[Frequency of neurologic diseases in cattle].

PubMed

Heim, D; Fatzer, R; Hörnlimann, B; Vandevelde, M

1997-01-01

The cases of neurological diseases at the Institute of Animal Neurology, University of Berne, from 1985-1994 were assessed. During this period 532 cattle with neurological symptoms were examined. After 1980 differential diagnostic investigation of rabies negative brains were not pursued anymore and the number of examined cattle brains had declined to 25-30 per year. With the occurrence of bovine spongiform encephalopathy (BSE) in 1990 in Switzerland the number of cattle brains examined has increased to 75-80 yearly. The most frequently diagnosed neurological diseases found are BSE, followed by listeriosis and viral encephalitides.

[Neurologic disorders in Whipple's disease].

PubMed

Jović, N S; Jović, J Z

1996-01-01

The disease is named after George H. Whipple who, in 1907, was the first to describe an intestinal "lipodystrophy". Although Whipple's disease is generally recognized as a multisystem chronic granulomatous disease, primarily involving the digestive system, it can also appear as a primary neurological disorder in rare cases. Most often it is manifested with loss of weight, diarrhea, malabsorption, abdominal pain, lymphadenopathy, cardiopathy, hyperpigmentation and hypotension. The presence of periodic acid-Schiff (PAS)-positive macrophages in biopsy specimens (not only jejunal) and demonstration of "Whipple's bacilli" visible by electron microscopy, are diagnostic signs of active Whipple's disease. Whipple's disease confined to the CNS is rare. It is rarely found in the differential diagnosis of patients with progressive neurological deterioration. The most common neurological picture includes progressive dementia, external ophalmoplegia, myoclonus, seizures, ataxia, hypothalamic dysfunction (sleep disorders, hyperphagia, polydipsia) and meningitis. Oculofacial-skeletal myorhythmia as a movement disorder, associated with Whipple's disease, is reported. Fulminant course of cerebral Whipple's disease is unusual and unfavourable. The confusing and nonspecific clinical appearance is typical for primary CNS involvement. It has recently been suggested that CNS involvement occurs in all cases, although only 10-20% of patients may show it. The CNS is the most common site of disease relapse. The CT scans and MRI of the brain are often normal, but may show cortical/subcortical atrophy, hydrocephalus, focal or intracerebral mass lesions. The cerebrospinal fluid can sometimes contain PAS-positive macrophages. Brain biopsy is suggested as a diagnostic method in cases of high suspicion of CNS Whipple's disease. However, the lesions are frequently inaccessible and false negative. Without extended antibiotic therapy, the course of Whipple's disease is lethal. Now, the prognosis is

Clinical Uses of Melatonin in Neurological Diseases and Mental and Behavioural Disorders.

PubMed

Sanchez-Barcelo, Emilio J; Rueda, Noemi; Mediavilla, María D; Martinez-Cue, Carmen; Reiter, Russel J

2017-11-20

Melatonin is a molecule with numerous properties applicable to the treatment of neurological diseases. Among these properties are the following: potent scavenger of oxygen and nitrogen reactive species, anti-inflammatory features, immuno-enhancing nature, and modulation of circadian rhythmicity. Furthermore, low concentrations of melatonin are usually found in patients with neurological diseases and mental disorders. The positive results obtained in experimental models of diverse pathologies, including diseases of the nervous system (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, epilepsy, headaches, etc.) as well as mental and behavioural disordes (e.g., autism spectrum disorders, attention-deficit hyperactivity disorders, etc.), have served as a basis for the design of clinical trials to study melatonin's possible usefulness in human pathology, although the satisfactory results obtained from the laboratory "bench" are not always applicable to the patient's "bedside". In this article, we review those papers describing the results of the administration of melatonin to humans for various therapeutic purposes in the field of neuropathology. Clinical trials with strong methodologies and appropriate doses of melatonin are necessary to support or reject the usefulness of melatonin in neurological diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Dysphagia in stroke and neurologic disease.

PubMed

González-Fernández, Marlís; Daniels, Stephanie K

2008-11-01

Dysphagia is a common problem in neurologic disease. The authors describe rates of dysphagia in selected neurologic diseases, and the evaluation and treatment of dysphagia in this population. Applicable physiology and aspects of neural control are reviewed. The decision-making process to determine oral feeding versus alternative means of alimentation is examined.

Caenorhabditis elegans as an experimental tool for the study of complex neurological diseases: Parkinson's disease, Alzheimer's disease and autism spectrum disorder.

PubMed

Calahorro, Fernando; Ruiz-Rubio, Manuel

2011-12-01

The nematode Caenorhabditis elegans has a very well-defined and genetically tractable nervous system which offers an effective model to explore basic mechanistic pathways that might be underpin complex human neurological diseases. Here, the role C. elegans is playing in understanding two neurodegenerative conditions, Parkinson's and Alzheimer's disease (AD), and a complex neurological condition, autism, is used as an exemplar of the utility of this model system. C. elegans is an imperfect model of Parkinson's disease because it lacks orthologues of the human disease-related genes PARK1 and LRRK2 which are linked to the autosomal dominant form of this disease. Despite this fact, the nematode is a good model because it allows transgenic expression of these human genes and the study of the impact on dopaminergic neurons in several genetic backgrounds and environmental conditions. For AD, C. elegans has orthologues of the amyloid precursor protein and both human presenilins, PS1 and PS2. In addition, many of the neurotoxic properties linked with Aβ amyloid and tau peptides can be studied in the nematode. Autism spectrum disorder is a complex neurodevelopmental disorder characterised by impairments in human social interaction, difficulties in communication, and restrictive and repetitive behaviours. Establishing C. elegans as a model for this complex behavioural disorder is difficult; however, abnormalities in neuronal synaptic communication are implicated in the aetiology of the disorder. Numerous studies have associated autism with mutations in several genes involved in excitatory and inhibitory synapses in the mammalian brain, including neuroligin, neurexin and shank, for which there are C. elegans orthologues. Thus, several molecular pathways and behavioural phenotypes in C. elegans have been related to autism. In general, the nematode offers a series of advantages that combined with knowledge from other animal models and human research, provides a powerful

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.

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

[Personal genome research and neurological diseases: overview].

PubMed

Toda, Tatsushi

2013-03-01

Neurological diseases include those caused by a single defective gene,e.g., Huntington's disease, other polyglutamine diseases, and muscular dystrophies, and those that are mostly sporadic but rarely show Mendelian inheritance in some families, e.g., Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and epilepsy. The latter diseases are considered polygenic disorders. Both sporadic and Mendelian cases of these diseases are believed to share some common pathological mechanisms. Since the detection of causal genes for the Mendelian cases, studies have been initiated on disease pathology. SNPs and rare gene variants play important roles in common neurological diseases. From a technological perspective, next-generation sequencers have become widely available and have contributed to the advancement of research based on individual genome sequences (personal genome). This paper presents an overview, as well as a historical context, of the contribution of personal genome research to neurological disease studies.

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.

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

Rare neurological diseases: a Pandora's box for neurology (an European and Italian perspective).

PubMed

Federico, A

2013-02-01

Rare neurological diseases are a heterogeneous group of disorders mainly affecting the central and peripheral nervous systems and muscle, representing almost 50% of all rare diseases; this means that neurologists are among the main specialists involved in their diagnosis and research. However, the classical interest of neurologists is primarily directed towards the more common diseases such as dementia, multiple sclerosis, headache, epilepsy and stroke, while avoiding the follow-up of rare neurological diseases that have, taken altogether, had such a major impact on health systems in Europe as well as in other countries around the world. Rare diseases are also considered 'orphan' diseases, as only a few of them have treatments. In Europe as in the USA in recent years, considerable interest has been generated by these disorders, thereby stimulating more specific programs of care and management. In fact, the difficulty of diagnosis and the need for super-specialization in this field has led to the organization of dedicated centers in different countries to collect patients' data within a network for diagnosis, treatment and research. The present report describes our experience in Siena with such a reference center for these disorders and their diagnosis and treatment, and also includes a discussion of the organization of care for rare neurological diseases in Europe and Italy. Finally, this report also covers the new initiative of the Italian Neurological Society to promote an information center for rare neurological diseases to disseminate information and knowledge to all neurologists working in this field. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Neuroprotective role of Agmatine in Neurological Diseases.

PubMed

Xu, Weilin; Gao, Liansheng; Li, Tao; Shao, Anwen; Zhang, Jianmin

2017-08-08

Neurological diseases have always been one of the leading cause of mobility and mortality world-widely. However, it is still lack of efficient agents. Agmatine, an endogenous polyamine, exerts its diverse biological characteristics and therapeutic potential in varied aspects. Moreover, there has been numerous studies demonstrated the neuroprotective effect of agmatine in varied types of neurological diseases, including acute attack (stroke and trauma brain injury) and chronic neurodegenerative diseases (Parkinson's disease, Alzheimer's disease). The potential mechanism of agmatine -induced neuroprotection includes anti-oxidation, anti-apoptosis, anti-inflammation, brain blood barrier (BBB) protection and brain edema prevention. In this review, we will introduce the neuroprotective effects of agmatine and the underlying mechanisms in the setting of neurological diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

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.

[Nutrition and dietary supplements in neurological diseases].

PubMed

Erbguth, F; Himmerich, H

2014-12-01

"Healthy" diets and supplements are widely used for prevention and disease modification in vascular, inflammatory and degenerative neurological diseases. Apart from a large number of cross-sectional and prospective cohort studies, there are only few interventional studies on individual dietary measures. A recent study confirmed the stroke preventive effect of a Mediterranean diet rich in olive oil and nuts; a ketogenic diet reduces seizure frequency in epilepsy. Supplementation of riboflavin, magnesium and coenzyme Q10 are probably effective in migraine prophylaxis. Creatine can improve muscle strength in muscular dystrophy and myositis. There is insufficient evidence to recommend any of the many dietary supplements, such as vitamins, omega-3 fatty acids and other substances for the prevention or improvement of all other neurological diseases. This review critically evaluates the present data on the role of nutrition and dietary supplements in neurological diseases.

Novel test of motor and other dysfunctions in mouse neurological disease models.

PubMed

Barth, Albert M I; Mody, Istvan

2014-01-15

Just like human neurological disorders, corresponding mouse models present multiple deficiencies. Estimating disease progression or potential treatment effectiveness in such models necessitates the use of time consuming and multiple tests usually requiring a large number of scarcely available genetically modified animals. Here we present a novel and simple single camera arrangement and analysis software for detailed motor function evaluation in mice walking on a wire mesh that provides complex 3D information (instantaneous position, speed, distance traveled, foot fault depth, duration, location, relationship to speed of movement, etc.). We investigated 3 groups of mice with various neurological deficits: (1) unilateral motor cortical stroke; (2) effects of moderate ethanol doses; and (3) aging (96-99 weeks old). We show that post stroke recovery can be divided into separate stages based on strikingly different characteristics of motor function deficits, some resembling the human motor neglect syndrome. Mice treated with moderate dose of alcohol and aged mice showed specific motor and exploratory deficits. Other tests rely either partially or entirely on manual video analysis introducing a significant subjective component into the analysis, and analyze a single aspect of motor function. Our novel experimental approach provides qualitatively new, complex information about motor impairments and locomotor/exploratory activity. It should be useful for the detailed characterization of a broad range of human neurological disease models in mice, and for the more accurate assessment of disease progression or treatment effectiveness. Copyright © 2013 Elsevier B.V. All rights reserved.

Predominance of neurologic diseases in international aeromedical transportation.

PubMed

Chen, Wan-Lin; Lin, Yu-Ming; Ma, Hong-Ping; Chiu, Wen-Ta; Tsai, Shin-Han

2009-12-01

International travel industry in Taiwan is expanding. The number of people traveling abroad was approximately 480,000 people in 1980; 2,940,000 in 1990; 7,320,000 in 2000, and in 2007, it has reached 8,960,000, which was more than one third of total population. Air medical transportation will be necessary when local medical facilities do not approximate the international standards. No previous study on epidemiology in Taiwan on patients received international medical repatriation. This is the first report to discuss the epidemiology of Taiwan's international aeromedical transportation and its focus on neurologic diseases. Retrospective analysis of all international aeromedical transports on Taiwanese patients from October 2005 to September 2007 was performed. All materials were collected from the databank of International SOS, Taipei. The data were analyzed with Microsoft Excel and SPSS v. 11.0 software (SPSS, Chicago, Ill). A total of 416 patients were transported. Excluding expatriates transported outbound and 2-stage inbound transports, the Taiwanese patient number with international aeromedical transport was 379; 51 by air ambulance and 328 commercially. There were 271 male (72%) and 108 female patients (18%). Of the 379 patients, 178 (47%) were neurologic diseases. Two hundred ninety-five (78%) patients were transported from China. Patient transports peaked in autumn by 105 (28%). Of all 33 ventilated patients, 12 (36%) were neurologic diseases. In-flight complications occurred in 10% of neurologic and 2% of nonneurologic cases. No in-flight mortality occurred in both groups. Neurologic diseases comprise most of the Taiwanese patients that requires medical transportation. With relatively suboptimal medical standard and high medical expenses in China, patients with neurologic conditions need timely and safe aeromedical transport than those with other diseases. Transport of patients with neurologic diseases, either by air ambulance or commercial flights, can

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.

Circular RNA: a new star in neurological diseases.

PubMed

Li, Tao-Ran; Jia, Yan-Jie; Wang, Qun; Shao, Xiao-Qiu; Lv, Rui-Juan

2017-08-01

Circular RNAs (circRNAs) are novel endogenous non-coding RNAs characterized by the presence of a covalent bond linking the 3' and 5' ends generated by backsplicing. In this review, we summarize a number of the latest theories regarding the biogenesis, properties and functions of circRNAs. Specifically, we focus on the advancing characteristics and functions of circRNAs in the brain and neurological diseases. CircRNAs exhibit the characteristics of species conservation, abundance and tissue/developmental-stage-specific expression in the brain. We also describe the relationship between circRNAs and several neurological diseases and highlight their functions in neurological diseases.

Human Neurological Development: Past, Present and Future

NASA Technical Reports Server (NTRS)

Pelligra, R. (Editor)

1978-01-01

Neurological development is considered as the major human potential. Vision, vestibular function, intelligence, and nutrition are discussed as well as the treatment of neurological disfunctions, coma, and convulsive seizures.

Happiness and neurological diseases.

PubMed

Barak, Yoram; Achiron, Anat

2009-04-01

Happiness is an emotional state reflecting positive feelings and satisfaction with life, which, as an outcome in disease states or as an end point in clinical trials, is a neglected concept in most therapeutic areas. In neurological disease, happiness is important as it can be diminished either as a direct result of damage to neuronal tissue or as a reaction to a poor prognosis. The monitoring and maintenance of happiness and wellbeing have historically been considered to be peripheral to medicine. However, as happiness interacts with the patient's physical health, it is an important parameter to assess alongside all aspects of any given disease. Happiness provides a reliable overview of the patient's general status over and above standard parameters for quality of life, and is more wide-ranging than the narrow measures of disease activity or treatment efficacy that are the focus of most clinical trials. In many studies, happiness has been associated with health and success in most areas of life, including performance at work, sporting achievement and social functioning. For approximately a decade, previously studied aspects of psychology have been grouped under the label of positive psychology (PoP). Principles of this discipline are now being used to guide some treatments in neurological and psychiatric diseases. PoP aims to define patient wellbeing in scientific terms and to increase understanding of happiness, meaning in life, resilience and character strengths, as well as to determine how this knowledge can be applied clinically to promote health. Some evidence has emerged recently suggesting that improvements in patient status can result from interventions to improve the patient's level of happiness in diseases, including epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and stroke. Several effective approaches to increase happiness employ activities to engage and stimulate patients who might otherwise be unoccupied and isolated. In

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.

Placebo effects in neurological diseases.

PubMed

Dumitriu, Alina; Popescu, Bogdan O

2010-01-01

There is an imperious need of redefining placebo effect in contemporary times. The effects of sham medical intervention, combined with a careful observation of the natural evolution of a disease, could reveal the true efficiency and impact of active drugs. This interest is not driven only by a scientific curiosity, but also by the pragmatic fact that the standard process of approving new medicines through supportive clinical trials requires a comparison against placebo. A complete understanding of the placebo effect should include both its psychological mechanisms and the underlying neurobiology. In contrast to other type of conditions, neurological disorders could provide specific clues in understanding the placebo effect, since the pathogenic mechanisms of different diseases might interfere with neuronal circuitry involved in the perception of disease symptoms. However, there are ethical considerations dictating the limits of using placebo. This paper reviews recent articles about placebo effect, with an emphasis on its importance in several neurological conditions (Parkinson's disease, neuropathic pain, headache, multiple sclerosis, epilepsy), and intends to offer new insights on this major topic.

Synthetic Nucleic Acids and Treatment of Neurological Diseases.

PubMed

Corey, David R

2016-10-01

The ability to control gene expression with antisense oligonucleotides (ASOs) could provide a new treatment strategy for disease. To review the use of ASOs for the treatment of neurological disorders. Articles were identified through a search of PubMed references from 2000 to 2016 for articles describing the use of ASOs to treat disease, with specific attention to neurological disease. We concentrated our review on articles pertaining to activation of frataxin expression (Friedreich's ataxia) and production of active survival motor neuron 2 (SMN2, spinal muscular atrophy). Many neurological diseases are caused by inappropriate expression of a protein. Mutations may reduce expression of a wild-type protein, and strategies to activate expression may provide therapeutic benefit. For other diseases, a mutant protein may be expressed too highly and methods that reduce mutant protein expression might form the basis for drug development. Synthetic ASOs can recognize cellular RNA and control gene expression. Antisense oligonucleotides are not a new concept, but successful clinical development has proceeded at a slow pace. Advances in ASO chemistry, biological understanding, and clinical design are making successful applications more likely. Both laboratory and clinical studies are demonstrating the potential of ASOs as a source of drugs to treat neurological disease.

Positron emission tomography in neurological diseases.

PubMed

Kumar, Sudhir; Rajshekher, G; Prabhakar, Subhashini

2005-06-01

Positron emission tomography (PET) is the study of human physiology by electronic detection of positron-emitting radiopharmaceuticals. It is one of the noninvasive technologies that can measure the metabolic and functional activity of living tissue. Positron emission tomography finds its clinical applications in broadly three specialties--oncology, cardiology, and neurology. The current review focuses on its indications in neurological diseases. Recently published literature on the use of PET in neurology has been thoroughly analyzed. Several reports regarding the usage of PET in epilepsy, stroke, dementia, and movement disorders are available. Positron emission tomography does not appear to be useful as a primary or sole imaging technique in these conditions. On the other hand, it is useful in very specific situations, which have been elaborated in the review. It is also noteworthy that PET is complementary to the computed tomography/magnetic resonance imaging findings and data obtained from combining these modalities can be valuable in situations such as localization of the epileptogenic focus in cases of refractory epilepsy or for prediction of the outcome after thrombolysis in acute ischemic stroke. The major handicaps in widespread use of PET appear to be its lack of availability and its relatively high cost. Nevertheless, a review such as this would be helpful in judiciously selecting those patients who would benefit from undergoing a PET scan, at a time when PET imaging facility is likely to be available soon in the Indian private sector.

Neurological symptoms in patients with biopsy proven celiac disease.

PubMed

Bürk, Katrin; Farecki, Marie-Louise; Lamprecht, Georg; Roth, Guenter; Decker, Patrice; Weller, Michael; Rammensee, Hans-Georg; Oertel, Wolfang

2009-12-15

In celiac disease (CD), the gut is the typical manifestation site but atypical neurological presentations are thought to occur in 6 to 10% with cerebellar ataxia being the most frequent symptom. Most studies in this field are focused on patients under primary neurological care. To exclude such an observation bias, patients with biopsy proven celiac disease were screened for neurological disease. A total of 72 patients with biopsy proven celiac disease (CD) (mean age 51 +/- 15 years, mean disease duration 8 +/- 11 years) were recruited through advertisements. All participants adhered to a gluten-free diet. Patients were interviewed following a standard questionnaire and examined clinically for neurological symptoms. Medical history revealed neurological disorders such as migraine (28%), carpal tunnel syndrome (20%), vestibular dysfunction (8%), seizures (6%), and myelitis (3%). Interestingly, 35% of patients with CD reported of a history of psychiatric disease including depression, personality changes, or even psychosis. Physical examination yielded stance and gait problems in about one third of patients that could be attributed to afferent ataxia in 26%, vestibular dysfunction in 6%, and cerebellar ataxia in 6%. Other motor features such as basal ganglia symptoms, pyramidal tract signs, tics, and myoclonus were infrequent. 35% of patients with CD showed deep sensory loss and reduced ankle reflexes in 14%. Gait disturbances in CD do not only result from cerebellar ataxia but also from proprioceptive or vestibular impairment. Neurological problems may even develop despite strict adherence to a gluten-free diet. (c) 2009 Movement Disorder Society.

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.

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

Lineage 2 west nile virus as cause of fatal neurologic disease in horses, South Africa.

PubMed

Venter, Marietjie; Human, Stacey; Zaayman, Dewald; Gerdes, Gertruida H; Williams, June; Steyl, Johan; Leman, Patricia A; Paweska, Janusz Tadeusz; Setzkorn, Hildegard; Rous, Gavin; Murray, Sue; Parker, Rissa; Donnellan, Cynthia; Swanepoel, Robert

2009-06-01

Serologic evidence suggests that West Nile virus (WNV) is widely distributed in horses in southern Africa. However, because few neurologic cases have been reported, endemic lineage 2 strains were postulated to be nonpathogenic in horses. Recent evidence suggests that highly neuroinvasive lineage 2 strains exist in humans and mice. To determine whether neurologic cases are being missed in South Africa, we tested 80 serum or brain specimens from horses with unexplained fever (n = 48) and/or neurologic signs (n = 32) for WNV. From March 2007 through June 2008, using reverse transcription-PCR (RT-PCR) and immunoglobulin (Ig) M ELISA, we found WNV RNA or IgM in 7/32 horses with acute neurologic disease; 5 horses died or were euthanized. In 5/7 horses, no other pathogen was detected. DNA sequencing for all 5 RT-PCR-positive cases showed the virus belonged to lineage 2. WNV lineage 2 may cause neurologic disease in horses in South Africa.

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.

Viral vectors for therapy of neurologic diseases

PubMed Central

Choudhury, Sourav R.; Hudry, Eloise; Maguire, Casey A.; Sena-Esteves, Miguel; Breakefield, Xandra O.; Grandi, Paola

2018-01-01

Neurological disorders – disorders of the brain, spine and associated nerves – are a leading contributor to global disease burden with a shockingly large associated economic cost. Various treatment approaches – pharmaceutical medication, device-based therapy, physiotherapy, surgical intervention, among others – have been explored to alleviate the resulting extent of human suffering. In recent years, gene therapy using viral vectors – encoding a therapeutic gene or inhibitory RNA into a “gutted” viral capsid and supplying it to the nervous system – has emerged as a clinically viable option for therapy of brain disorders. In this Review, we provide an overview of the current state and advances in the field of viral vector-mediated gene therapy for neurological disorders. Vector tools and delivery methods have evolved considerably over recent years, with the goal of providing greater and safer genetic access to the central nervous system. Better etiological understanding of brain disorders has concurrently led to identification of improved therapeutic targets. We focus on the vector technology, as well as preclinical and clinical progress made thus far for brain cancer and various neurodegenerative and neurometabolic disorders, and point out the challenges and limitations that accompany this new medical modality. Finally, we explore the directions that neurological gene therapy is likely to evolve towards in the future. PMID:26905292

Probiotics and Disease: A Comprehensive Summary-Part 1, Mental and Neurological Health.

PubMed

Dolan, Keren E; Finley, Heather J; Burns, Cathleen M; Gasta, Margaret G; Gossard, Crystal M; Parker, Emily C; Pizano, Jessica M; Williamson, Christy B; Lipski, Elizabeth A

2016-10-01

This article series provides a literature review of the disease-specific probiotic strains studied in published clinical trials in humans and animals. The goal of the series is to provide clinically useful tools. The table designs allow for quick access to supportive data related to disease states and will be helpful as a guide for both researchers and clinicians. This first article (part 1) focuses on mental health and neurological conditions. Future articles in this series will review conditions related to cardiometabolic and fatigue syndromes; ear, nose, throat, respiratory, and infectious diseases; immune and dermatological conditions; cancer, gastrointestinal and genitourinary; followed by an article focused on food-based probiotic strains and nutritional supplements. This literature review is specific to condition, probiotic, and strain and also lists currently available products and foods in which these probiotics can be found. In part 1, we explore the role of probiotics in balancing mental health and neurological issues. Conditions in mental health include anxiety, depression, attention-deficit/hyperactivity disorder, and autism. Neurological conditions include age-related cognitive decline, hepatic encephalopathy, cerebral ischemia and reperfusion, traumatic brain injury, and multiple sclerosis.

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.

Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review.

PubMed

Block, Valerie A J; Pitsch, Erica; Tahir, Peggy; Cree, Bruce A C; Allen, Diane D; Gelfand, Jeffrey M

2016-01-01

To perform a systematic review of studies using remote physical activity monitoring in neurological diseases, highlighting advances and determining gaps. Studies were systematically identified in PubMed/MEDLINE, CINAHL and SCOPUS from January 2004 to December 2014 that monitored physical activity for ≥24 hours in adults with neurological diseases. Studies that measured only involuntary motor activity (tremor, seizures), energy expenditure or sleep were excluded. Feasibility, findings, and protocols were examined. 137 studies met inclusion criteria in multiple sclerosis (MS) (61 studies); stroke (41); Parkinson's Disease (PD) (20); dementia (11); traumatic brain injury (2) and ataxia (1). Physical activity levels measured by remote monitoring are consistently low in people with MS, stroke and dementia, and patterns of physical activity are altered in PD. In MS, decreased ambulatory activity assessed via remote monitoring is associated with greater disability and lower quality of life. In stroke, remote measures of upper limb function and ambulation are associated with functional recovery following rehabilitation and goal-directed interventions. In PD, remote monitoring may help to predict falls. In dementia, remote physical activity measures correlate with disease severity and can detect wandering. These studies show that remote physical activity monitoring is feasible in neurological diseases, including in people with moderate to severe neurological disability. Remote monitoring can be a psychometrically sound and responsive way to assess physical activity in neurological disease. Further research is needed to ensure these tools provide meaningful information in the context of specific neurological disorders and patterns of neurological disability.

Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review

PubMed Central

Block, Valerie A. J.; Pitsch, Erica; Tahir, Peggy; Cree, Bruce A. C.; Allen, Diane D.; Gelfand, Jeffrey M.

2016-01-01

Objective To perform a systematic review of studies using remote physical activity monitoring in neurological diseases, highlighting advances and determining gaps. Methods Studies were systematically identified in PubMed/MEDLINE, CINAHL and SCOPUS from January 2004 to December 2014 that monitored physical activity for ≥24 hours in adults with neurological diseases. Studies that measured only involuntary motor activity (tremor, seizures), energy expenditure or sleep were excluded. Feasibility, findings, and protocols were examined. Results 137 studies met inclusion criteria in multiple sclerosis (MS) (61 studies); stroke (41); Parkinson's Disease (PD) (20); dementia (11); traumatic brain injury (2) and ataxia (1). Physical activity levels measured by remote monitoring are consistently low in people with MS, stroke and dementia, and patterns of physical activity are altered in PD. In MS, decreased ambulatory activity assessed via remote monitoring is associated with greater disability and lower quality of life. In stroke, remote measures of upper limb function and ambulation are associated with functional recovery following rehabilitation and goal-directed interventions. In PD, remote monitoring may help to predict falls. In dementia, remote physical activity measures correlate with disease severity and can detect wandering. Conclusions These studies show that remote physical activity monitoring is feasible in neurological diseases, including in people with moderate to severe neurological disability. Remote monitoring can be a psychometrically sound and responsive way to assess physical activity in neurological disease. Further research is needed to ensure these tools provide meaningful information in the context of specific neurological disorders and patterns of neurological disability. PMID:27124611

Symptomatic treatment of neurologic symptoms in Wilson disease.

PubMed

Litwin, Tomasz; Dušek, Petr; Członkowska, Anna

2017-01-01

Wilson disease (WD) is a potentially treatable neurodegenerative disorder. In the majority of cases, treatment with drugs that induce a negative copper balance (usually chelators or zinc salts) leads to improvements in liver function and neurologic signs. However, some patients show severe neurologic symptoms at diagnosis, such as tremor, dystonia, parkinsonism, and chorea. In this patient group, some neurologic deficits may persist despite adequate treatment, and further neurologic deterioration may be observed after treatment initiation. Such patients may require additional treatment to alleviate neurologic symptoms. Apart from general recommendations for WD anticopper treatment, there are currently no guidelines for managing neurologic symptoms in WD. The aim of this chapter is to summarize possible treatments of neurologic symptoms in WD based on the presently available medical literature. © 2017 Elsevier B.V. All rights reserved.

[Neurological diseases detected in the Lille Multidisciplinary Falls Consultation].

PubMed

Guillochon, A; Crinquette, C; Gaxatte, C; Pardessus, V; Bombois, S; Deramecourt, V; Boulanger, E; Puisieux, F

2010-02-01

People with neurological disorders including stroke, dementia, Parkinson's disease, and polyneuropathy are known to have an increased risk of falls. To evaluate the prevalence and nature of neurological risk factors among the patients attending the Multidisciplinary Falls Consultation of the University Hospital of Lille (France), and to analyze the characteristic features of patients termed "neurological fallers" with neurological risk factors. The study included 266 consecutive patients who were initially assessed by a geriatrician, a neurologist and a physiatrist, and again, six months later, by the same geriatrician. Two out of three patients had neurological signs that can be regarded as neurological risk factors of falling. These neurological signs had not been diagnosed before the consultation in 85% of cases. The most common conditions were deficit of lower extremity proprioception (59% of patients) and cognitive impairment (43%). The most frequently evoked neurological diseases were dementia (40% of patients), polyneuropathy (17%) and stroke (8%). Compared with other patients, "neurological fallers" were more frequently living in a nursing home, had lower ADL and MMSE scores at baseline, had experienced more falls in the six preceding months, had a lower probability of having a timed Up-and-Go test less than 20 seconds and a single limb stance equal to 5 seconds. In the follow-up, "neurological fallers" reported hospitalizations more often. The findings show that a large proportion of old persons presenting at the Multidisciplinary Falls Consultation have unrecognized neurological disorders. Comprehensive neurological examination including an evaluation of cognition is required in every elderly faller. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Neurological disorders and inflammatory bowel diseases

PubMed Central

Casella, Giovanni; Tontini, Gian Eugenio; Bassotti, Gabrio; Pastorelli, Luca; Villanacci, Vincenzo; Spina, Luisa; Baldini, Vittorio; Vecchi, Maurizio

2014-01-01

Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease (IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms. PMID:25083051

Insomnia in central neurologic diseases--occurrence and management.

PubMed

Mayer, Geert; Jennum, Poul; Riemann, Dieter; Dauvilliers, Yves

2011-12-01

The objective of this review is to highlight the impact of insomnia in central neurological disorders by providing information on its prevalence and give recommendations for diagnosis and treatment. Insomnia in neurological disorders is a frequent, but underestimated symptom. Its occurrence may be a direct consequence of the disease itself or may be secondary to pain, depression, other sleep disorders or the effects of medications. Insomnia can have a significant impact on the patient's cognitive and physical function and may be associated with psychological distress and depression. Diagnosis of insomnia is primarily based on medical history and validated questionnaires. Actigraphy is a helpful diagnostic tool for assessing the circadian sleep-wake rhythm. For differential diagnosis and to measure the duration of sleep full polysomnography may be recommended. Prior to initiating treatment the cause of insomnia must be clearly identified. First line treatment aims at the underlying neurologic disease. The few high quality treatment studies show that short term treatment with hypnotics may be recommended in most disorders after having ruled out high risk for adverse effects. Sedating antidepressants may be an effective treatment for insomnia in stroke and Parkinson's disease (PD) patients. Melatonin and light treatment can stabilize the sleep-wake circadian rhythm and shorten sleep latency in dementias and PD. Cognitive behavioral therapy (CBT) can be effective in treating insomnia symptoms associated with most of the central neurological diseases. The prevalence and treatment of insomnia in neurological diseases still need to be studied in larger patient groups with randomized clinical trials to a) better understand their impact and causal relationship and b) to develop and improve specific evidence-based treatment strategies. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Approach of gene medical treatment in neurological diseases with the neurologist's. "Approach of support to the patients with inherited and incurable neurological diseases"].

PubMed

Hazama, Takanori; Sawada, Jin-ichi; Toda, Tatsushi

2009-11-01

Advancements in medical genetics have increased access to genetic diagnosis in clinical neurology and accompanying genetic counseling. However, its use has not yet spread and the frequency of general biochemistry inspection in medical treatment and by patients remains low. Many problems remain for doctors, though sociocultural and other various causes exist. Thus, a network of care specialists for inherited and incurable neurological diseases has been established, consisting of multi-occupational categories in medical treatment, health, and welfare such as clinical inheritance specialists, psychiatrists, public health nurses, and medical social workers, to meet the rise in availability of such methods. Businesses in areas such as training, consultation, and field research have arisen. An educational campaign for neurologists who have taken a central role in treatment of inherited and incurable neurological diseases, and related information have been disseminated to those working in fields related to regional welfare of neurological medicine, and patients are now supported totally by team and regional counseling. These new developments in support systems for inherited and incurable neurological diseases, have steadily achieved the respective goals. We aim to promote its evolution to a more advanced network to promote the independence of individual patients in the future.

Adverse neurological outcomes in Nigerian children with sickle cell disease.

PubMed

Lagunju, I A; Brown, B J

2012-12-01

Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria.

Neurological diseases associated with viral and Mycoplasma pneumoniae infections

PubMed Central

Assaad, F.; Gispen, R.; Kleemola, M.; Syrůček, L.; Esteves, K.

1980-01-01

In 1963 the World Health Organization established a system for the collection and dissemination of information on viral infections and by 1976, laboratories in 49 countries were participating in this scheme. The present study is in two parts: part 1 is an analysis of almost 60 000 reports on neurological disease associated with viral and Mycoplasma pneumoniae infections reported during the 10-year period 1967-76. This analysis showed a steady increase in the yearly number of reports of viral neurological diseases, which closely followed the general increase in the overall reporting of virus diseases. Likewise, the seasonal pattern was similar to that seen in general for any given virus. Over 75% of the cases were in children. Over half of all viral neurological diseases were associated with enteroviruses, while the myxoviruses accounted for almost 30%. Among the myxoviruses, mumps virus was by far the most frequently reported. The polioviruses were the agents most commonly detected in cases of paralytic disease. The other enteroviruses, mumps virus, and the herpesviruses were the most frequently reported viruses in cases of aseptic meningitis or encephalitis. On the other hand, one-third to over one-half of the reports on the myxoviruses (excluding mumps and measles) related to ill-defined clinical conditions. Part 2 of the study deals in particular with viruses whose role in neurological disease is less well documented. One laboratory reported an outbreak of adenoviral aseptic meningitis in Czechoslovakia, while another described neurological disease associated with M. pneumoniae infection in Finland. Part 2 also includes a detailed appraisal of viral infections diagnosed in the Netherlands during the period 1973-76. The results are very similar to those routinely reported. PMID:6249511

[Neurological manifestations of Whipple disease].

PubMed

Vital Durand, D; Gérard, A; Rousset, H

2002-10-01

Whipple disease is an uncommon chronic bacterial infection due to Tropheryma whipplei. Clinical manifestations are protean (joint pain, fever, weight loss, abdominal pain, lymphadenopathies), and the diagnosis is often delayed. Although previously considered a late manifestation of Whipple disease, neurological involvement is now frequently the initial clinical manifestation and represents the greatest risk for long-term disability. All patients should be treated and monitored as if they had central nervous system disease even if they are asymptomatic. Neurological manifestations include dementia (56 percent), abnormalities of eye movements (33p. cent), involuntary movements (28 percent), seizures, hypothalamic dysfunction, myelopathy, ataxia and psychiatric manifestations. Uveitis, retinitis, optic neuritis and papilloedema may be found. 80 percent of the reported cases of neuro-Whipple had associated systemic symptoms or signs but many patients are presenting without concurrent intestinal manifestation. Thus, the disease may remain undiagnosed or misdiagnosed, as rheumatoid arthritis or sarcoidosis. Traditionally, the diagnostic procedure of choice is biopsy of the duodenal mucosa by demonstrating PAS-positive foamy macrophages. However, not all cases have small bowel infiltration and tissue obtained from sites clinically affected may be helpful. CT and MR images of the central nervous system are normal or not specific: atrophic changes, mass lesions, focal abnormalities and hydrocephalus. The application of a PCR assay against Tropheryma whipplei has transformed the diagnosis. Positive results have been obtained from several tissues and from CSF and PCR is more sensitive than other techniques. All patients must be treated with antibiotics which cross the blood-brain barrier. Most agree that initial treatment with a combination of parenteral penicillin and streptomycin for at least 14 days is appropriate, thereafter cotrimoxazole orally 3 times a day for at least

Neurological complication in HIV patients

NASA Astrophysics Data System (ADS)

Ritarwan, K.

2018-03-01

Human Immunodeficiency Virus (HIV) is neurotropic and immunotropic, making themassive destruction of both systems. Although their amount has been reduced, there is still neurological presentations and complications of HIV remain common in the era of combination antiretroviral therapy (cART). Neurological opportunistic infections (OI) occur in advanced HIV diseases such as primary cerebral lymphoma, cryptococcal meningitis, cerebral toxoplasmosis, and progressive multifocal encephalopathy. Neurological problem directly related to HIV appear at any stage in the progress of HIV disease, from AIDS-associated dementia to the aseptic meningitis of primary HIV infection observed in subjects with an immune deficiency. The replication of peripheral HIV viral is able to be controlled in the era of effective antiretroviral therapy. Non-HIV-related neurological disease such as stroke increased important as the HIV population ages.

Systems-level thinking for nanoparticle-mediated therapeutic delivery to neurological diseases.

PubMed

Curtis, Chad; Zhang, Mengying; Liao, Rick; Wood, Thomas; Nance, Elizabeth

2017-03-01

Neurological diseases account for 13% of the global burden of disease. As a result, treating these diseases costs $750 billion a year. Nanotechnology, which consists of small (~1-100 nm) but highly tailorable platforms, can provide significant opportunities for improving therapeutic delivery to the brain. Nanoparticles can increase drug solubility, overcome the blood-brain and brain penetration barriers, and provide timed release of a drug at a site of interest. Many researchers have successfully used nanotechnology to overcome individual barriers to therapeutic delivery to the brain, yet no platform has translated into a standard of care for any neurological disease. The challenge in translating nanotechnology platforms into clinical use for patients with neurological disease necessitates a new approach to: (1) collect information from the fields associated with understanding and treating brain diseases and (2) apply that information using scalable technologies in a clinically-relevant way. This approach requires systems-level thinking to integrate an understanding of biological barriers to therapeutic intervention in the brain with the engineering of nanoparticle material properties to overcome those barriers. To demonstrate how a systems perspective can tackle the challenge of treating neurological diseases using nanotechnology, this review will first present physiological barriers to drug delivery in the brain and common neurological disease hallmarks that influence these barriers. We will then analyze the design of nanotechnology platforms in preclinical in vivo efficacy studies for treatment of neurological disease, and map concepts for the interaction of nanoparticle physicochemical properties and pathophysiological hallmarks in the brain. WIREs Nanomed Nanobiotechnol 2017, 9:e1422. doi: 10.1002/wnan.1422 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

DNA testing in neurologic diseases.

PubMed

O'Brien, D P; Leeb, T

2014-01-01

DNA testing is available for a growing number of hereditary diseases in neurology and other specialties. In addition to guiding breeding decisions, DNA tests are important tools in the diagnosis of diseases, particularly in conditions for which clinical signs are relatively nonspecific. DNA testing also can provide valuable insight into the risk of hereditary disease when decisions about treating comorbidities are being made. Advances in technology and bioinformatics will make broad screening for potential disease-causing mutations available soon. As DNA tests come into more common use, it is critical that clinicians understand the proper application and interpretation of these test results. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Neurological diseases and bullous pemphigoid: A case-control study in Iranian patients.

PubMed

Daneshpazhooh, Maryam; Khorassani, Javad; Balighi, Kamran; Ghandi, Narges; Mahmoudi, Hamidreza; Tohidinik, Hamidreza; Hamzelou, Shahin; Chams-Davatchi, Cheyda

2017-01-01

Neurological diseases are important co-morbidities found in association with bullous pemphigoid. Various neurological conditions (stroke, Parkinson's disease, dementia, epilepsy and multiple sclerosis) have been reported as associations of this bullous disease; whether these are significant has not been definitely proved. However, the presence of neurological conditions is a predictor of poorer prognosis. Our aim was to examine the association of bullous pemphigoid and neurological diseases in Iranian bullous pemphigoid patients. The medical records of one hundred and sixty consecutive bullous pemphigoid patients who presented to the Autoimmune Bullous Diseases Research Center, Tehran, Iran, from 2006 to 2011 were examined for evidence of any neurological disease. The control group comprised of 317 age- and sex-matched subjects. Neurological diseases were seen in 42 (26.4%) patients with bullous pemphigoid and in 29 (9.1%) controls (odds ratio: 3.53 (2.1-5.9), P< 0.001). Comparing cases to controls, stroke was seen in 17.5% versus 4.1%, odds ratio 4.96 (2.49-9.88); dementia in 5.6% versus 1.9%, odds ratio 3.09 (1.08-8.84); Parkinson's disease in 2.5% versus 2.2%, odds ratio 1.14 (0.33-3.94); epilepsy in 2.5% versus 0.6%, odds ratio 4.04 (0.73-22.3); and multiple sclerosis in 0 versus 0.3% odds ratio 1.00 (0.98-1.01). The main limitations of our study were referral bias, retrospective design and a rather low sample size. Neurological diseases in general, and stroke and dementia in particular, were significantly associated with bullous pemphigoid in our study.

Toxicities of Immunosuppressive Treatment of Autoimmune Neurologic Diseases

PubMed Central

Lallana, Enrico C; Fadul, Camilo E

2011-01-01

In parallel to our better understanding of the role of the immune system in neurologic diseases, there has been an increased availability in therapeutic options for autoimmune neurologic diseases such as multiple sclerosis, myasthenia gravis, polyneuropathies, central nervous system vasculitides and neurosarcoidosis. In many cases, the purported benefits of this class of therapy are anecdotal and not the result of good controlled clinical trials. Nonetheless, their potential efficacy is better known than their adverse event profile. A rationale therapeutic decision by the clinician will depend on a comprehensive understanding of the ratio between efficacy and toxicity. In this review, we outline the most commonly used immune suppressive medications in neurologic disease: cytotoxic chemotherapy, nucleoside analogues, calcineurin inhibitors, monoclonal antibodies and miscellaneous immune suppressants. A discussion of their mechanisms of action and related toxicity is highlighted, with the goal that the reader will be able to recognize the most commonly associated toxicities and identify strategies to prevent and manage problems that are expected to arise with their use. PMID:22379461

Ethical clinical translation of stem cell interventions for neurologic disease.

PubMed

Cote, David J; Bredenoord, Annelien L; Smith, Timothy R; Ammirati, Mario; Brennum, Jannick; Mendez, Ivar; Ammar, Ahmed S; Balak, Naci; Bolles, Gene; Esene, Ignatius Ngene; Mathiesen, Tiit; Broekman, Marike L

2017-01-17

The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell interventions for neurologic disease, based primarily on the new Guidelines for Stem Cell Research and Clinical Translation released by the International Society for Stem Cell Research in May 2016. Important considerations in the ethical translation of stem cells to clinical practice include regulatory oversight, conflicts of interest, data sharing, the nature of investigation (e.g., within vs outside of a clinical trial), informed consent, risk-benefit ratios, the therapeutic misconception, and patient vulnerability. To help guide the translation of stem cells from the laboratory into the neurosurgical clinic in an ethically sound manner, we present an ethical discussion of these major issues at stake in the field of stem cell clinical research for neurologic disease. © 2016 American Academy of Neurology.

Chapter 50: history of tropical neurology.

PubMed

Ogunniyi, Adesola

2010-01-01

Tropical neurology began less than two centuries ago. Consumption of dietary toxins predominated at the beginning and gave birth to the geographic entity. The story moved from lathyrism through Jamaican neuropathy to cassava-induced epidemic neuropathy, which was contrasted with Konzo, also associated with cassava. Other tropical diseases enumerated with chronological details include: Chaga's diseases, kwashiorkor, Madras type of motor neuron disease, atlanto-axial dislocation, Burkitt's lymphoma and Kuru, associated with cannibalism among the Fore linguistic group in New Guinea. More recent documentation includes the Cuban neuropathy in 1991 with an epidemic of visual loss and neuropathy, Anaphe venata entomophagy in Nigeria presenting as seasonal ataxia, and neurological aspects of the human immunodeficiency virus infection complete the picture. With time, professional associations were formed and the pioneers were given prominence. The World Federation of Neurology featured Geographic Neurology as a theme in 1977 and Tropical Neurology was given prominence at its 1989 meeting in New Delhi, India. The situation remains unchanged with regards to rare diseases like Meniere's, multiple sclerosis, hereditary disorders. However, with westernization and continued urbanization, changing disease patterns are being observed and tropical neurology may depart from dietary toxins to more western world-type disorders.

Measuring outcomes for neurological disorders: a review of disease-specific health status instruments for three degenerative neurological conditions.

