhibiting analgesic properties, probably through inhibition of pain neurotransmitters release. Copyright © 2012 Elsevier España, S.L. All rights reserved.

[Voltage-gated potassium channels and human neurological diseases].

PubMed

Jin, Hong-Wei; Wang, Xiao-Liang

2002-01-01

Voltage-gated potassium channels (Kv) is the largest, most complex in potassium channel superfamily. It can be divided into Kv alpha subunit and auxiliary two groups. The roles of some Kv channels types, e.g. rapidly inactivating (A-Type channel) and muscarine sensitive channels (M-type channel) are beginning to be understood. They are prominent in nervous system, acting in delicate and accurate ways to control or modify many physiological and pathological functions including membrane excitability, neurotransmitter release, cell proliferation or degeneration, signal transduction in neuronal network. Many human neurological disease pathogenesis are found to be related to mutant of Kv-channels subunit or subtype, such as, learning and memory impairing, ataxia, epilepsy, deafness, etc.

How integrated are neurology and palliative care services? Results of a multicentre mapping exercise.

PubMed

van Vliet, Liesbeth M; Gao, Wei; DiFrancesco, Daniel; Crosby, Vincent; Wilcock, Andrew; Byrne, Anthony; Al-Chalabi, Ammar; Chaudhuri, K Ray; Evans, Catherine; Silber, Eli; Young, Carolyn; Malik, Farida; Quibell, Rachel; Higginson, Irene J

2016-05-10

Patients affected by progressive long-term neurological conditions might benefit from specialist palliative care involvement. However, little is known on how neurology and specialist palliative care services interact. This study aimed to map the current level of connections and integration between these services. The mapping exercise was conducted in eight centres with neurology and palliative care services in the United Kingdom. The data were provided by the respective neurology and specialist palliative care teams. Questions focused on: i) catchment and population served; ii) service provision and staffing; iii) integration and relationships. Centres varied in size of catchment areas (39-5,840 square miles) and population served (142,000-3,500,000). Neurology and specialist palliative care were often not co-terminus. Service provisions for neurology and specialist palliative care were also varied. For example, neurology services varied in the number and type of provided clinics and palliative care services in the settings they work in. Integration was most developed in Motor Neuron Disease (MND), e.g., joint meetings were often held, followed by Parkinsonism (made up of Parkinson's Disease (PD), Multiple-System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP), with integration being more developed for MSA and PSP) and least in Multiple Sclerosis (MS), e.g., most sites had no formal links. The number of neurology patients per annum receiving specialist palliative care reflected these differences in integration (range: 9-88 MND, 3-25 Parkinsonism, and 0-5 MS). This mapping exercise showed heterogeneity in service provision and integration between neurology and specialist palliative care services, which varied not only between sites but also between diseases. This highlights the need and opportunities for improved models of integration, which should be rigorously tested for effectiveness.

From Connectivity Models to Region Labels: Identifying Foci of a Neurological Disorder

PubMed Central

Venkataraman, Archana; Kubicki, Marek; Golland, Polina

2014-01-01

We propose a novel approach to identify the foci of a neurological disorder based on anatomical and functional connectivity information. Specifically, we formulate a generative model that characterizes the network of abnormal functional connectivity emanating from the affected foci. This allows us to aggregate pairwise connectivity changes into a region-based representation of the disease. We employ the variational expectation-maximization algorithm to fit the model and subsequently identify both the afflicted regions and the differences in connectivity induced by the disorder. We demonstrate our method on a population study of schizophrenia. PMID:23864168

Fractals in the neurosciences, Part II: clinical applications and future perspectives.

PubMed

Di Ieva, Antonio; Esteban, Francisco J; Grizzi, Fabio; Klonowski, Wlodzimierz; Martín-Landrove, Miguel

2015-02-01

It has been ascertained that the human brain is a complex system studied at multiple scales, from neurons and microcircuits to macronetworks. The brain is characterized by a hierarchical organization that gives rise to its highly topological and functional complexity. Over the last decades, fractal geometry has been shown as a universal tool for the analysis and quantification of the geometric complexity of natural objects, including the brain. The fractal dimension has been identified as a quantitative parameter for the evaluation of the roughness of neural structures, the estimation of time series, and the description of patterns, thus able to discriminate different states of the brain in its entire physiopathological spectrum. Fractal-based computational analyses have been applied to the neurosciences, particularly in the field of clinical neurosciences including neuroimaging and neuroradiology, neurology and neurosurgery, psychiatry and psychology, and neuro-oncology and neuropathology. After a review of the basic concepts of fractal analysis and its main applications to the basic neurosciences in part I of this series, here, we review the main applications of fractals to the clinical neurosciences for a holistic approach towards a fractal geometry model of the brain. © The Author(s) 2013.

[The optimization of an early rehabilitation program for cerebral stroke patients: the use of different methods of magneto- and laser therapy].

PubMed

Kochetkov, A V; Gorbunov, F E; Minenkov, A A; Strel'tsova, E N; Filina, T F; Krupennikov, A I

2000-01-01

Magnetotherapy and laser therapy were used in complex and complex-combined regimens in 75 patients after cerebral ischemic or hemorrhagic stroke starting on the poststroke week 4-5. Clinico-neurologic, neurophysiological and cerebrohemodynamic findings evidence for the highest effectiveness of neurorehabilitation including complex magneto-laser therapy in hemispheric ischemic and hemorrhagic stroke of subcortical location in the absence of marked clinico-tomographic signs of dyscirculatory encephalopathy. Complex-combined magneto-laser therapy is more effective for correction of spastic dystonia. Mutual potentiation of magnetotherapy and laser therapy results in maximal development of collateral circulation and cerebral hemodynamic reserve (84% of the patients). Complex effects manifest in arteriodilating and venotonic effects. Complex magneto-laser therapy is accompanied by reduction of hyperthrombocythemia and hyperfibrinogenemia.

Control of Abnormal Synchronization in Neurological Disorders

PubMed Central

Popovych, Oleksandr V.; Tass, Peter A.

2014-01-01

In the nervous system, synchronization processes play an important role, e.g., in the context of information processing and motor control. However, pathological, excessive synchronization may strongly impair brain function and is a hallmark of several neurological disorders. This focused review addresses the question of how an abnormal neuronal synchronization can specifically be counteracted by invasive and non-invasive brain stimulation as, for instance, by deep brain stimulation for the treatment of Parkinson’s disease, or by acoustic stimulation for the treatment of tinnitus. On the example of coordinated reset (CR) neuromodulation, we illustrate how insights into the dynamics of complex systems contribute to successful model-based approaches, which use methods from synergetics, non-linear dynamics, and statistical physics, for the development of novel therapies for normalization of brain function and synaptic connectivity. Based on the intrinsic multistability of the neuronal populations induced by spike timing-dependent plasticity (STDP), CR neuromodulation utilizes the mutual interdependence between synaptic connectivity and dynamics of the neuronal networks in order to restore more physiological patterns of connectivity via desynchronization of neuronal activity. The very goal is to shift the neuronal population by stimulation from an abnormally coupled and synchronized state to a desynchronized regime with normalized synaptic connectivity, which significantly outlasts the stimulation cessation, so that long-lasting therapeutic effects can be achieved. PMID:25566174

A Mixture of Persistent Organic Pollutants and Perfluorooctanesulfonic Acid Induces Similar Behavioural Responses, but Different Gene Expression Profiles in Zebrafish Larvae

PubMed Central

Khezri, Abdolrahman; Fraser, Thomas W. K.; Nourizadeh-Lillabadi, Rasoul; Kamstra, Jorke H.; Berg, Vidar; Zimmer, Karin E.; Ropstad, Erik

2017-01-01

Persistent organic pollutants (POPs) are widespread in the environment and some may be neurotoxic. As we are exposed to complex mixtures of POPs, we aimed to investigate how a POP mixture based on Scandinavian human blood data affects behaviour and neurodevelopment during early life in zebrafish. Embryos/larvae were exposed to a series of sub-lethal doses and behaviour was examined at 96 h post fertilization (hpf). In order to determine the sensitivity window to the POP mixture, exposure models of 6 to 48 and 48 to 96 hpf were used. The expression of genes related to neurological development was also assessed. Results indicate that the POP mixture increases the swimming speed of larval zebrafish following exposure between 48 to 96 hpf. This behavioural effect was associated with the perfluorinated compounds, and more specifically with perfluorooctanesulfonic acid (PFOS). The expression of genes related to the stress response, GABAergic, dopaminergic, histaminergic, serotoninergic, cholinergic systems and neuronal maintenance, were altered. However, there was little overlap in those genes that were significantly altered by the POP mixture and PFOS. Our findings show that the POP mixture and PFOS can have a similar effect on behaviour, yet alter the expression of genes relevant to neurological development differently. PMID:28146072

Tourette Syndrome: School-Based Interventions for Tics and Associated Conditions

ERIC Educational Resources Information Center

Koutsoklenis, Athanasios; Theodoridou, Zoe

2012-01-01

Tourette syndrome (TS) is a neurological disorder characterized by motor and phonic tics that follow a fluctuating pattern of severity, intensity and frequency. TS is often associated with other conditions such as attention-deficit/hyperactivity disorder, obsessive-compulsive disorder and learning difficulties. This complex phenotype affects the…

Brain Mechanisms of Attentional Control.

ERIC Educational Resources Information Center

Wilke, Thomas

Lack of attentional control--inability to concentrate--has often made the difference between successful and unsuccessful performance on the part of athletes. Attention is controlled neurologically by a very complex interaction of a large portion of the cerebrum and is not localized to any one structure. The mechanism involves a memory retrieval…

Learning through Seeing and Doing: Visual Supports for Children with Autism

ERIC Educational Resources Information Center

Rao, Shaila M.; Gagie, Brenda

2006-01-01

Autism is a life-long, complex developmental disorder that causes impairment in the way individuals process information. Autism belongs to heterogeneous categories of developmental disabilities where neurological disorders lead to deficits in a child's ability to communicate, understand language, play, develop social skills, and relate to others.…

Testing the Sarcocystis neurona vaccine using an equine protozoal myeloencephalitis challenge model.

PubMed

Saville, William J A; Dubey, Jitender P; Marsh, Antoinette E; Reed, Stephen M; Keene, Robert O; Howe, Daniel K; Morrow, Jennifer; Workman, Jeffrey D

2017-11-30

Equine protozoal myeloencephalitis (EPM) is an important equine neurologic disorder, and treatments for the disease are often unrewarding. Prevention of the disease is the most important aspect for EPM, and a killed vaccine was previously developed for just that purpose. Evaluation of the vaccine had been hampered by lack of post vaccination challenge. The purpose of this study was to determine if the vaccine could prevent development of clinical signs after challenge with Sarcocystis neurona sporocysts in an equine challenge model. Seventy horses that were negative for antibodies to S. neurona and were neurologically normal were randomly assigned to vaccine or placebo groups and divided into short-term duration of immunity (study #1) and long-term duration of immunity (study #2) studies. S. neurona sporocysts used for the challenge were generated in the opossum/raccoon cycle isolate SN 37-R. Study #1 horses received an initial vaccination and a booster, and were challenged 34days post second vaccination. Study #2 horses received a vaccination and two boosters and were challenged 139days post third vaccination. All horses in study #1 developed neurologic signs (n=30) and there was no difference between the vaccinates and controls (P=0.7683). All but four horses in study #2 developed detectable neurologic deficits. The neurologic signs, although not statistically significant, were worse in the vaccinated horses (P=0.1559). In these two studies, vaccination with the S. neurona vaccine failed to prevent development of clinical neurologic deficits. Copyright © 2017 Elsevier B.V. All rights reserved.

[Children's medically complex diseases unit. A model required in all our hospitals].

PubMed

Climent Alcalá, Francisco José; García Fernández de Villalta, Marta; Escosa García, Luis; Rodríguez Alonso, Aroa; Albajara Velasco, Luis Adolfo

2018-01-01

The increase in survival of children with severe diseases has led to the rise of children with chronic diseases, sometimes with lifelong disabilities. In 2008, a unit for the specific care of medically complex children (MCC) was created in Hospital La Paz. To describe the work and care activities of this Unit. Patients and methods An analysis was performed on all discharge reports of the Unit between January 2014 and July 2016. The MCC Unit has 6 beds and daily outpatient clinic. A total of 1,027 patients have been treated since the creation of the unit, with 243 from 2014. The median age was 24.2 months (IQ: 10.21-84.25). The large majority (92.59%) have multiple diseases, the most frequent chronic conditions observed were neurological (76.95%), gastrointestinal (63.78%), and respiratory diseases (61.72%). More than two-thirds (69.54%) of MCC are dependent on technology, 53.49% on respiratory support, and 35.80% on nutritional support. Hospital admission rates have increased annually. There have been 403 admissions since 2014, of which 8.93% were re-admissions within 30 days of hospital discharge. The median stay during 2014-2016 was 6 days (IQ: 3-14). The occupancy rate has been above 100% for this period. Currently, 210 patients remain on follow-up (86.42%), and 11 children (4.53%) were discharged to their referral hospitals. The mortality rate is 9.05% (22 deaths). The main condition of these 22 patients was neurological (9 patients). Infectious diseases were the leading cause of death. MCC should be treated in specialized units in tertiary or high-level hospitals. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Phenotype of CNTNAP1: a study of patients demonstrating a specific severe congenital hypomyelinating neuropathy with survival beyond infancy.

PubMed

Low, K J; Stals, K; Caswell, R; Wakeling, M; Clayton-Smith, J; Donaldson, A; Foulds, N; Norman, A; Splitt, M; Urankar, K; Vijayakumar, K; Majumdar, A; Study, Ddd; Ellard, S; Smithson, S F

2018-06-01

CHN is genetically heterogeneous and its genetic basis is difficult to determine on features alone. CNTNAP1 encodes CASPR, integral in the paranodal junction high molecular mass complex. Nineteen individuals with biallelic variants have been described in association with severe congenital hypomyelinating neuropathy, respiratory compromise, profound intellectual disability and death within the first year. We report 7 additional patients ascertained through exome sequencing. We identified 9 novel CNTNAP1 variants in 6 families: three missense variants, four nonsense variants, one frameshift variant and one splice site variant. Significant polyhydramnios occurred in 6/7 pregnancies. Severe respiratory compromise was seen in 6/7 (tracheostomy in 5). A complex neurological phenotype was seen in all patients who had marked brain hypomyelination/demyelination and profound developmental delay. Additional neurological findings included cranial nerve compromise: orobulbar dysfunction in 5/7, facial nerve weakness in 4/7 and vocal cord paresis in 5/7. Dystonia occurred in 2/7 patients and limb contractures in 5/7. All had severe gastroesophageal reflux, and a gastrostomy was required in 5/7. In contrast to most previous reports, only one patient died in the first year of life. Protein modelling was performed for all detected CNTNAP1 variants. We propose a genotype-phenotype correlation, whereby hypomorphic missense variants partially ameliorate the phenotype, prolonging survival. This study suggests that biallelic variants in CNTNAP1 cause a distinct recognisable syndrome, which is not caused by other genes associated with CHN. Neonates presenting with this phenotype will benefit from early genetic definition to inform clinical management and enable essential genetic counselling for their families.

Electroacupuncture modulates stromal cell-derived factor-1α expression and mobilization of bone marrow endothelial progenitor cells in focal cerebral ischemia/reperfusion model rats.

PubMed

Xie, Chenchen; Gao, Xiang; Luo, Yong; Pang, Yueshan; Li, Man

2016-10-01

Stromal cell-derived factor-1α(SDF-1α) plays a crucial role in regulating the mobilization, migration and homing of endothelial progenitor cells(EPCs). Electroacupuncture(EA), a modern version of Traditional Chinese Medicine, can improve neurological recovery and angiogenesis in cerebral ischemic area. This study aimed to investigate the effects of electroacupuncture(EA) on the mobilization and migration of bone marrow EPCs and neurological functional recovery in rats model after focal cerebral ischemia/reperfusion and the potentially involved mechanisms. Sprague-Dawley rats received filament occlusion of the right middle cerebral artery for 2h followed by reperfusion for 12h, 1d, 2d, 3d, 7d respectively. Rats were randomly divided into sham group, model group and EA group. After 2h of the reperfusion, EA was given at the "Baihui" (GV 20)/Siguan ("Hegu" (LI 4)/"Taichong" (LR 3)) acupoints in the EA group. Modified neurological severity score (mNSS) was used to assess the neurological functional recovery. EPCs number and SDF-1α level in bone marrow(BM) and peripheral blood(PB) were detected by using fluorescence-activated cell sorting (FACS) analysis and quantitative real time polymerase chain reaction (qRT-PCR) respectively. An mNSS test showed that EA treatment significantly improved the neurological functional outcome. EPCs number in PB and BM were obviously increased in the EA group. After cerebral ischemia, the SDF-1α level was decreased in BM while it was increased in PB, which implied a gradient of SDF-1α among BM and PB after ischemia. It suggested that the forming of SDF-1α concentration gradient can induce the mobilization and homing of EPCs. Eletroacupuncture as a treatment can accelerate and increase the forming of SDF-1α concentration gradient to further induce the mobilization of EPCs and angiogenesis in ischemic brain and improve the neurological function recovery. Copyright © 2016 Elsevier B.V. All rights reserved.

Critical determinants of the epilepsy treatment gap: a cross-national analysis in resource-limited settings

PubMed Central

Meyer, Ana-Claire L.; Dua, Tarun; Boscardin, John; Escarce, José J.; Saxena, Shekhar; Birbeck, Gretchen L.

2013-01-01

Purpose Epilepsy is one of the most common serious neurological disorders worldwide. Our objective was to determine which economic, healthcare, neurology and epilepsy specific resources were associated with untreated epilepsy in resource-constrained settings. Methods A systematic review of the literature identified community-based studies in resource-constrained settings that calculated the epilepsy treatment gap, the proportion with untreated epilepsy, from prevalent active epilepsy cases. Economic, healthcare, neurology and epilepsy specific resources were taken from existing datasets. Poisson regression models with jackknifed standard errors were used to create bivariate and multivariate models comparing the association between treatment status and economic and health resource indicators. Relative risks were reported. Key Findings Forty-seven studies of 8285 individuals from 24 countries met inclusion criteria. Bivariate analysis demonstrated that individuals residing in rural locations had significantly higher risks of untreated epilepsy [Relative Risk(RR)=1.63; 95% confidence interval(CI):1.26,2.11]. Significantly lower risks of untreated epilepsy were observed for higher physician density [RR=0.65, 95% CI:0.55,0.78], presence of a lay [RR=0.74, 95%CI:0.60,0.91] or professional association for epilepsy [RR=0.73, 95%CI:0.59,0.91], or post-graduate neurology training program [RR=0.67, 95%CI:0.55, 0.82]. In multivariate models, higher physician density maintained significant effects [RR=0.67; 95%CI:0.52,0.88]. Significance Even among resource-limited regions, people with epilepsy in countries with fewer economic, healthcare, neurology and epilepsy specific resources are more likely to have untreated epilepsy. Community-based epilepsy care programs have improved access to treatment but in order to decrease the epilepsy treatment gap, poverty and inequalities of healthcare, neurological and epilepsy resources must be dealt with at the local, national, and global levels. PMID:23106784

Murine Sialidase Neu3 facilitates GM2 degradation and bypass in mouse model of Tay-Sachs disease.

PubMed

Seyrantepe, Volkan; Demir, Secil Akyildiz; Timur, Zehra Kevser; Von Gerichten, Johanna; Marsching, Christian; Erdemli, Esra; Oztas, Emin; Takahashi, Kohta; Yamaguchi, Kazunori; Ates, Nurselin; Dönmez Demir, Buket; Dalkara, Turgay; Erich, Katrin; Hopf, Carsten; Sandhoff, Roger; Miyagi, Taeko

2018-01-01

Tay-Sachs disease is a severe lysosomal storage disorder caused by mutations in Hexa, the gene that encodes for the α subunit of lysosomal β-hexosaminidase A (HEXA), which converts GM2 to GM3 ganglioside. Unexpectedly, Hexa -/- mice have a normal lifespan and show no obvious neurological impairment until at least one year of age. These mice catabolize stored GM2 ganglioside using sialidase(s) to remove sialic acid and form the glycolipid GA2, which is further processed by β-hexosaminidase B. Therefore, the presence of the sialidase (s) allows the consequences of the Hexa defect to be bypassed. To determine if the sialidase NEU3 contributes to GM2 ganglioside degradation, we generated a mouse model with combined deficiencies of HEXA and NEU3. The Hexa -/- Neu3 -/- mice were healthy at birth, but died at 1.5 to 4.5months of age. Thin-layer chromatography and mass spectrometric analysis of the brains of Hexa -/- Neu3 -/- mice revealed the abnormal accumulation of GM2 ganglioside. Histological and immunohistochemical analysis demonstrated cytoplasmic vacuolation in the neurons. Electron microscopic examination of the brain, kidneys and testes revealed pleomorphic inclusions of many small vesicles and complex lamellar structures. The Hexa -/- Neu3 -/- mice exhibited progressive neurodegeneration with neuronal loss, Purkinje cell depletion, and astrogliosis. Slow movement, ataxia, and tremors were the prominent neurological abnormalities observed in these mice. Furthermore, radiographs revealed abnormalities in the skeletal bones of the Hexa -/- Neu3 -/- mice. Thus, the Hexa -/- Neu3 -/- mice mimic the neuropathological and clinical abnormalities of the classical early-onset Tay-Sachs patients, and provide a suitable model for the future pre-clinical testing of potential treatments for this condition. Copyright © 2017 Elsevier Inc. All rights reserved.

A simplified clinical prediction rule for prognosticating independent walking after spinal cord injury: a prospective study from a Canadian multicenter spinal cord injury registry.

PubMed

Hicks, Katharine E; Zhao, Yichen; Fallah, Nader; Rivers, Carly S; Noonan, Vanessa K; Plashkes, Tova; Wai, Eugene K; Roffey, Darren M; Tsai, Eve C; Paquet, Jerome; Attabib, Najmedden; Marion, Travis; Ahn, Henry; Phan, Philippe

2017-10-01

Traumatic spinal cord injury (SCI) is a debilitating condition with limited treatment options for neurologic or functional recovery. The ability to predict the prognosis of walking post injury with emerging prediction models could aid in rehabilitation strategies and reintegration into the community. To revalidate an existing clinical prediction model for independent ambulation (van Middendorp et al., 2011) using acute and long-term post-injury follow-up data, and to investigatethe accuracy of a simplified model using prospectively collected data from a Canadian multicenter SCI database, the Rick Hansen Spinal Cord Injury Registry (RHSCIR). Prospective cohort study. The analysis cohort consisted of 278 adult individuals with traumatic SCI enrolled in the RHSCIR for whom complete neurologic examination data and Functional Independence Measure (FIM) outcome data were available. The FIM locomotor score was used to assess independent walking ability (defined as modified or complete independence in walk or combined walk and wheelchair modality) at 1-year follow-up for each participant. A logistic regression (LR) model based on age and four neurologic variables was applied to our cohort of 278 RHSCIR participants. Additionally, a simplified LR model was created. The Hosmer-Lemeshow goodness of fit test was used to check if the predictive model is applicable to our data set. The performance of the model was verified by calculating the area under the receiver operating characteristic curve (AUC). The accuracy of the model was tested using a cross-validation technique. This study was supported by a grant from The Ottawa Hospital Academic Medical Organization ($50,000 over 2 years). The RHSCIR is sponsored by the Rick Hansen Institute and is supported by funding from Health Canada, Western Economic Diversification Canada, and the provincial governments of Alberta, British Columbia, Manitoba, and Ontario. ET and JP report receiving grants from the Rick Hansen Institute (approximately $60,000 and $30,000 per year, respectively). DMR reports receiving remuneration for consulting services provided to Palladian Health, LLC and Pacira Pharmaceuticals, Inc ($20,000-$30,000 annually), although neither relationship presents a potential conflict of interest with the submitted work. KEH received a grant for involvement in the present study from the Government of Canada as part of the Canada Summer Jobs Program ($3,000). JP reports receiving an educational grant from Medtronic Canada outside of the submitted work ($75,000 annually). TM reports receiving educational fellowship support from AO Spine, AO Trauma, and Medtronic; however, none of these relationships are financial in nature. All remaining authors have no conflicts of interest to disclose. The fitted prediction model generated 85% overall classification accuracy, 79% sensitivity, and 90% specificity. The prediction model was able to accurately classify independent walking ability (AUC 0.889, 95% confidence interval [CI] 0.846-0.933, p<.001) compared with the existing prediction model, despite the use of a different outcome measure (FIM vs. Spinal Cord Independence Measure) to qualify walking ability. A simplified, three-variable LR model based on age and two neurologic variables had an overall classification accuracy of 84%, with 76% sensitivity and 90% specificity, demonstrating comparable accuracy with its five-variable prediction model counterpart. The AUC was 0.866 (95% CI 0.816-0.916, p<.01), only marginally less than that of the existing prediction model. A simplified predictive model with similar accuracy to a more complex model for predicting independent walking was created, which improves utility in a clinical setting. Such models will allow clinicians to better predict the prognosis of ambulation in individuals who have sustained a traumatic SCI. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Reported time to onset of neurological adverse drug reactions among different age and gender groups using metoclopramide: an analysis of the global database Vigibase®.

PubMed

Svendsen, Kristian; Wood, Mollie; Olsson, Erika; Nordeng, Hedvig

2018-05-01

Despite FDA and EMA warnings of long-term use, little is known regarding the time to onset (TTO) of neurological adverse drug reactions (ADR) for metoclopramide. The aims of this study were, first, to evaluate whether neurological ADRs are more commonly reported for metoclopramide than for other medications, and second, to describe how time to onset of neurological ADRs differs by age and gender. All ADR reports with metoclopramide as the suspected/interacting drug were extracted from the WHOs Global ADR database Vigibase® between 1967 and May 2016. Cox proportional hazards models were fit using TTO of neurological ADRs as the outcome and age, gender, and type of ADR as predictors. Proportional Reporting Ratios (PRRs) for neurological ADRs were compared across age and gender. Lawyer reports were excluded in the analysis. Over 47,000 ADR reports with metoclopramide were identified. Over one third (35.6%) of the reports came from lawyers. The majority of ADRs in general and neurological ADRs in specific occurred within the first 5 days of metoclopramide use (median 1 day). TTO increased with age. Neurological ADRs were reported two to four times as frequently for metoclopramide than for other drugs, with the highest PRRs observed in children (PRR = 4.24 for girls and 4.60 for boys). Most adverse drug reactions occur within the first 5 days of treatment with metoclopramide. Patients requiring use of metoclopramide should be carefully monitored for neurological ADRs during the first days of treatment.

DETERMINATION OF MERCURY IN HAIR OF CHILDREN.

PubMed

Pino, A; Bocca, B; Forte, G; Majorani, C; Petrucci, F; Senofonte, O; Alimonti, A

2018-06-25

Although high or repeated exposure to different forms of Hg can have serious health consequences, the most important toxicity risk for humans is as methylmercury (MeHg) which exposure is mainly through consumption of fish. Generally, more than the 80% of Hg in hair is as MeHg, which is taken up by hair follicles as MeHg-cysteine complexes. In this context, hair samples were collected from 200 children (7 years) living in a site in the North East (A) and from 299 children (6-11 years) living in a urban area of South Italy (B) to determine the levels of MeHg. Considering the neurotoxicity of MeHg, children were subjected to cognitive and neuropsychological tests. The hair values of Hg in the children population groups were comparable with data reported in other international surveys. On the other hand, combining results of the neurological tests with Hg levels, a possible relationship between Hg and an increase of the errors average reported in some neurological has been noted. Although the Hg levels were not elevated, a possible neurological influence in children, a population more susceptible than adults, might not be excluded. But the influence on neurological performances of the children could be also due to the family environment (socio economic status, educational level, etc.). Copyright © 2018. Published by Elsevier B.V.

Recurrence of Neurological Deficits in an F/A-18D Pilot Following Loss of Cabin Pressure at Altitude.

PubMed

Robinson, Tom; Evangelista, Jose S; Latham, Emi; Mukherjee, Samir T; Pilmanis, Andrew

2016-08-01

Supersonic, high altitude aviation places its pilots and aircrew in complex environments, which may lead to injury that is not easily diagnosed or simply treated. Decompression illness (either venous or arterial) and environmental conditions (e.g., abnormal gases and pressure) are the most likely adverse effects aircrew often face. Though symptomatic aircrew personnel may occasionally require hyperbaric oxygen treatment, it is rare to require more than one treatment before returning to baseline function. This challenging aviation case details the clinical course and discusses the salient physiological factors of an F/A-18D pilot who presented with neurological symptoms following loss of cabin pressure at altitude. Most crucial to this discussion was the requirement for multiple hyperbaric oxygen treatments over several days due to recurrence of symptoms. The likelihood of recurrence during and after future flights cannot be estimated with accuracy. This case illustrates a degree of recurrences for neurological symptoms in aviation (hypobaric exposure to hyperbaric baseline environment) that has not previously been described. Robinson T, Evangelista JS III, Latham E, Mukherjee ST, Pilmanis A. Recurrence of neurological deficits in an F/A-18D pilot following loss of cabin pressure at altitude. Aerosp Med Hum Perform. 2016; 87(8):740-744.

On the personal facets of quality of life in chronic neurological disorders.

PubMed

Giovagnoli, Anna R; Martins da Silva, Antonio; Federico, Antonio; Cornelio, Ferdinando

2009-01-01

Quality of life (QOL) is an important clinical endpoint, but it remarkably varies in patients with similar neurological conditions. This study explored the role of spirituality (i.e., the complex of personal transcendence, connectedness, purpose, and values) in determining QOL in chronic neurological disorders.~Seventy-two patients with epilepsy, brain tumours or ischemic or immune-mediate brain damage compiled inventories for QOL (WHOQOL 100), spirituality (Spiritual, Religious and Personal Beliefs, WHOSRPB), depression (Beck Depression Inventory, BDI), anxiety (State-Trait Anxiety Inventory, STAI), and cognitive self-efficacy (Multiple Ability Self-Report Questionnaire, MASQ) and underwent neuropsychological testing. With respect to 45 healthy controls, the patients reported worse QOL, with no difference between the four patient subgroups. Factor analyses of the WHOSRPB, STAI, and BDI scores and of the MASQ and neuropsychological test scores yielded four (Personal Meaning, Inner Energy, Awe and Openness, Mood) and three factors (Control Functions, Cognition, Memory), respectively. Mood, Cognition, Inner Energy, schooling, and subjective health status correlated with the WHOQOL scores, but at regression analysis only Mood and Inner Energy predicted QOL. This suggests that spirituality, as a personal dimension distinct from mood, contributes to determine QOL. A multidimensional assessment of QOL, including personal facets, may explain differences between patients with chronic neurological disorders.

