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.

Modulatory Effects of Dietary Amino Acids on Neurodegenerative Diseases.

PubMed

Rajagopal, Senthilkumar; Sangam, Supraj Raja; Singh, Shubham; Joginapally, Venkateswara Rao

2016-01-01

Proteins are playing a vital role in maintaining the cellular integrity and function, as well as for brain cells. Protein intake and supplementation of individual amino acids can affect the brain functioning and mental health, and many of the neurotransmitters in the brain are made from amino acids. The amino acid supplementation has been found to reduce symptoms, as they are converted into neurotransmitters which in turn extenuate the mental disorders. The biosynthesis of amino acids in the brain is regulated by the concentration of amino acids in plasma. The brain diseases such as depression, bipolar disorder, schizophrenia, obsessive-compulsive disorder (OCD), and Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD) are the most common mental disorders that are currently widespread in numerous countries. The intricate biochemical and molecular machinery contributing to the neurological disorders is still unknown, and in this chapter, we revealed the involvement of dietary amino acids on neurological diseases.

Mitochondrial metals as a potential therapeutic target in neurodegeneration

PubMed Central

Grubman, A; White, A R; Liddell, J R

2014-01-01

Transition metals are critical for enzyme function and protein folding, but in excess can mediate neurotoxic oxidative processes. As mitochondria are particularly vulnerable to oxidative damage due to radicals generated during ATP production, mitochondrial biometal homeostasis must therefore be tightly controlled to safely harness the redox potential of metal enzyme cofactors. Dysregulation of metal functions is evident in numerous neurological disorders including Alzheimer's disease, stroke, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and Friedrich's ataxia. This review describes the mitochondrial metal defects in these disorders and highlights novel metal-based therapeutic approaches that target mitochondrial metal homeostasis in neurological disorders. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24206195

mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome.

PubMed

Johnson, Simon C; Yanos, Melana E; Kayser, Ernst-Bernhard; Quintana, Albert; Sangesland, Maya; Castanza, Anthony; Uhde, Lauren; Hui, Jessica; Wall, Valerie Z; Gagnidze, Arni; Oh, Kelly; Wasko, Brian M; Ramos, Fresnida J; Palmiter, Richard D; Rabinovitch, Peter S; Morgan, Philip G; Sedensky, Margaret M; Kaeberlein, Matt

2013-12-20

Mitochondrial dysfunction contributes to numerous health problems, including neurological and muscular degeneration, cardiomyopathies, cancer, diabetes, and pathologies of aging. Severe mitochondrial defects can result in childhood disorders such as Leigh syndrome, for which there are no effective therapies. We found that rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, robustly enhances survival and attenuates disease progression in a mouse model of Leigh syndrome. Administration of rapamycin to these mice, which are deficient in the mitochondrial respiratory chain subunit Ndufs4 [NADH dehydrogenase (ubiquinone) Fe-S protein 4], delays onset of neurological symptoms, reduces neuroinflammation, and prevents brain lesions. Although the precise mechanism of rescue remains to be determined, rapamycin induces a metabolic shift toward amino acid catabolism and away from glycolysis, alleviating the buildup of glycolytic intermediates. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases.

Parkinson's disease and the quest for preclinical diagnosis: an interview with Professor Werner Poewe.

PubMed

Poewe, Werner

2017-10-01

Werner Poewe speaks to Laura Dormer, Editorial Director: Professor Werner Poewe is Professor of Neurology and Director of the Department of Neurology at Innsbruck Medical University in Innsbruck, Austria. He held a Residency in Clinical Neurology and Psychiatry at the University of Innsbruck, Austria, from 1977 to 1984. From 1984 to 1985 he teamed up with Gerald Stern and Andrew Lees as a British Council Research Fellow at University College and Middlesex Hospital's Medical School in London to perform clinical studies into levodopa-induced dystonia and pharmacokinetics of levodopa in naive versus L-Dopa treated Parkinson's disease. Following his return to Austria, he held a position as Senior Lecturer in the Department of Neurology at the University of Innsbruck (1986-1989) after which he took over as Professor of Neurology and Acting Director of the Department of Neurology at Virchow Hospital of the Free University of Berlin (1990-1994). Professor Poewe's main research interests in the field of movement disorders are focused on differential and early diagnosis of Parkinson's disease, its natural history and pharmacological treatment. He has been involved in the steering committees of numerous drug trials in different stages of Parkinson's disease for the past 20 years and has authored and coauthored more than 500 original articles and reviews in the field of movement disorders. Professor Poewe served as President of the Austrian Society of Neurology from 2002 to 2004 as well as President of the Austrian Parkinson's Disease Society from 1996 to 2009. He has been awarded honorary membership of the German Society of Neurology as well as the Japanese Society of Neurology. His awards include the Walther-Birkmayer-Prize of the Austrian PD Society, the Dingebauer-Prize of the German Neurological Society as well as the Research Excellence Award of Innsbruck Medical University. Professor Poewe served as President of the International Movement Disorder Society (MDS) from 2000 to 2002, during which period he initiated the creation of important MDS task forces related to the critique and development of rating scales and of evidence-based treatment reviews. In his presidency, fell the negotiations between the European Section of MDS and the European Federation of Neurological Societies that resulted in formal agreements about joint European congresses. This model served as an important underpinning of the success of the MDS European Section in the past 15 years. Professor Poewe took over as chair of the MDS European Section from 2011 to 2013 and has recently been made an honorary member of the MDS. He is currently active as member of the Managing Board of the Movement Disorder Scientific Panel of the European Academy of Neurology.

Sex, hormones, and genotype interact to influence psychiatric disease, treatment, and behavioral research.

PubMed

Gobinath, Aarthi R; Choleris, Elena; Galea, Liisa A M

2017-01-02

Sex differences exist in the vulnerability, incidence, manifestation, and treatment of numerous neurological and psychiatric diseases. Despite this observation prominent in the literature, little consideration has been given to possible sex differences in outcome in both preclinical and clinical research. This Mini-Review highlights evidence supporting why studying sex differences matter for advances in brain health as well as improving treatment for neurological and psychiatric disease. Additionally, we discuss some statistical and methodological considerations in evaluating sex differences as well as how differences in the physiology of the sexes can contribute to sex difference in disease incidence and manifestation. Furthermore, we review literature demonstrating that the reproductive experience in the female can render the female brain differentially vulnerable to disease across age. Finally, we discuss how genes interact with sex to influence disease risk and treatment and argue that sex must be considered in precision medicine. Together the evidence reviewed here supports the inclusion of males and females at all levels of neuroscience research. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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 complementary experimental approach for understanding the molecular mechanisms and underlying aetiology of complex neurological diseases.

Metabolic disorders causing childhood ataxia.

PubMed

Parker, Colette C; Evans, Owen B

2003-09-01

Ataxia is a common neurologic finding in many disease processes of the nervous system, and has classically been associated with numerous metabolic disorders. An error of metabolism should be considered when the ataxia is either intermittent or progressive. Acute exacerbation or worsening after high protein ingestion, concurrent febrile illness, or other physical stress is also suggestive. A positive family history can be an important diagnostic clue. Progressive molecular and biochemical techniques are revolutionizing this area of medicine, and there has been rapid advancement in understanding of the disease processes.

Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders.

PubMed

Nguyen, Linda; Thomas, Kelan L; Lucke-Wold, Brandon P; Cavendish, John Z; Crowe, Molly S; Matsumoto, Rae R

2016-03-01

Dextromethorphan (DM) is a commonly used antitussive and is currently the only FDA-approved pharmaceutical treatment for pseudobulbar affect. Its safety profile and diverse pharmacologic actions in the central nervous system have stimulated new interest for repurposing it. Numerous preclinical investigations and many open-label or blinded clinical studies have demonstrated its beneficial effects across a variety of neurological and psychiatric disorders. However, the optimal dose and safety of chronic dosing are not fully known. This review summarizes the preclinical and clinical effects of DM and its putative mechanisms of action, focusing on depression, stroke, traumatic brain injury, seizure, pain, methotrexate neurotoxicity, Parkinson's disease and autism. Moreover, we offer suggestions for future research with DM to advance the treatment for these and other neurological and psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Gene delivery with viral vectors for cerebrovascular diseases

PubMed Central

Gan, Yu; Jing, Zheng; Stetler, R. Anne; Cao, Guodong

2017-01-01

Recent achievements in the understanding of molecular events involved in the pathogenesis of central nervous system (CNS) injury have made gene transfer a promising approach for various neurological disorders, including cerebrovascular diseases. However, special obstacles, including the post-mitotic nature of neurons and the blood-brain barrier (BBB), constitute key challenges for gene delivery to the CNS. Despite the various limitations in current gene delivery systems, a spectrum of viral vectors has been successfully used to deliver genes to the CNS. Furthermore, recent advancements in vector engineering have improved the safety and delivery of viral vectors. Numerous viral vector-based clinical trials for neurological disorders have been initiated. This review will summarize the current implementation of viral gene delivery in the context of cerebrovascular diseases including ischemic stroke, hemorrhagic stroke and subarachnoid hemorrhage (SAH). In particular, we will discuss the potentially feasible ways in which viral vectors can be manipulated and exploited for use in neural delivery and therapy. PMID:23276981

Talking while walking: Cognitive loading and injurious falls in Parkinson's disease.

PubMed

LaPointe, Leonard L; Stierwalt, Julie A G; Maitland, Charles G

2010-10-01

Multitasking has become a way of life, from operating multiple software packages simultaneously on a computer, to carrying on a conversation on a cell phone while driving. Perhaps one of the most common dual tasks performed is talking while walking. In isolation, neither task would be considered difficult to perform, yet when coupled, the relative ease of each task may change. This paper details significant problems that result from injurious falls, and points out the vulnerability of those who have been diagnosed with Parkinson's disease. In addition, it provides an illustrative study that demonstrates the potential danger of talking while walking, especially when the cognitive-linguistic complexity of verbal tasks is manipulated. In this investigation, 25 participants with Parkinson's disease and 13 participants without neurological compromise completed gait tasks while conducting tasks of low (counting by ones), middle (serial subtraction of threes), and high load (alpha-numeric sequencing). The results indicated that cognitive-linguistic demand had an impact on gait, the effects of which were demonstrated in individuals without neurological compromise as well as those with Parkinson's disease. One finding, altered double-support time, distinguished the Parkinson group from the control participants. These results suggest that it might be prudent for healthcare professionals and caregivers to alter expectations and monitor the cognitive-linguistic demands placed on elderly individuals, particularly those with neurological compromise who might be at greater risk for injurious falls.

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.

Endocannabinoid System in Neurological Disorders.

PubMed

Ranieri, Roberta; Laezza, Chiara; Bifulco, Maurizio; Marasco, Daniela; Malfitano, Anna M

2016-01-01

Several studies support the evidence that the endocannabinoid system and cannabimimetic drugs might have therapeutic potential in numerous pathologies. These pathologies range from neurological disorders, atherosclerosis, stroke, cancer to obesity/metabolic syndrome and others. In this paper we review the endocannabinoid system signaling and its alteration in neurodegenerative disorders like multiple sclerosis, Alzheimer's disease, Parkinson's disease and Huntington's disease and discuss the main findings about the use of cannabinoids in the therapy of these pathologies. Despite different etiologies, neurodegenerative disorders exhibit similar mechanisms like neuro-inflammation, excitotoxicity, deregulation of intercellular communication, mitochondrial dysfunction and disruption of brain tissue homeostasis. Current treatments ameliorate the symptoms but are not curative. Interfering with the endocannabinoid signaling might be a valid therapeutic option in neuro-degeneration. To this aim, pharmacological intervention to modulate the endocannabinoid system and the use of natural and synthetic cannabimimetic drugs have been assessed. CB1 and CB2 receptor signaling contributes to the control of Ca2+ homeostasis, trophic support, mitochondrial activity, and inflammatory conditions. Several studies and patents suggest that the endocannabinoid system has neuro-protective properties and might be a target in neurodegenerative diseases.

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.

Treatment of vascular dementia. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

PubMed Central

Brucki, Sonia Maria Dozzi; Ferraz, Ana Cláudia; de Freitas, Gabriel R.; Massaro, Ayrton Roberto; Radanovic, Márcia; Schultz, Rodrigo Rizek

2011-01-01

Scientific Department of Cognitive Neurology and Aging of ABN had a consensus meeting to write recommendations on treatment of vascular dementia, there was no previous issue. This disease has numerous particularities and can be considered a preventable dementia. Prevention treatment is primary care of vascular risk factors or a secondary prevention of factors that could cause recurrence of ischemic or hemorrhagic brain modifications. In these guidelines we suggested only symptomatic treatment, pharmacologic or non-pharmacologic. We have reviewed current publications on MEDLINE (PubMed), LILACS e Cochrane Library databases. Recommendations are concern to the following factors and their prevention evidences, association, or treatment of vascular dementia: physical activity, tobacco use, diet and food supplements, arterial hypertension, diabetes mellitus, obesity, statins, cardiac failure, atrial fibrillation, antithrombotics, sleep apnea, carotid revascularization, symptomatic pharmacological treatment. PMID:29213754

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

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 PMID:12077031

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

Chapter 24: the coming of molecular biology and its impact on clinical neurology.

PubMed

Smith, Christopher U M

2010-01-01

Although the chemical study of the nervous system dates back well into the 19th century, molecular biology and especially molecular neurobiology only began to be established in the second half of the 20th century. This chapter reviews their impact on clinical neuroscience during the 50 years since Watson and Crick published their seminal paper. After a short review of the part played by F.O. Schmitt in establishing molecular neuroscience the chapter outlines work that led to a detailed understanding of the biochemical structure and function of nerve cell membranes and their embedded channel proteins, receptors, and other molecules. The chapter then turns to the numerous pathologies that result from disorders of these elements: the various channel and gap-junction pathologies. The chapter continues with a discussion of some of the diseases caused by defective DNA, especially the trinucleotide repeat expansion diseases (TREDs) and ends with a short account of the development of molecular approaches to prion diseases, myasthenia gravis, and the neurodegenerative diseases of old age. Francis Bacon said long ago that "knowledge is power." The hope is that increasing molecular knowledge will help cure some of the human suffering seen in the neurological ward and clinic.

Capnography in patients with severe neurological impairment.

PubMed

Jacob, Ron; Nelkenbaum, Annette; Merrick, Joav; Brik, Riva

2014-06-01

Respiratory disease is a common reason for hospitalization and mortality in persons with severe intellectual and developmental disability. Capnography is the measurement and numerical display of end-tidal carbon dioxide (EtCO2). This was a prospective, case controlled, cross sectional study to assess differences of baseline EtCO2 values between neurologically impaired patients and healthy individuals. 86 neurologically impaired patients were evaluated in the study group. Their mean age ± SD was 25.65 ± 10.48 years with 41% males. 53 healthy children and young adults were evaluated in the control group. Their mean age ± SD was 21.95 ± 10.38 years with 54.7% males. Patients with severe neurological impairment had higher baseline EtCO2 values than healthy individuals. Kyphoscoliosis and the use of antipsychotic drugs were the major factors to increase EtCO2 levels. Knowing the patient's baseline EtCO2 value, as well as baseline oximetry, could guide treatment decisions, when assessing the patient's oxygenation and ventilation during acute respiratory illness, and can potentially prevent unnecessary laboratory and imaging investigations as well as over treatment. Future research can shed light on the utility of capnometry and clinical implications of higher baseline EtCO2 values among neurologically impaired patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

[Neurological complications of inflammatory bowel diseases].

PubMed

Cieplik, N; Stangel, M; Bachmann, O

2013-02-01

Inflammatory bowel diseases, such as Crohn's disease, ulcerative colitis, autoantibody driven celiac disease and infectious Whipple's disease can all be associated with neurological symptoms. The neurological manifestation may occur even before the gastrointestinal symptoms or the enteropathic symptoms can even be absent as in celiac disease. These diseases can be caused by malresorption and lack of vitamins due to enteral inflammation as well as (auto-)immunological mechanisms and drug-associated side effects. Thus, inflammatory bowel diseases have to be considered in the differential diagnosis. In this review the most common neurological manifestations of these diseases will be described as well as the diagnostic approach.

Fas/CD95 regulatory protein Faim2 is neuroprotective after transient brain ischemia.

PubMed

Reich, Arno; Spering, Christopher; Gertz, Karen; Harms, Christoph; Gerhardt, Ellen; Kronenberg, Golo; Nave, Klaus A; Schwab, Markus; Tauber, Simone C; Drinkut, Anja; Harms, Kristian; Beier, Chrstioph P; Voigt, Aaron; Göbbels, Sandra; Endres, Matthias; Schulz, Jörg B

2011-01-05

Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and cell proliferation. Identification of regulatory proteins that control the switch between apoptotic and alternative DR signaling opens new therapeutic opportunities. Fas apoptotic inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor of Fas/CD95-mediated apoptosis. To investigate its role during development and in disease models, we generated Faim2-deficient mice. The ubiquitous null mutation displayed a viable and fertile phenotype without overt deficiencies. However, lack of Faim2 caused an increase in susceptibility to combined oxygen-glucose deprivation in primary neurons in vitro as well as in caspase-associated cell death, stroke volume, and neurological impairment after cerebral ischemia in vivo. These processes were rescued by lentiviral Faim2 gene transfer. In summary, we provide evidence that Faim2 is a novel neuroprotective molecule in the context of cerebral ischemia.

Acyl Coenzyme A Thioesterase 7 Regulates Neuronal Fatty Acid Metabolism To Prevent Neurotoxicity

PubMed Central

Ellis, Jessica M.; Wong, G. William

2013-01-01

Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7N−/−, revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7N−/− mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7N−/− mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity. PMID:23459938

Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity.

PubMed

Ellis, Jessica M; Wong, G William; Wolfgang, Michael J

2013-05-01

Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7(N-/-), revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7(N-/-) mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7(N-/-) mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity.

Protein Kinases and Parkinson's Disease.

PubMed

Mehdi, Syed Jafar; Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M; Barger, Steven W; Sarkar, Sumit; Paule, Merle G; Ali, Syed F; Imam, Syed Z

2016-09-20

Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson's disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson's disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson's disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules.

THE NEUROLOGICAL FACE OF CELIAC DISEASE.

PubMed

Işikay, Sedat; Kocamaz, Halil

2015-01-01

Several neurological disorders have also been widely described in celiac disease patients. The aim of this study was to determine the incidence of accompanying different neurologic manifestations in children with celiac disease at the time of diagnosis and to discuss these manifestations in the light of the recent literature. This prospective cross sectional study included 297 children diagnosed with celiac disease. The medical records of all patients were reviewed. In neurological evaluation, totally 40 (13. 5%) of the 297 celiac patients had a neurological finding including headache, epilepsy, migraine, mental retardation, breath holding spells, ataxia, cerebral palsy, attention deficit hyperactivity disorder, Down syndrome and Turner syndrome in order of frequency. There was not any significant difference between the laboratory data of the patients with and without neurological manifestations. However; type 3a biopsy was statistically significantly more common among patients without neurological manifestations, while type 3b biopsy was statistically significantly more common among patients with neurological manifestations. It is important to keep in mind that in clinical course of celiac disease different neurological manifestations may be reported.

Sleep Disorders in Childhood Neurological Diseases

PubMed Central

Liu, Zhao

2017-01-01

Sleep problems are frequently addressed as a primary or secondary concern during the visit to the pediatric neurology clinic. Sleep disorders can mimic other neurologic diseases (e.g., epilepsy and movement disorders), and this adds challenges to the diagnostic process. Sleep disorders can significantly affect the quality of life and functionality of children in general and those with comorbid neurological diseases in particular. Understanding the pathophysiology of sleep disorders, recognizing the implications of sleep disorder in children with neurologic diseases and behavioral difficulties, and early intervention continue to evolve resulting in better neurocognitive outcomes. PMID:28937639

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

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.

A functional SNP catalog of overlapping miRNA-binding sites in genes implicated in prion disease and other neurodegenerative disorders.