PubMed

Heffernan, Catherine; Jenkinson, Crispin

2005-06-01

Health-related quality-of-life measures have been increasingly used in research into neurological disorders in recent years. The aim of this paper is to provide an objective appraisal of the evidence in regard to disease-specific quality-of-life measures used in research on health interventions for three degenerative neurological disorders: multiple sclerosis, motor neurone disease/amyotrophic lateral sclerosis and Parkinson's disease. A comprehensive search strategy was developed to include nine relevant electronic databases. Only studies pertaining to patient-based outcome measurements in multiple sclerosis, motor neurone disease and Parkinson's disease were included. We identified 76 eligible studies. As studies consisted of descriptive and cross-sectional survey study designs, results were reported qualitatively rather than in the form of a meta-analysis. Four disease-specific measures were found for Parkinson's disease, 11 for multiple sclerosis and one for motor neurone disease. We conclude that health-related quality-of-life measures are useful in assessing the impact of treatments and interventions for neurological disorders. However, further research is needed on the development of instruments using psychometric methods and on the validation, utilization and responsiveness of instruments to change.

[Neurological manifestations of Behçet's disease].

PubMed

Noel, N; Drier, A; Wechsler, B; Piette, J-C; De Paz, R; Dormont, D; Cacoub, P; Saadoun, D

2014-02-01

Neurological manifestations of Behçet's disease (BD) occur in 5.3 to more than 50% of patients. They are divided into two major forms: "parenchymal" lesions, which include mainly meningoencephalitis as opposed to "extra-parenchymal" lesions (i.e. cerebral venous thrombosis and arterial aneurysms). Myelitis or peripheral neuropathy is exceptional. The neuro-Behçet syndrome (NBS) should be considered in the setting of neurological manifestations, particularly headache and pyramidal signs, in a young man diagnosed with BD. However, its recognition may be difficult when neurological manifestations are the presenting features of BD (one third of cases), and requires a thorough knowledge of clinical manifestations and morphological lesions. Thus, parenchymal NB lesions classically exhibit inflammatory characteristics on MRI and are located at the meso-diencephalic junction and in the brainstem, rarely with a supratentorial extension. Meningitis is not systematically associated, and may be absent in about 30% of cases. The pathogenesis of these lesions is incompletely understood, but inflammatory infiltrates include mainly neutrophils and activated T cells (mainly Th17). Differential diagnoses include infectious diseases (herpes, listeria, tuberculosis), and inflammatory diseases (i.e. multiple sclerosis and sarcoidosis). A prompt recognition of NBS should lead to initiate adequate therapies in order to limit the risk of sequelae, relapses or death. Copyright © 2013. Published by Elsevier SAS.

The Neurologic Manifestations of Mitochondrial Disease

ERIC Educational Resources Information Center

Parikh, Sumit

2010-01-01

The nervous system contains some of the body's most metabolically demanding cells that are highly dependent on ATP produced via mitochondrial oxidative phosphorylation. Thus, the neurological system is consistently involved in patients with mitochondrial disease. Symptoms differ depending on the part of the nervous system affected. Although almost…

Management of Neurologic Manifestations in Patients with Liver Disease.

PubMed

Ferro, José M; Viana, Pedro; Santos, Patrícia

2016-08-01

Liver disease, both in its acute and chronic forms, can be associated with a wide spectrum of neurologic manifestations, both central and peripheral, ranging in severity from subclinical changes to neurocritical conditions. Neurologists are frequently consulted to participate in their management. In this review, we present an overview of management strategies for patients with hepatic disease whose clinical course is complicated by neurologic manifestations. Type A hepatic encephalopathy (HE), which occurs in acute liver failure, is a neurologic emergency, and multiple measures should be taken to prevent and treat cerebral edema. In Type C HE, which occurs in chronic liver disease, management should be aimed at correcting precipitant factors and hyperammonemia. There is an increasing spectrum of drug treatments available to minimize ammonia toxicity. Acquired hepatocerebral degeneration is a rare complication of the chronic form of HE, with typical clinical and brain MRI findings, whose most effective treatment is liver transplantation. Epilepsy is frequent and of multifactorial cause in patients with hepatic disease, and careful considerations should be made regarding choice of the appropriate anti-epileptic drugs. Several mechanisms increase the risk of stroke in hepatic disease, but many of the drugs used to treat and prevent stroke are contraindicated in severe hepatic failure. Hepatitis C infection increases the risk of ischemic stroke. Hemorrhagic stroke is more frequent in patients with liver disease of alcoholic etiology. Viral hepatitis is associated with a wide range of immune-mediated complications, mostly in the peripheral nervous system, which respond to different types of immunomodulatory treatment. Several drugs used to treat hepatic disease, such as the classical and the new direct-acting antivirals, may have neurologic complications which in some cases preclude its continued use.

Risk of serious neurologic disease after immunization of young children in Britain and Ireland.

PubMed

Ward, Katherine N; Bryant, Naomi J; Andrews, Nick J; Bowley, Jennifer S; Ohrling, Anu; Verity, Christopher M; Ross, Euan M; Miller, Elizabeth

2007-08-01

We sought to investigate the risk of serious neurologic disease after immunization in early childhood. The results of a 3-year prospective study of children (2-35 months old) in Britain and Ireland with encephalitis and/or severe illness with convulsions and fever were linked to each child's vaccine history. Cases were reported via the British Paediatric Surveillance Unit's network. The self-controlled case-series method was used to investigate associations between immunization and acute potential adverse events. The risk periods investigated were 0 to 3 and 0 to 7 days post-diphtheria, tetanus, whole cell pertussis, Haemophilus influenzae type b or meningococcal C conjugate vaccine and 6 to 11 and 15 to 35 days post-measles, mumps, rubella vaccine. A total of 157 disease episodes from 155 children met the analytical case definition. There were 11 cases of herpes simplex encephalitis and 23 cases of primary human herpesvirus 6 and/or 7 infection. There was no evidence of a raised relative incidence of serious neurologic disease in any of the specified risk periods with the exception of a raised relative incidence of 5.68 in the 6-11 days after measles, mumps, rubella vaccine. Based on this relative incidence, between 3 and 6 of the 6 cases in this period were estimated to be attributable to the vaccine with a best estimate of 5. The 6 cases all had fever with convulsions lasting >30 minutes; in all but 1, there was complete recovery by discharge from hospital. Of the 5 patients who recovered, 1 had a concurrent primary human herpesvirus 6 infection and one a primary human herpesvirus 7. Six to 11 days after measles, mumps, rubella vaccine there is an increased risk of fever and convulsions lasting >30 minutes. All 6 of the episodes temporally related to immunization met the criteria for complex febrile convulsions. The estimated attributable risk of serious neurological disease was similar to that previously found for measles vaccine.

Prevalence and patterns of neurological involvement in Behcet's disease: a prospective study from Iraq

PubMed Central

Al-Araji, A; Sharquie, K; Al-Rawi, Z

2003-01-01

Objectives: To determine the prevalence of neurological involvement in Behcet's disease in a prospective study, and to describe the clinical patterns of neurological presentation in this disease in patients attending a multidisciplinary clinic in Baghdad. Methods: All patients attending the clinic who fulfilled the international study group criteria for the diagnosis of Behcet's disease were studied during a two year period starting in April 1999. Patients were assessed neurologically by a neuro-Behcetologist. All those with clinical neurological manifestations were sent for CSF examination, cranial magnetic resonance imaging, and magnetic resonance venography and were followed up to explore the patterns of neurological relapse. Results: 140 patients with Behcet's disease were studied. Their mean age was 34.2 years (range 16 to 66); 105 (75%) were men and 35 (25%) were women. The mean duration of the disease was 4.2 years (range 0.4 to 26). Twenty patients (14%) had neurological involvement (neuro-Behcet's disease); 14 of these (70%) were men and six (30%) women. The mean age at the first neurological presentation was 34.1 years. The mean duration of follow up of patients with neuro-Behcet's disease was 20.7 months. Ten patients with neuro-Behcet's disease (50%) presented with parenchymal CNS involvement, six (30%) with intracranial hypertension, and four (20%) with a mixed pattern of both parenchymal CNS involvement and intracranial hypertension. Conclusions: Careful neurological assessment of patients with Behcet's disease may show a relatively high prevalence of neuro-Behcet features, and though the clinical patterns of presentation are characteristic a mixed pattern may occur. PMID:12700303

Approaching neurological diseases to reduce mobility limitations in older persons.

PubMed

Lauretani, Fulvio; Ceda, Gian Paolo; Pelliccioni, Pio; Ruffini, Livia; Nardelli, Anna; Cherubini, Antonio; Maggio, Marcello

2014-01-01

The rapidly increasing elderly population poses a major challenge for future health-care systems. Neurological diseases in older persons are particularly common and coexist with other clinical conditions. This is not surprising given that, for example, even patients with Alzheimer Disease (AD) could have relevant extrapyramidal signs at the moment of the diagnosis with motor signs having more negative prognostic value. Longitudinal studies conducted on Parkinson Disease (PD) showed that, after 20 years, dementia is not only present in almost all survivors but is also the main factor influencing nursing home admission. Recently, it has been reported the importance of Comprehensive Geriatric Assessment (CGA: comprehensive evaluation of cognition, depressive symptoms, mobility and functional assessment) as a tool reducing morbidity in frail older patients admitted to any acute hospital unit. The CGA should be considered as a technological device, for physicians who take care of older persons affected by overlapping neurological diseases. CGA is an extraordinary and cost effective instrument even in patients with advanced neurological diseases where allows to collect valuable information for an effective plan of management.

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.

Burden of neurological diseases in the US revealed by web searches

PubMed Central

Baeza-Yates, Ricardo; Sangal, Puneet Mohan

2017-01-01

Background Analyzing the disease-related web searches of Internet users provides insight into the interests of the general population as well as the healthcare industry, which can be used to shape health care policies. Methods We analyzed the searches related to neurological diseases and drugs used in neurology using the most popular search engines in the US, Google and Bing/Yahoo. Results We found that the most frequently searched diseases were common diseases such as dementia or Attention Deficit/Hyperactivity Disorder (ADHD), as well as medium frequency diseases with high social impact such as Parkinson’s disease, MS and ALS. The most frequently searched CNS drugs were generic drugs used for pain, followed by sleep disorders, dementia, ADHD, stroke and Parkinson’s disease. Regarding the interests of the healthcare industry, ADHD, Alzheimer’s disease, MS, ALS, meningitis, and hypersomnia received the higher advertising bids for neurological diseases, while painkillers and drugs for neuropathic pain, drugs for dementia or insomnia, and triptans had the highest advertising bidding prices. Conclusions Web searches reflect the interest of people and the healthcare industry, and are based either on the frequency or social impact of the disease. PMID:28531237

Burden of neurological diseases in the US revealed by web searches.

PubMed

Baeza-Yates, Ricardo; Sangal, Puneet Mohan; Villoslada, Pablo

2017-01-01

Analyzing the disease-related web searches of Internet users provides insight into the interests of the general population as well as the healthcare industry, which can be used to shape health care policies. We analyzed the searches related to neurological diseases and drugs used in neurology using the most popular search engines in the US, Google and Bing/Yahoo. We found that the most frequently searched diseases were common diseases such as dementia or Attention Deficit/Hyperactivity Disorder (ADHD), as well as medium frequency diseases with high social impact such as Parkinson's disease, MS and ALS. The most frequently searched CNS drugs were generic drugs used for pain, followed by sleep disorders, dementia, ADHD, stroke and Parkinson's disease. Regarding the interests of the healthcare industry, ADHD, Alzheimer's disease, MS, ALS, meningitis, and hypersomnia received the higher advertising bids for neurological diseases, while painkillers and drugs for neuropathic pain, drugs for dementia or insomnia, and triptans had the highest advertising bidding prices. Web searches reflect the interest of people and the healthcare industry, and are based either on the frequency or social impact of the disease.

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

Estimating and communicating prognosis in advanced neurologic disease

PubMed Central

Gramling, Robert; Kelly, Adam G.

2013-01-01

Prognosis can no longer be relegated behind diagnosis and therapy in high-quality neurologic care. High-stakes decisions that patients (or their surrogates) make often rest upon perceptions and beliefs about prognosis, many of which are poorly informed. The new science of prognostication—the estimating and communication “what to expect”—is in its infancy and the evidence base to support “best practices” is lacking. We propose a framework for formulating a prediction and communicating “what to expect” with patients, families, and surrogates in the context of common neurologic illnesses. Because neurologic disease affects function as much as survival, we specifically address 2 important prognostic questions: “How long?” and “How well?” We provide a summary of prognostic information and highlight key points when tailoring a prognosis for common neurologic diseases. We discuss the challenges of managing prognostic uncertainty, balancing hope and realism, and ways to effectively engage surrogate decision-makers. We also describe what is known about the nocebo effects and the self-fulfilling prophecy when communicating prognoses. There is an urgent need to establish research and educational priorities to build a credible evidence base to support best practices, improve communication skills, and optimize decision-making. Confronting the challenges of prognosis is necessary to fulfill the promise of delivering high-quality, patient-centered care. PMID:23420894

Glia-neuron interactions in neurological diseases: Testing non-cell autonomy in a dish.

PubMed

Meyer, Kathrin; Kaspar, Brian K

2017-02-01

For the past century, research on neurological disorders has largely focused on the most prominently affected cell types - the neurons. However, with increasing knowledge of the diverse physiological functions of glial cells, their impact on these diseases has become more evident. Thus, many conditions appear to have more complex origins than initially thought. Since neurological pathologies are often sporadic with unknown etiology, animal models are difficult to create and might only reflect a small portion of patients in which a mutation in a gene has been identified. Therefore, reliable in vitro systems to studying these disorders are urgently needed. They might be a pre-requisite for improving our understanding of the disease mechanisms as well as for the development of potential new therapies. In this review, we will briefly summarize the function of different glial cell types in the healthy central nervous system (CNS) and outline their implication in the development or progression of neurological conditions. We will then describe different types of culture systems to model non-cell autonomous interactions in vitro and evaluate advantages and disadvantages. This article is part of a Special Issue entitled SI: Exploiting human neurons. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigation of brain science and neurological/psychiatric disorders using genetically modified non-human primates.

PubMed

Okano, Hideyuki; Kishi, Noriyuki

2018-06-01

Although mice have been the most frequently used experimental animals in many research fields due to well-established gene manipulation techniques, recent evidence has revealed that rodent models do not always recapitulate pathophysiology of human neurological and psychiatric diseases due to the differences between humans and rodents. The recent developments in gene manipulation of non-human primate have been attracting much attention in the biomedical research field, because non-human primates have more applicable brain structure and function than rodents. In this review, we summarize recent progress on genetically-modified non-human primates including transgenic and knockout animals using genome editing technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

National response to neurological diseases in Malaysia: planning for the future.

PubMed

Abdullah, Jafri Malin; Hussin, Ahmad Munnawir; Tharakan, John; Abdullah, Mohamed Rusli; Saad, Ramli; Kamari, Zaidun; Hussin, Zabidi Azhar Mohd; Razak, Dzulkifli Abdul

2006-07-01

The number of cases of neurological disease is expected to rise in the next 10 years, making this the second leading cause of morbidity and mortality after heart disease in Malaysia. The lack of human resources in the neurological field currently serving the Malaysian population may cause a deficiency in specialized care, especially in rural areas where neurological and neurosurgical care may be lacking. Thus, a resolve was made to increase the numbers of specialists by the Universiti Sains Malaysia (USM) with the help of the Ministry of Health of Malaysia. A study was made to evaluate the number of referral centers needed in strategic parts of Malaysia. Our calculation was based on service demands and operative procedures following the guidelines of the Association of British Neurologists (ABN) where 15 minutes of service time was equivalent to 1 unit. Based on 2 million population covered in the state of Kelantan by this University Hospital, 4.27 neurologists are needed to meet service demands with a consultant to population ratio (CPR) of 1:468,384, compared to 7.46 neurosurgeons, with a CPR of 1:268,097. According to the current service demands, one neurologist has to work more than 407 hours per year and one neurosurgeon 1,219 hours per year in our hospital. Hospitals with a larger catchment area would need to have more neurologists and neurosurgeons for optimal care in their area. Thus, more neurologists and neurosurgeons are needed to be produced, since the existing numbers are too small for quality care in Malaysia.

Multiomics tools for the diagnosis and treatment of rare neurological disease.

PubMed

Crowther, L M; Poms, M; Plecko, Barbara

2018-05-01

Conventional workup of rare neurological disease is frequently hampered by diagnostic delay or lack of diagnosis. While biomarkers have been established for many neurometabolic disorders, improved methods are required for diagnosis of previously unidentified or underreported causes of rare neurological disease. This would result in a higher diagnostic yield and increased patient numbers required for interventional studies. Recent studies using next-generation sequencing and metabolomics have led to identification of novel disease-causing genes and biomarkers. This combined approach can assist in overcoming challenges associated with analyzing and interpreting the large amount of data obtained from each technique. In particular, metabolomics can support the pathogenicity of sequence variants in genes encoding enzymes or transporters involved in metabolic pathways. Moreover, metabolomics can show the broader perturbation caused by inborn errors of metabolism and identify a metabolic fingerprint of metabolic disorders. As such, using "omics" has great potential to meet the current needs for improved diagnosis and elucidation of rare neurological disease.

An autoinflammatory neurological disease due to interleukin 6 hypersecretion

PubMed Central

2013-01-01

Autoinflammatory diseases are rare illnesses characterized by apparently unprovoked inflammation without high-titer auto-antibodies or antigen-specific T cells. They may cause neurological manifestations, such as meningitis and hearing loss, but they are also characterized by non-neurological manifestations. In this work we studied a 30-year-old man who had a chronic disease characterized by meningitis, progressive hearing loss, persistently raised inflammatory markers and diffuse leukoencephalopathy on brain MRI. He also suffered from chronic recurrent osteomyelitis of the mandible. The hypothesis of an autoinflammatory disease prompted us to test for the presence of mutations in interleukin-1−pathway genes and to investigate the function of this pathway in the mononuclear cells obtained from the patient. Search for mutations in genes associated with interleukin-1−pathway demonstrated a novel NLRP3 (CIAS1) mutation (p.I288M) and a previously described MEFV mutation (p.R761H), but their combination was found to be non-pathogenic. On the other hand, we uncovered a selective interleukin-6 hypersecretion within the central nervous system as the likely pathogenic mechanism. This is also supported by the response to the anti-interleukin-6−receptor monoclonal antibody tocilizumab, but not to the recombinant interleukin-1−receptor antagonist anakinra. Exome sequencing failed to identify mutations in other genes known to be involved in autoinflammatory diseases. We propose that the disease described in this patient might be a prototype of a novel category of autoinflammatory diseases characterized by prominent neurological involvement. PMID:23432807

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.

Emerging Viral Infections and Their Impact on the Global Burden of Neurological Disease.

PubMed

Muñoz, Laura S; Garcia, Maria A; Gordon-Lipkin, Eliza; Parra, Beatriz; Pardo, Carlos A

2018-04-01

Emerging viral infections of the nervous system represent a major global public health concern in the 21st century. They are caused primarily by RNA viruses and are mostly associated with acute or subacute encephalitis. The spectrum of associated central or peripheral nervous system disorders is broad, and results either from a direct viral effect or due to the host immune responses against the infection. Emerging viral infections impose substantial neurological morbidity and mortality, particularly in low- and middle-income regions. In the past five decades, vector-borne viruses primarily transmitted by arthropods, or arboviruses, have been responsible for epidemics with a high burden of neurological disease, like the 2015-2016 Zika virus epidemic in the Americas. Viruses that have become neurovirulent for humans after geographical expansion include West Nile, Dengue, and Zika viruses. Factors such as animal migration, disruption of ecological niches, and cross-species contact have caused old viruses to reappear and cause neurological disease, as is the case of Ebola virus. In addition to these biological challenges, current preventive strategies, vaccination, and diagnostic and therapeutic approaches remain limited. We review the clinical-virological features and global impact of the most relevant emerging viral infections of the nervous system as they are projected over the 21st century. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

J.-M. Charcot and simulated neurologic disease: attitudes and diagnostic strategies.

PubMed

Goetz, Christopher G

2007-07-03

Neurologists have long wrestled with the diagnosis of elaborated or feigned disease. Studies have not focused on early techniques utilized to diagnose malingering. To analyze cases of purposeful neurologic malingering among patients treated by the 19th century neurologist J.-M. Charcot, describe his attitudes, and study his methods to separate malingering from primary neurologic diseases. A study was conducted of Charcot's printed and original documents from the Bibliothèque Charcot, Paris, and added documents on American neurology. Charcot recognized that purposeful simulation occurred in isolation as well as in established neurologic disorders. Charcot was strict with subjects motivated by greed or spite, but showed forbearance and wonder in those who created illness as "art for art's sake." Charcot developed diagnostic equipment that measured inspiratory depth and muscle activity as a strategy to identify malingerers. His approach strikingly contrasted with contemporary military medical treatises on malingering and S.W. Mitchell's civilian neurologic approaches that unmasked patients through more aggressive strategies. Charcot provided an academically professional approach to the assessment of neurologic malingering, with a stern, often patronizing attitude, but without categorical condemnation. His diagnostic techniques are echoed by contemporary approaches and emphasized an attention to enhanced and inconsistent patterns of behaviors by malingerers.

Undiagnosed neurological disease as a potential cause of male lower urinary tract symptoms.

PubMed

Wei, Diana Y; Drake, Marcus J

2016-01-01

In the central nervous system there are many regulatory processes controlling the lower urinary tract. This review considers the possibility that urinary dysfunction may precede diagnosis of neurological disease. Lower urinary tract symptoms (LUTS) occur early in multiple system atrophy, Parkinson's disease and normal pressure hydrocephalus, and may present before neurological diagnosis. Some people present with LUTS and subsequently are diagnosed with multiple sclerosis or a spinal condition. In male LUTS, the symptoms could reflect early stages of a neurological disease, which has not yet been diagnosed ('occult neurology'). Key symptoms include erectile dysfunction, retrograde ejaculation, enuresis, loss of filling sensation or unexplained stress urinary incontinence. Directed questioning should enquire about visual symptoms, back pain, anosmia, bowel dysfunction and incontinence, or memory loss. Examination features can include resting tremor, 'croaky' speech, abnormal gait, orthostatic hypotension, ataxia, or altered perineal sensation. Imaging, such as MRI scan, should only be requested after expert neurological examination, to ensure the correct parts of the central nervous system are scanned with appropriate radiological protocols. Urologists should consider an undiagnosed neurological condition can be present in a few cases. Any finding should be further evaluated by colleagues with relevant expertise.

Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

PubMed

Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

2015-01-01

The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1β, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. Copyright © 2015 Mosby, Inc. All rights reserved.

Dysprosody nonassociated with neurological diseases--a case report.

PubMed

Pinto, José Antonio; Corso, Renato José; Guilherme, Ana Cláudia Rocha; Pinho, Sílvia Rebelo; Nóbrega, Monica de Oliveira

2004-03-01

Dysprosody also known as pseudo-foreign dialect, is the rarest neurological speech disorder. It is characterized by alterations in intensity, in the timing of utterance segments, and in rhythm, cadency, and intonation of words. The terms refers to changes as to duration, fundamental frequency, and intensity of tonic and atonic syllables of the sentences spoken, which deprive an individual's particular speech of its characteristics. The cause of this disease is usually associated with neurological pathologies such as brain vascular accidents, cranioencephalic traumatisms, and brain tumors. The authors report a case of dysprosody attended to at the Núcleo de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço de São Paulo (NOSP). It is about a female patient with bilateral III degree Reinke's edema and normal neurological examinations that started presenting characteristics of the German dialect following a larynx microsurgery.

The Application of Nanomaterials in Stem Cell Therapy for Some Neurological Diseases.

PubMed

Zhang, Guilong; Khan, Ahsan Ali; Wu, Hao; Chen, Lukui; Gu, Yuchun; Gu, Ning

2018-02-08

Stem cell therapy provides great promising therapeutic benefits for various neurological disorders. Cell transplantation has emerged as cell replacement application for nerve damage. Recently, nanomaterials obtain wide development in various industrial and medical fields, and nanoparticles have been applied in the neurological field for tracking and treating nervous system diseases. Combining stem cells with nanotechnology has raised more and more attentions; and it has demonstrated that the combination has huge effects on clinical diagnosis and therapeutics in multiple central nervous system diseases, meanwhile, improves prognosis. The aim of this review was to give a brief overview of the application of nanomaterials in stem cell therapy for neurological diseases. Nanoparticles not only promote stem cell proliferation and differentiation in vitro or in vivo, but also play dominant roles on stem cell imaging and tracking. Furthermore, via delivering genes or drugs, nanoparticles can participate in stem cell therapeutic applications for various neurological diseases, such as ischemic stroke, spinal cord injury (SCI), multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD) and gliomas. However, nanoparticles have potential cytotoxic effects on nerve cells, which are related to their physicochemical properties. Nano-stem cell-based therapy as a promising strategy has the ability to affect neuronal repair and regeneration in the central nervous system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Association between bullous pemphigoid and neurologic diseases: a case-control study.

PubMed

Casas-de-la-Asunción, E; Ruano-Ruiz, J; Rodríguez-Martín, A M; Vélez García-Nieto, A; Moreno-Giménez, J C

2014-11-01

In the past 10 years, bullous pemphigoid has been associated with other comorbidities and neurologic and psychiatric conditions in particular. Case series, small case-control studies, and large population-based studies in different Asian populations, mainland Europe, and the United Kingdom have confirmed this association. However, no data are available for the Spanish population. This was an observational, retrospective, case-control study with 1:2 matching. Fifty-four patients with bullous pemphigoid were selected. We compared the percentage of patients in each group with concurrent neurologic conditions, ischemic heart disease, diabetes, chronic obstructive pulmonary disease, and solid tumors using univariate logistic regression. An association model was constructed with conditional multiple logistic regression. The case group had a significantly higher percentage of patients with cerebrovascular accident and/or transient ischemic attack (odds ratio [OR], 3.06; 95% CI, 1.19-7.87], dementia (OR, 5.52; 95% CI, 2.19-13.93), and Parkinson disease (OR, 5; 95% CI, 1.57-15.94). A significantly higher percentage of cases had neurologic conditions (OR, 6.34; 95% CI, 2.89-13.91). Dementia and Parkinson disease were independently associated with bullous pemphigoid in the multivariate analysis. Patients with bullous pemphigoid have a higher frequency of neurologic conditions. Copyright © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved.

Understanding Neurological Disease Mechanisms in the Era of Epigenetics

PubMed Central

Qureshi, Irfan A.; Mehler, Mark F.

2015-01-01

The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type–specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues. PMID:23571666

Neurologic and neuropsychiatric syndrome features of mold and mycotoxin exposure.

PubMed

Empting, L D

2009-01-01

Human exposure to molds, mycotoxins, and water-damaged buildings can cause neurologic and neuropsychiatric signs and symptoms. Many of these clinical features can partly mimic or be similar to classic neurologic disorders including pain syndromes, movement disorders, delirium, dementia, and disorders of balance and coordination. In this article, the author delineates the signs and symptoms of a syndrome precipitated by mold and mycotoxin exposure and contrasts and separates these findings neurodiagnostically from known neurologic diseases. This clinical process is designed to further the scientific exploration of the underlying neuropathophysiologic processes and to promote better understanding of effects of mold/mycotoxin/water-damaged buildings on the human nervous system and diseases of the nervous system. It is clear that mycotoxins can affect sensitive individuals, and possibly accelerate underlying neurologic/pathologic processes, but it is crucial to separate known neurologic and neuropsychiatric disorders from mycotoxin effects in order to study it properly.

Functional neurological disorders in Parkinson disease.

PubMed

Wissel, Benjamin D; Dwivedi, Alok K; Merola, Aristide; Chin, Danielle; Jacob, Cara; Duker, Andrew P; Vaughan, Jennifer E; Lovera, Lilia; LaFaver, Kathrin; Levy, Ariel; Lang, Anthony E; Morgante, Francesca; Nirenberg, Melissa Jill; Stephen, Christopher; Sharma, Nutan; Romagnolo, Alberto; Lopiano, Leonardo; Balint, Bettina; Yu, Xin X; Bhatia, Kailash P; Espay, Alberto J

2018-06-01

To ascertain demographic and clinical features of Parkinson disease (PD) associated with functional neurological features. A standardised form was used to extract data from electronic records of 53 PD patients with associated functional neurological disorders (PD-FND) across eight movement disorders centres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only). Logistic regression analysis was used to compare both groups after adjusting for clustering effect. Functional symptoms preceded or co-occurred with PD onset in 34% of cases, nearly always in the most affected body side. Compared with PD-only subjects, PD-FND were predominantly female (68%), had longer delay to PD diagnosis, greater prevalence of dyskinesia (42% vs 18%; P=0.023), worse depression and anxiety (P=0.033 and 0.025, respectively), higher levodopa-equivalent daily dose (972±701 vs 741±559 mg; P=0.029) and lower motor severity (P=0.019). These patients also exhibited greater healthcare resource utilisation, higher use of [(123)I]FP-CIT SPECT and were more likely to have had a pre-existing psychiatric disorder (P=0.008) and family history of PD (P=0.036). A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chagas disease in a Texan horse with neurologic deficits.

PubMed

Bryan, Laura K; Hamer, Sarah A; Shaw, Sarah; Curtis-Robles, Rachel; Auckland, Lisa D; Hodo, Carolyn L; Chaffin, Keith; Rech, Raquel R

2016-01-30

A 10-year-old Quarter Horse gelding presented to the Texas A&M University Veterinary Teaching Hospital with a six month-history of ataxia and lameness in the hind limbs. The horse was treated presumptively for equine protozoal myeloencephalitis (EPM) based on clinical signs but was ultimately euthanized after its condition worsened. Gross lesions were limited to a small area of reddening in the gray matter of the thoracic spinal cord. Histologically, trypanosome amastigotes morphologically similar to Trypanosoma cruzi, the agent of Chagas disease in humans and dogs, were sporadically detected within segments of the thoracic spinal cord surrounded by mild lymphoplasmacytic inflammation. Ancillary testing for Sarcocystis neurona, Neospora spp., Toxoplasma gondii and Leishmania spp. was negative. Conventional and real time polymerase chain reaction (PCR) of affected paraffin embedded spinal cord were positive for T. cruzi, and sequencing of the amplified T. cruzi satellite DNA PCR fragment from the horse was homologous with various clones of T. cruzi in GenBank. While canine Chagas disease cases have been widely reported in southern Texas, this is the first report of clinical T. cruzi infection in an equid with demonstrable amastigotes in the spinal cord. In contrast to previous instances of Chagas disease in the central nervous system (CNS) of dogs and humans, no inflammation or T. cruzi amastigotes were detected in the heart of the horse. Based on clinical signs, there is a potential for misdiagnosis of Chagas disease with other infectious diseases that affect the equine CNS. T. cruzi should be considered as a differential diagnosis in horses with neurologic clinical signs and histologic evidence of meningomyelitis that originate in areas where Chagas disease is present. The prevalence of T. cruzi in horses and the role of equids in the parasite life cycle require further study. Copyright © 2015 Elsevier B.V. All rights reserved.

Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress.

PubMed

Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang

2014-11-18

Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.

Divergent Astrovirus Associated with Neurologic Disease in Cattle

PubMed Central

Li, Linlin; Diab, Santiago; McGraw, Sabrina; Barr, Bradd; Traslavina, Ryan; Higgins, Robert; Talbot, Tom; Blanchard, Pat; Rimoldi, Guillermo; Fahsbender, Elizabeth; Page, Brady; Phan, Tung Gia; Wang, Chunlin; Deng, Xutao; Delwart, Eric

2013-01-01

Using viral metagenomics of brain tissue from a young adult crossbreed steer with acute onset of neurologic disease, we sequenced the complete genome of a novel astrovirus (BoAstV-NeuroS1) that was phylogenetically related to an ovine astrovirus. In a retrospective analysis of 32 cases of bovine encephalitides of unknown etiology, 3 other infected animals were detected by using PCR and in situ hybridization for viral RNA. Viral RNA was restricted to the nervous system and detected in the cytoplasm of affected neurons within the spinal cord, brainstem, and cerebellum. Microscopically, the lesions were of widespread neuronal necrosis, microgliosis, and perivascular cuffing preferentially distributed in gray matter and most severe in the cerebellum and brainstem, with increasing intensity caudally down the spinal cord. These results suggest that infection with BoAstV-NeuroS1 is a potential cause of neurologic disease in cattle. PMID:23965613

Neurological and cardiac complications in a cohort of children with end-stage renal disease.

PubMed

Albaramki, Jumana H; Al-Ammouri, Iyad A; Akl, Kamal F

2016-05-01

Adult patients with chronic kidney disease are at risk of major neurologic and cardiac complications. The purpose of this study is to review the neurological and cardiac complications in children with end-stage renal disease (ESRD). A retrospective review of medical records of children with ESRD at Jordan University Hospital was performed. All neurological and cardiac events were recorded and analyzed. Data of a total of 68 children with ESRD presenting between 2002 and 2013 were reviewed. Neurological complications occurred in 32.4%; seizures were the most common event. Uncontrolled hypertension was the leading cause of neurological events. Cardiac complications occurred in 39.7%, the most common being pericardial effusion. Mortality from neurological complications was 45%. Neurological and cardiac complications occurred in around a third of children with ESRD with a high mortality rate. More effective control of hypertension, anemia, and intensive and gentle dialysis are needed.

Granins as disease-biomarkers: translational potential for psychiatric and neurological disorders.

PubMed

Bartolomucci, A; Pasinetti, G M; Salton, S R J

2010-09-29

The identification of biomarkers represents a fundamental medical advance that can lead to an improved understanding of disease pathogenesis, and holds the potential to define surrogate diagnostic and prognostic endpoints. Because of the inherent difficulties in assessing brain function in patients and objectively identifying neurological and cognitive/emotional symptoms, future application of biomarkers to neurological and psychiatric disorders is extremely desirable. This article discusses the biomarker potential of the granin family, a group of acidic proteins present in the secretory granules of a wide variety of endocrine, neuronal and neuroendocrine cells: chromogranin A (CgA), CgB, Secretogranin II (SgII), SgIII, HISL-19 antigen, 7B2, NESP55, VGF and ProSAAS. Their relative abundance, functional significance, and secretion into the cerebrospinal fluid (CSF), saliva, and the general circulation have made granins tractable targets as biomarkers for many diseases of neuronal and endocrine origin, recently impacting diagnosis of a number of neurological and psychiatric disorders including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, frontotemporal dementia, and schizophrenia. Although research has not yet validated the clinical utility of granins as surrogate endpoints for the progression or treatment of neurological or psychiatric disease, a growing body of experimental evidence indicates that the use of granins as biomarkers might be of great potential clinical interest. Advances that further elucidate the mechanism(s) of action of granins, coupled with improvements in biomarker technology and direct clinical application, should increase the translational effectiveness of this family of proteins in disease diagnosis and drug discovery. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease.

PubMed Central

Urnovitz, H B; Murphy, W H

1996-01-01

Retroviral diagnostics have become standard in human laboratory medicine. While current emphasis is placed on the human exogenous viruses (human immunodeficiency virus and human T-cell leukemia virus), evidence implicating human endogenous retroviruses (HERVs) in various human disease entities continues to mount. Literature on the occurrence of HERVs in human tissues and cells was analyzed. Substantial evidence documents that retrovirus particles were clearly demonstrable in various tissues and cells in both health and disease and were abundant in the placenta and that their occurrence could be implicated in some of the reproductive diseases. The characteristics of HERVs are summarized, mechanisms of replication and regulation are outlined, and the consistent hormonal responsiveness of HERVs is noted. Clear evidence implicating HERV gene products as participants in glomerulonephritis in some cases of systemic lupus erythematosus is adduced. Data implicating HERVs as etiologic factors in reproductive diseases, in some of the autoimmune diseases, in some forms of rheumatoid arthritis and connective tissue disease, in psoriasis, and in some of the inflammatory neurologic diseases are reviewed. The current major needs are to improve methods for HERV detection, to identify the most appropriate HERV prototypes, and to develop diagnostic reagents so that the putative biologic and pathologic roles of HERVs can be better evaluated. PMID:8665478

Risk of neurological diseases among survivors of electric shocks: a nationwide cohort study, Denmark, 1968-2008.

PubMed

Grell, Kathrine; Meersohn, Andrea; Schüz, Joachim; Johansen, Christoffer

2012-09-01

Several studies suggest a link between electric injuries and neurological diseases, where electric shocks may explain elevated risks for neuronal degeneration and, subsequently, neurological diseases. We conducted a retrospective cohort study on the risk of neurological diseases among people in Denmark who had survived an electric accident in 1968-2008. The cohort included 3,133 people and occurrences of neurological diseases were determined by linkage to the nationwide population-based Danish National Register of Patients. The numbers of cases observed at first hospital contact in the cohort were compared with the respective rates of first hospital contacts for neurological diseases in the general population. We observed significantly increased risks for peripheral nerve diseases (standardized hospitalization ratio (SHR), 1.66; 95% confidence interval (CI), 1.22-2.22), for migraine (SHR, 1.80; 95% CI, 1.23-2.54), for vertigo (SHR, 1.60; 95% CI, 1.22-2.05), and for epilepsy (SHR, 1.45; 95% CI, 1.11-1.85). Only small numbers of cases of other neurological diseases were found, making the risk estimates unstable. These findings suggest an association between a single electric shock and increased risks for peripheral nerve diseases, migraines, vertigo, and epilepsy, but confirmation of these observations is needed. Copyright © 2012 Wiley Periodicals, Inc.

Trophic factors in neurologic disease.

PubMed

Stewart, S S; Appel, S H

1988-01-01

Recent studies suggest that diffusible factors released by neural targets enhance the survival, growth, and differentiation of neurons both peripherally and in the central nervous system. Evidence for such trophic factors exists for many of the neural systems involved in the degenerative neurologic diseases Alzheimer's disease, parkinsonism, and amyotrophic lateral sclerosis. It is our hypothesis that for each of these disorders there is both a primary insult and a secondary effect. The primary insult may have multiple etiologies, but the secondary effect is the result of retrograde degeneration. Such retrograde degeneration occurs because of an impairment of trophic factor function or an inadequacy of trophic effects to keep pace with the primary destructive process. Accordingly, it may be possible to exploit such trophic mechanisms to define further the pathobiology of neural degeneration and to develop specific treatments for currently incurable illnesses.

Neurologic features of chronic Minamata disease (organic mercury poisoning) certified at autopsy.

PubMed

Uchino, M; Okajima, T; Eto, K; Kumamoto, T; Mishima, I; Ando, M

1995-08-01

To better understand the neurologic events related to chronic Minamata disease (organic mercury poisoning), we studied data from 77 patients with Minamata disease as certified at autopsies performed from 1976 to 1994 (mean age: 72.3 years). Major neurologic findings included: sensory impairment in 80.5% of the patients which was limited to the extremities in 42.9%. Impairment of lower extremity coordination was present in 35.8% of the patients, constriction of the visual fields in 28.8%, and retrocochlear hearing loss in 15.3%. There was no correlation between the degree of cerebellar incoordination and the methylmercury concentration in the cerebellum. Compared with the classic type of Minamata disease, the incidence of major neurologic findings was markedly decreased. In light of these findings, supplemental examinations including brain computed tomography (CT), magnetic resonance imaging (MRI), short latency somatosensory evoked potential (SSEP), or tremogram may be necessary to clinically diagnose Minamata disease, especially in atypical or mild cases.

Development of neurologic diseases in a patient with primate T lymphotropic virus type 1 (PTLV-1).

PubMed

Enose-Akahata, Yoshimi; Caruso, Breanna; Haner, Benjamin; Charlip, Emily; Nair, Govind; Massoud, Raya; Billioux, Bridgette J; Ohayon, Joan; Switzer, William M; Jacobson, Steven

2016-08-12

Virus transmission from various wild and domestic animals contributes to an increased risk of emerging infectious diseases in human populations. HTLV-1 is a human retrovirus associated with acute T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 originated from ancient zoonotic transmission from nonhuman primates, although cases of zoonotic infections continue to occur. Similar to HTLV-1, the simian counterpart, STLV-1, causes chronic infection and leukemia and lymphoma in naturally infected monkeys, and combined are called primate T-lymphotropic viruses (PTLV-1). However, other clinical syndromes typically seen in humans such as a chronic progressive myelopathy have not been observed in nonhuman primates. Little is known about the development of neurologic and inflammatory diseases in human populations infected with STLV-1-like viruses following nonhuman primate exposure. We performed detailed laboratory analyses on an HTLV-1 seropositive patient with typical HAM/TSP who was born in Liberia and now resides in the United States. Using a novel droplet digital PCR for the detection of the HTLV-1 tax gene, the proviral load in PBMC and cerebrospinal fluid cells was 12.98 and 51.68 %, respectively; however, we observed a distinct difference in fluorescence amplitude of the positive droplet population suggesting possible mutations in proviral DNA. A complete PTLV-1 proviral genome was amplified from the patient's PBMC DNA using an overlapping PCR strategy. Phylogenetic analysis of the envelope and LTR sequences showed the virus was highly related to PTLV-1 from sooty mangabey monkeys (smm) and humans exposed via nonhuman primates in West Africa. These results demonstrate the patient is infected with a simian variant of PTLV-1, suggesting for the first time that PTLV-1smm infection in humans may be associated with a chronic progressive neurologic disease.

Discussions about treatment restrictions in chronic neurologic diseases: a structured review.

PubMed

Seeber, Antje A; Hijdra, Albert; Vermeulen, Marinus; Willems, Dick L

2012-02-21

Many incurable neurologic diseases have predictable complications during their course or at their end stage. Timely discussions of potential treatment restrictions may improve the quality of treatment decisions toward the end of life. What is known about the actual practice of these discussions? We performed a literature search in MEDLINE, EMBASE, and CINAHL for empirical studies about discussions and decisions to restrict treatment in the course of 6 conditions: motor neuron disease (amyotrophic lateral sclerosis [ALS]), primary malignant brain tumors, multiple sclerosis, stroke, Parkinson disease, and dementia (Alzheimer disease). In 10 of 43 studies, the actual practice of decision-making was studied; in the remaining 33, caregivers were interviewed about this practice. Three scenarios were described: 1) acute devastating disease (severe stroke); 2) stable severe neurologic deficit with complications (poststroke brain damage); and 3) chronic progressive disease with complications (dementia and ALS). We found no studies concerning the other conditions. In all 3 scenarios, discussions and decisions seemed to be mostly triggered by the occurrence of life-threatening situations, either caused by the disease itself (1), or complications (2 and 3, including many patients with ALS). Some ALS studies showed that timely discussion of treatment options improved end-of-life decision-making. The actual practice of discussions about treatment restrictions in chronic neurologic disease has hardly been studied. The currently available empirical data suggest that discussions are mainly triggered by life-threatening situations, whereas anticipation of such situations may be beneficial for patients and their families.

Retinitis pigmentosa, pigmentary retinopathies, and neurologic diseases.

PubMed

Bhatti, M Tariq

2006-09-01

Retinitis pigmentosa (RP) refers to a group of inherited retinal diseases with phenotypic and genetic heterogeneity. The pathophysiologic basis of the progressive visual loss in patients with RP is not completely understood but is felt to be due to a primary retinal photoreceptor cell degenerative process mainly affecting the rods of the peripheral retina. In most cases RP is seen in isolation (nonsyndromic), but in some other cases it may be a part of a genetic, metabolic, or neurologic syndrome or disorder. Nyctalopia, or night blindness, is the most common symptom of RP. The classic fundus appearance of RP includes retinal pigment epithelial cell changes resulting in retinal hypo- or hyperpigmentation ("salt-and-pepper"), retinal granularity, and bone spicule formation. The retinal vessels are often narrowed or attenuated and there is a waxy pallor appearance of the optic nerve head. Electroretinography will demonstrate rod and cone photoreceptor cell dysfunction and is a helpful test in the diagnosis and monitoring of patients with RP. A detailed history with pedigree analysis, a complete ocular examination, and the appropriate paraclinical testing should be performed in patients complaining of visual difficulties at night or in dim light. This review discusses the clinical manifestations of RP as well as describing the various systemic diseases, with a special emphasis on neurologic diseases, associated with a pigmentary retinopathy.

First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features

PubMed Central

Spencer, Michael D; Knight, Richard S G; Will, Robert G

2002-01-01

Objective To describe the early psychiatric and neurological features of variant Creutzfeldt-Jakob disease. Design Cohort study. Setting National surveillance system for Creutzfeldt-Jakob disease in the United Kingdom. Participants The first 100 cases of variant Creutzfeldt-Jakob disease identified in the United Kingdom. Main outcome measures The timing and nature of early psychiatric and neurological symptoms in variant Creutzfeldt-Jakob disease. Results The early stages of variant Creutzfeldt-Jakob disease are dominated by psychiatric symptoms, but neurological symptoms precede psychiatric symptoms in 15% of cases and are present in combination with psychiatric symptoms in 22% of cases from the onset of disease. Common early psychiatric features include dysphoria, withdrawal, anxiety, insomnia, and loss of interest. No common early neurological features exist, but a significant proportion of patients do exhibit neurological symptoms within 4 months of clinical onset, including poor memory, pain, sensory symptoms, unsteadiness of gait, and dysarthria. Conclusions Although the diagnosis of variant Creutzfeldt-Jakob disease may be impossible in the early stages of the illness, particular combinations of psychiatric and neurological features may allow early diagnosis in an appreciable proportion of patients. What is already known on this topicThe early stages of variant Creutzfeldt-Jakob disease are dominated by psychiatric symptomatologySome patients have early neurological features that might suggest the presence of an underlying neurological disorderWhat this study addsThis study provides a comprehensive description of the evolution of psychiatric and neurological features in variant Creutzfeldt-Jakob diseaseAn appreciable proportion of patients have early neurological symptomsA high proportion of patients have a combination of psychiatric and neurological features within four months of clinical onset that suggest the diagnosis of variant Creutzfeldt-Jakob disease

Minds on replay: musical hallucinations and their relationship to neurological disease.