Critical illness polyneuropathy (CIP) in neurological early rehabilitation: clinical and neurophysiological features.

PubMed

Schmidt, Simone B; Rollnik, Jens D

2016-12-15

Critical illness polyneuropathy (CIP) is a complex disease affecting 30-70% of critically ill patients. Clinical (Barthel index, length of stay (LOS), morbidity, duration of mechanical ventilation, routine lab results) and neurophysiological (neurography) data of 191 patients admitted to neurological early rehabilitation and diagnosed with CIP have been analyzed retrospectively. CIP diagnosis was correct in 159 cases (83%). In this study, systemic inflammation, sepsis, systemic inflammatory response syndrome (SIRS), multiple organic failure (MOF), chronic renal failure, liver dysfunction, mechanical ventilation, diabetes, dyslipidemia and impaired ion homeostasis (hypocalcaemia, hypokalemia) were associated with CIP. Neurography, in particular of the peroneal, sural, tibial and median nerves, helped to identify CIP patients. Compound muscle action potential amplitude (r = -0.324, p < 0.05), as well as sensory (r = -0.389, p < 0.05) and motor conduction velocity (r = -0.347, p < 0.05) of the median nerve correlated with LOS in neurological early rehabilitation but not with outcome measures. In most cases, diagnosis of CIP among neurological early rehabilitation patients seems to be correct. Neurography may help to verify the diagnosis and to learn more about CIP pathophysiology, but it does not allow outcome prediction. Further studies on CIP are strongly encouraged.

Cyclodextrins, blood-brain barrier, and treatment of neurological diseases.

PubMed

Vecsernyés, Miklós; Fenyvesi, Ferenc; Bácskay, Ildikó; Deli, Mária A; Szente, Lajos; Fenyvesi, Éva

2014-11-01

Biological barriers are the main defense systems of the homeostasis of the organism and protected organs. The blood-brain barrier (BBB), formed by the endothelial cells of brain capillaries, not only provides nutrients and protection to the central nervous system but also restricts the entry of drugs, emphasizing its importance in the treatment of neurological diseases. Cyclodextrins are increasingly used in human pharmacotherapy. Due to their favorable profile to form hydrophilic inclusion complexes with poorly soluble active pharmaceutical ingredients, they are present as excipients in many marketed drugs. Application of cyclodextrins is widespread in formulations for oral, parenteral, nasal, pulmonary, and skin delivery of drugs. Experimental and clinical data suggest that cyclodextrins can be used not only as excipients for centrally acting marketed drugs like antiepileptics, but also as active pharmaceutical ingredients to treat neurological diseases. Hydroxypropyl-β-cyclodextrin received orphan drug designation for the treatment of Niemann-Pick type C disease. In addition to this rare lysosomal storage disease with neurological symptoms, experimental research revealed the potential therapeutic use of cyclodextrins and cyclodextrin nanoparticles in neurodegenerative diseases, stroke, neuroinfections and brain tumors. In this context, the biological effects of cyclodextrins, their interaction with plasma membranes and extraction of different lipids are highly relevant at the level of the BBB. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Inflammasomes link vascular disease with neuroinflammation and brain disorders

PubMed Central

Lénárt, Nikolett; Brough, David

2016-01-01

The role of inflammation in neurological disorders is increasingly recognised. Inflammatory processes are associated with the aetiology and clinical progression of migraine, psychiatric conditions, epilepsy, cerebrovascular diseases, dementia and neurodegeneration, such as seen in Alzheimer’s or Parkinson’s disease. Both central and systemic inflammatory actions have been linked with the development of brain diseases, suggesting that complex neuro-immune interactions could contribute to pathological changes in the brain across multiple temporal and spatial scales. However, the mechanisms through which inflammation impacts on neurological disease are improperly defined. To develop effective therapeutic approaches, it is imperative to understand how detrimental inflammatory processes could be blocked selectively, or controlled for prolonged periods, without compromising essential immune defence mechanisms. Increasing evidence indicates that common risk factors for brain disorders, such as atherosclerosis, diabetes, hypertension, obesity or infection involve the activation of NLRP3, NLRP1, NLRC4 or AIM2 inflammasomes, which are also associated with various neurological diseases. This review focuses on the mechanisms whereby inflammasomes, which integrate diverse inflammatory signals in response to pathogen-driven stimuli, tissue injury or metabolic alterations in multiple cell types and different organs of the body, could functionally link vascular- and neurological diseases and hence represent a promising therapeutic target. PMID:27486046

Complex regional pain syndrome type I (RSD): pathology of skeletal muscle and peripheral nerve.

PubMed

van der Laan, L; ter Laak, H J; Gabreëls-Festen, A; Gabreëls, F; Goris, R J

1998-07-01

Reflex sympathetic dystrophy (RSD) (recently reclassified as complex regional pain syndrome type I) is a syndrome occurring in extremities and, when chronic, results in severe disability and untractable pain. RSD may be accompanied by neurologic symptoms even when there is no previous neurologic lesion. There is no consensus as to the pathogenic mechanism involved in RSD. To gain insight into the pathophysiology of RSD, we studied histopathology of skeletal muscle and peripheral nerve from patients with chronic RSD in a lower extremity. In eight patients with chronic RSD, an above-the-knee amputation was performed because of a nonfunctional limb. Specimens of sural nerves, tibial nerves, common peroneal nerves, gastrocnemius muscles, and soleus muscles were obtained from the amputated legs and analyzed by light and electron microscopy. In all patients, the affected leg showed similar neurologic symptoms such as spontaneous pain, hyperpathy, allodynia, paresis, and anesthesia dolorosa. The nerves showed no consistent abnormalities of myelinated fibers. In four patients, the C-fibers showed electron microscopic pathology. In all patients, the gastrocnemius and soleus muscle specimens showed a decrease of type I fibers, an increase of lipofuscin pigment, atrophic fibers, and severely thickened basal membrane layers of the capillaries. In chronic RSD, efferent nerve fibers were histologically unaffected; from afferent fibers, only C-fibers showed histopathologic abnormalities. Skeletal muscle showed a variety of histopathologic findings, which are similar to the histologic abnormalities found in muscles of patients with diabetes.

MeCP2 co-ordinates liver lipid metabolism with the NCoR1/HDAC3 corepressor complex

PubMed Central

Kyle, Stephanie M.; Saha, Pradip K.; Brown, Hannah M.; Chan, Lawrence C.; Justice, Monica J.

2016-01-01

Rett syndrome (RTT; OMIM 312750), a progressive neurological disorder, is caused by mutations in methyl-CpG-binding protein 2 (MECP2; OMIM 300005), a ubiquitously expressed factor. A genetic suppressor screen designed to identify therapeutic targets surprisingly revealed that downregulation of the cholesterol biosynthesis pathway improves neurological phenotypes in Mecp2 mutant mice. Here, we show that MeCP2 plays a direct role in regulating lipid metabolism. Mecp2 deletion in mice results in a host of severe metabolic defects caused by lipid accumulation, including insulin resistance, fatty liver, perturbed energy utilization, and adipose inflammation by macrophage infiltration. We show that MeCP2 regulates lipid homeostasis by anchoring the repressor complex containing NCoR1 and HDAC3 to its lipogenesis targets in hepatocytes. Consistently, we find that liver targeted deletion of Mecp2 causes fatty liver disease and dyslipidemia similar to HDAC3 liver-specific deletion. These findings position MeCP2 as a novel component in metabolic homeostasis. Rett syndrome patients also show signs of peripheral dyslipidemia; thus, together these data suggest that RTT should be classified as a neurological disorder with systemic metabolic components. We previously showed that treatment of Mecp2 mice with statin drugs alleviated motor symptoms and improved health and longevity. Lipid metabolism is a highly treatable target; therefore, our results shed light on new metabolic pathways for treatment of Rett syndrome. PMID:27288453

Three-Dimensional Blood-Brain Barrier Model for in vitro Studies of Neurovascular Pathology

NASA Astrophysics Data System (ADS)

Cho, Hansang; Seo, Ji Hae; Wong, Keith H. K.; Terasaki, Yasukazu; Park, Joseph; Bong, Kiwan; Arai, Ken; Lo, Eng H.; Irimia, Daniel

2015-10-01

Blood-brain barrier (BBB) pathology leads to neurovascular disorders and is an important target for therapies. However, the study of BBB pathology is difficult in the absence of models that are simple and relevant. In vivo animal models are highly relevant, however they are hampered by complex, multi-cellular interactions that are difficult to decouple. In vitro models of BBB are simpler, however they have limited functionality and relevance to disease processes. To address these limitations, we developed a 3-dimensional (3D) model of BBB on a microfluidic platform. We verified the tightness of the BBB by showing its ability to reduce the leakage of dyes and to block the transmigration of immune cells towards chemoattractants. Moreover, we verified the localization at endothelial cell boundaries of ZO-1 and VE-Cadherin, two components of tight and adherens junctions. To validate the functionality of the BBB model, we probed its disruption by neuro-inflammation mediators and ischemic conditions and measured the protective function of antioxidant and ROCK-inhibitor treatments. Overall, our 3D BBB model provides a robust platform, adequate for detailed functional studies of BBB and for the screening of BBB-targeting drugs in neurological diseases.

The translational potential of human induced pluripotent stem cells for clinical neurology : The translational potential of hiPSCs in neurology.

PubMed

Devine, Helen; Patani, Rickie

2017-04-01

The induced pluripotent state represents a decade-old Nobel prize-winning discovery. Human-induced pluripotent stem cells (hiPSCs) are generated by the nuclear reprogramming of any somatic cell using a variety of established but evolving methods. This approach offers medical science unparalleled experimental opportunity to model an individual patient's disease "in a dish." HiPSCs permit developmentally rationalized directed differentiation into any cell type, which express donor cell mutation(s) at pathophysiological levels and thus hold considerable potential for disease modeling, drug discovery, and potentially cell-based therapies. This review will focus on the translational potential of hiPSCs in clinical neurology and the importance of integrating this approach with complementary model systems to increase the translational yield of preclinical testing for the benefit of patients. This strategy is particularly important given the expected increase in prevalence of neurodegenerative disease, which poses a major burden to global health over the coming decades.

A mouse model of DEPDC5-related epilepsy: Neuronal loss of Depdc5 causes dysplastic and ectopic neurons, increased mTOR signaling, and seizure susceptibility.

PubMed

Yuskaitis, Christopher J; Jones, Brandon M; Wolfson, Rachel L; Super, Chloe E; Dhamne, Sameer C; Rotenberg, Alexander; Sabatini, David M; Sahin, Mustafa; Poduri, Annapurna

2018-03-01

DEPDC5 is a newly identified epilepsy-related gene implicated in focal epilepsy, brain malformations, and Sudden Unexplained Death in Epilepsy (SUDEP). In vitro, DEPDC5 negatively regulates amino acid sensing by the mTOR complex 1 (mTORC1) pathway, but the role of DEPDC5 in neurodevelopment and epilepsy has not been described. No animal model of DEPDC5-related epilepsy has recapitulated the neurological phenotypes seen in patients, and germline knockout rodent models are embryonic lethal. Here, we establish a neuron-specific Depdc5 conditional knockout mouse by cre-recombination under the Synapsin1 promotor. Depdc5 flox/flox -Syn1 Cre (Depdc5cc+) mice survive to adulthood with a progressive neurologic phenotype that includes motor abnormalities (i.e., hind limb clasping) and reduced survival compared to littermate control mice. Depdc5cc+ mice have larger brains with increased cortical neuron size and dysplastic neurons throughout the cortex, comparable to the abnormal neurons seen in human focal cortical dysplasia specimens. Depdc5 results in constitutive mTORC1 hyperactivation exclusively in neurons as measured by the increased phosphorylation of the downstream ribosomal protein S6. Despite a lack of increased mTORC1 signaling within astrocytes, Depdc5cc+ brains show reactive astrogliosis. We observed two Depdc5cc+ mice to have spontaneous seizures, including a terminal seizure. We demonstrate that as a group Depdc5cc+ mice have lowered seizure thresholds, as evidenced by decreased latency to seizures after chemoconvulsant injection and increased mortality from pentylenetetrazole-induced seizures. In summary, our neuron-specific Depdc5 knockout mouse model recapitulates clinical, pathological, and biochemical features of human DEPDC5-related epilepsy and brain malformations. We thereby present an important model in which to study targeted therapeutic strategies for DEPDC5-related conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs.

PubMed

Fu, Lina; Xu, Xiuling; Ren, Ruotong; Wu, Jun; Zhang, Weiqi; Yang, Jiping; Ren, Xiaoqing; Wang, Si; Zhao, Yang; Sun, Liang; Yu, Yang; Wang, Zhaoxia; Yang, Ze; Yuan, Yun; Qiao, Jie; Izpisua Belmonte, Juan Carlos; Qu, Jing; Liu, Guang-Hui

2016-03-01

Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.

Heterogeneous Intracellular Trafficking Dynamics of Brain-Derived Neurotrophic Factor Complexes in the Neuronal Soma Revealed by Single Quantum Dot Tracking

PubMed Central

Vermehren-Schmaedick, Anke; Krueger, Wesley; Jacob, Thomas; Ramunno-Johnson, Damien; Balkowiec, Agnieszka; Lidke, Keith A.; Vu, Tania Q.

2014-01-01

Accumulating evidence underscores the importance of ligand-receptor dynamics in shaping cellular signaling. In the nervous system, growth factor-activated Trk receptor trafficking serves to convey biochemical signaling that underlies fundamental neural functions. Focus has been placed on axonal trafficking but little is known about growth factor-activated Trk dynamics in the neuronal soma, particularly at the molecular scale, due in large part to technical hurdles in observing individual growth factor-Trk complexes for long periods of time inside live cells. Quantum dots (QDs) are intensely fluorescent nanoparticles that have been used to study the dynamics of ligand-receptor complexes at the plasma membrane but the value of QDs for investigating ligand-receptor intracellular dynamics has not been well exploited. The current study establishes that QD conjugated brain-derived neurotrophic factor (QD-BDNF) binds to TrkB receptors with high specificity, activates TrkB downstream signaling, and allows single QD tracking capability for long recording durations deep within the soma of live neurons. QD-BDNF complexes undergo internalization, recycling, and intracellular trafficking in the neuronal soma. These trafficking events exhibit little time-synchrony and diverse heterogeneity in underlying dynamics that include phases of sustained rapid motor transport without pause as well as immobility of surprisingly long-lasting duration (several minutes). Moreover, the trajectories formed by dynamic individual BDNF complexes show no apparent end destination; BDNF complexes can be found meandering over long distances of several microns throughout the expanse of the neuronal soma in a circuitous fashion. The complex, heterogeneous nature of neuronal soma trafficking dynamics contrasts the reported linear nature of axonal transport data and calls for models that surpass our generally limited notions of nuclear-directed transport in the soma. QD-ligand probes are poised to provide understanding of how the molecular mechanisms underlying intracellular ligand-receptor trafficking shape cell signaling under conditions of both healthy and dysfunctional neurological disease models. PMID:24732948

Neurological and mental health outcomes among conventional and organic farmers in Indiana, USA.

PubMed

Khan, Khalid M; Baidya, Retushi; Aryal, Ashamsa; Farmer, James R; Valliant, Julia

2018-06-20

Every farming method, whether conventional or organic, has been associated with some sort of risky behaviors leading to health issues among farmers. Substantial evidence is not available in the literature to determine whether the magnitudes of health outcomes vary between conventional and organic farmers. The study investigated whether self-reported neurological and mental health symptoms differ between conventional and organic farmers living in Indiana, USA. A self-reported questionnaire survey collected information from 200 conventional and 157 organic farmers of Indiana on demographic characteristics, depression and neurological symptoms. Statistical analyses were conducted to observe the differences in self-reported symptoms by groups of farmers. It was observed that the conventional farmers had significantly higher age-adjusted mean neurological symptom score (p<0.01) than the organic farmers. Regression models revealed positive and significant associations of conventional farming with total (β =1.34; p=0.02), sensory (β =0.83; p=0.001) and behavioural (β =0.09; p=0.03) symptoms after accounting for age, income, education and years in farming. Positive but non-significant associations were also observed in conventional farmers with cognitive and motor symptoms, and with all subscales of depression symptoms in the adjusted models. The findings obtained suggest the importance of a larger study to further explain the difference in mental and neurological health effects in these two categories of farmers.

Effect of Anatomically Realistic Full-Head Model on Activation of Cortical Neurons in Subdural Cortical Stimulation—A Computational Study

NASA Astrophysics Data System (ADS)

Seo, Hyeon; Kim, Donghyeon; Jun, Sung Chan

2016-06-01

Electrical brain stimulation (EBS) is an emerging therapy for the treatment of neurological disorders, and computational modeling studies of EBS have been used to determine the optimal parameters for highly cost-effective electrotherapy. Recent notable growth in computing capability has enabled researchers to consider an anatomically realistic head model that represents the full head and complex geometry of the brain rather than the previous simplified partial head model (extruded slab) that represents only the precentral gyrus. In this work, subdural cortical stimulation (SuCS) was found to offer a better understanding of the differential activation of cortical neurons in the anatomically realistic full-head model than in the simplified partial-head models. We observed that layer 3 pyramidal neurons had comparable stimulation thresholds in both head models, while layer 5 pyramidal neurons showed a notable discrepancy between the models; in particular, layer 5 pyramidal neurons demonstrated asymmetry in the thresholds and action potential initiation sites in the anatomically realistic full-head model. Overall, the anatomically realistic full-head model may offer a better understanding of layer 5 pyramidal neuronal responses. Accordingly, the effects of using the realistic full-head model in SuCS are compelling in computational modeling studies, even though this modeling requires substantially more effort.

Application of induced pluripotent stem cells to understand neurobiological basis of bipolar disorder and schizophrenia.

PubMed

Liu, Yao-Nan; Lu, Si-Yao; Yao, Jun

2017-09-01

The etiology of neuropsychiatric disorders, such as schizophrenia and bipolar disorder, usually involves complex combinations of genetic defects/variations and environmental impacts, which hindered, for a long time, research efforts based on animal models and patients' non-neuronal cells or post-mortem tissues. However, the development of human induced pluripotent stem cell (iPSC) technology by the Yamanaka group was immediately applied to establish cell research models for neuronal disorders. Since then, techniques to achieve highly efficient differentiation of different types of neural cells following iPSC modeling have made much progress. The fast-growing iPSC and neural differentiation techniques have brought valuable insights into the pathology and neurobiology of neuropsychiatric disorders. In this article, we first review the application of iPSC technology in modeling neuronal disorders and discuss the progress in the accompanying neural differentiation. Then, we summarize the progress in iPSC-based research that has been accomplished so far regarding schizophrenia and bipolar disorder. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

Independent or Integrated? The Impact on Subject Examination Scores of Changing a Neuropsychiatry Clerkship to Independent Clerkships in Psychiatry and Neurology.

PubMed

Anderson, Heather S; Gabrielli, William F; Paolo, Anthony; Walling, Anne

2017-08-01

This study was undertaken to assess any impact on National Board of Medical Examiners (NBME) neurology and psychiatry subject examination scores of changing from an integrated neuropsychiatry clerkship to independent neurology and psychiatry clerkships. NBME psychiatry and neurology subject examinations scores were compared for all 625 students completing the required neuropsychiatry clerkship in academic years 2005-2006 through 2008-2009 with all 650 students completing the independent neurology and psychiatry clerkships in academic years 2009-2010 through 2012-2013. Statistical adjustments were made to ensure comparability across groups and over time. A significant improvement in subject examination scores was associated with the independent clerkships. The independent clerkship model was associated with a modest improvement in NBME subject examination scores. This finding may be attributable to many causes or combination of causes other than curricular design. Curricular planners need to pay attention to the potential impact of course integration on specialty-specific NBME subject examination performance.

Association of blood lead level with neurological features in 972 children affected by an acute severe lead poisoning outbreak in Zamfara State, northern Nigeria.

PubMed

Greig, Jane; Thurtle, Natalie; Cooney, Lauren; Ariti, Cono; Ahmed, Abdulkadir Ola; Ashagre, Teshome; Ayela, Anthony; Chukwumalu, Kingsley; Criado-Perez, Alison; Gómez-Restrepo, Camilo; Meredith, Caitlin; Neri, Antonio; Stellmach, Darryl; Sani-Gwarzo, Nasir; Nasidi, Abdulsalami; Shanks, Leslie; Dargan, Paul I

2014-01-01

In 2010, Médecins Sans Frontières (MSF) investigated reports of high mortality in young children in Zamfara State, Nigeria, leading to confirmation of villages with widespread acute severe lead poisoning. In a retrospective analysis, we aimed to determine venous blood lead level (VBLL) thresholds and risk factors for encephalopathy using MSF programmatic data from the first year of the outbreak response. We included children aged ≤5 years with VBLL ≥45 µg/dL before any chelation and recorded neurological status. Odds ratios (OR) for neurological features were estimated; the final model was adjusted for age and baseline VBLL, using random effects for village of residence. 972 children met inclusion criteria: 885 (91%) had no neurological features; 34 (4%) had severe features; 47 (5%) had reported recent seizures; and six (1%) had other neurological abnormalities. The geometric mean VBLLs for all groups with neurological features were >100 µg/dL vs 65.9 µg/dL for those without neurological features. The adjusted OR for neurological features increased with increasing VBLL: from 2.75, 95%CI 1.27-5.98 (80-99.9 µg/dL) to 22.95, 95%CI 10.54-49.96 (≥120 µg/dL). Neurological features were associated with younger age (OR 4.77 [95% CI 2.50-9.11] for 1-<2 years and 2.69 [95%CI 1.15-6.26] for 2-<3 years, both vs 3-5 years). Severe neurological features were seen at VBLL <105 µg/dL only in those with malaria. Increasing VBLL (from ≥80 µg/dL) and age 1-<3 years were strongly associated with neurological features; in those tested for malaria, a positive test was also strongly associated. These factors will help clinicians managing children with lead poisoning in prioritising therapy and developing chelation protocols.

Neuroprotective effects of ebselen in traumatic brain injury model: involvement of nitric oxide and p38 mitogen-activated protein kinase signalling pathway.

PubMed

Wei, Liang; Zhang, Yanfei; Yang, Cheng; Wang, Qi; Zhuang, Zhongwei; Sun, Zhiyang

2014-02-01

Previous investigations have found that ebselen is able to treat neurodegenerative diseases caused by radical and acute total cerebral ischaemia. The aim of the present study was to investigate the neuroprotective effects of ebselen in a traumatic brain injury (TBI) model. Ninety Sprague-Dawley rats were randomly divided into five groups (n = 18 in each): (i) sham operation; (ii) an injury model group; (iii) low-dose (3 mg/kg) ebselen-treated group; (iv) a moderate-dose (10 mg/kg) ebselen-treated group; and (v) a high-dose (30 mg/kg) ebselen-treated group. The TBI model was created according using a modified weight-drop model. Neurological severity score (NSS), brain water content and histopathological deficits were assessed as parameters of injury severity. Expression of nitric oxide (NO), inducible NO synthase (iNOS) mRNA, Toll-like receptor (TLR) and phosphorylated (p-) p38 mitogen-activated protein kinase (MAPK) were examined by chemical colorimetry, quantitative polymerase chain reaction and western blotting 24 h after intragastric ebselen administration. Rats in the TBI model group exhibited markedly more severe neurological injury (higher NSS, more brain water content and more histopathological deficits) than those in the sham-operated group. Ebselen treatment significantly ameliorated the neurological injury of TBI rats in a dose-dependent manner. Moreover, ebselen significantly reduced the NO and iNOS mRNA levels and inhibited TLR4 and p-p38 MAPK expression, indicating the involvement of NO and p38 MAPK signalling pathways in the neuroprotection afforded by ebselen. In conclusion, ebselen ameliorated neurological injury, possibly by reducing NO levels and modulating the TLR4-mediated p38 MAPK signalling pathway. Therefore, ebselen may have potential to treat secondary injuries of TBI. © 2013 Wiley Publishing Asia Pty Ltd.

Profile of Epilepsy in a Regional Hospital in Al Qassim, Saudi Arabia

PubMed Central

Hamdy, Nermin A; Alamgir, Mohammad Jawad; Mohammad, El Gamri E; Khedr, Mahmoud H; Fazili, Shafat

2014-01-01

Introduction Epilepsy is a diverse set of chronic neurological disorders characterized by seizures. It is one of the most common of the serious neurological disorders. About 3% of people will be diagnosed with epilepsy at some time in their lives. Objectives We aimed to address the commonest types of seizures, their aetiologies, EEG and neuroimaging results and prognosis of patients presented to neurology services of the King Fahad Specialist Hospital- AlQassim (KFSH). Methodology In this retrospective epidemiological study we investigated the medical records of patients with epilepsy, who attended the neurology services of KFSH, during the study period (26/10/2011–26/4/2012). Results The study included 341 patients; 189 (55.4%) males and 152 (44.6%) females. Their ages ranged between 12 and 85 years (mean ± SD = 31±16.9). The majority of patients had Generalised Tonic Clonic Seizures (76.2%), followed by Complex Partial Seizures (7.6%). 73% of our patients had idiopathic epilepsy. The commonest causes for symptomatic epilepsy were Cerebro Vascular Accidents and Head trauma. Hemiplegia, mental retardation and psychiatric illness were the commonest comorbidity. 69.3% of patients had controlled seizures. Patients with idiopathic epilepsy were significantly controlled than patients with symptomatic epilepsy (P=0.01), and those using one Anti Epileptic Drug were significantly controlled compared to patients using polytherapy (P=0.0001) there was no significant relation between controlled seizure and duration of illness or hospitalization or EEG changes. Conclusion Seizure types, aetiology, drug therapy, Comorbidities and outcome in a tertiary care hospital in Saudi Arabia are similar to previous local and international studies. 35.3% of patients were hospitalized, higher rates than previous studies. Seizure control was better in generalized seizures and idiopathic epilepsy compared to complex partial seizures or partial seizures with secondary generalization and symptomatic epilepsy. PMID:25505860

Microbiota and neurologic diseases: potential effects of probiotics.

PubMed

Umbrello, Giulia; Esposito, Susanna

2016-10-19

The microbiota colonizing the gastrointestinal tract have been associated with both gastrointestinal and extra-gastrointestinal diseases. In recent years, considerable interest has been devoted to their role in the development of neurologic diseases, as many studies have described bidirectional communication between the central nervous system and the gut, the so-called "microbiota-gut-brain axis". Considering the ability of probiotics (i.e., live non-pathogenic microorganisms) to restore the normal microbial population and produce benefits for the host, their potential effects have been investigated in the context of neurologic diseases. The main aims of this review are to analyse the relationship between the gut microbiota and brain disorders and to evaluate the current evidence for the use of probiotics in the treatment and prevention of neurologic conditions. Overall, trials involving animal models and adults have reported encouraging results, suggesting that the administration of probiotic strains may exert some prophylactic and therapeutic effects in a wide range of neurologic conditions. Studies involving children have mainly focused on autism spectrum disorder and have shown that probiotics seem to improve neuro behavioural symptoms. However, the available data are incomplete and far from conclusive. The potential usefulness of probiotics in preventing or treating neurologic diseases is becoming a topic of great interest. However, deeper studies are needed to understand which formulation, dosage and timing might represent the optimal regimen for each specific neurologic disease and what populations can benefit. Moreover, future trials should also consider the tolerability and safety of probiotics in patients with neurologic diseases.

Psychiatric and neurological disorders in late adolescence and risk of convictions for violent crime in men.

PubMed

Moberg, Tomas; Stenbacka, Marlene; Tengström, Anders; Jönsson, Erik G; Nordström, Peter; Jokinen, Jussi

2015-11-23

The relationship between mental illness and violent crime is complex because of the involvement of many other confounding risk factors. In the present study, we analysed psychiatric and neurological disorders in relation to the risk of convictions for violent crime, taking into account early behavioural and socio-economic risk factors. The study population consisted of 49,398 Swedish men, who were thoroughly assessed at conscription for compulsory military service during the years 1969-1970 and followed in national crime registers up to 2006. Five diagnostic groups were analysed: anxiety-depression/neuroses, personality disorders, substance-related disorders, mental retardation and neurological conditions. In addition, eight confounders measured at conscription and based on the literature on violence risk assessment, were added to the analyses. The relative risks of convictions for violent crime during 35 years after conscription were examined in relation to psychiatric diagnoses and other risk factors at conscription, as measured by odds ratios (ORs) and confidence intervals (CIs) from bivariate and multivariate logistic regression analyses. In the bivariate analyses there was a significant association between receiving a psychiatric diagnosis at conscription and a future conviction for violent crime (OR = 3.83, 95 % CI = 3.47-4.22), whereas no significant association between neurological conditions and future violent crime (OR = 1.03, 95 % CI = 0.48-2.21) was found. In the fully adjusted multivariate logistic regression model, mental retardation had the strongest association with future violent crime (OR = 3.60, 95 % CI = 2.73-4.75), followed by substance-related disorders (OR = 2.81, 95 % CI = 2.18-3.62), personality disorders (OR = 2.66, 95 % CI = 2.21-3.19) and anxiety-depression (OR = 1.29, 95 % CI = 1.07-1.55). Among the other risk factors, early behavioural problem had the strongest association with convictions for violent crime. Mental retardation, substance-related disorders, personality disorders and early behavioural problems are important predictors of convictions for violent crime in men.

Logistic model analysis of neurological findings in Minamata disease and the predicting index.