PubMed

Saba, Reuben; Medina, Sarah J; Booth, Stephanie A

2014-10-01

The involvement of SNPs in miRNA target sites remains poorly investigated in neurodegenerative disease. In addition to associations with disease risk, such genetic variations can also provide novel insight into mechanistic pathways that may be responsible for disease etiology and/or pathobiology. To identify SNPs associated specifically with degenerating neurons, we restricted our analysis to genes that are dysregulated in CA1 hippocampal neurons of mice during early, preclinical phase of Prion disease. The 125 genes chosen are also implicated in other numerous degenerative and neurological diseases and disorders and are therefore likely to be of fundamental importance. We predicted those SNPs that could increase, decrease, or have neutral effects on miRNA binding. This group of genes was more likely to possess DNA variants than were genes chosen at random. Furthermore, many of the SNPs are common within the human population, and could contribute to the growing awareness that miRNAs and associated SNPs could account for detrimental neurological states. Interestingly, SNPs that overlapped miRNA-binding sites in the 3'-UTR of GABA-receptor subunit coding genes were particularly enriched. Moreover, we demonstrated that SNP rs9291296 would strengthen miR-26a-5p binding to a highly conserved site in the 3'-UTR of gamma-aminobutyric acid receptor subunit alpha-4. © 2014 WILEY PERIODICALS, INC.

Challenges and Opportunities in the Discovery of New Therapeutics Targeting the Kynurenine Pathway.

PubMed

Dounay, Amy B; Tuttle, Jamison B; Verhoest, Patrick R

2015-11-25

The kynurenine pathway is responsible for the metabolism of more than 95% of dietary tryptophan (TRP) and produces numerous bioactive metabolites. Recent studies have focused on three enzymes in this pathway: indoleamine dioxygenase (IDO1), kynurenine monooxygenase (KMO), and kynurenine aminotransferase II (KAT II). IDO1 inhibitors are currently in clinical trials for the treatment of cancer, and these agents may also have therapeutic utility in neurological disorders, including multiple sclerosis. KMO inhibitors are being investigated as potential treatments for neurodegenerative diseases, such as Huntington's and Alzheimer's diseases. KAT II inhibitors have been proposed in new therapeutic approaches toward psychiatric and cognitive disorders, including cognitive impairment associated with schizophrenia. Numerous medicinal chemistry studies are currently aimed at the design of novel, potent, and selective inhibitors for each of these enzymes. The emerging opportunities and significant challenges associated with pharmacological modulation of these enzymes will be explored in this review.

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.

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.

Curcumin, a component of turmeric: from farm to pharmacy.

PubMed

Gupta, Subash C; Kismali, Gorkem; Aggarwal, Bharat B

2013-01-01

Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Calculation of prevalence estimates through differential equations: application to stroke-related disability.

PubMed

Mar, Javier; Sainz-Ezkerra, María; Moler-Cuiral, Jose Antonio

2008-01-01

Neurological diseases now make up 6.3% of the global burden of disease mainly because they cause disability. To assess disability, prevalence estimates are needed. The objective of this study is to apply a method based on differential equations to calculate the prevalence of stroke-related disability. On the basis of a flow diagram, a set of differential equations for each age group was constructed. The linear system was solved analytically and numerically. The parameters of the system were obtained from the literature. The model was validated and calibrated by comparison with previous results. The stroke prevalence rate per 100,000 men was 828, and the rate for stroke-related disability was 331. The rates steadily rose with age, but the group between the ages of 65 and 74 years had the highest total number of individuals. Differential equations are useful to represent the natural history of neurological diseases and to make possible the calculation of the prevalence for the various states of disability. In our experience, when compared with the results obtained by Markov models, the benefit of the continuous use of time outweighs the mathematical requirements of our model. (c) 2008 S. Karger AG, Basel.

Beneficial Effects of Spices in Food Preservation and Safety

PubMed Central

Gottardi, Davide; Bukvicki, Danka; Prasad, Sahdeo; Tyagi, Amit K.

2016-01-01

Spices have been used since ancient times. Although they have been employed mainly as flavoring and coloring agents, their role in food safety and preservation have also been studied in vitro and in vivo. Spices have exhibited numerous health benefits in preventing and treating a wide variety of diseases such as cancer, aging, metabolic, neurological, cardiovascular, and inflammatory diseases. The present review aims to provide a comprehensive summary of the most relevant and recent findings on spices and their active compounds in terms of targets and mode of action; in particular, their potential use in food preservation and enhancement of shelf life as a natural bioingredient. PMID:27708620

Indole alkaloid marine natural products: An established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases

PubMed Central

Gul, Waseem; Hamann, Mark T.

2016-01-01

The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets. Historically marine natural products have largely been explored as anticancer agents. The indole alkaloids are a class of marine natural products that show unique promise in the development of new drug leads. This report reviews the literature on indole alkaloids of marine origin and also highlights our own research. Specific biological activities of indole alkaloids presented here include: cytotoxicity, antiviral, antiparasitic, anti-inflammatory, serotonin antagonism, Ca-releasing, calmodulin antagonism, and other pharmacological activities. PMID:16236327

MITOCHONDRIAL DISEASES PART III: THERAPEUTIC INTERVENTIONS IN MOUSE MODELS OF OXPHOS DEFICIENCIES

PubMed Central

Peralta, Susana; Torraco, Alessandra; Iommarini, Luisa; Diaz, Francisca

2015-01-01

Mitochondrial defects are the cause of numerous disorders affecting the oxidative phosphorylation system (OXPHOS) in humans leading predominantly to neurological and muscular degeneration. The molecular origin, manifestations, and progression of mitochondrial diseases have a broad spectrum, which makes very challenging to find a globally effective therapy. The study of the molecular mechanisms underlying the mitochondrial dysfunction indicates that there is a wide range of pathways, enzymes and molecules that could be potentially targeted for therapeutic purpose. Therefore, focusing on the pathology of the disease is essential to design new treatments. In this review, we will summarize and discuss the different therapeutic interventions tested in some mouse models of mitochondrial diseases laying emphasis on the molecular mechanisms of action and their potential applications. PMID:25638392

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.

Molecular Targets of Cannabidiol in Neurological Disorders.

PubMed

Ibeas Bih, Clementino; Chen, Tong; Nunn, Alistair V W; Bazelot, Michaël; Dallas, Mark; Whalley, Benjamin J

2015-10-01

Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excluding unlikely and implausible targets, the remaining molecular targets of CBD with plausible evidence for involvement in therapeutic effects in neurological disorders (e.g., voltage-dependent anion channel 1, G protein-coupled receptor 55, CaV3.x, etc.) are associated with either the regulation of, or responses to changes in, intracellular calcium levels. While no causal proof yet exists for CBD's effects at these targets, they represent the most probable for such investigations and should be prioritized in further studies of CBD's therapeutic mechanism of action.

Patient-Specific Pluripotent Stem Cells in Neurological Diseases

PubMed Central

Durnaoglu, Serpen; Genc, Sermin; Genc, Kursad

2011-01-01

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

[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.

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 that while TPP1 protein delivered via the CSF may protect these cells, preservation of the remainder of the retina will require delivery of normal TPP1 more directly to the retina, probably via the vitreous body. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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.

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.

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.

Prolonged controlled delivery of nerve growth factor using porous silicon nanostructures.

PubMed

Zilony, Neta; Rosenberg, Michal; Holtzman, Liran; Schori, Hadas; Shefi, Orit; Segal, Ester

2017-07-10

Although nerve growth factor (NGF) is beneficial for the treatment of numerous neurological and non-neurological diseases, its therapeutic administration represents a significant challenge, due to the difficulty to locally deliver relevant doses in a safe and non-invasive manner. In this work, we employ degradable nanostructured porous silicon (PSi) films as carriers for NGF, allowing its continuous and prolonged release, while retaining its bioactivity. The PSi carriers exhibit high loading efficacy (up to 90%) of NGF and a continuous release, with no burst, over a period of>26days. The released NGF bioactivity is compared to that of free NGF in both PC12 cells and dissociated dorsal root ganglion (DRG) neurons. We show that the NGF has retained its bioactivity and induces neurite outgrowth and profound differentiation (of >50% for PC12 cells) throughout the period of release within a single administration. Thus, this proof-of-concept study demonstrates the immense therapeutic potential of these tunable carriers as long-term implants of NGF reservoirs and paves the way for new localized treatment strategies of neurodegenerative diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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.

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.

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.

Neurological complications are avoidable during CABG.

PubMed

Haider, Zulfiqar; Jalal, Anjum; Alamgir, Asif Rashid; Rasheed, Irfan

2018-01-01

To review the incidence of stroke in patients undergoing CABG and the impact of a preventive strategy adopted at tertiary care unit of cardiac surgery. The data of all patients who underwent isolated CABG (N= 722) from July 2016 to August 2017 at Faisalabad Institute of Cardiology was retrieved for this retrospective study. All operations were done on cardiopulmonary bypass and cold blood cardioplegia. Numeric data was summarized as Mean ± Standard Deviation while categoric variables were summarized into frequency and percentage. Mean age of patients was 53.83±8.8 years. Mean Parsonnet and Logistic EuroScore were 4.3±3.2 and 3.3±0.9 respectively. Forty nine patients (6.78%) had significant carotid artery disease. Mean number of grafts was 2.8±0.82. Diabetes was present in 27.8% patients. Neurological complications were noticed in 14 patients (1.94%) who included 12 permanent paralyses. Further subgroup analysis revealed that 67 patients who were operated by single clamp technique remained free of neurological complications. This is clinically remarkable finding but due to small population size it is statistically non- significant. The incidence of neurological complications can be reduced significantly by adopting the appropriate preventing measures. Use of Single Clamp technique may be the reasons of such a low incidence of stroke in this study.

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.

[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.

Determining whether curcumin degradation/condensation is actually bioactivation (Review).

PubMed

Jankun, Jerzy; Wyganowska-Świątkowska, Marzena; Dettlaff, Katarzyna; Jelińska, Anna; Surdacka, Anna; Wątróbska-Świetlikowska, Dorota; Skrzypczak-Jankun, Ewa

2016-05-01

Curcumin has been shown to exert therapeutic or protective effects against a variety of diseases, such as cancer, pulmonary diseases, neurological, liver, metabolic, autoimmune, cardiovascular diseases and numerous other chronic ailments. Over 116 clinical studies on curcumin in humans were registered with the US National Institutes of Health in 2015. However, it is mystifying how curcumin can be so effective in the treatment of many diseases since it has very low water solubility and bioavailability. Furthermore, curcumin is not stable under various conditions; its degradation or condensation into different bioactive compounds may be responsible for its biological activities rather than curcumin itself. In this review, we provide evidence of curcumin degradation and condensation into different compounds which have or may have health benefits themselves. Literature reviews strongly suggest that these molecules contribute to the observed health benefits, rather than curcumin itself.

Brain MRI analysis for Alzheimer's disease diagnosis using an ensemble system of deep convolutional neural networks.

PubMed

Islam, Jyoti; Zhang, Yanqing

2018-05-31

Alzheimer's disease is an incurable, progressive neurological brain disorder. Earlier detection of Alzheimer's disease can help with proper treatment and prevent brain tissue damage. Several statistical and machine learning models have been exploited by researchers for Alzheimer's disease diagnosis. Analyzing magnetic resonance imaging (MRI) is a common practice for Alzheimer's disease diagnosis in clinical research. Detection of Alzheimer's disease is exacting due to the similarity in Alzheimer's disease MRI data and standard healthy MRI data of older people. Recently, advanced deep learning techniques have successfully demonstrated human-level performance in numerous fields including medical image analysis. We propose a deep convolutional neural network for Alzheimer's disease diagnosis using brain MRI data analysis. While most of the existing approaches perform binary classification, our model can identify different stages of Alzheimer's disease and obtains superior performance for early-stage diagnosis. We conducted ample experiments to demonstrate that our proposed model outperformed comparative baselines on the Open Access Series of Imaging Studies dataset.

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.

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

The neurology of parasitic diseases and malaria.

PubMed

Román, Gustavo C

2011-02-01

Neurologists should be aware of parasitic diseases occurring in travelers and recent migrants because the world has become a global village as a result of tourism and immigration. Global warming is changing the distribution of diseases formerly confined to the tropics. The two most common parasitic diseases of the nervous system are Plasmodium falciparum malaria presenting as a febrile encephalopathy with normal CSF and neurocysticercosis causing seizures with focal MRI lesions or with intracranial hypertension. Numerous parasites may cause larva migrans with eosinophilic meningitis. Spinal cord involvement is the signature presentation of schistosomiasis. Trypanosoma cruzi, the agent of Chagas disease in the Americas, may cause myocardiopathy and embolic stroke. Sleeping sickness remains the most common manifestation of African trypanosomiasis. These conditions are challenging to diagnose unless a history of travel is elicited. Prospective travelers should be advised of preventive measures to avoid potentially severe infections of the nervous system.

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

Neurological and ocular fascioliasis in humans.

PubMed

Mas-Coma, Santiago; Agramunt, Verónica H; Valero, María Adela

2014-01-01

Fascioliasis is a food-borne parasitic disease caused by the trematode species Fasciola hepatica, distributed worldwide, and Fasciola gigantica, restricted to given regions of Africa and Asia. This disease in humans shows an increasing importance, which relies on its recent widespread emergence related to climate and global changes and also on its pathogenicity in the invasive, biliary, and advanced chronic phases in the human endemic areas, mainly of developing countries. In spite of the large neurological affection capacity of Fasciola, this important pathogenic aspect of the disease has been pronouncedly overlooked in the past decades and has not even appear within the numerous reviews on the parasitic diseases of the central nervous system. The aim of this wide retrospective review is an in-depth analysis of the characteristics of neurological and ocular fascioliasis caused by these two fasciolid species. The terms of neurofascioliasis and ophthalmofascioliasis are restricted to cases in which the direct affection of the central nervous system or the eye by a migrant ectopic fasciolid fluke is demonstrated by an aetiological diagnosis of recovered flukes after surgery or spontaneous moving-out of the fluke through the orbit. Cases in which the ectopic fluke is not recovered and the symptoms cannot be explained by an indirect affection at distance may also be included in these terms. Neurofascioliasis and ophthalmofascioliasis cases are reviewed and discussed. With regard to fascioliasis infection giving an indirect rise to neurological affection, the distribution and frequency of cases are analysed according to geography, sex, and age. Minor symptoms and major manifestations are discussed. Three main types of cases are distinguished depending on the characteristics of their manifestations: genuine neurological, meningeal, and psychiatric or neuropsychic. The impressive symptoms and signs appearing in each type of these cases are included. Brain examination techniques and neuroimaging useful for the diagnosis of neurological cases are exposed. Within fascioliasis infection indirectly causing ocular manifestations, case distribution and frequency are similarly analysed. A short analysis is devoted to clarify the first reports of a human eye infection. The affection of related and close organs is discussed by differentiating between cases of the dorsal spine, pulmonary manifestations, heart and vessel affection, findings in blood vessels, skin and dermatologic reactions, cases of ectopic mature flukes, and upper body locations. The clinical complexity of the puzzling polymorphisms, the disconcerting multifocality of the manifestations, and their changes along the evolution of the disease in the same patient, as well as the differences between the clinical pictures shown by different patients, are highlighted. The many syndromes involved are enumerated. The pathogenic and physiological mechanisms underlying neurofascioliasis and ophthalmofascioliasis caused by ectopic flukes and the physiopathogenic processes indirectly affecting the central nervous system and causing genuine neurological, meningeal, psychiatric, and ocular manifestations are discussed. The diagnosis of neurological and ophthalmologic fascioliasis is analysed in depth, including clinical and paraclinical diagnosis, eosinophilia in the blood and cerebrospinal fluid, differential diagnosis from other parasitic infections such as helminthiases and myiases, an update of human fascioliasis diagnosis, and fluke and/or fluke egg recovery by surgery. Diagnostic analyses with faecal and blood samples for fascioliasis patients are updated. Therapy for patients with major neurological manifestations includes both antiparasitic treatments and anti-inflammatory therapeutics. Prognosis in fascioliasis patients with neurological manifestations is discussed, with emphasis on sequelae and fatal cases, and the care of patients with ophthalmologic manifestations is added. Conclusions indicate that neurological cases are overlooked in human fascioliasis endemic areas and also in developing countries in general. In remote zones, rural health centres and small hospitals in or near the human endemic areas do not dispose of the appropriate equipments for neurological analyses. Moreover, physicians may not be aware about the potential relationship between liver fluke infection and neurological implications, and such cases may therefore remain misdiagnosed, even in developed countries. Priority should henceforth be given to the consideration of neurological and ocular affection in human endemic areas, and efforts should be implemented to assess their characteristics and frequency. Their impact should also be considered when estimating the global burden of fascioliasis. © 2014 Elsevier Ltd All rights reserved.

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.

[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.

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

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.

Decision Making: from Neuroscience to Psychiatry

PubMed Central

Lee, Daeyeol

2013-01-01

Adaptive behaviors increase the likelihood of survival and reproduction and improve the quality of life. However, it is often difficult to identify optimal behaviors in real life due to the complexity of the decision maker’s environment and social dynamics. As a result, although many different brain areas and circuits are involved in decision making, evolutionary and learning solutions adopted by individual decision makers sometimes produce suboptimal outcomes. Although these problems are exacerbated in numerous neurological and psychiatric disorders, their underlying neurobiological causes remain incompletely understood. In this review, theoretical frameworks in economics and machine learning and their applications in recent behavioral and neurobiological studies are summarized. Examples of such applications in clinical domains are also discussed for substance abuse, Parkinson’s disease, attention-deficit/hyperactivity disorder, schizophrenia, mood disorders, and autism. Findings from these studies have begun to lay the foundations necessary to improve diagnostics and treatment for various neurological and psychiatric disorders. PMID:23622061

Occupational Health Problems among Dentists in Croatia

PubMed Central

Vodanović, Marin; Sović, Slavica; Galić, Ivan

2016-01-01

Aim To assess the health status among dentists in Croatia regarding the symptoms of musculoskeletal, dermatological, sight, hearing and neurological disorders. Methods The anonymous online survey was conducted among 506 Croatian dentists. Results It was found that over 78.18% of the surveyed dentists experienced work related pain in upper back, 76.97% of them in lower back. Work-related skin problems were reported by 29.29% of dentists. Vision problems were reported by 46.87% and hearing problems by 19.03% of participants. Neurological disorders were reported by 15.76% of dentists. Conclusion This study is the first to report on the overall health status of Croatian dentists and, unfortunately, it showed undesirable results. Numerous health hazards, increased professional requirements and limited ergonomics in the work environment of Croatian dental practitioners cause various health disorders, and the prevalence of occupational diseases is very high. PMID:28275278

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.

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/

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.

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.

Pattern of traditional medicine use by adult Saudi patients with neurological disorders.

PubMed

Mohammad, Yousef; Al-Ahmari, Ahmed; Al-Dashash, Fahad; Al-Hussain, Fawaz; Al-Masnour, Firas; Masoud, Abdullah; Jradi, Hoda

2015-04-01

Traditional medicine (TM) has been established as a two-edged sword. On one edge numerous forms of TM have been proven safe and effective, while on the other edge various modes of TM have been shown to be futile and potentially dangerous. Resorting to TM, especially for chronic diseases, is common world-wide and includes Saudi Arabia. Most neurological diseases are chronic. No data is available on the utilization of TM among patients with neurological disorders. We conducted this study to assess for the prevalence, pattern, perception and triggers for TM use by the adult Saudi patients with neurological disorders. A survey written in Arabic and comprised of 15 questions was used to collect data on the practice of TM among the neurology patients of King Saud University Ambulatory Clinic. The questions in the survey pertain mainly to the frequency of TM practice, its form and the patient's opinion of this practice. The data was collected through a face to face interview by three medical students who were instructed on the survey questions prior to the launch of the study. 292 patients completed the survey (35.9% males and 64.0% females). 67% (n = 196) of the sample used TM. Cupping or what is commonly known as "hojamah" was the most prevalent method (45.4%) followed by herbs, skin cauterization and the Reciting of the Holy Quran (42.3%, 33.7% and 20.4% respectively). The prevalence of TM use did not differ across gender (chi-sq = 2.02; p-value = 0.15), level of education (chi-sq = 4.02; p-value = 0.40), health status (chi-sq = 2.29; p-value = 0.68), age groups (chi-sq = 5.12; p-value = 0.16), or perception toward TM (chi-sq = 2.67; p-value = 0.26) in this population. The practice of TM is common among the neurology patients of Saudi Arabia. Cupping, herbs, and skin cauterization, which can be harmful when wrongly employed, are frequently utilized in this patient population. Measures and policies to endorse the appropriate use of TM by Saudi society must be implemented promptly.

77 FR 40620 - AHRQ Workgroups on ICD-10-CM/PCS Conversion of Quality Indicators (QIs) - Extension Date for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

... with relevant clinical expertise (e.g., cardiovascular disease, neurologic disease, orthopedic and... measurement using administrative data in specific, relevant clinical domains (e.g., cardiovascular disease... (e.g., cardiovascular disease, neurologic disease, orthopedic and musculoskeletal disease, obstetrics...

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.