PubMed

Golden, Erin C; Josephs, Keith A

2015-12-01

The phenomenon of musical hallucinations, in which individuals perceive music in the absence of an external auditory stimulus, has been described sparingly in the literature through small case reports and series. Musical hallucinations have been linked to multiple associated conditions, including psychiatric and neurologic disease, brain lesions, drug effect, and hearing impairment. This study aimed to review the demographics of subjects with musical hallucinations and to determine the prevalence of neurological disorders, particularly neurodegenerative disease. Through the Mayo medical record, 393 subjects with musical hallucinations were identified and divided into five categories based on comorbid conditions that have been associated with musical hallucinations: neurological, psychiatric, structural, drug effect and not otherwise classifiable. Variables, including hearing impairment and the presence of visual and other auditory hallucinations, were evaluated independently in all five groups. The mean age at onset of the hallucinations was 56 years, ranging from 18 to 98 years, and 65.4% of the subjects were female. Neurological disease and focal brain lesions were found in 25% and 9% of the total subjects, respectively. Sixty-five subjects were identified with a neurodegenerative disorder, with the Lewy body disorders being the most common. Visual hallucinations were more common in the group with neurological disease compared to the psychiatric, structural, and not otherwise classifiable groups (P < 0.001), whereas auditory hallucinations were more common in the psychiatric group compared to all other groups (P < 0.001). Structural lesions associated with musical hallucinations involved both hemispheres with a preference towards the left, and all but two included the temporal lobe. Hearing impairment was common, particularly in the not otherwise classifiable category where 67.2% had documented hearing impairment, more than in any other group (P < 0.001). Those

Quality improvement in neurology: AAN Parkinson disease quality measures

PubMed Central

Cheng, E.M.; Tonn, S.; Swain-Eng, R.; Factor, S.A.; Weiner, W.J.; Bever, C.T.

2010-01-01

Background: Measuring the quality of health care is a fundamental step toward improving health care and is increasingly used in pay-for-performance initiatives and maintenance of certification requirements. Measure development to date has focused on primary care and common conditions such as diabetes; thus, the number of measures that apply to neurologic care is limited. The American Academy of Neurology (AAN) identified the need for neurologists to develop measures of neurologic care and to establish a process to accomplish this. Objective: To adapt and test the feasibility of a process for independent development by the AAN of measures for neurologic conditions for national measurement programs. Methods: A process that has been used nationally for measure development was adapted for use by the AAN. Topics for measure development are chosen based upon national priorities, available evidence base from a systematic literature search, gaps in care, and the potential impact for quality improvement. A panel composed of subject matter and measure development methodology experts oversees the development of the measures. Recommendation statements and their corresponding level of evidence are reviewed and considered for development into draft candidate measures. The candidate measures are refined by the expert panel during a 30-day public comment period and by review by the American Medical Association for Current Procedural Terminology (CPT) II codes. All final AAN measures are approved by the AAN Board of Directors. Results: Parkinson disease (PD) was chosen for measure development. A review of the medical literature identified 258 relevant recommendation statements. A 28-member panel approved 10 quality measures for PD that included full specifications and CPT II codes. Conclusion: The AAN has adapted a measure development process that is suitable for national measurement programs and has demonstrated its capability to independently develop quality measures. GLOSSARY

The progression of coeliac disease: its neurological and psychiatric implications.

PubMed

Campagna, Giovanna; Pesce, Mirko; Tatangelo, Raffaella; Rizzuto, Alessia; La Fratta, Irene; Grilli, Alfredo

2017-06-01

The aim of the paper is to show the various neurological and psychiatric symptoms in coeliac disease (CD). CD is a T cell-mediated, tissue-specific autoimmune disease which affects genetically susceptible individuals after dietary exposure to proline- and glutamine-rich proteins contained in certain cereal grains. Genetics, environmental factors and different immune systems, together with the presence of auto-antigens, are taken into account when identifying the pathogenesis of CD. CD pathogenesis is related to immune dysregulation, which involves the gastrointestinal system, and the extra-intestinal systems such as the nervous system, whose neurological symptoms are evidenced in CD patients. A gluten-free diet (GFD) could avoid cerebellar ataxia, epilepsy, neuropathies, migraine and mild cognitive impairment. Furthermore, untreated CD patients have more symptoms and psychiatric co-morbidities than those treated with a GFD. Common psychiatric symptoms in untreated CD adult patients include depression, apathy, anxiety, and irritability and schizophrenia is also common in untreated CD. Several studies show improvement in psychiatric symptoms after the start of a GFD. The present review discusses the state of the art regarding neurological and psychiatric complications in CD and highlights the evidence supporting a role for GFD in reducing neurological and psychiatric complications.

Unintended Effects of Orphan Product Designation for Rare Neurological Diseases

PubMed Central

Murphy, Sinéad M; Puwanant, Araya; Griggs, Robert C.

2012-01-01

Since the introduction of the Orphan Drug Act in 1983, designed to promote development of treatments for rare diseases, at least 378 orphan drugs have been approved. Incentives include financial support, tax credits and, perhaps most importantly, extended market exclusivity. These incentives have encouraged industry interest and accelerated research on rare diseases, allowing patients with orphan diseases access to treatments. However, extended market exclusivity has been associated with unacceptably high drug costs; both for newly developed drugs and even for drugs which were previously widely available. We suggest that a paradoxical effect of orphan product exclusivity can be reduced patient access to existing drugs. In addition, the costs of each new drug are arguably unsustainable for patients and for the American health care system. Of all the specialties, neurology has the third highest number of orphan product designations, and neurological diseases account for at least one fifth of rare diseases. Citing the use of tetrabenazine for chorea in Huntington’s disease, adrenocorticotropic hormone for infantile spasms and enzyme replacement therapy with alglucosidase alpha for Pompe’s disease we highlight these paradoxical effects. PMID:23109143

Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress

PubMed Central

ZHANG, Xiao-Liang; PANG, Wei; HU, Xin-Tian; LI, Jia-Li; YAO, Yong-Gang; ZHENG, Yong-Tang

2014-01-01

Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China’s growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China’s life sciences and pharmaceutical industry, and enhance China’s position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China. PMID:25465081

[Neurology in medieval regimina sanitatis].

PubMed

de Frutos González, V; Guerrero Peral, A L

2011-09-01

In medical medieval literature some works about dietetics stand out. Dietetics, as a separate branch of medicine, includes not only food or drinks, but other environmental factors influencing on health. They are known as regimina sanitatis or salutis, and specially developed in the Christian west. They generally consisted of a balance between the Galenic "six non-natural things"; factors regulating health and its protection: environment, exercise, food, sleep, bowel movements and emotions. After reviewing the sources and defining the different stages of this genre, we have considered three of the most out-standing medieval regimina, the anonymous Regimen sanitatis salernitanum, Arnaldo de Vilanova's Regimen sanitatis ad regem aragonum and Bernardo de Gordon's Tractatus of conservatione vite humane. In them we review references to neurological disease. Though not independently considered, there is a significant presence of neurological diseases in the regimina. Dietetics measures are proposed to preserve memory, nerves, or hearing, as well as for the treatment of migraine, epilepsy, stroke or dizziness. Regimina are quiet representative among medical medieval literature, and they show medieval physicians vision of neurological diseases. Dietetics was considered useful to preserve health, and therapeutics was based on natural remedies. 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Neurological Diseases, Disorders and Injuries in Canada: Highlights of a National Study.

PubMed

Bray, Garth M; Huggett, Deanna L

2016-01-01

The National Population Health Study of Neurological Conditions, a partnership between Neurological Health Charities Canada and the Government of Canada, was the largest study of neurological diseases, disorders, and injuries ever conducted in Canada. Undertaken between 2009 and 2013, the expansive program of research addressed the epidemiology, impacts, health services, and risk factors of 18 neurological conditions and estimated the health outcomes and costs of these conditions in Canada through 2031. This review summarizes highlights from the component projects of the study as presented in the synthesis report, Mapping Connections: An Understanding of Neurological Conditions in Canada. The key findings included new prevalence and incidence estimates, documentation of the diverse and often debilitating effects of neurological conditions, and identification of the utilization, economic costs, and current limitations of related health services. The study findings will support health charities, governments, and other stakeholders to reduce the impact of neurological conditions in Canada.

K-Cl cotransporters, cell volume homeostasis, and neurological disease

PubMed Central

Kahle, Kristopher T.; Khanna, Arjun R.; Alper, Seth L.; Adragna, Norma C.; Lauf, Peter K.; Sun, Dandan; Delpire, Eric

2016-01-01

K+-Cl− cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. PMID:26142773

K-Cl cotransporters, cell volume homeostasis, and neurological disease.

PubMed

Kahle, Kristopher T; Khanna, Arjun R; Alper, Seth L; Adragna, Norma C; Lauf, Peter K; Sun, Dandan; Delpire, Eric

2015-08-01

K(+)-Cl(-) cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Preoperative Neurological Evaluation

PubMed Central

Probasco, John; Sahin, Bogachan; Tran, Tung; Chung, Tae Hwan; Rosenthal, Liana Shapiro; Mari, Zoltan; Levy, Michael

2013-01-01

Neurological diseases are prevalent in the general population, and the neurohospitalist has an important role to play in the preoperative planning for patients with and at risk for developing neurological disease. The neurohospitalist can provide patients and their families as well as anesthesiologists, surgeons, hospitalists, and other providers guidance in particular to the patient’s neurological disease and those he or she is at risk for. Here we present considerations and guidance for the neurohospitalist providing preoperative consultation for the neurological patient with or at risk of disturbances of consciousness, cerebrovascular and carotid disease, epilepsy, neuromuscular disease, and Parkinson disease. PMID:24198903

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.

Bioactivation of cyanide to cyanate in sulfur amino acid deficiency: relevance to neurological disease in humans subsisting on cassava.

PubMed

Tor-Agbidye, J; Palmer, V S; Lasarev, M R; Craig, A M; Blythe, L L; Sabri, M I; Spencer, P S

1999-08-01

Neurological disorders have been reported from parts of Africa with protein-deficient populations and attributed to cyanide (CN-) exposure from prolonged dietary use of cassava, a cyanophoric plant. Cyanide is normally metabolized to thiocyanate (SCN-) by the sulfur-dependent enzyme rhodanese. However, in protein-deficient subjects where sulfur amino acids (SAA) are low, CN may conceivably be converted to cyanate (OCN-), which is known to cause neurodegenerative disease in humans and animals. This study investigates the fate of potassium cyanide administered orally to rats maintained for up to 4 weeks on either a balanced diet (BD) or a diet lacking the SAAs, L-cystine and L-methionine. In both groups, there was a time-dependent increase in plasma cyanate, with exponential OCN- increases in SAA-deficient rats. A strongly positive linear relationship between blood CN- and plasma OCN- concentrations was observed in these animals. These data are consistent with the hypothesis that cyanate is an important mediator of chronic cyanide neurotoxicity during protein-calorie deficiency. The potential role of thiocyanate in cassava-associated konzo is discussed in relationship to the etiology of the comparable pattern of motor-system disease (spastic paraparesis) seen in lathyrism.

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.

Intraindividual variability as a marker of neurological dysfunction: a comparison of Alzheimer's disease and Parkinson's disease.

PubMed

Burton, Catherine L; Strauss, Esther; Hultsch, David F; Moll, Alex; Hunter, Michael A

2006-01-01

Individuals with certain neurological conditions may demonstrate greater inconsistency (i.e., intraindividual variability) on cognitive tasks compared to healthy controls. Several researchers have suggested that intraindividual variability may be a behavioral marker of compromised neurobiological mechanisms associated with aging, disease, or injury. The present study sought to investigate whether intraindividual variability is associated with general nervous system compromise, or rather, with certain types of neurological disturbances by comparing healthy adults, adults with Alzheimer's disease (AD), and Parkinson's disease (PD). Participants were assessed on four separate occasions using measures of reaction time and memory. Results indicated that inconsistency was correlated with indices of severity of impairment suggesting a dose-response relationship between cognitive disturbance and intraindividual variability: the more severe the cognitive disturbance, the greater the inconsistency. However, participants with AD were more inconsistent than those with PD, with both groups being more variable than the healthy group, even when controlling for group differences in overall severity of cognitive impairment or cognitive decline. Consequently, intraindividual variability may index both the severity of cognitive impairment and the nature of the neurological disturbance.

Infection of immunodeficient horses with Sarcocystis neurona does not result in neurologic disease.

PubMed

Sellon, Debra C; Knowles, Donald P; Greiner, Ellis C; Long, Maureen T; Hines, Melissa T; Hochstatter, Tressa; Tibary, Ahmed; Dame, John B

2004-11-01

Equine protozoal myeloencephalitis is a progressive neurologic disease of horses most commonly caused by infection with the apicomplexan parasite Sarcocystis neurona. Factors affecting neuroinvasion and neurovirulence have not been determined. We investigated the pathogenesis of infection with S. neurona in horses with severe combined immune deficiency (SCID). Two immunocompetent (IC) Arabian horses and two Arabian horses with SCID were infected orally with 5 x 10(5) sporocysts of S. neurona. Four IC horses and one SCID horse were infected intravenously (i.v.) with 5 x 10(8) merozoites of the WSU-1 isolate of S. neurona. Despite prolonged parasitemia and persistent infection of visceral tissues (skeletal muscle, cardiac muscle, lung, liver, and spleen) as demonstrated by PCR and culture, SCID horses did not develop neurologic signs after oral or i.v. infection. S. neurona was undetectable in the neuronal tissues of SCID horses by either PCR, immunohistochemistry, or culture. In contrast, although parasitemia was undetectable in orally infected IC horses and of only short duration in i.v. infected IC horses, four of six IC horses developed neurologic signs. S. neurona was detectable by PCR and/or culture of neural tissue but not visceral tissue of IC horses with neurologic disease. Infected SCID horses are unable to clear S. neurona from visceral tissues, but the infection does not result in neurologic signs; in contrast, IC horses rapidly control parasitemia and infection of visceral tissues but frequently experience neuroinvasion and exhibit clinical signs of neurologic disease.

Infection of Immunodeficient Horses with Sarcocystis neurona Does Not Result in Neurologic Disease

PubMed Central

Sellon, Debra C.; Knowles, Donald P.; Greiner, Ellis C.; Long, Maureen T.; Hines, Melissa T.; Hochstatter, Tressa; Tibary, Ahmed; Dame, John B.

2004-01-01

Equine protozoal myeloencephalitis is a progressive neurologic disease of horses most commonly caused by infection with the apicomplexan parasite Sarcocystis neurona. Factors affecting neuroinvasion and neurovirulence have not been determined. We investigated the pathogenesis of infection with S. neurona in horses with severe combined immune deficiency (SCID). Two immunocompetent (IC) Arabian horses and two Arabian horses with SCID were infected orally with 5 × 105 sporocysts of S. neurona. Four IC horses and one SCID horse were infected intravenously (i.v.) with 5 × 108 merozoites of the WSU-1 isolate of S. neurona. Despite prolonged parasitemia and persistent infection of visceral tissues (skeletal muscle, cardiac muscle, lung, liver, and spleen) as demonstrated by PCR and culture, SCID horses did not develop neurologic signs after oral or i.v. infection. S. neurona was undetectable in the neuronal tissues of SCID horses by either PCR, immunohistochemistry, or culture. In contrast, although parasitemia was undetectable in orally infected IC horses and of only short duration in i.v. infected IC horses, four of six IC horses developed neurologic signs. S. neurona was detectable by PCR and/or culture of neural tissue but not visceral tissue of IC horses with neurologic disease. Infected SCID horses are unable to clear S. neurona from visceral tissues, but the infection does not result in neurologic signs; in contrast, IC horses rapidly control parasitemia and infection of visceral tissues but frequently experience neuroinvasion and exhibit clinical signs of neurologic disease. PMID:15539518

Human West Nile Virus Disease Outbreak in Pakistan, 2015-2016.

PubMed

Khan, Erum; Barr, Kelli L; Farooqi, Joveria Qais; Prakoso, Dhani; Abbas, Alizae; Khan, Zain Y; Ashi, Shanze; Imtiaz, Kehkashan; Aziz, Z; Malik, Faisal; Lednicky, John A; Long, Maureen T

2018-01-01

Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological disease in human patients in this country. Of 997 enrolled patients presenting with clinical features suggestive of arboviral disease, 105 were positive for WNV IgM antibodies, and 71 of these patients possessed WNV-specific neutralizing antibodies. Cross-reactivity of WNV IgM antibodies with Japanese encephalitis virus (JEV) occurred in 75 of these 105 patients. WNV co-infections with Dengue viruses were not a contributing factor for the severity of disease. Nor did prior exposure to dengue virus contribute to incidence of neurological involvement in WNV-infected patients. Patients with WNV infections were more likely to present with altered mental status, seizures, and reduced Glasgow Coma scores when compared with JEV-infected patients. Human WNV cases and vector numbers exhibited a temporal correlation with climate.

Genital herpes simplex virus type 2 infection in humanized HIV-transgenic mice triggers HIV shedding and is associated with greater neurological disease.

PubMed

Nixon, Briana; Fakioglu, Esra; Stefanidou, Martha; Wang, Yanhua; Dutta, Monica; Goldstein, Harris; Herold, Betsy C

2014-02-15

Epidemiological studies consistently demonstrate synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1). Higher HIV-1 loads are observed in coinfected individuals, and conversely, HIV-1 is associated with more-severe herpetic disease. A small animal model of coinfection would facilitate identification of the biological mechanisms underlying this synergy and provide the opportunity to evaluate interventions. Mice transgenic for HIV-1 provirus and human cyclin T1 under the control of a CD4 promoter (JR-CSF/hu-cycT1) were intravaginally infected with HSV-2 and evaluated for disease progression, HIV shedding, and mucosal immune responses. HSV-2 infection resulted in higher vaginal HIV loads and genital tissue expression of HIV RNA, compared with HSV-uninfected JR-CSF/hu-cycT1 mice. There was an increase in genital tract inflammatory cells, cytokines, chemokines, and interferons in response to HSV-2, although the kinetics of the response were delayed in HIV-transgenic, compared with control mice. Moreover, the JR-CSF/hu-cycT1 mice exhibited earlier and more-severe neurological disease. The latter was associated with downregulation of secretory leukocyte protease inhibitor expression in neuronal tissue, a molecule with antiinflammatory, antiviral, and neuroprotective properties. JR-CSF/hu-cycT1 mice provide a valuable model to study HIV/HSV-2 coinfection and identify potential mechanisms by which HSV-2 facilitates HIV-1 transmission and HIV modulates HSV-2-mediated disease.

The CJD Neurological Status Scale: A New Tool for Evaluation of Disease Severity and Progression in Creutzfeldt - Jakob disease

PubMed Central

Cohen, Oren S.; Prohovnik, Isak; Korczyn, Amos D.; Ephraty, Lilach; Nitsan, Zeev; Tsabari, Rakefet; Appel, Shmuel; Rosenmann, Hanna; Kahana, Ester; Chapman, Joab

2011-01-01

Objectives To develop a scale sensitive for the neurological manifestations of Creutzfeldt-Jakob disease (CJD). Methods A 26-item CJD neurological status scale (CJD-NS) was created based on characteristic disease manifestations. Each sign was assigned to one of eight neurological systems to calculate a total scale score (TSS) and a system involvement score (SIS). The scale was administered to 37 CJD patients, 101 healthy first-degree relatives of the patients and 14 elderly patients with Parkinson's disease (PD). Results The mean TSS (±SD) was significantly higher in patients with CJD (13.19±5.63) compared to normal controls (0.41±0.78) and PD patients (9.71±3.05). The mean SIS was also significantly different between the CJD (5.19±1.22) and PD (2.78±1.18 p<0.01) groups reflecting the disseminated nature of neurological involvement in CJD. Using a cutoff of TSS>4 yielded a sensitivity of 97% for CJD, and specificity of 100% against healthy controls. All individual items showed excellent specificity against healthy subjects, but sensitivity was highly variable. Repeat assessments of CJD patients over 3-9 months revealed a time-dependent increase of both the TSS and the SIS reflecting the scale's ability to track disease progression. Conclusions The CJD-NS scale is sensitive to neurological signs and their progression in CJD patients. PMID:21303352

Clinical Characteristics and Functional Motor Outcomes of Enterovirus 71 Neurological Disease in Children.

PubMed

Teoh, Hooi-Ling; Mohammad, Shekeeb S; Britton, Philip N; Kandula, Tejaswi; Lorentzos, Michelle S; Booy, Robert; Jones, Cheryl A; Rawlinson, William; Ramachandran, Vidiya; Rodriguez, Michael L; Andrews, P Ian; Dale, Russell C; Farrar, Michelle A; Sampaio, Hugo

2016-03-01

Enterovirus 71 (EV71) causes a spectrum of neurological complications with significant morbidity and mortality. Further understanding of the characteristics of EV71-related neurological disease, factors related to outcome, and potential responsiveness to treatments is important in developing therapeutic guidelines. To further characterize EV71-related neurological disease and neurological outcome in children. Prospective 2-hospital (The Sydney Children's Hospitals Network) inpatient study of 61 children with enterovirus-related neurological disease during a 2013 outbreak of EV71 in Sydney, Australia. The dates of our analysis were January 1, to June 30, 2013. Clinical, neuroimaging, laboratory, and pathological characteristics, together with treatment administered and functional motor outcomes, were assessed. Among 61 patients, there were 4 precipitous deaths (7%), despite resuscitation at presentation. Among 57 surviving patients, the age range was 0.3 to 5.2 years (median age, 1.5 years), and 36 (63%) were male. Fever (100% [57 of 57]), myoclonic jerks (86% [49 of 57]), ataxia (54% [29 of 54]), and vomiting (54% [29 of 54]) were common initial clinical manifestations. In 57 surviving patients, EV71 neurological disease included encephalomyelitis in 23 (40%), brainstem encephalitis in 20 (35%), encephalitis in 6 (11%), acute flaccid paralysis in 4 (7%), and autonomic dysregulation with pulmonary edema in 4 (7%). Enterovirus RNA was more commonly identified in feces (42 of 44 [95%]), rectal swabs (35 of 37 [95%]), and throat swabs (33 of 39 [85%]) rather than in cerebrospinal fluid (10 of 41 [24%]). Magnetic resonance imaging revealed characteristic increased T2-weighted signal in the dorsal pons and spinal cord. All 4 patients with pulmonary edema (severe disease) demonstrated dorsal brainstem restricted diffusion (odds ratio, 2; 95% CI, 1-4; P = .001). Brainstem or motor dysfunction had resolved in 44 of 57 (77%) at 2 months and in 51 of 57 (90%) at 12 months

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.

Clinical neurologic indices of toxicity in animals.

PubMed Central

O'Donoghue, J L

1996-01-01

The fundamental structures and functions of the nervous systems of animals and humans are conserved in many ways across species. These similarities provide a basis for developing common neurologic examinations for a number of species of animals and also provide a basis for developing risk assessments across species for neurologic end points. The neurologic examination requires no expensive equipment and can be conducted in the field or wherever impaired animals are identified. The proper conduct of neurologic examinations in animals assumes that the examiner has a fundamental understanding of the normal structure and function of the nervous system as well as knowledge about the spontaneous disease background of the species being studied. PMID:9182039

[Today and tomorrow in child neurology at a neurological clinic for children--the importance of child neurology as the life-long neurology].

PubMed

Nomura, Yoshiko

2005-05-01

Segawa Neurological Clinic for Children was founded in 1973, and specializes in neurological disorders that start in childhood. In thirty-one years since the foundation, about 16,000 patients visited this clinic. The ages of the first visit to this clinic of the patients are mostly below 15 years. The main diseases are epilepsy, autism, mental retardation with various etiologies, Tourette syndrome, and other neurological disorders. Most of the diseases follow a chronic course and require long term follow-up. In this clinic those patients who need the continuous follow-up are seen even after reaching to adulthood. The average age of patients who were seen in the clinic during 2003 was about 21 years of age (20.77 +/- 14.28), suggesting that many of the patients are followed in this clinic for 20-30 years. The etiologies and pathophysiologies of most of these diseases are not fully understood. Therefore, the treatments based on the causes are difficult. The pathophysiologies of these diseases are modified by the ages. For example, some patients with epilepsy develop psychiatric symptoms in adulthood, and require the consultation by psychiatrists. The long-term follow up of certain disorders and evaluations of the disorders at different ages up to the adulthood have lead to new scientific discoveries. Examples include age-dependent symptoms observed in Segawa disease, psychiatric symptoms developing in frontal lobe epilepsy cases, alterations of behaviors in autism and Tourette syndrome. This knowledge suggests insights for the early prevention of later adverse outcomes. Social awareness and understanding of these neurological problems occurring in childhood are essential. The medical economic base for child neurology is another challenging and urgent issue to be solved. The importance of child neurology in the life-long neurology is stressed.

Neurological features and management of Wilson disease in children: an evaluation of 12 cases.

PubMed

Bayram, Ayşe Kaçar; Gümüş, Hakan; Arslan, Duran; Özçora, Güldemet Kaya; Kumandaş, Sefer; Karacabey, Neslihan; Canpolat, Mehmet; Per, Hüseyin

2016-03-01

Wilson's disease is an autosomal recessive disorder of copper metabolism which leads to copper overload in different tissues of the body. The aim of this study was to present the neurologic features of Wilson's disease and to assess the clinical course of neurological findings in children receiving anti-copper treatment. Twelve children with a diagnosis of Wilson's disease and findings of central nervous system involvement who were followed up in the Department of Pediatric Neurology and Pediatric Gastroenterology of the School of Medicine at Erciyes University were enrolled in the study. The study cases consisted of five boys (42%) and seven girls (58%). The mean age at the time of diagnosis was 9.9±3.4 years (5-15 years). The mean duration of follow-up was 49.0±36.4 months (15-128 months). Neurological findings at presentation included headache in seven cases (58%), tremor in seven cases (58%), dystonia in three cases (25%), ataxia in two cases (17%), dizziness in two cases (17%), numbness in the hands and acute weakness in one case (8%) and syncope in one case (8%). Headache, dizziness, syncope, numbness in hands and acute weakness symptoms resolved completely within six months after receiving treatment. Movement disorders either decreased or remained stable in seven of the eight cases. However, one patient developed progressively worsening dystonia despite to all treatments. Wilson's disease can be manifested with signs and symptoms of central nervous system in the childhood. Wilson's disease should be considered in all children presenting with movement disorders. A complete neurological assessment should be carried out in all cases with Wilson's disease.

Recovery of neurological functions in non-human primate model of Parkinson's disease by transplantation of encapsulated neonatal porcine choroid plexus cells.

PubMed

Luo, Xian-Ming; Lin, Hai; Wang, Wei; Geaney, Marilyn S; Law, Lee; Wynyard, Shaun; Shaikh, Shamim B; Waldvogel, Henry; Faull, Richard L M; Elliott, Robert B; Skinner, Stephen J M; Lee, Jacqueline E; Tan, Paul L-J

2013-01-01

Parkinson's disease (PD) is a neurodegenerative disease that is primarily characterized by degeneration of dopaminergic (DA) neurons in the substantia nigra (SN) and a loss of their fibre projections in the striatum. We utilized the neonatal porcine choroid plexus (CP), an organ that secretes cerebrospinal fluid containing various types of neurotrophic and neuroprotective factors, to ameliorate the Parkinsonian symptoms in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated rhesus monkeys without requiring immunosuppression. We demonstrate that transplanted encapsulated CP clusters (eCPs) significantly improved neurological functions in MPTP-treated monkeys during the course of six months after transplantation (p < 0.001) when compared with monkeys implanted with empty capsules or subjected to sham surgery. The improvement in neurological scores was accompanied by a corresponding improvement in apomorphine-induced circling behaviour (p < 0.001) as well as increased tyrosine hydroxylase (TH) staining in the striatum. Our results suggest that eCPs are a promising cell therapeutic agent to treat Parkinson's disease.

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.

Neurological complications of Zika virus infection.

PubMed

Carod-Artal, Francisco Javier

2018-05-01

Zika virus (ZIKV) disease is a vector-borne infectious disease transmitted by Aedes mosquitoes. Recently, ZIKV has caused outbreaks in most American countries. Areas covered: Publications about neurological complications of ZIKV infection retrieved from pubmed searchers were reviewed, and reference lists and relevant articles from review articles were also examined. Vertical/intrauterine transmission leads to congenital infection and causes microcephaly and congenital ZIKV syndrome. ZIKV preferentially infects human neural progenitor cells and triggers cell apoptosis. ZIKV RNA has been identified in foetal brain tissue and brains of microcephalic infants who died; amniotic fluid and placentas of pregnant mothers; and umbilical cord, cerebro-spinal fluid and meninges of newborns. The increase in the number of Guillain-Barre syndrome (GBS) cases during the ZIKV outbreak in the Americas provides epidemiological evidence for the link between ZIKV infection and GBS. Less frequently reported ZIKV neurological complications include encephalitis/meningoencephalitis, acute disseminated encephalomyelitis, myelitis, cerebrovascular complications (ischemic infarction; vasculopathy), seizures and encephalopathy, sensory polyneuropathy and sensory neuronopathy. Analysis of GBS incidence could serve as an epidemiological 'marker' or sentinel for ZIKV disease and other neurological complications associated to ZIKV. Expert commentary: An expanding spectrum of neurological complications associated with ZIKV infection is being recognised.

Human West Nile Virus Disease Outbreak in Pakistan, 2015–2016

PubMed Central

Khan, Erum; Barr, Kelli L.; Farooqi, Joveria Qais; Prakoso, Dhani; Abbas, Alizae; Khan, Zain Y.; Ashi, Shanze; Imtiaz, Kehkashan; Aziz, Z.; Malik, Faisal; Lednicky, John A.; Long, Maureen T.

2018-01-01

Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological disease in human patients in this country. Of 997 enrolled patients presenting with clinical features suggestive of arboviral disease, 105 were positive for WNV IgM antibodies, and 71 of these patients possessed WNV-specific neutralizing antibodies. Cross-reactivity of WNV IgM antibodies with Japanese encephalitis virus (JEV) occurred in 75 of these 105 patients. WNV co-infections with Dengue viruses were not a contributing factor for the severity of disease. Nor did prior exposure to dengue virus contribute to incidence of neurological involvement in WNV-infected patients. Patients with WNV infections were more likely to present with altered mental status, seizures, and reduced Glasgow Coma scores when compared with JEV-infected patients. Human WNV cases and vector numbers exhibited a temporal correlation with climate. PMID:29535994

Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD.

PubMed

Picker-Minh, Sylvie; Mignot, Cyril; Doummar, Diane; Hashem, Mais; Faqeih, Eissa; Josset, Patrice; Dubern, Béatrice; Alkuraya, Fowzan S; Kraemer, Nadine; Kaindl, Angela M

2016-04-29

Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity.

Neurological features and management of Wilson disease in children: an evaluation of 12 cases

PubMed Central

Bayram, Ayşe Kaçar; Gümüş, Hakan; Arslan, Duran; Özçora, Güldemet Kaya; Kumandaş, Sefer; Karacabey, Neslihan; Canpolat, Mehmet; Per, Hüseyin

2016-01-01

Aim: Wilson’s disease is an autosomal recessive disorder of copper metabolism which leads to copper overload in different tissues of the body. The aim of this study was to present the neurologic features of Wilson’s disease and to assess the clinical course of neurological findings in children receiving anti-copper treatment. Material and Methods: Twelve children with a diagnosis of Wilson’s disease and findings of central nervous system involvement who were followed up in the Department of Pediatric Neurology and Pediatric Gastroenterology of the School of Medicine at Erciyes University were enrolled in the study. Results: The study cases consisted of five boys (42%) and seven girls (58%). The mean age at the time of diagnosis was 9.9±3.4 years (5–15 years). The mean duration of follow-up was 49.0±36.4 months (15–128 months). Neurological findings at presentation included headache in seven cases (58%), tremor in seven cases (58%), dystonia in three cases (25%), ataxia in two cases (17%), dizziness in two cases (17%), numbness in the hands and acute weakness in one case (8%) and syncope in one case (8%). Headache, dizziness, syncope, numbness in hands and acute weakness symptoms resolved completely within six months after receiving treatment. Movement disorders either decreased or remained stable in seven of the eight cases. However, one patient developed progressively worsening dystonia despite to all treatments. Conclusions: Wilson’s disease can be manifested with signs and symptoms of central nervous system in the childhood. Wilson’s disease should be considered in all children presenting with movement disorders. A complete neurological assessment should be carried out in all cases with Wilson’s disease. PMID:27103860

Neurologic complications of vaccinations.

PubMed

Miravalle, Augusto A; Schreiner, Teri

2014-01-01

This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination. © 2014 Elsevier B.V. All rights reserved.

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.

[Neurological disease and facial recognition].

PubMed

Kawamura, Mitsuru; Sugimoto, Azusa; Kobayakawa, Mutsutaka; Tsuruya, Natsuko

2012-07-01

To discuss the neurological basis of facial recognition, we present our case reports of impaired recognition and a review of previous literature. First, we present a case of infarction and discuss prosopagnosia, which has had a large impact on face recognition research. From a study of patient symptoms, we assume that prosopagnosia may be caused by unilateral right occipitotemporal lesion and right cerebral dominance of facial recognition. Further, circumscribed lesion and degenerative disease may also cause progressive prosopagnosia. Apperceptive prosopagnosia is observed in patients with posterior cortical atrophy (PCA), pathologically considered as Alzheimer's disease, and associative prosopagnosia in frontotemporal lobar degeneration (FTLD). Second, we discuss face recognition as part of communication. Patients with Parkinson disease show social cognitive impairments, such as difficulty in facial expression recognition and deficits in theory of mind as detected by the reading the mind in the eyes test. Pathological and functional imaging studies indicate that social cognitive impairment in Parkinson disease is possibly related to damages in the amygdalae and surrounding limbic system. The social cognitive deficits can be observed in the early stages of Parkinson disease, and even in the prodromal stage, for example, patients with rapid eye movement (REM) sleep behavior disorder (RBD) show impairment in facial expression recognition. Further, patients with myotonic dystrophy type 1 (DM 1), which is a multisystem disease that mainly affects the muscles, show social cognitive impairment similar to that of Parkinson disease. Our previous study showed that facial expression recognition impairment of DM 1 patients is associated with lesion in the amygdalae and insulae. Our study results indicate that behaviors and personality traits in DM 1 patients, which are revealed by social cognitive impairment, are attributable to dysfunction of the limbic system.

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.

Serum creatine kinase isoenzymes and macroenzymes in dogs with different neurologic diseases.

PubMed

Paltrinieri, Saverio; Pintore, Laura; Balducci, Federica; Giordano, Alessia; Costabile, Annaluce; Bernardini, Marco

2017-03-01

Increased serum activity of CK isoenzymes and macroenzymes, and in particular of the brain isoenzyme (CK-BB) has been reported in dogs with central nervous system (CNS) disorders. However, no studies on the possible differences in serum activities of CK iso- or macroenzymes (Macro-CK1 and Macro-CK2) in different neurologic diseases are available. The aim of this study was to describe the electrophoretic distribution of CK iso- and macroenzymes in dogs with CNS disorders in order to assess whether this distribution depends on a specific neurologic disease. This study was done on sera from 45 dogs with neurologic diseases (degenerative, n = 7; idiopathic epilepsy [IE], n = 14; inflammatory, n = 16; space occupying lesions [SOL], n = 8) and from 10 clinically healthy dogs. The separation of serum CK isoenzymes and macroenzymes was performed using an automated electrophoretic method already validated in dogs. Compared with healthy dogs, dogs with CNS disorders had significantly higher total CK and CK-BB activities, and a significantly lower Macro-CK2 activity (P < .001). Comparison of pathologic subgroups and healthy dogs revealed significant differences (P < .01) in dogs with IE and inflammatory disorders for total CK activity, in all the subgroups for CK-BB (P < .01), and in dogs with IE and SOL for Macro-CK2 (P < .01). The results of this study suggest that CK-BB is released by neurons damaged by inflammatory or degenerative conditions or due to compressive effects of SOL. However, the neurologic diseases cannot be differentiated based on CK-BB or Macro-CK2 activities, unless further studies allow the definition of diagnostic thresholds. © 2017 American Society for Veterinary Clinical Pathology.

The spectrum of neurological disorders presenting at a neurology clinic in Yaoundé, Cameroon.

PubMed

Tegueu, Callixte Kuate; Nguefack, Séraphin; Doumbe, Jacques; Fogang, Yannick Fogoum; Mbonda, Paul Chimi; Mbonda, Elie

2013-01-01

The burden of these neurological diseases is higher in developing countries. However, there is a paucity and scarcity of literature on neurological diseases in sub-Saharan Africa. This study was therefore undertaken to determine the pattern of neurological diseases in this setting and then, compare to those elsewhere in the African continent and also serve as a baseline for planning and care for neurological disorders in Cameroon. The study was conducted at the Clinique Bastos, in Yaoundé, city capital of Cameroon, centre region. Over a period of six years, all medical records were reviewed by a neurologist and neurological diagnoses classified according to ICD-10. Out of 4526 admissions 912 patients (20.15%) were given a neurological diagnosis. The most frequent neurological disorders were headache (31.9%), epilepsy (9.86%), intervertebral disc disorder (7.67%), followed by lumbar and cervical arthrosis, polyneuropathy, stroke, Parkinson disease and dementia. According to ICD-10 classification, Episodic and paroxysmal disorders (headaches, epilepsy, cerebrovascular, sleep disorders) were observed on 424 (46.48%) patients; followed by nerve, nerve root and plexus disorders in 115 (12.6%) patients. The above data emphasizes that neurological disease contributes substantially to morbidity in an urban African hospital. Headaches, epilepsy and intervertebral disc disorders are major causes of morbidity.

Managing Pain Caused By Neurological Disease

PubMed Central

Tunks, Eldon

1985-01-01

Stabbing paroxysmal pain due to neurological disease can often be controlled by anticonvulsants, whereas steady burning pain is often responsive to tricyclic antidepressants, and to neuroleptics. Overuse of opiates may actually aggravate the pain, necessitating detoxification. Transcutaneous electrical nerve stimulation is helpful for conditions in which pain is localized, especially if there is a ‘trigger area’ or neuroma, or if paresthesias can be stimulated within the painful area. Local anesthetic injection, possibly with corticosteroid, relieves painful scars and neuromas, neuritis, and tender trigger points. Sympathetic blocks are used for post-herpetic neuralgia and sympathetic dystrophies. Relaxation therapy is a very useful psychological treatment. PMID:21274032

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

Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases.

PubMed

Arru, G; Mameli, G; Deiana, G A; Rassu, A L; Piredda, R; Sechi, E; Caggiu, E; Bo, M; Nako, E; Urso, D; Mariotto, S; Ferrari, S; Zanusso, G; Monaco, S; Sechi, G; Sechi, L A

2018-03-31

Human endogenous retroviruses (HERV) K/W seem to play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) was investigated for ALS, multiple sclerosis (MS) and Alzheimer's disease patients and in healthy controls. Four antigenic peptides derived respectively from HERV-K and HERV-W env-su proteins were studied in 21 definite or probable ALS patients, 26 possible or definite relapsing-remitting MS patients, 18 patients with Alzheimer's disease and 39 healthy controls. An indirect enzyme-linked immunosorbent assay was set up to detect specific antibodies (Abs) against env-su peptides. Amongst the measured levels of Abs against the four different HERV-K peptide fragments, only HERV-K env-su 19-37 was significantly elevated in ALS compared to other groups, both in serum and CSF. Instead, amongst the Abs levels directed against the four different HERV-W peptide fragments, only HERV-W env-su 93-108 and HERV-W env-su 248-262 were significantly elevated, in the serum and CSF of the MS group compared to other groups. In ALS patients, the HERV-K env-su 19-37 Abs levels were significantly correlated with clinical measures of disease severity, both in serum and CSF. Increased circulating levels of Abs directed against the HERV-W env-su 93-108 and HERV-W env-su 248-262 peptide fragments could serve as possible biomarkers in patients with MS. Similarly, increased circulating levels of Abs directed against the HERV-K env-su 19-37 peptide fragment could serve as a possible early novel biomarker in patients with ALS. © 2018 EAN.

Neurology in a globalizing world: World Congress of Neurology, Vienna, 2013.

PubMed

Hachinski, Vladimir

2013-06-11

The World Congress of Neurology (figure 1) theme "Neurology in a Globalizing World" acknowledges that science and increasingly medicine and neurology are becoming globalized. The best way to manage change is to shape it. It is becoming increasingly clear that brain diseases, particularly stroke and dementia, are projected to rise at a rate that could overwhelm our clinics and hospitals. Hence a new emphasis on prevention and the need to work across disciplines beyond our traditional roles. Neurologists are the guardians of the brain and need to take the lead role in advancing new approaches in stemming the tide of neurologic diseases.

Olfactory Disorder Pattern In Patients With Neurological Diseases Excluding Psychiatric And Traumatic Aetiologies.

PubMed

de Haro-Licer, Josep; González-Fernández, Adela; Planas-Comes, Albert; González-Ares, Josep Antón

2018-03-23

The most common cause of olfactory ENT disorders are colds and flu, chronic sinusitis, allergies and traumatic brain injury. Rarer aetiologies include certain neurological, psychiatric and metabolic injuries. The aim of this paper was to check the sort of olfactory disorders found in people who have suffered a brain injury, excluding: cranial traumas, psychiatric diseases, epilepsy, Parkinson's and Alzheimer's disease, and synaesthesia. A descriptive study based on 61 patients with diagnoses of various neurological injuries, which were tested by BAST-24 olfactometer. The results were compared with those of a control group (n= 120). The results show major impairment in these patients' olfactory sense. The neurological injury patients were able to detect from 60-77% of the odours, while the control group were able to detect between 98-100%. The neurological patients were able, at best, to identify, 11-32% of the odours correctly, while the control group were able to correctly detect between 59 -75%. The differences between odour detection and correct identification were statistically significant (p<.05). We concluded: a) Neurological injury, not caused by traumatic brain injury, psychiatric disorders or ENT diseases, ranged from 68-89% of the olfactory failures. b) We must bear in mind that these sorts of injuries can cause olfactory disorders. c) ENT and Neurologists should collaborate in the treatment of these disorders. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

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

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.

Alzheimer's disease and other neurological disorders.

PubMed

Henderson, V W

2007-10-01

Menopausal status and estrogen-containing hormone therapy may influence several neurological disorders, including Alzheimer's disease, epilepsy, migraine headache, multiple sclerosis, Parkinson's disease, sleep disorders, and stroke. For most of these illnesses, evidence on hormone therapy is insufficient to guide practice decisions. For stroke, clinical trial evidence indicates that hormone therapy increases risk of cerebral infarction. For women with Alzheimer's disease, estrogen treatment trials have tended to be small and of short duration. Most suggest that estrogen started after the onset of dementia symptoms does not meaningfully improve cognition or slow disease progression. Hormone therapy initiated after age 64 increased all-cause dementia in the Women's Health Initiative Memory Study. Many observational studies, however, report protective associations between hormone use and Alzheimer risk. Apparent risk reduction may represent a bias toward hormone therapy, since hormones are more often prescribed to healthier women. However, when compared to the Women's Health Initiative Memory Study, estrogen exposures in many observational studies reflect hormone initiation at a younger age, closer to the time of menopause. One intriguing hypothesis is that hormone therapy initiated or used during an early critical window may reduce later Alzheimer incidence. Public health implications of this hypothesis are important, but current data are inadequate to decide the issue.

[Cortical spreading depolarization: a new pathophysiological mechanism in neurological diseases].

PubMed

Sánchez-Porras, Renán; Robles-Cabrera, Adriana; Santos, Edgar

2014-05-20

Cortical spreading depolarization is a wave of almost complete depolarization of the neuronal and glial cells that occurs in different neurological diseases such as migraine with aura, subarachnoid hemorrhage, intracerebral hemorrhage, head trauma and stroke. These depolarization waves are characterized by a change in the negative potential with an amplitude between -10 and -30mV, duration of ∼1min and changes in the ion homeostasis between the intra- and extracellular space. This results in neuronal edema and dendritic distortion. Under pathologic states of hypoperfusion, cortical spreading depolarization can produce oxidative stress, worsen hypoxia and induce neuronal death. This is due to intense arterial vasoconstriction produced by an inverse response called spreading ischemia. Only in the last years there has been an electrophysiological confirmation of cortical spreading depolarization in human brains. Occurrence of cortical spreading depolarization has been associated with worse outcome in patients. Currently, increased knowledge regarding the pathophysiologic mechanisms supports the hypothetical correlation of cortical spreading depolarization with brain damage in humans. There are diverse therapeutic alternatives that promise inhibition of cortical spreading depolarization and subsequent better outcomes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

The neurological basis of occupation.

PubMed

Gutman, Sharon A; Schindler, Victoria P

2007-01-01

The purpose of the present paper was to survey the literature about the neurological basis of human activity and its relationship to occupation and health. Activities related to neurological function were organized into three categories: those that activate the brain's reward system; those that promote the relaxation response; and those that preserve cognitive function into old age. The results from the literature review correlating neurological evidence and activities showed that purposeful and meaningful activities could counter the effects of stress-related diseases and reduce the risk for dementia. Specifically, it was found that music, drawing, meditation, reading, arts and crafts, and home repairs, for example, can stimulate the neurogical system and enhance health and well-being, Prospective research studies are needed to examine the effects of purposeful activities on reducing stress and slowing the rate of cognitive decline.

Neurology and international organizations.

PubMed

Mateen, Farrah J

2013-07-23

A growing number of international stakeholders are engaged with neurologic diseases. This article provides a brief overview of important international stakeholders in the practice of neurology, including global disease-specific programs, United Nations agencies, governmental agencies with international influence, nongovernmental organizations, international professional organizations, large private donors, private-public partnerships, commercial interests, armed forces, and universities and colleges. The continued engagement of neurologists is essential for the growing number of international organizations that can and should incorporate neurologic disease into their global agendas.

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

[Circular RNA in human disease and their potential clinic significance].