PubMed

Nakagawa, Masanori; Kodama, Tomoko; Akiba, Suminori; Arimura, Kimiyoshi; Wakamiya, Junji; Futatsuka, Makoto; Kitano, Takao; Osame, Mitsuhiro

2002-01-01

To establish a statistical diagnostic method to identify patients with Minamata disease (MD) considering factors of aging and sex, we analyzed the neurological findings in MD patients, inhabitants in a methylmercury polluted (MP) area, and inhabitants in a non-MP area. We compared the neurological findings in MD patients and inhabitants aged more than 40 years in the non-MP area. Based on the different frequencies of the neurological signs in the two groups, we devised the following formula to calculate the predicting index for MD: predicting index = 1/(1+e(-x)) x 100 (The value of x was calculated using the regression coefficients of each neurological finding obtained from logistic analysis. The index 100 indicated MD, and 0, non-MD). Using this method, we found that 100% of male and 98% of female patients with MD (95 cases) gave predicting indices higher than 95. Five percent of the aged inhabitants in the MP area (598 inhabitants) and 0.2% of those in the non-MP area (558 inhabitants) gave predicting indices of 50 or higher. Our statistical diagnostic method for MD was useful in distinguishing MD patients from healthy elders based on their neurological findings.

Advantages of Structure-Based Drug Design Approaches in Neurological Disorders

PubMed Central

Aarthy, Murali; Panwar, Umesh; Selvaraj, Chandrabose; Singh, Sanjeev Kumar

2017-01-01

Objective: The purpose of the review is to portray the theoretical concept on neurological disorders from research data. Background: The freak changes in chemical response of nerve impulse causes neurological disorders. The research evidence of the effort done in the older history suggests that the biological drug targets and their effective feature with responsive drugs could be valuable in promoting the future development of health statistics structure for improved treatment for curing the nervous disorders. Methods: In this review, we summarized the most iterative theoretical concept of structure based drug design approaches in various neurological disorders to unfathomable understanding of reported information for future drug design and development. Results: On the premise of reported information we analyzed the model of theoretical drug designing process for understanding the mechanism and pathology of the neurological diseases which covers the development of potentially effective inhibitors against the biological drug targets. Finally, it also suggests the management and implementation of the current treatment in improving the human health system behaviors. Conclusion: With the survey of reported information we concluded the development strategies of diagnosis and treatment against neurological diseases which leads to supportive progress in the drug discovery. PMID:28042767

Adverse events associated with poor neurological outcome during targeted temperature management and advanced critical care after out-of-hospital cardiac arrest.

PubMed

Kim, Young-Min; Youn, Chun Song; Kim, Soo Hyun; Lee, Byung Kook; Cho, In Soo; Cho, Gyu Chong; Jeung, Kyung Woon; Oh, Sang Hoon; Choi, Seung Pill; Shin, Jong Hwan; Cha, Kyoung-Chul; Oh, Joo Suk; Yim, Hyeon Woo; Park, Kyu Nam

2015-07-22

The aim of this study was to investigate the association of adverse events (AEs) during targeted temperature management (TTM) and other AEs and concomitant treatments during the advanced critical care period with poor neurological outcome at hospital discharge in adult out-of-hospital cardiac arrest (OHCA) patients. This was a retrospective study using Korean Hypothermia Network registry data of adult OHCA patients treated with TTM in 24 teaching hospitals throughout South Korea from 2007 to 2012. Demographic characteristics, resuscitation and post-resuscitation variables, AEs, and concomitant treatments during TTM and the advanced critical care were collected. The primary outcome was poor neurological outcome, defined as a cerebral performance category (CPC) score of 3-5 at hospital discharge. The AEs and concomitant treatments were individually entered into the best multivariable predictive model of poor neurological outcome to evaluate the associations between each variable and outcome. A total of 930 patients, including 704 for whom a complete dataset of AEs and covariates was available for multivariable modeling, were included in the analysis; 476 of these patients exhibited poor neurological outcome [CPC 3 = 50 (7.1%), CPC 4 = 214 (30.4%), and CPC 5 = 212 (30.1%)]. Common AEs included hyperglycemia (45.6%), hypokalemia (31.3%), arrhythmia (21.3%) and hypotension (29%) during cooling, and hypotension (21.6%) during rewarming. Bleeding (5%) during TTM was a rare AE. Common AEs during the advanced critical care included pneumonia (39.6%), myoclonus (21.9%), seizures (21.7%) and hypoglycemia within 72 hours (23%). After adjusting for independent predictors of outcome, cooling- and rewarming-related AEs were not significantly associated with poor neurological outcome. However, sepsis, myoclonus, seizure, hypoglycemia within 72 hours and anticonvulsant use during the advanced critical care were associated with poor neurological outcome [adjusted odds ratios (95% confidence intervals) of 3.12 (1.40-6.97), 3.72 (1.93-7.16), 4.02 (2.04-7.91), 2.03 (1.09-3.78), and 1.69 (1.03-2.77), respectively]. Alternatively, neuromuscular blocker use was inversely associated with poor neurological outcome (0.48 [0.28-0.84]). Cooling- and rewarming-related AEs were not associated with poor neurological outcome at hospital discharge. Sepsis, myoclonus, seizure, hypoglycemia within 72 hours and anticonvulsant use during the advanced critical care period were associated with poor neurological outcome at hospital discharge in our study.

Immunotherapy by targeting of VGKC complex for seizure control and prevention of cognitive impairment in a mouse model of epilepsy.

PubMed

Fan, Zhiliang; Feng, Xiaojuan; Fan, Zhigang; Zhu, Xingyuan; Yin, Shaohua

2018-05-09

Epilepsy is a type of refractory neurologic disorder mental disease, which is associated with cognitive impairments and memory dysfunction. However, the potential mechanisms of epilepsy are not well understood. Previous evidence has identified the voltage gated potassium channel complex (VGKC) as a target in various cohorts of patients with epilepsy. In the present study, the efficacy of an antibody against VGKC (anti‑VGKC) for the treatment of epilepsy in mice was investigated. A mouse model of lithium‑pilocarpine temporal lobe epilepsy was established and anti‑VGKC treatment was administered for 30 days. Memory impairment, anxiety, visual attention, inhibitory control and neuronal loss were measured in the mouse model of lithium‑pilocarpine temporal lobe epilepsy. The results revealed that epileptic mice treated with anti‑VGKC were able to learn the task and presented attention impairment, even a tendency toward impulsivity and compulsivity. It was also exhibited that anti‑VGKC treatment decreased neuronal loss in structures classically associated with attentional performance in hippocampus. Mice who received Anti‑VGKC treatment had inhibited motor seizures and hippocampal damage as compared with control mice. In conclusion, these results indicated that anti‑VGKC treatment may present benefits for improvements of the condition of motor attention impairment and cognitive competence, which suggests that VGKC may be a potential target for the treatment of epilepsy.

Diagnosis by integrating model-based reasoning with knowledge-based reasoning

NASA Technical Reports Server (NTRS)

Bylander, Tom

1988-01-01

Our research investigates how observations can be categorized by integrating a qualitative physical model with experiential knowledge. Our domain is diagnosis of pathologic gait in humans, in which the observations are the gait motions, muscle activity during gait, and physical exam data, and the diagnostic hypotheses are the potential muscle weaknesses, muscle mistimings, and joint restrictions. Patients with underlying neurological disorders typically have several malfunctions. Among the problems that need to be faced are: the ambiguity of the observations, the ambiguity of the qualitative physical model, correspondence of the observations and hypotheses to the qualitative physical model, the inherent uncertainty of experiential knowledge, and the combinatorics involved in forming composite hypotheses. Our system divides the work so that the knowledge-based reasoning suggests which hypotheses appear more likely than others, the qualitative physical model is used to determine which hypotheses explain which observations, and another process combines these functionalities to construct a composite hypothesis based on explanatory power and plausibility. We speculate that the reasoning architecture of our system is generally applicable to complex domains in which a less-than-perfect physical model and less-than-perfect experiential knowledge need to be combined to perform diagnosis.

Endovascular ischemic stroke models of adult rhesus monkeys: a comparison of two endovascular methods.

PubMed

Wu, Di; Chen, Jian; Wang, Bincheng; Zhang, Mo; Shi, Jingfei; Ma, Yanhui; Zhu, Zixin; Yan, Feng; He, Xiaoduo; Li, Shengli; Dornbos Iii, David; Ding, Yuchuan; Ji, Xunming

2016-08-18

To further investigate and improve upon current stroke models in nonhuman primates, infarct size, neurologic function and survival were evaluated in two endovascular ischemic models in sixteen rhesus monkeys. The first method utilized a micro-catheter or an inflatable balloon to occlude the M1 segment in six monkeys. In the second model, an autologous clot was injected via a micro-catheter into the M1 segment in ten monkeys. MRI scanning was performed on all monkeys both at baseline and 3 hours after the onset of ischemia. Spetzler neurologic functions were assessed post-operatively, and selective perfusion deficits were confirmed by DSA and MRI in all monkeys. Animals undergoing micro-catheter or balloon occlusion demonstrated more profound hemiparesis, larger infarct sizes, lower Spetzler neurologic scores and increased mortality compared to the thrombus occlusion group. In animals injected with the clot, there was no evidence of dissolution, and the thrombus was either near the injection site (M1) or flushed into the superior division of the MCA (M2). All animals survived the M2 occlusion. M1 occlusion with thrombus generated 50% mortality. This study highlighted clinically important differences in these two models, providing a platform for further study of a translational thromboembolic model of acute ischemic stroke.

Eculizumab treatment in severe pediatric STEC-HUS: a multicenter retrospective study.

PubMed

Percheron, Lucas; Gramada, Raluca; Tellier, Stéphanie; Salomon, Remi; Harambat, Jérôme; Llanas, Brigitte; Fila, Marc; Allain-Launay, Emma; Lapeyraque, Anne-Laure; Leroy, Valerie; Adra, Anne-Laure; Bérard, Etienne; Bourdat-Michel, Guylhène; Chehade, Hassid; Eckart, Philippe; Merieau, Elodie; Piètrement, Christine; Sellier-Leclerc, Anne-Laure; Frémeaux-Bacchi, Véronique; Dimeglio, Chloe; Garnier, Arnaud

2018-03-23

Hemolytic uremic syndrome related to Shiga-toxin-secreting Escherichia coli infection (STEC-HUS) remains a common cause of acute kidney injury in young children. No specific treatment has been validated for this severe disease. Recently, experimental studies highlight the potential role of complement in STEC-HUS pathophysiology. Eculizumab (EC), a monoclonal antibody against terminal complement complex, has been used in severe STEC-HUS patients, mostly during the 2011 German outbreak, with conflicting results. On behalf of the French Society of Pediatric Nephrology, we retrospectively studied 33 children from 15 centers treated with EC for severe STEC-HUS. Indication for EC was neurologic involvement in 20 patients, cardiac and neurologic involvement in 8, cardiac involvement in 2, and digestive involvement in 3. Based on medical status at last follow-up, patients were divided into two groups: favorable (n = 15) and unfavorable outcomes (n = 18). Among patients with favorable outcome, 11/14 patients (79%) displayed persistent blockade of complement activity before each EC reinjection. Conversely, in patients with unfavorable outcome, only 9/15 (53%) had persistent blockade (p = n.s.). Among 28 patients presenting neurological symptoms, 19 had favorable neurological outcome including 17 with prompt recovery following first EC injection. Only two adverse effects potentially related to EC treatment were reported. Taken together, these results may support EC use in severe STEC-HUS patients, especially those presenting severe neurological symptoms. The study, however, is limited by absence of a control group and use of multiple therapeutic interventions in treatment groups. Thus, prospective, controlled trials should be undertaken.

First Indian single center experience with pipeline embolization device for complex intracranial aneurysms.

PubMed

Cherian, Mathew P; Yadav, Manish Kumar; Mehta, Pankaj; Vijayan, K; Arulselvan, V; Jayabalan, Suresh

2014-01-01

Flow diversion is a novel method of therapy wherein an endoluminal sleeve, the flow diverter stent is placed across the neck of complex aneurysms to curatively reconstruct abnormal vasculature. We present the first Indian single center experience with the pipeline embolization device (PED) and 6 months follow-up results of 5 patients. Five complex or recurrent intracranial aneurysms in five patients were treated with PED. The patients were followed-up with magnetic resonance angiography (MRA) after 4 weeks and conventional angiography after 6 months. Feasibility, complications, clinical outcome, early 1-month MRA and 6 months conventional angiographic follow-up results were analyzed. Of the five aneurysms treated, four were in the anterior circulation and one in the posterior circulation. All five patients were treated with a single PED in each, and additionally coils were used in one patient. At 1-month MRA follow-up, complete occlusion was seen in 2 (40%) of the five cases. Post 6 months conventional angiography showed complete occlusion of the aneurysm sac in all five cases (100%). Side branch ostia were covered in three patients, all of which were patent (100%). There was no incidence of major neurological morbidity or mortality. One patient (20%) who had basilar top aneurysm experienced minor neurological disability after 5 days which partially improved. Pipeline embolization device for complex and recurrent aneurysms is technically feasible, safe, offers low complication rate, and definitive vascular reconstruction. PED can be used without fear of occlusion of covered eloquent side branches and perforators.

Teacher Support in the Implementation of Classroom Interventions for Middle School Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Pantoja, Danitza

2014-01-01

Autism spectrum disorder is generally regarded as complex, neurologically based, developmental disability that typically has its onset early in life (Myles & Simpson, 2001). Autism spectrum disorder is considered a universal disorder that affects children across all socioeconomic and educational levels (Wilkinson, 2010). Autism spectrum…

A Critical Review of the Postulated Role of the Cyanobacterial Metabolite, Beta-N-Methylamino-L-Alanine (BMAA) in Neurodegenerative Disease in Humans

EPA Science Inventory

The compound BMAA (β-N-methylamino-L-alanine) has been hypothesized to play a significant role in four serious neurological diseases in humans: Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) found on Guam, and ALS, parkinsonism, and dementia that occur...

Teaching Students with Autism Spectrum Disorders: Technology, Curriculum, and Common Sense

ERIC Educational Resources Information Center

Ennis-Cole, Demetria

2012-01-01

Autism is a spectrum of disorders which comprises Asperger's Syndrome, Pervasive Developmental Delay-Not Otherwise Specified (PDD-NOS), Rett's Syndrome, Childhood Disintegrative Disorder, and Autistic Disorder. It affects 1 in 110 children (Center for Disease Control and Prevention, [CDC], 2011), and it is a complex neurological disorder that is…

Cognition and Emotions in the Creative Process

ERIC Educational Resources Information Center

Gnezda, Nicole M.

2011-01-01

Art teachers are most successful when they teach the whole child, with an awareness of the student inside as well as the work that is being produced outside. Therefore, when teaching students about their own creativity and that of artists they study, it is helpful to understand complex neurological and emotional operations that are active during…

Traumatic Brain Injury: Are We Conducting Enough Resarch

DTIC Science & Technology

2017-04-17

Autism Spectrum Disorder (ASD), whose current rate of total study growth was 2.08. Within subsets of ASD studies, the current rate of RCT growth was...the lack of emerging treatments. As neurological disorders are notoriously complex, we set out to compare the state of TBI research to that of the 11

One Hundred Ninety-five Cases of High-voltage Electric Injury

DTIC Science & Technology

2005-08-01

that level; and T4 to T5 paraplegia, secondary to fractures of T4 to T7. In 3 cases, frac- tures were not present: one case of a T11 to T12 sensory ...problems, including fractures, neurological inju- ries, ocular injuries, and complex reconstructive and re- habilitative needs, underscores the

Detestable or Marvelous? Neuroanatomical Correlates of Character Judgments

ERIC Educational Resources Information Center

Croft, Katie E.; Duff, Melissa C.; Kovach, Christopher K.; Anderson, Steven W.; Adolphs, Ralph; Tranel, Daniel

2010-01-01

As we learn new information about the social and moral behaviors of other people, we form and update character judgments of them, and this can profoundly influence how we regard and act towards others. In the study reported here, we capitalized on two interesting neurological patient populations where this process of complex "moral…

Prevalence and risk factors for neurological disorders in children aged 6 months to 2 years in northern India.

PubMed

Kumar, Rashmi; Bhave, Anupama; Bhargava, Roli; Agarwal, Girdhar G

2013-04-01

To study prevalence and risk factors for neurological disorders--epilepsy, global developmental delay, and motor, vision, and hearing defects--in children aged 6 months to 2 years in northern India. A two-stage community survey for neurological disorders was conducted in rural and urban areas of Lucknow. After initial screening with a new instrument, the Lucknow Neurodevelopment Screen, screen positives and a random proportion of screen negatives were validated using predefined criteria. Prevalence was calculated by weighted estimates. Demographic, socio-economic, and medical risk factors were compared between validated children who were positive and negative for neurological disorders by univariate and logistic regression analysis. Of 4801 children screened (mean age [SD] 15.32mo [5.96]; 2542 males, 2259 females), 196 were positive; 190 screen positives and 269 screen negatives were validated. Prevalence of neurological disorders was 27.92 per 1000 (weighted 95% confidence interval 12.24-43.60). Significant risk factors (p≤0.01) for neurological disorders were higher age in months (p=0.010), lower mean number of appliances in the household (p=0.001), consanguineous marriage of parents (p=0.010), family history of neurological disorder (p=0.001), and infants born exceptionally small (parental description; p=0.009). On logistic regression, the final model included age (p=0.0193), number of appliances (p=0.0161), delayed cry at birth (p=0.0270), postneonatal meningoencephalitis (p=0.0549), and consanguinity (p=0.0801). Perinatal factors, lower socio-economic status, and consanguinity emerged as predictors of neurological disorders. These factors are largely modifiable. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

Neural prostheses in clinical applications--trends from precision mechanics towards biomedical microsystems in neurological rehabilitation.

PubMed

Stieglitz, T; Schuettler, M; Koch, K P

2004-04-01

Neural prostheses partially restore body functions by technical nerve excitation after trauma or neurological diseases. External devices and implants have been developed since the early 1960s for many applications. Several systems have reached nowadays clinical practice: Cochlea implants help the deaf to hear, micturition is induced by bladder stimulators in paralyzed persons and deep brain stimulation helps patients with Parkinson's disease to participate in daily life again. So far, clinical neural prostheses are fabricated with means of precision mechanics. Since microsystem technology opens the opportunity to design and develop complex systems with a high number of electrodes to interface with the nervous systems, the opportunity for selective stimulation and complex implant scenarios seems to be feasible in the near future. The potentials and limitations with regard to biomedical microdevices are introduced and discussed in this paper. Target specifications are derived from existing implants and are discussed on selected applications that has been investigated in experimental research: a micromachined implant to interface a nerve stump with a sieve electrode, cuff electrodes with integrated electronics, and an epiretinal vision prosthesis.

Leigh and Leigh-like syndrome in children and adults.

PubMed

Finsterer, Josef

2008-10-01

Leigh syndrome (also termed subacute, necrotizing encephalopathy) is a devastating neurodegenerative disorder, characterized by almost identical brain changes, e.g., focal, bilaterally symmetric lesions, particularly in the basal ganglia, thalamus, and brainstem, but with considerable clinical and genetic heterogeneity. Clinically, Leigh syndrome is characterized by a wide variety of abnormalities, from severe neurologic problems to a near absence of abnormalities. Most frequently the central nervous system is affected, with psychomotor retardation, seizures, nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure. Some patients also present with peripheral nervous system involvement, including polyneuropathy or myopathy, or non-neurologic abnormalities, e.g., diabetes, short stature, hypertrichosis, cardiomyopathy, anemia, renal failure, vomiting, or diarrhea (Leigh-like syndrome). In the majority of cases, onset is in early childhood, but in a small number of cases, adults are affected. In the majority of cases, dysfunction of the respiratory chain (particularly complexes I, II, IV, or V), of coenzyme Q, or of the pyruvate dehydrogenase complex are responsible for the disease. Associated mutations affect genes of the mitochondrial or nuclear genome. Leigh syndrome and Leigh-like syndrome are the mitochondrial disorders with the largest genetic heterogeneity.

Neurogenic stuttering: a review of the literature.

PubMed

Cruz, C; Amorim, H; Beca, G; Nunes, R

2018-01-16

Neurogenic stuttering is a disorder of neurologic origin in the rhythm of speech during which the patient knows exactly what he wants to say but is unable to because of an involuntary prolongation, cessation or repetition of a sound. To assemble new insights regarding the epidemiology, pathophysiology, diagnosis, evaluation and treatment of neurogenic stuttering. A review of all PubMed and Scopus published articles between January 2000 and September 2016 was performed. Thirty-three publications were analyzed. Neurogenic stuttering is a rare entity whose epidemiological incidence is yet not fully established. It is correlated with several neurological diseases and with several possible localizations within the nervous system. Notwithstanding the recent advances in the understanding of the underlying mechanism, it is not yet possible to establish a single pathophysiological mechanism of neurogenic stuttering. The differential diagnosis is complex and requires the detailed knowledge of other language disorders. The treatment is currently based on specific speech language therapy strategies. Neurogenic stuttering is a complex disorder which is not fully understood. Additional studies might help to better explain the underlying pathophysiological mechanism and to open doors to novel therapeutic methods.

Neuropsychiatry: a management model for academic medicine.

PubMed

Schiffer, Randolph B; Bowen, Beverly; Hinderliter, Josie; Hurst, Daniel L; Lajara-Nanson, Walter A; Packard, Russell C

2004-01-01

Neuropsychiatry has become the subject of a number of editorials and position papers in recent years. Historical, philosophical, clinical, scientific, and educational dimensions of neuropsychiatry have been discussed in these papers. The potential business aspects of this topic, however, have received little, if any, comment. In this paper, the authors describe the business performance characteristics of an integrated neuropsychiatry department, formed through the merger of two traditional departments of psychiatry and neurology. The merger of neurology and psychiatry to create an integrated neuropsychiatry department according to the model described produced significant improvement in financial performance.

Survey of physician requirements in six specialties: manpower needs in anesthesiology, neurology, nuclear medicine, pathology, physical medicine and rehabilitation, radiology. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wills, J.

1980-07-01

This report was prepared to assist the Graduate Medical Education National Advisory Committee (GMENAC) in its efforts to model physician manpower requirements in six specialties: anesthesiology, neurology, nuclear medicine, pathology, physical medicine and rehabilitation, and radiology. The purpose of this report is to (1) survey and present the existing literature on manpower requirements in each of these six specialties, and (2) discuss the special problems present in each specialty in modeling manpower requirements, and where possible, suggest possible avenues of resolution.

Prospects for neural stem cell-based therapies for neurological diseases.

PubMed

Imitola, Jaime

2007-10-01

Neural stem and progenitor cells have great potential for the treatment of neurological disorders. However, many obstacles remain to translate this field to the patient's bedside, including rationales for using neural stem cells in individual neurological disorders; the challenges of neural stem cell biology; and the caveats of current strategies of isolation and culturing neural precursors. Addressing these challenges is critical for the translation of neural stem cell biology to the clinic. Recent work using neural stem cells has yielded novel biologic concepts such as the importance of the reciprocal interaction between neural stem cells and the neurodegenerative environment. The prospect of using transplants of neural stem cells and progenitors to treat neurological diseases requires a better understanding of the molecular mechanisms of both neural stem cell behavior in experimental models and the intrinsic repair capacity of the injured brain.

The Workforce Task Force report: clinical implications for neurology.

PubMed

Freeman, William D; Vatz, Kenneth A; Griggs, Robert C; Pedley, Timothy

2013-07-30

The American Academy of Neurology Workforce Task Force (WFTF) report predicts a future shortfall of neurologists in the United States. The WFTF data also suggest that for most states, the current demand for neurologist services already exceeds the supply, and by 2025 the demand for neurologists will be even higher. This future demand is fueled by the aging of the US population, the higher health care utilization rates of neurologic services, and by a greater number of patients gaining access to the health care system due to the Patient Protection and Affordable Care Act. Uncertainties in health care delivery and patient access exist due to looming concerns about further Medicare reimbursement cuts. This uncertainty is set against a backdrop of Congressional volatility on a variety of issues, including the repeal of the sustainable growth rate for physician reimbursement. The impact of these US health care changes on the neurology workforce, future increasing demands, reimbursement, and alternative health care delivery models including accountable care organizations, nonphysician providers such as nurse practitioners and physician assistants, and teleneurology for both stroke and general neurology are discussed. The data lead to the conclusion that neurologists will need to play an even larger role in caring for the aging US population by 2025. We propose solutions to increase the availability of neurologic services in the future and provide other ways of meeting the anticipated increased demand for neurologic care.

[A complex study of the movement biomechanics in patients with post-stroke hemiparesis].

PubMed

Skvortsov, D V; Bulatova, M A; Kovrazhkina, E A; Suvorov, A Iu; Ivanova, G E; Skvortsova, V I

2012-01-01

The authors present results of a pilot study on biomechanics of non-cyclic movements of the human consequent verticalization in the ontogenesis of patients with post-stroke hemiparesis (10 patients in the acute stage of cerebral stroke) and 10 healthy volunteers without neurologic and orthopedic pathology. Some movements of therapeutic exercises Balance (a model of ontogenetic kinesitherapy) have been selected for the study. Cinematic parameters have been recorded using a system of motion 3D video analysis, a kinematic model was build in accordance to standard protocols. The skin (native and straightened) electromyogram (EMG) was recorded synchronously with kinematic data using 16-channel electromyography from the following pairs of muscles: mm. sternocleido-mastoideus, trapezius (горизонтальная порция), biceps brachii, triceps brachii, rectus femoris, adductor magnus. Major differences in the EMG picture between patients and controls were: 1) the EMG "monotony" with the involvement of multiple additional muscles in locomotions with the prevalence of the peculiar "tonic" muscle activity (low amplitudes without distinct peaks), stretching along the whole cycle of movement. In controls, EMG demonstrated variability and had mostly "phasic" character with distinct 1 or 2 peaks; 2) the asymmetry of EMG profile in symmetric movements. i.e. when performed simultaneously from the right and from the left sides. The latter feature may be considered as predictive because it was never found in healthy people. It allows to identify objectively weak muscles even in the absence of visible parethis during the routine neurological examination.

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

PubMed Central

Ferrari, Michele; Jain, Isha H.; Goldberger, Olga; Rezoagli, Emanuele; Thoonen, Robrecht; Cheng, Kai-Hung; Sosnovik, David E.; Scherrer-Crosbie, Marielle; Mootha, Vamsi K.; Zapol, Warren M.

2017-01-01

The most common pediatric mitochondrial disease is Leigh syndrome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that continuously breathing normobaric 11% O2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated survival curves and organ pathology in Ndufs4 KO mice exposed to hypoxia or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as continuous normobaric 17% O2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O2 in mice with late-stage encephalopathy reverses their established neurological disease, evidenced by improved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hypoxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials. PMID:28483998

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome.

PubMed

Ferrari, Michele; Jain, Isha H; Goldberger, Olga; Rezoagli, Emanuele; Thoonen, Robrecht; Cheng, Kai-Hung; Sosnovik, David E; Scherrer-Crosbie, Marielle; Mootha, Vamsi K; Zapol, Warren M

2017-05-23

The most common pediatric mitochondrial disease is Leigh syndrome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that continuously breathing normobaric 11% O 2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated survival curves and organ pathology in Ndufs4 KO mice exposed to hypoxia or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as continuous normobaric 17% O 2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O 2 in mice with late-stage encephalopathy reverses their established neurological disease, evidenced by improved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hypoxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials.

PTEN Loss Increases the Connectivity of Fast Synaptic Motifs and Functional Connectivity in a Developing Hippocampal Network.

PubMed

Barrows, Caitlynn M; McCabe, Matthew P; Chen, Hongmei; Swann, John W; Weston, Matthew C

2017-09-06

Changes in synaptic strength and connectivity are thought to be a major mechanism through which many gene variants cause neurological disease. Hyperactivation of the PI3K-mTOR signaling network, via loss of function of repressors such as PTEN, causes epilepsy in humans and animal models, and altered mTOR signaling may contribute to a broad range of neurological diseases. Changes in synaptic transmission have been reported in animal models of PTEN loss; however, the full extent of these changes, and their effect on network function, is still unknown. To better understand the scope of these changes, we recorded from pairs of mouse hippocampal neurons cultured in a two-neuron microcircuit configuration that allowed us to characterize all four major connection types within the hippocampus. Loss of PTEN caused changes in excitatory and inhibitory connectivity, and these changes were postsynaptic, presynaptic, and transynaptic, suggesting that disruption of PTEN has the potential to affect most connection types in the hippocampal circuit. Given the complexity of the changes at the synaptic level, we measured changes in network behavior after deleting Pten from neurons in an organotypic hippocampal slice network. Slices containing Pten -deleted neurons showed increased recruitment of neurons into network bursts. Importantly, these changes were not confined to Pten -deleted neurons, but involved the entire network, suggesting that the extensive changes in synaptic connectivity rewire the entire network in such a way that promotes a widespread increase in functional connectivity. SIGNIFICANCE STATEMENT Homozygous deletion of the Pten gene in neuronal subpopulations in the mouse serves as a valuable model of epilepsy caused by mTOR hyperactivation. To better understand how gene deletions lead to altered neuronal activity, we investigated the synaptic and network effects that occur 1 week after Pten deletion. PTEN loss increased the connectivity of all four types of hippocampal synaptic connections, including two forms of increased inhibition of inhibition, and increased network functional connectivity. These data suggest that single gene mutations that cause neurological diseases such as epilepsy may affect a surprising range of connection types. Moreover, given the robustness of homeostatic plasticity, these diverse effects on connection types may be necessary to cause network phenotypes such as increased synchrony. Copyright © 2017 the authors 0270-6474/17/378595-17$15.00/0.

PTEN Loss Increases the Connectivity of Fast Synaptic Motifs and Functional Connectivity in a Developing Hippocampal Network

PubMed Central

McCabe, Matthew P.; Chen, Hongmei; Swann, John W.