The position of nervous diseases between internal medicine and psychiatry in the XIXth century.

PubMed

Shterenshis, M V

1999-12-01

It is frequently said and believed that the history of clinical neurology of the 19th century has much in common with the history of psychiatry. Though neurology and psychiatry are neighboring clinical disciplines, the development of clinical neurology differs from that of psychiatry in 19th century Europe. The history of bedside neurology is that of gradual separation of nervous diseases from other internal diseases. Despite the efforts of the German psychiatrists, any influence of psychiatry on that process was very limited.

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

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.

Astaxanthin as a Potential Neuroprotective Agent for Neurological Diseases

PubMed Central

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

2015-01-01

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

SUMOylation in Neurological Diseases.

PubMed

Liu, F-Y; Liu, Y-F; Yang, Y; Luo, Z-W; Xiang, J-W; Chen, Z-G; Qi, R-L; Yang, T-H; Xiao, Y; Qing, W-J; Li, D W-C

2017-01-01

Since the discovery of SUMOs (small ubiquitin-like modifiers) over 20 years ago, sumoylation has recently emerged as an important posttranslational modification involved in almost all aspects of cellular physiology. In neurons, sumoylation dynamically modulates protein function and consequently plays an important role in neuronal maturation, synapse formation and plasticity. Thus, the dysfunction of sumoylation pathway is associated with many different neurological disorders. Hundreds of different proteins implicated in the pathogenesis of neurological disorders are SUMO-modified, indicating the importance of sumoylation involved in the neurological diseases. In this review, we summarize the growing findings on protein sumoylation in neuronal function and dysfunction. It is essential to have a thorough understanding on the mechanism how sumoylation contributes to neurological diseases in developing efficient therapy for these diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ambulatory training in neurology education.

PubMed

Lukas, Rimas V; Blood, Angela D; Brorson, James R; Albert, Dara V F

2017-01-15

Much of the care provided by practicing neurologists takes place in outpatient clinics. However, neurology trainees often have limited exposure to this setting. Adequate incorporation of outpatient care in neurology training is vital; however it is often hampered by numerous challenges. We detail a number of these challenges and suggest potential means for improvement. Copyright © 2016 Elsevier B.V. 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.

Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease.

PubMed

Fox, Ira J; Daley, George Q; Goldman, Steven A; Huard, Johnny; Kamp, Timothy J; Trucco, Massimo

2014-08-22

Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful cell transplantation will require optimizing the best cell type and site for engraftment, overcoming limitations to cell migration and tissue integration, and occasionally needing to control immunologic reactivity, as well as a number of other challenges. Collaboration among scientists, clinicians, and industry is critical for generating new stem cell-based therapies. Copyright © 2014, American Association for the Advancement of Science.

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 complications are avoidable during CABG

PubMed Central

Haider, Zulfiqar; Jalal, Anjum; Alamgir, Asif Rashid; Rasheed, Irfan

2018-01-01

Objective: To review the incidence of stroke in patients undergoing CABG and the impact of a preventive strategy adopted at tertiary care unit of cardiac surgery. Methods: The data of all patients who underwent isolated CABG (N= 722) from July 2016 to August 2017 at Faisalabad Institute of Cardiology was retrieved for this retrospective study. All operations were done on cardiopulmonary bypass and cold blood cardioplegia. Numeric data was summarized as Mean ± Standard Deviation while categoric variables were summarized into frequency and percentage. Results: Mean age of patients was 53.83±8.8 years. Mean Parsonnet and Logistic EuroScore were 4.3±3.2 and 3.3±0.9 respectively. Forty nine patients (6.78%) had significant carotid artery disease. Mean number of grafts was 2.8±0.82. Diabetes was present in 27.8% patients. Neurological complications were noticed in 14 patients (1.94%) who included 12 permanent paralyses. Further subgroup analysis revealed that 67 patients who were operated by single clamp technique remained free of neurological complications. This is clinically remarkable finding but due to small population size it is statistically non- significant. Conclusion: The incidence of neurological complications can be reduced significantly by adopting the appropriate preventing measures. Use of Single Clamp technique may be the reasons of such a low incidence of stroke in this study. PMID:29643869

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.

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.

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.

Acid Lipase Disease

MedlinePlus

... of Neurological Disorders and Stroke conducts and supports research to understand lipid storage diseases such as acid lipase deficiency and ... of Neurological Disorders and Stroke conducts and supports research to understand lipid storage diseases such as acid lipase deficiency and ...

Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy

PubMed Central

Barretto, Robert P. J.; Ko, Tony H.; Jung, Juergen C.; Wang, Tammy J.; Capps, George; Waters, Allison C.; Ziv, Yaniv; Attardo, Alessio; Recht, Lawrence; Schnitzer, Mark J.

2013-01-01

The combination of intravital microscopy and animal models of disease has propelled studies of disease mechanisms and treatments. However, many disorders afflict tissues inaccessible to light microscopy in live subjects. Here we introduce cellular-level time-lapse imaging deep within the live mammalian brain by one- and two-photon fluorescence microendoscopy over multiple weeks. Bilateral imaging sites allowed longitudinal comparisons within individual subjects, including of normal and diseased tissues. Using this approach we tracked CA1 hippocampal pyramidal neuron dendrites in adult mice, revealing these dendrites' extreme stability (>8,000 day mean lifetime) and rare examples of their structural alterations. To illustrate disease studies, we tracked deep lying gliomas by observing tumor growth, visualizing three-dimensional vasculature structure, and determining microcirculatory speeds. Average erythrocyte speeds in gliomas declined markedly as the disease advanced, notwithstanding significant increases in capillary diameters. Time-lapse microendoscopy will be applicable to studies of numerous disorders, including neurovascular, neurological, cancerous, and trauma-induced conditions. PMID:21240263

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.

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.

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

PubMed Central

Torres, Viviana I.; Vallejo, Daniela

2017-01-01

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

Therapeutic Use of Botulinum Toxin in Neurorehabilitation

PubMed Central

Intiso, Domenico

2012-01-01

The botulinum toxins (BTX), type A and type B by blocking vesicle acetylcholine release at neuro-muscular and neuro-secretory junctions can result efficacious therapeutic agents for the treatment of numerous disorders in patients requiring neuro-rehabilitative intervention. Its use for the reduction of focal spasticity following stroke, brain injury, and cerebral palsy is provided. Although the reduction of spasticity is widely demonstrated with BTX type A injection, its impact on the improvement of dexterity and functional outcome remains controversial. The use of BTX for the rehabilitation of children with obstetrical brachial plexus palsy and in treating sialorrhea which can complicate the course of some severe neurological diseases such as amyotrophic lateral sclerosis and Parkinson's disease is also addressed. Adverse events and neutralizing antibodies formation after repeated BTX injections can occur. Since impaired neurological persons can have complex disabling feature, BTX treatment should be viewed as adjunct measure to other rehabilitative strategies that are based on the individual's residual ability and competence and targeted to achieve the best functional recovery. BTX therapy has high cost and transient effect, but its benefits outweigh these disadvantages. Future studies must clarify if this agent alone or adjunctive to other rehabilitative procedures works best on functional outcome. PMID:21941544

Neuroprotective and Anti-Aging Potentials of Essential Oils from Aromatic and Medicinal Plants

PubMed Central

Ayaz, Muhammad; Sadiq, Abdul; Junaid, Muhammad; Ullah, Farhat; Subhan, Fazal; Ahmed, Jawad

2017-01-01

The use of essential oils (EOs) and their components is known since long in traditional medicine and aromatherapy for the management of various diseases, and is further increased in the recent times. The neuroprotective and anti-aging potentials of EOs and their possible mechanism of actions were evaluated by numerous researchers around the globe. Several clinically important EOs and their components from Nigella sativa, Acorus gramineus, Lavandula angustifolia, Eucalyptus globulus, Mentha piperita, Rosmarinus officinalis, Jasminum sambac, Piper nigrum and so many other plants are reported for neuroprotective effects. This review article was aimed to summarize the current finding on EOs tested against neurodegenerative disorders like Alzheimer disease (AD) and dementia. The effects of EOs on pathological targets of AD and dementia including amyloid deposition (Aβ), neurofibrillary tangles (NFTs), cholinergic hypofunction, oxidative stress and glutamatergic abnormalities were focused. Furthermore, effects of EOs on other neurological disorders including anxiety, depression, cognitive hypofunction epilepsy and convulsions were also evaluated in detail. In conclusion, EOs were effective on several pathological targets and have improved cognitive performance in animal models and human subjects. Thus, EOs can be developed as multi-potent agents against neurological disorders with better efficacy, safety and cost effectiveness. PMID:28611658

Genomic and Epigenomic Insights into Nutrition and Brain Disorders

PubMed Central

Dauncey, Margaret Joy

2013-01-01

Considerable evidence links many neuropsychiatric, neurodevelopmental and neurodegenerative disorders with multiple complex interactions between genetics and environmental factors such as nutrition. Mental health problems, autism, eating disorders, Alzheimer’s disease, schizophrenia, Parkinson’s disease and brain tumours are related to individual variability in numerous protein-coding and non-coding regions of the genome. However, genotype does not necessarily determine neurological phenotype because the epigenome modulates gene expression in response to endogenous and exogenous regulators, throughout the life-cycle. Studies using both genome-wide analysis of multiple genes and comprehensive analysis of specific genes are providing new insights into genetic and epigenetic mechanisms underlying nutrition and neuroscience. This review provides a critical evaluation of the following related areas: (1) recent advances in genomic and epigenomic technologies, and their relevance to brain disorders; (2) the emerging role of non-coding RNAs as key regulators of transcription, epigenetic processes and gene silencing; (3) novel approaches to nutrition, epigenetics and neuroscience; (4) gene-environment interactions, especially in the serotonergic system, as a paradigm of the multiple signalling pathways affected in neuropsychiatric and neurological disorders. Current and future advances in these four areas should contribute significantly to the prevention, amelioration and treatment of multiple devastating brain disorders. PMID:23503168

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.

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 diseases and pain

PubMed Central

2012-01-01

Chronic pain is a frequent component of many neurological disorders, affecting 20–40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). Chronic pain should thus be considered a brain disease in which alterations in neural networks affect multiple aspects of brain function, structure and chemistry. The study and treatment of this disease is greatly complicated by the lack of objective measures for either the symptoms or the underlying mechanisms of chronic pain. In pain associated with neurological disease, it is sometimes difficult to obtain even a subjective evaluation of pain, as is the case for patients in a vegetative state or end-stage Alzheimer's disease. It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain. PMID:22067541

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.

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.

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]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Bill & Melinda Gates Foundation. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC-BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Development of learning objectives for neurology in a veterinary curriculum: part I: undergraduates.

PubMed

Lin, Yu-Wei; Volk, Holger A; Penderis, Jacques; Tipold, Andrea; Ehlers, Jan P

2015-01-13

With an increasing caseload of veterinary neurology patients in first opinion practice, there is a requirement to establish relevant learning objectives for veterinary neurology encompassing knowledge, skills and attitudes for veterinary undergraduate students in Europe. With help of experts in veterinary neurology from the European College of Veterinary Neurology (ECVN) and the European Society of Veterinary Neurology (ESVN) a survey of veterinary neurologic learning objectives using a modified Delphi method was conducted. The first phase comprised the development of a draft job description and learning objectives by a working group established by the ECVN. In the second phase, a quantitative questionnaire (multiple choice, Likert scale and free text) covering 140 learning objectives and subdivided into 8 categories was sent to 341 ESVN and ECVN members and a return rate of 62% (n = 213/341) was achieved. Of these 140 learning objectives ECVN Diplomates and ESVN members considered 42 (30%) objectives as not necessary for standard clinical veterinary neurology training, 94 (67%) were graded to be learned at a beginner level and 4 (3%) at an advanced level. The following objectives were interpreted as the most important day one skills: interpret laboratory tests, perform a neurological examination and establish a neuroanatomical localization. In this survey the three most important diseases of the central nervous system included epilepsy, intervertebral disc disease and inflammatory diseases. The three most important diseases of the peripheral nervous system included polyradiculoneuritis, myasthenia gravis and toxic neuropathies. The results of this study should help to reform the veterinary curriculum regarding neurology and may reduce the phenomenon of "Neurophobia".

Prevalence and incidence of neurological disorders among adult Ugandans in rural and urban Mukono district; a cross-sectional study.

PubMed

Kaddumukasa, Mark; Mugenyi, Leviticus; Kaddumukasa, Martin N; Ddumba, Edward; Devereaux, Michael; Furlan, Anthony; Sajatovic, Martha; Katabira, Elly

2016-11-17

The burden of neurological diseases is increasing in developing countries. However, there is a prominent scarcity of literature on the incidence of neurological diseases in sub-Saharan Africa. This study was therefore undertaken to determine the prevalence and incidence of neurological diseases in this setting to serve as a baseline for planning and care for neurological disorders in Uganda. The study was conducted within rural and urban Mukono district, east of Kampala city of Uganda, central region. Over a period of six months, a cross sectional survey was conducted and screening was performed using a standardized questionnaire. All subjects with neurological symptoms and signs were reviewed by a team of neurologists and neurological diagnoses made. Of the 3000 study subjects, 50.3% (1510/3000) were from the rural setting. Out of the participants screened, 67.4% were female, with a median age of 33 years. Among the 98 subjects with confirmed neurological disorders, the frequency of diseases was as follows; peripheral neuropathy (46.2%), chronic headaches (26.4%), and epilepsy (8.5%), followed by pain syndromes (7.5%), stroke (6.6%) and tremors/Parkinson disease (3.8%). The crude prevalence rates of these disorders (95% CI) were 14.3% (8.5-24.1); 13.3% (7.7-22.8); 33.7% (23.9-47.4) for stroke, epilepsy and peripheral neuropathy respectively. Peripheral neuropathy followed by chronic headaches had the highest estimated incidence/1000 years. Stroke had an estimated incidence of 3.6 new cases with 95% CI of (2.1-6.1)/1000 years. Peripheral neuropathy, chronic headaches and epilepsy disorders are major causes of morbidity in Sub-Saharan settings. There is an urgent need of more robust and powered studies to determine the incidence of these diseases.

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.

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

PubMed

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

2014-12-01

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

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.

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.

[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.

[Effect of pharmacologic treatment of the nutritional status of neurologic patients].

PubMed

Piñeiro Corrales, Guadalupe; Vázquez López, Cristina; Álvarez Payero, Miriam

2014-01-01

Clinical manifestations accompanying neurological diseases are diverse and affect multiple organs. Nutritional status of patients with certain neurological diseases such as stroke, Alzheimer's disease, Parkinson's disease, Epilepsy and Multiple Sclerosis can be altered because of symptoms associated with disease course, including certain micronutrient deficiency (folic acid, zinc, vitamin B6 and B12, vitamin D, vitamin E and vitamin C), changes in energy expenditure, intake decreased, gastrointestinal disorders and dysfunction of the bone mass. Also, we have to take in account other factors as: advanced age, multiple co morbidities, polypharmacy, the use of herbal products, social habits, diet and pharmacological treatments effect. An assessment of the factors related to neurological treatment that cause alterations in metabolic and nutritional status was performed: side effects of anti-Parkinson drugs, antiepileptic drugs, and multiple sclerosis drugs; drug-nutrient interactions; and nutrient-drug interactions.

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 ...

[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.

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.

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.

[Neurologic diagnosis and certification in persons chronically exposed to certain organic solvents in light of personal cases].

PubMed

Sińczuk-Walczak, H

1995-01-01

A clinical picture of selected cases diagnosed or suspected of chronic poisoning by organic solvents such as: Trichlorethylene (TRI), Tetrachlorethylene (PER), Carbon Disulfide (CS2) is presented. Based on examples of diagnosed neurological syndromes, some diagnostic and certification issues concerning occupational diseases of the neurological system, are analysed. An objective assessment of patients' complaints, differentiation between occupational diseases, so called idiopathic diseases of the nervous system, selection of appropropriate diagnostic methods in order to confirm or exclude these diseases belong to essential problems among those discussed.

Disease Specific Aspects of Malnutrition in Neurogeriatric Patients

PubMed Central

Prell, Tino; Perner, Caroline

2018-01-01

Malnutrition in elderly patients is a common condition. Nevertheless, there is evidence on specific risk factors and problems of malnutrition in geriatric patients with neurological diseases. In this review, we summarize recent knowledge on malnutrition in different neurological diseases with a focus on elderly patients. This overview also provides strategies for a more specific and profound assessment of neurogeriatric patients to improve identification and treatment of malnutrition. Early and consequent treatment of malnutrition can lead to a decreased progression of the neurological disease and to a better quality of life in geriatric patients. PMID:29628887

Whole gene expression profile in blood reveals multiple pathways deregulation in R6/2 mouse model

PubMed Central

2013-01-01

Background Huntington Disease (HD) is a progressive neurological disorder, with pathological manifestations in brain areas and in periphery caused by the ubiquitous expression of mutant Huntingtin protein. Transcriptional dysregulation is considered a key molecular mechanism responsible of HD pathogenesis but, although numerous studies investigated mRNA alterations in HD, so far none evaluated a whole gene expression profile in blood of R6/2 mouse model. Findings To discover novel pathogenic mechanisms and potential peripheral biomarkers useful to monitor disease progression or drug efficacy, a microarray study was performed in blood of R6/2 at manifest stage and wild type littermate mice. This approach allowed to propose new peripheral molecular processes involved in HD and to suggest different panels of candidate biomarkers. Among the discovered deregulated processes, we focused on specific ones: complement and coagulation cascades, PPAR signaling, cardiac muscle contraction, and dilated cardiomyopathy pathways. Selected genes derived from these pathways were additionally investigated in other accessible tissues to validate these matrices as source of biomarkers, and in brain, to link central and peripheral disease manifestations. Conclusions Our findings validated the skeletal muscle as suitable source to investigate peripheral transcriptional alterations in HD and supported the hypothesis that immunological alteration may contribute to neurological degeneration. Moreover, the identification of altered signaling in mouse blood enforce R6/2 transgenic mouse as a powerful HD model while suggesting novel disease biomarkers for pre-clinical investigation. PMID:24252798

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 only be safely performed by well-trained medical escorts and comprehensive logistic arrangements.

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.

Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

PubMed

Milo, Ron

2015-04-01

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

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.

Global Cerebral Ischemia: Synaptic and Cognitive Dysfunction

PubMed Central

Neumann, Jake T.; Cohan, Charles H.; Dave, Kunjan R.; Wright, Clinton B.; Perez-Pinzon, Miguel A.

2018-01-01

Cardiopulmonary arrest is one of the leading causes of death and disability, primarily occurring in the aged population. Numerous global cerebral ischemia animal models induce neuronal damage similar to cardiac arrest. These global cerebral ischemia models range from vessel occlusion to total cessation of cardiac function, both of which have allowed for the investigation of this multifaceted disease and detection of numerous agents that are neuroprotective. Synapses endure a variety of alterations after global cerebral ischemia from the resulting excitotoxicity and have been a major target for neuroprotection; however, neuroprotective agents have proven unsuccessful in clinical trials, as neurological outcomes have not displayed significant improvements in patients. A majority of these neuroprotective agents have specific neuronal targets, where the success of future neuroprotective agents may depend on non-specific targets and numerous cognitive improvements. This review focuses on the different models of global cerebral ischemia, neuronal synaptic alterations, synaptic neuroprotection and behavioral tests that can be used to determine deficits in cognitive function after global cerebral ischemia. PMID:23170794

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

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.

[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.

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.

Swallowing Disorders

MedlinePlus

... most common cause of dysphagia); traumatic brain injury; cerebral palsy; Parkinson disease and other degenerative neurological disorders such ... most common cause of dysphagia); traumatic brain injury; cerebral palsy; Parkinson disease and other degenerative neurological disorders such ...

Advanced Parkinson's disease: clinical characteristics and treatment. Part II.

PubMed

Kulisevsky, J; Luquin, M R; Arbelo, J M; Burguera, J A; Carrillo, F; Castro, A; Chacón, J; García-Ruiz, P J; Lezcano, E; Mir, P; Martinez-Castrillo, J C; Martínez-Torres, I; Puente, V; Sesar, A; Valldeoriola-Serra, F; Yañez, R

2013-01-01

Many patients who have had Parkinson's disease (PD) for several years will present severe motor fluctuations and dyskinesias which require more aggressive therapies. The different approaches which are now available include deep brain stimulation of the subthalamic nucleus or medial globus pallidus, subcutaneous infusion of apomorphine, and intestinal infusion of levodopa-carbidopa. To define the indications and results for the 3 available therapies for advanced PD. Exhaustive review of the literature concerning the indications and results of deep brain stimulation, subcutaneous apomorphine infusion and duodenal infusion of levodopa/carbidopa gel to treat patients with advanced Parkinson disease. Although numerous studies have confirmed the efficacy of the 3 different therapies in advanced PD, there are no comparative studies that would allow us to define the best candidate for each technique. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

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.