PubMed

Chen, Yonghua; Li, Cheng; Tan, Chunlu; Mai, Gang; Liu, Xubao

2017-02-10

Circular RNAs (circ RNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. They share a stable structure, high expression and often exhibit tissue/developmental-stage-specific expression. Emerging evidence indicates that circRNAs might play important roles in human disease, such as cancer, neurological disorders and atherosclerotic vascular disease risk. The huge potentials of circRNAs are recently being discovered from the laboratory to the clinic. CircRNAs might be developed as a potential novel and stable biomarker and potential drugs used in disease diagnosis and treatment. Here, we review the current understanding of the roles of circRNAs in human disease and their potential clinic significance in disease.

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

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.

Neurology and international organizations

PubMed Central

2013-01-01

A growing number of international stakeholders are engaged with neurologic diseases. This article provides a brief overview of important international stakeholders in the practice of neurology, including global disease-specific programs, United Nations agencies, governmental agencies with international influence, nongovernmental organizations, international professional organizations, large private donors, private–public partnerships, commercial interests, armed forces, and universities and colleges. The continued engagement of neurologists is essential for the growing number of international organizations that can and should incorporate neurologic disease into their global agendas. PMID:23877795

Between destiny and disease: genetics and molecular pathways of human central nervous system aging.

PubMed

Glorioso, Christin; Sibille, Etienne

2011-02-01

Aging of the human brain is associated with "normal" functional, structural, and molecular changes that underlie alterations in cognition, memory, mood and motor function, amongst other processes. Normal aging also imposes a robust constraint on the onset of many neurological diseases, ranging from late onset neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's diseases (PD), to early onset psychiatric disorders, such as bipolar disorder (BPD) and schizophrenia (SCZ). The molecular mechanisms and genetic underpinnings of age-related changes in the brain are understudied, and, while they share some overlap with peripheral mechanisms of aging, many are unique to the largely non-mitotic brain. Hence, understanding mechanisms of brain aging and identifying associated modulators may have profound consequences for the prevention and treatment of age-related impairments and diseases. Here we review current knowledge on age-related functional and structural changes, their molecular and genetic underpinnings, and discuss how these pathways may contribute to the vulnerability to develop age-related neurological diseases. We highlight recent findings from human post-mortem brain microarray studies, which we hypothesize, point to a potential genetically controlled transcriptional program underlying molecular changes and age-gating of neurological diseases. Finally, we discuss the implications of this model for understanding basic mechanisms of brain aging and for the future investigation of therapeutic approaches. Copyright © 2010 Elsevier Ltd. All rights reserved.

Management of faecal incontinence and constipation in adults with central neurological diseases.

PubMed

Coggrave, M; Wiesel, P H; Norton, C

2006-04-19

People with neurological disease have a much higher risk of both faecal incontinence and constipation than the general population. There is often a fine line between the two conditions, with any management intended to ameliorate one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical with a limited research base. To determine the effects of management strategies for faecal incontinence and constipation in people with neurological diseases affecting the central nervous system. We searched the Cochrane Incontinence Group Specialised Trials Register (searched 26 January 2005), the Cochrane Central Register of Controlled Trials (Issue 2, 2005), MEDLINE (January 1966 to May 2005), EMBASE (January 1998 to May 2005) and all reference lists of relevant articles. All randomised or quasi-randomised trials evaluating any types of conservative or surgical measure for the management of faecal incontinence and constipation in people with neurological diseases were selected. Specific therapies for the treatment of neurological diseases that indirectly affect bowel dysfunction were also considered. Two reviewers assessed the methodological quality of eligible trials and two reviewers independently extracted data from included trials using a range of pre-specified outcome measures. Ten trials were identified by the search strategy, most were small and of poor quality. Oral medications for constipation were the subject of four trials. Cisapride does not seem to have clinically useful effects in people with spinal cord injuries (three trials). Psyllium was associated with increased stool frequency in people with Parkinson's disease but did not alter colonic transit time (one trial). Prucalopride, an enterokinetic did not demonstrate obvious benefits in this patient group (one study). Some rectal preparations to initiate defaecation produced faster

Engineered BDNF producing cells as a potential treatment for neurologic disease

PubMed Central

Deng, Peter; Anderson, Johnathon D.; Yu, Abigail S.; Annett, Geralyn; Fink, Kyle D.; Nolta, Jan A.

2018-01-01

Introduction Brain-derived neurotrophic factor (BDNF) has been implicated in wide range of neurological diseases and injury. This neurotrophic factor is vital for neuronal health, survival, and synaptic connectivity. Many therapies focus on the restoration or enhancement of BDNF following injury or disease progression. Areas covered The present review will focus on the mechanisms in which BDNF exerts its beneficial functioning, current BDNF therapies, issues and potential solutions for delivery of neurotrophic factors to the central nervous system, and other disease indications that may benefit from overexpression or restoration of BDNF. Expert opinion Due to the role of BDNF in neuronal development, maturation, and health, BDNF is implicated in numerous neurological diseases making it a prime therapeutic agent. Numerous studies have shown the therapeutic potential of BDNF in a number of neurodegenerative disease models and in acute CNS injury, however clinical translation has fallen short due to issues in delivering this molecule. The use of MSC as a delivery platform for BDNF holds great promise for clinical advancement of neurotrophic factor restoration. The ease with which MSC can be engineered opens the door to the possibility of using this cell-based delivery system to advance a BDNF therapy to the clinic. PMID:27159050

Burden of neurological conditions in Canada.

PubMed

Gaskin, J; Gomes, J; Darshan, S; Krewski, D

2017-07-01

Neurological conditions are among the leading causes of disability in the Canadian population and are associated with a large public health burden. An increase in life expectancy and a declining birth rate has resulted in an aging Canadian population, and the proportion of age-adjusted mortality due to non-communicable diseases has been steadily increasing. These conditions are frequently associated with chronic disability and an increasing burden of care for patients, their families and caregivers. The National Population Health Study of Neurological Conditions (NPHSNC) aims to improve knowledge about neurological conditions and their impacts on individuals, their families, caregivers and health care system. The Systematic Review of Determinants of Neurological Conditions, a specific objective within the NPHSNC, is a compendium of systematic reviews on risk factors affecting onset and progression of the following 14 priority neurological conditions: Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), brain tumours (BT), cerebral palsy (CP), dystonia, epilepsy, Huntington's disease (HD), hydrocephalus, multiple sclerosis (MS), muscular dystrophies (MD), neurotrauma, Parkinson's disease (PD), spina bifida (SB), and Tourette's syndrome (TS). The burden of neurological disease is expected to increase as the population ages, and this trend is presented in greater detail for Alzheimer's and Parkinson's disease because the incidence of these two common neurological diseases increases significantly with age over 65 years. This article provides an overview of burden of neurological diseases in Canada to set the stage for the in-depth systematic reviews of the 14 priority neurological conditions presented in subsequent articles in this issue. Copyright © 2016. Published by Elsevier B.V.

Functional progression of patients with neurological diseases in a tertiary paediatric intensive care unit: Our experience.

PubMed

Madurga Revilla, P; López Pisón, J; Samper Villagrasa, P; García Íñiguez, J P; Garcés Gómez, R; Domínguez Cajal, M; Gil Hernández, I

2017-11-23

Neurological diseases explain a considerable proportion of admissions to paediatric intensive care units (PICU), and are a significant cause of morbidity and mortality. This study aims to analyse the functional progression of children with critical neurological conditions. Retrospective descriptive study of children admitted to PICU with neurological diseases over a period of 3 years (2012-2014), assessing vital and functional prognosis at PICU discharge and at one year according to the Pediatric Cerebral and Overall Performance Category scales (PCPC-POPC) and the Functional Status Scale (FSS). The results are compared with our previous data (1990-1999), and those of the international multicentre PANGEA study. A total of 266 children were studied. The mortality rate was 3%; the PRISM-III and PIM2 models did not show predictive ability. Clinically significant worsening was observed in functional health at discharge in 30% of the sample, according to POPC, 15% according to PCPC, and 5% according to FSS. After one year, functional performance improved according to PCPC-POPC, but not according to FSS. Children with no underlying neurological disease had a higher degree of functional impairment; this was prolonged over time. We observed a decrease in overall and neurocritical mortality compared with our previous data (5.60 vs. 2.1%, P=.0003, and 8.44 vs. 2.63%, P=.0014, respectively). Compared with the PANGEA study, both mortality and cerebral functional impairment in neurocritical children were lower in our study (1.05 vs. 13.32%, P<.0001, and 10.47% vs. 23.79%, P<.0001, respectively). Nearly one-third of critically ill children have neurological diseases. A significant percentage, mainly children without underlying neurological diseases, had a clinically significant functional impact at PICU discharge and after a year. Neuromonitoring and neuroprotection measures and the evaluation of functional progression are necessary to improve critical child care. Copyright �

Selenium in the Therapy of Neurological Diseases. Where is it Going?

PubMed Central

Dominiak, Agnieszka; Wilkaniec, Anna; Wroczyńsk, Piotr; Adamczyk, Agata

2016-01-01

Selenium (34Se), an antioxidant trace element, is an important regulator of brain function. These beneficial properties that Se possesses are attributed to its ability to be incorporated into selenoproteins as an amino acid. Several selenoproteins are expressed in the brain, in which some of them, e.g. glutathione peroxidases (GPxs), thioredoxin reductases (TrxRs) or selenoprotein P (SelP), are strongly involved in antioxidant defence and in maintaining intercellular reducing conditions. Since increased oxidative stress has been implicated in neurological disorders, including Parkinson’s disease, Alzheimer’s disease, stroke, epilepsy and others, a growing body of evidence suggests that Se depletion followed by decreased activity of Se-dependent enzymes may be important factors connected with those pathologies. Undoubtedly, the remarkable progress that has been made in understanding the biological function of Se in the brain has opened up new potential possibilities for the treatment of neurological diseases by using Se as a potential drug. However, further research in the search for optimal Se donors is necessary in order to achieve an effective and safe therapeutic income. PMID:26549649

A review of the emerging potential therapy for neurological disorders: human embryonic stem cell therapy

PubMed Central

Shroff, Geeta; Dhanda Titus, Jyoti; Shroff, Rhea

2017-01-01

The first human embryonic stem cell (hESC) line was developed in the late nineties. hESCs are capable of proliferating indefinitely and differentiate into all the three embryonic germ layers. Further, the differentiation of hESC lines into neural precursor cells and neurons, astrocytes and oligodendrocytes showed their potential in treating several incurable neurological disorders such as spinal cord injury (SCI), cerebral palsy (CP), Parkinson’s disease (PD). In this review, we will discuss the global scenario of research and therapeutic use of hESCs in the treatment of neurological disorders. Following this, we will discuss the development of a unique hESC line, how it differs from the other available hESC lines and its use in the treatment of neurological disorders. hESCs were isolated from mixture of neuronal and non-neuronal progenitor cells in their pre progenitor state in a Good Laboratory Practices, Good Tissue Practices and Good Manufacturing Practices compliant laboratory. Blastomere cells have served as a source to derive the hESCs and the xeno-free culture was demonstrated to be more safe and effective in clinical therapeutic application of hESCs. All the patients showed a remarkable improvement in their conditions and no serious adverse events were reported. This study concluded that hESC lines could be scalable and used in the treatment of various neurological disorders such as SCI, CP, and PD. PMID:28533935

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.

Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders.

PubMed

Mohammadi, Alireza; Maleki-Jamshid, Ali; Sanooghi, Davood; Milan, Peiman Brouki; Rahmani, Arash; Sefat, Farshid; Shahpasand, Koorosh; Soleimani, Mansoureh; Bakhtiari, Mehrdad; Belali, Rafie; Faghihi, Faezeh; Joghataei, Mohammad Taghi; Perry, George; Mozafari, Masoud

2018-03-16

A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer's disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. Graphical Abstract ᅟ.

An update of neurological manifestations of vasculitides and connective tissue diseases: a literature review

PubMed Central

Bougea, Anastasia; Anagnostou, Evangelos; Spandideas, Nikolaos; Triantafyllou, Nikolaos; Kararizou, Evangelia

2015-01-01

Vasculitides comprise a heterogeneous group of autoimmune disorders, occurring as primary or secondary to a broad variety of systemic infectious, malignant or connective tissue diseases. The latter occur more often but their pathogenic mechanisms have not been fully established. Frequent and varied central and peripheral nervous system complications occur in vasculitides and connective tissue diseases. In many cases, the neurological disorders have an atypical clinical course or even an early onset, and the healthcare professionals should be aware of them. The purpose of this brief review was to give an update of the main neurological disorders of common vasculitis and connective tissue diseases, aiming at accurate diagnosis and management, with an emphasis on pathophysiologic mechanisms. PMID:26313435

Disability, distress and unemployment in neurology outpatients with symptoms 'unexplained by organic disease'.

PubMed

Carson, A; Stone, J; Hibberd, C; Murray, G; Duncan, R; Coleman, R; Warlow, C; Roberts, R; Pelosi, A; Cavanagh, J; Matthews, K; Goldbeck, R; Hansen, C; Sharpe, M

2011-07-01

To determine the disability, distress and employment status of new neurology outpatients with physical symptoms unexplained by organic disease and to compare them with patients with symptoms explained by organic disease. As part of a cohort study (the Scottish Neurological Symptoms Study) neurologists rated the extent to which each new patient's symptoms were explained by organic disease. Patients whose symptoms were rated as 'not at all' or only 'somewhat' explained by disease were considered cases, and those whose symptoms were 'largely' or 'completely' explained by disease were considered controls. All patients completed self-ratings of disability, health status (Medical Outcomes Study Short Form 12-Item Scale (SF-12)) and emotional distress (Hospital Anxiety and Depression Scale) and also reported their employment and state financial benefit status. 3781 patients were recruited: 1144 (30%) cases and 2637 (70%) controls. Cases had worse physical health status (SF-12 score 42 vs 44; difference in means 1.7 (95% CI -2.5 to 0.9)) and worse mental health status (SF-12 score 43 vs 47; difference in means -3.5 (95% CI -4.3 to to 2.7)). Unemployment was similar in cases and controls (50% vs 50%) but cases were more likely not to be working for health reasons (54% vs 37% of the 50% not working; OR 2.0 (95% CI 1.6 to 2.4)) and also more likely to be receiving disability-related state financial benefits (27% vs 22%; (OR 1.3, 95% CI 1.1 to 1.6)). New neurology patients with symptoms unexplained by organic disease have more disability-, distress- and disability-related state financial benefits than patients with symptoms explained by disease.

Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

PubMed Central

Ndhlovu, L C; Snyder-Cappione, J E; Carvalho, K I; Leal, F E; Loo, C P; bruno, F R; Jha, A R; Devita, D; Hasenkrug, A M; Barbosa, H M R; Segurado, A C; Nixon, D F; Murphy, E L; Kallas, E G

2009-01-01

Human T lymphotropic virus type 1 (HTLV-1) infects 10–20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4+ and fewer CD8+ cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4+ NK T subset are associated with HTLV-1 disease progression. PMID:19778295

Microglial Lectins in Health and Neurological Diseases

PubMed Central

Siew, Jian Jing; Chern, Yijuang

2018-01-01

. Most importantly, multiple studies have reported dysregulation of lectins in neurological disorders. Here, we reviewed recent studies on microglial lectins and their functions in CNS health and disease, and suggest that these lectin families are novel, potent therapeutic targets for neurological diseases. PMID:29867350

Neurology in Asia.

PubMed

Tan, Chong-Tin

2015-02-10

Asia is important as it accounts for more than half of the world population. The majority of Asian countries fall into the middle income category. As for cultural traditions, Asia is highly varied, with many languages spoken. The pattern of neurologic diseases in Asia is largely similar to the West, with some disease features being specific to Asia. Whereas Asia constitutes 60% of the world's population, it contains only 20% of the world's neurologists. This disparity is particularly evident in South and South East Asia. As for neurologic care, it is highly variable depending on whether it is an urban or rural setting, the level of economic development, and the system of health care financing. To help remedy the shortage of neurologists, most counties with larger populations have established training programs in neurology. These programs are diverse, with many areas of concern. There are regional organizations serving as a vehicle for networking in neurology and various subspecialties, as well as an official journal (Neurology Asia). The Asian Epilepsy Academy, with its emphasis on workshops in various locations, EEG certification examination, and fellowships, may provide a template of effective regional networking for improving neurology care in the region. © 2015 American Academy of Neurology.

Clinical and immunological relevance of anti-neuronal antibodies in celiac disease with neurological manifestations

PubMed Central

Caio, Giacomo; Giorgio, Roberto De; Venturi, Alessandro; Giancola, Fiorella; Latorre, Rocco; Boschetti, Elisa; Serra, Mauro; Ruggeri, Eugenio; Volta, Umberto

2015-01-01

Aim: To assess anti-neuronal antibodies (NA) prevalence and their correlation with neurological disorders and bowel habits in celiac disease (CD) patients. Background: Neurological manifestations are estimated to occur in about 10% of celiac disease patients and NA to central nervous system (CNS) and enteric nervous system (ENS) are found in a significant proportion of them. Little is known about the clinical and immunological features in CD patients with neurological manifestations. Patients and methods: NA to CNS and ENS were investigated in 106 CD patients and in 60 controls with autoimmune disorders by indirect immunofluorescence on rat / primate cerebellar cortex and intestinal (small and large bowel) sections. Results: IgG NA to CNS (titer 1:50 - 1:400) were positive in 23 celiacs (21%), being more frequently detected in those with neurological disorders that in those without neurological dysfunction (49% vs. 8%, P< 0.0001). Of the 26 celiacs (24%) with IgG NA to ENS, 11 out of 12 with an antibody titer > 1:200 had severe constipation. Only one patient with cerebellar ataxia and intestinal sub-occlusion was positive for NA to CNS and ENS. NA to CNS and ENS were found in 7% and 5% of controls, respectively. Conclusion: In CD the positivity of NA to CNS can be regarded as a marker of neurological manifestations. High titer NA to ENS are associated with severe constipation. The demonstration of NA to CNS and ENS suggests an immune-mediated pathogenesis leading to central neural impairment as well as gut dysfunction (hence constipation), respectively. PMID:25926940

[Features of neurologic semiotics at chronic obstructive pulmonary disease].

PubMed

Litvinenko, I V; Baranov, V L; Kolcheva, Iu A

2011-01-01

Chronic obstructive pulmonary disease (COPD) is actual pathology, when it forms the mixed hypoxemia. In the conditions of a chronic hypoxemia structures of organism with high level of metabolic processes, namely brain tissues, suffer. Character of defeat of the central nervous system at that pathology is insufficiently studied. In this article we studied and analysed the presence of such changes as depression, anxiety, cognitive impairment and features of neurologic semiotics at COPD in 50 patients.

Frequency and Pathological Phenotype of Bovine Astrovirus CH13/NeuroS1 Infection in Neurologically-Diseased Cattle: Towards Assessment of Causality.

PubMed

Selimovic-Hamza, Senija; Boujon, Céline L; Hilbe, Monika; Oevermann, Anna; Seuberlich, Torsten

2017-01-18

Next-generation sequencing (NGS) has opened up the possibility of detecting new viruses in unresolved diseases. Recently, astrovirus brain infections have been identified in neurologically diseased humans and animals by NGS, among them bovine astrovirus (BoAstV) CH13/NeuroS1, which has been found in brain tissues of cattle with non-suppurative encephalitis. Only a few studies are available on neurotropic astroviruses and a causal relationship between BoAstV CH13/NeuroS1 infections and neurological disease has been postulated, but remains unproven. Aiming at making a step forward towards assessing the causality, we collected brain samples of 97 cases of cattle diagnosed with unresolved non-suppurative encephalitis, and analyzed them by in situ hybridization and immunohistochemistry, to determine the frequency and neuropathological distribution of the BoAstV CH13/NeuroS1 and its topographical correlation to the pathology. We detected BoAstV CH13/NeuroS1 RNA or proteins in neurons throughout all parts of the central nervous system (CNS) in 34% of all cases, but none were detected in cattle of the control group. In general, brain lesions had a high correlation with the presence of the virus. These findings show that a substantial proportion of cattle with non-suppurative encephalitis are infected with BoAstV CH13/NeuroS1 and further substantiate the causal relationship between neurological disease and astrovirus infections.

Frequency and Pathological Phenotype of Bovine Astrovirus CH13/NeuroS1 Infection in Neurologically-Diseased Cattle: Towards Assessment of Causality

PubMed Central

Selimovic-Hamza, Senija; Boujon, Céline L.; Hilbe, Monika; Oevermann, Anna; Seuberlich, Torsten

2017-01-01

Next-generation sequencing (NGS) has opened up the possibility of detecting new viruses in unresolved diseases. Recently, astrovirus brain infections have been identified in neurologically diseased humans and animals by NGS, among them bovine astrovirus (BoAstV) CH13/NeuroS1, which has been found in brain tissues of cattle with non-suppurative encephalitis. Only a few studies are available on neurotropic astroviruses and a causal relationship between BoAstV CH13/NeuroS1 infections and neurological disease has been postulated, but remains unproven. Aiming at making a step forward towards assessing the causality, we collected brain samples of 97 cases of cattle diagnosed with unresolved non-suppurative encephalitis, and analyzed them by in situ hybridization and immunohistochemistry, to determine the frequency and neuropathological distribution of the BoAstV CH13/NeuroS1 and its topographical correlation to the pathology. We detected BoAstV CH13/NeuroS1 RNA or proteins in neurons throughout all parts of the central nervous system (CNS) in 34% of all cases, but none were detected in cattle of the control group. In general, brain lesions had a high correlation with the presence of the virus. These findings show that a substantial proportion of cattle with non-suppurative encephalitis are infected with BoAstV CH13/NeuroS1 and further substantiate the causal relationship between neurological disease and astrovirus infections. PMID:28106800

[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.

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

[Domestic violence in patients and caregivers dyads in neurological diseases].

PubMed

Sánchez-Guzmán, María Alejandra; Paz-Rodríguez, Francisco; Espinola-Nadurille, Mariana; Trujillo-De Los Santos, Zoila

2015-01-01

Patients with neurological diseases are susceptible to abuse and neglect. Studies on violence in this context have mainly focused on abuse perpetrated by a caregiver to the patient directionally. In this study we describe violence in dyads of caregivers and patients with neurological disorders according to frequency, directionality, and type of relation. One-hundred-and-eighty-five caregiver-patient dyads were assessed by means of the National Survey of Violence Against Women (NSVAW) guidelines and the Zarit and Pfeiffer questionnaires. Bivariate analysis and Spearman correlation tests were performed. Violence was reported by 32.5% of caregivers and 33.5% of patients. In both groups, psychological abuse was the most common. Mutual violence (54.5%) is the most common type of abuse and the caregiver reported as having more violent behavior is the intimate partner. Epilepsy was the neurological disorder where violence was more prevalent (47.6%). The prevalence of violence in our sample is higher than the one for the general population of 21%, as reported by the NSVAW. Clinical neurologists and healthcare services are key elements for the detection of abuse in this context.

Cognitive Abilities of Children With Neurological and Liver Forms of Wilson Disease.

PubMed

Favre, Emilie; Lion-François, Laurence; Canton, Marie; Vanlemmens, Claire; Bonneton, Marjorie; Bouillet, Lise; Brunet, Anne-Sophie; Lachaux, Alain

2017-03-01

Cognitive impairment in adult patients experiencing Wilson disease is now more clearly described, even in liver forms of the disease. Although this condition can appear during childhood, the cognitive abilities of children have not yet been reported in a substantial case series. This retrospective study included 21 children with Wilson disease who had undergone general cognitive assessment. The results argue in favor of a poor working memory capacity in the liver form of the disease, and more extensive cognitive impairments in its neurological form. Extensive neuropsychological investigations on all children experiencing Wilson disease are thus required.

Neuropsychological Assessment of Driving Safety Risk in Older Adults With and Without Neurologic Disease

PubMed Central

Anderson, Steven W.; Aksan, Nazan; Dawson, Jeffrey D.; Uc, Ergun Y.; Johnson, Amy M.; Rizzo, Matthew

2013-01-01

Decline in cognitive abilities can be an important contributor to the driving problems encountered by older adults, and neuropsychological assessment may provide a practical approach to evaluating this aspect of driving safety risk. The purpose of the present study was to evaluate several commonly used neuropsychological tests in the assessment of driving safety risk in older adults with and without neurological disease. A further goal of this study was to identify brief combinations of neuropsychological tests that sample performances in key functional domains and thus could be used to efficiently assess driving safety risk. 345 legally licensed and active drivers over the age of 50, with either no neurologic disease (N=185), probable Alzheimer's disease (N=40), Parkinson's disease (N=91), or stroke (N=29), completed vision testing, a battery of 10 neuropsychological tests, and an 18 mile drive on urban and rural roads in an instrumented vehicle. Performances on all neuropsychological tests were significantly correlated with driving safety errors. Confirmatory factor analysis was used to identify 3 key cognitive domains assessed by the tests (speed of processing, visuospatial abilities, and memory), and several brief batteries consisting of one test from each domain showed moderate corrected correlations with driving performance. These findings are consistent with the notion that driving places demands on multiple cognitive abilities that can be affected by aging and age-related neurological disease, and that neuropsychological assessment may provide a practical off-road window into the functional status of these cognitive systems. PMID:22943767

Neuropsychological assessment of driving safety risk in older adults with and without neurologic disease.

PubMed

Anderson, Steven W; Aksan, Nazan; Dawson, Jeffrey D; Uc, Ergun Y; Johnson, Amy M; Rizzo, Matthew

2012-01-01

Decline in cognitive abilities can be an important contributor to the driving problems encountered by older adults, and neuropsychological assessment may provide a practical approach to evaluating this aspect of driving safety risk. The purpose of the present study was to evaluate several commonly used neuropsychological tests in the assessment of driving safety risk in older adults with and without neurological disease. A further goal of this study was to identify brief combinations of neuropsychological tests that sample performances in key functional domains and thus could be used to efficiently assess driving safety risk. A total of 345 legally licensed and active drivers over the age of 50, with no neurologic disease (N = 185), probable Alzheimer's disease (N = 40), Parkinson's disease (N = 91), or stroke (N = 29), completed vision testing, a battery of 10 neuropsychological tests, and an 18-mile drive on urban and rural roads in an instrumented vehicle. Performances on all neuropsychological tests were significantly correlated with driving safety errors. Confirmatory factor analysis was used to identify 3 key cognitive domains assessed by the tests (speed of processing, visuospatial abilities, and memory), and several brief batteries consisting of one test from each domain showed moderate corrected correlations with driving performance. These findings are consistent with the notion that driving places demands on multiple cognitive abilities that can be affected by aging and age-related neurological disease, and that neuropsychological assessment may provide a practical off-road window into the functional status of these cognitive systems.

Multiple sclerosis in children and adolescents. An important differential diagnosis of acute neurological disease.

PubMed

Sandvig, Inger; Barlinn, Jon; Nedregaard, Bård; Skjeldal, Ola H

2015-03-01

Multiple sclerosis (MS) has traditionally been considered a disease of adults. However, in recent years, there have been numerous reports about the disease occurring in childhood and adolescence. The purpose of this article is to document Norwegian experience of this population based on clinical observations and neuroradiological findings. Children and adolescents diagnosed with MS at the Department of Child Neurology, Oslo University Hospital, between 1 January 2004 and 1 May 2012 were included. Gender, previous diseases, age, symptoms at first attack, spinal fluid findings and cerebral magnetic resonance tomography (MRI) findings were recorded. The course of the disease, treatment and sequelae was noted. The study includes 18 patients who received MS diagnosis. Median age at onset was 10 years and six months. The presenting symptoms and MRI findings varied. Almost all patients were treated with steroids in the acute phase and later with interferon-beta. Some patients were treated with natalizumab when there was lack of efficiency of interferon-beta. Seven patients developed permanent, moderate sequelae in terms of motor, sensory, or cerebellar symptoms. Nine patients had cognitive difficulties and 11 specified increased fatigability. MS in children and adolescents is a disease with varying acute neurological symptoms and findings. The patients were treated with the same medicines as adults with MS and tolerated it well. We found that cognitive sequelae and fatigue were common also in this young age group. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Neurology and literature 2.

PubMed

Iniesta, I

2014-05-01

Good literary fiction has the potential to move us, extend our sense of life, transform our prospective views and help us in the face of adversity. A neurological disorder is likely to be the most challenging experience a human being may have to confront in a lifetime. As such, literary recreations of illnesses have a doubly powerful effect. Study the synergies between neurology and fictional literature with particular reference to narrative based medicine (NBM). Doctors establish boundaries between the normal and the abnormal. Taking a clinical history is an act of interpretation in which the doctor integrates the science of objective signs and measurable quantities with the art of subjective clinical judgment. The more discrepancy there is between the patient's experience with the illness and the doctor's interpretation of that disease, the less likely the doctor-patient interaction is to succeed. NBM contributes to a better discernment of the meanings, thus considering disease as a biographical event rather than just a natural fact. Drawing from their own experience with disease, writers of fiction provide universal insights through their narratives, whilst neuroscientists, like Cajal, have occasionally devoted their scientific knowledge to literary narratives. Furthermore, neurologists from Alzheimer to Oliver Sacks remind us of the essential value of NBM in the clinic. Integrating NBM (the narrative of patients) and the classic holistic approach to patients with our current paradigm of evidence based medicine represents a challenge as relevant to neurologists as keeping up with technological and scientific advances. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Targeting cellular energy production in neurological disorders.

PubMed

Baker, Steven K; Tarnopolsky, Mark A

2003-10-01

The concepts of energy dysregulation and oxidative stress and their complicated interdependence have rapidly evolved to assume primary importance in understanding the pathophysiology of numerous neurological disorders. Therefore, neuroprotective strategies addressing specific bioenergetic defects hold particular promise in the treatment of these conditions (i.e., amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, Friedreich's ataxia, mitochondrial cytopathies and other neuromuscular diseases), all of which, to some extent, share 'the final common pathway' leading to cell death through either necrosis or apoptosis. Compounds such as creatine monohydrate and coenzyme Q(10) offer substantial neuroprotection against ischaemia, trauma, oxidative damage and neurotoxins. Miscellaneous agents, including alpha-lipoic acid, beta-OH-beta-methylbutyrate, riboflavin and nicotinamide, have also been shown to improve various metabolic parameters in brain and/or muscle. This review will highlight the biological function of each of the above mentioned compounds followed by a discussion of their utility in animal models and human neurological disease. The balance of this work will be comprised of discussions on the therapeutic applications of creatine and coenzyme Q(10).

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

Neurological disease in man following administration of suckling mouse brain antirabies vaccine.

PubMed

Held, J R; Adaros, H L

1972-01-01

In Latin America, suckling mouse brain (SMB) vaccine has become the most commonly used vaccine for immunization of both man and animals against rabies. This vaccine is highly immunogenic, is relatively economical and easy to produce, and is believed to be free of the immunoencephalitogenic factor. From 1964 to the end of 1969, there were 40 reported cases of neurological disease following administration of SMB vaccine, 32 of which met the criteria for inclusion in this report. These 32 cases occurred in 8 different countries. In contrast to neurological disease following the administration of other types of nervous tissue vaccine, the majority of the cases following vaccination with SMB vaccine had a Guillain-Barré-type syndrome with peripheral nervous system involvement and a higher case-fatality rate. The causative agent has not been demonstrated. Modifications in the production and handling of the vaccine may be producing changes that are responsible.

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.

The Use of Signal-Transduction and Metabolic Pathways to Predict Human Disease Targets from Electric and Magnetic Fields Using in vitro Data in Human Cell Lines

PubMed Central

Parham, Fred; Portier, Christopher J.; Chang, Xiaoqing; Mevissen, Meike

2016-01-01

Using in vitro data in human cell lines, several research groups have investigated changes in gene expression in cellular systems following exposure to extremely low frequency (ELF) and radiofrequency (RF) electromagnetic fields (EMF). For ELF EMF, we obtained five studies with complete microarray data and three studies with only lists of significantly altered genes. Likewise, for RF EMF, we obtained 13 complete microarray datasets and 5 limited datasets. Plausible linkages between exposure to ELF and RF EMF and human diseases were identified using a three-step process: (a) linking genes associated with classes of human diseases to molecular pathways, (b) linking pathways to ELF and RF EMF microarray data, and (c) identifying associations between human disease and EMF exposures where the pathways are significantly similar. A total of 60 pathways were associated with human diseases, mostly focused on basic cellular functions like JAK–STAT signaling or metabolic functions like xenobiotic metabolism by cytochrome P450 enzymes. ELF EMF datasets were sporadically linked to human diseases, but no clear pattern emerged. Individual datasets showed some linkage to cancer, chemical dependency, metabolic disorders, and neurological disorders. RF EMF datasets were not strongly linked to any disorders but strongly linked to changes in several pathways. Based on these analyses, the most promising area for further research would be to focus on EMF and neurological function and disorders. PMID:27656641

Management of lower urinary tract symptoms in Parkinson's disease in the neurology clinic.

PubMed

Madan, Arina; Ray, Sudeshna; Burdick, Daniel; Agarwal, Pinky

2017-12-01

This clinical review aims to evaluate lower urinary tract symptoms (LUTS) in Parkinson's disease (PD) patients and the current treatment options available for these symptoms in a neurology setting. The review also addresses when referral to urology is appropriate. A literature search was conducted using the keywords 'LUTS', 'non-motor symptoms', 'overactive bladder', 'Parkinson's disease' and 'urinary symptoms' using the Medline/Pubmed search engine. Data collected ranged from 2000 to present with emphasis on recent publications. This review was conducted because LUTS in PD has a major impact on quality of life and is associated with early institutionalization. Emphasis is placed on treating overactive bladder with conservative strategies and medical management in the neurology setting. Quality of life can be improved and institutionalization can be delayed with a multimodal approach to bladder care.

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.

[Neurological diseases after lightning strike : Lightning strikes twice].

PubMed

Gruhn, K M; Knossalla, Frauke; Schwenkreis, Peter; Hamsen, Uwe; Schildhauer, Thomas A; Tegenthoff, Martin; Sczesny-Kaiser, Matthias

2016-06-01

Lightning strikes rarely occur but 85 % of patients have lightning-related neurological complications. This report provides an overview about different modes of energy transfer and neurological conditions related to lightning strikes. Moreover, two case reports demonstrate the importance of interdisciplinary treatment and the spectrum of neurological complications after lightning strikes.

MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases

PubMed Central

2011-01-01

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of mi- RNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly onto center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress. PMID:22194706

Newer insights to the neurological diseases among biblical characters of old testament

PubMed Central

Mathew, Stephen K.; Pandian, Jeyaraj D.

2010-01-01

Many people over the years have studied the Bible from a medical point of view offering diagnoses for the symptoms and signs that appear to have afflicted numerous individuals in the Bible. We review the biblical characters in the Old Testament and offer newer insights to their neurological diseases. We first look at the battle between Goliath and David. Interestingly, Goliath probably suffered from acromegaly. We propose autism as a diagnosis for Samson which would precede the first known case of autism by centuries. Isaac was a diabetic, and he probably had autonomic neuropathy. Few verses from the books of I Samuel, Psalms, and Ezekiel reveal symptoms suggestive of stroke. Jacob suffered from sciatica, and the child of the Shunnamite woman in II Kings had a subarachnoid hemorrhage. These instances among others found in the Old Testament of the Bible offer newer insights on the history of current neurological diseases. PMID:21085524

Texas Occurrence of Lyme Disease and Its Neurological Manifestations.

PubMed

Dandashi, Jad A; Nizamutdinov, Damir; Dayawansa, Samantha; Fonkem, Ekokobe; Huang, Jason H

2016-06-01

Today, Lyme disease is the most commonly reported tick-borne disease in the United States and Europe. The culprits behind Lyme disease are the Borrelia species of bacteria. In the USA, Borrelia burgdorferi causes the majority of cases, while in Europe and Asia Borrelia afzelii and Borrelia garinii carry the greatest burden of disease. The clinical manifestations of Lyme disease have been identified as early localized, early disseminated, and late chronic. The neurological effects of Lyme disease include both peripheral and central nervous systems involvement, including focal nerve abnormalities, cranial neuropathies, painful radiculoneuritis, meningitis, and/or toxic metabolic encephalopathy, known as Lyme encephalopathy. Given the geographic predominance of Lyme disease in the Northeast and Midwest of the USA, no major studies have been conducted regarding Southern states. Between 2005 and 2014, the Center for Disease Control has reported 582 confirmed cases of Lyme disease in Texas. Because of the potential for increased incidence and prevalence in Texas, it has become essential for research and clinical efforts to be diverted to the region. The Texas A&M College of Veterinary Medicine and Biomedical Sciences Lyme Lab has been investigating the ecology of Lyme disease in Texas and developing a pan-specific serological test for Lyme diagnosis. This report aimed to exposure materials and raise awareness of Lyme disease to healthcare providers.

Neurological Sequelae Resulting from Encephalitic Alphavirus Infection

PubMed Central

Ronca, Shannon E.; Dineley, Kelly T.; Paessler, Slobodan

2016-01-01

The recent surge in viral clinical cases and associated neurological deficits have reminded us that viral infections can lead to detrimental, long-term effects, termed sequelae, in survivors. Alphaviruses are enveloped, single-stranded positive-sense RNA viruses in the Togaviridae family. Transmission of alphaviruses between and within species occurs mainly via the bite of an infected mosquito bite, giving alphaviruses a place among arboviruses, or arthropod-borne viruses. Alphaviruses are found throughout the world and typically cause arthralgic or encephalitic disease in infected humans. Originally detected in the 1930s, today the major encephalitic viruses include Venezuelan, Western, and Eastern equine encephalitis viruses (VEEV, WEEV, and EEEV, respectively). VEEV, WEEV, and EEEV are endemic to the Americas and are important human pathogens, leading to thousands of human infections each year. Despite awareness of these viruses for nearly 100 years, we possess little mechanistic understanding regarding the complications (sequelae) that emerge after resolution of acute infection. Neurological sequelae are those complications involving damage to the central nervous system that results in cognitive, sensory, or motor deficits that may also manifest as emotional instability and seizures in the most severe cases. This article serves to provide an overview of clinical cases documented in the past century as well as a summary of the reported neurological sequelae due to VEEV, WEEV, and EEEV infection. We conclude with a treatise on the utility of, and practical considerations for animal models applied to the problem of neurological sequelae of viral encephalopathies in order to decipher mechanisms and interventional strategies. PMID:27379085

Mosapride for gastroesophageal reflux disease in neurologically impaired patients.

PubMed

Komura, Makoto; Kanamori, Yutaka; Tanaka, Yujiro; Kodaka, Tetsuro; Sugiyama, Masahiko; Terawaki, Kan; Suzuki, Kan; Iwanaka, Tadashi

2017-03-01

The prokinetic agent cisapride is effective for the treatment of gastroesophageal reflux disease (GERD) in infants and children, but is no longer used for this purpose because of safety concerns. Therefore, other pharmacological agents need to be investigated for efficacy in GERD treatment. In this study, we examined the effectiveness and safety of mosapride for the treatment of neurologically impaired children and adolescents with GERD. Mosapride (0.3 mg/kg/day) was administered to 11 neurologically impaired patients with GERD (five male; median age, 12.3 years). Esophageal acid exposure was measured using esophageal pH monitoring before and at >5 days after the start of mosapride treatment. The pressure and length of the lower esophageal sphincter were compared before and after mosapride treatment. In the 11 patients, median reflux index (percentage of the total monitoring period during which recorded pH was <4.0) was 17.5% (range, 4.4-59%) before and 8.2% (range, 2.8-20.7%) after mosapride treatment (P = 0.02). Median esophageal clearance was 1.0 min/reflux (range, 0.5-2.1 min/reflux) before and 0.7 min/reflux (range, 0.4-1.2 min/reflux) after treatment with mosapride (P = 0.02). The median number of reflux episodes before (219) and after (122) drug treatment did not differ significantly. The decreased reflux index in neurologically impaired patients with GERD is due to mosapride, therefore mosapride may be a candidate for GERD treatment. © 2016 Japan Pediatric Society.

Functional Performance and Associations between Performance Tests and Neurological Assessment Differ in Men and Women with Parkinson's Disease.

PubMed

Medijainen, Kadri; Pääsuke, Mati; Lukmann, Aet; Taba, Pille

2015-01-01

Neurological assessment of a patient with Parkinson's disease (PD) is expected to reflect upon functional performance. As women are known to report more limitations even for same observed functional performance level, present study was designed to examine whether associations between neurological assessments and functional performance differ across genders. 14 men and 14 women with PD participated. Functional performance was assessed by measuring walking speeds on 10-meter walk test (10MWT) and by performing timed-up-and-go-test (TUG). Neurological assessment included Hoehn and Yahr Scale (HY), Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Schwab and England Activities of Daily Living Scale (S-E), and Mini Mental State Examination (MMSE). In women with PD, Kendall's tau-b correlation analyses revealed significant correlations between functional performance tests and neurological assessment measures, with the exception in MMSE. No corresponding associations were found for men, although they demonstrated better functional performance, as expected. Men in similar clinical stage of the PD perform better on functional tests than women. Disease severity reflects upon functional performance differently in men and women with PD. Results indicate that when interpreting the assessment results of both functional performance and neurological assessment tests, the gender of the patient should be taken into consideration.

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.

Neurological Disease associated with Folate Deficiency

PubMed Central

Reynolds, E. H.; Rothfeld, P.; Pincus, Jonathen H.

1973-01-01

In a general medical hospital population the neurological status of 24 patients with severe folate deficiency was compared with that of a control group of 21 patients with normal serum folate. A significant increase of organic brain syndrome and pyramidal tract damage was found in the folate-deficient group. These findings were independent of the degree of anaemia or the presence of alcoholism. These data are consistent with the view that severe folate deficiency may cause neurological deficits. PMID:4703098

Wikipedia and neurological disorders.

PubMed

Brigo, Francesco; Igwe, Stanley C; Nardone, Raffaele; Lochner, Piergiorgio; Tezzon, Frediano; Otte, Willem M

2015-07-01

Our aim was to evaluate Wikipedia page visits in relation to the most common neurological disorders by determining which factors are related to peaks in Wikipedia searches for these conditions. Millions of people worldwide use the internet daily as a source of health information. Wikipedia is a popular free online encyclopedia used by patients and physicians to search for health-related information. The following Wikipedia articles were considered: Alzheimer's disease; Amyotrophic lateral sclerosis; Dementia; Epilepsy; Epileptic seizure; Migraine; Multiple sclerosis; Parkinson's disease; Stroke; Traumatic brain injury. We analyzed information regarding the total article views for 90 days and the rank of these articles among all those available in Wikipedia. We determined the highest search volume peaks to identify possible relation with online news headlines. No relation between incidence or prevalence of neurological disorders and the search volume for the related articles was found. Seven out of 10 neurological conditions showed relations in search volume peaks and news headlines. Six out of these seven peaks were related to news about famous people suffering from neurological disorders, especially those from showbusiness. Identification of discrepancies between disease burden and health seeking behavior on Wikipedia is useful in the planning of public health campaigns. Celebrities who publicly announce their neurological diagnosis might effectively promote awareness programs, increase public knowledge and reduce stigma related to diagnoses of neurological disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Paraneoplastic neurologic syndrome and autoimmune Addison disease in a patient with thymoma.

PubMed

Morita, Hiroyuki; Hirota, Takuo; Mune, Tomoatsu; Suwa, Tetsuya; Ishizuka, Tatsuo; Inuzuka, Takashi; Tanaka, Keiko; Ishimori, Masatoshi; Nakamura, Shigenori; Yasuda, Keigo

2005-01-01

A 48-year-old man with autoimmune Addison disease developed the following paraneoplastic neurologic syndromes (PNNS): limbic encephalitis, opsoclonus/myoclonus, and sensorimotor and autonomic neuropathies. An anterior mediastinal mass detected on a chest computed tomographic scan was found on resection to be a noninvasive lymphocytic thymoma. The PNNS went into remission 1 year after the thymectomy. This is the first case of thymoma associated with autoimmune Addison disease and PNNS to be described in the literature.

The "Growing" Reality of the Neurological Complications of Global "Stem Cell Tourism".

PubMed

Julian, Katie; Yuhasz, Nick; Hollingsworth, Ethan; Imitola, Jaime

2018-04-01

"Stem cell tourism" is defined as the unethical practice of offering unproven cellular preparations to patients suffering from various medical conditions. This phenomenon is rising in the field of neurology as patients are requesting information and opportunities for treatment with stem cells for incurable conditions such as multiple sclerosis and amyotrophic lateral sclerosis, despite their clinical research and experimental designation. Here, we review the recent trends in "stem cell tourism" in both the United States and abroad, and discuss the recent reports of neurological complications from these activities. Finally, we frame critical questions for the field of neurology regarding training in the ethical, legal, and societal issues of the global "stem cell tourism," as well as suggest strategies to alleviate this problem. Although there are ongoing legitimate clinical trials with stem cells for neurological diseases, procedures offered by "stem cell clinics" cannot be defined as clinical research. They lack the experimental and state-of-the-art framework defined by peers and the FDA that focus on human research that safeguard the protection of human subjects against economical exploitation, unwanted side effects, and futility of unproven procedures. "Stem cell tourism" ultimately exploits therapeutic hope of patients and families with incurable neurological diseases and can put in danger the legitimacy of stem cell research as a whole. We posit that an improvement in education, regulation, legislation, and involvement of authorities in global health in neurology and neurosurgery is required. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neurologic manifestations in Sagliker syndrome: uglifying human face appearance in severe and late secondary hyperparathyroidism in chronic renal failure patients.