2017-01-01

Changes in synaptic strength and connectivity are thought to be a major mechanism through which many gene variants cause neurological disease. Hyperactivation of the PI3K-mTOR signaling network, via loss of function of repressors such as PTEN, causes epilepsy in humans and animal models, and altered mTOR signaling may contribute to a broad range of neurological diseases. Changes in synaptic transmission have been reported in animal models of PTEN loss; however, the full extent of these changes, and their effect on network function, is still unknown. To better understand the scope of these changes, we recorded from pairs of mouse hippocampal neurons cultured in a two-neuron microcircuit configuration that allowed us to characterize all four major connection types within the hippocampus. Loss of PTEN caused changes in excitatory and inhibitory connectivity, and these changes were postsynaptic, presynaptic, and transynaptic, suggesting that disruption of PTEN has the potential to affect most connection types in the hippocampal circuit. Given the complexity of the changes at the synaptic level, we measured changes in network behavior after deleting Pten from neurons in an organotypic hippocampal slice network. Slices containing Pten-deleted neurons showed increased recruitment of neurons into network bursts. Importantly, these changes were not confined to Pten-deleted neurons, but involved the entire network, suggesting that the extensive changes in synaptic connectivity rewire the entire network in such a way that promotes a widespread increase in functional connectivity. SIGNIFICANCE STATEMENT Homozygous deletion of the Pten gene in neuronal subpopulations in the mouse serves as a valuable model of epilepsy caused by mTOR hyperactivation. To better understand how gene deletions lead to altered neuronal activity, we investigated the synaptic and network effects that occur 1 week after Pten deletion. PTEN loss increased the connectivity of all four types of hippocampal synaptic connections, including two forms of increased inhibition of inhibition, and increased network functional connectivity. These data suggest that single gene mutations that cause neurological diseases such as epilepsy may affect a surprising range of connection types. Moreover, given the robustness of homeostatic plasticity, these diverse effects on connection types may be necessary to cause network phenotypes such as increased synchrony. PMID:28751459

Neuropsychology in a Memory Disorder Clinic.

PubMed

Ruchinskas, Robert A; Cullum, C Munro

2018-05-01

The rationale for and factors related to embedding a neuropsychologist in the midst of a neurology-based memory disorder clinic are discussed. Common conditions encountered are briefly reviewed, along with an evaluation aimed at assisting with differential diagnosis. Advice for neuropsychologists is offered in terms of creating and refining a working model in a neurology clinic and strategies to improve communication and effectiveness are presented.

[Autistic Children Developmental Disabilities Conference, Johns Hopkins University (Baltimore, Maryland, March 14-16, 1983). Abstracts of Papers Presented.

ERIC Educational Resources Information Center

1983

Abstracts of 13 papers given at a 1983 conference on autistic children are presented: "Autism--Is There a Neurological Basis?" (G. McKhann); "The Syndrome of Autism: A Medical Model" (E. Ritvo) (full paper); "Neuropsychological Testing of Peripheral and Central Communicative Disorders" (H. Mark); "A Psychiatrist Views the Neurological Basis of the…

Eliminating barriers to personalized medicine: learning from neurofibromatosis type 1.

PubMed

Gutmann, David H

2014-07-29

With the emergence of high-throughput discovery platforms, robust preclinical small-animal models, and efficient clinical trial pipelines, it is becoming possible to envision a time when the treatment of human neurologic diseases will become personalized. The emergence of precision medicine will require the identification of subgroups of patients most likely to respond to specific biologically based therapies. This stratification only becomes possible when the determinants that contribute to disease heterogeneity become more fully elucidated. This review discusses the defining factors that underlie disease heterogeneity relevant to the potential for individualized brain tumor (optic pathway glioma) treatments arising in the common single-gene cancer predisposition syndrome, neurofibromatosis type 1 (NF1). In this regard, NF1 is posited as a model genetic condition to establish a workable paradigm for actualizing precision therapeutics for other neurologic disorders. © 2014 American Academy of Neurology.

Melatonin mitigate cerebral vasospasm after experimental subarachnoid hemorrhage: a study of synchrotron radiation angiography

NASA Astrophysics Data System (ADS)

Cai, J.; He, C.; Chen, L.; Han, T.; Huang, S.; Huang, Y.; Bai, Y.; Bao, Y.; Zhang, H.; Ling, F.

2013-06-01

Cerebral vasospasm (CV) after subarachnoid hemorrhage (SAH) is a devastating and unsolved clinical issue. In this study, the rat models, which had been induced SAH by prechiasmatic cistern injection, were treated with melatonin. Synchrotron radiation angiography (SRA) was employed to detect and evaluate CV of animal models. Neurological scoring and histological examinations were used to assess the neurological deficits and CV as well. Using SRA techniques and histological analyses, the anterior cerebral artery diameters of SAH rats with melatonin administration were larger than those without melatonin treatment (p < 0.05). The neurological deficits of SAH rats treated with melatonin were less than those without melatonin treatment (p < 0.05). We concluded that SRA was a precise and in vivo tool to observe and evaluate CV of SAH rats; intraperitoneally administration of melatonin could mitigate CV after experimental SAH.

Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease.

PubMed

Coffey, Lark L; Keesler, Rebekah I; Pesavento, Patricia A; Woolard, Kevin; Singapuri, Anil; Watanabe, Jennifer; Cruzen, Christina; Christe, Kari L; Usachenko, Jodie; Yee, JoAnn; Heng, Victoria A; Bliss-Moreau, Eliza; Reader, J Rachel; von Morgenland, Wilhelm; Gibbons, Anne M; Jackson, Kenneth; Ardeshir, Amir; Heimsath, Holly; Permar, Sallie; Senthamaraikannan, Paranthaman; Presicce, Pietro; Kallapur, Suhas G; Linnen, Jeffrey M; Gao, Kui; Orr, Robert; MacGill, Tracy; McClure, Michelle; McFarland, Richard; Morrison, John H; Van Rompay, Koen K A

2018-06-20

Zika virus (ZIKV) infection of pregnant women can cause fetal microcephaly and other neurologic defects. We describe the development of a non-human primate model to better understand fetal pathogenesis. To reliably induce fetal infection at defined times, four pregnant rhesus macaques are inoculated intravenously and intraamniotically with ZIKV at gestational day (GD) 41, 50, 64, or 90, corresponding to first and second trimester of gestation. The GD41-inoculated animal, experiencing fetal death 7 days later, has high virus levels in fetal and placental tissues, implicating ZIKV as cause of death. The other three fetuses are carried to near term and euthanized; while none display gross microcephaly, all show ZIKV RNA in many tissues, especially in the brain, which exhibits calcifications and reduced neural precursor cells. Given that this model consistently recapitulates neurologic defects of human congenital Zika syndrome, it is highly relevant to unravel determinants of fetal neuropathogenesis and to explore interventions.

[Risk, cause and disease in the occupational environment. Neurologic risk factors].

PubMed

Maqueda-Blasco, J

In this paper we study the epidemiological criteria and those of etiological investigation which should be considered when analysing and investigating problems with health due to exposure to occupational hazards, with special attention to neurological damage due to chemical or physical contamination or to the ergonometric requirements of the task. We define the part played by occupational hazards in causing disease both professional and related to other occupations. The different preventive models used in the history of prevention of professional hazards are analysed. Particular attention is paid to the so-called socio-technical model which considers illness as dysfunction of the relation man/work. The neurological risk factors are analysed separately; therefore we emphasize the different neurotoxic chemicals, physical and ergonomic agents (the latter may be considered a pandemic in the workplace), and we establish the relationships with the main clinical and functional disorders of the central and peripheral nervous systems and the musculoskeletal system.

Functional neurological symptom disorder (conversion disorder): A role for microglial-based plasticity mechanisms?

PubMed

Stephenson, Chris P; Baguley, Ian J

2018-02-01

Functional Neurological Symptom Disorder (FND) is a relatively common neurological condition, accounting for approximately 3-6% of neurologist referrals. FND is considered a transient disorder of neuronal function, sometimes linked to physical trauma and psychological stress. Despite this, chronic disability is common, for example, around 40% of adults with motor FND have permanent disability. Building on current theoretical models, this paper proposes that microglial dysfunction could perpetuate functional changes within acute motor FND, thus providing a pathophysiological mechanism underlying the chronic stage of the motor FND phenotypes seen clinically. Core to our argument is microglia's dual role in modulating neuroimmunity and their control of synaptic plasticity, which places them at a pathophysiological nexus wherein coincident physical trauma and psychological stress could cause long-term change in neuronal networks without producing macroscopic structural abnormality. This model proposes a range of hypotheses that are testable with current technologies. Copyright © 2017. Published by Elsevier Ltd.

The Neurological Ecology of Fear: Insights Neuroscientists and Ecologists Have to Offer one Another

PubMed Central

Clinchy, Michael; Schulkin, Jay; Zanette, Liana Y.; Sheriff, Michael J.; McGowan, Patrick O.; Boonstra, Rudy

2011-01-01

That the fear and stress of life-threatening experiences can leave an indelible trace on the brain is most clearly exemplified by post-traumatic stress disorder (PTSD). Many researchers studying the animal model of PTSD have adopted utilizing exposure to a predator as a life-threatening psychological stressor, to emulate the experience in humans, and the resulting body of literature has demonstrated numerous long-lasting neurological effects paralleling those in PTSD patients. Even though much more extreme, predator-induced fear and stress in animals in the wild was, until the 1990s, not thought to have any lasting effects, whereas recent experiments have demonstrated that the effects on free-living animals are sufficiently long-lasting to even affect reproduction, though the lasting neurological effects remain unexplored. We suggest neuroscientists and ecologists both have much to gain from collaborating in studying the neurological effects of predator-induced fear and stress in animals in the wild. We outline the approaches taken in the lab that appear most readily translatable to the field, and detail the advantages that studying animals in the wild can offer researchers investigating the “predator model of PTSD.” PMID:21629856

Genetic and phenotypic characterization of complex hereditary spastic paraplegia

PubMed Central

Kara, Eleanna; Tucci, Arianna; Manzoni, Claudia; Lynch, David S.; Elpidorou, Marilena; Bettencourt, Conceicao; Chelban, Viorica; Manole, Andreea; Hamed, Sherifa A.; Haridy, Nourelhoda A.; Federoff, Monica; Preza, Elisavet; Hughes, Deborah; Pittman, Alan; Jaunmuktane, Zane; Brandner, Sebastian; Xiromerisiou, Georgia; Wiethoff, Sarah; Schottlaender, Lucia; Proukakis, Christos; Morris, Huw; Warner, Tom; Bhatia, Kailash P.; Korlipara, L.V. Prasad; Singleton, Andrew B.; Hardy, John; Wood, Nicholas W.; Lewis, Patrick A.

2016-01-01

Abstract The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15 , SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease-causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next generation sequencing was carried out revealing variants in a number of other known complex spastic paraplegia genes, including five in SPG7 (5/97), four in FA2H (also known as SPG35 ) (4/97) and two in ZFYVE26 / SPG15 . Variants were identified in genes usually associated with pure spastic paraplegia and also in the Parkinson’s disease-associated gene ATP13A2 , neuronal ceroid lipofuscinosis gene TPP1 and the hereditary motor and sensory neuropathy DNMT1 gene, highlighting the genetic heterogeneity of spastic paraplegia. No plausible genetic cause was identified in 51% of probands, likely indicating the existence of as yet unidentified genes. PMID:27217339

Regulating the chromatin landscape: structural and mechanistic perspectives.

PubMed

Bartholomew, Blaine

2014-01-01

A large family of chromatin remodelers that noncovalently modify chromatin is crucial in cell development and differentiation. They are often the targets of cancer, neurological disorders, and other human diseases. These complexes alter nucleosome positioning, higher-order chromatin structure, and nuclear organization. They also assemble chromatin, exchange out histone variants, and disassemble chromatin at defined locations. We review aspects of the structural organization of these complexes, the functional properties of their protein domains, and variation between complexes. We also address the mechanistic details of these complexes in mobilizing nucleosomes and altering chromatin structure. A better understanding of these issues will be vital for further analyses of subunits of these chromatin remodelers, which are being identified as targets in human diseases by NGS (next-generation sequencing).

[The carrier model of neurology in Hungary: a proposal for the solution until 2020].

PubMed

Bereczki, Dániel; Csiba, László; Komoly, Sámuel; Vécsei, László; Ajtay, András

2011-11-30

Based on our previous survey on the capacities of neurological services and on the predictable changes in the neurologist workforce in Hungary, we present a proposal for the organization of the structure of neurological services in the future. We discuss the diagnostic groups treated by neurologists, the neurological services and their progressive organization. Using the current capacities as baseline, we propose patient groups to be treated by neurologists in the future, and the levels of services. Based on the tendencies seen in the last years we suggest to consider to allocate acute stroke services exclusively to stroke units in neurological departments, and we identify a few other diagnostic groups where neurology should have a larger share in patient care. We define three levels for inpatient care: university departments, regional/county hospitals, city hospitals. Instead of minimum criteria we assign outpatient and inpatient standards that are functional from the economic point of view as well. University departments cover all areas of neurological services, have a function in graduate and postgraduate training, and on a regional basis they participate in professional quality assurance activities at the county and city hospital levels, and would have a more independent role in residency training. As far as patient care is concerned, the task of the regional/county hospitals would be similar to that of university departments - without the exclusively university functions. A general neurological service would be offered at the city hospital level - the representation of all subspecialties of neurology is not required. Neurorehabilitation would be organized at special units of neurological wards at the city hospital level, at independent neurorehabilitation wards in regional/county hospitals, and also as an outpatient service offered at the patients' home. The most significant organizational change would affect the outpatient neurological services. In addition to the special outpatient units associated with university departments and regional/county hospitals, the general neurological outpatient services would be organized as private practices, similarly to the current system of general practitioners, where the individual practices contract independently with the health insurance fund. Their task would be a general neurological service offered 30 hours per week, and also basic, screening neurophysiological and neurosonological examinations, with proper equipment and trained assistance. A transformation in residency training and a change in financing is needed for this plan to fulfill.

Global medical education partnerships to expand specialty expertise: a case report on building neurology clinical and research capacity.

PubMed

Kaddumukasa, Mark; Katabira, Elly; Salata, Robert A; Costa, Marco A; Ddumba, Edward; Furlan, Anthony; Kakooza-Mwesige, Angelina; Kamya, Moses R; Kayima, James; Longenecker, Chris T; Mayanja-Kizza, Harriet; Mondo, Charles; Moore, Shirley; Pundik, Svetlana; Sewankambo, Nelson; Simon, Daniel I; Smyth, Kathleen A; Sajatovic, Martha

2014-12-30

Neurological disorders are a common cause of morbidity and mortality in sub-Saharan African, but resources for their management are scarce. Collaborations between training institutions in developed and resource-limited countries can be a successful model for supporting specialty medical education and increasing clinical and research capacity. This report describes a US National Institutes of Health (NIH) funded Medical Education Partnership Initiative (MEPI) to enhance expertise in neurology, developed between Makerere University College of Health Sciences in Kampala, Uganda, and Case Western Reserve University School of Medicine in Cleveland, OH, USA. This collaborative model is based on a successful medical education and research model that has been developed over the past two decades. The Ugandan and US teams have accumulated knowledge and 'lessons learned' that facilitate specialty expertise in neurological conditions, which are widespread and associated with substantial disability in resource-limited countries. Strengths of the model include a focus on community health care settings and a strong research component. Key elements include strong local leadership; use of remote technology, templates to standardize performance; shared exchanges; mechanisms to optimize sustainability and of dissemination activities that expand impact of the original initiative. Efficient collaborations are further enhanced by external and institutional support, and can be sequentially refined. Models such as the Makerere University College of Health Sciences - Case Western Reserve University partnership may help other groups initiate collaborative education programmes and establish successful partnerships that may provide the opportunity to expand to other chronic diseases. A benefit of collaboration is that learning is two-directional, and interaction with other international medical education collaborators is likely to be of benefit to the larger global health community.

Merits and complexities of modeling multiple sclerosis in non-human primates: implications for drug discovery.

PubMed

't Hart, Bert A; Laman, Jon D; Kap, Yolanda S

2018-05-01

The translation of scientific discoveries made in animal models into effective treatments for patients often fails, indicating that currently used disease models in preclinical research are insufficiently predictive for clinical success. An often-used model in the preclinical research of autoimmune neurological diseases, multiple sclerosis in particular, is experimental autoimmune encephalomyelitis (EAE). Most EAE models are based on genetically susceptible inbred/SPF mouse strains used at adolescent age (10-12 weeks), which lack exposure to genetic and microbial factors which shape the human immune system. Areas covered: Herein, the authors ask whether an EAE model in adult non-human primates from an outbred conventionally-housed colony could help bridge the translational gap between rodent EAE models and MS patients. Particularly, the authors discuss a novel and translationally relevant EAE model in common marmosets (Callithrix jacchus) that shares remarkable pathological similarity with MS. Expert opinion: The MS-like pathology in this model is caused by the interaction of effector memory T cells with B cells infected with the γ1-herpesvirus (CalHV3), both present in the pathogen-educated marmoset immune repertoire. The authors postulate that depletion of only the small subset (<0.05%) of CalHV3-infected B cells may be sufficient to limit chronic inflammatory demyelination.

Improved Neuropsychological and Neurological Functioning Across Three Antiretroviral Regimens in Diverse Resource-Limited Settings: AIDS Clinical Trials Group Study A5199, the International Neurological Study

PubMed Central

Robertson, K.; Jiang, H.; Kumwenda, J.; Supparatpinyo, K.; Evans, S.; Campbell, T. B.; Price, R.; Tripathy, S.; Kumarasamy, N.; La Rosa, A.; Santos, B.; Silva, M. T.; Montano, S.; Kanyama, C.; Faesen, S.; Murphy, R.; Hall, C.; Marra, C. M.; Marcus, C.; Berzins, B.; Allen, R.; Housseinipour, M.; Amod, F.; Sanne, I.; Hakim, J.; Walawander, A.; Nair, A.

2012-01-01

Background. AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. Methods. Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. Results. The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). Conclusions. The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization –recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. Clinical trials registration.  NCT00096824. PMID:22661489

A Case for Telestroke in Military Medicine: A Retrospective Analysis of Stroke Cost and Outcomes in U.S. Military Health-Care System.

PubMed

Dave, Ajal; Cagniart, Kendra; Holtkamp, Matthew D

2018-06-07

The development of primary stroke centers has improved outcomes for stroke patients. Telestroke networks have expanded the reach of stroke experts to underserved, geographically remote areas. This study illustrates the outcome and cost differences between neurology and primary care ischemic stroke admissions to demonstrate a need for telestroke networks within the Military Health System (MHS). All adult admissions with a primary diagnosis of ischemic stroke in the MHS Military Mart database from calendar years 2010 to 2015 were reviewed. Neurology, primary care, and intensive care unit (ICU) admissions were compared across primary outcomes of (1) disposition status and (2) intravenous tissue plasminogen activator administration and for secondary outcomes of (1) total cost of hospitalization and (2) length of stay (LOS). A total of 3623 admissions met the study's parameters. The composition was neurology 462 (12.8%), primary care 2324 (64.1%), ICU 677 (18.7%), and other/unknown 160 (4.4%). Almost all neurology admissions (97%) were at the 3 neurology training programs, whereas a strong majority of primary care admissions (80%) were at hospitals without a neurology admitting service. Hospitals without a neurology admitting service had more discharges to rehabilitation facilities and higher rates of in-hospital mortality. LOS was also longer in primary care admissions. Ischemic stroke admissions to neurology had better outcomes and decreased LOS when compared to primary care within the MHS. This demonstrates a possible gap in care. Implementation of a hub and spoke telestroke model is a potential solution. Published by Elsevier Inc.

Children with central and peripheral neurologic disorders have distinguishable patterns of dysphagia on videofluoroscopic swallow study.

PubMed

van den Engel-Hoek, Lenie; Erasmus, Corrie E; van Hulst, Karen C M; Arvedson, Joan C; de Groot, Imelda J M; de Swart, Bert J M

2014-05-01

To determine whether findings on videofluoroscopic swallow studies reveal different patterns of dysphagia between children with central and peripheral neurologic disorders, a retrospective study of 118 videofluoroscopic swallow studies was completed. There were 3 groups: cerebral palsy with only spastic features (n = 53), cerebral palsy with dyskinetic features (n = 34), and neuromuscular disorders (myotonic dystrophy I, n = 5; spinal muscular atrophy I-II, n = 8; Duchenne muscular dystrophy, n = 8; other neuromuscular disorder, n = 10). Interpretation of the videofluoroscopic swallow studies was not blinded. The video fluoroscopic swallow study findings were compared dichotomously between the groups. Children with cerebral palsy demonstrated dysphagia in 1 or all phases of swallowing. In neuromuscular disorder, muscle weakness results in pharyngeal residue after swallow. The underlying swallowing problem in neuromuscular disorder is muscle weakness whereas that in cerebral palsy is more complex, having to do with abnormal control of swallowing. This study serves as a first exploration on specific characteristics of swallowing in different neurologic conditions and will help clinicians anticipate what they might expect.

Genetics of hereditary neurological disorders in children.

PubMed

Huang, Yue; Yu, Sui; Wu, Zhanhe; Tang, Beisha

2014-04-01

Hereditary neurological disorders (HNDs) are relatively common in children compared to those occurring in adulthood. Recognising clinical manifestations of HNDs is important for the selection of genetic testing, genetic testing results interpretation, and genetic consultation. Meanwhile, advances in next generation sequencing (NGS) technologies have significantly enabled the discovery of genetic causes of HNDs and also challenge paediatricians on applying genetic investigation. Combination of both clinical information and advanced technologies will enhance the genetic test yields in clinical setting. This review summarises the clinical presentations as well as genetic causes of paediatric neurological disorders in four major areas including movement disorders, neuropsychiatric disorders, neuron peripheral disorders and epilepsy. The aim of this review is to help paediatric neurologists not only to see the clinical features but also the complex genetic aspect of HNDs in order to utilise genetic investigation confidently in their clinical practice. A smooth transition from research based to clinical use of comprehensive genetic testing in HNDs in children could be foreseen in the near future while genetic testing, genetic counselling and genetic data interpretation are in place appropriately.

Neuroproteomic profiling of human body fluids.

PubMed

Häggmark, Anna; Schwenk, Jochen M; Nilsson, Peter

2016-04-01

Analysis of protein expression and abundance provides a possibility to extend the current knowledge on disease-associated processes and pathways. The human brain is a complex organ and dysfunction or damage can give rise to a variety of neurological diseases. Although many proteins potentially reflecting disease progress are originating from brain, the scarce availability of human tissue material has lead to utilization of body fluids such as cerebrospinal fluid and blood in disease-related research. Within the most common neurological disorders, much effort has been spent on studying the role of a few hallmark proteins in disease pathogenesis but despite extensive investigation, the signatures they provide seem insufficient to fully understand and predict disease progress. In order to expand the view the field of neuroproteomics has lately emerged alongside developing technologies, such as affinity proteomics and mass spectrometry, for multiplexed and high-throughput protein profiling. Here, we provide an overview of how such technologies have been applied to study neurological disease and we also discuss some important considerations concerning discovery of disease-associated profiles. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Implantable and transdermal polymeric drug delivery technologies for the treatment of central nervous system disorders.

PubMed

Govender, Thiresen; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Modi, Girish; Naidoo, Dinesh; Pillay, Viness

2017-06-01

The complexity of the brain and the membranous blood-brain barrier (BBB) has proved to be a significant limitation to the systemic delivery of pharmaceuticals to the brain rendering them sub-therapeutic and ineffective in the treatment of neurological diseases. Apart from this, lack of innovation in product development to counteract the problem is also a major contributing factor to a poor therapeutic outcome. Various innovative strategies show potential in treating some of the neurological disorders; however, drug delivery remains the most popular. To attain therapeutic drug levels in the central nervous system, large, intolerable systemic doses are generally administered. The major factors responsible for the success maintenance therapy of neurological diseases included controlled and sustained release of neurotherapeutics, reduced frequency of administration, higher bioavailability, and patient compliances. Conventional oral or injectable formulations cannot satisfy all the requirements in many circumstances. This article reviews the therapeutic implantable polymeric and transdermal devices employed in an attempt to effectively achieve therapeutic quantities of drug across the BBB over a prolonged period, to improve patient disease prognosis.

Acute abdominal pain as the only symptom of a thoracic demyelinating lesion in multiple sclerosis.

PubMed

Nomura, Shohei; Shimakawa, Shuichi; Kashiwagi, Mitsuru; Tanabe, Takuya; Fukui, Miho; Tamai, Hiroshi

2015-11-01

Multiple sclerosis (MS) is a syndrome characterized by complex neurological symptoms resulting from demyelinating lesions in the central nervous system. We report a child with a relapse of MS whose only presenting symptom was severe abdominal pain. Dysfunctional intestinal mobility was assessed by abdominal computed tomography. Findings resembled paralytic ileus resulting from peritonitis. However, the patient demonstrated no other symptoms of peritonitis. A T2-weighted magnetic resonance image revealed a new demyelinating lesion localized to thoracic segments T4-T12. The lesion presumably affected autonomic efferents involved in intestinal mobility. Treatment with a pulse of methylprednisolone reduced both abdominal pain and lesion size. To our knowledge, this is the first reported case of a pediatric MS patient with a demyelinating lesion associated with an autonomic symptom of altered intestinal mobility in the absence of neurological symptoms. This atypical presentation of MS highlights the need for physicians' vigilance when treating this patient population. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The dumbest mistake I ever made.

PubMed

Reichman, O Howard

2015-01-01

Life as a Neurological Surgeon is a foreboding responsibility and a gratifying opportunity. Having the confidence and trust of individuals faced with a life or death situation requires extensive training and experience. Curiosity provides the motivation to continuously seek better understanding of complex disease problems, better technology, improved diagnostic capability, and surgical skills. Solution of these challenges has been a constant process for several decades and continues to pose opportunities for progress. Early observation of results provides important information, but in many circumstances it may require long-term evaluation to fully document the benefit, or lack of benefit, for any treatment procedure. The focus of attention by the Neurological Surgeon must be on the proper immediate management of each given situation, but it is also important, and a responsibility to consider the long-term consequences or results. This presents a difficult challenge because patients move into distant places and Neurological Surgeons frequently move to accept new opportunities. It is expensive and cumbersome to retain records for many years. It is also unpredictable which patient's information will become particularly significant. It is an opportunity to describe experience with four patients to illustrate this dilemma.

NeuroLOG: a community-driven middleware design.

PubMed

Montagnat, Johan; Gaignard, Alban; Lingrand, Diane; Rojas Balderrama, Javier; Collet, Philippe; Lahire, Philippe

2008-01-01

The NeuroLOG project designs an ambitious neurosciences middleware, gaining from many existing components and learning from past project experiences. It is targeting a focused application area and adopting a user-centric perspective to meet the neuroscientists expectations. It aims at fostering the adoption of HealthGrids in a pre-clinical community. This paper details the project's design study and methodology which were proposed to achieve the integration of heterogeneous site data schemas and the definition of a site-centric policy. The NeuroLOG middleware will bridge HealthGrid and local resources to match user desires to control their resources and provide a transitional model towards HealthGrids.

Current Concepts in Diagnosis and Treatment of Functional Neurological Disorders.

PubMed

Espay, Alberto J; Aybek, Selma; Carson, Alan; Edwards, Mark J; Goldstein, Laura H; Hallett, Mark; LaFaver, Kathrin; LaFrance, W Curt; Lang, Anthony E; Nicholson, Tim; Nielsen, Glenn; Reuber, Markus; Voon, Valerie; Stone, Jon; Morgante, Francesca

2018-06-04

Functional neurological disorders (FND) are common sources of disability in medicine. Patients have often been misdiagnosed, correctly diagnosed after lengthy delays, and/or subjected to poorly delivered diagnoses that prevent diagnostic understanding and lead to inappropriate treatments, iatrogenic harm, unnecessary and costly evaluations, and poor outcomes. Functional Neurological Symptom Disorder/Conversion Disorder was adopted by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, replacing the term psychogenic with functional and removing the criterion of psychological stress as a prerequisite for FND. A diagnosis can now be made in an inclusionary manner by identifying neurological signs that are specific to FNDs without reliance on presence or absence of psychological stressors or suggestive historical clues. The new model highlights a wider range of past sensitizing events, such as physical trauma, medical illness, or physiological/psychophysiological events. In this model, strong ideas and expectations about these events correlate with abnormal predictions of sensory data and body-focused attention. Neurobiological abnormalities include hypoactivation of the supplementary motor area and relative disconnection with areas that select or inhibit movements and are associated with a sense of agency. Promising evidence has accumulated for the benefit of specific physical rehabilitation and psychological interventions alone or in combination, but clinical trial evidence remains limited. Functional neurological disorders are a neglected but potentially reversible source of disability. Further research is needed to determine the dose and duration of various interventions, the value of combination treatments and multidisciplinary therapy, and the therapeutic modality best suited for each patient.

Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility.

PubMed

Roos-Araujo, Deidré; Stuart, Shani; Lea, Rod A; Haupt, Larisa M; Griffiths, Lyn R

2014-06-10

Migraine is a common neurological disorder classified by the World Health Organisation (WHO) as one of the top twenty most debilitating diseases in the developed world. Current therapies are only effective for a proportion of sufferers and new therapeutic targets are desperately needed to alleviate this burden. Recently the role of epigenetics in the development of many complex diseases including migraine has become an emerging topic. By understanding the importance of acetylation, methylation and other epigenetic modifications, it then follows that this modification process is a potential target to manipulate epigenetic status with the goal of treating disease. Bisulphite sequencing and methylated DNA immunoprecipitation have been used to demonstrate the presence of methylated cytosines in the human D-loop of mitochondrial DNA (mtDNA), proving that the mitochondrial genome is methylated. For the first time, it has been shown that there is a difference in mtDNA epigenetic status between healthy controls and those with disease, especially for neurodegenerative and age related conditions. Given co-morbidities with migraine and the suggestive link between mitochondrial dysfunction and the lowered threshold for triggering a migraine attack, mitochondrial methylation may be a new avenue to pursue. Creative thinking and new approaches are needed to solve complex problems and a systems biology approach, where multiple layers of information are integrated is becoming more important in complex disease modelling. Copyright © 2014 Elsevier B.V. All rights reserved.

Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms

PubMed Central

Ishibashi, Hidetoshi; Minakawa, Eiko N.; Motohashi, Hideyuki H.; Takayama, Osamu; Popiel, H. Akiko; Puentes, Sandra; Owari, Kensuke; Nakatani, Terumi; Nogami, Naotake; Yamamoto, Kazuhiro; Yonekawa, Takahiro; Tanaka, Yoko; Fujita, Naoko; Suzuki, Hikaru; Aizawa, Shu; Nagano, Seiichi; Yamada, Daisuke; Wada, Keiji; Kohsaka, Shinichi

2017-01-01

Abstract Age-associated neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3–4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases. PMID:28374014

[Neurological soft signs in schizophrenia: correlations with age, sex, educational status and psychopathology].