Peroxisomes in brain development and function☆

PubMed Central

Berger, Johannes; Dorninger, Fabian; Forss-Petter, Sonja; Kunze, Markus

2016-01-01

Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer’s disease, autism and amyotrophic lateral sclerosis. This article is part of a Special Issue entitled: Peroxisomes edited by Ralf Erdmann. PMID:26686055

A Guide to Neurotoxic Animal Models of Parkinson’s Disease

PubMed Central

Tieu, Kim

2011-01-01

Parkinson’s disease (PD) is a neurological movement disorder primarily resulting from damage to the nigrostriatal dopaminergic pathway. To elucidate the pathogenesis, mechanisms of cell death, and to evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. The primary objectives of this article are twofold: First, to assist new investigators who are contemplating embarking on PD research to navigate through the available animal models. Emphasis will be placed on common neurotoxic murine models in which toxic molecules are used to lesion the nigrostriatal dopaminergic system. And second, to provide an overview of basic technical requirements for assessing the pathology, structure, and function of the nigrostriatal pathway. PMID:22229125

Is the French palliative care policy effective everywhere? Geographic variation in changes in inpatient death rates among older patients in France, 2010-2013.

PubMed

Weeks, William B; Ventelou, Bruno; Bendiane, Marc Karim

2016-10-01

Recently, French policymakers have tried to improve care at the end-of-life, by improving access to community-based palliative care, particularly for patients with cancer and neurological diseases. If effective, these efforts should reduce the proportion of such patients who die in the hospital. In light of these policies, we sought to determine the effectiveness of these efforts on reducing inpatient deaths by conducting a retrospective, observational analysis of patients aged 65 and older who were admitted to hospitals in France between 2010 and 2013 for 1 of 3 non-surgical conditions. We calculated department-specific age- and sex-adjusted inpatient death rates for 3 types of nonsurgical admissions and modeled expected number of inpatient deaths had their rates for patients with cancer or neurological disease tracked those of patients with non-cancer non-neurological diseases. We found that patients admitted with a cancer diagnosis experienced 20,394 (13.0%) fewer inpatient deaths that expected had non-surgical cancer diagnosis admission rates tracked those of nonsurgical non-cancer and non-neurological admission rates; patients admitted with a primary neurological disease diagnosis experienced 513 (4.5%) fewer inpatient deaths than expected. During the study period, observed-to-expected inpatient deaths fell more dramatically and consistently for patients admitted with cancer diagnoses than for those admitted with neurological diseases. Observed-to-expected ratios fell least in departments that were on the periphery of the French mainland. Our findings suggest that, in France, efforts to reduce inpatient death rates among patients with cancer or neurological disease diagnoses appear to be effective. However, their effectiveness varies geographically, suggesting that targeted efforts to improve lower performing departments may generate substantial performance improvements.

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

West Nile virus lineage 2 as a cause of zoonotic neurological disease in humans and horses in southern Africa.

PubMed

Venter, Marietjie; Swanepoel, Robert

2010-10-01

West Nile virus (WNV) is widely distributed in South Africa, but since a few cases of neurological disease have been reported from this region, endemic lineage 2 strains were postulated to be of low virulence. Several cases of nonfatal encephalitis in humans as well as fatal cases in a foal, dog, and ostrich chicks have, however, been associated with lineage 2 WNV in South Africa. The pathogenesis of lineage 2 WNV strains was investigated using mouse neuroinvasive experiments, gene expression experiments, and genome sequence comparisons which indicated that lineage 2 strains that are highly pathogenic exist. To determine whether cases of WNV were being missed in South Africa, horses with fever and neurological disease were investigated. Several cases of WNV were identified, all associated with severe neurological disease, 85% of which had to be euthanized or died. All cases positive by RT-PCR were shown to belong to lineage 2 WNV by DNA sequencing and phylogenetic analysis. Two cases of occupational infection were investigated, including a case of zoonotic transmission to a veterinarian who performed an autopsy on one of the horses as well as a laboratory infection after a needle stick injury with a neuroinvasive lineage 2 strain. Both resulted in neurological disease. Cytokine expression was investigated in the second case to assess the immunopathogenesis of WNV. Collectively, these studies suggest that lineage 2 WNV may be significantly under estimated as a cause of neurological disease in South Africa.

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 © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Pathology, immunohistochemistry, and ultrastructural findings associated with neurological sarcocystosis in cattle

USDA-ARS?s Scientific Manuscript database

The case of neurological sarcocystosis in a nine months old bull calf that died in 1982 was restudied. The bull was suspected to have rabies. Therefore, only brain was examined histologically. Thirty four years later, we restudied sections from paraffin-embedded blocks of brain. Numerous schizonts a...

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

Natural history of Niemann-Pick disease type C in a multicentre observational retrospective cohort study.

PubMed

Wraith, J E; Guffon, N; Rohrbach, M; Hwu, W L; Korenke, G C; Bembi, B; Luzy, C; Giorgino, R; Sedel, F

2009-11-01

Niemann-Pick disease type C (NP-C) is a devastating genetic disorder characterised by progressive neurological deterioration. However, data on the progression of neurological manifestations, particularly across different patient age-of-disease onsets, are limited. This is an observational retrospective cohort study designed to assess the progression of neurological disease in patients with NP-C. Physicians were asked to retrospectively complete a web-based questionnaire for each patient, at diagnosis and at up to three follow-up visits. An NP-C-specific disability scale was used to measure disease progression. The scale comprised four key parameters of neurological disease progression; ambulation, manipulation, language and swallowing. Disease progression was evaluated based on the annual rate of change in each parameter and the composite score using a linear mixed model analysis, and by classifying patients according to the number of worsened parameters during the observation period. Data were collected from 57 patients. The rate of deterioration was similar across the four individual parameters of the disability scale. The mean (95% CI) annual disease progression was +0.12 (0.09, 0.15) units. Among patients with a time interval of at least 1 year between diagnosis and last visit (n=49), 42 (86%) patients had progressed disease and 7 (14%) patients had stable disease. Disease progression was consistently more rapid in patients diagnosed in early childhood, compared with those diagnosed in late childhood, or with juvenile or adult presentation. In conclusion, our findings showed a progression in all four parameters of the disability scale, representing a continuous, unbroken progression of neurological manifestations.

Crimean-Congo Hemorrhagic Fever in Humanized Mice Reveals Glial Cells as Primary Targets of Neurological Infection.

PubMed

Spengler, Jessica R; Kelly Keating, M; McElroy, Anita K; Zivcec, Marko; Coleman-McCray, JoAnn D; Harmon, Jessica R; Bollweg, Brigid C; Goldsmith, Cynthia S; Bergeron, Éric; Keck, James G; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

2017-12-12

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral hemorrhagic disease seen exclusively in humans. Central nervous system (CNS) infection and neurological involvement have also been reported in CCHF. In the current study, we inoculated NSG-SGM3 mice engrafted with human hematopoietic CD34+ stem cells with low-passage CCHF virus strains isolated from human patients. In humanized mice, lethal disease develops, characterized by histopathological change in the liver and brain. To date, targets of neurological infection and disease have not been investigated in CCHF. CNS disease in humanized mice was characterized by gliosis, meningitis, and meningoencephalitis, and glial cells were identified as principal targets of infection. Humanized mice represent a novel lethal model for studies of CCHF countermeasures, and CCHF-associated CNS disease. Our data suggest a role for astrocyte dysfunction in neurological disease and identify key regions of infection in the CNS for future investigations of CCHF. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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.

The classification of conversion disorder (functional neurologic symptom disorder) in ICD and DSM.

PubMed

Levenson, J L; Sharpe, M

2016-01-01

The name given to functional neurologic symptoms has evolved over time in the different editions of the International Classification of Diseases (ICD) and the Diagnostic and Statistical Manual of Mental Disorders (DSM), reflecting a gradual move away from an etiologic conception rooted in hysterical conversion to an empiric phenomenologic one, emphasizing the central role of the neurologic examination and testing in demonstrating that the symptoms are incompatible with recognized neurologic disease pathophysiology, or are internally inconsistent. © 2016 Elsevier B.V. All rights reserved.

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.

[Development, problems and results of specialty-specific genetic counseling at the Neurology Clinic of the Karl Marx University].

PubMed

Bachmann, H

1987-11-01

Genetic counselling for inherited neurological diseases has been established at the Clinic for Neurology of Karl Marx University. Comprehensive experiences have been got with the specific and sometimes markedly different problems and aims of counselling in Wilsons disease, X-linked recessive muscular dystrophies, myotonic dystrophy and other neuromuscular disorders, Huntingtons chorea and hereditary ataxias.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2016-06-01

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

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.

Stuck in traffic: an emerging theme in diseases of the nervous system.

PubMed

Neefjes, Jacques; van der Kant, Rik

2014-02-01

The past decade has seen an explosion of DNA sequencing activities and many mutations and genetic variances underlying neurological and neurodegenerative diseases have been determined. This wealth of genetic data is now placed in molecular pathways revealing the nodes that underlie the disrupted processes. Many mutations in neurological diseases affect proteins controlling endosomal/lysosomal transport. Although the age of onset of these diseases range from juvenile [i.e., Niemann-Pick type C (NPC) and Charcot-Marie-Tooth (CMT) disease] to late onset (Parkinson's and Alzheimer's disease), deregulation of endosomal transport is a common theme. This review summarizes how elucidating the genetic basis for the various neurological diseases has advanced our understanding of the endo-lysosomal system and why the various mutations all translate into similar disease phenotypes. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

[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 neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease. On MRI, the lesions mainly involve the anterior horn of spinal cord, medulla oblongata and pons. At follow-ups, most patients have no neurologic sequel and the visualized lesions will be absorbed after active treatment.

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

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

Somatosensory disturbance by methylmercury exposure.

PubMed

Takaoka, Shigeru; Kawakami, Yoshinobu; Fujino, Tadashi; Oh-ishi, Fumihiro; Motokura, Fukuo; Kumagai, Yoshio; Miyaoka, Tetsu

2008-05-01

Minamata disease is methylmercury poisoning from consuming fish and shellfish contaminated by industrial waste. The polluted seafood was widely consumed in the area around Minamata, but many individuals were never examined for or classified as having Minamata disease. Following the determination of the Supreme Court of Japan in October 2004 that the Japanese Government was responsible for spreading Minamata disease, over 13,000 residents came forward to be examined for Minamata disease. We studied 197 residents from the Minamata area who had a history of fish consumption during the polluted period to determine the importance of sensory symptoms and findings in making a diagnosis of Minamata disease. We divided the exposed subjects into non-complicated (E) and complicated (E+N) groups based on the absence or presence of other neurological or neurologically related disorders and compared them to residents in control area (C) after matching for age and sex. We quantitatively measured four somatosensory modalities (minimal tactile sense by Semmes-Weinstein monofilaments, vibration sense, position sense, and two-point discrimination) and did psychophysical tests of fine-surface-texture discrimination. Subjective complaints were higher in groups E and E+N than C. Over 90% of E+N and E subjects displayed a sensory disturbance on conventional neurological examination and 28% had visual constriction. About 50% of the E and E +N groups had upper and lower extremity ataxia and about 70% had truncal ataxia. The prevalence of these neurological findings was significantly higher in exposed subjects than controls. All sensory modalities were impaired in the E and E+N groups. All four quantitatively measured sensory modalities were correlated. The prevalence of complaints, neurological findings, and sensory impairment was similar or a little worse in group E+N than in group E. We conclude that sensory symptoms and findings are important in making the diagnosis of Minamata disease and that they can be determined even in the presence of neurological or neurologically related diseases.

A Neuroprosthesis System Utilizing Optical Spatial Feedback Control

DTIC Science & Technology

2004-03-19

tetraplegia, muscular dystrophy, amyotrophic lateral sclerosis (i.e., “Lou Gehrig’s disease ”), and other neurological or musculoskeletal disease ...commonly used by individuals with high tetraplegia, muscular dystrophy, amyotrophic lateral sclerosis (i.e., “Lou Gehrig’s disease ”), and other...neurological or musculoskeletal disease . - 5 - REPORT ORGANIZATION This report is organized into the following sections: 1. Introduction: An

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.

Current Opinion on the Role of Neurogenesis in the Therapeutic Strategies for Alzheimer Disease, Parkinson Disease, and Ischemic Stroke; Considering Neuronal Voiding Function

PubMed Central

Lee, Eun-Hye

2016-01-01

Neurological diseases such as Alzheimer, Parkinson, and ischemic stroke have increased in occurrence and become important health issues throughout the world. There is currently no effective therapeutic strategy for addressing neurological deficits after the development of these major neurological disorders. In recent years, it has become accepted that adult neural stem cells located in the subventricular and subgranular zones have the ability to proliferate and differentiate in order to replace lost or damaged neural cells. There have been many limitations in the clinical application of both endogenous and exogenous neurogenesis for neurological disorders. However, many studies have investigated novel mechanisms in neurogenesis and have shown that these limitations can potentially be overcome with appropriate stimulation and various approaches. We will review concepts related to possible therapeutic strategies focused on the perspective of neurogenesis for the treatment of patients diagnosed with Alzheimer disease, Parkinson disease, and ischemic stroke based on current reports. PMID:28043116

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.

Essential Tremor vs. Parkinson's Disease: How Do They Differ?

MedlinePlus

... Arif Herekar , MD, Chairman and Head, Department of Neurology, Baqai Medical University; and member of the IETF Medical Advisory Board. Joseph Jankovic , MD, Professor of Neurology, Distinguished Chair in Movement Disorders, Director, Parkinson’s Disease ...

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.

The Report of Three Rare Cases of the Niemann-pick Disease in Birjand, South Khorasan, Eastern Iran.

PubMed

Noroozi Asl, Samaneh; Vakili, Rahim; Ghaemi, Nosrat; Eshraghi, Peyman

2017-01-01

Niemann-Pick disease type C (NP-C) is a rare neurovisceral and irreversible disease leading to premature death and disabling neurological signs. This autosomal recessive disease with incidence rate of 1:120000 is caused by mutations in either the NPC1 or the NPC2 gene, which leads to accumulation of cholesterol in body tissues especially brain and progressive neurological symptoms. NP-C is characterized by nonspecific visceral, neurological and psychiatric manifestations in infants. The neurological involvement is typically proceeded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno-or hepatosplenomegaly in infancy or childhood). Early detection of NPC is important so that therapy with miglustat can delay onset of neurological symptoms and prolong survival. We describe here three infants from Birjand, South Khorasan, eastern Iran in 2016 with splenomegaly and different neurological signs that diagnosis was confirmed by genetic study. In all of them, NPC-509 was pathologically increased. They also had an unreported homozygous mutation (c.1415T>C, p.Leu472Pro) in exon 9 of the NPC1 gene. We found unreported homozygous mutation in NPC gene. Knowing this mutation is significant to our people. Genotype-phenotype correlations for this specific mutation needs to be further studied.

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.

Neurological abnormalities in localized scleroderma of the face and head: a case series study for evaluation of imaging findings and clinical course.

PubMed

Lis-Święty, Anna; Brzezińska-Wcisło, Ligia; Arasiewicz, Hubert

2017-09-01

Localized scleroderma (LoS) of the face and head is often associated with neurological manifestations and/or imaging abnormalities in the central nervous system (CNS). We present an analysis of 20 cases of LoS affecting the face and head. The CNS symptoms and/or abnormalities in high-resolution computed tomography (HRCT) and/or magnetic resonance imaging (MRI) were observed in 12 patients (60%). In addition to the mild and unspecific disorders (e.g. headaches), serious neurological complications probably in the course of vasculitis were revealed: epilepsy (in two patients), epilepsy and pyramidal sings (in one patient). Neurological disorders and LoS occurred at the same time (in three patients) or at the course of the disease (nine patients) and no later than 29 years since the onset of the disease. No link between neurological disorders and the LoS clinical morphology, immunological and other laboratory parameters has been established. CNS involvement is not correlated with the clinical course of the facial and head LoS and may occur years after the disease initial symptomatology. Imaging follow-up is not required if there is not any emerging neurological symptom. In some cases, however, both HRCT and MRI are useful for monitoring disease evolution and addressing therapeutic choices.

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.

Artificial intelligence in neurodegenerative disease research: use of IBM Watson to identify additional RNA-binding proteins altered in amyotrophic lateral sclerosis.

PubMed

Bakkar, Nadine; Kovalik, Tina; Lorenzini, Ileana; Spangler, Scott; Lacoste, Alix; Sponaugle, Kyle; Ferrante, Philip; Argentinis, Elenee; Sattler, Rita; Bowser, Robert

2018-02-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with no effective treatments. Numerous RNA-binding proteins (RBPs) have been shown to be altered in ALS, with mutations in 11 RBPs causing familial forms of the disease, and 6 more RBPs showing abnormal expression/distribution in ALS albeit without any known mutations. RBP dysregulation is widely accepted as a contributing factor in ALS pathobiology. There are at least 1542 RBPs in the human genome; therefore, other unidentified RBPs may also be linked to the pathogenesis of ALS. We used IBM Watson ® to sieve through all RBPs in the genome and identify new RBPs linked to ALS (ALS-RBPs). IBM Watson extracted features from published literature to create semantic similarities and identify new connections between entities of interest. IBM Watson analyzed all published abstracts of previously known ALS-RBPs, and applied that text-based knowledge to all RBPs in the genome, ranking them by semantic similarity to the known set. We then validated the Watson top-ten-ranked RBPs at the protein and RNA levels in tissues from ALS and non-neurological disease controls, as well as in patient-derived induced pluripotent stem cells. 5 RBPs previously unlinked to ALS, hnRNPU, Syncrip, RBMS3, Caprin-1 and NUPL2, showed significant alterations in ALS compared to controls. Overall, we successfully used IBM Watson to help identify additional RBPs altered in ALS, highlighting the use of artificial intelligence tools to accelerate scientific discovery in ALS and possibly other complex neurological disorders.

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.

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

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.

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.

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.

[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.

Succinic Semialdehyde Dehydrogenase: Biochemical–Molecular–Clinical Disease Mechanisms, Redox Regulation, and Functional Significance

PubMed Central

Kim, Kyung-Jin; Pearl, Phillip L.; Jensen, Kimmo; Snead, O. Carter; Malaspina, Patrizia; Jakobs, Cornelis

2011-01-01

Abstract Succinic semialdehyde dehydrogenase (SSADH; aldehyde dehydrogenase 5a1, ALDH5A1; E.C. 1.2.1.24; OMIM 610045, 271980) deficiency is a rare heritable disorder that disrupts the metabolism of the inhibitory neurotransmitter 4-aminobutyric acid (GABA). Identified in conjunction with increased urinary excretion of the GABA analog gamma-hydroxybutyric acid (GHB), numerous patients have been identified worldwide and the autosomal-recessive disorder has been modeled in mice. The phenotype is one of nonprogressive neurological dysfunction in which seizures may be prominently displayed. The murine model is a reasonable phenocopy of the human disorder, yet the severity of the seizure disorder in the mouse exceeds that observed in SSADH-deficient patients. Abnormalities in GABAergic and GHBergic neurotransmission, documented in patients and mice, form a component of disease pathophysiology, although numerous other disturbances (metabolite accumulations, myelin abnormalities, oxidant stress, neurosteroid depletion, altered bioenergetics, etc.) are also likely to be involved in developing the disease phenotype. Most recently, the demonstration of a redox control system in the SSADH protein active site has provided new insights into the regulation of SSADH by the cellular oxidation/reduction potential. The current review summarizes some 30 years of research on this protein and disease, addressing pathological mechanisms in human and mouse at the protein, metabolic, molecular, and whole-animal level. Antioxid. Redox Signal. 15, 691–718. PMID:20973619

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

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

Histone deacetylases in memory and cognition.