PubMed

Giray, Semih; Sagliker, Yahya; Yildiz, Ismail; Halvaci, Ilker; Paylar, Nuray; Ocal, Fatih; Balal, Mustafa; Ozkaynak, Piril Sagliker; Paydas, Saime; Sagliker, Cemal; Sagliker, Hasan Sabit; Kiralp, Necati; Adam, Siddik Momin; Esenturk, Mustafa; Gocmez, Erdal; Taskapan, Hulya; Yuksekgonul, Musa; Emir, Idris; Guler, Turgay; Yakar, Hasan; Sekin, Oktay; Kayali, Erkan; Caliskan, Sihli; Eskiocak, Ali Fuat; Ogruk, Bulent; Guzelyurt, Tamer; Kurt, Cemal

2006-07-01

Patients with chronic renal failure (CRF) often have signs and symptoms related to fluid and electrolyte disturbances, anemia, malnutrition, bone disease, and gastrointestinal problems. Vascular and neurologic impairment in particular remain an important source of morbidity and mortality in this vulnerable patient population. Sagliker syndrome is a novel syndrome that was recently described in 2004 in patients with CRF and severe and late secondary hyperparathyroidism who suffered from severe skull and facial bone changes, particularly from uglifying human face appearances and neuropsychiatric disorders. The goal of this study was to assess neuropsychiatric manifestations occurring in CRF patients with Sagliker syndrome. Four female and 8 male patients with CRF on regular dialysis at the hemodialysis units of the Internal Medicine Departments around southern Turkey participated in the study. All patients underwent a clinical neurologic examination performed by the same neurologist. Neuropsychiatric signs and symptoms were found in all cases. The results showed that the most frequent neurologic manifestations in CRF patients with Sagliker syndrome were headache, polyneuropathy, cranial neuropathy, fatigue, and psychiatric disorders.

Targeting the brain: considerations in 332 consecutive patients treated by deep brain stimulation (DBS) for severe neurological diseases.

PubMed

Franzini, Angelo; Cordella, Roberto; Messina, Giuseppe; Marras, Carlo Efisio; Romito, Luigi Michele; Albanese, Alberto; Rizzi, Michele; Nardocci, Nardo; Zorzi, Giovanna; Zekaj, Edvin; Villani, Flavio; Leone, Massimo; Gambini, Orsola; Broggi, Giovanni

2012-12-01

Deep brain stimulation (DBS) extends the treatment of some severe neurological diseases beyond pharmacological and conservative therapy. Our experience extends the field of DBS beyond the treatment of Parkinson disease and dystonia, including several other diseases such as cluster headache and disruptive behavior. Since 1993, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan, 580 deep brain electrodes were implanted in 332 patients. The DBS targets include Stn, GPi, Voa, Vop, Vim, CM-pf, pHyp, cZi, Nacc, IC, PPN, and Brodmann areas 24 and 25. Three hundred patients are still available for follow-up and therapeutic considerations. DBS gave a new therapeutic chance to these patients affected by severe neurological diseases and in some cases controlled life-threatening pathological conditions, which would otherwise result in the death of the patient such as in status dystonicus, status epilepticus and post-stroke hemiballismus. The balance of DBS in severe neurological disease is strongly positive even if further investigations and studies are needed to search for new applications and refine the selection criteria for the actual indications.

Yellow fever vaccine-associated neurological disease, a suspicious case.

PubMed

Beirão, Pedro; Pereira, Patrícia; Nunes, Andreia; Antunes, Pedro

2017-03-02

A 70-year-old man with known cardiovascular risk factors, presented with acute onset expression aphasia, agraphia, dyscalculia, right-left disorientation and finger agnosia, without fever or meningeal signs. Stroke was thought to be the cause, but cerebrovascular disease investigation was negative. Interviewing the family revealed he had undergone yellow fever vaccination 18 days before. Lumbar puncture revealed mild protein elevation. Cultural examinations, Coxiella burnetti, and neurotropic virus serologies were negative. Regarding the yellow fever virus, IgG was identified in serum and cerebrospinal fluid (CSF), with negative IgM and virus PCR in CSF. EEG showed an encephalopathic pattern. The patient improved gradually and a week after discharge was his usual self. Only criteria for suspect neurotropic disease were met, but it's possible the time spent between symptom onset and lumbar puncture prevented a definite diagnosis of yellow fever vaccine-associated neurological disease. This gap would have been smaller if the vaccination history had been collected earlier. 2017 BMJ Publishing Group Ltd.

Fibrinolytic activity in cerebrospinal fluid of dogs with different neurological disorders.

PubMed

de la Fuente, C; Monreal, L; Cerón, J; Pastor, J; Viu, J; Añor, S

2012-01-01

Fibrinolytic activity in cerebrospinal fluid (CSF) is activated in humans by different pathologic processes. To investigate fibrinolytic activity in the CSF of dogs with neurological disorders by measuring CSF D-dimer concentrations. One hundred and sixty-nine dogs with neurological disorders, 7 dogs with systemic inflammatory diseases without central nervous system involvement (SID), and 7 healthy Beagles were included in the study. Dogs with neurological disorders included 11 with steroid-responsive meningitis-arteritis (SRMA), 37 with other inflammatory neurological diseases (INF), 38 with neoplasia affecting the central nervous system (NEO), 28 with spinal compressive disorders (SCC), 15 with idiopathic epilepsy (IE), and 40 with noninflammatory neurological disorders (NON-INF). Prospective observational study. D-dimers and C-reactive protein (CRP) were simultaneously measured in paired CSF and blood samples. D-dimers and CRP were detected in 79/183 (43%) and in 182/183 (99.5%) CSF samples, respectively. All dogs with IE, SID, and controls had undetectable concentrations of D-dimers in the CSF. CSF D-dimer concentrations were significantly (P < .001) higher in dogs with SRMA than in dogs with other diseases and controls. CSF CRP concentration in dogs with SRMA was significantly (P < .001) higher than in dogs of other groups and controls, except for the SID group. No correlation was found between blood and CSF D-dimer concentrations. Intrathecal fibrinolytic activity seems to be activated in some canine neurological disorders, and it is high in severe meningeal inflammatory diseases. CSF D-dimer concentrations may be considered a diagnostic marker for SRMA. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Fatal degenerative neurologic illnesses in men who participated in wild game feasts--Wisconsin, 2002.

PubMed

2003-02-21

Creutzfeldt-Jakob disease (CJD) is a fatal neurologic disorder in humans. CJD is one of a group of conditions known as transmissible spongiform encephalopathies (TSEs), or prion diseases, that are believed to be caused by abnormally configured, host-encoded prion proteins that accumulate in the central nervous tissue. CJD has an annual incidence of approximately 1 case per million population in the United States and occurs in three forms: sporadic, genetically determined, and acquired by infection. In the latter form, the incubation period is measured typically in years. Recent evidence that prion infection can cross the species barrier between humans and cattle has raised increasing public health concerns about the possible transmission to humans of a TSE among deer and elk known as chronic wasting disease (CWD). During 1993-1999, three men who participated in wild game feasts in northern Wisconsin died of degenerative neurologic illnesses. This report documents the investigation of these deaths, which was initiated in August 2002 and which confirmed the death of only one person from CJD. Although no association between CWD and CJD was found, continued surveillance of both diseases remains important to assess the possible risk for CWD transmission to humans.

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.

Physical activity and exercise attenuate neuroinflammation in neurological diseases.

PubMed

Spielman, Lindsay Joy; Little, Jonathan Peter; Klegeris, Andis

2016-07-01

Major depressive disorder (MDD), schizophrenia (SCH), Alzheimer's disease (AD), and Parkinson's disease (PD) are devastating neurological disorders, which increasingly contribute to global morbidity and mortality. Although the pathogenic mechanisms of these conditions are quite diverse, chronic neuroinflammation is one underlying feature shared by all these diseases. Even though the specific root causes of these diseases remain to be identified, evidence indicates that the observed neuroinflammation is initiated by unique pathological features associated with each specific disease. If the initial acute inflammation is not resolved, a chronic neuroinflammatory state develops and ultimately contributes to disease progression. Chronic neuroinflammation is characterized by adverse and non-specific activation of glial cells, which can lead to collateral damage of nearby neurons and other glia. This misdirected neuroinflammatory response is hypothesized to contribute to neuropathology in MDD, SCH, AD, and PD. Physical activity (PA), which is critical for maintenance of whole body and brain health, may also beneficially modify neuroimmune responses. Since PA has neuroimmune-modifying properties, and the common underlying feature of MDD, SCH, AD, and PD is chronic neuroinflammation, we hypothesize that PA could minimize brain diseases by modifying glia-mediated neuroinflammation. This review highlights current evidence supporting the disease-altering potential of PA and exercise through modifications of neuroimmune responses, specifically in MDD, SCH, AD and PD. Copyright © 2016 Elsevier Inc. All rights reserved.

Neurological Manifestations of Autosomal Dominant Alzheimer’s Disease from the DIAN cohort and a meta-analysis

PubMed Central

Tang, Mengxuan; Ryman, Davis C.; McDade, Eric; Jasielec, Mateusz S.; Buckles, Virginia D.; Cairns, Nigel J.; Fagan, Anne M.; Goate, Alison; Marcus, Daniel S.; Xiong, Chengjie; Allegri, Ricardo F.; Chhatwal, Jasmeer P.; Danek, Adrian; Farlow, Martin R.; Fox, Nick; Ghetti, Bernardino; Graff-Radford, Neill R.; Laske, Christopher; Martins, Ralph N.; Masters, Colin L.; Mayeux, Richard P.; Ringman, John M.; Rossor, Martin N.; Salloway, Stephen P.; Schofield, Peter R.; Morris, John C.; Bateman, Randall J.

2016-01-01

Background To evaluate the prevalence rates of non-amnestic neurological symptoms of autosomal dominant Alzheimer’s disease (ADAD) in the DIAN Observational Study (DIAN–OBS) and the published literature. Analyses were conducted to clarify the prevalence of neurological manifestations of ADAD mutation carriers as a group. Methods Using the DIAN-OBS study database and 189 peer-reviewed publications on ADAD families, we extracted individual-level data on age of symptom onset, disease course from onset to death, and the presence of fourteen neurological findings that have been reported in association with ADAD and included symptomatic subjects only. The primary outcomes were the rates of various neurological symptoms and the contribution of age and specific mutations on the prevalence of the neurological symptoms. Analyses were done using descriptive statistics, comparisons of means and frequencies and multivariable linear regression. Findings Our meta-analysis dataset includes 1228 affected individuals, with detailed clinical descriptions of 753. The DIAN–OBS dataset included 107 individuals with detailed clinical data. The most prevalent non-amnestic cognitive manifestations in DIAN were those typical of mild-moderate Alzheimer’s disease, including visual agnosia (95% CI 45·7%–64·6%), aphasia (43·8%–62·7%), and behavioral changes (51·5%–70·0%). The prevalence of non-amnestic cognitive manifestations from the published literature were (95% CI 3·9%–7·2%) for visual agnosia, (20%–26%) for aphasia, and (28·4%–35·1%) for behavioral changes. Prevalence of non-cognitive neurological manifestations in DIAN was low, including myoclonus and spasticity (3·8%–15·0%), seizures (0·5%–9·1%) and moderate for parkinsonism (5·3%–17·1%). Whereas, in the published literature the prevalence was (95% CI 16·6%–22·2% and 12·5%–17·6%) for myoclonus and spasticity, (10·1%–15·0%) for parkinsonism, and (17·4%–23·2%) for seizures. Age of

Current neurology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Appel, S.H.

1988-01-01

The topics covered in this book include: Duchenne muscular dystrophy: DNA diagnosis in practice; Central nervous system magnetic resonance imaging; and Magnetic resonance spectroscopy of neurologic diseases.

International Survey of Critically Ill Children With Acute Neurologic Insults: The Prevalence of Acute Critical Neurological Disease in Children: A Global Epidemiological Assessment Study.

PubMed

Fink, Ericka L; Kochanek, Patrick M; Tasker, Robert C; Beca, John; Bell, Michael J; Clark, Robert S B; Hutchison, Jamie; Vavilala, Monica S; Fabio, Anthony; Angus, Derek C; Watson, R Scott

2017-04-01

The international scope of critical neurologic insults in children is unknown. Our objective was to assess the prevalence and outcomes of children admitted to PICUs with acute neurologic insults. Prospective study. Multicenter (n = 107 PICUs) and multinational (23 countries, 79% in North America and Europe). Children 7 days to 17 years old admitted to the ICU with new traumatic brain injury, stroke, cardiac arrest, CNS infection or inflammation, status epilepticus, spinal cord injury, hydrocephalus, or brain mass. None. We evaluated the prevalence and outcomes of children with predetermined acute neurologic insults. Child and center characteristics were recorded. Unfavorable outcome was defined as change in pre-post insult Pediatric Cerebral Performance Category score greater than or equal to 2 or death at hospital discharge or 3 months, whichever came first. Screening data yielded overall prevalence of 16.2%. Of 924 children with acute neurologic insults, cardiac arrest (23%) and traumatic brain injury (19%) were the most common. All-cause mortality at hospital discharge was 12%. Cardiac arrest subjects had highest mortality (24%), and traumatic brain injury subjects had the most unfavorable outcomes (49%). The most common neurologic insult was infection/inflammation in South America, Asia, and the single African site but cardiac arrest in the remaining regions. Neurologic insults are a significant pediatric international health issue. They are frequent and contribute substantial morbidity and mortality. These data suggest a need for an increased focus on acute critical neurologic diseases in infants and children including additional research, enhanced availability of clinical resources, and the development of new therapies.

Longing for homeliness: exploring mealtime experiences of patients suffering from a neurological disease.

PubMed

Beck, Malene; Poulsen, Ingrid; Martinsen, Bente; Birkelund, Regner

2018-03-01

Many patients suffering from a neurological disease experience eating difficulties during mealtimes in the hospital. Consequently, they often refrain from eating in public places to avoid potentially awkward situations. Eating is an essential part of life, providing patients with comfort during their hospitalisation. Therefore, attention should be paid to these patients, who encounter eating difficulties to foster a positive mealtime experience. To study what patients afflicted with a neurological disease experience and assign meaning when participating in mealtimes during hospitalisation. Ten semi-structured interviews with patients were conducted and recorded. After transcription the text was analysed, and interpreted compromising three methodological steps inspired by the French philosopher, Paul Ricouer. Three themes were identified through data analysis and interpretation: i) The missing feeling of homeliness, ii) The battle between socialisation vs. isolation, and iii) The sense of time, rhythm, and presence. To patients suffering from a neurological disease, mealtimes are not only a manageable task, but also a part of existential care that leads to positive experience. Aesthetic elements were shown to have the potential of making the patients feel comfortable and homely when hospitalised. This was important, as our study also identified that patients were longing for homeliness when participating in mealtimes during hospitalisation. Our findings emphasised the need of proceeding to interventions that includes mealtime assistance and protects the mealtime activity. Hence, it informs hospital organisations of the importance of restructuring mealtime environment, so that existential care can take place. © 2017 Nordic College of Caring Science.

The crystal structure of human GlnRS provides basis for the development of neurological disorders

DOE PAGES

Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen; ...

2016-02-10

Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggestmore » that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords« less

The crystal structure of human GlnRS provides basis for the development of neurological disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen

Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggestmore » that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords« less

Neurologic Deterioration in Patients with Moyamoya Disease during Pregnancy, Delivery, and Puerperium.

PubMed

Park, Wonhyoung; Ahn, Jae Sung; Chung, Jaewoo; Chung, Yeongu; Lee, Seungjoo; Park, Jung Cheol; Kwun, Byung Duk

2018-03-01

We reviewed our clinical experience of patients with moyamoya disease (MMD) who gave birth and assessed characteristics of those experiencing neurologic deterioration. The patients were classified into patients diagnosed with MMD during pregnancy and puerperium (group 1) and those diagnosed before pregnancy (group 2). We retrospectively reviewed patient characteristics, MMD treatment, neurologic symptoms before and during pregnancy and/after puerperium, obstetrical history, and delivery type in groups 1 and 2. Group 1 included 2 patients with deterioration of pre-existing transient ischemic attacks (TIAs) and acute cerebral infarction and 1 patient with seizures and newly developed TIAs during pregnancy and/or puerperium. Group 2 included 20 patients with 23 pregnancies. In group 2, 4 patients had deterioration of TIAs during pregnancy and puerperium. There were significant differences between the cases without neurologic deterioration and with deterioration in group 2 (TIAs ≥10 before pregnancy, 0% vs. 75%, P = 0.002; severely reduced regional cerebrovascular reserve on single-photon emission computed tomography, 10.5% vs. 100%, P = 0.002; and surgical revascularization before pregnancy, 75% vs. 15.8%, P = 0.04). In groups 1 and 2, 6 of the 7 cases in which TIAs occurred or worsened during pregnancy or puerperium recovered to prepregnancy TIA levels after puerperium. Patients with severely reduced regional cerebrovascular reserve on single-photon emission computed tomography and frequent TIAs before pregnancy may experience neurologic deterioration during pregnancy, delivery, and puerperium. Surgical revascularization before pregnancy may decrease neurologic deterioration during these periods. Copyright © 2017 Elsevier Inc. All rights reserved.

Consensus guidelines for lumbar puncture in patients with neurological diseases.

PubMed

Engelborghs, Sebastiaan; Niemantsverdriet, Ellis; Struyfs, Hanne; Blennow, Kaj; Brouns, Raf; Comabella, Manuel; Dujmovic, Irena; van der Flier, Wiesje; Frölich, Lutz; Galimberti, Daniela; Gnanapavan, Sharmilee; Hemmer, Bernhard; Hoff, Erik; Hort, Jakub; Iacobaeus, Ellen; Ingelsson, Martin; Jan de Jong, Frank; Jonsson, Michael; Khalil, Michael; Kuhle, Jens; Lleó, Alberto; de Mendonça, Alexandre; Molinuevo, José Luis; Nagels, Guy; Paquet, Claire; Parnetti, Lucilla; Roks, Gerwin; Rosa-Neto, Pedro; Scheltens, Philip; Skårsgard, Constance; Stomrud, Erik; Tumani, Hayrettin; Visser, Pieter Jelle; Wallin, Anders; Winblad, Bengt; Zetterberg, Henrik; Duits, Flora; Teunissen, Charlotte E

2017-01-01

Cerebrospinal fluid collection by lumbar puncture (LP) is performed in the diagnostic workup of several neurological brain diseases. Reluctance to perform the procedure is among others due to a lack of standards and guidelines to minimize the risk of complications, such as post-LP headache or back pain. We provide consensus guidelines for the LP procedure to minimize the risk of complications. The recommendations are based on (1) data from a large multicenter LP feasibility study (evidence level II-2), (2) systematic literature review on LP needle characteristics and post-LP complications (evidence level II-2), (3) discussion of best practice within the Joint Programme Neurodegenerative Disease Research Biomarkers for Alzheimer's disease and Parkinson's Disease and Biomarkers for Multiple Sclerosis consortia (evidence level III). Our consensus guidelines address contraindications, as well as patient-related and procedure-related risk factors that can influence the development of post-LP complications. When an LP is performed correctly, the procedure is well tolerated and accepted with a low complication rate.

Dendritic transport of tick-borne flavivirus RNA by neuronal granules affects development of neurological disease.

PubMed

Hirano, Minato; Muto, Memi; Sakai, Mizuki; Kondo, Hirofumi; Kobayashi, Shintaro; Kariwa, Hiroaki; Yoshii, Kentaro

2017-09-12

Neurological diseases caused by encephalitic flaviviruses are severe and associated with high levels of mortality. However, little is known about the detailed mechanisms of viral replication and pathogenicity in the brain. Previously, we reported that the genomic RNA of tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus , is transported and replicated in the dendrites of neurons. In the present study, we analyzed the transport mechanism of the viral genome to dendrites. We identified specific sequences of the 5' untranslated region of TBEV genomic RNA that act as a cis -acting element for RNA transport. Mutated TBEV with impaired RNA transport in dendrites caused a reduction in neurological symptoms in infected mice. We show that neuronal granules, which regulate the transport and local translation of dendritic mRNAs, are involved in TBEV genomic RNA transport. TBEV genomic RNA bound an RNA-binding protein of neuronal granules and disturbed the transport of dendritic mRNAs. These results demonstrated a neuropathogenic virus hijacking the neuronal granule system for the transport of viral genomic RNA in dendrites, resulting in severe neurological disease.

Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease.

PubMed

Whiting, Rebecca E H; Jensen, Cheryl A; Pearce, Jacqueline W; Gillespie, Lauren E; Bristow, Daniel E; Katz, Martin L

2016-05-01

CLN2 disease is one of a group of lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene that cause an insufficiency or complete lack of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein degradation, and lack of this enzyme results in the accumulation of protein-rich autofluorescent lysosomal storage bodies in numerous cell types including neurons throughout the central nervous system and the retina. CLN2 disease is characterized primarily by progressive loss of neurological functions and vision as well as generalized neurodegeneration and retinal degeneration. In children the progressive loss of neurological functions typically results in death by the early teenage years. A Dachshund model of CLN2 disease with a null mutation in TPP1 closely recapitulates the human disorder with a progression from disease onset at approximately 4 months of age to end-stage at 10-11 months. Delivery of functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of the recombinant protein or by a single administration of a TPP1 gene therapy vector to the CSF, significantly delays the onset and progression of neurological signs and prolongs life span but does not prevent the loss of vision or modest retinal degeneration that occurs by 11 months of age. In this study we found that in dogs that received the CSF gene therapy treatment, the degeneration of the retina and loss of retinal function continued to progress during the prolonged life spans of the treated dogs. Eventually the normal cell layers of the retina almost completely disappeared. An exception was the ganglion cell layer. In affected dogs that received TPP1 gene therapy to the CSF and survived an average of 80 weeks, ganglion cell axons were present in numbers comparable to those of normal Dachshunds of similar age. The selective preservation of the retinal ganglion cells suggests

Neurological and Psychiatric Diseases and Their Unique Cognitive Profiles: Implications for Nursing Practice and Research

PubMed Central

Vance, David E.; Dodson, Joan E.; Watkins, Jason; Kennedy, Bridgett H.; Keltner, Norman L.

2013-01-01

To successfully negotiate and interact with one’s environment, optimal cognitive functioning is needed. Unfortunately, many neurological and psychiatric diseases impede certain cognitive abilities such as executive functioning or speed of processing; this can produce a poor fit between the patient and the cognitive demands of his or her environment. Such non-dementia diseases include bipolar disorder, schizophrenia, post-traumatic stress syndrome, depression, and anxiety disorders, just to name a few. Each of these diseases negatively affects particular areas of the brain, resulting in distinct cognitive profiles (e.g., deficits in executive functioning but normal speed of processing as seen in schizophrenia). In fact, it is from these cognitive deficits in which such behavioral and emotional symptoms may manifest (e.g., delusions, paranoia). This article highlights the distinct cognitive profiles of such common neurological and psychiatric diseases. An understanding of such disease-specific cognitive profiles can assist nurses in providing care to patients by knowing what cognitive deficits are associated with each disease and how these cognitive deficits impact everyday functioning and social interactions. Implications for nursing practice and research are posited within the framework of cognitive reserve and neuroplasticity. PMID:23422693

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

DNA Secondary Structure at Chromosomal Fragile Sites in Human Disease

PubMed Central

Thys, Ryan G; Lehman, Christine E; Pierce, Levi C. T; Wang, Yuh-Hwa

2015-01-01

DNA has the ability to form a variety of secondary structures that can interfere with normal cellular processes, and many of these structures have been associated with neurological diseases and cancer. Secondary structure-forming sequences are often found at chromosomal fragile sites, which are hotspots for sister chromatid exchange, chromosomal translocations, and deletions. Structures formed at fragile sites can lead to instability by disrupting normal cellular processes such as DNA replication and transcription. The instability caused by disruption of replication and transcription can lead to DNA breakage, resulting in gene rearrangements and deletions that cause disease. In this review, we discuss the role of DNA secondary structure at fragile sites in human disease. PMID:25937814

Neurologic manifestations of hypothyroidism in dogs.

PubMed

Bertalan, Abigail; Kent, Marc; Glass, Eric

2013-03-01

Hypothyroidism is a common endocrine disease in dogs. A variety of clinicopathologic abnormalities may be present; however, neurologic deficits are rare. In some instances, neurologic deficits may be the sole manifestation of hypothyroidism. Consequent ly, the diagnosis and management of the neurologic disorders associated with hypothyroidism can be challenging. This article describes several neurologic manifestations of primary hypothyroidism in dogs; discusses the pathophysiology of hypothyroidism-induced neurologic disorders affecting the peripheral and central nervous systems; and reviews the evidence for the neurologic effects of hypothyroidism.

Autonomic deficit not the cause of death in West Nile virus neurological disease.

PubMed

Wang, Hong; Siddharthan, Venkatraman; Hall, Jeffery O; Morrey, John D

2014-02-01

Some West Nile virus (WNV)-infected patients have been reported to manifest disease signs consistent with autonomic dysfunction. Moreover, WNV infection in hamsters causes reduced electromyography amplitudes of the gastrointestinal tract and diaphragm, and they have reduced heart rate variability (HRV), a read-out for the parasympathetic autonomic function. HRV was measured in both hamsters and mice using radiotelemetry to identify autonomic deficits. To identify areas of WNV infection within the medulla oblongata mapping to the dorsal motor nucleus of vagus (DMNV) and the nucleus ambiguus (NA), fluorogold dye was injected into the cervical trunk of the vagus nerve of hamsters. As a measurement of the loss of parasympathetic function, tachycardia was monitored contiguously over the time course of the disease. Decrease of HRV did not occur in all animals that died, which is not consistent with autonomic function being the mechanism of death. Fluorogold-stained cells in the DMNV were not stained for WNV envelope protein. Fourteen percent of WNV-stained cells were co-localized with fluorogold-stained cells in the NA. These data, however, did not suggest a fatal loss of autonomic functions because tachycardia was not observed in WNV-infected hamsters. Parasympathetic autonomic function deficit was not a likely mechanism of death in WNV-infected rodents and possibly in human patients with fatal WN neurological disease.

Samuel Alexander Kinnier Wilson. Wilson's disease, Queen Square and neurology.

PubMed

Broussolle, E; Trocello, J-M; Woimant, F; Lachaux, A; Quinn, N

2013-12-01

This historical article describes the life and work of the British physician Samuel Alexander Kinnier Wilson (1878-1937), who was one of the world's greatest neurologists of the first half of the 20th century. Early in his career, Wilson spent one year in Paris in 1903 where he learned from Pierre-Marie at Bicêtre Hospital. He subsequently retained uninterrupted links with French neurology. He also visited in Leipzig the German anatomist Paul Flechsig. In 1904, Wilson returned to London, where he worked for the rest of his life at the National Hospital for the Paralysed and Epileptic (later the National Hospital for Nervous Diseases, and today the National Hospital for Neurology and Neurosurgery) in Queen Square, and also at Kings' College Hospital. He wrote on 'the old motor system and the new', on disorders of motility and muscle tone, on the epilepsies, on aphasia, apraxia, tics, and pathologic laughing and crying, and most importantly on Wilson's disease. The other objective of our paper is to commemorate the centenary of Wilson's most important work published in 1912 in Brain, and also in Revue Neurologique, on an illness newly recognized and characterized by him entitled "Progressive lenticular degeneration, a familial nervous disease associated with liver cirrhosis". He analyzed 12 clinical cases, four of whom he followed himself, but also four cases previously published by others and a further two that he considered in retrospect had the same disease as he was describing. The pathological profile combined necrotic damage in the lenticular nuclei of the brain and hepatic cirrhosis. This major original work is summarized and discussed in the present paper. Wilson not only delineated what was later called hepato-lenticular degeneration and Wilson's disease, but also introduced for the first time the terms extrapyramidal syndrome and extrapyramidal system, stressing the role of the basal ganglia in motility. The present historical work emphasizes the special

Genetic neurological channelopathies: molecular genetics and clinical phenotypes.

PubMed

Spillane, J; Kullmann, D M; Hanna, M G

2016-01-01

Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. 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/

PPAR agonists as therapeutics for CNS trauma and neurological diseases

PubMed Central

Mandrekar-Colucci, Shweta; Sauerbeck, Andrew; Popovich, Phillip G.; McTigue, Dana M.

2013-01-01

Traumatic injury or disease of the spinal cord and brain elicits multiple cellular and biochemical reactions that together cause or are associated with neuropathology. Specifically, injury or disease elicits acute infiltration and activation of immune cells, death of neurons and glia, mitochondrial dysfunction, and the secretion of substrates that inhibit axon regeneration. In some diseases, inflammation is chronic or non-resolving. Ligands that target PPARs (peroxisome proliferator-activated receptors), a group of ligand-activated transcription factors, are promising therapeutics for neurologic disease and CNS injury because their activation affects many, if not all, of these interrelated pathologic mechanisms. PPAR activation can simultaneously weaken or reprogram the immune response, stimulate metabolic and mitochondrial function, promote axon growth and induce progenitor cells to differentiate into myelinating oligodendrocytes. PPAR activation has beneficial effects in many pre-clinical models of neurodegenerative diseases and CNS injury; however, the mechanisms through which PPARs exert these effects have yet to be fully elucidated. In this review we discuss current literature supporting the role of PPAR activation as a therapeutic target for treating traumatic injury and degenerative diseases of the CNS. PMID:24215544

Neurologic outcome after thoracolumbar partial lateral corpectomy for intervertebral disc disease in 72 dogs.

PubMed

Salger, Florian; Ziegler, Luisa; Böttcher, Irene Christine; Oechtering, Gerhard; Böttcher, Peter; Flegel, Thomas

2014-07-01

To determine neurologic outcome and factors influencing outcome after thoracolumbar partial lateral corpectomy (PLC) in dogs with intervertebral disc disease (IVDD) causing ventral spinal cord compression. Retrospective case series. Dogs with IVDD (n = 72; 87 PLC). Dogs with IVDD between T9 and L5 were included if treated by at least 1 PLC. Exclusion criteria were: previous spinal surgery, combination of PLC with another surgical procedure. Neurologic outcome was assessed by: (1) modified Frankel score (MFS) based on neurologic examinations at 4 time points (before surgery, immediately after PLC, at discharge and 4 weeks after PLC); and (2) owner questionnaire. The association of the following factors with neurologic outcome was analyzed: age, body weight, duration of current neurologic dysfunction (acute, chronic), IVDD localization, breed (chondrodystrophic, nonchondrodystrophic), number of PLCs, degree of presurgical spinal cord compression and postsurgical decompression, slot depth, presurgical MFS. Presurgical spinal cord compression was determined by CT myelography (71 dogs) or MRI (1 dog), whereas postsurgical decompression and slot depth were determined on CT myelography (69 dogs). MFS was improved in 18.7%, 31.7%, and 64.2% of dogs at the 3 postsurgical assessments, whereas it was unchanged in 62.6%, 52.8%, and 32.0% at corresponding time points. Based on owner questionnaire, 91.4% of dogs were ambulatory 6 months postsurgically with 74.5% having a normal gait. Most improvement in neurologic function developed within 6 months after surgery. Presurgical MFS was the only variable significantly associated with several neurologic outcome measurements (P < .01). PLC is an option for decompression in ventrally compressing thoracolumbar IVDD. Prognosis is associated with presurgical neurologic condition. © Copyright 2014 by The American College of Veterinary Surgeons.

Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.

PubMed

2017-11-01

Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million

Feeding problems in children with neurological disorders.

PubMed

Jamroz, Ewa; Głuszkiewicz, Ewa; Grzybowska-Chlebowczyk, Urszula; Woś, Halina

2012-01-01

The aim of this study was to evaluate the prevalence of selected risk factors of weight deficiency in children with chronic metabolic diseases. The study group involved 160 children, from 2 months to 15 years (mean age 3.14 years), with diseases of the nervous system and body weight deficiency. According to the type of neurological disease the following groups of patients were separated: static encephalopathies, progressive encephalopathies, disorders of mental development of undetermined etiology, genetically determined diseases. As the exponent of malnutrition, z-score of weight-for-age standards was used. An inclusion criterion for the study group was z-score of weight-for-age < - 2SD. The analysed risk factors of body weight deficiency were: mode of feeding children, neurological disorders, oral motor dysfunction, diseases of other organs, gastrointestinal motility disorders (oral cavity, esophagus, intestines) and type of nutritional therapy. The most advanced malnutrition was in children with progressive encephalopathies and genetically determined diseases. Seizures and muscular hypotonia were most common neurological disorders. Oral motor dysfunctions were observed in 40% of patients. Malnutrition in children with neurological disorders is associated mainly with neurological deficits. In this group of children monitoring of somatic development and early nutritional intervention are necessary.

Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines.

PubMed

Fujimori, Koki; Tezuka, Toshiki; Ishiura, Hiroyuki; Mitsui, Jun; Doi, Koichiro; Yoshimura, Jun; Tada, Hirobumi; Matsumoto, Takuya; Isoda, Miho; Hashimoto, Ryota; Hattori, Nubutaka; Takahashi, Takuya; Morishita, Shinichi; Tsuji, Shoji; Akamatsu, Wado; Okano, Hideyuki

2016-10-03

Patient-specific induced pluripotent stem cells (iPSCs) facilitate understanding of the etiology of diseases, discovery of new drugs and development of novel therapeutic interventions. A frequently used starting source of cells for generating iPSCs has been dermal fibroblasts (DFs) isolated from skin biopsies. However, there are also numerous repositories containing lymphoblastoid B-cell lines (LCLs) generated from a variety of patients. To date, this rich bioresource of LCLs has been underused for generating iPSCs, and its use would greatly expand the range of targeted diseases that could be studied by using patient-specific iPSCs. However, it remains unclear whether patient's LCL-derived iPSCs (LiPSCs) can function as a disease model. Therefore, we generated Parkinson's disease patient-specific LiPSCs and evaluated their utility as tools for modeling neurological diseases. We established iPSCs from two LCL clones, which were derived from a healthy donor and a patient carrying PARK2 mutations, by using existing non-integrating episomal protocols. Whole genome sequencing (WGS) and comparative genomic hybridization (CGH) analyses showed that the appearance of somatic variations in the genomes of the iPSCs did not vary substantially according to the original cell types (LCLs, T-cells and fibroblasts). Furthermore, LiPSCs could be differentiated into functional neurons by using the direct neurosphere conversion method (dNS method), and they showed several Parkinson's disease phenotypes that were similar to those of DF-iPSCs. These data indicate that the global LCL repositories can be used as a resource for generating iPSCs and disease models. Thus, LCLs are the powerful tools for generating iPSCs and modeling neurological diseases.

Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: an observational cohort study.

PubMed

Patterson, Marc C; Mengel, Eugen; Vanier, Marie T; Schwierin, Barbara; Muller, Audrey; Cornelisse, Peter; Pineda, Mercè

2015-05-28

Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat. The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if <3 scores were lower/unchanged between enrolment and last follow-up visit. In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (<2 years), 27 (32 %) had late-infantile (2 to <6 years), 30 (36 %) had juvenile (6 to <15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest

[Neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease : clinical features, MRI findings and follow-up study].

PubMed

Liu, Kun; Ma, Yan-xu; Zhang, Cheng-bing; Chen, Yi-ping; Ye, Xin-jian; Bai, Guang-hui; Yu, Zhi-kang; Yan, Zhi-han

2012-07-03

To explore the clinical and magnetic resonance imaging (MRI) characteristics and the follow-up outcomes of neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease. The clinical and MRI manifestations and follow-up outcomes in 35 children, at Second Affiliated Hospital, Wenzhou Medical College from August 2008 to November 2010, hospitalized with neurologic complications of enterovirus 71-infected hand-foot-mouth disease were retrospectively analyzed. Six children with aseptic meningitis presented the clinical symptoms and signs of meningitis. Five of them showed subdural effusion and ventriculomegaly, or both on MRI. At follow-ups, neurologic sequel could not be found. Among 24 cases with brainstem encephalitis, there were myoclonic jerks and tremor, ataxia, or both (grade I disease, n = 12), myoclonus and cranial-nerve involvement (grade II disease, n = 4), and cardiopulmonary failure after brain-stem infection (grade III disease, n = 8). In patients with brainstem encephalitis, lesions were predominantly located at the posterior portions of medulla and pons with hypointensity on T1WI and hyperintensity on T2WI. Cerebellar dentate nucleus, caudate nucleus and lenticular nucleus could also be involved. At follow-ups, the patients with mild symptoms had no neurologic sequel and the lesions within brain stem became small or vanished in most cases. While in the majority of serious patients, neurologic sequel could be found and the lesions located at brain stem became encephalomalacia. Fourteen cases with acute flaccid paralysis presented acute limb myasthenia with tendon reflex and muscular tension decreased. On spinal MRI, the lesions predominantly involved anterior horn regions of spinal cord with hypointensity on T1WI and hyperintensity on T2WI. Most patients improved their muscle strength and most lesions of spinal cord became smaller or vanished during follow-ups. MRI is the most effective modality of diagnosis and follow-up for

[Deficiency, disability, neurology and literature].

PubMed

Collado-Vázquez, Susana; Cano-de-la-Cuerda, Roberto; Jiménez-Antona, Carmen; Muñoz-Hellín, Elena

2012-08-01

Literature has always been attracted to neurological pathologies and the numerous works published on the subject are proof of this. Likewise, a number of physicians have been fiction writers and have drawn on their scientific knowledge to help develop their stories. The study addresses the appearance of neurological pathologies in a sample of literary works and examines the description of the disease, its treatment, the patient's view and the relationship between healthcare professionals and the socio-familial milieu. We review some of the greatest literary works of all times that deal with neurological pathologies, such as Don Quixote, Julius Caesar, David Copperfield, The Idiot or Miau, and many of them are seen to offer a very faithful portrayal of the disease. Similarly, we have also reviewed works that provide a personal account of life with neurological diseases and the ensuing disability written either by the patients themselves or by their relatives, examples being The Diving Bell and the Butterfly, My Left Foot or One Chance in a Thousand. Literature has helped to offer a realistic vision of neurologically-based pathologies and the healthcare professionals who work with them; there are many examples that portray the experiences of the patients themselves and the importance of support from the family is a feature that is constantly underlined.

Neurological Complications Following Endoluminal Repair of Thoracic Aortic Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morales, J. P.; Taylor, P. R.; Bell, R. E.

2007-09-15

Open surgery for thoracic aortic disease is associated with significant morbidity and the reported rates for paraplegia and stroke are 3%-19% and 6%-11%, respectively. Spinal cord ischemia and stroke have also been reported following endoluminal repair. This study reviews the incidence of paraplegia and stroke in a series of 186 patients treated with thoracic stent grafts. From July 1997 to September 2006, 186 patients (125 men) underwent endoluminal repair of thoracic aortic pathology. Mean age was 71 years (range, 17-90 years). One hundred twenty-eight patients were treated electively and 58 patients had urgent procedures. Anesthesia was epidural in 131, generalmore » in 50, and local in 5 patients. Seven patients developed paraplegia (3.8%; two urgent and five elective). All occurred in-hospital apart from one associated with severe hypotension after a myocardial infarction at 3 weeks. Four of these recovered with cerebrospinal fluid (CSF) drainage. One patient with paraplegia died and two had permanent neurological deficit. The rate of permanent paraplegia and death was 1.6%. There were seven strokes (3.8%; four urgent and three elective). Three patients made a complete recovery, one had permanent expressive dysphasia, and three died. The rate of permanent stroke and death was 2.1%. Endoluminal treatment of thoracic aortic disease is an attractive alternative to open surgery; however, there is still a risk of paraplegia and stroke. Permanent neurological deficits and death occurred in 3.7% of the patients in this series. We conclude that prompt recognition of paraplegia and immediate insertion of a CSF drain can be an effective way of recovering spinal cord function and improving the prognosis.« less

Profile of neurological admissions at the University of Nigeria Teaching Hospital Enugu.

PubMed

Ekenze, O S; Onwuekwe, I O; Ezeala Adikaibe, B A

2010-01-01

The burden of Neurological diseases may be on the increase especially in developing countries. Improved outcome in these settings may require appreciation of the spectrum of Neurological diseases and the impediments to their management. We aim to determine the profile of neurological admissions and the challenges of managing these diseases at the University of Nigeria Teaching Hospital Enugu South East Nigeria. Analysis of Neurological admissions into the medical wards of the University of Nigeria Teaching Hospital Enugu from January 2003 to December 2007. Neurological admissions comprise about 14.8% of medical admissions. There were 640 (51%) males and 609 (49%) females. The spectrum of neurological diseases were stroke 64.9%, central nervous system infections (21.8% ), HIV related neurological diseases 3.5%, hypertensive encephalopathy (3.4%), dementia (3%), subarachnoid haemorrhage (2.2%), Guillian Barre syndrome (1.2%), Parkinson's disease (1.1%), myasthenia gravis (1.0%), motor neurone disease and peripheral neuropathy and accounted for 0.8% and 0.6% respectively. Overall, noninfectious disease accounted for 78.2% of neurological admissions while infectious diseases accounted for 11.8%. A wide spectrum of neurological diseases occurs in our setting. The high incidence of CNS infections indicates that efforts should be geared towards preventive measures. A major challenge to be addressed in the management of neurological diseases in our setting is the lack of specialized facilities.

Effectiveness of endoscopic cricopharyngeal myotomy in adults with neurological disease: systematic review.

PubMed

Gilheaney, Ó; Kerr, P; Béchet, S; Walshe, M

2016-12-01

To determine the effectiveness of endoscopic cricopharyngeal myotomy on upper oesophageal sphincter dysfunction in adults with upper oesophageal sphincter dysfunction and neurological disease. Published and unpublished studies with a quasi-experimental design investigating endoscopic cricopharyngeal myotomy effects on upper oesophageal sphincter dysfunction in humans were considered eligible. Electronic databases, grey literature and reference lists of included studies were systematically searched. Data were extracted by two independent reviewers. Methodological quality was assessed independently using the PEDro scale and MINORS tool. Of 2938 records identified, 2 studies were eligible. Risk of bias assessment indicated areas of methodological concern in the literature. Statistical analysis was not possible because of the limited number of eligible studies. No determinations could be made regarding endoscopic cricopharyngeal myotomy effectiveness in the cohort of interest. Reliable and valid evidence on the following is required to support increasing clinical usage of endoscopic cricopharyngeal myotomy: optimal candidacy selection; standardised post-operative management protocol; complications; and endoscopic cricopharyngeal myotomy effects on aspiration of food and laryngeal penetration, mean upper oesophageal sphincter resting pressure and quality of life.

Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease

PubMed Central

Shroff, Geeta

2016-01-01

Case series Patient: Male, 42 • Female, 30 Final Diagnosis: Human embryonic stem cells showed good therapeutic potential for treatment of multiple sclerosis with lyme disease Symptoms: Fatigue • weakness in limbs Medication: — Clinical Procedure: Human embryonic stem cells transplantation Specialty: Transplantology Objective: Rare disease Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. Case Report: Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD. The hESCs were administered via different routes including intramuscular, intravenous, and supplemental routes (e.g., deep spinal, caudal, intercostal through eye drops) to regenerate the injured cells. Both the patients showed remarkable improvement in their functional skills, overall stamina, cognitive abilities, and muscle strength. Furthermore, the improvement in the patients’ conditions were assessed by magnetic resonance tractography and single photon emission computed tomography (SPECT). Conclusions: Therapy with hESCs might emerge as an effective and safe treatment for patients with both MS and LD. Well-designed clinical trials and follow-up studies are needed to prove the long-term efficacy and safety of hESC therapy in the treatment of patients with MS and LD. PMID:27956736

[Status and perspectives in modern neurology. Problems of organization of neurologic services worldwide and in Croatia].

PubMed

Barac, Bosko

2002-05-01

Modern neurology has completely changed in its concepts of science and medical discipline regarding the etiologies and the capabilities in the diagnostics, management, rehabilitation and prevention of neurological diseases. Advances in neurological sciences produced a rapid growth in the number of neurologists, new subspecialties and neurological institutions worldwide, opening questions on their possible application due to financial restrictions in many countries. Neurology in Croatia followed the modern tendencies in the world: in line with its humanistic tradition its orientation to the patient early appeared. From this experience developed a care on the optimal organization of neurological services, later on initiated in the Research Group on the Organization and Delivery of Neurological Services, founded in the World Federation of Neurology. The main activities and the Recommendations related to Neurology in Public Health are described, with the proposed levels of organization of neurological services, aiming at the optimal and rational neurological care. Problems of international collaboration on cost-effectiveness in neurology are accentuated.

N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities

PubMed Central

Bavarsad Shahripour, Reza; Harrigan, Mark R; Alexandrov, Andrei V

2014-01-01

Background There is an expanding field of research investigating the benefits of medicines with multiple mechanisms of action across neurological disorders. N-acetylcysteine (NAC), widely known as an antidote to acetaminophen overdose, is now emerging as treatment of vascular and nonvascular neurological disorders. NAC as a precursor to the antioxidant glutathione modulates glutamatergic, neurotrophic, and inflammatory pathways. Aim and discussion Most NAC studies up to date have been carried out in animal models of various neurological disorders with only a few studies completed in humans. In psychiatry, NAC has been tested in over 20 clinical trials as an adjunctive treatment; however, this topic is beyond the scope of this review. Herein, we discuss NAC molecular, intracellular, and systemic effects, focusing on its potential applications in neurodegenerative diseases including spinocerebellar ataxia, Parkinson's disease, tardive dyskinesia, myoclonus epilepsy of the Unverricht–Lundbor type as well as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Conclusion Finally, we review the potential applications of NAC to facilitate recovery after traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular vasospasm after subarachnoid hemorrhage. PMID:24683506

Genetics Home Reference: Tay-Sachs disease

MedlinePlus

... NIH Resources (4 links) GeneEd National Human Genome Research Institute National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet National Institute of Neurological ...

[Education and training in neurology: update].