PubMed

Panagiotidis, P; Kaprinis, G; Iacovides, A; Fountoulakis, K

2013-01-01

Though the pathobiology of schizophrenia can be examined in multiple levels, the organic notion of brain disease suggests that neurological features will be present. One straightforward, inexpensive method of investigating brain dysfunction in schizophrenia is thought the bedside assessment of neurological abnormalities with a standard neurological examination. Neurological abnormalities are traditionally classified as "hard signs" (impairments in basic motor, sensory, and reflex behaviors, which do not appear to be affected in schizophrenia) and "soft signs", which refer to more complex phenomena such as abnormalities in motor control, integrative sensory function, sensorimotor integration, and cerebral laterality. Additionally, neurological soft signs (NSS) are minor motor and sensory abnormalities that are considered to be normal in the course of early development but abnormal when elicited in later life or persist beyond childhood. Soft signs also, have no definitive localizing significance but are indicative of subtle brain dysfunction. Most authors believe that they are a reflection not only of deficient integration between the sensory and motor systems, but also of dysfunctional neuronal circuits linking subcortical brain structures such as the basal ganglia, the brain stem, and the limbic system. Throughout the last four decades, studies have consistently shown that NSS are more frequently present in patients with schizophrenia than in normal subjects and non-psychotic psychiatric patients. However, the functional relevance of NSS remains unclear and their specificity has often been challenged, even though there is indication for a relative specificity with regard to diagnosis, or symptomatology. Many studies have considered soft signs as categorical variables thus hampering the evaluation of fluctuation with symptomatology and/or treatment, whereas other studies included insufficient number of assessed signs, or lacked a comprehensive assessment of extrapyramidal symptomatology. Factors such as sex, age or family history of schizophrenia, are said to influence the performance of neurological examination, whereas relative few studies have provided longitudinal follow-up data on neurological soft signs in a sufficient number of patients, in order to address a possible deterioration of neurological functions. Finally, one additional difficulty when analyzing the NSS literature lies in the diversity of symptoms that are evaluated in the studies and/or non-standardized procedures or scoring. We will review some basic issues concerning recurrent difficulties in the measurement and definition of soft signs, as well as controversies on the significance of these signs with respect to clinical subtyping of schizophrenia, and social and demographic variables.

Neurophysiology of Drosophila Models of Parkinson's Disease

PubMed Central

West, Ryan J. H.; Furmston, Rebecca; Williams, Charles A. C.; Elliott, Christopher J. H.

2015-01-01

We provide an insight into the role Drosophila has played in elucidating neurophysiological perturbations associated with Parkinson's disease- (PD-) related genes. Synaptic signalling deficits are observed in motor, central, and sensory systems. Given the neurological impact of disease causing mutations within these same genes in humans the phenotypes observed in fly are of significant interest. As such we observe four unique opportunities provided by fly nervous system models of Parkinson's disease. Firstly, Drosophila models are instrumental in exploring the mechanisms of neurodegeneration, with several PD-related mutations eliciting related phenotypes including sensitivity to energy supply and vesicular deformities. These are leading to the identification of plausible cellular mechanisms, which may be specific to (dopaminergic) neurons and synapses rather than general cellular phenotypes. Secondly, models show noncell autonomous signalling within the nervous system, offering the opportunity to develop our understanding of the way pathogenic signalling propagates, resembling Braak's scheme of spreading pathology in PD. Thirdly, the models link physiological deficits to changes in synaptic structure. While the structure-function relationship is complex, the genetic tractability of Drosophila offers the chance to separate fundamental changes from downstream consequences. Finally, the strong neuronal phenotypes permit relevant first in vivo drug testing. PMID:25960916

The mTOR signalling cascade: paving new roads to cure neurological disease.

PubMed

Crino, Peter B

2016-07-01

Defining the multiple roles of the mechanistic (formerly 'mammalian') target of rapamycin (mTOR) signalling pathway in neurological diseases has been an exciting and rapidly evolving story of bench-to-bedside translational research that has spanned gene mutation discovery, functional experimental validation of mutations, pharmacological pathway manipulation, and clinical trials. Alterations in the dual contributions of mTOR - regulation of cell growth and proliferation, as well as autophagy and cell death - have been found in developmental brain malformations, epilepsy, autism and intellectual disability, hypoxic-ischaemic and traumatic brain injuries, brain tumours, and neurodegenerative disorders. mTOR integrates a variety of cues, such as growth factor levels, oxygen levels, and nutrient and energy availability, to regulate protein synthesis and cell growth. In line with the positioning of mTOR as a pivotal cell signalling node, altered mTOR activation has been associated with a group of phenotypically diverse neurological disorders. To understand how altered mTOR signalling leads to such divergent phenotypes, we need insight into the differential effects of enhanced or diminished mTOR activation, the developmental context of these changes, and the cell type affected by altered signalling. A particularly exciting feature of the tale of mTOR discovery is that pharmacological mTOR inhibitors have shown clinical benefits in some neurological disorders, such as tuberous sclerosis complex, and are being considered for clinical trials in epilepsy, autism, dementia, traumatic brain injury, and stroke.

Mitochondrial Complex I Activity Suppresses Inflammation and Enhances Bone Resorption by Tipping the Balance of Macrophage-Osteoclast Polarization

PubMed Central

Jin, Zixue; Wei, Wei; Yang, Marie; Du, Yang; Wan, Yihong

2014-01-01

SUMMARY Mitochondrial complex I (CI) deficiency is associated with multiple neurological and metabolic disorders. However, its effect on innate immunity and bone remodeling is unclear. Using deletion of the essential CI subunit Ndufs4 as a model for mitochondrial dysfunction, we report that mitochondria suppress macrophage activation and inflammation while promoting osteoclast differentiation and bone resorption via both cell-autonomous and systemic regulation. Global Ndufs4 deletion causes systemic inflammation and osteopetrosis. Hematopoietic Ndufs4 deletion causes an intrinsic lineage shift from osteoclast to macrophage. Liver Ndufs4 deletion causes a metabolic shift from fatty acid oxidation to glycolysis, accumulating fatty acids and lactate (FA/LAC) in circulation. FA/LAC further activates Ndufs4−/− macrophages via ROS induction, and diminishes osteoclast lineage commitment in Ndufs4−/− progenitors; both inflammation and osteopetrosis in Ndufs4−/− mice are attenuated by TLR4/2 deletion. Together, these findings reveal mitochondrial CI as a critical rheostat of innate immunity and skeletal homeostasis. PMID:25130399

Clinical Applications for EPs in the ICU.

PubMed

Koenig, Matthew A; Kaplan, Peter W

2015-12-01

In critically ill patients, evoked potential (EP) testing is an important tool for measuring neurologic function, signal transmission, and secondary processing of sensory information in real time. Evoked potential measures conduction along the peripheral and central sensory pathways with longer-latency potentials representing more complex thalamocortical and intracortical processing. In critically ill patients with limited neurologic exams, EP provides a window into brain function and the potential for recovery of consciousness. The most common EP modalities in clinical use in the intensive care unit include somatosensory evoked potentials, brainstem auditory EPs, and cortical event-related potentials. The primary indications for EP in critically ill patients are prognostication in anoxic-ischemic or traumatic coma, monitoring for neurologic improvement or decline, and confirmation of brain death. Somatosensory evoked potentials had become an important prognostic tool for coma recovery, especially in comatose survivors of cardiac arrest. In this population, the bilateral absence of cortical somatosensory evoked potentials has nearly 100% specificity for death or persistent vegetative state. Historically, EP has been regarded as a negative prognostic test, that is, the absence of cortical potentials is associated with poor outcomes while the presence cortical potentials are prognostically indeterminate. In recent studies, the presence of middle-latency and long-latency potentials as well as the amplitude of cortical potentials is more specific for good outcomes. Event-related potentials, particularly mismatch negativity of complex auditory patterns, is emerging as an important positive prognostic test in patients under comatose. Multimodality predictive algorithms that combine somatosensory evoked potentials, event-related potentials, and clinical and radiographic factors are gaining favor for coma prognostication.

Association of Blood Lead Level with Neurological Features in 972 Children Affected by an Acute Severe Lead Poisoning Outbreak in Zamfara State, Northern Nigeria

PubMed Central

Greig, Jane; Thurtle, Natalie; Cooney, Lauren; Ariti, Cono; Ahmed, Abdulkadir Ola; Ashagre, Teshome; Ayela, Anthony; Chukwumalu, Kingsley; Criado-Perez, Alison; Gómez-Restrepo, Camilo; Meredith, Caitlin; Neri, Antonio; Stellmach, Darryl; Sani-Gwarzo, Nasir; Nasidi, Abdulsalami; Shanks, Leslie; Dargan, Paul I.

2014-01-01

Background In 2010, Médecins Sans Frontières (MSF) investigated reports of high mortality in young children in Zamfara State, Nigeria, leading to confirmation of villages with widespread acute severe lead poisoning. In a retrospective analysis, we aimed to determine venous blood lead level (VBLL) thresholds and risk factors for encephalopathy using MSF programmatic data from the first year of the outbreak response. Methods and Findings We included children aged ≤5 years with VBLL ≥45 µg/dL before any chelation and recorded neurological status. Odds ratios (OR) for neurological features were estimated; the final model was adjusted for age and baseline VBLL, using random effects for village of residence. 972 children met inclusion criteria: 885 (91%) had no neurological features; 34 (4%) had severe features; 47 (5%) had reported recent seizures; and six (1%) had other neurological abnormalities. The geometric mean VBLLs for all groups with neurological features were >100 µg/dL vs 65.9 µg/dL for those without neurological features. The adjusted OR for neurological features increased with increasing VBLL: from 2.75, 95%CI 1.27–5.98 (80–99.9 µg/dL) to 22.95, 95%CI 10.54–49.96 (≥120 µg/dL). Neurological features were associated with younger age (OR 4.77 [95% CI 2.50–9.11] for 1–<2 years and 2.69 [95%CI 1.15–6.26] for 2–<3 years, both vs 3–5 years). Severe neurological features were seen at VBLL <105 µg/dL only in those with malaria. Interpretation Increasing VBLL (from ≥80 µg/dL) and age 1–<3 years were strongly associated with neurological features; in those tested for malaria, a positive test was also strongly associated. These factors will help clinicians managing children with lead poisoning in prioritising therapy and developing chelation protocols. PMID:24740291

Concise Review: Adult Mesenchymal Stem Cells, Adult Neural Crest Stem Cells, and Therapy of Neurological Pathologies: A State of Play

PubMed Central

Neirinckx, Virginie; Coste, Cécile; Rogister, Bernard

2013-01-01

Adult stem cells are endowed with in vitro multilineage differentiation abilities and constitute an attractive autologous source of material for cell therapy in neurological disorders. With regard to lately published results, the ability of adult mesenchymal stem cells (MSCs) and neural crest stem cells (NCSCs) to integrate and differentiate into neurons once inside the central nervous system (CNS) is currently questioned. For this review, we collected exhaustive data on MSC/NCSC neural differentiation in vitro. We then analyzed preclinical cell therapy experiments in different models for neurological diseases and concluded that neural differentiation is probably not the leading property of adult MSCs and NCSCs concerning neurological pathology management. A fine analysis of the molecules that are secreted by MSCs and NCSCs would definitely be of significant interest regarding their important contribution to the clinical and pathological recovery after CNS lesions. PMID:23486833

Physical Therapy for Neurological Conditions in Geriatric Populations.

PubMed

Carmeli, Eli

2017-01-01

With more of the world's population surviving longer, individuals often face age-related neurology disorders and decline of function that can affect lifestyle and well-being. Despite neurophysiological changes affecting the brain function and structure, the aged brain, in some degree, can learn and relearn due to neuroplasticity. Recent advances in rehabilitation techniques have produced better functional outcomes in age-related neurological conditions. Physical therapy (PT) of the elderly individual focuses in particular on sensory-motor impairments, postural control coordination, and prevention of sarcopenia. Geriatric PT has a significant influence on quality of life, independent living, and life expectancy. However, in many developed and developing countries, the profession of PT is underfunded and understaffed. This article provides a brief overview on (a) age-related disease of central nervous system and (b) the principles, approaches, and doctrines of motor skill learning and point out the most common treatment models that PTs use for neurological patients.

Physical Therapy for Neurological Conditions in Geriatric Populations

PubMed Central

Carmeli, Eli

2017-01-01

With more of the world’s population surviving longer, individuals often face age-related neurology disorders and decline of function that can affect lifestyle and well-being. Despite neurophysiological changes affecting the brain function and structure, the aged brain, in some degree, can learn and relearn due to neuroplasticity. Recent advances in rehabilitation techniques have produced better functional outcomes in age-related neurological conditions. Physical therapy (PT) of the elderly individual focuses in particular on sensory–motor impairments, postural control coordination, and prevention of sarcopenia. Geriatric PT has a significant influence on quality of life, independent living, and life expectancy. However, in many developed and developing countries, the profession of PT is underfunded and understaffed. This article provides a brief overview on (a) age-related disease of central nervous system and (b) the principles, approaches, and doctrines of motor skill learning and point out the most common treatment models that PTs use for neurological patients. PMID:29270402

Development and validation of the positive affect and well-being scale for the neurology quality of life (Neuro-QOL) measurement system.

PubMed

Salsman, John M; Victorson, David; Choi, Seung W; Peterman, Amy H; Heinemann, Allen W; Nowinski, Cindy; Cella, David

2013-11-01

To develop and validate an item-response theory-based patient-reported outcomes assessment tool of positive affect and well-being (PAW). This is part of a larger NINDS-funded study to develop a health-related quality of life measurement system across major neurological disorders, called Neuro-QOL. Informed by a literature review and qualitative input from clinicians and patients, item pools were created to assess PAW concepts. Items were administered to a general population sample (N = 513) and a group of individuals with a variety of neurologic conditions (N = 581) for calibration and validation purposes, respectively. A 23-item calibrated bank and a 9-item short form of PAW was developed, reflecting components of positive affect, life satisfaction, or an overall sense of purpose and meaning. The Neuro-QOL PAW measure demonstrated sufficient unidimensionality and displayed good internal consistency, test-retest reliability, model fit, convergent and discriminant validity, and responsiveness. The Neuro-QOL PAW measure was designed to aid clinicians and researchers to better evaluate and understand the potential role of positive health processes for individuals with chronic neurological conditions. Further psychometric testing within and between neurological conditions, as well as testing in non-neurologic chronic diseases, will help evaluate the generalizability of this new tool.

[The importance of neurological examinations in the age of the technological revolution].

PubMed

Berbel-García, A; González-Spínola, J; Martínez-Salio, A; Porta-Etessam, J; Pérez-Martínez, D A; de Toledo, M; Sáiz-Díaz, R A

Neurologic practice and care have been modified in many important ways during the past ten years, to adapt to the explosion of new information and new technology. Students, residents and practicing physicians have been continuing programs to a model that focuses almost exclusively on the applications to neurologic disorders of the new knowledge obtained from biomedical research. On the other hand high demand for outpatient neurologic care prevents adequate patient's evaluation. Case 1: 65 years old female. Occipital headache diagnosed of tensional origin (normal computerized tomography). Two months later is re-evaluated due to intractable pain and hypoglossal lesion. An amplified computerized tomography revealed a occipital condyle metastasis. Case 2: 21 years old female. Clinical suspicion of demyelinating disease due to repeated facial paresis and sensitive disorder. General exploration and computerized tomography revealed temporo-mandibular joint. Case 3: 60 years old female. Valuation of anticoagulant therapy due to repeated transient ischemic attacks. She suffered from peripheral facial palsy related to auditory cholesteatoma. Neurologic education is nowadays orientated to new technologies. On the other hand, excessive demand prevents adequate valuation and a minute exploration is substituted by complementary evaluations. These situations generate diagnostic mistakes or iatrogenic. It would be important a consideration of the neurologic education profiles and fulfillment of consultations time recommendations for outpatients care.

The Dynamics of the Stapedial Acoustic Reflex.

NASA Astrophysics Data System (ADS)

Moss, Sherrin Mary

Available from UMI in association with The British Library. This thesis aims to separate the neural and muscular components of the stapedial acoustic reflex, both anatomically and physiologically. It aims to present an hypothesis to account for the differences between ipsilateral and contralateral reflex characteristics which have so far been unexplained, and achieve a greater understanding of the mechanisms underlying the reflex dynamics. A technique enabling faithful reproduction of the time course of the reflex is used throughout the experimental work. The technique measures tympanic membrane displacement as a result of reflex stapedius muscle contraction. The recorded response can be directly related to the mechanics of the middle ear and stapedius muscle contraction. Some development of the technique is undertaken by the author. A model of the reflex neural arc and stapedius muscle dynamics is evolved that is based upon a second order system. The model is unique in that it includes a latency in the ipsilateral negative feedback loop. Oscillations commonly observed on reflex responses are seen to be produced because of the inclusion of a latency in the feedback loop. The model demonstrates and explains the complex relationships between neural and muscle dynamic parameters observed in the experimental work. This more comprehensive understanding of the interaction between the stapedius dynamics and the neural arc of the reflex would not usually have been possible using human subjects, coupled with a non-invasive measurement technique. Evidence from the experimental work revealed the ipsilateral reflex to have, on average, a 5 dB lower threshold than the contralateral reflex. The oscillatory charcteristics, and the steady state response, of the contralateral reflex are also seen to be significantly different from those of the ipsilateral reflex. An hypothesis to account for the experimental observations is proposed. It is propounded that chemical neurotransmitters, and their effect upon the contralateral reflex arc from the site of the superior olivary complex to the motoneurones innervating the stapedius, account for the difference between the contralateral and ipsilateral reflex thresholds and dynamic characteristics. In the past two years the measurement technique used for the experimental work has developed from an audiological to a neurological diagnostic tool. This has enabled the results from the study to be applied in the field for valuable biomechanical and neurological explanations of the reflex response. (Abstract shortened by UMI.).

Operative management of brainstem cavernous malformations.

PubMed

Asaad, Wael F; Walcott, Brian P; Nahed, Brian V; Ogilvy, Christopher S

2010-09-01

Brainstem cavernous malformations (CMs) are complex lesions associated with hemorrhage and neurological deficit. In this review, the authors describe the anatomical nuances relating to the operative techniques for these challenging lesions. The resection of brainstem CMs in properly selected patients has been demonstrated to reduce the risk of rehemorrhage and can be achieved relatively safely in experienced hands.

Beyond Accommodations: Designing for Nonverbal/Nonauditory Learners in the Inclusive Art Room

ERIC Educational Resources Information Center

Wexler, Alice; Luethi-Garrecht, Aleánna

2015-01-01

The ability to verbalize--and therefore think and learn abstractly--has conditioned people to see the world in logical patterns. People are trained to do so by the wiring of the neurologically typical (neurotypical) brain and the increasing complexity of the environment that shapes it. Public schools are also designed for students with…

Isolating Attention Systems: A Cognitive-Anatomical Analysis. Cognitive Science Program, Technical Report No. 86-3.

ERIC Educational Resources Information Center

Posner, Michael I.; And Others

Recently, knowledge of the mechanisms of visual-spatial attention has improved due to studies employing single cell recording with alert monkeys and studies using performance analysis of neurological patients. These studies suggest that a complex neural network including parts of the posterior parietal lobe and midbrain are involved in covert…

A critical review of the postulated role of the non-essential amino acid, β-N-methylamino-L-alanine, in neurodegenerative disease in humans

EPA Science Inventory

The compound BMAA (β-N-methylamino-L-alanine) has been hypothesized to play a significant role in four serious neurological diseases in humans: Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) found on Guam, and ALS, parkinsonism, and dementia that occur glob...

Three-Dimensional Printed Modeling of Diffuse Low-Grade Gliomas and Associated White Matter Tract Anatomy.

PubMed

Thawani, Jayesh P; Singh, Nickpreet; Pisapia, Jared M; Abdullah, Kalil G; Parker, Drew; Pukenas, Bryan A; Zager, Eric L; Verma, Ragini; Brem, Steven

2017-04-01

Diffuse low-grade gliomas (DLGGs) represent several pathological entities that infiltrate and invade cortical and subcortical structures in the brain. To describe methods for rapid prototyping of DLGGs and surgically relevant anatomy. Using high-definition imaging data and rapid prototyping technologies, we were able to generate 3 patient DLGGs to scale and represent the associated white matter tracts in 3 dimensions using advanced diffusion tensor imaging techniques. This report represents a novel application of 3-dimensional (3-D) printing in neurosurgery and a means to model individualized tumors in 3-D space with respect to subcortical white matter tract anatomy. Faculty and resident evaluations of this technology were favorable at our institution. Developing an understanding of the anatomic relationships existing within individuals is fundamental to successful neurosurgical therapy. Imaging-based rapid prototyping may improve on our ability to plan for and treat complex neuro-oncologic pathology. Copyright © 2017 by the Congress of Neurological Surgeons

Structural analyses of Ca2+/CaM interaction with NaV channel C-termini reveal mechanisms of calcium-dependent regulation

PubMed Central

Wang, Chaojian; Chung, Ben C.; Yan, Haidun; Wang, Hong-Gang; Lee, Seok-Yong; Pitt, Geoffrey S.

2014-01-01

Ca2+ regulates voltage-gated Na+ (NaV) channels and perturbed Ca2+ regulation of NaV function is associated with epilepsy syndromes, autism, and cardiac arrhythmias. Understanding the disease mechanisms, however, has been hindered by a lack of structural information and competing models for how Ca2+ affects NaV channel function. Here, we report the crystal structures of two ternary complexes of a human NaV cytosolic C-terminal domain (CTD), a fibroblast growth factor homologous factor, and Ca2+/calmodulin (Ca2+/CaM). These structures rule out direct binding of Ca2+ to the NaV CTD, and uncover new contacts between CaM and the NaV CTD. Probing these new contacts with biochemical and functional experiments allows us to propose a mechanism by which Ca2+ could regulate NaV channels. Further, our model provides hints towards understanding the molecular basis of the neurologic disorders and cardiac arrhythmias caused by NaV channel mutations. PMID:25232683

Physics, Techniques and Review of Neuroradiological Applications of Diffusion Kurtosis Imaging (DKI).

PubMed

Marrale, M; Collura, G; Brai, M; Toschi, N; Midiri, F; La Tona, G; Lo Casto, A; Gagliardo, C

2016-12-01

In recent years many papers about diagnostic applications of diffusion tensor imaging (DTI) have been published. This is because DTI allows to evaluate in vivo and in a non-invasive way the process of diffusion of water molecules in biological tissues. However, the simplified description of the diffusion process assumed in DTI does not permit to completely map the complex underlying cellular components and structures, which hinder and restrict the diffusion of water molecules. These limitations can be partially overcome by means of diffusion kurtosis imaging (DKI). The aim of this paper is the description of the theory of DKI, a new topic of growing interest in radiology. DKI is a higher order diffusion model that is a straightforward extension of the DTI model. Here, we analyze the physics underlying this method, we report our MRI acquisition protocol with the preprocessing pipeline used and the DKI parametric maps obtained on a 1.5 T scanner, and we review the most relevant clinical applications of this technique in various neurological diseases.

Biological and medical applications of a brain-on-a-chip

PubMed Central

2016-01-01

The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical trials normally crucial for drug development. Current animal models have limited predictivity for drug efficacy in humans as the large majority of drugs fails in clinical trials. We have limited understanding of the function of the central nervous system and the complexity of the brain, especially during development and neuronal plasticity. Simple in vitro systems do not represent physiology and function of the brain. Moreover, the difficulty of studying interactions between human genetics and environmental factors leads to lack of knowledge about the events that induce neurological diseases. Microphysiological systems (MPS) promise to generate more complex in vitro human models that better simulate the organ’s biology and function. MPS combine different cell types in a specific three-dimensional (3D) configuration to simulate organs with a concrete function. The final aim of these MPS is to combine different “organoids” to generate a human-on-a-chip, an approach that would allow studies of complex physiological organ interactions. The recent discovery of induced pluripotent stem cells (iPSCs) gives a range of possibilities allowing cellular studies of individuals with different genetic backgrounds (e.g., human disease models). Application of iPSCs from different donors in MPS gives the opportunity to better understand mechanisms of the disease and can be a novel tool in drug development, toxicology, and medicine. In order to generate a brain-on-a-chip, we have established a 3D model from human iPSCs based on our experience with a 3D rat primary aggregating brain model. After four weeks of differentiation, human 3D aggregates stain positive for different neuronal markers and show higher gene expression of various neuronal differentiation markers compared to 2D cultures. Here we present the applications and challenges of this emerging technology. PMID:24912505

On data modeling for neurological application

NASA Astrophysics Data System (ADS)

Woźniak, Karol; Mulawka, Jan

The aim of this paper is to design and implement information system containing large database dedicated to support neurological-psychiatric examinations focused on human brain after stroke. This approach encompasses the following steps: analysis of software requirements, presentation of the problem solving concept, design and implementation of the final information system. Certain experiments were performed in order to verify the correctness of the project ideas. The approach can be considered as an interdisciplinary venture. Elaboration of the system architecture, data model and the tools supporting medical examinations are provided. The achievement of the design goals is demonstrated in the final conclusion.

Physical exercise improves functional recovery through mitigation of autophagy, attenuation of apoptosis and enhancement of neurogenesis after MCAO in rats.

PubMed

Zhang, Liying; Hu, Xiquan; Luo, Jing; Li, Lili; Chen, Xingyong; Huang, Ruxun; Pei, Zhong

2013-04-08

Physical exercise improves functional recovery after stroke through a complex mechanism that is not fully understood. Transient focal cerebral ischemia induces autophagy, apoptosis and neurogenesis in the peri-infarct region. This study is aimed to examine the effects of physical exercise on autophagy, apoptosis and neurogenesis in the peri-infarct region in a rat model of transient middle cerebral artery occlusion (MCAO). We found that autophagosomes, as labeled by microtubule-associated protein 1A light chain 3-II (LC3-II), were evident in the peri-infarct region at 3 days after 90-minute MCAO. Moreover, 44.6% of LC3-positive cells were also stained with TUNEL. The number of LC3 positive cells was significantly lower in physical exercise group than in control group at 14 and 21 days after MCAO. Suppression of autophagosomes by physical exercise was positively associated with improvement of neurological function. In addition, physical exercise significantly decreased the number of TUNEL-positive cells and increased the numbers of Ki67-positive, a proliferative marker, and insulin-like growth factor-1 (IGF-1) positive cells at 7, 14, and 21 days after MCAO. The present results demonstrate that physical exercise enhances neurological function possibly by reduction of autophagosome accumulation, attenuation of apoptosis and enhancement of neurogenesis in the peri-infarct region after transient MCAO in rats.

Spatacsin and spastizin act in the same pathway required for proper spinal motor neuron axon outgrowth in zebrafish.

PubMed

Martin, Elodie; Yanicostas, Constantin; Rastetter, Agnès; Alavi Naini, Seyedeh Maryam; Maouedj, Alissia; Kabashi, Edor; Rivaud-Péchoux, Sophie; Brice, Alexis; Stevanin, Giovanni; Soussi-Yanicostas, Nadia

2012-12-01

Hereditary spastic paraplegias (HSPs) are rare neurological conditions caused by degeneration of the long axons of the cerebrospinal tracts, leading to locomotor impairment and additional neurological symptoms. There are more than 40 different causative genes, 24 of which have been identified, including SPG11 and SPG15 mutated in complex clinical forms. Since the vast majority of the causative mutations lead to loss of function of the corresponding proteins, we made use of morpholino-oligonucleotide (MO)-mediated gene knock-down to generate zebrafish models of both SPG11 and SPG15 and determine how invalidation of the causative genes (zspg11 and zspg15) during development might contribute to the disease. Micro-injection of MOs targeting each gene caused locomotor impairment and abnormal branching of spinal cord motor neurons at the neuromuscular junction. More severe phenotypes with abnormal tail developments were also seen. Moreover, partial depletion of both proteins at sub-phenotypic levels resulted in the same phenotypes, suggesting for the first time, in vivo, a genetic interaction between these genes. In conclusion, the zebrafish orthologues of the SPG11 and SPG15 genes are important for proper development of the axons of spinal motor neurons and likely act in a common pathway to promote their proper path finding towards the neuromuscular junction. Copyright © 2012 Elsevier Inc. All rights reserved.

Ribonucleoprotein complexes in neurologic diseases.

PubMed

Ule, Jernej

2008-10-01

Ribonucleoprotein (RNP) complexes regulate the tissue-specific RNA processing and transport that increases the coding capacity of our genome and the ability to respond quickly and precisely to the diverse set of signals. This review focuses on three proteins that are part of RNP complexes in most cells of our body: TAR DNA-binding protein (TDP-43), the survival motor neuron protein (SMN), and fragile-X mental retardation protein (FMRP). In particular, the review asks the question why these ubiquitous proteins are primarily associated with defects in specific regions of the central nervous system? To understand this question, it is important to understand the role of genetic and cellular environment in causing the defect in the protein, as well as how the defective protein leads to misregulation of specific target RNAs. Two approaches for comprehensive analysis of defective RNA-protein interactions are presented. The first approach defines the RNA code or the collection of proteins that bind to a certain cis-acting RNA site in order to lead to a predictable outcome. The second approach defines the RNA map or the summary of positions on target RNAs where binding of a particular RNA-binding protein leads to a predictable outcome. As we learn more about the RNA codes and maps that guide the action of the dynamic RNP world in our brain, possibilities for new treatments of neurologic diseases are bound to emerge.

Solitary Metastasis to the Facial/Vestibulocochlear Nerve Complex: Case Report and Review of the Literature.

PubMed

Ariai, M Shafie; Eggers, Scott D; Giannini, Caterina; Driscoll, Colin L W; Link, Michael J

2015-10-01

Distant metastasis of mucinous adenocarcinoma from the gastrointestinal tract, ovaries, pancreas, lungs, breast, or urogenital system is a well-described entity. Mucinous adenocarcinomas from different primary sites are histologically identical with gland cells producing a copious amount of mucin. This report describes a very rare solitary metastasis of a mucinous adenocarcinoma of unknown origin to the facial/vestibulocochlear nerve complex in the cerebellopontine angle. A 71-year-old woman presented with several month history of progressive neurological decline and a negative extensive workup performed elsewhere. She presented to our institution with complete left facial weakness, left-sided deafness, gait unsteadiness, headache and anorexia. A repeat magnetic resonance imaging scan of the head revealed a cystic, enhancing abnormality involving the left cerebellopontine angle and internal auditory canal. A left retrosigmoid craniotomy was performed and the lesion was completely resected. The final pathology was a mucinous adenocarcinoma of indeterminate origin. Postoperatively, the patient continued with her preoperative deficits and subsequently died of her systemic disease 6 weeks after discharge. The facial/vestibulocochlear nerve complex is an unusual location for metastatic disease in the central nervous system. Clinicians should consider metastatic tumor as the possible etiology of an unusual appearing mass in this location causing profound neurological deficits. The prognosis after metastatic mucinous adenocarcinoma to the cranial nerves in the cerebellopontine angle may be poor. Copyright © 2015 Elsevier Inc. All rights reserved.