PubMed

Penney, Jay; Tsai, Li-Huei

2014-12-09

Over the past 30 years, lysine acetylation of histone and nonhistone proteins has become established as a key modulator of gene expression regulating numerous aspects of cell biology. Neuronal growth and plasticity are no exception; roles for lysine acetylation and deacetylation in brain function and dysfunction continue to be uncovered. Transcriptional programs coupling synaptic activity to changes in gene expression are critical to the plasticity mechanisms underlying higher brain functions. These transcriptional programs can be modulated by changes in histone acetylation, and in many cases, transcription factors and histone-modifying enzymes are recruited together to plasticity-associated genes. Lysine acetylation, catalyzed by lysine acetyltransferases (KATs), generally promotes cognitive performance, whereas the opposing process, catalyzed by histone lysine deacetylases (HDACs), appears to negatively regulate cognition in multiple brain regions. Consistently, mutation or deregulation of different KATs or HDACs contributes to neurological dysfunction and neurodegeneration. HDAC inhibitors have shown promise as a treatment to combat the cognitive decline associated with aging and neurodegenerative disease, as well as to ameliorate the symptoms of depression and posttraumatic stress disorder, among others. In this review, we discuss the evidence for the roles of HDACs in cognitive function as well as in neurological disorders and disease. In particular, we focus on HDAC2, which plays a central role in coupling lysine acetylation to synaptic plasticity and mediates many of the effects of HDAC inhibition in cognition and disease. Copyright © 2014, American Association for the Advancement of Science.

Two Disease-Causing SNAP-25B Mutations Selectively Impair SNARE C-terminal Assembly.

PubMed

Rebane, Aleksander A; Wang, Bigeng; Ma, Lu; Qu, Hong; Coleman, Jeff; Krishnakumar, Shyam; Rothman, James E; Zhang, Yongli

2018-02-16

Synaptic exocytosis relies on assembly of three soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins into a parallel four-helix bundle to drive membrane fusion. SNARE assembly occurs by stepwise zippering of the vesicle-associated SNARE (v-SNARE) onto a binary SNARE complex on the target plasma membrane (t-SNARE). Zippering begins with slow N-terminal association followed by rapid C-terminal zippering, which serves as a power stroke to drive membrane fusion. SNARE mutations have been associated with numerous diseases, especially neurological disorders. It remains unclear how these mutations affect SNARE zippering, partly due to difficulties to quantify the energetics and kinetics of SNARE assembly. Here, we used single-molecule optical tweezers to measure the assembly energy and kinetics of SNARE complexes containing single mutations I67T/N in neuronal SNARE synaptosomal-associated protein of 25kDa (SNAP-25B), which disrupt neurotransmitter release and have been implicated in neurological disorders. We found that both mutations significantly reduced the energy of C-terminal zippering by ~10 k B T, but did not affect N-terminal assembly. In addition, we observed that both mutations lead to unfolding of the C-terminal region in the t-SNARE complex. Our findings suggest that both SNAP-25B mutations impair synaptic exocytosis by destabilizing SNARE assembly, rather than stabilizing SNARE assembly as previously proposed. Therefore, our measurements provide insights into the molecular mechanism of the disease caused by SNARE mutations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Batten's Disease: Determining Educational Interventions.

ERIC Educational Resources Information Center

Johnson, Barbara; Jochum, Julie

1996-01-01

This article presents basic information on the causes, physical and emotional characteristics, diagnosis and treatment, and educational implications of Batten's Disease, a degenerative neurological disorder which strikes children and adults, causes progressive loss of neurological function, and leads to eventual premature death. Discussion also…

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 research necessary to develop better prevention and treatment options. PMID:25658103

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.

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.

Swainsonine-induced lysosomal storage disease in goats caused by the ingestion of Sida rodrigoi Monteiro in North-western Argentina.

PubMed

Micheloud, Juan Francisco; Marin, Raúl; Colque-Caro, Luis Adrián; Martínez, Olga Gladys; Gardner, Dale; Gimeno, Eduardo Juan

2017-03-15

There are numerous poisonous plants that can induce intralysosomal accumulation of glycoproteins and neurologic syndromes. Here we describe for the first time, a disease caused by ingesting Sida rodrigoi Monteiro in goats in North-western Argentina. The animals showed weight loss, indifference to the environment, unsteady gait and ataxia. Histopathologic studies showed vacuolization in cells of various organs, mainly in the CNS. The material deposited in the cells was positive for LCA (Lens culinaris agglutinin), WGA (Triticum vulgaris agglutinin), sWGA (succinyl-Triticum vulgaris agglutinin) and Con-A (Concanavalia ensiformis agglutinin) lectins. Finally, toxic levels of swansonine were identified in the plant. The present investigation allowed to recognize S. rodrigoi Monteiro poisoning as a plant induced α-mannosidosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Advantages and limitations of teleneurology.

PubMed

Wechsler, Lawrence R

2015-03-01

The growing disparity between the demand for neurological services and the need for neurologists requires new and innovative strategies for delivering care. Teleneurology allows neurological expertise to be delivered to remote locations to supplement or replace in-person neurological care. To summarize the current status of teleneurology. Applications of teleneurology include acute care, outpatient teleneurology, and teleconsultations. Existing barriers to further expansion of teleneurology are also discussed. Published studies pertaining to teleneurology were reviewed. Practical experience with telemedicine in neurological practice contributed to the conclusions. Outcomes after intravenous tissue plasminogen activator treatment via telemedicine (telestroke) are similar to those achieved with in-person evaluations. Other aspects of teleneurology are less established but have demonstrated feasibility, high patient satisfaction, and, in some cases, cost savings. Teleneurology provides neurological expertise to rural areas with limited availability of neurologists and improves care for patients with difficulty traveling owing to neurological disease. It is likely that use of teleneurology will continue to grow and become incorporated into many aspects of neurological practice. Understanding the advantages and limitations of teleneurology is vital to delivering optimal clinical care for patients with neurological disease regardless of the setting.

[Headache case that responded to alendronate treatment in Paget's disease].

PubMed

Bozkurt, Dilek; Hiz, Fazilet; Çinar, Meral; Can, Meltem

2012-01-01

Paget's disease of the bone is a chronic, focal skeletal disease characterized by bone pain and deformity, pathological fractures and neurological symptoms such as headache, hearing loss and tinnitus, etc. The frequency of the disease increases in later ages. Viral and genetical factors play a role in the etiology. The majority of cases are asymptomatic. It is often diagnosed with an incidental finding on radiography or with an unexpected high serum alkaline phosphatase level. Bone fractures or neurological complications can negatively affect the quality of life. Early diagnosis and treatment are thus very important. Bisphosphonates are the most frequently used medication in the treatment. We present a case who sought medical help because of headache and was diagnosed as Paget's disease. Neurological complications and the diagnosis and treatment of Paget's disease are reviewed in the literature.

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.

Surgical treatment of neurologic complications of bacterial meningitis in children in Kosovo.

PubMed

Namani, Sadie A; Koci, Remzie A; Kuchar, Ernest; Dedushi, Kreshnike H

2012-04-01

Neurologic complications of bacterial meningitis can occur any time during the course of the disease and some of them need neurosurgical aproach. to determine the incidence of neurologic complications of bacterial meningitis in children requring neurosurgical treatment. a total of 277 children were followed and treated for bacterial meningitis at the Clinic of Infectious Diseases in Prishtina. The authors have analyzed cases who developed acute neurologic complications and treatment procedures. of the 277 children treated for bacterial meningitis, due to the suspicion for neurologic complications, 109 children underwent a head computerized tomography scan. About 47 cases (43%) had evident structural abnormalities while only 15/277 cases (5%) required neurosurgical treatment; 9/38 cases with subdural collections, 5 cases with hydrocephalus and 1 case of spinal abscess. Neurosurgical intervention were not common in pediatric bacterial meningitis cases (5%) but were highly significant in cases complicated with acute neurologic complications (32%).

Bioavailability of curcumin: problems and promises.

PubMed

Anand, Preetha; Kunnumakkara, Ajaikumar B; Newman, Robert A; Aggarwal, Bharat B

2007-01-01

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.

First confirmed case of Powassan neuroinvasive disease in Rhode Island.

PubMed

Patel, Kavin M; Johnson, Jennie; Zacharioudakis, Ioannis M; Boxerman, Jerrold L; Flanigan, Timothy P; Reece, Rebecca M

2018-01-01

The Powassan Virus is the arthropod-borne vector responsible for Powassan neuroinvasive disease. The virus was first isolated in 1958 and has been responsible for approximately 100 cases of neuroinvasive disease. Rates of infection have been on the rise over the past decade with numerous states reporting their first confirmed case; New Jersey, New Hampshire and Connecticut all reported their first case within the last five years. We present here the first confirmed case of Powassan neuroinvasive disease in the nearby state of Rhode Island. A previously healthy 81-year-old female with known tick exposure presented with fever, altered sensorium, seizures and focal neurological deficits. After an extensive work-up that was largely unrevealing Powassan encephalitis was suspected. The diagnosis was confirmed with serological testing consisting of Powassan IgM enzyme-linked immunosorbent assay and Powassan plaque reduction neutralization testing. The case study provides evidence for the increasing spread of Powassan neuroinvasive disease and reinforces the importance of requesting focused testing for Powassan Virus in patients from an endemic area with a clinically compatible syndrome.

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

PubMed

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

2016-05-10

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

[Indications for percutaneous endoscopic gastrostomy in patients with disorders of the nervous system].

PubMed

Ehler, E; Geier, P; Dostál, V; Novotná, A; Vyhnálek, P; Hájek, J; Sákra, L

2002-05-01

Percutaneous endoscopic gastrostomy (PEG) is an efficient endoscopic method that ensures enteral nutrition for a longer period of time in patients who cannot take food per os. This method is also indicated in patients suffering from disorders of the central or peripheral nervous system which developed suddenly, such as a stroke or craniocerebral injuries, or gradually, such as amyotrophic lateral sclerosis (ALS), dementia, and multiple sclerosis. It has become common practice in the cooperation between neurologists and a gastroenterologists to use PEG in patients hospitalized in a neurological ward with encephalomalacy and haemorrhage, or craniocerebral injuries (after the patient recovers from the acute stage of the disease and is transferred to a neurological ICU), as well as in patients with ALS in a progressive stage. We gradually extend the indications of PEG for other patients with neurological disorders such as patients suffering from dementia, progressive multiple sclerosis, Parkinson's disease, and progressive polyneuropathy. Of 62 patients hospitalized in a neurological ward during a period of 4.5 years, 56 patients suffered from sudden disorders of the nervous system (strokes and craniocerebral injuries) and 6 patients had gradually progressing neurological diseases (ALS, multiple sclerosis, Parkinson's disease, dementia, and polyneuropathy).

Adult human neural stem cell therapeutics: Current developmental status and prospect.

PubMed

Nam, Hyun; Lee, Kee-Hang; Nam, Do-Hyun; Joo, Kyeung Min

2015-01-26

Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as cell therapeutics for neurological disease. Compared with other types of stem cells, aNSCs have clinical advantages, such as limited proliferation, inborn differentiation potential into functional neural cells, and no ethical issues. In spite of the merits of aNSCs, difficulties in the isolation from the normal brain, and in the in vitro expansion, have blocked preclinical and clinical study using aNSCs. However, several groups have recently developed novel techniques to isolate and expand aNSCs from normal adult brains, and showed successful applications of aNSCs to neurological diseases. With new technologies for aNSCs and their clinical strengths, previous hurdles in stem cell therapies for neurological diseases could be overcome, to realize clinically efficacious regenerative stem cell therapeutics.

The emerging link between O-GlcNAcylation and neurological disorders.

PubMed

Ma, Xiaofeng; Li, He; He, Yating; Hao, Junwei

2017-10-01

O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is involved in the regulation of many cellular cascades and neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In the brain, the expression of O-GlcNAcylation is notably heightened, as is that of O-linked N-acetylglucosaminyltransferase (OGT) and β-N-acetylglucosaminidase (OGA), the presence of which is prominent in many regions of neurological importance. Most importantly, O-GlcNAcylation is believed to contribute to the normal functioning of neurons; conversely, its dysregulation participates in the pathogenesis of neurological disorders. In neurodegenerative diseases, O-GlcNAcylation of the brain's key proteins, such as tau and amyloid-β, interacts with their phosphorylation, thereby triggering the formation of neurofibrillary tangles and amyloid plaques. An increase of O-GlcNAcylation by pharmacological intervention prevents neuronal loss. Additionally, O-GlcNAcylation is stress sensitive, and its elevation is cytoprotective. Increased O-GlcNAcylation ameliorated brain damage in victims of both trauma-hemorrhage and stroke. In this review, we summarize the current understanding of O-GlcNAcylation's physiological and pathological roles in the nervous system and provide a foundation for development of a therapeutic strategy for neurological disorders.

Functional (Psychogenic) Cognitive Disorders: A Perspective from the Neurology Clinic.

PubMed

Stone, Jon; Pal, Suvankar; Blackburn, Daniel; Reuber, Markus; Thekkumpurath, Parvez; Carson, Alan

2015-09-24

Cognitive symptoms such as poor memory and concentration represent a common cause of morbidity among patients presenting to general practitioners and may result in referral for a neurological opinion. In many cases, these symptoms do not relate to an underlying neurological disease or dementia. In this article we present a personal perspective on the differential diagnosis of cognitive symptoms in the neurology clinic, especially as this applies to patients who seek advice about memory problems but have no neurological disease process. These overlapping categories include the following 'functional' categories: 1) cognitive symptoms as part of anxiety or depression; 2) "normal" cognitive symptoms that become the focus of attention; 3) isolated functional cognitive disorder in which symptoms are outwith 'normal' but not explained by anxiety; 4) health anxiety about dementia; 5) cognitive symptoms as part of another functional disorder; and 6) retrograde dissociative (psychogenic) amnesia. Other 'non-dementia' diagnoses to consider in addition are 1) cognitive symptoms secondary to prescribed medication or substance misuse; 2) diseases other than dementia causing cognitive disorders; 3) patients who appear to have functional cognitive symptoms but then go on to develop dementia/another neurological disease; and finally 4) exaggeration/malingering. We discuss previous attempts to classify the problem of functional cognitive symptoms, the importance of making a positive diagnosis for the patient, and the need for large cohort studies to better define and manage this large group of patients.

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.

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 much must be extrapolated from adult data. A high index of suspicion for acquired thyroid disease is paramount in the investigation of many neurological disorders of youth, as many reported sequelae of hypothyroidism and hyperthyroidism are reversible with appropriate endocrine management. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

[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 good, although the optimal antimicrobial regimen is not clearly established. Initial parenteral therapy (tetracycline, penicilline, streptomycine, chloramphenicol, ampicilline) and peroral long-term treatment with trimetoprime-sulphametoxasole, are recommended. As CNS relapse of Whipple's disease may occur after several years, long-term treatment should include antibiotics that are able to cross the blood-brain barrier. The CNS relapse, in contrast to the systemic ones, is resistant to the treatment. Appropriate therapy instituted earlier in the course of the disease is associated with a better neurological outcome. Early recognition can be critical in Whipple's disease because of irreversible neurological sequelae seen later in the course of this potentially treatable condition. In cases with high clinical suspicion in which Whipple's disease cannot be diagnosed with procedures such as jejunal biopsy, antibiotic therapy is recommended. Recovery of an established neurological deficit may rarely occur. Longterm follow-up studies would help to identify the optimal antibiotic regimen and duration of treatment.

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.

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

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.

The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders

PubMed Central

Stafstrom, Carl E.; Rho, Jong M.

2012-01-01

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

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.

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

Medical treatment with thiamine, coenzyme Q, vitamins E and C, and carnitine improved obstructive sleep apnea in an adult case of Leigh disease.

PubMed

Mermigkis, Charalampos; Bouloukaki, Izolde; Mastorodemos, Vasileios; Plaitakis, Andreas; Alogdianakis, Vangelis; Siafakas, Nikolaos; Schiza, Sophia

2013-12-01

The multi-organ involvement of mitochondrial diseases means that patients are likely to be more vulnerable to sleep disturbances. We aimed to assess if early recognition and treatment of obstructive sleep apnea (OSA) in patients with Leigh disease may influence primary disease outcome. We describe a case of adult-onset Leigh disease presenting as severe brainstem encephalopathy of subacute onset. Based on the clinical symptoms that developed after the appearance of the neurological disease, an attended overnight polysomnography examination was performed. A marked clinical recovery was seen after administration of high doses of thiamine, coenzyme Q, L-carnitine, and vitamins C and E, combined with effective treatment with continuous positive airway pressure for the underlying severe obstructive sleep apnea (OSA). The latter condition was diagnosed on the basis of suggestive symptoms that appeared a few weeks before the establishment of the neurological disease. The improvement in the neurological disease (based on clinical and brain MRI features) with the appropriate medical treatment also resulted in a significant improvement in the OSA. Early recognition and treatment of sleep apnea may not only improve sleep and overall quality of life but also ameliorate the deleterious effects of nocturnal desaturations on the neurological features. This may be crucial for disease outcome when added to the generally advised pharmacological therapy.

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.

CNS Diseases and Uveitis

PubMed Central

Allegri, Pia; Rissotto, Roberto; Herbort, Carl P.; Murialdo, Ugo

2011-01-01

A number of inflammatory, infectious, neoplastic and idiopathic disorders affect the eye and the central nervous system (CNS) concurrently or at different time frames. These conditions pose a diagnostic challenge to the clinician since they may present with similar ocular and neurological manifestations. The purpose of this review is to describe major neurological syndromes including multiple sclerosis, Vogt-Koyanagi-Harada disease, other autoimmune syndromes, and several infectious diseases which may affect the eye. This article may serve as a guide for the diagnosis and treatment of such disorders. It should be noted that these conditions have been viewed from a neurologist’s perspective thereby neurologic involvement is stressed. PMID:22454751

Illuminating Neural Circuits: From Molecules to MRI.

PubMed

Lee, Jin Hyung; Kreitzer, Anatol C; Singer, Annabelle C; Schiff, Nicholas D

2017-11-08

Neurological disease drives symptoms through pathological changes to circuit functions. Therefore, understanding circuit mechanisms that drive behavioral dysfunction is of critical importance for quantitative diagnosis and systematic treatment of neurological disease. Here, we describe key technologies that enable measurement and manipulation of neural activity and neural circuits. Applying these approaches led to the discovery of circuit mechanisms underlying pathological motor behavior, arousal regulation, and protein accumulation. Finally, we discuss how optogenetic functional magnetic resonance imaging reveals global scale circuit mechanisms, and how circuit manipulations could lead to new treatments of neurological diseases. Copyright © 2017 the authors 0270-6474/17/3710817-09$15.00/0.

Nuclear speckles: molecular organization, biological function and role in disease

PubMed Central

Galganski, Lukasz; Urbanek, Martyna O.

2017-01-01

Abstract The nucleoplasm is not homogenous; it consists of many types of nuclear bodies, also known as nuclear domains or nuclear subcompartments. These self-organizing structures gather machinery involved in various nuclear activities. Nuclear speckles (NSs) or splicing speckles, also called interchromatin granule clusters, were discovered as sites for splicing factor storage and modification. Further studies on transcription and mRNA maturation and export revealed a more general role for splicing speckles in RNA metabolism. Here, we discuss the functional implications of the localization of numerous proteins crucial for epigenetic regulation, chromatin organization, DNA repair and RNA modification to nuclear speckles. We highlight recent advances suggesting that NSs facilitate integrated regulation of gene expression. In addition, we consider the influence of abundant regulatory and signaling proteins, i.e. protein kinases and proteins involved in protein ubiquitination, phosphoinositide signaling and nucleoskeletal organization, on pre-mRNA synthesis and maturation. While many of these regulatory proteins act within NSs, direct evidence for mRNA metabolism events occurring in NSs is still lacking. NSs contribute to numerous human diseases, including cancers and viral infections. In addition, recent data have demonstrated close relationships between these structures and the development of neurological disorders. PMID:28977640

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…

Serum BAFF levels, Methypredsinolone therapy, Epstein-Barr Virus and Mycobacterium avium subsp. paratuberculosis infection in Multiple Sclerosis patients.

PubMed

Mameli, Giuseppe; Cocco, Eleonora; Frau, Jessica; Arru, Giannina; Caggiu, Elisa; Marrosu, Maria Giovanna; Sechi, Leonardo A

2016-07-07

Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease.

Inflammasomes link vascular disease with neuroinflammation and brain disorders

PubMed Central

Lénárt, Nikolett; Brough, David

2016-01-01

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

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.

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.

[Multiple bladder diverticula caused by occipital horn syndrome].