PubMed

Yanagisawa, Nobuo

2010-11-01

Progress in basic neurosciences and advances in technology in the last decades have contributed to clarification of neural mechanisms in behavior or cognition in health and disease. They have elaborated diagnosis and treatment of nervous diseases remarkably. Needs in neurologists in both primary and specific medical services are rapidly increasing, with aging society and progresses in medical care in Japan. Attraction of neurology for students and junior residents is a great concern of Japanese Society of Neurology. In the undergraduate education, recent achievement in basic neurosciences including neurogenetics, molecular cytology, physio-pathology and imaging technique should be taught comprehensively. In the early postgraduate course for two years, neurology is either elective or obligatory depending on the curriculum of training institutions. Work at the stroke care unit is strongly recommended in the course of emergency service, which is mandatory. Experiences in acute infectious diseases, in various stages of neurodegenerative diseases, in collaboration with other specialist doctors for systemic diseases including metabolic or collagen diseases, in collaboration with other medical personnel in care of dementia are all included in advanced stages of postgraduate education before board examination. In summary, studies for practical services as well as clinical researches, teaching of symptoms and signs based on neural functions, and socio-economical issues for chronic nervous diseases in aged society are important in the education in neurology.

[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.

Genetics and Genomics of Acute Neurologic Disorders.

PubMed

Maserati, Megan; Alexander, Sheila A

2018-01-01

Neurologic diseases and injuries are complex and multifactorial, making risk prediction, targeted treatment modalities, and outcome prognostication difficult and elusive. Genetics and genomics have affected clinical practice in many aspects in medicine, particularly cancer treatment. Advancements in knowledge of genetic and genomic variability in neurologic disease and injury are growing rapidly. Although these data are not yet ready for use in clinical practice, research continues to progress and elucidate information that eventually will provide answers to complex neurologic questions and serve as a platform to provide individualized care plans aimed at improving outcomes. This article provides a focused review of relevant literature on genetics, genomics, and common complex neurologic disease and injury likely to be seen in the acute care setting. ©2018 American Association of Critical-Care Nurses.

Review of the neurological benefits of phytocannabinoids.

PubMed

Maroon, Joseph; Bost, Jeff

2018-01-01

Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS. In 1980, Cunha et al . reported anticonvulsant benefits in 7/8 subjects with medically uncontrolled epilepsy using marijuana extracts in a phase I clinical trial. Since then neurological applications have been the major focus of renewed research using medical marijuana and phytocannabinoid extracts. Recent neurological uses include adjunctive treatment for malignant brain tumors, Parkinson's disease, Alzheimer's disease, multiple sclerosis, neuropathic pain, and the childhood seizure disorders Lennox-Gastaut and Dravet syndromes. In addition, psychiatric and mood disorders, such as schizophrenia, anxiety, depression, addiction, postconcussion syndrome, and posttraumatic stress disorders are being studied using phytocannabinoids. In this review we will provide animal and human research data on the current clinical neurological uses for CBD individually and in combination with Δ9-THC. We will emphasize the neuroprotective, antiinflammatory, and immunomodulatory benefits of phytocannabinoids and their applications in various clinical syndromes.

Review of the neurological benefits of phytocannabinoids

PubMed Central

Maroon, Joseph; Bost, Jeff

2018-01-01

Background: Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS. Methods: In 1980, Cunha et al. reported anticonvulsant benefits in 7/8 subjects with medically uncontrolled epilepsy using marijuana extracts in a phase I clinical trial. Since then neurological applications have been the major focus of renewed research using medical marijuana and phytocannabinoid extracts. Results: Recent neurological uses include adjunctive treatment for malignant brain tumors, Parkinson's disease, Alzheimer's disease, multiple sclerosis, neuropathic pain, and the childhood seizure disorders Lennox-Gastaut and Dravet syndromes. In addition, psychiatric and mood disorders, such as schizophrenia, anxiety, depression, addiction, postconcussion syndrome, and posttraumatic stress disorders are being studied using phytocannabinoids. Conclusions: In this review we will provide animal and human research data on the current clinical neurological uses for CBD individually and in combination with Δ9-THC. We will emphasize the neuroprotective, antiinflammatory, and immunomodulatory benefits of phytocannabinoids and their applications in various clinical syndromes. PMID:29770251

Retrospective study of the clinical effects of acupuncture on cervical neurological diseases in dogs.

PubMed

Liu, Ching Ming; Chang, Fang Chia; Lin, Chung Tien

2016-09-30

This study was conducted to evaluate new acupuncture protocols for the clinical treatment of cervical spinal cord diseases in 19 dogs. Three treatment options containing Jing-jiaji (cervical jiaji) were developed to treat neck pain, hemiparesis, and tetraparesis depending on the severity. The interval between the neurological disease onset and treatment (duration of signs), time to improvement after treatment, and recovery time were compared in dogs by body weight, age, and dry needle acupuncture (AP) with or without electro-AP (EAP). The duration of signs was longer in dogs weighing greater than 10 kg than in those weighing less than 10 kg (p＜ 0.05). Improvement and recovery times did not vary by body weight. Additionally, improvement and recovery times did not vary by age. The improvement and recovery times were longer in the AP+EAP group than the AP group (p＜ 0.05). Acupuncture with Jing-jiaji was effective in cervical spinal cord diseases in different sized dogs and in middle-aged and senior dogs. This report standardized AP treatment containing Jing-jiaji for canine cervical problems and evaluated its effects. The newly standardized AP methodology offers clinical practitioners an effective way to improve the outcomes of cervical neurological diseases in dogs.

The Global Burden of Mental, Neurological and Substance Use Disorders: An Analysis from the Global Burden of Disease Study 2010

PubMed Central

Whiteford, Harvey A.; Ferrari, Alize J.; Degenhardt, Louisa; Feigin, Valery; Vos, Theo

2015-01-01

Background The Global Burden of Disease Study 2010 (GBD 2010), estimated that a substantial proportion of the world’s disease burden came from mental, neurological and substance use disorders. In this paper, we used GBD 2010 data to investigate time, year, region and age specific trends in burden due to mental, neurological and substance use disorders. Method For each disorder, prevalence data were assembled from systematic literature reviews. DisMod-MR, a Bayesian meta-regression tool, was used to model prevalence by country, region, age, sex and year. Prevalence data were combined with disability weights derived from survey data to estimate years lived with disability (YLDs). Years lost to premature mortality (YLLs) were estimated by multiplying deaths occurring as a result of a given disorder by the reference standard life expectancy at the age death occurred. Disability-adjusted life years (DALYs) were computed as the sum of YLDs and YLLs. Results In 2010, mental, neurological and substance use disorders accounted for 10.4% of global DALYs, 2.3% of global YLLs and, 28.5% of global YLDs, making them the leading cause of YLDs. Mental disorders accounted for the largest proportion of DALYs (56.7%), followed by neurological disorders (28.6%) and substance use disorders (14.7%). DALYs peaked in early adulthood for mental and substance use disorders but were more consistent across age for neurological disorders. Females accounted for more DALYs in all mental and neurological disorders, except for mental disorders occurring in childhood, schizophrenia, substance use disorders, Parkinson’s disease and epilepsy where males accounted for more DALYs. Overall DALYs were highest in Eastern Europe/Central Asia and lowest in East Asia/the Pacific. Conclusion Mental, neurological and substance use disorders contribute to a significant proportion of disease burden. Health systems can respond by implementing established, cost effective interventions, or by supporting the

Global Neurology: Navigating Career Possibilities.

PubMed

Schiess, Nicoline; Saylor, Deanna; Zunt, Joseph

2018-04-01

Neurology has not typically been associated with international relief work; however, with the growth of chronic cardiovascular disease and stroke associated with unhealthy eating and sedentary ways, the appearance of "new" neurologic diseases, such as the Zika and West Nile viruses, and the high numbers of seizure disorders resulting from neuroinfectious diseases, more opportunities are arising for international and globally oriented neurologists. Multiple opportunities exist for developing a global clinician-educator career pathway, including private institutions, nongovernmental organizations, government-funded opportunities such as Medical Education Partnership Initiative, Fogarty and Fulbright Scholarships, and the American Academy of Neurology's Global Health Section. Furthermore, increasing research capacity in developing countries and increased funding opportunities for global health research have led to new opportunities for neurologists to establish global health research careers. These opportunities could not have come at a better time, as many faculty members have noted a particularly strong interest in global neurology from medical students and residents. Career categories and opportunities for neurologists desiring to work globally are discussed along with the emerging "global neurologist" academic pathway. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: A case series

PubMed Central

da Silva, Marcus Tulius Texeira; Rosala-Hallas, Anna; Jardim, Marcia Rodrigues; Burnside, Girvan; Pamplona, Luciana; Bhojak, Maneesh; Manohar, Radhika; da Silva, Gabriel Amorelli Medeiros; Adriano, Marcus Vinicius; Brasil, Patricia; Nogueira, Rita Maria Ribeiro; Dos Santos, Carolina Cardoso; Turtle, Lance; de Sequeira, Patricia Carvalho; Brown, David W.; Griffiths, Michael J.; de Filippis, Ana Maria Bispo

2018-01-01

Background During 2015–16 Brazil experienced the largest epidemic of Zika virus ever reported. This arthropod-borne virus (arbovirus) has been linked to Guillain-Barré syndrome (GBS) in adults but other neurological associations are uncertain. Chikungunya virus has caused outbreaks in Brazil since 2014 but associated neurological disease has rarely been reported here. We investigated adults with acute neurological disorders for Zika, chikungunya and dengue, another arbovirus circulating in Brazil. Methods We studied adults who had developed a new neurological condition following suspected Zika virus infection between 1st November 2015 and 1st June 2016. Cerebrospinal fluid (CSF), serum, and urine were tested for evidence of Zika, chikungunya, and dengue viruses. Results Of 35 patients studied, 22 had evidence of recent arboviral infection. Twelve had positive PCR or IgM for Zika, five of whom also had evidence for chikungunya, three for dengue, and one for all three viruses. Five of them presented with GBS; seven had presentations other than GBS, including meningoencephalitis, myelitis, radiculitis or combinations of these syndromes. Additionally, ten patients positive for chikungunya virus, two of whom also had evidence for dengue virus, presented with a similar range of neurological conditions. Conclusions Zika virus is associated with a wide range of neurological manifestations, including central nervous system disease. Chikungunya virus appears to have an equally important association with neurological disease in Brazil, and many patients had dual infection. To understand fully the burden of Zika we must look beyond GBS, and also investigate for other co-circulating arboviruses, particularly chikungunya. PMID:29432457

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.

Using phosphate supplementation to reverse hypophosphatemia and phosphate depletion in neurological disease and disturbance.

PubMed

Håglin, Lena

2016-06-01

Hypophosphatemia (HP) with or without intracellular depletion of inorganic phosphate (Pi) and adenosine triphosphate has been associated with central and peripheral nervous system complications and can be observed in various diseases and conditions related to respiratory alkalosis, alcoholism (alcohol withdrawal), diabetic ketoacidosis, malnutrition, obesity, and parenteral and enteral nutrition. In addition, HP may explain serious muscular, neurological, and haematological disorders and may cause peripheral neuropathy with paresthesias and metabolic encephalopathy, resulting in confusion and seizures. The neuropathy may be improved quickly after proper phosphate replacement. Phosphate depletion has been corrected using potassium-phosphate infusion, a treatment that can restore consciousness. In severe ataxia and tetra paresis, complete recovery can occur after adequate replacement of phosphate. Patients with multiple risk factors, often with a chronic disease and severe HP that contribute to phosphate depletion, are at risk for neurologic alterations. To predict both risk and optimal phosphate replenishment requires assessing the nutritional status and risk for re-feeding hypophosphatemia. The strategy for correcting HP depends on the severity of the underlying disease and the goal for re-establishing a phosphate balance to limit the consequences of phosphate depletion.

Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies

PubMed Central

Samsel, Anthony; Seneff, Stephanie

2015-01-01

Manganese (Mn) is an often overlooked but important nutrient, required in small amounts for multiple essential functions in the body. A recent study on cows fed genetically modified Roundup®-Ready feed revealed a severe depletion of serum Mn. Glyphosate, the active ingredient in Roundup®, has also been shown to severely deplete Mn levels in plants. Here, we investigate the impact of Mn on physiology, and its association with gut dysbiosis as well as neuropathologies such as autism, Alzheimer's disease (AD), depression, anxiety syndrome, Parkinson's disease (PD), and prion diseases. Glutamate overexpression in the brain in association with autism, AD, and other neurological diseases can be explained by Mn deficiency. Mn superoxide dismutase protects mitochondria from oxidative damage, and mitochondrial dysfunction is a key feature of autism and Alzheimer’s. Chondroitin sulfate synthesis depends on Mn, and its deficiency leads to osteoporosis and osteomalacia. Lactobacillus, depleted in autism, depend critically on Mn for antioxidant protection. Lactobacillus probiotics can treat anxiety, which is a comorbidity of autism and chronic fatigue syndrome. Reduced gut Lactobacillus leads to overgrowth of the pathogen, Salmonella, which is resistant to glyphosate toxicity, and Mn plays a role here as well. Sperm motility depends on Mn, and this may partially explain increased rates of infertility and birth defects. We further reason that, under conditions of adequate Mn in the diet, glyphosate, through its disruption of bile acid homeostasis, ironically promotes toxic accumulation of Mn in the brainstem, leading to conditions such as PD and prion diseases. PMID:25883837

The effects of aquatic therapy on mobility of individuals with neurological diseases: a systematic review.

PubMed

Marinho-Buzelli, Andresa R; Bonnyman, Alison M; Verrier, Mary C

2015-08-01

To summarize evidence on the effects of aquatic therapy on mobility in individuals with neurological diseases. MEDLINE, EMBASE, PsycInfo, CENTRAL, CINAHL, SPORTDiscus, PEDro, PsycBITE and OT Seeker were searched from inception to 15 September 2014. Hand-searching of reference lists was performed in the selected studies. The search included randomized controlled trials and quasi-experimental studies that investigated the use of aquatic therapy and its effect on mobility of adults with neurological diseases. One reviewer screened titles and abstracts of retrieved studies from the search strategy. Two reviewers independently examined the full texts and conducted the study selection, data extraction and quality assessment. A narrative synthesis of data was applied to summarize information from included studies. The Downs and Black Scale was used to assess methodological quality. A total of 116 articles were obtained for full text eligibility. Twenty studies met the specified inclusion criteria: four Randomized Controlled Trials (RCTs), four non-randomized studies and 12 before-and-after tests. Two RCTs (30 patients with stroke in the aquatic therapy groups), three non-randomized studies and three before-and-after studies showed "fair" evidence that aquatic therapy increases dynamic balance in participants with some neurological disorders. One RCT (seven patients with stroke in the aquatic therapy group) and two before-and-after tests (20 patients with multiple sclerosis) demonstrated "fair" evidence on improvement of gait speed after aquatic therapy. Our synthesis showed "fair" evidence supporting the use of aquatic therapy to improve dynamic balance and gait speed in adults with certain neurological conditions. © The Author(s) 2014.

Iron as a risk factor in neurological diseases

NASA Astrophysics Data System (ADS)

Galazka-Friedman, Jolanta

2008-02-01

In this review the properties of iron in various human brain structures (e.g. Substantia nigra, globus pallidus, hippocampus) were analyzed to assess the possibility of initiation of oxidative stress leading to such diseases as Parkinson’s and Alzheimer’s disease, and progressive supranuclear palsy. Our own studies with the use of Mössbauer spectroscopy, electron microscopy and enzyme-linked immuno-absorbent assay (ELISA) were confronted with other methods used in other laboratories. Our results suggest that hippocampus is the most fragile for oxidative stress structure in human brain (the death of nervous cells in hippocampus leads to Alzheimer’s disease). Changes in iron metabolism were also found in substantia nigra (the death of nervous cells of this structure produces Parkinson’s disease) and in globus pallidus (neurodegeneration of this structure causes progressive supranuclear palsy).

Neuromarketing and consumer neuroscience: contributions to neurology.

PubMed

Javor, Andrija; Koller, Monika; Lee, Nick; Chamberlain, Laura; Ransmayr, Gerhard

2013-02-06

'Neuromarketing' is a term that has often been used in the media in recent years. These public discussions have generally centered around potential ethical aspects and the public fear of negative consequences for society in general, and consumers in particular. However, positive contributions to the scientific discourse from developing a biological model that tries to explain context-situated human behavior such as consumption have often been neglected. We argue for a differentiated terminology, naming commercial applications of neuroscientific methods 'neuromarketing' and scientific ones 'consumer neuroscience'. While marketing scholars have eagerly integrated neuroscientific evidence into their theoretical framework, neurology has only recently started to draw its attention to the results of consumer neuroscience. In this paper we address key research topics of consumer neuroscience that we think are of interest for neurologists; namely the reward system, trust and ethical issues. We argue that there are overlapping research topics in neurology and consumer neuroscience where both sides can profit from collaboration. Further, neurologists joining the public discussion of ethical issues surrounding neuromarketing and consumer neuroscience could contribute standards and experience gained in clinical research. We identify the following areas where consumer neuroscience could contribute to the field of neurology:First, studies using game paradigms could help to gain further insights into the underlying pathophysiology of pathological gambling in Parkinson's disease, frontotemporal dementia, epilepsy, and Huntington's disease.Second, we identify compulsive buying as a common interest in neurology and consumer neuroscience. Paradigms commonly used in consumer neuroscience could be applied to patients suffering from Parkinson's disease and frontotemporal dementia to advance knowledge of this important behavioral symptom.Third, trust research in the medical context lacks

Neuromarketing and consumer neuroscience: contributions to neurology

PubMed Central

2013-01-01

Background ‘Neuromarketing’ is a term that has often been used in the media in recent years. These public discussions have generally centered around potential ethical aspects and the public fear of negative consequences for society in general, and consumers in particular. However, positive contributions to the scientific discourse from developing a biological model that tries to explain context-situated human behavior such as consumption have often been neglected. We argue for a differentiated terminology, naming commercial applications of neuroscientific methods ‘neuromarketing’ and scientific ones ‘consumer neuroscience’. While marketing scholars have eagerly integrated neuroscientific evidence into their theoretical framework, neurology has only recently started to draw its attention to the results of consumer neuroscience. Discussion In this paper we address key research topics of consumer neuroscience that we think are of interest for neurologists; namely the reward system, trust and ethical issues. We argue that there are overlapping research topics in neurology and consumer neuroscience where both sides can profit from collaboration. Further, neurologists joining the public discussion of ethical issues surrounding neuromarketing and consumer neuroscience could contribute standards and experience gained in clinical research. Summary We identify the following areas where consumer neuroscience could contribute to the field of neurology: First, studies using game paradigms could help to gain further insights into the underlying pathophysiology of pathological gambling in Parkinson’s disease, frontotemporal dementia, epilepsy, and Huntington’s disease. Second, we identify compulsive buying as a common interest in neurology and consumer neuroscience. Paradigms commonly used in consumer neuroscience could be applied to patients suffering from Parkinson’s disease and frontotemporal dementia to advance knowledge of this important behavioral symptom

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.

Neurological complications of sickle cell disease in Africa: protocol for a systematic review.

PubMed

Mengnjo, Michel K; Kamtchum-Tatuene, Joseph; Nicastro, Nicolas; Noubiap, Jean Jacques N

2016-10-19

Sickle cell disease (SCD) is highly prevalent in Africa. Considered as a public health problem, it is associated with high morbidity and mortality. Neurological complications of SCD can cause significant disability with important socioeconomic and psychological impact on the patients and their families, and can even lead to death if not properly managed. There are important knowledge gaps regarding the burden of neurological complications of SCD in African populations. We propose to conduct the first systematic review to summarise the epidemiological data available on neurological complications of SCD in Africa. We will search PubMed, MEDLINE, EMBASE and the African Index Medicus from 1 January 1950 to 31 May 2016 for studies of neurological complications of SCD in Africa. After study selection, full-text paper acquisition, data extraction and synthesis, we will assess all studies for quality, risk of bias and heterogeneity. Appropriate methods of meta-analysis will be used to pool prevalence estimates from studies with similar features, globally and in major subgroups. This protocol complies with the 2015 Preferred Reporting Items for Systematic reviews and Meta-Analysis protocols (PRISMA-P) guidelines. The proposed study will use published data. Therefore, there is no requirement for ethical approval. This review is expected to provide relevant data to help quantify the burden of neurological complications of SCD in African populations, inform policymakers and identify further research topics. The final report of the systematic review will be published in a peer-reviewed journal and presented at conferences. CRD42016039574. 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/.

Neurology in Federico Fellini?s work and life.

PubMed

Teive, Hélio Afonso Ghizoni; Caramelli, Paulo; Cardoso, Francisco Eduardo Costa

2014-09-01

The authors present a historical review of the neurological diseases related to the famous moviemaker Federico Fellini. There is an account of diseases depicted on his movies as well as his ischemic stroke and consequent neurological deficit - left spatial neglect.

[Neurological manifestations in patients with Gaucher disease and in their relatives].

PubMed

Giraldo, Pilar; Capablo, José Luis; Alfonso, Pilar; Latre, Paz; García, Beatriz; Pocoví, Miguel

2008-07-05

Gaucher disease (GD) is characterized by a wide spectrum of manifestations. Previous reports indicate that GD relatives could develop neurological abnormalities more frequently than the general population. We aimed to know the presence of neurological symptoms (NS) in GD patients and their relatives. From January to December 2006 we performed a postal survey contacting 42 physicians and 92 families to evaluate NS and correlate them with genetic characteristics. Statistical analysis using descriptive parameters, ANOVA, t-test and a correlation study including Pearson coefficient were performed. Information from 72 families (78.3% responses) including 99 patients and 266 relatives was obtained. Thirty type 1 GD (32.6%) reported NS: tremor 8 (8.7%), uncoordinated movements 9 (9.8%), concentration defects 11 (11.9%), strabism 7 (7.6%), deafness 8 (8.7%), Parkinson disease (PD) 7 (7.6%) and peripheral neuropathy 10 (10.9%). Thirty-six (13.5%) first or second degrees relatives presented the following NS: PD 14 (4.9%), epilepsy 8 (3.0%), tremor 7 (2.6%), deafness 2 (0.7%) and others 5 (1.9%). 17.3% of carriers had NS versus 5.7% in non-carriers (p = 0.0096). Patients with PD had mutations in S364R, D409H, L444P, [IVS4-2a ==> g; c.(-203)A ==> G], c.500insT and L336P. In relatives with PD a wide spectrum of mutations was observed: L444P, N370S, V398I, G202R, c.1439-1445del7, [E326K; N188S] and c.953delT. In other NS, predominant mutations were D409H, G195W, R120W, R147X, L336P and G377S. A higher incidence than expected of PD and other NS in GD type 1 patients and relatives was observed. These manifestations appear frequently in L444P or rare mutations carriers. It is important to perform a systematic neurological exam in type 1 GD patients and carriers with risk mutations.

Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease.

PubMed

Cario, Holger; Smith, Desirée E C; Blom, Henk; Blau, Nenad; Bode, Harald; Holzmann, Karlheinz; Pannicke, Ulrich; Hopfner, Karl-Peter; Rump, Eva-Maria; Ayric, Zuleya; Kohne, Elisabeth; Debatin, Klaus-Michael; Smulders, Yvo; Schwarz, Klaus

2011-02-11

The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency. We examined three children of healthy, distantly related parents presenting with megaloblastic anemia and cerebral folate deficiency causing neurologic disease with atypical childhood absence epilepsy. Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus. DHFR sequencing revealed a homozygous DHFR mutation, c.458A>T (p.Asp153Val), in all siblings. The patients' folate profile in red blood cells (RBC), plasma, and cerebrospinal fluid (CSF), analyzed by liquid chromatography tandem mass spectrometry, was compatible with DHFR deficiency. DHFR activity and fluorescein-labeled methotrexate (FMTX) binding were severely reduced in EBV-immortalized lymphoblastoid cells of all patients. Heterozygous cells displayed intermediate DHFR activity and FMTX binding. RT-PCR of DHFR mRNA revealed no differences between wild-type and DHFR mutation-carrying cells, whereas protein expression was reduced in cells with the DHFR mutation. Treatment with folinic acid resulted in the resolution of hematological abnormalities, normalization of CSF folate levels, and improvement of neurological symptoms. In conclusion, the homozygous DHFR mutation p.Asp153Val causes DHFR deficiency and leads to a complex hematological and neurological disease that can be successfully treated with folinic acid. DHFR is necessary for maintaining sufficient CSF and RBC folate levels, even in the presence of adequate nutritional folate supply and normal plasma folate. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Efficacy of menatetrenone (vitamin K2) against non-vertebral and hip fractures in patients with neurological diseases: meta-analysis of three randomized, controlled trials.

PubMed

Iwamoto, Jun; Matsumoto, Hideo; Takeda, Tsuyoshi

2009-01-01

Patients with neurological diseases such as Alzheimer's disease, stroke and Parkinson's disease have been reported to have vitamin K deficiency secondary to malnutrition, which increases the risk of non-vertebral and hip fractures. The purpose of the present study was to clarify the efficacy of menatetrenone (vitamin K(2)) against non-vertebral and hip fractures in patients with neurological diseases. A literature search was conducted on PubMed from January 1995 to July 2008 to identify randomized controlled trials (RCTs) of use of menatetrenone against non-vertebral and hip fractures in patients with neurological diseases. A meta-analysis of all RCTs meeting these criteria was then performed. Three RCTs of patients with Alzheimer's disease (n = 178, mean age 78 years), stroke (n = 99, mean age 66 years) and Parkinson's disease (n = 110, mean age 72 years) met the criteria for meta-analysis. These RCTs did not include placebo controls but did have non-treatment controls. According to the meta-analysis, the overall relative risks (95% confidence intervals) for non-vertebral and hip fractures with menatetrenone treatment compared with non-treatment were 0.13 (0.05, 0.35) and 0.14 (0.05, 0.43), respectively, in patients with neurological diseases. No severe adverse events were reported with menatetrenone treatment. The present meta-analysis of three RCTs suggests that there is efficacy for menatetrenone treatment against non-vertebral and hip fractures among patients with neurological diseases. Further larger placebo-controlled trials are needed to confirm the results of the present study.

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.

Neurological eponyms--who gets the credit? Essay review.

PubMed

Okun, Michael S

2003-03-01

The recent publication of Neurological Eponyms by Peter Koehler and colleagues has revived the interest in neurological eponyms and raised important questions about their use. Many investigators have contributed to the body of knowledge that defines the specialty of neurology. We honor them by associating their names with neurological diseases. The history of neurological eponyms provides us with an opportunity to reexamine the important question of who gets the credit. Additional issues have surfaced including why certain eponyms tend to stick in the literature and others disappear, as well as the important realization that lengthy modern descriptions may require name eponyms for simplification. Eponyms can be confusing as to whether they refer to a disease or a syndrome and this confusion can impact the diagnosis and treatment of patients. There is an inevitable evolution of certain eponyms as our understanding of entities expands. This paper provides an overview of neurological eponyms with the explanation of the potential reasons why names were associated with neurological diseases. These included first case reports, relating isolated cases, years of observation, defining neuroanatomy, physician sufferer, new physical examination maneuvers, academic climate, the advent of a new procedure, fame, and competition amongst investigators. Important issues have surfaced regarding sharing credit amongst investigators, name priority, crediting the wrong investigator, and lack of a defined system to award credit. Since eponym use is based on a peer dependent system, each neurologist must make a more critical appraisal of who gets the credit and understand the differences between diseases and syndromes in order to better preserve neurological history.

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

Education Research: Neurology resident education

PubMed Central

Mayans, David; Schneider, Logan; Adams, Nellie; Khawaja, Ayaz M.; Engstrom, John

2016-01-01

Objective: To survey US-trained graduating neurology residents who are American Academy of Neurology members, in an effort to trend perceived quality and completeness of graduate neurology education. Methods: An electronic survey was sent to all American Academy of Neurology members graduating from US neurology residency programs in the Spring of 2014. Results: Of 805 eligible respondents, 24% completed the survey. Ninety-three percent of adult neurology residents and 56% of child neurology residents reported plans to pursue fellowship training after residency. Respondents reported a desire for additional training in neurocritical care, neuro-oncology, neuromuscular diseases, botulinum toxin injection, and nerve blocks. There remains a clear deficit in business training of neurology residents, although there was notable improvement in knowledge of coding and office management compared to previous surveys. Discussion: Although there are still areas of perceived weakness in neurology training, graduating neurology residents feel generally well prepared for their chosen careers. However, most still pursue fellowship training for reasons that are little understood. In addition to certain subspecialties and procedures, practice management remains deficient in neurology training and is a point of future insecurity for most residents. Future curriculum changes should consider resident-reported gaps in knowledge, with careful consideration of improving business training. PMID:26976522

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.

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.

Shiga Toxin Mediated Neurologic Changes in Murine Model of Disease.

PubMed

Pradhan, Suman; Pellino, Christine; MacMaster, Kayleigh; Coyle, Dennis; Weiss, Alison A

2016-01-01

Seizures and neurologic involvement have been reported in patients infected with Shiga toxin (Stx) producing E. coli , and hemolytic uremic syndrome (HUS) with neurologic involvement is associated with more severe outcome. We investigated the extent of renal and neurologic damage in mice following injection of the highly potent form of Stx, Stx2a, and less potent Stx1. As observed in previous studies, Stx2a brought about moderate to acute tubular necrosis of proximal and distal tubules in the kidneys. Brain sections stained with hematoxylin and eosin (H&E) appeared normal, although some red blood cell congestion was observed. Microglial cell responses to neural injury include up-regulation of surface-marker expression (e.g., Iba1) and stereotypical morphological changes. Mice injected with Stx2a showed increased Iba1 staining, mild morphological changes associated with microglial activation (thickening of processes), and increased microglial staining per unit area. Microglial changes were observed in the cortex, hippocampus, and amygdala regions, but not the nucleus. Magnetic resonance imaging (MRI) of Stx2a-treated mice revealed no hyper-intensities in the brain, although magnetic resonance spectroscopy (MRS) revealed significantly decreased levels of phosphocreatine in the thalamus. Less dramatic changes were observed following Stx1 challenge. Neither immortalized microvascular endothelial cells from the cerebral cortex of mice (bEnd.3) nor primary human brain microvascular endothelial cells were found to be susceptible to Stx1 or Stx2a. The lack of susceptibility to Stx for both cell types correlated with an absence of receptor expression. These studies indicate Stx causes subtle, but identifiable changes in the mouse brain.

[Clinical applications of transcranial magnetic stimulation for the treatment of various neurological diseases].

PubMed

Tsuji, Sadatoshi

2005-11-01

Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in various neurological and psychiatric diseases including depression, Parkinson disease, spinocerebellar degeneration, epilepsy, urinary incontinence, movement disorders, chronic pain, migraine and chronic tinnitus, etc. Several reports showed the therapeutic effects of rTMS as a treatment of depression and Parkinson disease (PD), whereas others found no significant effects. It is by now not yet fully understood whether rTMS has a therapeutic effect on those diseases. The controversy arises from the differences of the stimulation parameters and evaluation methods of the effects in those studies. The Japanese multi-center, double blinded, sham stimulation controlled trial in 85 patients with PD showed an efficacy in both the rTMS-treated and sham stimulated patients. This result does not prove the efficacy of the rTMS in PD; on the other hand, it does not rule out the efficacy. Possible mechanism of favorable effects of rTMS is related to increasing the release of dopamine in the mesolimbic and mesostriatal system. The other Japanese multi-center, double blinded, sham stimulation controlled trial in 99 patients with spinocerebellar degeneration revealed significant therapeutic effects of rTMS in 51 patients with SCA6. We studied the effects of rTMS on seizure susceptibility in rats which prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. This finding suggests the possibility of therapeutic use of rTMS in epilepsy. Further studies should be performed aiming to reveal the optimal stimulation parameters, and are necessary to reveal the therapeutic role of the rTMS in neurological and psychiatric diseases.

Translational research on cognitive and behavioural disorders in neurological and psychiatric diseases.

PubMed

Corvol, Jean-Christophe; Goni, Sylvia; Bordet, Régis

2016-02-01

The important medical and social burden of nervous system diseases contrasts with the currently limited therapeutic armamentarium and with the difficulty encountered in developing new therapeutic options. These failures can be explained by the conjunction of various phenomena related to the limitations of animal models, the narrow focus of research on precise pathophysiological mechanisms, and methodological issues in clinical trials. It is perhaps the paradigm itself of the way research is conducted that may be the real reason for our incapacity to find effective strategies. The purpose of this workshop was to define overall lines of research that could lead to the development of effective novel therapeutic solutions. Research has long focused on diseases per se rather than on cognitive and behavioural dimensions common to several diseases. Their expression is often partial and variable, but can today be well-characterised using neurophysiological or imaging methods. This dimensional or syndromic vision should enable a new insight to the question, taking a transnosographic approach to re-position research and to propose: translational models exploring the same functions in animal models and in humans; identification of homogeneous groups of patients defined according to the clinical, anatomico-functional and molecular characteristics; and preclinical and clinical developments enriched by the use of cognitive-behavioural, biological neurological, and imaging biomarkers. For this mutation to be successful, it must be accompanied by synchronised action from the public authorities and by ad hoc measures from the regulatory agencies. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Advances in Reprogramming-Based Study of Neurologic Disorders

PubMed Central

Baldwin, Kristin K.

2015-01-01

The technology to convert adult human non-neural cells into neural lineages, through induced pluripotent stem cells (iPSCs), somatic cell nuclear transfer, and direct lineage reprogramming or transdifferentiation has progressed tremendously in recent years. Reprogramming-based approaches aimed at manipulating cellular identity have enormous potential for disease modeling, high-throughput drug screening, cell therapy, and personalized medicine. Human iPSC (hiPSC)-based cellular disease models have provided proof of principle evidence of the validity of this system. However, several challenges remain before patient-specific neurons produced by reprogramming can provide reliable insights into disease mechanisms or be efficiently applied to drug discovery and transplantation therapy. This review will first discuss limitations of currently available reprogramming-based methods in faithfully and reproducibly recapitulating disease pathology. Specifically, we will address issues such as culture heterogeneity, interline and inter-individual variability, and limitations of two-dimensional differentiation paradigms. Second, we will assess recent progress and the future prospects of reprogramming-based neurologic disease modeling. This includes three-dimensional disease modeling, advances in reprogramming technology, prescreening of hiPSCs and creating isogenic disease models using gene editing. PMID:25749371

N-methyl-D-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children.

PubMed

Wright, Sukhvir; Hacohen, Yael; Jacobson, Leslie; Agrawal, Shakti; Gupta, Rajat; Philip, Sunny; Smith, Martin; Lim, Ming; Wassmer, Evangeline; Vincent, Angela

2015-06-01

N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis is a well-recognised clinico-immunological syndrome that presents with neuropsychiatric symptoms cognitive decline, movement disorder and seizures. This study reports the clinical features, management and neurological outcomes of paediatric NMDAR-Ab-mediated neurological disease in the UK. A prospective surveillance study. Children with NMDAR-Ab-mediated neurological diseases were voluntarily reported to the British Neurological Surveillance Unit (BPNSU) from November 2010 to December 2011. Initial and follow-up questionnaires were sent out to physicians. Thirty-one children fulfilled the criteria for the study. Eight presented during the study period giving an incidence of 0.85 per million children per year (95% CI 0.64 to 1.06); 23 cases were historical. Behavioural change and neuropsychiatric features were present in 90% of patients, and seizures and movement disorders both in 67%. Typical NMDAR-Ab encephalitis was reported in 24 children and partial phenotype without encephalopathy in seven, including predominantly psychiatric (four) and movement disorder (three). All patients received steroids, 22 (71%) received intravenous immunoglobulin, 9 (29%) received plasma exchange,and 10 (32%) received second-line immunotherapy. Of the 23 patients who were diagnosed early, 18 (78%) made a full recovery compared with only 1 of 8 (13%) of the late diagnosed patients (p=0.002, Fisher's exact test). Seven patients relapsed, with four needing additional second-line immunotherapy. Paediatric NMDAR-Ab-mediated neurological disease appears to be similar to adult NMDAR-Ab encephalitis, but some presented with a partial phenotype. Early treatment was associated with a quick and often full recovery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Neurologic features of chronic minamata disease (organic mercury poisoning) and incidence of complications with aging.

PubMed

Uchino, M; Tanaka, Y; Ando, Y; Yonehara, T; Hara, A; Mishima, I; Okajima, T; Ando, M

1995-09-01

To elucidate the neurologic features of chronic Minamata disease, and the incidence of complications with aging, we studied 80 patients with documented Minamata disease (organic mercury poisoning) from 1986 to 1994 (mean age: 63 years). Of the cardinal neurologic findings, sensory impairment was seen with highest frequency in 98.8% of patients limited to the extremities in 86.3%. Impairment of lower extremity coordination was observed in 60%, constriction of the visual field in 51.9%, and retrocochlear hearing loss in 41%. To assess age-related complications, patients were separated into three groups by age: Group I (10 to 39 years); Group II (40 to 69 years); Group III (> or = 70 years). The incidences of hypertension and cerebrovascular diseases, organic ophthalmologic disorders (including cataracts), presbyacusis, and cervical spondylosis deformans increased significantly with age. Compared with a preceding survey (1981 to 1985, 171 patients, mean age: 63.5 years), the incidences of complicated hypertension and cataracts had decreased, whereas those of cerebrovascular disease and retinitis pigmentosa remained unchanged. The incidences of abnormal brain computed tomography (CT), presbyacusis, cervical spondylosis deformans, and positive tests for urine sugar also increased. The incidences of these complications other than retinitis pigmentosa were similar to those in the general population. These results accurately reflect the recent epidemiological disease tendencies in Japan toward a decreased incidence of hypertension and an increased incidence of diabetes.

Neurology and the Internet: a review.

PubMed

Moccia, Marcello; Brigo, Francesco; Tedeschi, Gioacchino; Bonavita, Simona; Lavorgna, Luigi

2018-06-01

Nowadays, the Internet is the major source to obtain information about diseases and their treatments. The Internet is gaining relevance in the neurological setting, considering the possibility of timely social interaction, contributing to general public awareness on otherwise less-well-known neurological conditions, promoting health equity and improving the health-related coping. Neurological patients can easily find several online opportunities for peer interactions and learning. On the other hand, neurologist can analyze user-generated data to better understand patient needs and to run epidemiological studies. Indeed, analyses of queries from Internet search engines on certain neurological diseases have shown a strict temporal and spatial correlation with the "real world." In this narrative review, we will discuss how the Internet is radically affecting the healthcare of people with neurological disorders and, most importantly, is shifting the paradigm of care from the hands of those who deliver care, into the hands of those who receive it. Besides, we will review possible limitations, such as safety concerns, financial issues, and the need for easy-to-access platforms.

Serious unexpected sinus infection discovered by CT scanning for presumed neurological disease.

PubMed

Swift, A C; Gill, G V

1994-03-01

Serious infection in the paranasal sinuses may present with symptoms suggestive of neurological disease and thus lead to delay in the diagnosis and subsequent treatment. We present three such cases in whom the initial diagnoses had been acute optic neuritis, a posterior communicating aneurysm and an intracranial space occupying lesion. The fourth patient had meningitis but the paranasal sinuses had not initially been considered as a possible source of infection. The current methods of diagnosing sinusitis are discussed.

New Advances in the Treatment of Neurological Diseases Using High Dose Intravenous Immunoglobulins

PubMed Central

2008-01-01

Since the incidental discovery in 1981 that intravenous immunoglobulins (IVIg) are immunomodulatory, they have been investigated in a large number of putative autoimmune diseases. This has led to licensing for idiopathic thrombocytopenic purpura, Kawasaki disease, and in neurological disorders for Guillain-Barré syndrome (GBS). Although not licensed, randomized controlled trials have also shown IVIg efficacy in other neuroimmunological diseases such as multifocal motor neuropathy (MMN), chronic inflammatory demyelinating neuropathy (CIDP), myasthenia gravis, dermatomyositis, and stiff-person syndrome. However, other indications are currently being explored including Alzheimer's disease, postpolio syndrome, and narcolepsy. There are even reports from experimental studies in stroke. The results of recently published clinical trials in both the classical neuroimmunological disorders as well as for new indications are reported and their role in clinical practice is discussed. PMID:21180569

RIT2: responsible and susceptible gene for neurological and psychiatric disorders.

PubMed

Daneshmandpour, Yousef; Darvish, Hossein; Emamalizadeh, Babak

2018-06-02

RIT2 gene was recently introduced as a susceptibility gene in neurological disorders, a group of major problems in human society affecting millions of people worldwide. Several variants, including single nucleotide polymorphisms and CNVs, have been identified and studied in different populations. In this review, we have summarized the studies relevant to the RIT2 gene and its related disorders, including Parkinson's disease, schizophrenia, and autism. The protein product of RIT2 is a member of the Ras superfamily that plays important roles in many vital cellular functions, such as differentiation and survival. We have also investigated the protein network of the RIT2 protein and the diseases related to members of this network so as to obtain some clues for future studies by identifying the molecular pathophysiology of neurological disorders and revealing new possible disorders related to RIT2.

Ventilatory Management and Extubation Criteria of the Neurological/Neurosurgical Patient

PubMed Central

Souter, M. J.; Manno, Edward M.

2013-01-01

Approximately 200 000 patients per year will require mechanical ventilation secondary to neurological injury or disease. The associated mortality, morbidity, and costs are significant. The neurological patient presents a unique set of challenges to airway management, mechanical ventilation, and defining extubation readiness. Neurological injury and disease can directly or indirectly involve the process involved with respiration or airway control. This article will review the basics of airway management and mechanical ventilation in the neurological patient. The current state of the literature evaluating extubation criteria in the neurological patient will also be reviewed. PMID:23983886

78 FR 45933 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Disorders and Stroke Special Emphasis Panel Huntington's Disease Ancillary Studies SEP. Date: August 7, 2013...

78 FR 66372 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory... Disorders and Stroke Special Emphasis Panel; Ancillary Studies in Huntington's Disease. Date: November 5...

The Spanish Burden of Disease 2010: Neurological, mental and substance use disorders.

PubMed

Lara, Elvira; Garin, Noé; Ferrari, Alize J; Tyrovolas, Stefanos; Olaya, Beatriz; Sànchez-Riera, Lidia; Whiteford, Harvey A; Haro, Josep Maria

2015-01-01

We used data from the Global Burden of Disease, Injuries, and Risk Factors Study 2010 to report on the burden of neuropsychiatric disorders in Spain. The summary measure of burden used in the study was the disability-adjusted life-year (DALY), which sums of the years of life lost due to premature mortality (YLLs) and the years lived with disability (YLDs). DALYs were adjusted for comorbidity and estimated with 95% uncertainty intervals. The burden of neuropsychiatric disorders accounted for 18.4% of total all-cause DALYs generated in Spain for 2010. Within this group, the top five leading causes of DALYs were: depressive disorders, Alzheimer's disease, migraine, substance-use disorders, and anxiety disorder, which accounted for 70.9% of all DALYs due to neuropsychiatric disorders. Neurological disorders represented 5.03% of total all cause YLLs, whereas mental and substance-use disorders accounted for 0.8%. Mental and substance-use disorders accounted for 22.4% of total YLDs, with depression being the most disabling disorder. Neurological disorders represented 8.3% of total YLDs. Neuropsychiatric disorders were one of the leading causes of disability in 2010. This finding contributes to our understanding of the burden of neuropsychiatric disorders in the Spanish population and highlights the importance of prioritising neuropsychiatric disorders in the Spanish public health system. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

Child Neurology Services in Africa

PubMed Central

Wilmshurst, Jo M.; Badoe, Eben; Wammanda, Robinson D.; Mallewa, Macpherson; Kakooza-Mwesige, Angelina; Venter, Andre; Newton, Charles R.

2013-01-01

The first African Child Neurology Association meeting identified key challenges that the continent faces to improve the health of children with neurology disorders. The capacity to diagnose common neurologic conditions and rare disorders is lacking. The burden of neurologic disease on the continent is not known, and this lack of knowledge limits the ability to lobby for better health care provision. Inability to practice in resource-limited settings has led to the migration of skilled professionals away from Africa. Referral systems from primary to tertiary are often unpredictable and chaotic. There is a lack of access to reliable supplies of basic neurology treatments such as antiepileptic drugs. Few countries have nationally accepted guidelines either for the management of epilepsy or status epilepticus. There is a great need to develop better training capacity across Africa in the recognition and management of neurologic conditions in children, from primary health care to the subspecialist level. PMID:22019842

Neurological sequelae of bacterial meningitis.

PubMed

Lucas, Marjolein J; Brouwer, Matthijs C; van de Beek, Diederik

2016-07-01

We reported on occurrence and impact of neurological sequelae after bacterial meningitis. We reviewed occurrence of neurological sequelae in children and adults after pneumococcal and meningococcal meningitis. Most frequently reported sequelae are focal neurological deficits, hearing loss, cognitive impairment and epilepsy. Adults with pneumococcal meningitis have the highest risk of developing focal neurological deficits, which are most commonly caused by cerebral infarction, but can also be due to cerebritis, subdural empyema, cerebral abscess or intracerebral bleeding. Focal deficits may improve during clinical course and even after discharge, but a proportion of patients will have persisting focal neurological deficits that often interfere in patient's daily life. Hearing loss occurs in a high proportion of patients with pneumococcal meningitis and has been associated with co-existing otitis. Children and adults recovering from bacterial meningitis without apparent neurological deficits are at risk for long-term cognitive deficits. Early identification of neurological sequelae is important for children to prevent additional developmental delay, and for adults to achieve successful return in society after the disease. Neurological sequelae occur in a substantial amount of patients following bacterial meningitis. Most frequently reported sequelae are focal neurological deficits, hearing loss, cognitive impairment and epilepsy. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders.