A clinically authentic mouse model of enterovirus 71 (EV-A71)-induced neurogenic pulmonary oedema.

PubMed

Victorio, Carla Bianca Luena; Xu, Yishi; Ng, Qimei; Chua, Beng Hooi; Alonso, Sylvie; Chow, Vincent T K; Chua, Kaw Bing

2016-06-30

Enterovirus 71 (EV-A71) is a neurotropic virus that sporadically causes fatal neurologic illness among infected children. Animal models of EV-A71 infection exist, but they do not recapitulate in animals the spectrum of disease and pathology observed in fatal human cases. Specifically, neurogenic pulmonary oedema (NPE)-the main cause of EV-A71 infection-related mortality-is not observed in any of these models. This limits their utility in understanding viral pathogenesis of neurologic infections. We report the development of a mouse model of EV-A71 infection displaying NPE in severely affected animals. We inoculated one-week-old BALB/c mice with an adapted EV-A71 strain and identified clinical signs consistent with observations in human cases and other animal models. We also observed respiratory distress in some mice. At necropsy, we found their lungs to be heavier and incompletely collapsed compared to other mice. Serum levels of catecholamines and histopathology of lung and brain tissues of these mice strongly indicated onset of NPE. The localization of virally-induced brain lesions also suggested a potential pathogenic mechanism for EV-A71-induced NPE. This novel mouse model of virally-induced NPE represents a valuable resource for studying viral mechanisms of neuro-pathogenesis and pre-clinical testing of potential therapeutics and prophylactics against EV-A71-related neurologic complications.

Video training and certification program improves reliability of postischemic neurologic deficit measurement in the rat.

PubMed

Taninishi, Hideki; Pearlstein, Molly; Sheng, Huaxin; Izutsu, Miwa; Chaparro, Rafael E; Goldstein, Larry B; Warner, David S

2016-12-01

Scoring systems are used to measure behavioral deficits in stroke research. Video-assisted training is used to standardize stroke-related neurologic deficit scoring in humans. We hypothesized that a video-assisted training and certification program can improve inter-rater reliability in assessing neurologic function after middle cerebral artery occlusion in rats. Three expert raters scored neurologic deficits in post-middle cerebral artery occlusion rats using three published systems having different complexity levels (3, 18, or 48 points). The system having the highest point estimate for the correlation between neurologic score and infarct size was selected to create a video-assisted training and certification program. Eight trainee raters completed the video-assisted training and certification program. Inter-rater agreement ( Κ: score) and agreement with expert consensus scores were measured before and after video-assisted training and certification program completion. The 48-point system correlated best with infarct size. Video-assisted training and certification improved agreement with expert consensus scores (pretraining = 65 ± 10, posttraining = 87 ± 14, 112 possible scores, P < 0.0001), median number of trainee raters with scores within ±2 points of the expert consensus score (pretraining = 4, posttraining = 6.5, P < 0.01), categories with Κ:  > 0.4 (pretraining = 4, posttraining = 9), and number of categories with an improvement in the Κ: score from pretraining to posttraining (n = 6). Video-assisted training and certification improved trainee inter-rater reliability and agreement with expert consensus behavioral scores in rats after middle cerebral artery occlusion. Video-assisted training and certification may be useful in multilaboratory preclinical studies. © The Author(s) 2015.

Diagnostic Testing and Hospital Outcomes of Children with Neurologic Impairment and Bacterial Pneumonia.

PubMed

Thomson, Joanna; Hall, Matt; Berry, Jay G; Stone, Bryan; Ambroggio, Lilliam; Srivastava, Rajendu; Shah, Samir S

2016-11-01

To assess hospital-level variability in diagnostic testing and outcomes for children with neurologic impairment hospitalized with pneumonia. A retrospective cohort study of 27 455 children ages 1-18 years with neurologic impairment hospitalized with pneumonia at 39 children's hospitals. K-means clustering was used to assign each hospital to 1 of 3 groups (termed A, B, and C) based on similar diagnostic testing patterns. Outcomes of hospital-level median length of stay (LOS), 30-day readmissions, and pneumonia-associated complications were compared while controlling for patient differences. Overall, 48.5% had comorbid complex chronic conditions, and 25.4% were assisted with medical technology. Outcomes and diagnostic testing varied across hospitals: median hospital-level LOS, 3.2 days (IQR 2.8-3.8); median readmission, 8.4% (IQR 6.8,-10.0); and median pneumonia-associated complication rate, 23.1% (IQR 18.7-26.8). Despite similar populations, hospitals in group A tended to perform fewer tests than those in groups B and C. Across hospital groups, there was a significant difference in adjusted readmission rates (group A 7.2%, group B 9.0%, group C 7.7%, P = .003). There was no significant difference in adjusted median LOS (group A 3.4 days, group B 3.2 days, group C 3.3 days, P = .3) or adjusted pneumonia-associated complication rates (group A 22.5%, group B 22.5%, group C 25.0%, P = .6). For children with neurologic impairment hospitalized with pneumonia, across hospital differences in diagnostic testing were not associated with clinically meaningful differences in outcomes. High-utilizing hospitals may be able to decrease diagnostic testing for children with neurologic impairment hospitalized with pneumonia without adversely impacting outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Newborn screening: A disease-changing intervention for glutaric aciduria type 1.

PubMed

Boy, Nikolas; Mengler, Katharina; Thimm, Eva; Schiergens, Katharina A; Marquardt, Thorsten; Weinhold, Natalie; Marquardt, Iris; Das, Anibh M; Freisinger, Peter; Grünert, Sarah C; Vossbeck, Judith; Steinfeld, Robert; Baumgartner, Matthias R; Beblo, Skadi; Dieckmann, Andrea; Näke, Andrea; Lindner, Martin; Heringer, Jana; Hoffmann, Georg F; Mühlhausen, Chris; Maier, Esther M; Ensenauer, Regina; Garbade, Sven F; Kölker, Stefan

2018-05-01

Untreated individuals with glutaric aciduria type 1 (GA1) commonly present with a complex, predominantly dystonic movement disorder (MD) following acute or insidious onset striatal damage. Implementation of GA1 into newborn screening (NBS) programs has improved the short-term outcome. It remains unclear, however, whether NBS changes the long-term outcome and which variables are predictive. This prospective, observational, multicenter study includes 87 patients identified by NBS, 4 patients missed by NBS, and 3 women with GA1 identified by positive NBS results of their unaffected children. The study population comprises 98.3% of individuals with GA1 identified by NBS in Germany during 1999-2016. Overall, cumulative sensitivity of NBS is 95.6%, but it is lower (84%) for patients with low excreter phenotype. The neurologic outcome of patients missed by NBS is as poor as in the pre-NBS era, and the clinical phenotype of diagnosed patients depends on the quality of therapeutic interventions rather than noninterventional variables. Presymptomatic start of treatment according to current guideline recommendations clearly improves the neurologic outcome (MD: 7% of patients), whereas delayed emergency treatment results in acute onset MD (100%), and deviations from maintenance treatment increase the risk of insidious onset MD (50%). Independent of the neurologic phenotype, kidney function tends to decline with age, a nonneurologic manifestation not predicted by any variable included in this study. NBS is a beneficial, disease-changing intervention for GA1. However, improved neurologic outcome critically depends on adherence to recommended therapy, whereas kidney dysfunction does not appear to be impacted by recommended therapy. Ann Neurol 2018;83:970-979. © 2018 American Neurological Association.

The Effectiveness of Singing or Playing a Wind Instrument in Improving Respiratory Function in Patients with Long-Term Neurological Conditions: A Systematic Review.

PubMed

Ang, Kexin; Maddocks, Matthew; Xu, Huiying; Higginson, Irene J

2017-03-01

Many long-term neurological conditions adversely affect respiratory function. Singing and playing wind instruments are relatively inexpensive interventions with potential for improving respiratory function; however, synthesis of current evidence is needed to inform research and clinical use of music in respiratory care. To critically appraise, analyze, and synthesize published evidence on the effectiveness of singing or playing a wind instrument to improve respiratory function in people with long-term neurological conditions. Systematic review of published randomized controlled trials and observational studies examining singing or playing wind instruments to improve respiratory function in individuals with long-term neurological conditions. Articles meeting specified inclusion criteria were identified through a search of the Medline, Embase, PsycINFO, Cochrane Library, CINAHL, Web of Science, CAIRSS for Music, WHO International Clinical Trials Registry Platform Search Portal, and AMED databases as early as 1806 through March 2015. Information on study design, clinical populations, interventions, and outcome measures was extracted and summarized using an electronic standardized coding form. Methodological quality was assessed and summarized across studies descriptively. From screening 584 references, 68 full texts were reviewed and five studies included. These concerned 109 participants. The studies were deemed of low quality, due to evidence of bias, in part due to intervention complexity. No adverse effects were reported. Overall, there was a trend toward improved respiratory function, but only one study on Parkinson's disease had significant between-group differences. The positive trend in respiratory function in people with long-term neurological conditions following singing or wind instrument therapy is of interest, and warrants further investigation. © the American Music Therapy Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Clinical presentation of anti-N-methyl-d-aspartate receptor and anti-voltage-gated potassium channel complex antibodies in children: A series of 24 cases.

PubMed

Konuskan, Bahadir; Yildirim, Mirac; Topaloglu, Haluk; Erol, Ilknur; Oztoprak, Ulkuhan; Tan, Huseyin; Gocmen, Rahsan; Anlar, Banu

2018-01-01

The symptomatology and paraclinical findings of antibody-mediated encephalitis, a relatively novel disorder, are still being characterized in adults and children. A high index of suspicion is needed in order to identify these cases among children presenting with various neurological symptoms. The aim of this study is to examine the clinical, demographic and laboratory findings and outcome of children with anti-NMDAR and anti-VGKC encephalitis for any typical or distinctive features. Cases diagnosed with anti-N-Methyl d-aspartate receptor (NMDAR) and anti-voltage gated potassium channel (VGKC) antibody-mediated encephalopathy in four major child neurology centers are described. In four years, 16 children with NMDAR and 8 children with VGKC antibody-associated disease were identified in the participating centers. The most frequent initial manifestation consisted of generalized seizures and cognitive symptoms in both groups. Movement abnormalities were frequent in anti-NMDAR patients and autonomic symptoms, in anti-VGKC patients. Cerebrospinal fluid (CSF) protein, cell count and IgG index were normal in 9/15 anti-NMDAR and 5/8 anti-VGKC patients tested. EEG and MRI findings were usually nonspecific and non-contributory. The rate and time of recovery was not related to age, sex, acute or subacute onset, antibody type, MRI, EEG or CSF results. Treatment within 3 months of onset was associated with normal neurological outcome. Our results suggest anti-NMDAR and VGKC encephalopathies mostly present with non-focal neurological symptoms longer than 3 weeks. In contrast with adult cases, routine CSF testing, MRI and EEG did not contribute to the diagnosis in this series. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Serum S100B is a useful surrogate marker for long-term outcomes in photochemically-induced thrombotic stroke rat models.

PubMed

Tanaka, Yu; Koizumi, Chie; Marumo, Toshiyuki; Omura, Tomohiro; Yoshida, Shigeru

2007-08-02

In recent years, serum S100B has been used as a secondary endpoint in some clinical trials, in which serum S100B has successfully indicated the benefits or harm done by the tested agents. Compared to clinical stroke studies, few experimental stroke studies report using serum S100B as a surrogate marker for estimating the long-term effects of neuroprotectants. This study sought to observe serum S100B kinetics in PIT stroke models and to clarify the association between serum S100B and both final infarct volumes and long-term neurological outcomes. Furthermore, to demonstrate that early elevations in serum S100B reflect successful neuroprotective treatment, a pharmacological study was performed with a non-competitive NMDA glutamate receptor antagonist, MK-801. Serum S100B levels were significantly elevated after PIT stroke, reaching peak values 48 h after the onset and declining thereafter. Single measurements of serum S100B as early as 48 h after PIT stroke correlated significantly with final infarct volumes and long-term neurological outcomes. Elevated serum S100B was significantly attenuated by MK-801, correlating significantly with long-term beneficial effects of MK-801 on infarct volumes and neurological outcomes. Our results showed that single measurements of serum S100B 48 h after PIT stroke would serve as an early and simple surrogate marker for long-term evaluation of histological and neurological outcomes in PIT stroke rat models.

The burden of mental, neurological, and substance use disorders in China and India: a systematic analysis of community representative epidemiological studies.

PubMed

Charlson, Fiona J; Baxter, Amanda J; Cheng, Hui G; Shidhaye, Rahul; Whiteford, Harvey A

2016-07-23

China and India jointly account for 38% of the world population, so understanding the burden attributed to mental, neurological, and substance use disorders within these two countries is essential. As part of the Lancet/Lancet Psychiatry China-India Mental Health Alliance Series, we aim to provide estimates of the burden of mental, neurological, and substance use disorders for China and India from the Global Burden of Disease Study 2013 (GBD 2013). In this systematic analysis for community representative epidemiological studies, we conducted systematic reviews in line with PRISMA guidelines for community representative epidemiological studies. We extracted estimates of prevalence, incidence, remission and duration, and mortality along with associated uncertainty intervals from GBD 2013. Using these data as primary inputs, DisMod-MR 2.0, a Bayesian meta-regression instrument, used a log rate and incidence-prevalence-mortality mathematical model to develop internally consistent epidemiological models. Disability-adjusted life-year (DALY) changes between 1990 and 2013 were decomposed to quantify change attributable to population growth and ageing. We projected DALYs from 2013 to 2025 for mental, neurological, and substance use disorders using United Nations population data. Around a third of global DALYs attributable to mental, neurological, and substance use disorders were found in China and India (66 million DALYs), a number greater than all developed countries combined (50 million DALYs). Disease burden profiles differed; India showed similarities with other developing countries (around 50% of DALYs attributable to non-communicable disease), whereas China more closely resembled developed countries (around 80% of DALYs attributable to non-communicable disease). The overall population growth in India explains a greater proportion of the increase in mental, neurological, and substance use disorder burden from 1990 to 2013 (44%) than in China (20%). The burden of mental, neurological, and substance use disorders is estimated to increase by 10% in China and 23% in India between 2013 and 2025. The current and projected burden of mental, neurological, and substance use disorders in China and India warrants the urgent prioritisation of programmes focused on targeted prevention, early identification, and effective treatment. China Medical Board, Bill & Melinda Gates Foundation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Considerations for Experimental Animal Models of Concussion, Traumatic Brain Injury, and Chronic Traumatic Encephalopathy—These Matters Matter

PubMed Central

Wojnarowicz, Mark W.; Fisher, Andrew M.; Minaeva, Olga; Goldstein, Lee E.

2017-01-01

Animal models of concussion, traumatic brain injury (TBI), and chronic traumatic encephalopathy (CTE) are widely available and routinely deployed in laboratories around the world. Effective animal modeling requires careful consideration of four basic principles. First, animal model use must be guided by clarity of definitions regarding the human disease or condition being modeled. Concussion, TBI, and CTE represent distinct clinical entities that require clear differentiation: concussion is a neurological syndrome, TBI is a neurological event, and CTE is a neurological disease. While these conditions are all associated with head injury, the pathophysiology, clinical course, and medical management of each are distinct. Investigators who use animal models of these conditions must take into account these clinical distinctions to avoid misinterpretation of results and category mistakes. Second, model selection must be grounded by clarity of purpose with respect to experimental questions and frame of reference of the investigation. Distinguishing injury context (“inputs”) from injury consequences (“outputs”) may be helpful during animal model selection, experimental design and execution, and interpretation of results. Vigilance is required to rout out, or rigorously control for, model artifacts with potential to interfere with primary endpoints. The widespread use of anesthetics in many animal models illustrates the many ways that model artifacts can confound preclinical results. Third, concordance between key features of the animal model and the human disease or condition being modeled is required to confirm model biofidelity. Fourth, experimental results observed in animals must be confirmed in human subjects for model validation. Adherence to these principles serves as a bulwark against flawed interpretation of results, study replication failure, and confusion in the field. Implementing these principles will advance basic science discovery and accelerate clinical translation to benefit people affected by concussion, TBI, and CTE. PMID:28620350

Ulinastatin alleviates neurological deficiencies evoked by transient cerebral ischemia via improving autophagy, Nrf-2-ARE and apoptosis signals in hippocampus.

PubMed

Jiang, Xiao-Ming; Hu, Jing-Hai; Wang, Lu-Lu; Ma, Chi; Wang, Xu; Liu, Xiao-Liang

2018-05-10

Ulinastatin [or called as urinary trypsin inhibitor (UTI)] plays a role in regulating neurological deficits evoked by transient cerebral ischemia. However, the underlying mechanisms still need to be determined. The present study was to examine the effects of UTI on autophagy, Nrf2-ARE and apoptosis signal pathway in the hippocampus in the process of neurological functions after cerebral ischemia using a rat model of cardiac arrest (CA). CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Western Blot analysis was employed to determine the expression of representative autophagy (namely, Atg5, LC3, Beclin 1), p62 protein (a maker of autophagic flux), and Nrf2-ARE pathways. Neuronal apoptosis was assessed by determining expression levels of Caspase-3 and Caspase-9, and by examining terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL). The modified neurological severity score (mNSS) and spatial working memory performance were used to assess neurological deficiencies in CA rats. Our results show that CA amplified autophagy and apoptotic Caspase-3/Caspase-9, and downregulated Nrf2-ARE pathway in the hippocampus CA1 region. Systemic administration of UTI attenuated autophagy and apoptosis, and largely restored Nrf2-ARE signal pathway following cerebral ischemia and thereby alleviated neurological deficits with increasing survival of CA rats. Our data suggest that UTI improves the worsened protein expression of autophagy and apoptosis, and restores Nrf2-ARE signals in the hippocampus and this is linked to inhibition of neurological deficiencies in transient cerebral ischemia. UTI plays a beneficial role in modulating neurological deficits induced by transient cerebral ischemia via central autophagy, apoptosis and Nrf2-ARE mechanisms.

Neurological surgery: the influence of physical and mental demands on humans performing complex operations.

PubMed

Bourne, Sarah K; Walcott, Brian P; Sheth, Sameer A; Coumans, Jean-Valery C E

2013-03-01

Performing neurological surgery is an inherently demanding task on the human body, both physically and mentally. Neurosurgeons routinely perform "high stakes" operations in the setting of mental and physical fatigue. These conditions may be not only the result of demanding operations, but also influential to their outcome. Similar to other performance-based endurance activities, training is paramount to successful outcomes. The inflection point, where training reaches the point of diminishing returns, is intensely debated. For the neurosurgeon, this point must be exploited to the maximum, as patients require both the best-trained and best-performing surgeon. In this review, we explore the delicate balance of training and performance, as well as some routinely used adjuncts to improve human performance. Copyright © 2012 Elsevier Ltd. All rights reserved.

Historical model for editor and Office of Research Integrity cooperation in handling allegations, investigation, and retraction in a contentious (Abbs) case of research misconduct.

PubMed

Price, Alan R; Daroff, Robert B

2015-01-01

Cooperation between a journal editor and the federal Office of Research Integrity (ORI) in addressing investigations of research misconduct, each performing their own responsibilities while keeping each other informed of events and evidence, can be critical to the professional and regulatory resolution of a case. This paper describes the history of one of ORI's most contentious investigations that involved falsification of research on Parkinson's disease patients by James Abbs, Professor of Neurology, University of Wisconsin, published in the journal Neurology, which was handled cooperatively by the authors, who were the chief ORI investigator and the Editor-in-Chief of Neurology, respectively.

A Population Intervention to Improve Outcomes in Children With Medical Complexity.

PubMed

Noritz, Garey; Madden, Melissa; Roldan, Dina; Wheeler, T Arthur; Conkol, Kimberly; Brilli, Richard J; Barnard, John; Gleeson, Sean

2017-01-01

Children with medical complexity experience frequent interactions with the medical system and often receive care that is costly, duplicative, and inefficient. The growth of value-based contracting creates incentives for systems to improve their care. This project was designed to improve the health, health care value, and utilization for a population-based cohort of children with neurologic impairment and feeding tubes. A freestanding children's hospital and affiliated accountable care organization jointly developed a quality improvement initiative. Children with a percutaneous feeding tube, a neurologic diagnosis, and Medicaid, were targeted for intervention within a catchment area of >300 000 children receiving Medicaid. Initiatives included standardizing feeding tube management, improving family education, and implementing a care coordination program. Between January 2011 and December 2014, there was an 18.0% decrease (P < .001) in admissions and a 31.9% decrease (P < .001) in the average length of stay for children in the cohort. Total inpatient charges were reduced by $11 764 856. There was an 8.2% increase (P < .001) in the percentage of children with weights between the fifth and 95th percentiles. The care coordination program enrolled 58.3% of the cohort. This population-based initiative to improve the care of children with medical complexity showed promising results, including a reduction in charges while improving weight status and implementing a care coordination program. A concerted institutional initiative, in the context of an accountable care organization, can be part of the solution for improving outcomes and health care value for children with medical complexity. Copyright © 2017 by the American Academy of Pediatrics.

Acquiring neural signals for developing a perception and cognition model

NASA Astrophysics Data System (ADS)

Li, Wei; Li, Yunyi; Chen, Genshe; Shen, Dan; Blasch, Erik; Pham, Khanh; Lynch, Robert

2012-06-01

The understanding of how humans process information, determine salience, and combine seemingly unrelated information is essential to automated processing of large amounts of information that is partially relevant, or of unknown relevance. Recent neurological science research in human perception, and in information science regarding contextbased modeling, provides us with a theoretical basis for using a bottom-up approach for automating the management of large amounts of information in ways directly useful for human operators. However, integration of human intelligence into a game theoretic framework for dynamic and adaptive decision support needs a perception and cognition model. For the purpose of cognitive modeling, we present a brain-computer-interface (BCI) based humanoid robot system to acquire brainwaves during human mental activities of imagining a humanoid robot-walking behavior. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model. The BCI system consists of a data acquisition unit with an electroencephalograph (EEG), a humanoid robot, and a charge couple CCD camera. An EEG electrode cup acquires brainwaves from the skin surface on scalp. The humanoid robot has 20 degrees of freedom (DOFs); 12 DOFs located on hips, knees, and ankles for humanoid robot walking, 6 DOFs on shoulders and arms for arms motion, and 2 DOFs for head yaw and pitch motion. The CCD camera takes video clips of the human subject's hand postures to identify mental activities that are correlated to the robot-walking behaviors. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model.

Multi-complexity ensemble measures for gait time series analysis: application to diagnostics, monitoring and biometrics.

PubMed

Gavrishchaka, Valeriy; Senyukova, Olga; Davis, Kristina

2015-01-01

Previously, we have proposed to use complementary complexity measures discovered by boosting-like ensemble learning for the enhancement of quantitative indicators dealing with necessarily short physiological time series. We have confirmed robustness of such multi-complexity measures for heart rate variability analysis with the emphasis on detection of emerging and intermittent cardiac abnormalities. Recently, we presented preliminary results suggesting that such ensemble-based approach could be also effective in discovering universal meta-indicators for early detection and convenient monitoring of neurological abnormalities using gait time series. Here, we argue and demonstrate that these multi-complexity ensemble measures for gait time series analysis could have significantly wider application scope ranging from diagnostics and early detection of physiological regime change to gait-based biometrics applications.

IMMUNOLOGY OF TAENIA SOLIUM TAENIASIS AND HUMAN CYSTICERCOSIS

PubMed Central

Garcia, Hector H.; Rodriguez, Silvia; Friedland, Jon S.

2018-01-01

The life cycle of Taenia solium, the pork tapeworm, is continuously closed in many rural settings in developing countries when free roaming pigs ingest human stools containing T. solium eggs and develop cysticercosis, and humans ingest pork infected with cystic larvae and develop intestinal taeniasis, or may also accidentally acquire cysticercosis by fecal-oral contamination. Cysticercosis of the human nervous system, neurocysticercosis, is a major cause of seizures and other neurological morbidity in most of the world. The dynamics of exposure, infection and disease as well as the location of parasites result in a complex interaction which involves immune evasion mechanisms and involutive or progressive disease along time. Moreover, existing data is limited by the relative lack of animal models. This manuscript manuscript revises the available information on the immunology of human taeniasis and cysticercosis. PMID:24962350

Immunology of Taenia solium taeniasis and human cysticercosis.

PubMed

Garcia, H H; Rodriguez, S; Friedland, J S

2014-08-01

The life cycle of Taenia solium, the pork tapeworm, is continuously closed in many rural settings in developing countries when free roaming pigs ingest human stools containing T. solium eggs and develop cysticercosis, and humans ingest pork infected with cystic larvae and develop intestinal taeniasis, or may also accidentally acquire cysticercosis by faecal-oral contamination. Cysticercosis of the human nervous system, neurocysticercosis, is a major cause of seizures and other neurological morbidity in most of the world. The dynamics of exposure, infection and disease as well as the location of parasites result in a complex interaction which involves immune evasion mechanisms and involutive or progressive disease along time. Moreover, existing data are limited by the relative lack of animal models. This manuscript revises the available information on the immunology of human taeniasis and cysticercosis. © 2014 John Wiley & Sons Ltd.

Neuroligins Provide Molecular Links Between Syndromic and Non-Syndromic Autism

PubMed Central

Singh, Sandeep K.; Eroglu, Cagla

2014-01-01

Autism is a common and heritable neuropsychiatric disorder that can be categorized into two types: syndromic and non-syndromic, the former of which are associated with other neurological disorders or syndromes. Molecular and functional links between syndromic and non-syndromic autism genes were lacking until studies aimed at understanding role of trans-synaptic adhesion molecule neuroligin, which is associated with non-syndromic autism, provided important connections. Here, we integrate data from these studies into a model of how neuroligin functions to control synaptic connectivity in the central nervous system and how neuroligin dysfunction may participate in the pathophysiology of autism. Understanding the complex functional interactions between neuroligins and other autism-associated proteins at the synapse is crucial to understand the pathology of autism. This understanding might bring us closer to development of therapeutic approaches for autism. PMID:23838185

Organoid technology for brain and therapeutics research.

PubMed

Wang, Zhi; Wang, Shu-Na; Xu, Tian-Ying; Miao, Zhu-Wei; Su, Ding-Feng; Miao, Chao-Yu

2017-10-01

Brain is one of the most complex organs in human. The current brain research is mainly based on the animal models and traditional cell culture. However, the inherent species differences between humans and animals as well as the gap between organ level and cell level make it difficult to study human brain development and associated disorders through traditional technologies. Recently, the brain organoids derived from pluripotent stem cells have been reported to recapitulate many key features of human brain in vivo, for example recapitulating the zone of putative outer radial glia cells. Brain organoids offer a new platform for scientists to study brain development, neurological diseases, drug discovery and personalized medicine, regenerative medicine, and so on. Here, we discuss the progress, applications, advantages, limitations, and prospects of brain organoid technology in neurosciences and related therapeutics. © 2017 John Wiley & Sons Ltd.

Supply and demand analysis of the current and future US neurology workforce

PubMed Central

Storm, Michael V.; Chakrabarti, Ritashree; Drogan, Oksana; Keran, Christopher M.; Donofrio, Peter D.; Henderson, Victor W.; Kaminski, Henry J.; Stevens, James C.; Vidic, Thomas R.

2013-01-01

Objective: This study estimates current and projects future neurologist supply and demand under alternative scenarios nationally and by state from 2012 through 2025. Methods: A microsimulation supply model simulates likely career choices of individual neurologists, taking into account the number of new neurologists trained each year and changing demographics of the neurology workforce. A microsimulation demand model simulates utilization of neurology services for each individual in a representative sample of the population in each state and for the United States as a whole. Demand projections reflect increased prevalence of neurologic conditions associated with population growth and aging, and expanded coverage under health care reform. Results: The estimated active supply of 16,366 neurologists in 2012 is projected to increase to 18,060 by 2025. Long wait times for patients to see a neurologist, difficulty hiring new neurologists, and large numbers of neurologists who do not accept new Medicaid patients are consistent with a current national shortfall of neurologists. Demand for neurologists is projected to increase from ∼18,180 in 2012 (11% shortfall) to 21,440 by 2025 (19% shortfall). This includes an increased demand of 520 full-time equivalent neurologists starting in 2014 from expanded medical insurance coverage associated with the Patient Protection and Affordable Care Act. Conclusions: In the absence of efforts to increase the number of neurology professionals and retain the existing workforce, current national and geographic shortfalls of neurologists are likely to worsen, exacerbating long wait times and reducing access to care for Medicaid beneficiaries. Current geographic differences in adequacy of supply likely will persist into the future. PMID:23596071

Supply and demand analysis of the current and future US neurology workforce.

PubMed

Dall, Timothy M; Storm, Michael V; Chakrabarti, Ritashree; Drogan, Oksana; Keran, Christopher M; Donofrio, Peter D; Henderson, Victor W; Kaminski, Henry J; Stevens, James C; Vidic, Thomas R

2013-07-30

This study estimates current and projects future neurologist supply and demand under alternative scenarios nationally and by state from 2012 through 2025. A microsimulation supply model simulates likely career choices of individual neurologists, taking into account the number of new neurologists trained each year and changing demographics of the neurology workforce. A microsimulation demand model simulates utilization of neurology services for each individual in a representative sample of the population in each state and for the United States as a whole. Demand projections reflect increased prevalence of neurologic conditions associated with population growth and aging, and expanded coverage under health care reform. The estimated active supply of 16,366 neurologists in 2012 is projected to increase to 18,060 by 2025. Long wait times for patients to see a neurologist, difficulty hiring new neurologists, and large numbers of neurologists who do not accept new Medicaid patients are consistent with a current national shortfall of neurologists. Demand for neurologists is projected to increase from ∼18,180 in 2012 (11% shortfall) to 21,440 by 2025 (19% shortfall). This includes an increased demand of 520 full-time equivalent neurologists starting in 2014 from expanded medical insurance coverage associated with the Patient Protection and Affordable Care Act. In the absence of efforts to increase the number of neurology professionals and retain the existing workforce, current national and geographic shortfalls of neurologists are likely to worsen, exacerbating long wait times and reducing access to care for Medicaid beneficiaries. Current geographic differences in adequacy of supply likely will persist into the future.