PubMed

Legros, L; Revencu, N; Nassogne, M-C; Wese, F-X; Feyaerts, A

2015-11-01

We report on the case of a child who presented with recurrent, multiple, and voluminous bladder diverticula. Bladder diverticula are defined as a herniation of the mucosa through the bladder muscle or the detrusor. Causes are numerous and diverticula can be classified into primary congenital diverticula (para-ureteral - or Hutch diverticula - and posterolateral diverticula); secondary diverticula (resulting from chronic mechanical obstruction or from neurological disease; and diverticula secondary to connective tissue or muscle fragility. The latter is seen in disease entities such as prune belly syndrome, Ehlers-Danlos syndrome, cutis laxa syndrome, OHS (occipital horn syndrome), Menkes disease, and Williams-Beuren syndrome. In this patient, the cause of these diverticula was OHS, a genetic, recessive X-chromosome-linked syndrome, responsible for abnormal tissue caused by a disorder in copper metabolism. This case reminds us of the importance of pushing the diagnostic workup when presented with multiple and/or large bladder diverticula, and in particular to search for rare malformation syndromes after exclusion of an obstacle. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Applied Neuroanatomy Elective to Reinforce and Promote Engagement with Neurosensory Pathways Using Interactive and Artistic Activities

ERIC Educational Resources Information Center

Dao, Vinh; Yeh, Pon-Hsiu; Vogel, Kristine S.; Moore, Charleen M.

2015-01-01

One in six Americans is currently affected by neurologic disease. As the United States population ages, the number of neurologic complaints is expected to increase. Thus, there is a pressing need for more neurologists as well as more neurology training in other specialties. Often interest in neurology begins during medical school, so improving…

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.

Developing Gene Silencing for the Study and Treatment of Dystonia

DTIC Science & Technology

2015-11-01

cause abnormal twisting postures. DYT1 dystonia is an autosomal dominant disease with onset of dystonia during childhood . The most common early onset...SUPPLEMENTARY NOTES 14. ABSTRACT Dystonia is a debilitating neurological disease with no cure. In dystonia, there are involuntary muscle contractions that...is a debilitating neurological disease with no cure that is characterized by involuntary muscle contractions that cause abnormal twisting postures

Acquired toxoplasmosis. A neglected cause of treatable nervous system disease.

PubMed

Townsend, J J; Wolinsky, J S; Baringer, J R; Johnson, P C

1975-05-01

The neurological manifestations of six cases of acquired central nervous system toxoplasmosis are compared with the 39 well-documented cases from the literature. Half of the patients had underlying systemic diseases (18 malignant neoplasms, two renal transplants, three collagen vascular diseases) treated with intensive immunosuppressive therapy. The remainder had primary toxoplasmosis. Three major neurological patterns were seen: (1) diffuse encephalopathy with or without seizures, (2) meningoencephalitis, and (3) singular or multiple progressive mass lesions. Routine neurological diagnostic studies were not helpful. The Sabin-Feldman dye test or IgM indirect fluorescent antibody test or both were effective in confirming the diagnosis. Twenty-seven patients died without a clinical diagnosis of toxoplasmosis. The diagnosis was made terminally in four additional patients. Thirteen of fourteen patients who received a full course of sulfadiazine or pyrimethamine or both did well. Toxoplasmosis should be considered in the immunosuppressed patient who appears with neurological involvement.

Neurologic Involvement in Scleroderma en Coup de Sabre

PubMed Central

Amaral, Tiago Nardi; Marques Neto, João Francisco; Lapa, Aline Tamires; Peres, Fernando Augusto; Guirau, Caio Rodrigues; Appenzeller, Simone

2012-01-01

Localized scleroderma is a rare disease, characterized by sclerotic lesions. A variety of presentations have been described, with different clinical characteristics and specific prognosis. In scleroderma en coup de sabre (LScs) the atrophic lesion in frontoparietal area is the disease hallmark. Skin and subcutaneous are the mainly affected tissues, but case reports of muscle, cartilage, and bone involvement are frequent. These cases pose a difficult differential diagnosis with Parry-Romberg syndrome. Once considered an exclusive cutaneous disorder, the neurologic involvement present in LScs has been described in several case reports. Seizures are most frequently observed, but focal neurologic deficits, movement disorders, trigeminal neuralgia, and mimics of hemiplegic migraines have been reported. Computed tomography and magnetic resonance imaging have aided the characterization of central nervous system lesions, and cerebral angiograms have pointed to vasculitis as a part of disease pathogenesis. In this paper we describe the clinical and radiologic aspects of neurologic involvement in LScs. PMID:22319646

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.

Can a low-cost webcam be used for a remote neurological exam?

PubMed

Wood, Jeffrey; Wallin, Mitchell; Finkelstein, Joseph

2013-01-01

Multiple sclerosis (MS) is a demyelinating and axonal degenerative disease of the central nervous system. It is the most common progressive neurological disorder of young adults affecting over 1 million persons worldwide. Despite the increased use of neuroimaging and other tools to measure MS morbidity, the neurological examination remains the primary method to document relapses and progression in disease. The goal of this study was to demonstrate the feasibility and validity of using a low-cost webcam for remote neurological examination in home-setting for patients with MS. Using cross-over design, 20 MS patients were evaluated in-person and via remote televisit and results of the neurological evaluation were compared. Overall, we found that agreement between face-to-face and remote EDSS evaluation was sufficient to provide clinically valid information. Another important finding of this study was high acceptance of patients and their providers of using remote televisits for conducting neurological examinations at MS patient homes. The results of this study demonstrated potential of using low-cost webcams for remote neurological exam in patients with MS.

[Neuropediatrics: epidemiological features and etiologies at the Dakar neurology service].

PubMed

Ndiaye, M; Sene-Diouf, F; Diop, A G; Ndao, A K; Ndiaye, M M; Ndiaye, I P

1999-01-01

Child neurology is a relatively young speciality of neurosciences which is at the frontier of Neurology and Paediatrics. Its development has been impulsed by the diagnosis techniques such as Neurobiology, Genetics, Neuroimaging and pedo-psychology. We conducted a retrospective survey among the in-patients from January 1980 to December 1997 in the service of Neurology of the University Hospital. Have been included children ranged from 0 to 15 years old without any racial, sexual or origin distinctive. In Neurology Department, children of 0 to 15 years old represent 10.06% of the in-patients received from 1980 to 1997. The mortality rate was 9.23%. The diseases are dominated by epilepsy and infantile encephalopathies with 31.02%, infectious diseases with 19.36% represented by tuberculosis, other bacterial, viral and parasitical etiologies, tumors with 10.36%, vascular pathology and degenerative disorders.

Neuropharmacological Potential and Delivery Prospects of Thymoquinone for Neurological Disorders

PubMed Central

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

2018-01-01

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

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.

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.

[Effects of a physical training program on quantitative neurological indices in mild stage type 2 spinocerebelar ataxia patients].

PubMed

Pérez-Avila, I; Fernández-Vieitez, J A; Martínez-Góngora, E; Ochoa-Mastrapa, R; Velázquez-Manresa, M G

Type 2 spinocerebelar ataxia (SCA2) is a neurodegenerative disease with higher prevalence and incidence in Holguín province, Cuba. At present, there is not any drug to counteract the loss of coordinative motor capacities of these patients. Thus physical training seems to be the only way to attenuate the course of disease. To evaluate the effectiveness of a physical training program on quantitative neurological indices in SCA2 patients. A samples of 87 SCA2 patients were studied. All subjects underwent a six month physical exercise program based on coordination, balance and muscular conditioning exercises. Quantitative tests were applied to all patients both before and after the application of the exercise program. Comparisons between pretest versus posttest values were made to evaluate the improvement in neurological indices. All neurological indices both with open eyes and closed eyes significantly improved from pretest to posttest. Static balance, evaluated by Romberg test, also enhanced with training. The exercise training program significantly improved the neurological indices in SCA2 patient with mild stage of disease.

Genetic disorders of thyroid metabolism and brain development

PubMed Central

Kurian, Manju A; Jungbluth, Heinz

2014-01-01

Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic ‘brain-thyroid’ disorders. PMID:24665922

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

PubMed

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

2003-01-01

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

Collagen XVII: A Shared Antigen in Neurodermatological Interactions?

PubMed Central

2013-01-01

Collagen XVII is a nonfibril-forming transmembrane collagen, which functions as both a matrix protein and a cell-surface receptor. It is particularly copious in the skin, where it is known to be a structural component of hemidesmosomes. In addition, collagen XVII has been found to be present in the central nervous system, thus offering an explanation for the statistical association between bullous pemphigoid, in which autoimmunity is directed against dermal collagen XVII, and neurological diseases. In support of the hypothesis that collagen XVII serves as a shared antigen mediating an immune response between skin and brain, research on animal and human tissue, as well as numerous epidemiological and case studies, is presented. PMID:23878581

Challenges and new strategies for therapeutic peptide delivery to the CNS.

PubMed

McGowan, Jeremy Wd; Bidwell, Gene L; Vig, Parminder Js

2015-07-01

Therapeutic peptides represent a largely untapped resource in medicine today, especially in the central nervous system. Despite their ease of design and remarkably high target specificity, it is difficult to deliver them beyond the blood-brain barrier or into the required intracellular compartments. In addition, the instability of these peptides in vivo precludes their use to combat the symptoms of numerous neurological disorders including Alzheimer's disease and spinocerebellar ataxia. In this review, we aim to characterize recent advances in the delivery of therapeutic peptides to the central nervous system past the blood-brain barrier and discuss the advantages and disadvantages of the examined methods as well as explore new potential directions.

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.

The Role of the Immune System in Triplet Repeat Expansion Diseases

PubMed Central

Urbanek, Martyna O.; Krzyzosiak, Wlodzimierz J.

2015-01-01

Trinucleotide repeat expansion disorders (TREDs) are a group of dominantly inherited neurological diseases caused by the expansion of unstable repeats in specific regions of the associated genes. Expansion of CAG repeat tracts in translated regions of the respective genes results in polyglutamine- (polyQ-) rich proteins that form intracellular aggregates that affect numerous cellular activities. Recent evidence suggests the involvement of an RNA toxicity component in polyQ expansion disorders, thus increasing the complexity of the pathogenic processes. Neurodegeneration, accompanied by reactive gliosis and astrocytosis is the common feature of most TREDs, which may suggest involvement of inflammation in pathogenesis. Indeed, a number of immune response markers have been observed in the blood and CNS of patients and mouse models, and the activation of these markers was even observed in the premanifest stage of the disease. Although inflammation is not an initiating factor of TREDs, growing evidence indicates that inflammatory responses involving astrocytes, microglia, and the peripheral immune system may contribute to disease progression. Herein, we review the involvement of the immune system in the pathogenesis of triplet repeat expansion diseases, with particular emphasis on polyglutamine disorders. We also present various therapeutic approaches targeting the dysregulated inflammation pathways in these diseases. PMID:25873774

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.

[Future directions of neurology - breakthrough to the next stage ].

PubMed

Tsuji, Shoji

2010-11-01

The 51st Annual Meeting of the Japanese Society of Neurology was held in Tokyo (Tokyo International Forum) from Thursday, May 20 to Saturday, May 22, 2010 with as many as 5,471 attendants. Our Society has been celebrating its 50th anniversary during the period from 2009 through 2010. At the 51st Annual Meeting in 2010, we looked toward the future, as we celebrate our 50th anniversary together with distinguished guests closely related to our Society. The theme for the 51st Annual Meeting was set as "Future of Neurology-Breakthrough to the next stage-." As represented in the theme, I hope that the Annual Meeting provided an excellent opportunity for all of us to look ahead to the future of Neurology and our Society in the next half-century. We have achieved tremendous advances in better understanding neurological diseases and developing more efficacious treatment over the last half century. Great strides have been made in all areas, of which diagnostic imaging, molecular genetics, immunology and physiology are just a few examples, and understanding of diseases has similarly taken a great leap forward. In Japan, the aging of society coupled with the declining birthrate has placed ever-increasing expectations on neurologists to provide better care for dementia, cerebrovascular disorders and neurodegenerative diseases. Given this situation our Society is required to provide outstanding education in both the pre- and post-graduate context, and, furthermore, to ensure that excellent training programs are available for young neurologists preparing for Board certification. Looking towards the future of neurology, we should continue to anticipate new, ground-breaking achievements for better understanding neurological diseases and establishing more effective treatment through our ongoing endeavors.

Predictors of neurologic and nonneurologic death in patients with brain metastasis initially treated with upfront stereotactic radiosurgery without whole-brain radiation therapy

PubMed Central

Johnson, Adam G.; Ruiz, Jimmy; Isom, Scott; Lucas, John T.; Hinson, William H.; Watabe, Kounosuke; Laxton, Adrian W.; Tatter, Stephen B.; Chan, Michael D.

2017-01-01

Abstract Background. In this study we attempted to discern the factors predictive of neurologic death in patients with brain metastasis treated with upfront stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) while accounting for the competing risk of nonneurologic death. Methods. We performed a retrospective single-institution analysis of patients with brain metastasis treated with upfront SRS without WBRT. Competing risks analysis was performed to estimate the subdistribution hazard ratios (HRs) for neurologic and nonneurologic death for predictor variables of interest. Results. Of 738 patients treated with upfront SRS alone, neurologic death occurred in 226 (30.6%), while nonneurologic death occurred in 309 (41.9%). Multivariate competing risks analysis identified an increased hazard of neurologic death associated with diagnosis-specific graded prognostic assessment (DS-GPA) ≤ 2 (P = .005), melanoma histology (P = .009), and increased number of brain metastases (P<.001), while there was a decreased hazard associated with higher SRS dose (P = .004). Targeted agents were associated with a decreased HR of neurologic death in the first 1.5 years (P = .04) but not afterwards. An increased hazard of nonneurologic death was seen with increasing age (P =.03), nonmelanoma histology (P<.001), presence of extracranial disease (P<.001), and progressive systemic disease (P =.004). Conclusions. Melanoma, DS-GPA, number of brain metastases, and SRS dose are predictive of neurologic death, while age, nonmelanoma histology, and more advanced systemic disease are predictive of nonneurologic death. Targeted agents appear to delay neurologic death. PMID:27571883

Management of melanoma brain metastases in the era of targeted therapy.

PubMed

Shapiro, Daniela Gonsalves; Samlowski, Wolfram E

2011-01-01

Disseminated metastatic disease, including brain metastases, is commonly encountered in malignant melanoma. The classical treatment approach for melanoma brain metastases has been neurosurgical resection followed by whole brain radiotherapy. Traditionally, if lesions were either too numerous or surgical intervention would cause substantial neurologic deficits, patients were either treated with whole brain radiotherapy or referred to hospice and supportive care. Chemotherapy has not proven effective in treating brain metastases. Improvements in surgery, radiosurgery, and new drug discoveries have provided a wider range of treatment options. Additionally, recently discovered mutations in the melanoma genome have led to the development of "targeted therapy." These vastly improved options are resulting in novel treatment paradigms for approaching melanoma brain metastases in patients with and without systemic metastatic disease. It is therefore likely that improved survival can currently be achieved in at least a subset of melanoma patients with brain metastases.

Growth of Malignant Non-CNS Tumors Alters Brain Metabolome

PubMed Central

Kovalchuk, Anna; Nersisyan, Lilit; Mandal, Rupasri; Wishart, David; Mancini, Maria; Sidransky, David; Kolb, Bryan; Kovalchuk, Olga

2018-01-01

Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as “tumor brain.” Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon. PMID:29515623

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-07-15

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

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. Focal paresis was evident in 23 of 57 (40%) at presentation and was the most common persisting clinical and functional problem at 12 months (observed in 5 of 6 patients), with 1 patient also requiring invasive ventilation. Patients initially seen with acute flaccid paralysis or pulmonary edema had significantly greater frequencies of motor dysfunction at follow-up compared with patients initially seen with other syndromes (odds ratio, 15; 95% CI, 3-79; P < .001). Enterovirus 71 may cause serious neurological disease in young patients. The distinct clinicoradiological syndromes, predominantly within the spinal cord and brainstem, enable rapid recognition within evolving outbreaks. Long-term functional neurological morbidity is associated with paresis linked to involvement of gray matter in the brainstem or spinal cord.

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.

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 CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value.

[Advanced Parkinson's disease: clinical characteristics and treatment (part 1)].

PubMed

Kulisevsky, J; Luquin, M R; Arbelo, J M; Burguera, J A; Carrillo, F; Castro, A; Chacón, J; García-Ruiz, P J; Lezcano, E; Mir, P; Martinez-Castrillo, J C; Martínez-Torres, I; Puente, V; Sesar, A; Valldeoriola-Serra, F; Yañez, R

2013-10-01

A large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease. To define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. This consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

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.

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.

[Anaesthesia in patients with maple syrup urine disease. Case report and perioperative anaesthetic management].

PubMed

Haberstich, P; Kindler, C H; Schürch, M

2010-10-01

Maple syrup urine disease is a rare autosomal-recessive metabolic disorder caused by a deficit of oxidative decarboxylation of branched-chain amino acids. First symptoms appear in the neonatal period. Without treatment the disease is characterized by rapid progression of neurological symptoms. During stressful situations, such as infection or surgery, patients may experience severe ketoacidosis, rapid neurological deterioration and hypoglycemia. The perioperative management of a 26-year-old man with maple syrup urine disease is described, a review of the disease is given and anaesthesia-related implications are discussed.

Poor Beard!! Charcot's internationalization of neurasthenia, the "American disease".

PubMed

Goetz, C G

2001-08-14

To analyze the role of the seminal 19th-century neurologist, Jean-Martin Charcot, in the internationalization of neurasthenia, previously known as "the American disease." The New York neurologist, George Beard, first described neurasthenia in 1869 and considered it a disorder related to the particular stress of modern civilization, most typified in the United States. Charcot's personal files on neurasthenia from the Bibliothèque Charcot, Salpêtrière Hospital, Paris, were studied and his teaching lessons and lectures were examined. Charcot presented numerous cases of neurasthenia, always crediting Beard with the original name and description. Calling Beard's 1880 work a "remarkable monograph," Charcot emphasized that patients with neurasthenia also comprised the bulk of his own private practice. Focusing on the signs of sexual impotency, fatigue, and a tight band of pressure around the head, Charcot categorically distinguished patients with neurasthenica from patients with hysteria. Like Beard, Charcot concluded that the origin of neurasthenia was psychological stress and felt the European society also fostered the environment to precipitate the disease. Charcot adamantly opposed extrapolations that called for early childhood educational reforms to reduce current classroom stress. Charcot sympathized more with the treating physician than the patient, calling neurasthenics insufferable (insupportables). On the front sheet of his neurasthenia file, he wrote in large script, "Poor Beard!!" By emphasizing the prevalence of neurasthenia and extending Beard's observations, Charcot internationally legitimized the new diagnosis. Adding neurasthenia to the other neurologic descriptions from the United States by Hammond, Mitchell, and Dana, Charcot helped to foster the recognition of the American Neurologic School.

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.

Biobanking of CSF: international standardization to optimize biomarker development.

PubMed

Teunissen, Charlotte E; Tumani, Hayrettin; Engelborghs, Sebastiaan; Mollenhauer, Brit

2014-03-01

Cerebrospinal fluid (CSF) reflects pathophysiological aspects of neurological diseases, where neuroprotective strategies and biomarkers are urgently needed. Therefore, biobanking is very relevant for biomarker discovery and evaluation of neurological diseases. Important and unique features of CSF biobanking are intensive collaboration in international networks and the tight application of standardized protocols. The current adoption of standardized protocols for CSF and blood collection as presented in this review enables biomarker studies in large cohorts of patients and controls. Another topic of this review is the selection of control groups, which influences the outcome of biomarker investigations. Control groups in CSF biobanks mainly consist of different disease controls. This is in part due to the fact that lumbar punctures are mostly performed for clinical indications and rarely for research purposes only, as it is a relatively invasive procedure. Moreover, there is a lack of homogenous criteria and definition of control groups. We therefore propose uniform consensus definitions for such control groups in biomarker research, i.e. Healthy controls (HC), Spinal anesthesia subjects (SAS), Symptomatic controls (SC), Inflammatory Neurological Disease Controls (CINDC), Peripheral Inflammatory Neurological Disease Controls (PINDC) and Non-inflammatory Neurological Disease Controls (NINDC). Another important aspect of CSF biobanking is quality control. Systematic studies to address effects of pre-analytical and storage variation on a broad range of CSF proteins are needed. In conclusion, biomarker research in neurodegenerative diseases has entered a new era due to the collaborative and multicenter efforts of many groups. The streamlining of biobanking procedures, including quality control, and the selection of optimal control groups for investigating biomarkers are important improvements to perform high quality biomarker studies. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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 among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data. Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years.

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.

[Can music therapy for patients with neurological disorders?].