PubMed

Posset, Roland; Garcia-Cazorla, Angeles; Valayannopoulos, Vassili; Teles, Elisa Leão; Dionisi-Vici, Carlo; Brassier, Anaïs; Burlina, Alberto B; Burgard, Peter; Cortès-Saladelafont, Elisenda; Dobbelaere, Dries; Couce, Maria L; Sykut-Cegielska, Jolanta; Häberle, Johannes; Lund, Allan M; Chakrapani, Anupam; Schiff, Manuel; Walter, John H; Zeman, Jiri; Vara, Roshni; Kölker, Stefan

2016-09-01

Patients with urea cycle disorders (UCDs) have an increased risk of neurological disease manifestation. Determining the effect of diagnostic and therapeutic interventions on the neurological outcome. Evaluation of baseline, regular follow-up and emergency visits of 456 UCD patients prospectively followed between 2011 and 2015 by the E-IMD patient registry. About two-thirds of UCD patients remained asymptomatic until age 12 days [i.e. the median age at diagnosis of patients identified by newborn screening (NBS)] suggesting a potential benefit of NBS. In fact, NBS lowered the age at diagnosis in patients with late onset of symptoms (>28 days), and a trend towards improved long-term neurological outcome was found for patients with argininosuccinate synthetase and lyase deficiency as well as argininemia identified by NBS. Three to 17 different drug combinations were used for maintenance therapy, but superiority of any single drug or specific drug combination above other combinations was not demonstrated. Importantly, non-interventional variables of disease severity, such as age at disease onset and peak ammonium level of the initial hyperammonemic crisis (cut-off level: 500 μmol/L) best predicted the neurological outcome. Promising results of NBS for late onset UCD patients are reported and should be re-evaluated in a larger and more advanced age group. However, non-interventional variables affect the neurological outcome of UCD patients. Available evidence-based guideline recommendations are currently heterogeneously implemented into practice, leading to a high variability of drug combinations that hamper our understanding of optimised long-term and emergency treatment.

When to consider thyroid dysfunction in the neurology clinic.

PubMed

Mistry, Niraj; Wass, John; Turner, Martin R

2009-06-01

There are many neurological manifestations of thyroid disease, and thyroid function has taken its place in the "routine bloods" of neurology practice. However, although conditions such as carpal tunnel syndrome prompt thyroid testing despite any clear evidence for this approach, other symptoms of potential significance in terms of thyroid disease may be overlooked in the busy general neurology clinic, or abnormal thyroid tests may be assumed to be incidental. Psychiatric disorders, loss of consciousness, movement disorders and weakness may all be manifestations of primary thyroid disease. This is a symptom-based review where we will consider the evidence (or lack of it) for the association of various neurological problems with thyroid dysfunction, and also the pitfalls in interpretation of the biochemical tests.

Transfer RNA and human disease.

PubMed

Abbott, Jamie A; Francklyn, Christopher S; Robey-Bond, Susan M

2014-01-01

Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA) genes are "hotspots" for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase), mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers), and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing). Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

Autoimmune Neurological Conditions Associated With Zika Virus Infection.

PubMed

Acosta-Ampudia, Yeny; Monsalve, Diana M; Castillo-Medina, Luis F; Rodríguez, Yhojan; Pacheco, Yovana; Halstead, Susan; Willison, Hugh J; Anaya, Juan-Manuel; Ramírez-Santana, Carolina

2018-01-01

Zika virus (ZIKV) is an emerging flavivirus rapidly spreading throughout the tropical Americas. Aedes mosquitoes is the principal way of transmission of the virus to humans. ZIKV can be spread by transplacental, perinatal, and body fluids. ZIKV infection is often asymptomatic and those with symptoms present minor illness after 3 to 12 days of incubation, characterized by a mild and self-limiting disease with low-grade fever, conjunctivitis, widespread pruritic maculopapular rash, arthralgia and myalgia. ZIKV has been linked to a number of central and peripheral nervous system injuries such as Guillain-Barré syndrome (GBS), transverse myelitis (TM), meningoencephalitis, ophthalmological manifestations, and other neurological complications. Nevertheless, mechanisms of host-pathogen neuro-immune interactions remain incompletely elucidated. This review provides a critical discussion about the possible mechanisms underlying the development of autoimmune neurological conditions associated with Zika virus infection.

Thyroid-related neurological disorders and complications in children.

PubMed

Nandi-Munshi, Debika; Taplin, Craig E

2015-04-01

Thyroid hormones exert critical roles throughout the body and play an important and permissive role in neuroendocrine, neurological, and neuromuscular function. We performed a PubMed search through June 2014 with search terms including "hypothyroidism," "hyperthyroidism," "neurological complications," "neuropathy," "myopathy," "congenital hypothyroidism," and "encephalopathy." Relevant publications reviewed included case series, individual case reports, systematic reviews, retrospective analyses, and randomized controlled trials. The neurological outcomes of congenital hypothyroidism were reviewed, along with the clinical features of associated neuromuscular syndromes of both hypothyroidism and hyperthyroidism, including other autoimmune conditions. Evidence for, and pathophysiological controversies surrounding, Hashimoto encephalopathy was also reviewed. The establishment of widespread newborn screening programs has been highly successful in attenuating or preventing early and irreversible neurological harm resulting from congenital thyroid hormone deficiency, but some children continue to display neuromuscular, sensory, and cognitive defects in later life. Acquired disorders of thyroid function such as Hashimoto thyroiditis and Graves' disease are associated with a spectrum of central nervous system and/or neuromuscular dysfunction. However, considerable variation in clinical phenotype is described, and much of our knowledge of the role of thyroid disease in childhood neurological disorders is derived from adult case series. Early and aggressive normalization of thyroxine levels in newborn infants with congenital hypothyroidism is important in minimizing neurological sequelae, but maternal thyroid hormone sources are also critically important to the early developing brain. A spectrum of neurological disorders has been reported in older children with acquired thyroid disease, but the frequency with which these occur remains poorly defined in the literature, and

Congenital and inherited neurologic diseases in dogs and cats: Legislation and its effect on purchase in Italy

PubMed Central

Passantino, Annamaria; Masucci, Marisa

2016-01-01

Many of the congenital neurologic diseases can result in incapacity or death of the animal. Some of them, such as idiopathic epilepsy and hydrocephalus, exhibit breed or familial predisposition and a genetic basis was proved or suggested. Some diseases can be presumptively diagnosed after a detailed signalment (breed predisposition), history (e.g. family history because many of these defects have familial tendencies), and through physical exam; other diagnostic methods (radiography, computed tomography, magnetic resonance, electrophysiologic tests, etc.) can provide supportive evidence for the congenital defect and help to confirm the diagnosis. Some cases can lead to civil law-suits when the lesions are congenital, but not easily recognizable, or when the lesions are hereditary but tend to became manifest only after some time (more than 12 months after the date of purchase, e.g., after the vice-free guarantee period has expired). Moreover, quite frequently an early diagnosis is not made because there are delays in consulting the veterinarian or the general practitioner veterinarian does not perceive subtle signs. This study was designed to focus on the medico-legal aspects concerning the buying and selling in Italy of dogs and cats affected by congenital and hereditary neurologic diseases that could constitute vice in these animals. While adequate provisions to regulate in detail the various aspects of pet sale have still to be drawn up by legislators, it may be helpful to involve breeders, by obliging them by contract to extend guarantees in the case of hereditary lesions, including neurologic diseases. PMID:27284217

Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.

PubMed

Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio

2017-04-01

We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.

Role of non-coding RNAs in non-aging-related neurological disorders.

PubMed

Vieira, A S; Dogini, D B; Lopes-Cendes, I

2018-06-11

Protein coding sequences represent only 2% of the human genome. Recent advances have demonstrated that a significant portion of the genome is actively transcribed as non-coding RNA molecules. These non-coding RNAs are emerging as key players in the regulation of biological processes, and act as "fine-tuners" of gene expression. Neurological disorders are caused by a wide range of genetic mutations, epigenetic and environmental factors, and the exact pathophysiology of many of these conditions is still unknown. It is currently recognized that dysregulations in the expression of non-coding RNAs are present in many neurological disorders and may be relevant in the mechanisms leading to disease. In addition, circulating non-coding RNAs are emerging as potential biomarkers with great potential impact in clinical practice. In this review, we discuss mainly the role of microRNAs and long non-coding RNAs in several neurological disorders, such as epilepsy, Huntington disease, fragile X-associated ataxia, spinocerebellar ataxias, amyotrophic lateral sclerosis (ALS), and pain. In addition, we give information about the conditions where microRNAs have demonstrated to be potential biomarkers such as in epilepsy, pain, and ALS.

Epidemiology, Treatment, and Prevention of Human T-Cell Leukemia Virus Type 1-Associated Diseases

PubMed Central

Gonçalves, Denise Utsch; Proietti, Fernando Augusto; Ribas, João Gabriel Ramos; Araújo, Marcelo Grossi; Pinheiro, Sônia Regina; Guedes, Antônio Carlos; Carneiro-Proietti, Anna Bárbara F.

2010-01-01

Summary: Human T-cell leukemia virus type 1 (HTLV-1), the first human retrovirus to be discovered, is present in diverse regions of the world, where its infection is usually neglected in health care settings and by public health authorities. Since it is usually asymptomatic in the beginning of the infection and disease typically manifests later in life, silent transmission occurs, which is associated with sexual relations, breastfeeding, and blood transfusions. There are no prospects of vaccines, and screening of blood banks and in prenatal care settings is not universal. Therefore, its transmission is active in many areas such as parts of Africa, South and Central America, the Caribbean region, Asia, and Melanesia. It causes serious diseases in humans, including adult T-cell leukemia/lymphoma (ATL) and an incapacitating neurological disease (HTLV-associated myelopathy/tropical spastic paraparesis [HAM/TSP]) besides other afflictions such as uveitis, rheumatic syndromes, and predisposition to helminthic and bacterial infections, among others. These diseases are not curable as yet, and current treatments as well as new perspectives are discussed in the present review. PMID:20610824

Association of Pesticide Exposure with Neurologic Dysfunction and Disease

PubMed Central

Kamel, Freya; Hoppin, Jane A.

2004-01-01

Poisoning by acute high-level exposure to certain pesticides has well-known neurotoxic effects, but whether chronic exposure to moderate levels of pesticides is also neurotoxic is more controversial. Most studies of moderate pesticide exposure have found increased prevalence of neurologic symptoms and changes in neurobehavioral performance, reflecting cognitive and psychomotor dysfunction. There is less evidence that moderate exposure is related to deficits in sensory or motor function or peripheral nerve conduction, but fewer studies have considered these outcomes. It is possible that the most sensitive manifestation of pesticide neurotoxicity is a general malaise lacking in specificity and related to mild cognitive dysfunction, similar to that described for Gulf War syndrome. Most studies have focused on organophosphate insecticides, but some found neuro-toxic effects from other pesticides, including fungicides, fumigants, and organochlorine and carbamate insecticides. Pesticide exposure may also be associated with increased risk of Parkinson disease; several classes of pesticides, including insecticides, herbicides, and fungicides, have been implicated. Studies of other neurodegenerative diseases are limited and inconclusive. Future studies will need to improve assessment of pesticide exposure in individuals and consider the role of genetic susceptibility. More studies of pesticides other than organophosphates are needed. Major unresolved issues include the relative importance of acute and chronic exposure, the effect of moderate exposure in the absence of poisoning, and the relationship of pesticide-related neurotoxicity to neurodegenerative disease. PMID:15198914

Human pluripotent stem cells as tools for neurodegenerative and neurodevelopmental disease modeling and drug discovery.

PubMed

Corti, Stefania; Faravelli, Irene; Cardano, Marina; Conti, Luciano

2015-06-01

Although intensive efforts have been made, effective treatments for neurodegenerative and neurodevelopmental diseases have not been yet discovered. Possible reasons for this include the lack of appropriate disease models of human neurons and a limited understanding of the etiological and neurobiological mechanisms. Recent advances in pluripotent stem cell (PSC) research have now opened the path to the generation of induced pluripotent stem cells (iPSCs) starting from somatic cells, thus offering an unlimited source of patient-specific disease-relevant neuronal cells. In this review, the authors focus on the use of human PSC-derived cells in modeling neurological disorders and discovering of new drugs and provide their expert perspectives on the field. The advent of human iPSC-based disease models has fuelled renewed enthusiasm and enormous expectations for insights of disease mechanisms and identification of more disease-relevant and novel molecular targets. Human PSCs offer a unique tool that is being profitably exploited for high-throughput screening (HTS) platforms. This process can lead to the identification and optimization of molecules/drugs and thus move forward new pharmacological therapies for a wide range of neurodegenerative and neurodevelopmental conditions. It is predicted that improvements in the production of mature neuronal subtypes, from patient-specific human-induced pluripotent stem cells and their adaptation to culture, to HTS platforms will allow the increased exploitation of human pluripotent stem cells in drug discovery programs.

Mitochondria in neuroplasticity and neurological disorders.

PubMed

Mattson, Mark P; Gleichmann, Marc; Cheng, Aiwu

2008-12-10

Mitochondrial electron transport generates the ATP that is essential for the excitability and survival of neurons, and the protein phosphorylation reactions that mediate synaptic signaling and related long-term changes in neuronal structure and function. Mitochondria are highly dynamic organelles that divide, fuse, and move purposefully within axons and dendrites. Major functions of mitochondria in neurons include the regulation of Ca(2+) and redox signaling, developmental and synaptic plasticity, and the arbitration of cell survival and death. The importance of mitochondria in neurons is evident in the neurological phenotypes in rare diseases caused by mutations in mitochondrial genes. Mitochondria-mediated oxidative stress, perturbed Ca(2+) homeostasis, and apoptosis may also contribute to the pathogenesis of prominent neurological diseases including Alzheimer's, Parkinson's, and Huntington's diseases; stroke; amyotrophic lateral sclerosis; and psychiatric disorders. Advances in understanding the molecular and cell biology of mitochondria are leading to novel approaches for the prevention and treatment of neurological disorders.

78 FR 18996 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Disorders and Stroke Special Emphasis Panel; Huntington's Disease SEP. Date: April 15, 2013. Time: 9:00 a.m...

Konzo: from poverty, cassava, and cyanogen intake to toxico-nutritional neurological disease.

PubMed

Nzwalo, Hipólito; Cliff, Julie

2011-06-01

Konzo is a distinct neurological entity with selective upper motor neuron damage, characterized by an abrupt onset of an irreversible, non-progressive, and symmetrical spastic para/tetraparesis. Despite its severity, konzo remains a neglected disease. The disease is associated with high dietary cyanogen consumption from insufficiently processed roots of bitter cassava combined with a protein-deficient diet. Epidemics occur when these conditions coincide at times of severe food shortage. Up to 1993, outbreaks in poor rural areas in Africa contributed to more than 3,700 cases of konzo. The number of affected people is underestimated. From unofficial reports, the number of cases was estimated to be at least 100,000 in 2000, in contrast to the 6,788 cases reported up to 2009 from published papers.

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.

Responsibilities of Health Care Professionals in Counseling and Educating Patients With Incurable Neurological Diseases Regarding "Stem Cell Tourism": Caveat Emptor.

PubMed

Bowman, Michelle; Racke, Michael; Kissel, John; Imitola, Jaime

2015-11-01

"Stem cell tourism" is a rising Internet-based industry that aims to offer unproven procedures to patients with incurable diseases. This unregulated activity is reaching the neurologist's office as well as across the world, as patients request information or clearance for such procedures. Herein, we posit the need for medical societies and licensing boards to bring this issue to the forefront of neurology because it has the potential to affect patient care with risk of morbidity and mortality, as well as to undermine public confidence in legitimate stem cell research for incurable neurological diseases such as multiple sclerosis and amyotrophic lateral sclerosis.

Cutaneous Adverse Effects of Neurologic Medications.

PubMed

Bahrani, Eman; Nunneley, Chloe E; Hsu, Sylvia; Kass, Joseph S

2016-03-01

Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication.

[Deficiency, disability, neurology and art].

PubMed

Cano de la Cuerda, Roberto; Collado-Vazquez, Susana

2010-07-16

Disability is a complex phenomenon, and the ways it has been conceived, explained and treated have varied notably throughout history. As the years go by, human beings have evolved and, at the same time, so have medicine and art. And therein lies the extraordinary value, from the ontological point of view, of many works of art, which would never have been produced without the intervention of disease and the practice of the medical art. The aim of this work is to address the study of some deficiencies, disabilities and neurological pathologies that have been represented in paintings at different times in history. This article begins with the study of pictures that deal with dwarves and other misnamed freaks of nature that have been represented by painters from Velazquez to Titian or Rubens. The study looks at paintings of cripples, pictures containing the mentally disabled, with examples by Bruegel the Elder or Munch, as well as certain neurological disorders that have been portrayed in paintings, such as Escaping criticism by Pere Borrell or Sad inheritance by Sorolla. Likewise, we also reflect on the trite concept of disease and artistic creativity. The artistic representation of deficiency and disability has evolved in parallel to the feelings of men and women in each period of history and, at the same time, their social evolution. Nowadays, this concept continues to advance and some artists no longer represent the sick person, but instead the illness itself.

Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases.

PubMed

Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

2016-01-01

There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and "others"). We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and "true" effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. The differences in reliability between biological psychiatry, neurology and somatic

The role of nanotechnology and nano and micro-electronics in monitoring and control of cardiovascular diseases and neurological disorders

NASA Astrophysics Data System (ADS)

Varadan, Vijay K.

2007-04-01

controlled manipulation of individual molecules and atoms that can interact with the human body at sub-cellular level. The recent progress in microelectronics and nanosensors crates very powerful tools for the early detection and diagnosis. The nanowire integrated potassium and dopamine sensors are ideal for the monitoring and control of many cardiovascular diseases and neurological disorders. Selected movies illustrating the applications of nanodevices to patients will be shown at the talk.

Changing child neurology training: evolution or revolution?

PubMed

Greenwood, Robert S

2012-02-01

Child neurology training must change as our understanding of the diseases of the developing nervous system increases. A proposed child neurology training path leading to certification in child neurology would eliminate all but 3 months of adult neurology training; however gaining approval for a new Accreditation Council for Graduate Medical Education (ACGME) training program would be an arduous task. I review why this change would add significant administrative and financial burdens and how this change in training could negatively affect the education of child neurology residents. I believe that modifications of the current training requirements already underway could achieve the same aims with fewer losses.

Immunization with neuronal nicotinic acetylcholine receptor induces neurological autoimmune disease

PubMed Central

Lennon, Vanda A.; Ermilov, Leonid G.; Szurszewski, Joseph H.; Vernino, Steven

2003-01-01

Neuronal nicotinic AChRs (nAChRs) are implicated in the pathogenesis of diverse neurological disorders and in the regulation of small-cell lung carcinoma growth. Twelve subunits have been identified in vertebrates, and mutations of one are recognized in a rare form of human epilepsy. Mice with genetically manipulated neuronal nAChR subunits exhibit behavioral or autonomic phenotypes. Here, we report the first model of an acquired neuronal nAChR disorder and evidence for its pertinence to paraneoplastic neurological autoimmunity. Rabbits immunized once with recombinant α3 subunit (residues 1–205) develop profound gastrointestinal hypomotility, dilated pupils with impaired light response, and grossly distended bladders. As in patients with idiopathic and paraneoplastic autoimmune autonomic neuropathy, the severity parallels serum levels of ganglionic nAChR autoantibody. Failure of neurotransmission through abdominal sympathetic ganglia, with retention of neuronal viability, confirms that the disorder is a postsynaptic channelopathy. In addition, we found ganglionic nAChR protein in small-cell carcinoma lines, identifying this cancer as a potential initiator of ganglionic nAChR autoimmunity. The data support our hypothesis that immune responses driven by distinct neuronal nAChR subtypes expressed in small-cell carcinomas account for several lung cancer–related paraneoplastic disorders affecting cholinergic systems, including autoimmune autonomic neuropathy, seizures, dementia, and movement disorders. PMID:12639997

Reliability of the Swedish version of the Exercise Self-Efficacy Scale (S-ESES): a test-retest study in adults with neurological disease.

PubMed

Ahlström, Isabell; Hellström, Karin; Emtner, Margareta; Anens, Elisabeth

2015-03-01

To examine the test-retest reliability of the Swedish translated version of the Exercise Self-Efficacy Scale (S-ESES) in people with neurological disease and to examine internal consistency. Test-retest study. A total of 30 adults with neurological diseases including: Parkinson's disease; Multiple Sclerosis; Cervical Dystonia; and Charcot-Marie-Tooth disease. The S-ESES was sent twice by surface mail. Completion interval mean was 16 days apart. Weighted kappa, intraclass correlation coefficient 2,1 [ICC (2,1)], standard error of measurement (SEM), also expressed as a percentage value (SEM%), and Cronbach's alpha were calculated. The relative reliability of the test-retest results showed substantial agreement measured using weighted kappa (MD = 0.62) and a very high-reliability ICC (2,1) (0.92). Absolute reliability measured using SEM was 5.3 and SEM% was 20.7. Excellent internal consistency was shown, with an alpha coefficient of 0.91 (test 1) and 0.93 (test 2). The S-ESES is recommended for use in research and in clinical work for people with neurological diseases. The low-absolute reliability, however, indicates a limited ability to measure changes on an individual level.

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

Setting the agenda for neurological nursing: strategic directions.

PubMed

Smith, Lorraine N

2006-11-01

This paper explores a range of issues related to neurological care. The scope and scale of neurological conditions is described in order to illustrate disparities in research funding and care delivery as compared with cancer and cardiovascular disease. Financial implications, ethical issues and health service development are outlined as a context for the state of the art of neurological nursing. Areas for potential neurological nursing research are identified. Finally, it is argued that policy and research must be linked if neurological care, research and education are to receive greater resource allocation.

The promise of telemedicine for chronic neurological disorders: the example of Parkinson's disease.

PubMed

Schneider, Ruth B; Biglan, Kevin M

2017-07-01

Disparities in access to health care, particularly specialist care, exist worldwide. As the prevalence of chronic neurological disorders increases with ageing populations, access to neurologist care is likely to worsen in many regions if there are no changes to models of care. Telemedicine-defined here as the use of real-time, synchronous videoconferencing to deliver medical care-could be used to improve access to neurologist care for patients with a range of chronic neurological disorders. In Parkinson's disease, several studies have shown the feasibility and potential benefits of telemedicine-delivered care. Further research is needed to establish whether telemedicine can deliver on the promise of improved access to neurologist care and whether telemedicine-delivered care is comparable to in-person care in terms of clinical outcomes. Many barriers to widespread implementation of telemedicine services remain to be addressed, including reimbursement, legal considerations, and technological issues. Copyright © 2017 Elsevier Ltd. All rights reserved.

History of neurologic examination books

PubMed Central

2015-01-01

The objective of this study was to create an annotated list of textbooks dedicated to teaching the neurologic examination. Monographs focused primarily on the complete neurologic examination published prior to 1960 were reviewed. This analysis was limited to books with the word “examination” in the title, with exceptions for the texts of Robert Wartenberg and Gordon Holmes. Ten manuals met the criteria. Works dedicated primarily to the neurologic examination without a major emphasis on disease description or treatment first appeared in the early 1900s. Georg Monrad-Krohn's “Blue Book of Neurology” (“Blue Bible”) was the earliest success. These treatises served the important purpose of educating trainees on proper neurologic examination technique. They could make a reputation and be profitable for the author (Monrad-Krohn), highlight how neurology was practiced at individual institutions (McKendree, Denny-Brown, Holmes, DeJong, Mayo Clinic authors), and honor retiring mentors (Mayo Clinic authors). PMID:25829645

Modern network science of neurological disorders.

PubMed

Stam, Cornelis J

2014-10-01

Modern network science has revealed fundamental aspects of normal brain-network organization, such as small-world and scale-free patterns, hierarchical modularity, hubs and rich clubs. The next challenge is to use this knowledge to gain a better understanding of brain disease. Recent developments in the application of network science to conditions such as Alzheimer's disease, multiple sclerosis, traumatic brain injury and epilepsy have challenged the classical concept of neurological disorders being either 'local' or 'global', and have pointed to the overload and failure of hubs as a possible final common pathway in neurological disorders.

Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response.

PubMed

MacLean, Lorna; Reiber, Hansotto; Kennedy, Peter G E; Sternberg, Jeremy M

2012-01-01

Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance. This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-β levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF. Our results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the

Mind-body interventions: applications in neurology.

PubMed

Wahbeh, Helané; Elsas, Siegward-M; Oken, Barry S

2008-06-10

Half of the adults in the United States use complementary and alternative medicine with mind-body therapy being the most commonly used form. Neurology patients often turn to their physicians for insight into the effectiveness of the therapies and resources to integrate them into their care. The objective of this article is to give a clinical overview of mind-body interventions and their applications in neurology. Medline and PsychInfo were searched on mind-body therapies and neurologic disease search terms for clinical trials and reviews and published evidence was graded. Meditation, relaxation, and breathing techniques, yoga, tai chi, and qigong, hypnosis, and biofeedback are described. Mind-body therapy application to general pain, back and neck pain, carpal tunnel syndrome, headaches, fibromyalgia, multiple sclerosis, epilepsy, muscular dysfunction, stroke, aging, Parkinson disease, stroke, and attention deficit-hyperactivity disorder are reviewed. There are several conditions where the evidence for mind-body therapies is quite strong such as migraine headache. Mind-body therapies for other neurology applications have limited evidence due mostly to small clinical trials and inadequate control groups.

Konzo: From Poverty, Cassava, and Cyanogen Intake to Toxico-Nutritional Neurological Disease

PubMed Central

Nzwalo, Hipólito; Cliff, Julie

2011-01-01

Konzo is a distinct neurological entity with selective upper motor neuron damage, characterized by an abrupt onset of an irreversible, non-progressive, and symmetrical spastic para/tetraparesis. Despite its severity, konzo remains a neglected disease. The disease is associated with high dietary cyanogen consumption from insufficiently processed roots of bitter cassava combined with a protein-deficient diet. Epidemics occur when these conditions coincide at times of severe food shortage. Up to 1993, outbreaks in poor rural areas in Africa contributed to more than 3,700 cases of konzo. The number of affected people is underestimated. From unofficial reports, the number of cases was estimated to be at least 100,000 in 2000, in contrast to the 6,788 cases reported up to 2009 from published papers. PMID:21738800

Stem cells for the treatment of neurological disorders

NASA Astrophysics Data System (ADS)

Lindvall, Olle; Kokaia, Zaal

2006-06-01

Many common neurological disorders, such as Parkinson's disease, stroke and multiple sclerosis, are caused by a loss of neurons and glial cells. In recent years, neurons and glia have been generated successfully from stem cells in culture, fuelling efforts to develop stem-cell-based transplantation therapies for human patients. More recently, efforts have been extended to stimulating the formation and preventing the death of neurons and glial cells produced by endogenous stem cells within the adult central nervous system. The next step is to translate these exciting advances from the laboratory into clinically useful therapies.

Neurological Manifestations of Dengue Infection.

PubMed

Li, Guo-Hong; Ning, Zhi-Jie; Liu, Yi-Ming; Li, Xiao-Hong

2017-01-01

Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS), peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

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...

A rare case of Niemann-Pick disease type C without neurological involvement in a 66-year-old patient.

PubMed

Greenberg, C R; Barnes, J G; Kogan, S; Seargeant, L E

2015-06-01

The case of a 66 year-old female - the oldest known living patient with Niemann-Pick disease type C (NP-C) who remains free of any neurological or psychiatric manifestations 18 years after presentation - is presented. An incidental finding of massive splenomegaly was detected during a routine pelvic ultrasound. The pathology report after splenectomy showed the presence of lipid-laden macrophages. Fibroblasts cultured in LDL-enriched medium revealed abnormal filipin staining consistent with cholesterol-filled vesicles and the rate of cholesterol esterification in response to stimulation of LDL-cholesterol uptake was significantly depressed at 6% of that seen in cells from normal controls, but at a level similar to that observed in an NP-C positive control. Molecular genetic testing later revealed a compound heterozygous mutant NP-C genotype comprising two previously described disease-causing mutations in the NPC1 gene, one in exon 8 (c.1133T>C [V378A]) and one in exon 13 (c.1990G>A [V664M]). These findings confirmed the diagnosis of NP-C. Only three patients with this disorder aged > 53 years have previously been reported, all of whom presented with neurological or neuropsychiatric manifestations. Our patient is the first reported NP-C patient, now in her seventh decade of life, who has to date only manifested splenomegaly. This case highlights the extreme clinical variability of NP-C, and the need to consider this disease in the differential diagnosis of organomegaly, even in the absence of neurological, psychiatric and related clinical signs. An elderly female patient with confirmed NP-C and isolated splenomegaly has remained asymptomatic for neurological, cognitive, psychiatric or ophthalmologic abnormailities into her seventh decade of life.

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.

Current research into brain barriers and the delivery of therapeutics for neurological diseases: a report on CNS barrier congress London, UK, 2017.

PubMed

Greenwood, John; Hammarlund-Udenaes, Margareta; Jones, Hazel C; Stitt, Alan W; Vandenbroucke, Roosmarijn E; Romero, Ignacio A; Campbell, Matthew; Fricker, Gert; Brodin, Birger; Manninga, Heiko; Gaillard, Pieter J; Schwaninger, Markus; Webster, Carl; Wicher, Krzysztof B; Khrestchatisky, Michel

2017-11-07

This is a report on the CNS barrier congress held in London, UK, March 22-23rd 2017 and sponsored by Kisaco Research Ltd. The two 1-day sessions were chaired by John Greenwood and Margareta Hammarlund-Udenaes, respectively, and each session ended with a discussion led by the chair. Speakers consisted of invited academic researchers studying the brain barriers in relation to neurological diseases and industry researchers studying new methods to deliver therapeutics to treat neurological diseases. We include here brief reports from the speakers.

[Epigenome: what we learned from Rett syndrome, a neurological disease caused by mutation of a methyl-CpG binding protein].

PubMed

Kubota, Takeo

2013-01-01

Epigenome is defined as DNA and histone modification-dependent gene regulation system. Abnormalities in this system are known to cause various neuro-developmental diseases. We recently reported that neurological symptoms of Rett syndrome, which is an autistic disorder caused by mutations in methyl-CpG binding protein 2 (MeCP2), was associated with failure of epigenomic gene regulation in neuronal cells, and that clinical differences in the identical twins with Rett syndrome in the differences in DNA methylation in neuronal genes, but not caused by DNA sequence differences. Since central nervus system requires precise gene regulation, neurological diseases including Alzheimer and Parkinson diseases may be caused by acquired DNA modification (epigenomic) changes that results in aberrant gene regulation as well as DNA sequence changes congenitally occurred (mutation).

Neuromodulation of lower limb motor control in restorative neurology.

PubMed

Minassian, Karen; Hofstoetter, Ursula; Tansey, Keith; Mayr, Winfried

2012-06-01

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system. Copyright © 2012 Elsevier B.V. All rights reserved.

Neuromodulation of lower limb motor control in restorative neurology

PubMed Central

Minassian, Karen; Hofstoetter, Ursula; Tansey, Keith; Mayr, Winfried

2012-01-01

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system. PMID:22464657

Adult neurology training during child neurology residency.

PubMed

Schor, Nina F

2012-08-21

As it is currently configured, completion of child neurology residency requires performance of 12 months of training in adult neurology. Exploration of whether or not this duration of training in adult neurology is appropriate for what child neurology is today must take into account the initial reasons for this requirement and the goals of adult neurology training during child neurology residency.

Awareness Status of Chronic Disabling Neurological Diseases among Elderly Veterans.

PubMed

Tan, Ji-Ping; Zhu, Lin-Qi; Zhang, Jun; Zhang, Shi-Min; Lan, Xiao-Yang; Cui, Bo; Deng, Yu-Cheng; Li, Ying-Hao; Ye, Guang-Hua; Wang, Lu-Ning

2015-05-20

The awareness, treatment and prevention of chronic diseases are generally poor among the elderly population of China, whereas the prevention and control of chronic diseases in elderly veteran communities have been ongoing for more than 30 years. Therefore, investigating the awareness status of chronic disabling neurological diseases (CDND) and common chronic diseases (CCD) among elderly veterans may provide references for related programs among the elderly in the general population. A cross-sectional survey was conducted among veterans ≥60 years old in veteran communities in Beijing. The awareness of preventive strategies against dementia, Alzheimer's disease (AD), Parkinson's disease (PD), sleep disorders, cerebrovascular disease (CVD) and CCD such as hypertension, and the approaches used to access this information, including media, word of mouth (verbal communication among the elderly) and health care professionals, were investigated via face-to-face interviews. The awareness rates for CCD and CVD were approximately 100%, but that for AD was the lowest at <10%. The awareness rates for sleep disorders, PD and dementia, were 51.0-89.4%. Media was the most commonly selected mode of communication by which veterans acquired knowledge about CCD and CVD. Media was used by approximately 80% of veterans. Both health care professionals and word of mouth were used by approximately 50% of veterans. With respect to the source of information about CDND excluding AD, the rates of the use of health care professionals, word of mouth and media were 10.6-28.2%, 56.5-76.5%, and approximately 50%, respectively. The awareness of CDND among elderly veterans was significantly lower than that of CCD. More information about CDND should be disseminated by health care professionals. Appropriate guidance will promote the rapid and extensive dissemination of information about the prevention of CDND by media and word-of-mouth peer education.

Awareness Status of Chronic Disabling Neurological Diseases among Elderly Veterans

PubMed Central

Tan, Ji-Ping; Zhu, Lin-Qi; Zhang, Jun; Zhang, Shi-Min; Lan, Xiao-Yang; Cui, Bo; Deng, Yu-Cheng; Li, Ying-Hao; Ye, Guang-Hua; Wang, Lu-Ning

2015-01-01

Background: The awareness, treatment and prevention of chronic diseases are generally poor among the elderly population of China, whereas the prevention and control of chronic diseases in elderly veteran communities have been ongoing for more than 30 years. Therefore, investigating the awareness status of chronic disabling neurological diseases (CDND) and common chronic diseases (CCD) among elderly veterans may provide references for related programs among the elderly in the general population. Methods: A cross-sectional survey was conducted among veterans ≥60 years old in veteran communities in Beijing. The awareness of preventive strategies against dementia, Alzheimer's disease (AD), Parkinson's disease (PD), sleep disorders, cerebrovascular disease (CVD) and CCD such as hypertension, and the approaches used to access this information, including media, word of mouth (verbal communication among the elderly) and health care professionals, were investigated via face-to-face interviews. Results: The awareness rates for CCD and CVD were approximately 100%, but that for AD was the lowest at <10%. The awareness rates for sleep disorders, PD and dementia, were 51.0–89.4%. Media was the most commonly selected mode of communication by which veterans acquired knowledge about CCD and CVD. Media was used by approximately 80% of veterans. Both health care professionals and word of mouth were used by approximately 50% of veterans. With respect to the source of information about CDND excluding AD, the rates of the use of health care professionals, word of mouth and media were 10.6–28.2%, 56.5–76.5%, and approximately 50%, respectively. Conclusions: The awareness of CDND among elderly veterans was significantly lower than that of CCD. More information about CDND should be disseminated by health care professionals. Appropriate guidance will promote the rapid and extensive dissemination of information about the prevention of CDND by media and word-of-mouth peer education

[Advance of genetics and genomics in neurology].

PubMed

Ginter, E K; Illarioshkin, S N

2012-01-01

Studies of genomic background of neurological disorders are very actual in view of their high population prevalence, severe course, serious impact on patients' disability and progressive mental and physical de-adaptation. In the paper, problems of genetic heterogeneity of hereditary neurological disorders and character of the respective genetic burden in the regions of Russian Federation are discussed in detail, a 'dynamic' type of mutations (increase in number of microsatellite repeats copies) attributable to many neurodegenerative diseases is analyzed, and achievements of Russian researchers in the identification of genes for hereditary neurological disorders and in the realization of pilot protocols of gene therapy are presented. Problems related to studies of genetic predisposition to common multifactorial diseases of the nervous system are discussed.

Long-term Continuous EEG Monitoring in Small Rodent Models of Human Disease Using the Epoch Wireless Transmitter System

PubMed Central

Zayachkivsky, Andrew; Lehmkuhle, Mark J.; Dudek, F. Edward

2015-01-01

Many progressive neurologic diseases in humans, such as epilepsy, require pre-clinical animal models that slowly develop the disease in order to test interventions at various stages of the disease process. These animal models are particularly difficult to implement in immature rodents, a classic model organism for laboratory study of these disorders. Recording continuous EEG in young animal models of seizures and other neurological disorders presents a technical challenge due to the small physical size of young rodents and their dependence on the dam prior to weaning. Therefore, there is not only a clear need for improving pre-clinical research that will better identify those therapies suitable for translation to the clinic but also a need for new devices capable of recording continuous EEG in immature rodents. Here, we describe the technology behind and demonstrate the use of a novel miniature telemetry system, specifically engineered for use in immature rats or mice, which is also effective for use in adult animals. PMID:26274779

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.

Consensus Statement on medication use in multiple sclerosis by the Spanish Society of Neurology's study group for demyelinating diseases.

PubMed

García-Merino, A; Fernández, O; Montalbán, X; de Andrés, C; Oreja-Guevara, C; Rodríguez-Antigüedad, A; Arbizu, T

2013-01-01

Treatments for multiple sclerosis therapy are rapidly evolving. It is believed that new drugs will be approved in the near future, thereby changing current indications for treatment. In this context, the Spanish Society of Neurology's study group on demyelinating diseases, which evaluates medication use in MS, has decided to draw up a consensus statement on the current indications and guidelines for multiple sclerosis treatment. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection. III. Neurologic and neuropsychological findings.

PubMed

Stern, Y; Marder, K; Bell, K; Chen, J; Dooneief, G; Goldstein, S; Mindry, D; Richards, M; Sano, M; Williams, J

1991-02-01

We explored the possibility that neurologic and neuropsychological changes constitute the earliest detectable manifestations of human immunodeficiency virus (HIV) infection. Without knowledge of HIV status, we assessed neurologic signs and symptoms and administered a battery of neuropsychological tests to 208 homosexual men, of whom 84 were HIV negative, 49 were HIV positive and asymptomatic, 29 were mildly symptomatic, and 46 had significant medical symptoms but not the acquired immunodeficiency syndrome. There was no difference between the HIV-negative and HIV-positive men in the frequency of neurologic signs or of defective or borderline performance on any neuropsychological test. However, HIV-positive men performed slightly but significantly worse than HIV-negative men on tests of verbal memory, executive function, and language. Similar results were obtained when comparisons were limited to HIV-positive medically asymptomatic and HIV-negative men. There was no degradation of neurologic status or neuropsychological performance across stages of HIV severity, but neurologic and neuropsychological summary scores correlated with CD4/CD8 ratios in the HIV-positive group. Ratings of neurologic signs and symptoms correlated with neuropsychological summary scores in the HIV-positive group only. Cognitive complaints were more frequent in the HIV-positive men; they correlated with actual test performance in the HIV-positive but not HIV-negative men. The constellation of subjective and objective neuropsychological and neurologic findings suggests the possibility of a definable syndrome associated with HIV infection in asymptomatic individuals.

Clinical NMR imaging of the brain in children: normal and neurologic disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, M.A,; Pennock, J.M.; Bydder, G.M.

1983-11-01

The results of initial clinical nuclear magnetic resonance imaging of the brain in eight normal and 52 children with a wide variety of neurologic diseases were reviewed. The high level of gray-white matter contrast available with inversion-recovery sequences provided a basis for visualizing normal myelination as well as delays or deficits in this process. The appearances seen in cases of parenchymal hemorrhage, cerebral infarction, and proencephalic cysts are described. Ventricular enlargement was readily identified and marginal edema was demonstrated with spin-echo sequences. Abnormalities were seen in cerebral palsy, congenital malformations, Hallervorden-Spatz disease, aminoaciduria, and meningitis. Space-occupying lesions were identified bymore » virtue of their increased relaxation times and mass effects. Nuclear magnetic resonance imaging has considerable potential in pediatric neuroradiologic practice, in some conditions supplying information not available by computed tomography or sonography.« less

mRNA Translation Gone Awry: Translation Fidelity and Neurological Disease.

PubMed

Kapur, Mridu; Ackerman, Susan L

2018-03-01

Errors during mRNA translation can lead to a reduction in the levels of functional proteins and an increase in deleterious molecules. Advances in next-generation sequencing have led to the discovery of rare genetic disorders, many caused by mutations in genes encoding the mRNA translation machinery, as well as to a better understanding of translational dynamics through ribosome profiling. We discuss here multiple neurological disorders that are linked to errors in tRNA aminoacylation and ribosome decoding. We draw on studies from genetic models, including yeast and mice, to enhance our understanding of the translational defects observed in these diseases. Finally, we emphasize the importance of tRNA, their associated enzymes, and the inextricable link between accuracy and efficiency in the maintenance of translational fidelity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Health-related quality of life among community-dwelling patients with intractable neurological diseases and their caregivers in Japan.

PubMed

Miyashita, Mitsunori; Narita, Yugo; Sakamoto, Aki; Kawada, Norikazu; Akiyama, Miki; Kayama, Mami; Suzukamo, Yoshimi; Fukuhara, Shunichi

2011-02-01

The aims of this study were: (i) to clarify the general quality of life (QOL) of patients with intractable neurological disease; (ii) to clarify the general QOL of the caregivers of these patients; and (iii) to explore the association of QOL in patient-caregiver pairs. A cross-sectional survey was conducted between November 2003 and May 2004 among community-dwelling patients diagnosed with Parkinson's disease (PD), spinocerebellar degeneration (SCD), multiple system atrophy (MSA), and amyotrophic lateral sclerosis (ALS) and their caregivers using a mailed, self-administered questionnaire. To measure QOL, we used the Medical Outcome Study 36-Item Short Form (SF-36) for patients and the short form of the health-related QOL scale SF-36 (SF-8) for caregivers. A total of 418 questionnaires were analyzed. For the patients, all of the general QOL domains of the SF-36 were significantly lower than the national standard value for all of the diagnoses. Physical function, role physical, and role emotional domains were also low. For caregivers, all of the QOL summary scores of the SF-8 for all diagnoses were significantly lower than the national standard value. Although there were several significant correlations of QOL between patients and caregivers, overall the correlations were low. Support for patients with neurological diseases and their caregivers is needed in order to maintain physical and mental QOL. © 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology.

Criteria for the diagnosis of Alzheimer’s disease: Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

PubMed Central

Frota, Norberto Anízio Ferreira; Nitrini, Ricardo; Damasceno, Benito Pereira; Forlenza, Orestes V.; Dias-Tosta, Elza; da Silva, Amauri B.; Herrera Junior, Emílio; Magaldi, Regina Miksian

2011-01-01

This consensus prepared by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology is aimed at recommending new criteria for the diagnosis of dementia and Alzheimer’s disease (AD) in Brazil. A revision was performed of the proposals of clinical and of research criteria suggested by other institutions and international consensuses. The new proposal for the diagnosis of dementia does not necessarily require memory impairment if the cognitive or behavioral compromise affects at least two of the following domains: memory, executive function, speech, visual-spatial ability and change in personality. For the purpose of diagnosis, AD is divided into three phases: dementia, mild cognitive impairment and pre-clinical phase, where the latter only applies to clinical research. In the dementia picture, other initial forms were accepted which do not involve amnesia and require a neuroimaging examination. Cerebrospinal fluid biomarkers are recommended for study, but can be utilized as optional instruments, when deemed appropriate by the clinician. PMID:29213739

Evidence based effects of yoga in neurological disorders.

PubMed

Mooventhan, A; Nivethitha, L

2017-09-01

Though yoga is one of the widely used mind-body medicine for health promotion, disease prevention and as a possible treatment modality for neurological disorders, there is a lack of evidence-based review. Hence, we performed a comprehensive search in the PubMed/Medline electronic database to review relevant articles in English, using keywords "yoga and neurological disorder, yoga and multiple sclerosis, yoga and stroke, yoga and epilepsy, yoga and Parkinson's disease, yoga and dementia, yoga and cerebrovascular disease, yoga and Alzheimer disease, yoga and neuropathy, yoga and myelopathy, and yoga and Guillain-Barre syndrome". A total of 700 articles published from 1963 to 14th December 2016 were available. Of 700 articles, 94 articles were included in this review. Based on the available literature, it could be concluded that yoga might be considered as an effective adjuvant for the patients with various neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

HIV-2 and its neurological manifestations.

PubMed

Rolfe, M

1994-08-01

The human immunodeficiency virus type 2 (HIV-2) produces a similar spectrum of illness as HIV-1, including AIDS, and is clinically indistinguishable. There is evidence that it is less pathogenic, with a longer natural history. HIV-2 infection is endemic in West Africa, especially in the former Portuguese and French colonies. Trade, migration, war and tourism have been important factors in the spread of the virus through the subregion and beyond. Diagnostic facilities necessary for the accurate diagnosis of neurological disease are not available in most of Africa and autopsy reports have been few. These constraints have restricted the information available on the pattern of neuropathology induced by HIV-2. However, it possesses neurotropic properties similar to those of HIV-1 and produces disease by means of direct action of the virus on the nervous system, and immunosuppression which allows opportunistic infections and tumours to occur.

Gene expression regulation by upstream open reading frames and human disease.

PubMed

Barbosa, Cristina; Peixeiro, Isabel; Romão, Luísa

2013-01-01

Upstream open reading frames (uORFs) are major gene expression regulatory elements. In many eukaryotic mRNAs, one or more uORFs precede the initiation codon of the main coding region. Indeed, several studies have revealed that almost half of human transcripts present uORFs. Very interesting examples have shown that these uORFs can impact gene expression of the downstream main ORF by triggering mRNA decay or by regulating translation. Also, evidence from recent genetic and bioinformatic studies implicates disturbed uORF-mediated translational control in the etiology of many human diseases, including malignancies, metabolic or neurologic disorders, and inherited syndromes. In this review, we will briefly present the mechanisms through which uORFs regulate gene expression and how they can impact on the organism's response to different cell stress conditions. Then, we will emphasize the importance of these structures by illustrating, with specific examples, how disturbed uORF-mediated translational control can be involved in the etiology of human diseases, giving special importance to genotype-phenotype correlations. Identifying and studying more cases of uORF-altering mutations will help us to understand and establish genotype-phenotype associations, leading to advancements in diagnosis, prognosis, and treatment of many human disorders.