Dysglycemia, Glycemic Variability, and Outcome After Cardiac Arrest and Temperature Management at 33°C and 36°C.

PubMed

Borgquist, Ola; Wise, Matt P; Nielsen, Niklas; Al-Subaie, Nawaf; Cranshaw, Julius; Cronberg, Tobias; Glover, Guy; Hassager, Christian; Kjaergaard, Jesper; Kuiper, Michael; Smid, Ondrej; Walden, Andrew; Friberg, Hans

2017-08-01

Dysglycemia and glycemic variability are associated with poor outcomes in critically ill patients. Targeted temperature management alters blood glucose homeostasis. We investigated the association between blood glucose concentrations and glycemic variability and the neurologic outcomes of patients randomized to targeted temperature management at 33°C or 36°C after cardiac arrest. Post hoc analysis of the multicenter TTM-trial. Primary outcome of this analysis was neurologic outcome after 6 months, referred to as "Cerebral Performance Category." Thirty-six sites in Europe and Australia. All 939 patients with out-of-hospital cardiac arrest of presumed cardiac cause that had been included in the TTM-trial. Targeted temperature management at 33°C or 36°C. Nonparametric tests as well as multiple logistic regression and mixed effects logistic regression models were used. Median glucose concentrations on hospital admission differed significantly between Cerebral Performance Category outcomes (p < 0.0001). Hyper- and hypoglycemia were associated with poor neurologic outcome (p = 0.001 and p = 0.054). In the multiple logistic regression models, the median glycemic level was an independent predictor of poor Cerebral Performance Category (Cerebral Performance Category, 3-5) with an odds ratio (OR) of 1.13 in the adjusted model (p = 0.008; 95% CI, 1.03-1.24). It was also a predictor in the mixed model, which served as a sensitivity analysis to adjust for the multiple time points. The proportion of hyperglycemia was higher in the 33°C group compared with the 36°C group. Higher blood glucose levels at admission and during the first 36 hours, and higher glycemic variability, were associated with poor neurologic outcome and death. More patients in the 33°C treatment arm had hyperglycemia.

New techniques for positron emission tomography in the study of human neurological disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhl, D.E.

1992-07-01

The general goals of the physics and kinetic modeling projects are to: (1) improve the quantitative information extractable from PET images, and (2) develop, implement and optimize tracer kinetic models for new PET neurotransmitter/receptor ligands aided by computer simulations. Work towards improving PET quantification has included projects evaluating: (1) iterative reconstruction algorithms using supplemental boundary information, (2) automated registration of dynamic PET emission and transmission data using sinogram edge detection, and (3) automated registration of multiple subjects to a common coordinate system, including the use of non-linear warping methods. Simulation routines have been developed providing more accurate representation of datamore » generated from neurotransmitter/receptor studies. Routines consider data generated from complex compartmental models, high or low specific activity administrations, non-specific binding, pre- or post-injection of cold or competing ligands, temporal resolution of the data, and radiolabeled metabolites. Computer simulations and human PET studies have been performed to optimize kinetic models for four new neurotransmitter/receptor ligands, [{sup 11}C]TRB (muscarinic), [{sup 11}C]flumazenil (benzodiazepine), [{sup 18}F]GBR12909, (dopamine), and [{sup 11}C]NMPB (muscarinic).« less

New techniques for positron emission tomography in the study of human neurological disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhl, D.E.

1992-01-01

The general goals of the physics and kinetic modeling projects are to: (1) improve the quantitative information extractable from PET images, and (2) develop, implement and optimize tracer kinetic models for new PET neurotransmitter/receptor ligands aided by computer simulations. Work towards improving PET quantification has included projects evaluating: (1) iterative reconstruction algorithms using supplemental boundary information, (2) automated registration of dynamic PET emission and transmission data using sinogram edge detection, and (3) automated registration of multiple subjects to a common coordinate system, including the use of non-linear warping methods. Simulation routines have been developed providing more accurate representation of datamore » generated from neurotransmitter/receptor studies. Routines consider data generated from complex compartmental models, high or low specific activity administrations, non-specific binding, pre- or post-injection of cold or competing ligands, temporal resolution of the data, and radiolabeled metabolites. Computer simulations and human PET studies have been performed to optimize kinetic models for four new neurotransmitter/receptor ligands, ({sup 11}C)TRB (muscarinic), ({sup 11}C)flumazenil (benzodiazepine), ({sup 18}F)GBR12909, (dopamine), and ({sup 11}C)NMPB (muscarinic).« less

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease

PubMed Central

Nguyen, Tammy T.; Oh, Sang S.; Weaver, David; Lewandowska, Agnieszka; Maxfield, Dane; Schuler, Max-Hinderk; Smith, Nathan K.; Macfarlane, Jane; Saunders, Gerald; Palmer, Cheryl A.; Debattisti, Valentina; Koshiba, Takumi; Pulst, Stefan; Feldman, Eva L.; Hajnóczky, György; Shaw, Janet M.

2014-01-01

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease. PMID:25136135

Vitamin B-12 status and neurologic function in older people: a cross-sectional analysis of baseline trial data from the Older People and Enhanced Neurological Function (OPEN) study.

PubMed

Miles, Lisa M; Allen, Elizabeth; Mills, Kerry; Clarke, Robert; Uauy, Ricardo; Dangour, Alan D

2016-09-01

Aging is associated with a progressive decline in vitamin B-12 status. Overt vitamin B-12 deficiency causes neurologic disturbances in peripheral and central motor and sensory systems, but the public health impact for neurologic disease of moderately low vitamin B-12 status in older people is unclear. Evidence from observational studies is limited by heterogeneity in the definition of vitamin B-12 status and imprecise measures of nerve function. We aimed to determine whether vitamin B-12 status is associated with electrophysiologic indexes of peripheral or central neurologic function in asymptomatic older people with moderately low vitamin B-12 status. We used a cross-sectional analysis of baseline data from the Older People and Enhanced Neurological Function study conducted in Southeast England. This trial investigated the effectiveness of vitamin B-12 supplementation on electrophysiologic indexes of neurologic function in asymptomatic older people (mean age: 80 y) with moderately low vitamin B-12 status (serum vitamin B-12 concentrations ≥107 and <210 pmol/L without anemia, n = 201). Vitamin B-12 status was assessed with the use of total vitamin B-12, holotranscobalamin, and a composite indicator of vitamin B-12 status (cB-12). Electrophysiologic measures of sensory and motor components of peripheral and central nerve function were assessed in all participants by a single observer. In multivariate models, there was no evidence of an association of vitamin B-12, holotranscobalamin, or cB-12 with any nerve conduction outcome. There was also no evidence of an association of vitamin B-12 status with clinical markers of neurologic function. This secondary analysis of high-quality trial data did not show any association of any measure of vitamin B-12 status with either peripheral or central neurologic function or any clinical markers of neurologic function in older people with moderately low vitamin B-12 status. The results of this study are unlikely to be generalizable to a less healthy older population with more severe vitamin B-12 deficiency. This trial was registered at www.controlled-trials.com as ISRCTN54195799. © 2016 American Society for Nutrition.

Dynamic diseases in neurology and psychiatry

NASA Astrophysics Data System (ADS)

Milton, John; Black, Deborah

1995-03-01

Thirty-two (32) periodic diseases of the nervous system are identified in which symptoms and/or signs recur. In 10/32, the recurrence of a symptom complex is one of the defining features of the illness, whereas in 22/32 oscillatory signs occur in the setting of an ongoing nervous system disorder. We discuss the possibility that these disorders may be dynamic diseases.

Short Duration Combined Mild Hypothermia Improves Resuscitation Outcomes in a Porcine Model of Prolonged Cardiac Arrest

PubMed Central

Yu, Tao; Yang, Zhengfei; Li, Heng; Ding, Youde; Huang, Zitong

2015-01-01

Objective. In this study, our aim was to investigate the effects of combined hypothermia with short duration maintenance on the resuscitation outcomes in a porcine model of ventricular fibrillation (VF). Methods. Fourteen porcine models were electrically induced with VF and untreated for 11 mins. All animals were successfully resuscitated manually and then randomized into two groups: combined mild hypothermia (CH group) and normothermia group (NT group). A combined hypothermia of ice cold saline infusion and surface cooling was implemented in the animals of the CH group and maintained for 4 hours. The survival outcomes and neurological function were evaluated every 24 hours until a maximum of 96 hours. Neuron apoptosis in hippocampus was analyzed. Results. There were no significant differences in baseline physiologies and primary resuscitation outcomes between both groups. Obvious improvements of cardiac output were observed in the CH group at 120, 180, and 240 mins following resuscitation. The animals demonstrated better survival at 96 hours in the CH group when compared to the NT group. In comparison with the NT group, favorable neurological functions were observed in the CH group. Conclusion. Short duration combined cooling initiated after resuscitation improves survival and neurological outcomes in a porcine model of prolonged VF. PMID:26558261

The clinical maze of mitochondrial neurology

PubMed Central

DiMauro, Salvatore; Schon, Eric A.; Carelli, Valerio; Hirano, Michio

2014-01-01

Mitochondrial diseases involve the respiratory chain, which is under the dual control of nuclear and mitochondrial DNA (mtDNA). The complexity of mitochondrial genetics provides one explanation for the clinical heterogeneity of mitochondrial diseases, but our understanding of disease pathogenesis remains limited. Classification of Mendelian mitochondrial encephalomyopathies has been laborious, but whole-exome sequencing studies have revealed unexpected molecular aetiologies for both typical and atypical mitochondrial disease phenotypes. Mendelian mitochondrial defects can affect five components of mitochondrial biology: subunits of respiratory chain complexes (direct hits); mitochondrial assembly proteins; mtDNA translation; phospholipid composition of the inner mitochondrial membrane; or mitochondrial dynamics. A sixth category—defects of mtDNA maintenance—combines features of Mendelian and mitochondrial genetics. Genetic defects in mitochondrial dynamics are especially important in neurology as they cause optic atrophy, hereditary spastic paraplegia, and Charcot–Marie–Tooth disease. Therapy is inadequate and mostly palliative, but promising new avenues are being identified. Here, we review current knowledge on the genetics and pathogenesis of the six categories of mitochondrial disorders outlined above, focusing on their salient clinical manifestations and highlighting novel clinical entities. An outline of diagnostic clues for the various forms of mitochondrial disease, as well as potential therapeutic strategies, is also discussed. PMID:23835535

Nanoformulation of Brain-Derived Neurotrophic Factor with Target Receptor-Triggered-Release in the Central Nervous System.

PubMed

Jiang, Yuhang; Fay, James M; Poon, Chi-Duen; Vinod, Natasha; Zhao, Yuling; Bullock, Kristin; Qin, Si; Manickam, Devika S; Yi, Xiang; Banks, William A; Kabanov, Alexander V

2018-02-07

Brain-derived neurotrophic factor (BDNF) is identified as a potent neuroprotective and neuroregenerative agent for many neurological diseases. Regrettably, its delivery to the brain is hampered by poor serum stability and rapid brain clearance. Here, a novel nanoformulation is reported composed of a bio-compatible polymer, poly(ethylene glycol)- b -poly(L-glutamic acid) (PEG-PLE), that hosts the BDNF molecule in a nanoscale complex, termed here Nano-BDNF. Upon simple mixture, Nano-BDNF spontaneously forms uniform spherical particles with a core-shell structure. Molecular dynamics simulations suggest that binding between BDNF and PEG-PLE is mediated through electrostatic coupling as well as transient hydrogen bonding. The formation of Nano-BDNF complex stabilizes BDNF and protects it from nonspecific binding with common proteins in the body fluid, while allowing it to associate with its receptors. Following intranasal administration, the nanoformulation improves BDNF delivery throughout the brain and displays a more preferable regional distribution pattern than the native protein. Furthermore, intranasally delivered Nano-BDNF results in superior neuroprotective effects in the mouse brain with lipopolysaccharides-induced inflammation, indicating promise for further evaluation of this agent for the therapy of neurologic diseases.

Behavioral testing strategies in a localized animal model of multiple sclerosis.

PubMed

Buddeberg, Bigna S; Kerschensteiner, Martin; Merkler, Doron; Stadelmann, Christine; Schwab, Martin E

2004-08-01

To assess neurological impairments quantitatively in an animal model of multiple sclerosis (MS), we have used a targeted model of experimental autoimmune encephalomyelitis (EAE), which leads to the formation of anatomically defined lesions in the spinal cord. Deficits in the hindlimb locomotion are therefore well defined and highly reproducible, in contrast to the situation in generalized EAE with disseminated lesions. Behavioral tests for hindlimb sensorimotor functions, originally established for traumatic spinal cord injury, revealed temporary or persistent deficits in open field locomotion, the grid walk, the narrow beam and the measurement of the foot exorotation angle. Such refined behavioral testing in EAE will be crucial for the analysis of new therapeutic approaches for MS that seek to improve or prevent neurological impairment.

The Workforce Task Force Report

PubMed Central

Vatz, Kenneth A.; Griggs, Robert C.; Pedley, Timothy

2013-01-01

The American Academy of Neurology Workforce Task Force (WFTF) report predicts a future shortfall of neurologists in the United States. The WFTF data also suggest that for most states, the current demand for neurologist services already exceeds the supply, and by 2025 the demand for neurologists will be even higher. This future demand is fueled by the aging of the US population, the higher health care utilization rates of neurologic services, and by a greater number of patients gaining access to the health care system due to the Patient Protection and Affordable Care Act. Uncertainties in health care delivery and patient access exist due to looming concerns about further Medicare reimbursement cuts. This uncertainty is set against a backdrop of Congressional volatility on a variety of issues, including the repeal of the sustainable growth rate for physician reimbursement. The impact of these US health care changes on the neurology workforce, future increasing demands, reimbursement, and alternative health care delivery models including accountable care organizations, nonphysician providers such as nurse practitioners and physician assistants, and teleneurology for both stroke and general neurology are discussed. The data lead to the conclusion that neurologists will need to play an even larger role in caring for the aging US population by 2025. We propose solutions to increase the availability of neurologic services in the future and provide other ways of meeting the anticipated increased demand for neurologic care. PMID:23783750

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

PubMed Central

Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

2011-01-01

BACKGROUND AND PURPOSE Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTS Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. PMID:21182490

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.

PubMed

Avraham, Y; Grigoriadis, Nc; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, Em

2011-04-01

Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferrari, Michele; Jain, Isha H.; Goldberger, Olga

The most common pediatric mitochondrial disease is Leigh syn-drome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that contin-uously breathing normobaric 11% O 2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated sur-vival curves and organ pathology in Ndufs4 KO mice exposed to hypoxiamore » or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as contin-uous normobaric 17% O 2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O 2 in mice with late-stage encephalopathy re-verses their established neurological disease, evidenced by im-proved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hyp-oxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials.« less

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

DOE PAGES

Ferrari, Michele; Jain, Isha H.; Goldberger, Olga; ...

2017-05-08

The most common pediatric mitochondrial disease is Leigh syn-drome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that contin-uously breathing normobaric 11% O 2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated sur-vival curves and organ pathology in Ndufs4 KO mice exposed to hypoxiamore » or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as contin-uous normobaric 17% O 2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O 2 in mice with late-stage encephalopathy re-verses their established neurological disease, evidenced by im-proved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hyp-oxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials.« less

A multi-views multi-learners approach towards dysarthric speech recognition using multi-nets artificial neural networks.

PubMed

Shahamiri, Seyed Reza; Salim, Siti Salwah Binti

2014-09-01

Automatic speech recognition (ASR) can be very helpful for speakers who suffer from dysarthria, a neurological disability that damages the control of motor speech articulators. Although a few attempts have been made to apply ASR technologies to sufferers of dysarthria, previous studies show that such ASR systems have not attained an adequate level of performance. In this study, a dysarthric multi-networks speech recognizer (DM-NSR) model is provided using a realization of multi-views multi-learners approach called multi-nets artificial neural networks, which tolerates variability of dysarthric speech. In particular, the DM-NSR model employs several ANNs (as learners) to approximate the likelihood of ASR vocabulary words and to deal with the complexity of dysarthric speech. The proposed DM-NSR approach was presented as both speaker-dependent and speaker-independent paradigms. In order to highlight the performance of the proposed model over legacy models, multi-views single-learner models of the DM-NSRs were also provided and their efficiencies were compared in detail. Moreover, a comparison among the prominent dysarthric ASR methods and the proposed one is provided. The results show that the DM-NSR recorded improved recognition rate by up to 24.67% and the error rate was reduced by up to 8.63% over the reference model.

Rapamycin enhances survival in a Drosophila model of mitochondrial disease.

PubMed

Wang, Adrienne; Mouser, Jacob; Pitt, Jason; Promislow, Daniel; Kaeberlein, Matt

2016-12-06

Pediatric mitochondrial disorders are a devastating category of diseases caused by deficiencies in mitochondrial function. Leigh Syndrome (LS) is the most common of these diseases with symptoms typically appearing within the first year of birth and progressing rapidly until death, usually by 6-7 years of age. Our lab has recently shown that genetic inhibition of the mechanistic target of rapamycin (TOR) rescues the short lifespan of yeast mutants with defective mitochondrial function, and that pharmacological inhibition of TOR by administration of rapamycin significantly rescues the shortened lifespan, neurological symptoms, and neurodegeneration in a mouse model of LS. However, the mechanism by which TOR inhibition exerts these effects, and the extent to which these effects can extend to other models of mitochondrial deficiency, are unknown. Here, we probe the effects of TOR inhibition in a Drosophila model of complex I deficiency. Treatment with rapamycin robustly suppresses the lifespan defect in this model of LS, without affecting behavioral phenotypes. Interestingly, this increased lifespan in response to TOR inhibition occurs in an autophagy-independent manner. Further, we identify a fat storage defect in the ND2 mutant flies that is rescued by rapamycin, supporting a model that rapamycin exerts its effects on mitochondrial disease in these animals by altering metabolism.

Residency Training: Determinants of burnout of neurology trainees in Attica, Greece.

PubMed

Zis, Panagiotis; Artemiadis, Artemios K; Lykouri, Maria; Xirou, Sophia; Roussopoulou, Andromachi; Papageorgiou, Ermioni; Bakola, Eleni; Anagnostopoulos, Fotios

2015-09-15

The purpose of our cross-sectional study was to estimate the rate of burnout and identify its determinants among neurology residents in Attica, Greece. In total, 131 placements for neurology training over 18 hospitals were available. All residents were approached and were asked to participate in the study by anonymously completing a questionnaire. Job demands and resources (JD-R) were examined via a 31-item questionnaire assessing 8 factors based on the JD-R model. Burnout was measured with the Maslach Burnout Inventory (MBI). The emotional exhaustion + 1 criterion was used to distinguish respondents with and without burnout. A total of 116 residents participated in the study (response rate 88.5%). In total, 18.1% of the participants were experiencing burnout. Multivariate analysis showed that each increased point in the total score of the factor regarding opportunities for professional development was associated with lowering the odds of burnout by 28.7%. Burnout among neurology residents is associated with decreased professional development. Educators and program directors need to identify those residents at high risk of burnout and design interventions to promote residents' resilience and mental health. © 2015 American Academy of Neurology.

Academicians and Neurologic Physical Therapy Residents Partner to Expand Clinical Reflection Using the SOLO Taxonomy: A Novel Approach.

PubMed

Pinto Zipp, Genevieve; Maher, Catherine; Donnelly, Erin; Fritz, Brian; Snowdon, Lauren

2016-01-01

Creating curriculums that develop physical therapy (PT) students into evidenced-based, critically reflective, entry-level practitioners is one of the primary goals for PT programs. Academic faculty partnering with neurologic residency programs to design learning environments that capitalize upon the strengths of both can create insightful educational experiences for students during their didactic training. These partnerships support the development of critical thinking skills and provide mentorship for residents transitioning from their role as a clinician to that of an educator. Using the SOLO (structure of observed learning outcomes) taxonomy as a framework for developing learning experiences, Seton Hall University neurologic academic faculty and program directors from the Kessler Institute for Rehabilitation Residency in Neurologic Physical Therapy have built a partnership that seeks to develop critical reflection skills in both the neurologic resident and entry-level PT students. While integration of residents into entry-level PT curriculum may not be novel, we believe that utilizing the SOLO model within this partnership is unique. This paper describes the partnership and learning experiences rooted in the SOLO taxonomy theoretical framework and discusses perceived benefits of this learning experience across professional health science programs.

Hospital admissions for neurological and renal diseases among dentists and dental assistants occupationally exposed to mercury.

PubMed

Thygesen, Lau Caspar; Flachs, Esben Meulengracht; Hanehøj, Kirsten; Kjuus, Helge; Juel, Knud

2011-12-01

For many years an amalgam containing metallic mercury, which has been associated with neurological and renal diseases, has been used in dentistry. In this nationwide study we compared hospital admissions due to neurological and renal diseases among dentists and dental assistants to admissions in controls. This register-based cohort study included all Danish workers employed in dental clinics, general practitioners' clinics or lawyers' offices between 1964 and 2006. We compared dentists with general practitioners and lawyers, and dental assistants with medical secretaries, nurses and legal secretaries. We also compared dentists and dental assistants employed during periods with high occupational mercury exposure with dentists and dental assistants employed during periods with less mercury exposure. We followed all subjects in a nationwide register of hospital admissions. We analysed risk of neurological diseases, Parkinson's disease and renal diseases using a Cox regression model. The cohort consisted of 122,481 workers including 5371 dentists and 33,858 dental assistants. For neurological diseases, no association was observed for dental assistants, while for dentists an increasing risk for periods with less mercury exposure was observed. Among dental assistants, a negative association between employment length and risk of neurological disease was observed. Admissions for renal disease among dental assistants were increased during periods with less mercury exposure compared with controls. For dentists a non-significant increased risk was observed between employment length and renal disease risk. Our nationwide study does not indicate that occupational exposure to mercury increases the risk of hospital admissions for neurological, Parkinson's or renal diseases.

Effects on locomotion and memory in 2 models of cerebral hypoperfusion in male Wistar rats.

PubMed

Martínez-Díaz, J A; García, L I; Hernández, M E; Aranda-Abreu, G E

2015-09-01

Cerebral ischaemia is one of the most common neurological diseases worldwide. Its many sequelae range from motor and sensory symptoms to cognitive decline and dementia. Animal models of cerebral ischaemia/hypoperfusion elicit effects on long term memory; however, the effects of these procedures on short term memory are not clearly understood and effects induced by alternative hypoperfusion models are completely unknown. We evaluated the effects of 2 cerebral hyperperfusion models on memory in 3-month-old male rats. Episodic memory and working memory were assessed using the new object recognition test and the spontaneous alteration test, respectively. Neurological assessment was also performed, along with an open field test to evaluate locomotor activity. Rats in both hyperperfusion models displayed no cognitive changes. Rats with unilateral left-sided ligation plus temporary ligation of the right carotid tended to show slightly impaired performance on the new object recognition test on the second day after the procedure. In contrast, the group with permanent unilateral ligation tended to display alterations in working and episodic memory 9 days after the procedure, but they subsequently recovered. Despite these differences, both hypoperfusion groups displayed clear signs of motor impairment 2 days after the procedure, as reflected by their decreased locomotor activity during the open field test. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Voltage-Gated Potassium Channel Antibodies in Slow-Progression Motor Neuron Disease.

PubMed

Godani, Massimiliano; Zoccarato, Marco; Beronio, Alessandro; Zuliani, Luigi; Benedetti, Luana; Giometto, Bruno; Del Sette, Massimo; Raggio, Elisa; Baldi, Roberta; Vincent, Angela

2017-01-01

The spectrum of autoimmune neurological diseases associated with voltage-gated potassium channel (VGKC)-complex antibodies (Abs) ranges from peripheral nerve disorders to limbic encephalitis. Recently, low titers of VGKC-complex Abs have also been reported in neurodegenerative disorders, but their clinical relevance is unknown. The aim of the study was to explore the prevalence of VGKC-complex Abs in slow-progression motor neuron disease (MND). We compared 11 patients affected by slow-progression MND with 9 patients presenting typical progression illness. Sera were tested for VGKC-complex Abs by radioimmunoassay. The distribution of VGKC-complex Abs was analyzed with the Mann-Whitney U test. The statistical analysis showed a significant difference between the mean values in the study and control groups. A case with long-survival MND harboring VGKC-complex Abs and treated with intravenous immunoglobulins is described. Although VGKC-complex Abs are not likely to be pathogenic, these results could reflect the coexistence of an immunological activation in patients with slow disease progression. © 2016 S. Karger AG, Basel.

Cockayne syndrome and xeroderma pigmentosum

PubMed Central

Rapin, I.; Lindenbaum, Y.; Dickson, D.W.; Kraemer, K.H.; Robbins, J.H.

2015-01-01

Objectives To review genetic variants of Cockayne syndrome (CS) and xeroderma pigmentosum (XP), autosomal recessive disorders of DNA repair that affect the nervous system, and to illustrate them by the first case of xeroderma pigmentosum–Cockayne syndrome (XP-CS) complex to undergo neuropathologic examination. Methods Published reports of clinical, pathologic, and molecular studies of CS, XP neurologic disease, and the XP-CS complex were reviewed, and a ninth case of XP-CS is summarized. Results CS is a multisystem disorder that causes both profound growth failure of the soma and brain and progressive cachexia, retinal, cochlear, and neurologic degeneration, with a leukodystrophy and demyelinating neuropathy without an increase in cancer. XP presents as extreme photosensitivity of the skin and eyes with a 1000-fold increased frequency of cutaneous basal and squamous cell carcinomas and melanomas and a small increase in nervous system neoplasms. Some 20% of patients with XP incur progressive degeneration of previously normally developed neurons resulting in cortical, basal ganglia, cerebellar, and spinal atrophy, cochlear degeneration, and a mixed distal axonal neuropathy. Cultured cells from patients with CS or XP are hypersensitive to killing by ultraviolet (UV) radiation. Both CS and most XP cells have defective DNA nucleotide excision repair of actively transcribing genes; in addition, XP cells have defective repair of the global genome. There are two complementation groups in CS and seven in XP. Patients with the XP-CS complex fall into three XP complementation groups. Despite their XP genotype, six of nine individuals with the XP-CS complex, including the boy we followed up to his death at age 6, had the typical clinically and pathologically severe CS phenotype. Cultured skin and blood cells had extreme sensitivity to killing by UV radiation, DNA repair was severely deficient, post-UV unscheduled DNA synthesis was reduced to less than 5%, and post-UV plasmid mutation frequency was increased. Conclusions The paradoxical lack of parallelism of phenotype to genotype is unexplained in these disorders. Perhaps diverse mutations responsible for UV sensitivity and deficient DNA repair may also produce profound failure of brain and somatic growth, progressive cachexia and premature aging, and tissue-selective neurologic deterioration by their roles in regulation of transcription and repair of endogenous oxidative DNA damage. PMID:11185579

[Comparative efficiency of nootropic drugs in complex treatment of patients with remote consequences of closed craniocereberal trauma].

PubMed

Hliebova, O S; Tkachenko, O V

2008-01-01

Main data of the research were data obtained after a complex treatment of 120 persons with late consequences of closed craniocereberal trauma (CCRCT). The treatment included administration of one of nootropic agents (noophen, aminolon or entropil), magnesium sulfate, group B vitamins. All patients have passed a complex examination: specially developed questionnaire, anamnesis gathering, neurologic status, neuropsychological status with the use of multiple-aspect scales and questionnaires, examination of fundus of eye, rheoencephalography, echoencephalography, brain MRT. Results of a complex examination proved positive effect of the use of nootropic agents, in particular noophen, entropil and aminolon in complex treatment of late consequences of closed craniocereberal trauma. For optimisation of the use of nootropic agents in the treatment of late consequences of closed craniocereberal trauma it is recommended to consider features of influence of nootropic agents on certain clinical aspects of the disease.

Cell-based interventions for neurologic conditions: ethical challenges for early human trials.

PubMed

Mathews, D J H; Sugarman, J; Bok, H; Blass, D M; Coyle, J T; Duggan, P; Finkel, J; Greely, H T; Hillis, A; Hoke, A; Johnson, R; Johnston, M; Kahn, J; Kerr, D; Kurtzberg, J; Liao, S M; McDonald, J W; McKhann, G; Nelson, K B; Rao, M; Regenberg, A; Siegel, A W; Smith, K; Solter, D; Song, H; Vescovi, A; Young, W; Gearhart, J D; Faden, R

2008-07-22

Attempts to translate basic stem cell research into treatments for neurologic diseases and injury are well under way. With a clinical trial for one such treatment approved and in progress in the United States, and additional proposals under review, we must begin to address the ethical issues raised by such early forays into human clinical trials for cell-based interventions for neurologic conditions. An interdisciplinary working group composed of experts in neuroscience, cell biology, bioethics, law, and transplantation, along with leading disease researchers, was convened twice over 2 years to identify and deliberate on the scientific and ethical issues raised by the transition from preclinical to clinical research of cell-based interventions for neurologic conditions. While the relevant ethical issues are in many respects standard challenges of human subjects research, they are heightened in complexity by the novelty of the science, the focus on the CNS, and the political climate in which the science is proceeding. Distinctive challenges confronting US scientists, administrators, institutional review boards, stem cell research oversight committees, and others who will need to make decisions about work involving stem cells and their derivatives and evaluate the ethics of early human trials include evaluating the risks, safety, and benefits of these trials, determining and evaluating cell line provenance, and determining inclusion criteria, informed consent, and the ethics of conducting early human trials in the public spotlight. Further study and deliberation by stakeholders is required to move toward professional and institutional policies and practices governing this research.

Triggers in advanced neurological conditions: prediction and management of the terminal phase.