PubMed

Myskja, Audun

2004-12-16

Recent developments in brain research and in the field of music therapy have led to the development of music-based methods specifically aimed at relieving symptoms of Parkinson's disease and other neurologic disorders. Rhythmic auditory stimulation uses external rhythmic auditory cues from song, music or metronome to aid patients improving their walking functioning and has been shown to be effective both within sessions and as a result of training over time. Melodic intonation therapy and related vocal techniques can improve expressive dysphasia and aid rehabilitation of neurologic disorders, particularly Parkinson's disease, stroke and developmental disorders.

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.

Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms

PubMed Central

Ishibashi, Hidetoshi; Minakawa, Eiko N.; Motohashi, Hideyuki H.; Takayama, Osamu; Popiel, H. Akiko; Puentes, Sandra; Owari, Kensuke; Nakatani, Terumi; Nogami, Naotake; Yamamoto, Kazuhiro; Yonekawa, Takahiro; Tanaka, Yoko; Fujita, Naoko; Suzuki, Hikaru; Aizawa, Shu; Nagano, Seiichi; Yamada, Daisuke; Wada, Keiji; Kohsaka, Shinichi

2017-01-01

Abstract Age-associated neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3–4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases. PMID:28374014

[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.

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.

The MiRNA Journey from Theory to Practice as a CNS Biomarker.

PubMed

Stoicea, Nicoleta; Du, Amy; Lakis, D Christie; Tipton, Courtney; Arias-Morales, Carlos E; Bergese, Sergio D

2016-01-01

MicroRNAs (miRNAs), small nucleotide sequences that control gene transcription, have the potential to serve an expanded function as indicators in the diagnosis and progression of neurological disorders. Studies involving debilitating neurological diseases such as, Alzheimer's disease, multiple sclerosis, traumatic brain injuries, Parkinson's disease and CNS tumors, already provide validation for their clinical diagnostic use. These small nucleotide sequences have several features, making them favorable candidates as biomarkers, including function in multiple tissues, stability in bodily fluids, a role in pathogenesis, and the ability to be detected early in the disease course. Cerebrospinal fluid, with its cell-free environment, collection process that minimizes tissue damage, and direct contact with the brain and spinal cord, is a promising source of miRNA in the diagnosis of many neurological disorders. Despite the advantages of miRNA analysis, current analytic technology is not yet affordable as a clinically viable diagnostic tool and requires standardization. The goal of this review is to explore the prospective use of CSF miRNA as a reliable and affordable biomarker for different neurological disorders.

The MiRNA Journey from Theory to Practice as a CNS Biomarker

PubMed Central

Stoicea, Nicoleta; Du, Amy; Lakis, D. Christie; Tipton, Courtney; Arias-Morales, Carlos E.; Bergese, Sergio D.

2016-01-01

MicroRNAs (miRNAs), small nucleotide sequences that control gene transcription, have the potential to serve an expanded function as indicators in the diagnosis and progression of neurological disorders. Studies involving debilitating neurological diseases such as, Alzheimer's disease, multiple sclerosis, traumatic brain injuries, Parkinson's disease and CNS tumors, already provide validation for their clinical diagnostic use. These small nucleotide sequences have several features, making them favorable candidates as biomarkers, including function in multiple tissues, stability in bodily fluids, a role in pathogenesis, and the ability to be detected early in the disease course. Cerebrospinal fluid, with its cell-free environment, collection process that minimizes tissue damage, and direct contact with the brain and spinal cord, is a promising source of miRNA in the diagnosis of many neurological disorders. Despite the advantages of miRNA analysis, current analytic technology is not yet affordable as a clinically viable diagnostic tool and requires standardization. The goal of this review is to explore the prospective use of CSF miRNA as a reliable and affordable biomarker for different neurological disorders. PMID:26904099

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.

Japanese encephalitis virus infection, diagnosis and control in domestic animals.

PubMed

Mansfield, Karen L; Hernández-Triana, Luis M; Banyard, Ashley C; Fooks, Anthony R; Johnson, Nicholas

2017-03-01

Japanese encephalitis virus (JEV) is a significant cause of neurological disease in humans throughout Asia causing an estimated 70,000 human cases each year with approximately 10,000 fatalities. The virus contains a positive sense RNA genome within a host-derived membrane and is classified within the family Flaviviridae. Like many flaviviruses, it is transmitted by mosquitoes, particularly those of the genus Culex in a natural cycle involving birds and some livestock species. Spill-over into domestic animals results in a spectrum of disease ranging from asymptomatic infection in some species to acute neurological signs in others. The impact of JEV infection is particularly apparent in pigs. Although infection in adult swine does not result in symptomatic disease, it is considered a significant reproductive problem causing abortion, still-birth and birth defects. Infected piglets can display fatal neurological disease. Equines are also infected, resulting in non-specific signs including pyrexia, but occasionally leading to overt neurological disease that in extreme cases can lead to death. Veterinary vaccination is available for both pigs and horses. This review of JEV disease in livestock considers the current diagnostic techniques available for detection of the virus. Options for disease control and prevention within the veterinary sector are discussed. Such measures are critical in breaking the link to zoonotic transmission into the human population where humans are dead-end hosts. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Neuropeptide Y Has a Protective Role during Murine Retrovirus-Induced Neurological Disease▿

PubMed Central

Du, Min; Butchi, Niranjan B.; Woods, Tyson; Morgan, Timothy W.; Peterson, Karin E.

2010-01-01

Viral infections in the central nervous system (CNS) can lead to neurological disease either directly by infection of neurons or indirectly through activation of glial cells and production of neurotoxic molecules. Understanding the effects of virus-mediated insults on neuronal responses and neurotrophic support is important in elucidating the underlying mechanisms of viral diseases of the CNS. In the current study, we examined the expression of neurotrophin- and neurotransmitter-related genes during infection of mice with neurovirulent polytropic retrovirus. In this model, virus-induced neuropathogenesis is indirect, as the virus predominantly infects macrophages and microglia and does not productively infect neurons or astrocytes. Virus infection is associated with glial cell activation and the production of proinflammatory cytokines in the CNS. In the current study, we identified increased expression of neuropeptide Y (NPY), a pleiotropic growth factor which can regulate both immune cells and neuronal cells, as a correlate with neurovirulent virus infection. Increased levels of Npy mRNA were consistently associated with neurological disease in multiple strains of mice and were induced only by neurovirulent, not avirulent, virus infection. NPY protein expression was primarily detected in neurons near areas of virus-infected cells. Interestingly, mice deficient in NPY developed neurological disease at a faster rate than wild-type mice, indicating a protective role for NPY. Analysis of NPY-deficient mice indicated that NPY may have multiple mechanisms by which it influences virus-induced neurological disease, including regulating the entry of virus-infected cells into the CNS. PMID:20702619

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

[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.

[Neuro-neutrophilic Disease and Dementia].

PubMed

Hisanaga, Kinya

2016-04-01

Neuro-neutrophilic diseases are multisystem inflammatory disorders that include neuro-Behçet and neuro-Sweet disease. These disorders ectopically damage the nervous system due to the abnormal chemotaxis of neutrophils. The neutrophils' chemotaxis is induced by oral muco-cutaneous bacterial infections and the dysregulation of cytokines, including interleukins. The frequencies of human leukocyte antigen (HLA)-B51 in neuro-Behçet disease and HLA-B54 as well as Cw1 in neuro-Sweet disease significantly higher than the levels present in Japanese normal controls. Notably, their frequencies are also higher in patients exhibiting neurological complications than in patients without neurological complications. These HLA types are considered risk factors that are directly related to the etiology of these diseases. Prednisolone and colchicine, which suppress neutrophil activation, are used to treat the acute phase of both diseases. Alternatively, dapsone is prescribed to prednisolone-dependent recurrent cases of neuro-Sweet disease. Dementia is a neurological symptom of these disorders, especially in the chronic progressive subtype of neuro-Behçet disease. Other immunosuppressant drugs, including methotrexate and infliximab, are administered to patients with the chronic progressive type of neuro-Behçet disease. Neuro-neutrophilic diseases are a form of dementia considered treatable.

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.

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

Invited article: Neurology education research.

PubMed

Stern, Barney J; Lowenstein, Daniel H; Schuh, Lori A

2008-03-11

There is a need to rigorously study the neurologic education of medical students, neurology residents, and neurologists to determine the effectiveness of our educational efforts. We review the status of neurologic education research as it pertains to the groups of interest. We identify opportunities and impediments for education research. The introduction of the Accreditation Council for Graduate Medical Education core competencies, the Accreditation Council of Continuing Medical Education requirement to link continuing medical education to improved physician behavior and patient care, and the American Board of Medical Specialties/American Board of Psychiatry and Neurology-mandated maintenance of certification program represent research opportunities. Challenges include numerous methodologic issues such as definition of the theoretical framework of the study, adequate sample size ascertainment, and securing research funding. State-of-the-art education research will require multidisciplinary research teams and innovative funding strategies. The central goal of all concerned should be defining educational efforts that improve patient outcomes.

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

PubMed

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

2016-10-17

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

[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).

Electromagnetic characteristics of eccentric figure-eight coils for transcranial magnetic stimulation: A numerical study

NASA Astrophysics Data System (ADS)

Kato, Takuya; Sekino, Masaki; Matsuzaki, Taiga; Nishikawa, Atsushi; Saitoh, Youichi; Ohsaki, Hiroyuki

2012-04-01

Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment of several neurological and psychiatric diseases. We proposed an eccentric figure-eight coil, which induces strong eddy currents in the target brain tissue. In this study, numerical analyses were carried out to obtain magnetic field distribution of the eccentric figure-eight coil and eddy current in the brain. The analyses were performed with various coil design parameters, such as the outer and inner diameters and number of turns, to investigate the influence of these parameters on the coil characteristics. Increases in the inner diameter, outer diameter, and number of turns caused increases in the maximum eddy current densities. Coil inductance, working voltage, and heat generation also became higher with the increases in these design parameters. In order to develop a compact stimulator system for use at home, we need to obtain strong eddy current density, keeping the working voltage as low as possible. Our results show that it is effective to enlarge the outer diameter.

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.

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.

Predictors of neurologic and nonneurologic death in patients with brain metastasis initially treated with upfront stereotactic radiosurgery without whole-brain radiation therapy.

PubMed

McTyre, Emory R; Johnson, Adam G; Ruiz, Jimmy; Isom, Scott; Lucas, John T; Hinson, William H; Watabe, Kounosuke; Laxton, Adrian W; Tatter, Stephen B; Chan, Michael D

2017-04-01

In this study we attempted to discern the factors predictive of neurologic death in patients with brain metastasis treated with upfront stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) while accounting for the competing risk of nonneurologic death. We performed a retrospective single-institution analysis of patients with brain metastasis treated with upfront SRS without WBRT. Competing risks analysis was performed to estimate the subdistribution hazard ratios (HRs) for neurologic and nonneurologic death for predictor variables of interest. Of 738 patients treated with upfront SRS alone, neurologic death occurred in 226 (30.6%), while nonneurologic death occurred in 309 (41.9%). Multivariate competing risks analysis identified an increased hazard of neurologic death associated with diagnosis-specific graded prognostic assessment (DS-GPA) ≤ 2 (P = .005), melanoma histology (P = .009), and increased number of brain metastases (P<.001), while there was a decreased hazard associated with higher SRS dose (P = .004). Targeted agents were associated with a decreased HR of neurologic death in the first 1.5 years (P = .04) but not afterwards. An increased hazard of nonneurologic death was seen with increasing age (P =.03), nonmelanoma histology (P<.001), presence of extracranial disease (P<.001), and progressive systemic disease (P =.004). Melanoma, DS-GPA, number of brain metastases, and SRS dose are predictive of neurologic death, while age, nonmelanoma histology, and more advanced systemic disease are predictive of nonneurologic death. Targeted agents appear to delay neurologic death. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

[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.

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.

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.

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.

Speech Motor Sequence Learning: Acquisition and Retention in Parkinson Disease and Normal Aging

ERIC Educational Resources Information Center

Whitfield, Jason A.; Goberman, Alexander M.

2017-01-01

Purpose: The aim of the current investigation was to examine speech motor sequence learning in neurologically healthy younger adults, neurologically healthy older adults, and individuals with Parkinson disease (PD) over a 2-day period. Method: A sequential nonword repetition task was used to examine learning over 2 days. Participants practiced a…

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.

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

ERIC Educational Resources Information Center

Morsink, Maarten C.; Dukers, Danny F.

2009-01-01

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

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.

The severity of Minamata disease declined in 25 years: temporal profile of the neurological findings analyzed by multiple logistic regression model.

PubMed

Uchino, Makoto; Hirano, Teruyuki; Satoh, Hiroshi; Arimura, Kimiyoshi; Nakagawa, Masanori; Wakamiya, Jyunji

2005-01-01

Minamata disease (MD) was caused by ingestion of seafood from the methylmercury-contaminated areas. Although 50 years have passed since the discovery of MD, there have been only a few studies on the temporal profile of neurological findings in certified MD patients. Thus, we evaluated changes in neurological symptoms and signs of MD using discriminants by multiple logistic regression analysis. The severity of predictive index declined in 25 years in most of the patients. Only a few patients showed aggravation of neurological findings, which was due to complications such as spino-cerebellar degeneration. Patients with chronic MD aged over 45 years had several concomitant diseases so that their clinical pictures were complicated. It was difficult to differentiate chronic MD using statistically established discriminants based on sensory disturbance alone. In conclusion, the severity of MD declined in 25 years along with the modification by age-related concomitant disorders.

Lymphatics in Neurological Disorders: A neuro-lympho-vascular Component of Multiple Sclerosis and Alzheimer’s Disease

PubMed Central

Louveau, Antoine; Mesquita, Sandro Da; Kipnis, Jonathan

2016-01-01

Summary Lymphatic vasculature drains interstitial fluids, which contain the tissue’s waste products and ensures immune surveillance of the tissues, allowing immune-cell recirculation. Until recently the central nervous system (CNS) was considered to be devoid of a conventional lymphatic vasculature. The recent discovery in the meninges of a lymphatic network that drains the CNS calls into question classic models for the drainage of macromolecules and immune cells from the CNS. In the context of neurological disorders, the presence of a lymphatic system draining the CNS potentially offers a new player and a new avenue for therapy. In this review, we will attempt to integrate the known primary functions of the tissue lymphatic vasculature that exists in peripheral organs with the proposed function of meningeal lymphatic vessels in neurological disorders, specifically multiple sclerosis and Alzheimer’s disease. We propose that these (and potentially other) neurological afflictions can be viewed as diseases with neuro-lympho-vascular component and should be therapeutically targeted as such. PMID:27608759

The rationale for integrated childhood meningoencephalitis surveillance: a case study from Cambodia

PubMed Central

Touch, Sok; Hills, Susan; Rani, Manju; Samnang, Chham; Khalakdina, Asheena; Jacobson, Julie

2009-01-01

Abstract Problem Recent progress in vaccine availability and affordability has raised prospects for reducing death and disability from neurological infections in children. In many Asian countries, however, the epidemiology and public health burden of neurological diseases such as Japanese encephalitis and bacterial meningitis are poorly understood. Approach A sentinel surveillance system for Japanese encephalitis was developed and embedded within the routine meningoencephalitis syndromic surveillance system in Cambodia in 2006. The sentinel surveillance system was designed so surveillance and laboratory testing for other etiologies of neurological infection could be incorporated. Local setting The Communicable Disease Control department of the Ministry of Health in Cambodia worked with partners to establish the sentinel surveillance system. Relevant changes The sentinel surveillance system has provided important information on the disease burden of Japanese encephalitis in Cambodia and is now providing a platform for expansion to incorporate laboratory testing for other vaccine-preventable neurological infections in children. Lessons learned Sentinel surveillance systems, when linked to syndromic reporting systems, can characterize the epidemiology of meningoencephalitis and identify the proportion of hospital-based neurological infection in children that is vaccine preventable. Integrated systems enable consistency in data collection, analysis and information dissemination, and they enhance the capacity of public health managers to provide more credible and integrated information to policy-makers. This will assist decision-making about the potential role of immunization in reducing the incidence of childhood neurological infections. PMID:19551241

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 with an underlying neurodegenerative disorder or isolated hearing impairment tended to hear more persistent music, which was often religious and patriotic compared to those with a structural lesion, where more modern music was heard, and those with psychiatric disorders where music was mood-congruent. This case series shows that musical hallucinations can occur in association with a wide variety of conditions, of which neurological disease and brain lesions represent a substantial proportion, and that Lewy body disorders are the most commonly associated neurodegenerative diseases. A future prospective study would be helpful to further delineate an association between musical hallucinations and neurodegenerative disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neuropeptide Y Negatively Influences Monocyte Recruitment to the Central Nervous System during Retrovirus Infection.

PubMed

Woods, Tyson A; Du, Min; Carmody, Aaron; Peterson, Karin E

2015-12-30

Monocyte infiltration into the CNS is a hallmark of several viral infections of the central nervous system (CNS), including retrovirus infection. Understanding the factors that mediate monocyte migration in the CNS is essential for the development of therapeutics that can alter the disease process. In the current study, we found that neuropeptide Y (NPY) suppressed monocyte recruitment to the CNS in a mouse model of polytropic retrovirus infection. NPY(-/-) mice had increased incidence and kinetics of retrovirus-induced neurological disease, which correlated with a significant increase in monocytes in the CNS compared to wild-type mice. Both Ly6C(hi) inflammatory and Ly6C(lo) alternatively activated monocytes were increased in the CNS of NPY(-/-) mice following virus infection, suggesting that NPY suppresses the infiltration of both cell types. Ex vivo analysis of myeloid cells from brain tissue demonstrated that infiltrating monocytes expressed high levels of the NPY receptor Y2R. Correlating with the expression of Y2R on monocytes, treatment of NPY(-/-) mice with a truncated, Y2R-specific NPY peptide suppressed the incidence of retrovirus-induced neurological disease. These data demonstrate a clear role for NPY as a negative regulator of monocyte recruitment into the CNS and provide a new mechanism for suppression of retrovirus-induced neurological disease. Monocyte recruitment to the brain is associated with multiple neurological diseases. However, the factors that influence the recruitment of these cells to the brain are still not well understood. In the current study, we found that neuropeptide Y, a protein produced by neurons, affected monocyte recruitment to the brain during retrovirus infection. We show that mice deficient in NPY have increased influx of monocytes into the brain and that this increase in monocytes correlates with neurological-disease development. These studies provide a mechanism by which the nervous system, through the production of NPY, can suppress monocyte trafficking to the brain and reduce retrovirus-induced neurological disease. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Niemann-Pick disease type C symptomatology: an expert-based clinical description

PubMed Central

2013-01-01

Niemann-Pick disease type C (NP-C) is a rare, progressive, irreversible disease leading to disabling neurological manifestations and premature death. The estimated disease incidence is 1:120,000 live births, but this likely represents an underestimate, as the disease may be under-diagnosed due to its highly heterogeneous presentation. NP-C is characterised by visceral, neurological and psychiatric manifestations that are not specific to the disease and that can be found in other conditions. The aim of this review is to provide non-specialists with an expert-based, detailed description of NP-C signs and symptoms, including how they present in patients and how they can be assessed. Early disease detection should rely on seeking a combination of signs and symptoms, rather than isolated findings. Examples of combinations which are strongly suggestive of NP-C include: splenomegaly and vertical supranuclear gaze palsy (VSGP); splenomegaly and clumsiness; splenomegaly and schizophrenia-like psychosis; psychotic symptoms and cognitive decline; and ataxia with dystonia, dysarthria/dysphagia and cognitive decline. VSGP is a hallmark of NP-C and becomes highly specific of the disease when it occurs in combination with other manifestations (e.g. splenomegaly, ataxia). In young infants (<2 years), abnormal saccades may first manifest as slowing and shortening of upward saccades, long before gaze palsy onset. While visceral manifestations tend to predominate during the perinatal and infantile period (2 months–6 years of age), neurological and psychiatric involvement is more prominent during the juvenile/adult period (>6 years of age). Psychosis in NP-C is atypical and variably responsive to treatment. Progressive cognitive decline, which always occurs in patients with NP-C, manifests as memory and executive impairment in juvenile/adult patients. Disease prognosis mainly correlates with the age at onset of the neurological signs, with early-onset forms progressing faster. Therefore, a detailed and descriptive picture of NP-C signs and symptoms may help improve disease detection and early diagnosis, so that therapy with miglustat (Zavesca®), the only available treatment approved to date, can be started as soon as neurological symptoms appear, in order to slow disease progression. PMID:24135395

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.

Neurological Complications Comparing Endoscopically vs. Open Harvest of the Radial Artery

ClinicalTrials.gov

2016-07-05

Complications Due to Coronary Artery Bypass Graft; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

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.