Homovanillic acid in cerebrospinal fluid of 1388 children with neurological disorders.

PubMed

Molero-Luis, Marta; Serrano, Mercedes; Ormazábal, Aida; Pérez-Dueñas, Belén; García-Cazorla, Angels; Pons, Roser; Artuch, Rafael

2013-06-01

To determine the prevalence of dopaminergic abnormalities in 1388 children with neurological disorders, and to analyse their clinical, neuroradiological, and electrophysiological characteristics. We studied biogenic amines in 1388 cerebrospinal fluid (CSF) samples from children with neurological disorders (mean age 3y 10mo, SD 4y 5mo; 712 males, 676 females. Correlations among CSF homovanillic acid (HVA) values and other biochemical, clinical, neuroradiological, and electrophysiological parameters were analysed. Twenty-one patients with primary dopaminergic deficiencies were identified. Of the whole sample, 20% showed altered HVA. We report neurological diseases with abnormal CSF HVA values such as pontocerebellar hypoplasia, perinatal asphyxia, central nervous system infections, mitochondrial disorders, and other genetic diseases. Overlapping HVA levels between primary and secondary dopamine deficiencies were observed. Prevalence of low CSF HVA levels was significantly higher in neonatal patients (χ(2) =84.8, p<0.001). Abnormalities in white matter were associated with low CSF HVA (odds ratio 2.3, 95% confidence interval 1.5-3.5). HVA abnormalities are observed in various neurological diseases, but some are probably an unspecific finding. No clear limits for CSF HVA values pointing towards primary diseases can be stated. We report several neurological diseases showing HVA alterations. No neuroimaging traits were associated with low HVA values, except for white matter abnormalities. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

Devices for Ambulatory Monitoring of Sleep-Associated Disorders in Children with Neurological Diseases.

PubMed

Ulate-Campos, Adriana; Tsuboyama, Melissa; Loddenkemper, Tobias

2017-12-25

Good sleep quality is essential for a child's wellbeing. Early sleep problems have been linked to the later development of emotional and behavioral disorders and can negatively impact the quality of life of the child and his or her family. Sleep-associated conditions are frequent in the pediatric population, and even more so in children with neurological problems. Monitoring devices can help to better characterize sleep efficiency and sleep quality. They can also be helpful to better characterize paroxysmal nocturnal events and differentiate between nocturnal seizures, parasomnias, and obstructive sleep apnea, each of which has a different management. Overnight ambulatory detection devices allow for a tolerable, low cost, objective assessment of sleep quality in the patient's natural environment. They can also be used as a notification system to allow for rapid recognition and prompt intervention of events like seizures. Optimal monitoring devices will be patient- and diagnosis-specific, but may include a combination of modalities such as ambulatory electroencephalograms, actigraphy, and pulse oximetry. We will summarize the current literature on ambulatory sleep devices for detecting sleep disorders in children with neurological diseases.

Neurological Aspects of Medical Use of Cannabidiol.

PubMed

Mannucci, Carmen; Navarra, Michele; Calapai, Fabrizio; Spagnolo, Elvira V; Busardò, Francesco P; Cas, Roberto D; Ippolito, Francesca M; Calapai, Gioacchino

2017-01-01

Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numerous pathological conditions. CBD neuroprotection is due to its antioxidant and antiinflammatory activities and the modulation of a large number of brain biological targets (receptors, channels) involved in the development and maintenance of neurodegenerative diseases. The aim of the present review was to describe the state of art about the pre-clinical research, the potential use and, when existing, the clinical evidence related to CBD in the neurological field. Collection of all the pre-clinical and clinical findings carried out investigating the effects of CBD alone, not in combination with other substances, in the neurological arena with the exclusion of studies on neuropsychiatric disorders. Laboratory and clinical studies on the potential role of CBD in Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), Huntington's disease (HD), amyotrophic lateral sclerosis ALS), cerebral ischemia, were examined. Pre-clinical evidence largely shows that CBD can produce beneficial effects in AD, PD and MS patients, but its employment for these disorders needs further confirmation from well designed clinical studies. CBD pre-clinical demonstration of antiepileptic activity is supported by recent clinical studies in human epileptic subjects resistant to standard antiepileptic drugs showing its potential use in children and young adults affected by refractory epilepsy. Evidence for use of CBD in PD is still not supported by sufficient data whereas only a few studies including a small number of patients are available. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The importance of de novo mutations for pediatric neurological disease--It is not all in utero or birth trauma.

PubMed

Erickson, Robert P

2016-01-01

The advent of next generation sequencing (NGS, which consists of massively parallel sequencing to perform TGS (total genome sequencing) or WES (whole exome sequencing)) has abundantly discovered many causative mutations in patients with pediatric neurological disease. A surprisingly high number of these are de novo mutations which have not been inherited from either parent. For epilepsy, autism spectrum disorders, and neuromotor disorders, including cerebral palsy, initial estimates put the frequency of causative de novo mutations at about 15% and about 10% of these are somatic. There are some shared mutated genes between these three classes of disease. Studies of copy number variation by comparative genomic hybridization (CGH) proceded the NGS approaches but they also detect de novo variation which is especially important for ASDs. There are interesting differences between the mutated genes detected by CGS and NGS. In summary, de novo mutations cause a very significant proportion of pediatric neurological disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Franklin Delano Roosevelt's (FDR's) (1882-1945) 1921 neurological disease revisited; the most likely diagnosis remains Guillain-Barré syndrome.

PubMed

Goldman, Armond S; Schmalstieg, Elisabeth J; Dreyer, Charles F; Schmalstieg, Frank C; Goldman, Daniel A

2016-11-01

In 2003, we published evidence that the most likely cause of FDR's 1921 neurological disease was Guillain-Barré syndrome. Afterwards, several historians and neurologists stated in their publications that FDR had paralytic poliomyelitis. However, significant criticism of our article or new support for that diagnosis was not revealed. One critic claimed that FDR's cerebrospinal fluid indicated poliomyelitis, but we did not find evidence that a lumbar puncture was performed. The diagnosis of FDR's neurological disease still depends upon documented clinical abnormalities. His age, prolonged symmetric ascending paralysis, transient numbness, protracted dysaesthesia (pain on slight touch), facial paralysis, bladder and bowel dysfunction, and absence of meningismus are typical of Guillain-Barré syndrome and are inconsistent with paralytic poliomyelitis. FDR's prolonged fever was atypical for both diseases. Finally, permanent paralysis, though commoner in paralytic poliomyelitis, is frequent in Guillain-Barré syndrome. Thus, the clinical findings indicate the most likely diagnosis in FDR's case remains Guillain-Barré syndrome. © IMechE 2015.

Salivary proteomics and biomarkers in neurology and psychiatry.

PubMed

Wormwood, Kelly L; Aslebagh, Roshanak; Channaveerappa, Devika; Dupree, Emmalyn J; Borland, Megan M; Ryan, Jeanne P; Darie, Costel C; Woods, Alisa G

2015-10-01

Biomarkers are greatly needed in the fields of neurology and psychiatry, to provide objective and earlier diagnoses of CNS conditions. Proteomics and other omics MS-based technologies are tools currently being utilized in much recent CNS research. Saliva is an interesting alternative biomaterial for the proteomic study of CNS disorders, with several advantages. Collection is noninvasive and saliva has many proteins. It is easier to collect than blood and can be collected by professionals without formal medical training. For psychiatric and neurological patients, supplying a saliva sample is less anxiety-provoking than providing a blood sample, and is less embarrassing than producing a urine specimen. The use of saliva as a biomaterial has been researched for the diagnosis of and greater understanding of several CNS conditions, including neurodegenerative diseases, autism, and depression. Salivary biomarkers could be used to rule out nonpsychiatric conditions that are often mistaken for psychiatric/neurological conditions, such as fibromyalgia, and potentially to assess cognitive ability in individuals with compromised brain function. As MS and omics technology advances, the sensitivity and utility of assessing CNS conditions using distal human biomaterials such as saliva is becoming increasingly possible. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

PubMed Central

Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

2016-01-01

Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability

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

Acute Neurological Issues in Pregnancy and the Peripartum

PubMed Central

Hosley, Catherine M.; McCullough, Louise D.

2011-01-01

Acute neurological diseases requiring hospitalization are relatively rare in women of childbearing age. However, during pregnancy and the postpartum period, several diseases increase in prevalence. Some are unique to the pregnant/postpartum state including preeclampsia and delivery-associated neuropathies. Others, although indirectly related to pregnancy, such as cerebral venous thrombosis, ischemic stroke, and intracerebral hemorrhage, increase in frequency and carry considerable risk of morbidity and mortality. In addition, treatment options are often limited. This review discusses the diseases more commonly seen during pregnancy and the postpartum period, with a focus on emergent neurological diseases and their management. Interventional therapies will also be discussed. PMID:23983844

Neurologic sequelae of deficiency diseases in World War II prisoners of war: Extracts from a videographic narrative.

PubMed

Kumar, Neeraj; Boes, Christopher J; Vilensky, Joel

2010-03-01

This report aims at bringing attention to still frames from a film that provides a videographic narrative of neurologic deficiency diseases in post World War II prisoners of war. An abbreviated version of the original film is provided as Supplementary material. Copyright 2009 Elsevier Ltd. All rights reserved.

Humanized mouse models: Application to human diseases.

PubMed

Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

2018-05-01

Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

Xeroderma pigmentosum neurological abnormalities correlate with colony-forming ability after ultraviolet radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrews, A.D.; Barrett, S.F.; Robbins, J.H.

1978-04-01

Xeroderma pigmentosum is an autosomal recessive disease in which DNA repair processes are defective. All xeroderma pigmentosum patients develop premature aging of sun exposed skin, and some develop neurological abnormalities due to premature death of nerve cells. Sensitivity to ultraviolet radiation of 24 xeroderma pigmentosum fibroblast strains was studied in vitro by measuring each strain's ability to divide and form colonies after irradiation. The most sensitive strains were derived from patients who had an early onset of neurological abnormalities; less sensitive strains were from patients with a later onset; and the most resistant strains were from patients without neurological abnormalities.more » The uv sensitivities of strains from each member of a sibling pair with xeroderma pigmentosum were identical, indicating that uv sensitivity of xeroderma pigmentosum strains is determined by the patient's inherited DNA repair defect. The results suggest that effective DNA repair is required to maintain the functional integrity of the human nervous system by preventing premature death of neurons.« less

Mathematical Modeling of Protein Misfolding Mechanisms in Neurological Diseases: A Historical Overview.

PubMed

Carbonell, Felix; Iturria-Medina, Yasser; Evans, Alan C

2018-01-01

Protein misfolding refers to a process where proteins become structurally abnormal and lose their specific 3-dimensional spatial configuration. The histopathological presence of misfolded protein (MP) aggregates has been associated as the primary evidence of multiple neurological diseases, including Prion diseases, Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jacob disease. However, the exact mechanisms of MP aggregation and propagation, as well as their impact in the long-term patient's clinical condition are still not well understood. With this aim, a variety of mathematical models has been proposed for a better insight into the kinetic rate laws that govern the microscopic processes of protein aggregation. Complementary, another class of large-scale models rely on modern molecular imaging techniques for describing the phenomenological effects of MP propagation over the whole brain. Unfortunately, those neuroimaging-based studies do not take full advantage of the tremendous capabilities offered by the chemical kinetics modeling approach. Actually, it has been barely acknowledged that the vast majority of large-scale models have foundations on previous mathematical approaches that describe the chemical kinetics of protein replication and propagation. The purpose of the current manuscript is to present a historical review about the development of mathematical models for describing both microscopic processes that occur during the MP aggregation and large-scale events that characterize the progression of neurodegenerative MP-mediated diseases.

The Spectrum and Burden of Influenza-Associated Neurological Disease in Children: Combined Encephalitis and Influenza Sentinel Site Surveillance From Australia, 2013-2015.

PubMed

Britton, Philip N; Blyth, Christopher C; Macartney, Kristine; Dale, Russell C; Li-Kim-Moy, Jean; Khandaker, Gulam; Crawford, Nigel W; Marshall, Helen; Clark, Julia E; Elliott, Elizabeth J; Booy, Robert; Cheng, Allen C; Jones, Cheryl A

2017-08-15

There are few longitudinal studies of seasonal influenza-associated neurological disease (IAND) and none from the Southern Hemisphere. We extracted prospectively acquired Australian surveillance data from 2 studies nested within the Paediatric Active Enhanced Disease Surveillance (PAEDS) network: the Influenza Complications Alert Network (FluCAN) study and the Australian Childhood Encephalitis (ACE) study between 2013 and 2015. We described the clinical features and severity of IAND in children, including influenza-associated encephalitis/encephalopathy (IAE). We calculated the proportion of hospitalized influenza that is associated with IAND and IAE, and incidence of IAE. Over 3 influenza seasons, we identified 54 cases of IAND at 2 tertiary children's hospitals from Australia that accounted for 7.6% of hospitalized influenza. These included 10 cases of IAE (1.4% hospitalized influenza). The mean annual incidence of IAE among Australian children (aged ≤14 years) was 2.8 per 1000000. The spectrum of IAND was broad and included IAE (n = 10) including distinct acute encephalopathy syndromes, simple febrile seizures (n = 14), other seizures (n = 16), acute ataxia (n = 4), and other subacute syndromes (transverse myelitis [n = 1], opsoclonus myoclonus [n = 1]). Two-thirds of children with IAND were aged ≤4 years; less than half had preexisting neurological disease or other risk factors for severe influenza. IAE caused death or neurological morbidity in half of cases. Seasonal influenza is an important cause of acute neurological disease in Australian children. The spectrum of seasonal IAND appears similar to that described during the 2009 H1N1 pandemic. IAE is associated with high morbidity and mortality.

Extreme hyponatraemia with intact neurological outcome in a young child with Addison’s disease

PubMed Central

Smith, John-Paul; Burren, Christine; Cherinet, Yonas

2011-01-01

The authors present the case of a 6-year-old boy with a good neurological outcome from extreme hyponatraemia caused by autoimmune hypoadrenalism. He presented with 1 week of reduced appetite, lethargy, vomiting and one episode of diarrhoea. He was described as being slightly unsteady on his feet. Clinically he was alert, although intermittently confused, with dry mucous membranes and sunken eyes. Serum sodium was 96 mmol/l with normal serum potassium and renal function. He was initially treated with 3% saline intravenously, and his serum sodium increased to 128 mmol/l by day 3. He developed slurred speech and ataxia on day 4, although MRI brain showed no evidence of pontine myelinosis, and the symptoms resolved over 1 week. A Synacthen test on day 10 confirmed a diagnosis of Addison’s disease and he was commenced on hydrocortisone and fludrocortisone replacement therapy. At 5 months follow-up there are no obvious neurological or developmental sequelae. PMID:22679234

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...

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.

Effects of music and music therapy on mood in neurological patients

PubMed Central

Raglio, Alfredo; Attardo, Lapo; Gontero, Giulia; Rollino, Silvia; Groppo, Elisabetta; Granieri, Enrico

2015-01-01

Mood disorder and depressive syndromes represent a common comorbid condition in neurological disorders with a prevalence rate that ranges between 20% and 50% of patients with stroke, epilepsy, multiple sclerosis, and Parkinson’s disease. Notwithstanding, these conditions are often under-diagnosed and under-treated in the clinical practice and negatively affect the functional recovery, the adherence to treatment, the quality of life, and even the mortality risk. In addition, a bidirectional association between depression and neurological disorders may be possible being that depressive syndromes may be considered as a risk factor for certain neurological diseases. Despite the large amount of evidence regarding the effects of music therapy (MT) and other musical interventions on different aspects of neurological disorders, no updated article reviewing outcomes such as mood, emotions, depression, activity of daily living and so on is actually available; for this reason, little is known about the effectiveness of music and MT on these important outcomes in neurological patients. The aim of this article is to provide a narrative review of the current literature on musical interventions and their effects on mood and depression in patients with neurological disorders. Searching on PubMed and PsycInfo databases, 25 studies corresponding to the inclusion criteria have been selected; 11 of them assess the effects of music or MT in Dementia, 9 explore the efficacy on patients with Stroke, and 5 regard other neurological diseases like Multiple Sclerosis, Amyotrophic Lateral Sclerosis/motor neuron disease, Chronic quadriplegia, Parkinson’s Disease, and Acquired Brain dysfunctions. Selected studies are based on relational and rehabilitative music therapy approaches or concern music listening interventions. Most of the studies support the efficacy of MT and other musical interventions on mood, depressive syndromes, and quality of life on neurological patients. PMID:25815256

Effects of music and music therapy on mood in neurological patients.

PubMed

Raglio, Alfredo; Attardo, Lapo; Gontero, Giulia; Rollino, Silvia; Groppo, Elisabetta; Granieri, Enrico

2015-03-22

Mood disorder and depressive syndromes represent a common comorbid condition in neurological disorders with a prevalence rate that ranges between 20% and 50% of patients with stroke, epilepsy, multiple sclerosis, and Parkinson's disease. Notwithstanding, these conditions are often under-diagnosed and under-treated in the clinical practice and negatively affect the functional recovery, the adherence to treatment, the quality of life, and even the mortality risk. In addition, a bidirectional association between depression and neurological disorders may be possible being that depressive syndromes may be considered as a risk factor for certain neurological diseases. Despite the large amount of evidence regarding the effects of music therapy (MT) and other musical interventions on different aspects of neurological disorders, no updated article reviewing outcomes such as mood, emotions, depression, activity of daily living and so on is actually available; for this reason, little is known about the effectiveness of music and MT on these important outcomes in neurological patients. The aim of this article is to provide a narrative review of the current literature on musical interventions and their effects on mood and depression in patients with neurological disorders. Searching on PubMed and PsycInfo databases, 25 studies corresponding to the inclusion criteria have been selected; 11 of them assess the effects of music or MT in Dementia, 9 explore the efficacy on patients with Stroke, and 5 regard other neurological diseases like Multiple Sclerosis, Amyotrophic Lateral Sclerosis/motor neuron disease, Chronic quadriplegia, Parkinson's Disease, and Acquired Brain dysfunctions. Selected studies are based on relational and rehabilitative music therapy approaches or concern music listening interventions. Most of the studies support the efficacy of MT and other musical interventions on mood, depressive syndromes, and quality of life on neurological patients.

Intravenous immunoglobulin in neurological disease: a specialist review.

PubMed

Wiles, C M; Brown, P; Chapel, H; Guerrini, R; Hughes, R A C; Martin, T D; McCrone, P; Newsom-Davis, J; Palace, J; Rees, J H; Rose, M R; Scolding, N; Webster, A D B

2002-04-01

Treatment of neurological disorders with intravenous immunoglobulin (IVIg) is an increasing feature of our practice for an expanding range of indications. For some there is evidence of benefit from randomised controlled trials, whereas for others evidence is anecdotal. The relative rarity of some of the disorders means that good randomised control trials will be difficult to deliver. Meanwhile, the treatment is costly and pressure to "do something" in often distressing disorders considerable. This review follows a 1 day meeting of the authors in November 2000 and examines current evidence for the use of IVIg in neurological conditions and comments on mechanisms of action, delivery, safety and tolerability, and health economic issues. Evidence of efficacy has been classified into levels for healthcare interventions (tables 1 and 2).

Novel paths towards neural cellular products for neurological disorders.

PubMed

Daadi, Marcel M

2011-11-01

The prospect of using neural cells derived from stem cells or from reprogrammed adult somatic cells provides a unique opportunity in cell therapy and drug discovery for developing novel strategies for brain repair. Cell-based therapeutic approaches for treating CNS afflictions caused by disease or injury aim to promote structural repair of the injured or diseased neural tissue, an outcome currently not achieved by drug therapy. Preclinical research in animal models of various diseases or injuries report that grafts of neural cells enhance endogenous repair, provide neurotrophic support to neurons undergoing degeneration and replace lost neural cells. In recent years, the sources of neural cells for treating neurological disorders have been rapidly expanding and in addition to offering therapeutic potential, neural cell products hold promise for disease modeling and drug discovery use. Specific neural cell types have been derived from adult or fetal brain, from human embryonic stem cells, from induced pluripotent stem cells and directly transdifferentiated from adult somatic cells, such as skin cells. It is yet to be determined if the latter approach will evolve into a paradigm shift in the fields of stem cell research and regenerative medicine. These multiple sources of neural cells cover a wide spectrum of safety that needs to be balanced with efficacy to determine the viability of the cellular product. In this article, we will review novel sources of neural cells and discuss current obstacles to developing them into viable cellular products for treating neurological disorders.

Pediatric residency preceding child neurology training.

PubMed

Schor, Nina F

2011-06-01

Training in child neurology requires formal training in other aspects of pediatrics. This pediatrics training affords the ability to obtain a developmentally appropriate history and physical examination at all stages of childhood and adolescence and to provide anticipatory guidance to children and families of all developmental ages; the ability to identify and respond appropriately to emergent, urgent, and/or life-critical need for medical and/or psychosocial intervention on behalf of children and/or their families; the ability to identify and provide for appropriate medical and psychosocial services and supports for children and families affected by chronic and/or fatal diseases; and the ability to identify and respond appropriately to nonneurologic manifestations of risk factors for or harbingers of neurologic diseases or conditions. In this context, it also allows the trainee to hone skills in communication, counseling, teaching, and critical thinking, all of which are important for the effective practice of child neurology. Copyright © 2011 Elsevier Inc. All rights reserved.

Human prion diseases: surgical lessons learned from iatrogenic prion transmission.

PubMed

Bonda, David J; Manjila, Sunil; Mehndiratta, Prachi; Khan, Fahd; Miller, Benjamin R; Onwuzulike, Kaine; Puoti, Gianfranco; Cohen, Mark L; Schonberger, Lawrence B; Cali, Ignazio

2016-07-01

The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission

Human prion diseases: surgical lessons learned from iatrogenic prion transmission

PubMed Central

Bonda, David J.; Manjila, Sunil; Mehndiratta, Prachi; Khan, Fahd; Miller, Benjamin R.; Onwuzulike, Kaine; Puoti, Gianfranco; Cohen, Mark L.; Schonberger, Lawrence B.; Cali, Ignazio

2016-01-01

The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood “infectious protein” has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial

Risk of psychiatric and neurological diseases in patients with workplace mobbing experience in Germany: a retrospective database analysis

PubMed Central

Kostev, Karel; Rex, Juliana; Waehlert, Lilia; Hog, Daniela; Heilmaier, Christina

2014-01-01

Introduction: The number of mobbing experiences recorded has increased during recent years and it has now been established as global phenomenon among the working population. The goal of our study was to analyze the incidence of certain neurologic and psychiatric diseases as a consequence of mobbing as compared with a control group and to examine the possible influence of previous diseases that occurred within one year before the first mobbing documentation on the incidence of mobbing. Material & methods: We used a large database (IMS® Disease Analyzer, Germany) to collect data from general practitioners in Germany from 01/2003 until 12/2012. Based on age, gender, and health insurance, patients with experience of mobbing were matched with a control group of patients who had not reported workplace mobbing and who were being treated by the same physicians. At first, diseases that occurred within one year before the bullying experience took place (“index date”) were noted and compared to a control group of similar composition in terms of gender, age, and health insurance. Subsequently, the prevalence of depression, anxiety, somatoform disorders, and sleep disorders following experiences of mobbing were determined. After adjustment to take into account the odds of bullying, the ratios of these diseases were assessed using a logistic regression model. Results: The study population consisted of n=2,625 patients and n=2,625 controls, of which 33% were men. The number of cases of bullying documented rose continuously from 2003 to 2011 and remained high in 2012. Those who would later become victims of mobbing demonstrated a considerably higher prevalence of diseases in general – these diseases were not confined to the neurologic-psychiatric spectrum. Following experiences of bullying, depression, anxiety, somatoform disorders, and sleep disorders were significantly more prevalent than in the control group (for all, p<0.05). Similarly, odds ratios (OR) representing the

Risk of psychiatric and neurological diseases in patients with workplace mobbing experience in Germany: a retrospective database analysis.

PubMed

Kostev, Karel; Rex, Juliana; Waehlert, Lilia; Hog, Daniela; Heilmaier, Christina

2014-01-01

The number of mobbing experiences recorded has increased during recent years and it has now been established as global phenomenon among the working population. The goal of our study was to analyze the incidence of certain neurologic and psychiatric diseases as a consequence of mobbing as compared with a control group and to examine the possible influence of previous diseases that occurred within one year before the first mobbing documentation on the incidence of mobbing. We used a large database (IMS® Disease Analyzer, Germany) to collect data from general practitioners in Germany from 01/2003 until 12/2012. Based on age, gender, and health insurance, patients with experience of mobbing were matched with a control group of patients who had not reported workplace mobbing and who were being treated by the same physicians. At first, diseases that occurred within one year before the bullying experience took place ("index date") were noted and compared to a control group of similar composition in terms of gender, age, and health insurance. Subsequently, the prevalence of depression, anxiety, somatoform disorders, and sleep disorders following experiences of mobbing were determined. After adjustment to take into account the odds of bullying, the ratios of these diseases were assessed using a logistic regression model. The study population consisted of n=2,625 patients and n=2,625 controls, of which 33% were men. The number of cases of bullying documented rose continuously from 2003 to 2011 and remained high in 2012. Those who would later become victims of mobbing demonstrated a considerably higher prevalence of diseases in general - these diseases were not confined to the neurologic-psychiatric spectrum. Following experiences of bullying, depression, anxiety, somatoform disorders, and sleep disorders were significantly more prevalent than in the control group (for all, p<0.05). Similarly, odds ratios (OR) representing the risk of suffering from diseases were higher in

Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease.

PubMed

Shroff, Geeta

2016-12-13

BACKGROUND Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. CASE REPORT Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD. The hESCs were administered via different routes including intramuscular, intravenous, and supplemental routes (e.g., deep spinal, caudal, intercostal through eye drops) to regenerate the injured cells. Both the patients showed remarkable improvement in their functional skills, overall stamina, cognitive abilities, and muscle strength. Furthermore, the improvement in the patients' conditions were assessed by magnetic resonance tractography and single photon emission computed tomography (SPECT). CONCLUSIONS Therapy with hESCs might emerge as an effective and safe treatment for patients with both MS and LD. Well-designed clinical trials and follow-up studies are needed to prove the long-term efficacy and safety of hESC therapy in the treatment of patients with MS and LD.

[Demyelinating disease and vaccination of the human papillomavirus].

PubMed

Álvarez-Soria, M Josefa; Hernández-González, Amalia; Carrasco-García de León, Sira; del Real-Francia, M Ángeles; Gallardo-Alcañiz, M José; López-Gómez, José L

2011-04-16

Primary prevention by prophylactic vaccination against the major cause of cervical cancer, the carcinogenic human papillomavirus (HPV) types 16 and 18, is now available worldwide. Postlicensure adverse neurological effects have been described. The studies realized after the license are descriptive and limited by the difficulty to obtain the information, despite most of the statistical indexes show that the adverse effects by the vaccine of the HPV are not upper compared with other vaccines, the substimation must be considered. We describe the cases of four young women that developed demyelinating disease after the vaccination of the HPV, with a rank of time between the administration of the dose and the development of the clinical of seven days to a month, with similar symptoms with the successive doses. We have described six episodes coinciding after the vaccination. Have been described seizures, autoimmune disorders such as Guillain-Barre syndrome, transverse myelitis, or motor neuron disease, probably adverse effects following immunization by HPV vaccine. So we suggest that vaccine may trigger an immunological mechanism leading to demyelinating events, perhaps in predisposed young.

Copper mediated neurological disorder: visions into amyotrophic lateral sclerosis, Alzheimer and Menkes disease.

PubMed

Ahuja, Anami; Dev, Kapil; Tanwar, Ranjeet S; Selwal, Krishan K; Tyagi, Pankaj K

2015-01-01

Copper (Cu) is a vital redox dynamic metal that is possibly poisonous in superfluous. Metals can traditionally or intricately cause propagation in reactive oxygen species (ROS) accretion in cells and this may effect in programmed cell death. Accumulation of Cu causes necrosis that looks to be facilitated by DNA damage, followed by activation of P53. Cu dyshomeostasis has also been concerned in neurodegenerative disorders such as Alzheimer, Amyotrophic lateral sclerosis (ALS) or Menkes disease and is directly related to neurodegenerative syndrome that usually produces senile dementia. These mortal syndromes are closely related with an immense damage of neurons and synaptic failure in the brain. This review focuses on copper mediated neurological disorders with insights into amyotrophic lateral sclerosis, Alzheimer and Menkes disease. Copyright © 2014 Elsevier GmbH. All rights reserved.

Sports neurology topics in neurologic practice

PubMed Central

Conidi, Francis X.; Drogan, Oksana; Giza, Christopher C.; Kutcher, Jeffery S.; Alessi, Anthony G.; Crutchfield, Kevin E.

2014-01-01

Summary We sought to assess neurologists' interest in sports neurology and learn about their experience in treating sports-related neurologic conditions. A survey was sent to a random sample of American Academy of Neurology members. A majority of members (77%) see at least some patients with sports-related neurologic issues. Concussion is the most common sports-related condition neurologists treat. More than half of survey participants (63%) did not receive any formal or informal training in sports neurology. At least two-thirds of respondents think it is very important to address the following issues: developing evidence-based return-to-play guidelines, identifying risk factors for long-term cognitive-behavioral sequelae, and developing objective diagnostic criteria for concussion. Our findings provide an up-to-date view of the subspecialty of sports neurology and identify areas for future research. PMID:24790800

Introduction to Focus Issue: Rhythms and Dynamic Transitions in Neurological Disease: Modeling, Computation, and Experiment

NASA Astrophysics Data System (ADS)

Kaper, Tasso J.; Kramer, Mark A.; Rotstein, Horacio G.

2013-12-01

Rhythmic neuronal oscillations across a broad range of frequencies, as well as spatiotemporal phenomena, such as waves and bumps, have been observed in various areas of the brain and proposed as critical to brain function. While there is a long and distinguished history of studying rhythms in nerve cells and neuronal networks in healthy organisms, the association and analysis of rhythms to diseases are more recent developments. Indeed, it is now thought that certain aspects of diseases of the nervous system, such as epilepsy, schizophrenia, Parkinson's, and sleep disorders, are associated with transitions or disruptions of neurological rhythms. This focus issue brings together articles presenting modeling, computational, analytical, and experimental perspectives about rhythms and dynamic transitions between them that are associated to various diseases.

The Spectrum and Burden of Influenza-Associated Neurological Disease in Children: Combined Encephalitis and Influenza Sentinel Site Surveillance from Australia 2013-2015.

PubMed

Britton, P N; Blyth, C C; Macartney, K; Dale, R C; Li-Kim-Moy, J; Khandaker, G; Crawford, N; Marshall, H; Clark, J; Elliott, E; Booy, R; Cheng, A C; Jones, C A

2017-04-29

There are few longitudinal studies of seasonal influenza associated neurological disease (IAND) and none from the Southern hemisphere. We extracted prospectively acquired Australian surveillance data from two studies nested within the Paediatric Active Enhanced Disease Surveillance (PAEDS) network: the Influenza Complications Alert Network (FluCAN) study and the Australian Childhood Encephalitis (ACE) study between 2013 and 2015. We described the clinical features and severity of IAND in children, including influenza associated encephalitis/encephalopathy (IAE). We calculated the proportion of hospitalised influenza that is associated with IAND and IAE, and incidence of IAE. Over three influenza seasons, we identified 54 cases of IAND at two tertiary children's hospitals from Australia that accounted for 7.6% of hospitalised influenza. These included 10 cases of IAE (1.4% hospitalised influenza). The mean annual incidence of IAE amongst Australian children (aged ≤14 years) was 2.8 per 1 000 000. The spectrum of IAND was broad and included: IAE (10) including distinct acute encephalopathy syndromes, simple febrile seizures (14), other seizures (16), acute ataxia (4), and other sub-acute syndromes (transverse myelitis (1), opsoclonus myoclonus (1)). Two thirds of children with IAND were aged ≤4 years; less than half had pre-existing neurological disease or other risk factors for severe influenza. IAE caused death or neurological morbidity in half of cases. Seasonal influenza is an important cause of acute neurological disease in Australian children. The spectrum of seasonal IAND appears similar to that described during the 2009 H1N1 pandemic. IAE is associated with high morbidity and mortality. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Identification and validation of clinical predictors for the risk of neurological involvement in children with hand, foot, and mouth disease in Sarawak

PubMed Central

2009-01-01

Background Human enterovirus 71 (HEV71) can cause Hand, foot, and mouth disease (HFMD) with neurological complications, which may rapidly progress to fulminant cardiorespiratory failure, and death. Early recognition of children at risk is the key to reduce acute mortality and morbidity. Methods We examined data collected through a prospective clinical study of HFMD conducted between 2000 and 2006 that included 3 distinct outbreaks of HEV71 to identify risk factors associated with neurological involvement in children with HFMD. Results Total duration of fever ≥ 3 days, peak temperature ≥ 38.5°C and history of lethargy were identified as independent risk factors for neurological involvement (evident by CSF pleocytosis) in the analysis of 725 children admitted during the first phase of the study. When they were validated in the second phase of the study, two or more (≥ 2) risk factors were present in 162 (65%) of 250 children with CSF pleocytosis compared with 56 (30%) of 186 children with no CSF pleocytosis (OR 4.27, 95% CI2.79–6.56, p < 0.0001). The usefulness of the three risk factors in identifying children with CSF pleocytosis on hospital admission during the second phase of the study was also tested. Peak temperature ≥ 38.5°C and history of lethargy had the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 28%(48/174), 89%(125/140), 76%(48/63) and 50%(125/251), respectively in predicting CSF pleocytosis in children that were seen within the first 2 days of febrile illness. For those presented on the 3rd or later day of febrile illness, the sensitivity, specificity, PPV and NPV of ≥ 2 risk factors predictive of CSF pleocytosis were 75%(57/76), 59%(27/46), 75%(57/76) and 59%(27/46), respectively. Conclusion Three readily elicited clinical risk factors were identified to help detect children at risk of neurological involvement. These risk factors may serve as a guide to clinicians to decide the need for

Novel Treatment with Neuroprotective and Antiviral Properties against a Neuroinvasive Human Respiratory Virus

PubMed Central

Brison, Elodie; Jacomy, Hélène

2014-01-01

ABSTRACT Human coronaviruses (HCoVs) are recognized respiratory pathogens with neuroinvasive and neurotropic properties in mice and humans. HCoV strain OC43 (HCoV-OC43) can infect and persist in human neural cells and activate neuroinflammatory and neurodegenerative mechanisms, suggesting that it could be involved in neurological disease of unknown etiology in humans. Moreover, we have shown that HCoV-OC43 is neurovirulent in susceptible mice, causing encephalitis, and that a viral mutant with a single point mutation in the viral surface spike (S) protein induces a paralytic disease that involves glutamate excitotoxicity in susceptible mice. Herein, we show that glutamate recycling via the glial transporter 1 protein transporter and glutamine synthetase are central to the dysregulation of glutamate homeostasis and development of motor dysfunctions and paralytic disease in HCoV-OC43-infected mice. Moreover, memantine, an N-methyl-d-aspartate receptor antagonist widely used in the treatment of neurological diseases in humans, improved clinical scores related to paralytic disease and motor disabilities by partially restoring the physiological neurofilament phosphorylation state in virus-infected mice. Interestingly, memantine attenuated mortality rates and body weight loss and reduced HCoV-OC43 replication in the central nervous system in a dose-dependent manner. This novel action of memantine on viral replication strongly suggests that it could be used as an antiviral agent to directly limit viral replication while improving neurological symptoms in various neurological diseases with a viral involvement. IMPORTANCE PMID:24227863

Survey of the professors of child neurology: neurology versus pediatrics home for child neurology.

PubMed

Pearl, Phillip L; McConnell, Emily R; Fernandez, Rosamary; Brooks-Kayal, Amy

2014-09-01

The optimal academic home for child neurology programs between adult neurology versus pediatric departments remains an open question. The Professors of Child Neurology, the national organization of child neurology department chairs, division chiefs, and training program directors, was surveyed to evaluate the placement of child neurology programs. Professors of Child Neurology members were surveyed regarding the placement of child neurology programs within adult neurology versus pediatric departments. Questions explored academic versus clinical lines of reporting and factors that may be advantages and disadvantages of these affiliations. Issues also addressed were the current status of board certification and number of clinics expected in academic child neurology departments. Of 120 surveys sent, 95 responses were received (79% response rate). The primary academic affiliation is in neurology in 54% of programs versus 46% in pediatrics, and the primary clinical affiliation is 45% neurology and 55% pediatrics. Advantages versus disadvantages of one's primary affiliation were similar whether the primary affiliation was in neurology or pediatrics. While 61% of respondents are presently board certified in pediatrics, only 2% of those with time-limited certification in general pediatrics plan to be recertified going forward. Typically six to eight half-day clinics per week are anticipated for child neurologists in academic departments without additional funding sources. Overall, leaders of child neurology departments and training programs would not change their affiliation if given the opportunity. Advantages and disadvantages associated with current affiliations did not change whether child neurology was located in neurology or pediatrics. Board certification by the American Board of Psychiatry and Neurology in child neurology is virtually universal, whereas pediatric board certification by the American Board of Pediatrics is being maintained by very few. Most academic

Physiological Aβ Concentrations Produce a More Biomimetic Representation of the Alzheimer's Disease Phenotype in iPSC Derived Human Neurons.

PubMed

Berry, Bonnie J; Smith, Alec S T; Long, Christopher J; Martin, Candace C; Hickman, James J

2018-05-22

Alzheimer's disease (AD) is characterized by slow, progressive neurodegeneration leading to severe neurological impairment, but current drug development efforts are limited by the lack of robust, human-based disease models. Amyloid-β (Aβ) is known to play an integral role in AD progression as it has been shown to interfere with neurological function. However, studies into AD pathology commonly apply Aβ to neurons for short durations at nonphysiological concentrations to induce an exaggerated dysfunctional phenotype. Such methods are unlikely to elucidate early stage disease dysfunction, when treatment is still possible, since damage to neurons by these high concentrations is extensive. In this study, we investigated chronic, pathologically relevant Aβ oligomer concentrations to induce an electrophysiological phenotype that is more representative of early AD progression compared to an acute high-dose application in human cortical neurons. The high, acute oligomer dose resulted in severe neuronal toxicity as well as upregulation of tau and phosphorylated tau. Chronic, low-dose treatment produced significant functional impairment without increased cell death or accumulation of tau protein. This in vitro phenotype more closely mirrors the status of early stage neural decline in AD pathology and could provide a valuable tool to further understanding of early stage AD pathophysiology and for screening potential therapeutic compounds.

Intravenous immunoglobulin in neurological disease: a specialist review

PubMed Central

Wiles, C; Brown, P; Chapel, H; Guerrini, R; Hughes, R; Martin, T; McCrone, P; Newsom-Davis, J; Palace, J; Rees, J; Rose, M; Scolding, N; Webster, A

2002-01-01

Treatment of neurological disorders with intravenous immunoglobulin (IVIg) is an increasing feature of our practice for an expanding range of indications. For some there is evidence of benefit from randomised controlled trials, whereas for others evidence is anecdotal. The relative rarity of some of the disorders means that good randomised control trials will be difficult to deliver. Meanwhile, the treatment is costly and pressure to "do something" in often distressing disorders considerable. This review follows a 1 day meeting of the authors in November 2000 and examines current evidence for the use of IVIg in neurological conditions and comments on mechanisms of action, delivery, safety and tolerability, and health economic issues. Evidence of efficacy has been classified into levels for healthcare interventions (tables 1 and 2). PMID:11909900

Exploring the role of microglia in cortical spreading depression in neurological disease

PubMed Central

Suzuki, Norihiro

2017-01-01

Microglia play a pivotal role in innate immunity in the brain. During development, they mature from myeloerythroid progenitor cells in the yolk sac and colonize the brain to establish a resident population of tissue macrophages. In the postnatal brain, they exert phagocytosis and induce inflammatory response against invading pathogens. Microglia also act as guardians of brain homeostasis by surveying the microenvironment using motile processes. Cortical spreading depression (CSD) is a slowly propagating (2–5 mm/min) wave of rapid, near-complete depolarization of neurons and astrocytes followed by a period of electrical suppression of a distinct population of cortical neurons. Not only has CSD been implicated in brain migraine aura, but CSD-like events have also been detected in stroke and traumatic injury. CSD causes a considerable perturbation of the ionic environment in the brain, which may be readily detected by microglia. Although CSD is known to activate microglia, the role of microglial activation in CSD-related neurological disorders remains poorly understood. In this article, we first provide an overview of microglial development and the multiple functions of microglia. Then, we review existing data on the relationship between microglia and CSD and discuss the relevance of CSD-induced microglial activation in neurological disease. PMID:28155572

Gastroesophageal Reflux in Neurologically Impaired Children: What Are the Risk Factors?

PubMed

Kim, Seung; Koh, Hong; Lee, Joon Soo

2017-03-15

Neurologically impaired patients frequently suffer from gastrointestinal tract problems, such as gastroesophageal reflux disease (GERD). In this study, we aimed to define the risk factors for GERD in neurologically impaired children. From May 2006 to March 2014, 101 neurologically impaired children who received 24-hour esophageal pH monitoring at Severance Children's Hospital were enrolled in the study. The esophageal pH finding and the clinical characteristics of the patients were analyzed. The reflux index was higher in patients with abnormal electroencephalography (EEG) results than in those with normal EEG results (p=0.027). Mitochondrial disease was associated with a higher reflux index than were epileptic disorders or cerebral palsy (p=0.009). Patient gender, feeding method, scoliosis, tracheostomy, and baclofen use did not lead to statistical differences in reflux index. Age of onset of neurological impairment was inversely correlated with DeMeester score and reflux index. Age at the time of examination, the duration of the disease, and the number of antiepileptic drugs were not correlated with GER severity. Early-onset neurological impairment, abnormal EEG results, and mitochondrial disease are risk factors for severe GERD.

Role of the gluten-free diet on neurological-EEG findings and sleep disordered breathing in children with celiac disease.

PubMed

Parisi, P; Pietropaoli, N; Ferretti, A; Nenna, R; Mastrogiorgio, G; Del Pozzo, M; Principessa, L; Bonamico, M; Villa, M P

2015-02-01

To determine whether celiac children are at risk for EEG-neurological features and sleep disordered breathing (SDB), and whether an appropriate gluten-free diet (GFD) influences these disorders. We consecutively enrolled 19 children with a new biopsy-proven celiac disease (CD) diagnosis. At CD diagnosis and after 6 months of GFD, each patient underwent a general and neurological examination, an electroencephalogram, a questionnaire about neurological features, and a validated questionnaire about SDB: OSA (obstructive sleep apnea) scores<0 predict normality; values>0 predict OSA. At CD diagnosis, 37% of patients complained headache that affected daily activities and 32% showed positive OSA score. The EEG examinations revealed abnormal finding in 48% of children. After 6 months of GFD headache disappeared in 72% of children and EEG abnormalities in 78%; all children showed negative OSA score. According to our preliminary data, in the presence of unexplained EEG abnormalities and/or other neurological disorders/SDB an atypical or silent CD should also be taken into account. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders.

PubMed

Lorenz, Carmen; Lesimple, Pierre; Bukowiecki, Raul; Zink, Annika; Inak, Gizem; Mlody, Barbara; Singh, Manvendra; Semtner, Marcus; Mah, Nancy; Auré, Karine; Leong, Megan; Zabiegalov, Oleksandr; Lyras, Ekaterini-Maria; Pfiffer, Vanessa; Fauler, Beatrix; Eichhorst, Jenny; Wiesner, Burkhard; Huebner, Norbert; Priller, Josef; Mielke, Thorsten; Meierhofer, David; Izsvák, Zsuzsanna; Meier, Jochen C; Bouillaud, Frédéric; Adjaye, James; Schuelke, Markus; Wanker, Erich E; Lombès, Anne; Prigione, Alessandro

2017-05-04

Mitochondrial DNA (mtDNA) mutations frequently cause neurological diseases. Modeling of these defects has been difficult because of the challenges associated with engineering mtDNA. We show here that neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) retain the parental mtDNA profile and exhibit a metabolic switch toward oxidative phosphorylation. NPCs derived in this way from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C) showed defective ATP production and abnormally high mitochondrial membrane potential (MMP), plus altered calcium homeostasis, which represents a potential cause of neural impairment. High-content screening of FDA-approved drugs using the MMP phenotype highlighted avanafil, which we found was able to partially rescue the calcium defect in patient NPCs and differentiated neurons. Overall, our results show that iPSC-derived NPCs provide an effective model for drug screening to target mtDNA disorders that affect the nervous system. Copyright © 2016 Elsevier Inc. All rights reserved.

Pediatric neurology: the diagnostic process.

PubMed

Neville, Brian G R

2013-01-01

Pediatric neurology comprises a very large of number of conditions exhibiting symptoms and signs in several functional domains arising from damage and dysfunction to the developing nervous system. The diagnostic process involves ensuring that data from all possible domains are sought including those that are unaffected. The subsequent analysis involves fitting these data into patterns of classical natural history and rigorous investigation of the aspects that do not appear to fit. There may be a pattern of illness that is immediately recognized or something that is a fairly close fit. However, the aim is to develop a pathogenic sequence for the condition particularly so that conditions that have been lumped together for convenience are separated into distinct disease entities. The major presentations of pediatric neurology of fixed central motor impairments (the cerebral palsies), the epilepsies, and the progressive degenerative diseases are in the process of being split into such pathogenic sequences so that definitive treatments and possible primary prevention can be added to aims of simple diagnostic recognition. Much of this is at an early stage and pediatric neurology is still a young and fast developing specialty. Copyright © 2013 Elsevier B.V. All rights reserved.

Diagnostic Exercise: Neurologic Disorder in a Cat

DTIC Science & Technology