PubMed

Hussain, Jamilla; Adams, Debi; Allgar, Victoria; Campbell, Colin

2014-03-01

The challenge to provide a palliative care service for individuals with advanced neurological conditions is compounded by variability in disease trajectories and symptom profiles. The National End of Life Care Programme (2010) recommended seven 'triggers' for a palliative approach to care for patients with advanced neurological conditions. To establish the frequency of triggers in the palliative phase, and if they could be reduced to fewer components. Management of the terminal phase also was evaluated. Retrospective study of 62 consecutive patients under the care of a specialist palliative neurology service, who had died. Principle component analysis (PCA) was performed to establish the interrelationship between triggers. Frequency of triggers increased as each patient approached death. PCA found that four symptom components explained 76.8% of the variance. These represented: rapid physical decline; significant complex symptoms, including pain; infection in combination with cognitive impairment; and risk of aspiration. Median follow-up under the palliative care service was 336 days. In 56.5% of patients, the cause of death was pneumonia. The terminal phase was recognised in 72.6%. The duration of the terminal phase was 8.8 days on average, and the Liverpool Care of the dying Pathway was commenced in 33.9%. All carers were offered bereavement support. Referral criteria based on the triggers can facilitate appropriate and timely patient access to palliative care. The components deduced through PCA have face validity; however larger studies prospectively validating the triggers are required. Closer scrutiny of the terminal phase is necessary to optimise management.

Robotic gait assistive technology as means to aggressive mobilization strategy in acute rehabilitation following severe diffuse axonal injury: a case study.

PubMed

Stam, Daniel; Fernandez, Jennifer

2017-07-01

Diffuse axonal injury is a prominent cause of disablement post-traumatic brain injury. Utilization of the rapid expansion of our current scientific knowledge base combined with greater access to neurological and assistive technology as adjuncts to providing sensorimotor experience may yield innovative new approaches to rehabilitation based upon a dynamic model of brain response following injury. A 24-year-old female who sustained a traumatic brain injury, bilateral subdural hemorrhage, subarachnoid hemorrhage and severe diffuse axonal injury secondary to a motor vehicle collision. Evidence-based appraisal of present literature suggests a link between graded intensity of aerobic activity to facilitation of neuro-plastic change and up-regulation of neurotrophins essential to functional recovery post-diffuse axonal injury. Following resolution of paroxysmal autonomic instability with dystonia, aggressive early mobilization techniques were progressed utilizing robotic assistive gait technology in combination with conventional therapy. This approach allowed for arguably greater repetition and cardiovascular demands across a six-month inpatient rehabilitation stay. Outcomes in this case suggest that the use of assistive technology to adjunct higher level and intensity rehabilitation strategies may be a safe and effective means towards reduction of disablement following severe traumatic brain and neurological injury. Implications for Rehabilitation Functional recovery and neuroplasticity following diffuse neurological injury involves a complex process determined by the sensorimotor experience provided by rehabilitation clinicians. This process is in part modulated by intrinsic brain biochemical processes correlated to cardiovascular intensity of the activity provided. It is important that rehabilitation professionals monitor physiological response to higher intensity activities to provide an adaptive versus maladaptive response of central nervous system plasticity with activity. Identification of early mobilization parameters and skill acquisition may assist selection of gait assistive technology adjunct in progressing early optimal physical rehabilitation outcomes in the acute inpatient setting.

[From reflex arc to psychic apparatus: neurology and psychoanalysis around 1900].

PubMed

Porath, Erik

2009-03-01

As a disciple of Ernst Wilhelm von Brücke and Theodor Meynert, Sigmund Freud was familiar with 19th century physiology and neurology. He started his career with laboratory work and began later on, when being a young medic to develop an explicit psychological method for curating hysterics. These cases of hysteria ask riddles to the established medical discourse and practice. Freud's long time unpublished Entwurf einer Psychologie (1895) makes the attempt of a "psychology for the neurologist". He tried to give a sufficient theory of the psychic apparatus on the basis of natural science. At the same time he (together with Josef Breuer) published his Studies on Hysteria, which--in addition to his earlier essay on Aphasia (1891)--argued, that there is no clear cut relation between body and soul. Despite the dubious, non-reductive character of the soma-psyche-relation, Freud gave reason to search for a complex field of interrelations between the physiological and psychological knowledge, beyond the divide of natural sciences and humanities. Not until his groundbreaking Traumdeutung (1900) Freud gave up the claim of reintegrating psychological knowledge into the neuroscientific field for now. But up to his latest work he always adheres to the principal project of unifying the natural and the psychical being of the subject. In the gap between the two spheres, for long occupied by the discursive figure of the 'psycho-physical parallelism', Freud situated the Unconscious. In the passage to a psychoanalytical theory of psychic events Freud took up the model of the reflex arc well known from neurology. The transmission into psychoanalysis complexifies the unilinearity of reflexes, so that the psychic apparatus can be analysed as a cybernetic mechanism 'avant la lettre'. It is interesting enough that inhibition as well as consciousness play a key role in the regulation of the psychic apparatus. In this context Freud stresses the importance of speech and language within the self-organising processes concerning the claims and aims of basic needs and drives.

The use of fish models to study human neurological disorders.

PubMed

Matsui, Hideaki

2017-07-01

Small teleost fish including zebrafish and medaka have been used as animal models in basic science research due to the relative ease of handling and transparency during embryogenesis. Current advances in genetic engineering and progress in disease genetics allowed utilization of these fish to study neurological diseases and psychiatric disorders. This review summarizes the advantages and disadvantages of using fish for neuropsychiatric research using primarily our own studies as examples. We discuss how fish belong to a class of vertebrates, are feasible for imaging, and include diverse species with multiple research possibilities yet to be discovered. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Serum soluble CD163 levels in patients with influenza-associated encephalopathy.

PubMed

Hasegawa, Shunji; Matsushige, Takeshi; Inoue, Hirofumi; Takahara, Midori; Kajimoto, Madoka; Momonaka, Hiroshi; Ishida, Chiemi; Tanaka, Saya; Morishima, Tsuneo; Ichiyama, Takashi

2013-08-01

Influenza-associated encephalopathy (IE) is a serious complication during influenza viral infection. Common clinical symptoms of IE include seizures and progressive coma with high-grade fever. We previously reported that hypercytokinemia and monocyte/macrophage activation may play an important role in the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin-haptoglobin complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163 (sCD163). However, there have been no reports regarding serum sCD163 levels in IE patients. We measured serum levels of sCD163 as a marker of monocyte/macrophage activation in IE patients with poor outcomes, those without neurological sequelae, influenza patients without IE, and control subjects. Serum sCD163 levels were significantly higher in IE patients with poor outcomes than in those without neurological sequelae. In particular, sCD163 levels in cases of death were significantly higher than those in other cases. Our results suggest that monocyte/macrophage activation is related to the pathogenesis of severe IE. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Paraneoplastic neurologic disorders in small cell lung carcinoma

PubMed Central

Woodhall, Mark; Chapman, Caroline; Nibber, Anjan; Waters, Patrick; Vincent, Angela; Lang, Bethan; Maddison, Paul

2015-01-01

Objective: To determine the frequency and range of paraneoplastic neurologic disorders (PNDs) and neuronal antibodies in small cell lung carcinoma (SCLC). Methods: Two hundred sixty-four consecutive patients with biopsy-proven SCLC were recruited at the time of tumor diagnosis. All patients underwent full neurologic examination. Serum samples were taken prior to chemotherapy and analyzed for 15 neuronal antibodies. Thirty-eight healthy controls were analyzed in parallel. Results: PNDs were quite prevalent (n = 24, 9.4%), most frequently Lambert-Eaton myasthenic syndrome (3.8%), sensory neuronopathy (1.9%), and limbic encephalitis (1.5%). Eighty-seven percent of all patients with PNDs had antibodies to SOX2 (62.5%), HuD (41.7%), or P/Q VGCC (50%), irrespective of their syndrome. Other neuronal antibodies were found at lower frequencies (GABAb receptor [12.5%] and N-type VGCC [20.8%]) or very rarely (GAD65, amphiphysin, Ri, CRMP5, Ma2, Yo, VGKC complex, CASPR2, LGI1, and NMDA receptor [all <5%]). Conclusions: The spectrum of PNDs is broader and the frequency is higher than previously appreciated, and selected antibody tests (SOX2, HuD, VGCC) can help determine the presence of an SCLC. PMID:26109714

Parkinson's disease (PD) in the elderly: an example of geriatric syndrome (GS)?

PubMed

Lauretani, Fulvio; Maggio, Marcello; Silvestrini, Claudio; Nardelli, Anna; Saccavini, Marsilio; Ceda, Gian Paolo

2012-01-01

PD is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. In the latest decade, the approach to PD was dramatically changed. In fact, although for many years PD has been considered only "a disease that affects walking", with a key role of the neurotransmitter dopamine, recently the neurological approach has been substantially modified. The approach for this disease is not only a neurological issue. Given the complexity of its clinical aspects, such as depression, anxiety, dementia, sleep disorder, pneumonia dysfagia-related and malnutrition, a multidisciplinary evaluation and not just a neurological evaluation is needed. We suggest a n multidisciplinary approach for this old actor, underlying a subtle link between neurophatological stages of the disease (Braak's classification) and clinical aspects (Braak's stages 1 and 2 associated with the premotor phase; Braak's stages 3-4 associated with the motor symptoms and Braak's stages 5-6 associated with cognitive impairment). In addition, we emphasize the usefulness of geriatric evaluation for the identification of frail "in situ", frail, and disable status for improving care and treatment in this multifaceted disease. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The bodily self and its disorders: neurological, psychological and social aspects.

PubMed

Brugger, Peter; Lenggenhager, Bigna

2014-12-01

The experience of ourselves as an embodied agent with a first-person perspective is referred to as 'bodily self'. We present a selective overview of relevant clinical and experimental studies. Sharing multisensory body space with others can be observed in patients with structurally altered bodies (amputations, congenital absence of limbs), with altered functionality after hemiplegia, such as denial of limb ownership (somatoparaphrenia) and with alterations in bodily self-consciousness on the level of the entire body (e.g. in autoscopic phenomena). In healthy participants, the mechanisms underpinning body ownership and observer perspective are empirically investigated by multisensory stimulation paradigms to alter the bodily self. The resulting illusions have promoted the understanding of complex disturbances of the bodily self, such as out-of-body experiences. We discuss the role of interoception in differentiating between self and others and review current advances in the study of body integrity identity disorder, a condition shaped as much by neurological as by social-psychological factors. We advocate a social neuroscience approach to the bodily self that takes into account the interactions between body, mind and society and might help close the divide between neurology and psychiatry.

MMACHC gene mutation in familial hypogonadism with neurological symptoms.

PubMed

Shi, Changhe; Shang, Dandan; Sun, Shilei; Mao, Chengyuan; Qin, Jie; Luo, Haiyang; Shao, Mingwei; Chen, Zhengguang; Liu, Yutao; Liu, Xinjing; Song, Bo; Xu, Yuming

2015-12-15

Recent studies have convincingly documented that hypogonadism is a component of various hereditary disorders and is often recognized as an important clinical feature in combination with various neurological symptoms, yet, the causative genes in a few related families are still unknown. High-throughput sequencing has become an efficient method to identify causative genes in related complex hereditary disorders. In this study, we performed exome sequencing in a family presenting hypergonadotropic hypogonadism with neurological presentations of mental retardation, epilepsy, ataxia, and leukodystrophy. After bioinformatic analysis and Sanger sequencing validation, we identified compound heterozygous mutations: c.482G>A (p.R161Q) and c.609G>A (p.W203X) in MMACHC gene in this pedigree. MMACHC was previously confirmed to be responsible for methylmalonic aciduria (MMA) combined with homocystinuria, cblC type (cblC disease), a hereditary vitamin B12 metabolic disorder. Biochemical and gas chromatography-mass spectrometry (GC-MS) examinations in this pedigree further supported the cblC disease diagnosis. These results indicated that hypergonadotropic hypogonadism may be a novel clinical manifestation of cblC disease, but more reports on additional patients are needed to support this hypothesis. Copyright © 2015 Elsevier B.V. All rights reserved.

The severity of Minamata disease declined in 25 years: temporal profile of the neurological findings analyzed by multiple logistic regression model.

PubMed

Uchino, Makoto; Hirano, Teruyuki; Satoh, Hiroshi; Arimura, Kimiyoshi; Nakagawa, Masanori; Wakamiya, Jyunji

2005-01-01

Minamata disease (MD) was caused by ingestion of seafood from the methylmercury-contaminated areas. Although 50 years have passed since the discovery of MD, there have been only a few studies on the temporal profile of neurological findings in certified MD patients. Thus, we evaluated changes in neurological symptoms and signs of MD using discriminants by multiple logistic regression analysis. The severity of predictive index declined in 25 years in most of the patients. Only a few patients showed aggravation of neurological findings, which was due to complications such as spino-cerebellar degeneration. Patients with chronic MD aged over 45 years had several concomitant diseases so that their clinical pictures were complicated. It was difficult to differentiate chronic MD using statistically established discriminants based on sensory disturbance alone. In conclusion, the severity of MD declined in 25 years along with the modification by age-related concomitant disorders.

Lymphatics in Neurological Disorders: A neuro-lympho-vascular Component of Multiple Sclerosis and Alzheimer’s Disease

PubMed Central

Louveau, Antoine; Mesquita, Sandro Da; Kipnis, Jonathan

2016-01-01

Summary Lymphatic vasculature drains interstitial fluids, which contain the tissue’s waste products and ensures immune surveillance of the tissues, allowing immune-cell recirculation. Until recently the central nervous system (CNS) was considered to be devoid of a conventional lymphatic vasculature. The recent discovery in the meninges of a lymphatic network that drains the CNS calls into question classic models for the drainage of macromolecules and immune cells from the CNS. In the context of neurological disorders, the presence of a lymphatic system draining the CNS potentially offers a new player and a new avenue for therapy. In this review, we will attempt to integrate the known primary functions of the tissue lymphatic vasculature that exists in peripheral organs with the proposed function of meningeal lymphatic vessels in neurological disorders, specifically multiple sclerosis and Alzheimer’s disease. We propose that these (and potentially other) neurological afflictions can be viewed as diseases with neuro-lympho-vascular component and should be therapeutically targeted as such. PMID:27608759

Evaluation of Problem- and Simulator-Based Learning in Lumbar Puncture in Adult Neurology Residency Training.

PubMed

Sun, Chenjing; Qi, Xiaokun

2018-01-01

Lumbar puncture (LP) is an essential part of adult neurology residency training. Technologic as well as nontechnologic training is needed. However, current assessment tools mostly focus on the technologic aspects of LP. We propose a training method-problem- and simulator-based learning (PSBL)-in LP residency training to develop overall skills of neurology residents. We enrolled 60 neurology postgraduate-year-1 residents from our standardized residents training center and randomly divided them into 2 groups: traditional teaching group and PSBL group. After training, we assessed the extent that the residents were ready to perform LP and tracked successful LPs performed by the residents. We then asked residents to complete questionnaires about the training models. Performance scores and the results of questionnaires were compared between the 2 groups. Students and faculty concluded that PSBL provided a more effective learning experience than the traditional teaching model. Although no statistical difference was found in the pretest, posttest, and improvement rate scores between the 2 groups, based on questionnaire scores and number of successful LPs after training, the PSBL group showed a statistically significant improvement compared with the traditional group. Findings indicated that nontechnical elements, such as planning before the procedure and controlling uncertainties during the procedure, are more crucial than technical elements. Compared with traditional teaching model, PSBL for LP training can develop overall surgical skills, including technical and nontechnical elements, improving performance. Residents in the PSBL group were more confident and effective in performing LP. Copyright © 2017 Elsevier Inc. All rights reserved.

A New Statistical Model of Electroencephalogram Noise Spectra for Real-Time Brain-Computer Interfaces.

PubMed

Paris, Alan; Atia, George K; Vosoughi, Azadeh; Berman, Stephen A

2017-08-01

A characteristic of neurological signal processing is high levels of noise from subcellular ion channels up to whole-brain processes. In this paper, we propose a new model of electroencephalogram (EEG) background periodograms, based on a family of functions which we call generalized van der Ziel-McWhorter (GVZM) power spectral densities (PSDs). To the best of our knowledge, the GVZM PSD function is the only EEG noise model that has relatively few parameters, matches recorded EEG PSD's with high accuracy from 0 to over 30 Hz, and has approximately 1/f θ behavior in the midfrequencies without infinities. We validate this model using three approaches. First, we show how GVZM PSDs can arise in a population of ion channels at maximum entropy equilibrium. Second, we present a class of mixed autoregressive models, which simulate brain background noise and whose periodograms are asymptotic to the GVZM PSD. Third, we present two real-time estimation algorithms for steady-state visual evoked potential (SSVEP) frequencies, and analyze their performance statistically. In pairwise comparisons, the GVZM-based algorithms showed statistically significant accuracy improvement over two well-known and widely used SSVEP estimators. The GVZM noise model can be a useful and reliable technique for EEG signal processing. Understanding EEG noise is essential for EEG-based neurology and applications such as real-time brain-computer interfaces, which must make accurate control decisions from very short data epochs. The GVZM approach represents a successful new paradigm for understanding and managing this neurological noise.

Modeling oscillatory dynamics in brain microcircuits as a way to help uncover neurological disease mechanisms: A proposal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skinner, F. K.; Department of Medicine; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8

There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of neurological disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with disease.more » Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical mechanisms underlying neurological disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.« less

Hospitalization Cost Model of Pediatric Surgical Treatment of Chiari Type 1 Malformation.

PubMed

Lam, Sandi K; Mayer, Rory R; Luerssen, Thomas G; Pan, I Wen

2016-12-01

To develop a cost model for hospitalization costs of surgery among children with Chiari malformation type 1 (CM-1) and to examine risk factors for increased costs. Data were extracted from the US National Healthcare Cost and Utilization Project 2009 Kids' Inpatient Database. The study cohort was comprised of patients aged 0-20 years who underwent CM-1 surgery. Patient charges were converted to costs by cost-to-charge ratios. Simple and multivariable generalized linear models were used to construct cost models and to determine factors associated with increased hospital costs of CM-1 surgery. A total of 1075 patients were included. Median age was 11 years (IQR 5-16 years). Payers included public (32.9%) and private (61.5%) insurers. Median wage-adjusted cost and length-of-stay for CM-1 surgery were US $13 598 (IQR $10 475-$18 266) and 3 days (IQR 3-4 days). Higher costs were found at freestanding children's hospitals: average incremental-increased cost (AIIC) was US $5155 (95% CI $2067-$8749). Factors most associated with increased hospitalization costs were patients with device-dependent complex chronic conditions (AIIC $20 617, 95% CI $13 721-$29 026) and medical complications (AIIC $13 632, 95% CI $7163-$21 845). Neurologic and neuromuscular, metabolic, gastrointestinal, and other congenital genetic defect complex chronic conditions were also associated with higher hospital costs. This study examined cost drivers for surgery for CM-1; the results may serve as a starting point in informing the development of financial risk models, such as bundled payments or prospective payment systems for these procedures. Beyond financial implications, the study identified specific risk factors associated with increased costs. Copyright © 2016 Elsevier Inc. All rights reserved.

Modeling human neurological disorders with induced pluripotent stem cells.

PubMed

Imaizumi, Yoichi; Okano, Hideyuki

2014-05-01

Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. The production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient-specific genetic information. Furthermore, innovations of gene-editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases-specific iPS cell research and described recently obtained knowledge in the form of actual examples. © 2013 International Society for Neurochemistry.

Interaction of Plant Extracts with Central Nervous System Receptors

PubMed Central

Lundstrom, Kenneth; Pham, Huyen Thanh; Dinh, Long Doan

2017-01-01

Background: Plant extracts have been used in traditional medicine for the treatment of various maladies including neurological diseases. Several central nervous system receptors have been demonstrated to interact with plant extracts and components affecting the pharmacology and thereby potentially playing a role in human disease and treatment. For instance, extracts from Hypericum perforatum (St. John’s wort) targeted several CNS receptors. Similarly, extracts from Piper nigrum, Stephania cambodica, and Styphnolobium japonicum exerted inhibition of agonist-induced activity of the human neurokinin-1 receptor. Methods: Different methods have been established for receptor binding and functional assays based on radioactive and fluorescence-labeled ligands in cell lines and primary cell cultures. Behavioral studies of the effect of plant extracts have been conducted in rodents. Plant extracts have further been subjected to mood and cognition studies in humans. Results: Mechanisms of action at molecular and cellular levels have been elucidated for medicinal plants in support of standardization of herbal products and identification of active extract compounds. In several studies, plant extracts demonstrated affinity to a number of CNS receptors in parallel indicating the complexity of this interaction. In vivo studies showed modifications of CNS receptor affinity and behavioral responses in animal models after treatment with medicinal herbs. Certain plant extracts demonstrated neuroprotection and enhanced cognitive performance, respectively, when evaluated in humans. Noteworthy, the penetration of plant extracts and their protective effect on the blood-brain-barrier are discussed. Conclusion: The affinity of plant extracts and their isolated compounds for CNS receptors indicates an important role for medicinal plants in the treatment of neurological disorders. Moreover, studies in animal and human models have confirmed a scientific basis for the application of medicinal herbs. However, additional investigations related to plant extracts and their isolated compounds, as well as their application in animal models and the conducting of clinical trials, are required. PMID:28930228

Sustainability in a Hospital-Based Biobank and University-Based DNA Biorepository: Strategic Roadmaps.

PubMed

Seiler, Catherine Y; Eschbacher, Jennifer; Bowser, Robert; LaBaer, Joshua

2015-12-01

Sustainability in the biobanking community has recently become an important and oft-discussed issue as biorepositories struggle to balance limited external funding and complex cost recovery models with high operating costs and the desire to provide the highest quality materials and services to the research community. A multi-faceted view of biobanking sustainability requires consideration of operational and social sustainability in addition to the historical focus exclusively on financial sustainability. Planning and implementing this three pillar model creates a well-rounded biorepository that meets the needs of all the major stakeholders: the funders, the patients/depositors, and the researcher recipients. Often the creation of a detailed business plan is the first step to develop goals and objectives that lead down a path towards sustainability. The definition of sustainability and the complexity of a sustainable business plan may differ for each biorepository. The DNASU Plasmid Repository at Arizona State University stores and distributes DNA plasmids to researchers worldwide, and the Biobank Core Facility at St. Joseph's Hospital and Barrow Neurological Institute consents patients and collects, stores, and distributes human tissue and blood samples. We will discuss these two biorepositories, their similar and different approaches to sustainability and business planning, their challenges in creating and implementing their sustainability plan, and their responses to some of these challenges. From these experiences, the biobanks share lessons learned about planning for sustainability that are applicable to all biorepositories.

Neurological Disease Rises from Ocean to Bring Model for Human Epilepsy to Life

PubMed Central

Ramsdell, John S.

2010-01-01

Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe epilepsy (TLE) a year after the event. Nearly a decade later, several thousand sea lions have stranded on California beaches with neurological symptoms. Analysis of the animals stranded over an eight year period indicated five clusters of acute neurological poisoning; however, nearly a quarter have stranded individually outside these events with clinical signs of a chronic neurological syndrome similar to TLE. These poisonings are not limited to sea lions, which serve as readily observed sentinels for other marine animals that strand during domoic acid poisoning events, including several species of dolphin and whales. Acute domoic acid poisoning is five-times more prominent in adult female sea lions as a result of the proximity of their year-round breeding grounds to major domoic acid bloom events. The chronic neurological syndrome, on the other hand, is more prevalent in young animals, with many potentially poisoned in utero. The sea lion rookeries of the Channel Islands are at the crossroads of domoic acid producing harmful algal blooms and a huge industrial discharge site for dichlorodiphenyltrichloroethane (DDTs). Studies in experimental animals suggest that chronic poisoning observed in immature sea lions may result from a spatial and temporal coincidence of DDTs and domoic acid during early life stages. Emergence of an epilepsy syndrome from the ocean brings a human epilepsy model to life and provides unexpected insights into interaction with legacy contaminants and expression of disease at different life stages. PMID:22069654

Prediction of developmental performance in preterm infants at two years of corrected age: contribution of the neurological assessment at term age.

PubMed

Simard, Marie-Noëlle; Lambert, Jean; Lachance, Christian; Audibert, François; Gosselin, Julie

2011-12-01

The population of preterm infants is increasing and resources available for follow-up are limited. Early markers are needed to identify children who will show major as well as more subtle neurodevelopmental impairments. Such a challenge could be achieved with the Amiel-Tison Neurological Assessment at Term (ATNAT). This study assesses the usefulness of the ATNAT in the prediction of developmental problems at two years of corrected age (CA) in infants born between 29 and 37 weeks of gestation. Inclusion criteria were: gestational age between 29(0/7) and 36(6/7) weeks inclusively, birth weight below 2500g and minimal 24-hour stay in the Neonatal Intensive Care Unit of Sainte-Justine Hospital. A sample of 147 was prospectively recruited and assessed at two ages: at term with the ATNAT and at 24months CA with Bayley Scales of Infant Development-II. No major impairment such as cerebral palsy and no neurosensory impairment were observed. Developmental delay defined by an index<70 on the mental or psychomotor scale was reported respectively in 6.2% and 5.4% of the cohort. Significant differences in mental, psychomotor and behavioral performances were found according to neurological status. Neurological status was the only variable to enter the predictive model for psychomotor and behavioral indexes. Gender and neurological status remained in the predictive model for mental performance. This study supports the inclusion of the ATNAT among the eligibility criteria for systematic neurodevelopmental surveillance as it allows early identification of infants at higher risk of low developmental performances at 24months CA. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neurological disease rises from ocean to bring model for human epilepsy to life.

PubMed

Ramsdell, John S

2010-07-01

Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe epilepsy (TLE) a year after the event. Nearly a decade later, several thousand sea lions have stranded on California beaches with neurological symptoms. Analysis of the animals stranded over an eight year period indicated five clusters of acute neurological poisoning; however, nearly a quarter have stranded individually outside these events with clinical signs of a chronic neurological syndrome similar to TLE. These poisonings are not limited to sea lions, which serve as readily observed sentinels for other marine animals that strand during domoic acid poisoning events, including several species of dolphin and whales. Acute domoic acid poisoning is five-times more prominent in adult female sea lions as a result of the proximity of their year-round breeding grounds to major domoic acid bloom events. The chronic neurological syndrome, on the other hand, is more prevalent in young animals, with many potentially poisoned in utero. The sea lion rookeries of the Channel Islands are at the crossroads of domoic acid producing harmful algal blooms and a huge industrial discharge site for dichlorodiphenyltrichloroethane (DDTs). Studies in experimental animals suggest that chronic poisoning observed in immature sea lions may result from a spatial and temporal coincidence of DDTs and domoic acid during early life stages. Emergence of an epilepsy syndrome from the ocean brings a human epilepsy model to life and provides unexpected insights into interaction with legacy contaminants and expression of disease at different life stages.

Neurotrophin-3 provides neuroprotection via TrkC receptor dependent pErk5 activation in a rat surgical brain injury model.

PubMed

Akyol, Onat; Sherchan, Prativa; Yilmaz, Gokce; Reis, Cesar; Ho, Wingi Man; Wang, Yuechun; Huang, Lei; Solaroglu, Ihsan; Zhang, John H

2018-06-05

Surgical brain injury (SBI) which occurs due to the inadvertent injury inflicted to surrounding brain tissue during neurosurgical procedures can potentiate blood brain barrier (BBB) permeability, brain edema and neurological deficits. This study investigated the role of neurotrophin 3 (NT-3) and tropomyosin related kinase receptor C (TrkC) against brain edema and neurological deficits in a rat SBI model. SBI was induced in male Sprague Dawley rats by partial right frontal lobe resection. Temporal expression of endogenous NT-3 and TrkC was evaluated at 6, 12, 24 and 72 h after SBI. SBI rats received recombinant NT-3 which was directly applied to the brain surgical injury site using gelfoam. Brain edema and neurological function was evaluated at 24 and 72 h after SBI. Small interfering RNA (siRNA) for TrkC and Rap1 was administered via intracerebroventricular injection 24 h before SBI. BBB permeability assay and western blot was performed at 24 h after SBI. Endogenous NT-3 was decreased and TrkC expression increased after SBI. Topical administration of recombinant NT-3 reduced brain edema, BBB permeability and improved neurological function after SBI. Recombinant NT-3 administration increased the expression of phosphorylated Rap1 and Erk5. The protective effect of NT-3 was reversed with TrkC siRNA but not Rap1 siRNA. Topical application of NT-3 reduced brain edema, BBB permeability and improved neurological function after SBI. The protective effect of NT-3 was possibly mediated via TrkC dependent activation of Erk5. Copyright © 2018 Elsevier Inc. All rights reserved.

Xenon improves neurological outcome and reduces secondary injury following trauma in an in vivo model of traumatic brain injury

PubMed Central

Luh, Clara; Gruss, Marco; Radyushkin, Konstantin; Hirnet, Tobias; Werner, Christian; Engelhard, Kristin; Franks, Nicholas P; Thal, Serge C; Dickinson, Robert

2015-01-01

Objectives To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury, and to determine whether application of xenon has a clinically relevant therapeutic time window. Design Controlled animal study. Setting University research laboratory. Subjects Male C57BL/6N mice (n=196) Interventions 75% xenon, 50% xenon or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact. Measurements & Main Results Outcome following trauma was measured using: 1) functional neurological outcome score, 2) histological measurement of contusion volume, 3) analysis of locomotor function and gait. Our study shows that xenon-treatment improves outcome following traumatic brain injury. Neurological outcome scores were significantly (p<0.05) better in xenon-treated groups in the early phase (24 hours) and up to 4 days after injury. Contusion volume was significantly (p<0.05) reduced in the xenon-treated groups. Xenon treatment significantly (p<0.05) reduced contusion volume when xenon was given 15 minutes after injury or when treatment was delayed 1 hour or 3 hours after injury. Neurological outcome was significantly (p<0.05) improved when xenon treatment was given 15 minutes or 1 hour after injury. Improvements in locomotor function (p<0.05) were observed in the xenon-treated group, 1 month after trauma. Conclusions These results show for the first time that xenon improves neurological outcome and reduces contusion volume following traumatic brain injury in mice. In this model, xenon application has a therapeutic time window of up to at least 3 hours. These findings support the idea that xenon may be of benefit as a neuroprotective treatment in brain trauma patients. PMID:25188549