"Scleroderma linearis: hemiatrophia faciei progressiva (Parry-Romberg syndrom) without any changes in CNS and linear scleroderma "en coup de sabre" with CNS tumor

PubMed Central

Bergler-Czop, Beata; Lis-Święty, Anna; Brzezińska-Wcisło, Ligia

2009-01-01

Background Hemifacial atrophy (Parry-Romberg syndrome) is a relatively rare disease. The etiology of the disease is not clear. Some authors postulate its relation with limited scleroderma linearis. Linear scleroderma "en coup de sabre" is characterized by clinical presence of most commonly one-sided linear syndrome. In a number of patients, neurological affection is the medium of the disease. The treatment of both scleroderma varieties is similar to the treatment of limited systemic sclerosis. Case presentation We present two cases of a disease: a case of a 49-year-old woman with a typical image of hemifacial atrophy, without any changes of the nervous system and a case of a 33-year-old patient with an "en coup de sabre" scleroderma and with CNS tumor. Conclusion We described typical cases of a rare diseases, hemifacial atrophy and "en coup de sabre" scleroderma. In the patient diagnosed with Parry-Romberg syndrome, with Borrelia burgdoferi infection and with minor neurological symptoms, despite a four-year case history, there was a lack of proper diagnosis and treatment. In the second patient only skin changes without any neurological symptoms could be observed and only a precise neurological diagnosis revealed the presence of CNS tumor. PMID:19635150

Cognitive profile in Wilson's disease: a case series of 31 patients.

PubMed

Wenisch, E; De Tassigny, A; Trocello, J-M; Beretti, J; Girardot-Tinant, N; Woimant, F

2013-12-01

Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism. If untreated, WD, which is initially a liver disease, can turn into a multi-systemic disease with neurological involvement. Very few studies have described cognitive impairment in WD. The aim of this study is to report the cognitive profile of 31 treated WD patients. Patients were classed into two groups using the Unified Wilson Disease Rating Scale (UWDRS): WD patients without neurological signs (WD-N(-)) (n=13), and WD patients with neurological signs (WD-N(+)) (n=18). The patients participated in a neuropsychological assessment evaluating memory, executive function and visuo-spatial abilities. Both groups performed well for verbal intelligence and episodic memory skills. However, the majority of these patients exhibited altered performance for at least one cognitive test, particularly in the executive domain. The WD-N(+) group performed less well than the WD-N(-) group on cognitive tests involving rapid motor function, abstract thinking, working memory and top-down inhibitory control. Cognitive impairment in treated WD patients essentially affects executive function involving fronto-striatal circuits. Verbal intelligence and episodic memory abilities seem to be remarkably preserved. Neuropsychological assessment is a valuable tool to evaluate the presence and the consequences of these cognitive impairments in WD patients with or without neurological signs in the course of this chronic disease. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Representation of numerosity in posterior parietal cortex

PubMed Central

Roitman, Jamie D.; Brannon, Elizabeth M.; Platt, Michael L.

2012-01-01

Humans and animals appear to share a similar representation of number as an analog magnitude on an internal, subjective scale. Neurological and neurophysiological data suggest that posterior parietal cortex (PPC) is a critical component of the circuits that form the basis of numerical abilities in humans. Patients with parietal lesions are impaired in their ability to access the deep meaning of numbers. Acalculiac patients with inferior parietal damage often have difficulty performing arithmetic (2 + 4?) or number bisection (what is between 3 and 5?) tasks, but are able to recite multiplication tables and read or write numerals. Functional imaging studies of neurologically intact humans performing subtraction, number comparison, and non-verbal magnitude comparison tasks show activity in areas within the intraparietal sulcus (IPS). Taken together, clinical cases and imaging studies support a critical role for parietal cortex in the mental manipulation of numerical quantities. Further, responses of single PPC neurons in non-human primates are sensitive to the numerosity of visual stimuli independent of low-level stimulus qualities. When monkeys are trained to make explicit judgments about the numerical value of such stimuli, PPC neurons encode their cardinal numerical value; without such training PPC neurons appear to encode numerical magnitude in an analog fashion. Here we suggest that the spatial and integrative properties of PPC neurons contribute to their critical role in numerical cognition. PMID:22666194

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

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.

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

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

Molecular diagnostics of neurodegenerative disorders.

PubMed

Agrawal, Megha; Biswas, Abhijit

2015-01-01

Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer's and Parkinson's disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

Neurology cases evaluated by the U.S. Air Force School of Aerospace Medicine 2000-2012.

PubMed

Hesselbrock, Roger; Heaton, John

2014-05-01

Historically, neurologic conditions are a major cause for removing aviators from flying status. Early neuropsychiatry studies included psychiatric conditions along with neurologic disorders. Previously reported data specifically addressing neurologic conditions in aviators are limited. And there is little current neurology-specific data reported. A retrospective review was done on patients with diagnoses evaluated by Neurology at the U.S. Air Force School of Aerospace Medicine Aeromedical Consultation Service (ACS) between 2000 and 2012 using ACS records and databases to identify cases. Patient demographics, major diagnoses with associated International Classification of Diseases (9th rev.) codes, and aeromedical disposition recommendations were abstracted into a separate database for analysis. In total, 871 cases were identified. Patients were predominantly male (91%) with average age 34 and were predominantly pilots (69%). The top neurology-related diagnoses found in our series were headaches, head injuries, and radiculopathies. Of the cases evaluated, 570 aviators (65%) were recommended by ACS to return to flying status. Waiver authorities accepted 88% of ACS recommendations. Current patterns in neurologic conditions in the selected population of cases evaluated by the ACS were presented. Of the neurologic diagnoses seen, a novel finding was the prominence of head injuries in our series not seen in previous studies. This may be due to more stringent aeromedical standards with advances in medical practice and underscores that this issue is not just about disability but affects aircrew operational readiness. Most cases of neurologic disease evaluated by the ACS were recommended for return to flying status.

Lysine acetyltransferase inhibitors: structure-activity relationships and potential therapeutic implications.

PubMed

Fiorentino, Francesco; Mai, Antonello; Rotili, Dante

2018-05-01

Lysine acetylation is a post-translational modification of both histone and nonhistone proteins that is catalyzed by lysine acetyltransferases and plays a key role in numerous biological contexts. The dysregulation of this enzyme activity is implicated in many human pathologies such as cancer, neurological and inflammatory disorders. Many lysine acetyltransferase inhibitors (KATi) have been developed so far, but there is still the need for new, more potent, metabolically stable and selective KATi as chemical tools for studying KAT biology and/or as potential therapeutic agents. This review will examine the features of KAT enzymes and related diseases, with particular emphasis on KATi (bisubstrate analogs, natural compounds and synthetic derivatives), analyzing their mechanism of action, structure-activity relationships, pharmacokinetic/pharmacodynamic properties and potential future applications.

Non-invasive measurement of cerebral oxygen metabolism in the mouse brain by ultra-high field 17O MR spectroscopy

PubMed Central

Cui, Weina; Zhu, Xiao-Hong; Vollmers, Manda L; Colonna, Emily T; Adriany, Gregor; Tramm, Brandon; Dubinsky, Janet M; Öz, Gülin

2013-01-01

To assess cerebral energetics in transgenic mouse models of neurologic disease, a robust, efficient, and practical method for quantification of cerebral oxygen consumption is needed. 17O magnetic resonance spectroscopy (MRS) has been validated to measure cerebral metabolic rate of oxygen (CMRO2) in the rat brain; however, mice present unique challenges because of their small size. We show that CMRO2 measurements with 17O MRS in the mouse brain are highly reproducible using 16.4 Tesla and a newly designed oxygen delivery system. The method can be utilized to measure mitochondrial function in mice quickly and repeatedly, without oral intubation, and has numerous potential applications to study cerebral energetics. PMID:24064490

Regulation of autophagy by amino acid availability in S. cerevisiae and mammalian cells.

PubMed

Abeliovich, Hagai

2015-10-01

Autophagy is a catabolic membrane-trafficking process that occurs in all eukaryotic organisms analyzed to date. The study of autophagy has exploded over the last decade or so, branching into numerous aspects of cellular and organismal physiology. From basic functions in starvation and quality control, autophagy has expanded into innate immunity, aging, neurological diseases, redox regulation, and ciliogenesis, to name a few roles. In the present review, I would like to narrow the discussion to the more classical roles of autophagy in supporting viability under nutrient limitation. My aim is to provide a semblance of a historical overview, together with a concise, and perhaps subjective, mechanistic and functional analysis of the central questions in the autophagy field.

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.

Conversion disorder: current problems and potential solutions for DSM-5.

PubMed

Stone, Jon; LaFrance, W Curt; Brown, Richard; Spiegel, David; Levenson, James L; Sharpe, Michael

2011-12-01

Conversion disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) describes neurological symptoms, including weakness, numbness and events resembling epilepsy or syncope, which can be positively identified as not being due to recognised neurological disease. This review combines perspectives from psychiatry, psychology and neurology to identify and discuss key problems with the current diagnostic DSM-IV criteria for conversion disorder and to make the following proposals for DSM-5: (a) abandoning the label "conversion disorder" and replacing it with an alternative term that is both theoretically neutral and potentially more acceptable to patients and practitioners; (b) relegating the requirements for "association of psychological factors" and the "exclusion of feigning" to the accompanying text; (c) adding a criterion requiring clinical findings of internal inconsistency or incongruity with recognised neurological or medical disease and altering the current 'disease exclusion' criteria to one in which the symptom must not be 'better explained' by a disease if present, (d) adding a 'cognitive symptoms' subtype. We also discuss whether conversion symptoms are better classified with other somatic symptom disorders or with dissociative disorders and how we might address the potential heterogeneity of conversion symptoms in classification. 2011 Elsevier Inc. All rights reserved.

Neuro-Behçet syndrome.

PubMed

Saip, Sabahattin; Akman-Demir, Gulsen; Siva, Aksel

2014-01-01

Behçet syndrome (BS) is an idiopathic chronic relapsing multisystem vascular-inflammatory disease of unknown origin. As the disease affects many organs and systems and shows a wide range of clinical manifestations and presentations, it is prefereable to call Behçet's a syndrome (BS) rather than a disease. Nervous system involvement, known as "neuro-BS" (NBS), is seen in about 5-10% of all cases. Clinical and imaging evidence suggests that primary neurologic involvement in BS may be subclassified into two major forms: the first, which is seen in the majority of patients, may be characterized as a vascular-inflammatory central nervous system disease with focal or multifocal parenchymal involvement, mostly presenting with a subacute brainstem syndrome and hemiparesis (intra-axial NBS); the other, which has few symptoms and a better neurologic prognosis, may be caused by isolated cerebral venous sinus thrombosis and intracranial hypertension (extra-axial NBS), occurring in 10-20% of the cases. These two types are rarely seen in the same individual, and their pathogenesis is likely to be different. Isolated behavioral syndromes and peripheral nervous system involvement are rare, whereas a vascular type headache is relatively common and independent from neurologic involvement. Neurologic complications secondary to systemic involvement of BS, as well as neurologic complications related to BS treatments are considered as secondary neurologic involvement of the syndrome. The core histopathologic phenomenon seems to be a vasculitic involvement in some cases, and low-grade chronic nonspecific inflammation in others. As the neurologic involvement in this syndrome is so heterogeneous, it is difficult to predict its course and prognosis, and its response to treatment. Currently, treatment options for NBS are limited to attack therapies with high-dose intravenous methylprednisolone followed by a prolonged oral taper, symptomatic management, and generally the use of azathioprine, cyclophosphamide, interferon-α and anti-TNF agents for long-term preventive treatment, although there no evidence for their efficacy. © 2014 Elsevier B.V. All rights reserved.

[Evaluation of elderly patients with community-acquired pneumonia admitted to our hospital, who have neurologic disease, such as late effects of cerebral strokes in the past and medical history].

PubMed

Ono, Hiroshi; Taniguchi, Yasuyuki; Kudoh, Shoji

2008-09-01

Hospitalized cases of community-acquired pneumonia (CAP) of the elderly with a history of neurologic diseases have not been examined in detail in the past. We extracted 15 cases with a history of neurologic disease (neurological history group, NH, all cases were over 70 years old), and 22 age-matched cases without a history of neurological diseases (non neurologic history group, non-NH) among 47 CAP patients who admitted to our hospital from home during the past year, and compared the two groups in terms of: (1) the score of severity of pneumonia by A-DROP system, (2) outcome (3) the duration of hospitalization, (4) the duration from end of treatment of antibiotic treatment to discharge, compared between the survival discharge cases out of two groups (11 vs 22 cases), (5) the bacteria that were detected. (1) In the NH group, the score was significantly higher than that in the non-NH group. (2) In the NH group, 4 cases died while none did in the non-NH group. (3) In the NH group, it was 30.8 +/- 22.8 (average +/- standard deviation) days, significantly higher than the 17.6 +/- 5.9 days in the non-NH group, (4) In the NH group, it was 16.6 +/- 14.1 days, which was significantly higher than the 6.7 +/- 4.8 days in the non-NH group. (5) In the NH group, there was a high rate of detection of Klebsiella pneumoniae, Escherichia coli and Serratia marcesscense. An original comprehensive plan of treatment and care support is necessary for NH because the NH is different from other CAP conditions.

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.

A Morpholino Strategy to Assess TSC Gene Function in Zebrafish

DTIC Science & Technology

2006-11-01

ABSTRACT Tuberous sclerosis complex (TSC) is a genetic disorder associated with severe neurological symptoms including mental retardation, autism ...ABSTRACT Tuberous sclerosis complex (TSC) is a genetic disorder associated with severe neurological symptoms including mental retardation, autism ...devastating autosomal dominant disease that results in severe neurological symptoms including mental retardation, autism , and seizures (DiMario, 2004

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.

Quality improvement and practice-based research in neurology using the electronic medical record

PubMed Central

Frigerio, Roberta; Kazmi, Nazia; Meyers, Steven L.; Sefa, Meredith; Walters, Shaun A.; Silverstein, Jonathan C.

2015-01-01

Abstract We describe quality improvement and practice-based research using the electronic medical record (EMR) in a community health system–based department of neurology. Our care transformation initiative targets 10 neurologic disorders (brain tumors, epilepsy, migraine, memory disorders, mild traumatic brain injury, multiple sclerosis, neuropathy, Parkinson disease, restless legs syndrome, and stroke) and brain health (risk assessments and interventions to prevent Alzheimer disease and related disorders in targeted populations). Our informatics methods include building and implementing structured clinical documentation support tools in the EMR; electronic data capture; enrollment, data quality, and descriptive reports; quality improvement projects; clinical decision support tools; subgroup-based adaptive assignments and pragmatic trials; and DNA biobanking. We are sharing EMR tools and deidentified data with other departments toward the creation of a Neurology Practice-Based Research Network. We discuss practical points to assist other clinical practices to make quality improvements and practice-based research in neurology using the EMR a reality. PMID:26576324

Handwriting changes due to aging and Parkinson's syndrome.

PubMed

Walton, J

1997-08-22

Wills signed by elderly people are often contested on the grounds the the signature is different from their earlier specimen signatures. Neurological disease, which can affect handwriting, is very common and progressive amongst elderly people. Handwriting change due to old age and neurological disease is poorly understood. To better understand this subject, we carried out a large methodical study based on almost 200 handwriting specimens of Parkinson patients and age-matched controls. Interestingly, our findings indicate that some of the handwriting changes which occur in these populations tend to resemble forgery indicia although upon close inspection they are distinguishable from them. Thus, document examiners are urged to exercise caution in assessing purported forgeries on wills and other documents signed of written during older age or a writer suffering from neurological disease.

Cell reprogramming and neuronal differentiation applied to neurodegenerative diseases: Focus on Parkinson's disease.

PubMed

Wenker, Shirley D; Casalía, Mariana; Candedo, Verónica Cavaliere; Casabona, Juan Cruz; Pitossi, Fernando J

2015-11-14

Adult cells from patients can be reprogrammed to induced pluripotent stem cells (iPSCs) which successively can be used to obtain specific cells such as neurons. This remarkable breakthrough represents a new way of studying diseases and brought new therapeutic perspectives in the field of regenerative medicine. This is particular true in the neurology field, where few techniques are amenable to study the affected tissue of the patient during illness progression, in addition to the lack of neuroprotective therapies for many diseases. In this review we discuss the advantages and unresolved issues of cell reprogramming and neuronal differentiation. We reviewed evidence using iPSCs-derived neurons from neurological patients. Focusing on data obtained from Parkinson's disease (PD) patients, we show that iPSC-derived neurons possess morphological and functional characteristics of this disease and build a case for the use of this technology to study PD and other neuropathologies while disease is in progress. These data show the enormous impact that this new technology starts to have on different purposes such as the study and design of future therapies of neurological disease, especially PD. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. 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.

Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory neuropathy maps to chromosome 2q37.3.

PubMed

Klebe, Stephan; Azzedine, Hamid; Durr, Alexandra; Bastien, Patrick; Bouslam, Naima; Elleuch, Nizar; Forlani, Sylvie; Charon, Celine; Koenig, Michel; Melki, Judith; Brice, Alexis; Stevanin, Giovanni

2006-06-01

The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive spasticity in the lower limbs. Twenty-nine different loci (SPG) have been mapped so far, and 11 responsible genes have been identified. Clinically, one distinguishes between pure and complex HSP forms which are variably associated with numerous combinations of neurological and extra-neurological signs. Less is known about autosomal recessive forms (ARHSP) since the mapped loci have been identified often in single families and account for only a small percentage of patients. We report a new ARHSP locus (SPG30) on chromosome 2q37.3 in a consanguineous family with seven unaffected and four affected members of Algerian origin living in Eastern France with a significant multipoint lod score of 3.8. Ten other families from France (n = 4), Tunisia (n = 2), Algeria (n = 3) and the Czech Republic (n = 1) were not linked to the newly identified locus thus demonstrating further genetic heterogeneity. The phenotype of the linked family consists of spastic paraparesis and peripheral neuropathy associated with slight cerebellar signs confirmed by cerebellar atrophy on one CT scan.

Neurology and Don Quixote.

PubMed

Palma, Jose-Alberto; Palma, Fermin

2012-01-01

Don Quixote de la Mancha, which is considered one of the most important and influential works of Western modern prose, contains many references of interest for almost all of the medical specialties. In this regard, numerous references to neurology can be found in Cervantes' immortal work. In this study, we aimed to read Don Quixote from a neurologist's point of view, describing the neurological phenomena scattered throughout the novel, including tremors, sleep disturbances, neuropsychiatric symptoms, dementia, epilepsy, paralysis, stroke, syncope, traumatic head injury, and headache; we relate these symptoms with depictions of those conditions in the medical literature of the time. We also review Cervantes' sources of neurological information, including the works by renowned Spanish authors such as Juan Huarte de San Juan, Dionisio Daza Chacón and Juan Valverde de Amusco, and we hypothesize that Don Quixote's disorder was actually a neurological condition. Although Cervantes wrote it four centuries ago, Don Quixote contains plenty of references to neurology, and many of the ideas and concepts reflected in it are still of interest. Copyright © 2012 S. Karger AG, Basel.

Using Telemedicine to Improve Spasticity Diagnosis Rates

ClinicalTrials.gov

2018-02-20

Spasticity, Muscle; Muscular Diseases; Musculoskeletal Disease; Muscle Hypertonia; Muscle Spasticity; Neuromuscular Manifestations; Signs and Symptoms; Nervous System Diseases; Neurologic Manifestations

Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases.

PubMed

Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Padmavathi, Ganesan; Monisha, Javadi; Roy, Nand Kishor; Prasad, Sahdeo; Aggarwal, Bharat B

2017-06-01

Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti-inflammatory activity through the suppression of numerous cell signalling pathways including NF-κB, STAT3, Nrf2, ROS and COX-2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases

PubMed Central

Bordoloi, Devivasha; Padmavathi, Ganesan; Monisha, Javadi; Roy, Nand Kishor; Prasad, Sahdeo

2016-01-01

Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti‐inflammatory activity through the suppression of numerous cell signalling pathways including NF‐κB, STAT3, Nrf2, ROS and COX‐2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc PMID:27638428

Missense-depleted regions in population exomes implicate ras superfamily nucleotide-binding protein alteration in patients with brain malformation

PubMed Central

Ge, Xiaoyan; Gong, Henry; Dumas, Kevin; Litwin, Jessica; Phillips, Joanna J; Waisfisz, Quinten; Weiss, Marjan M; Hendriks, Yvonne; Stuurman, Kyra E; Nelson, Stanley F; Grody, Wayne W; Lee, Hane; Kwok, Pui-Yan; Shieh, Joseph T C

2016-01-01

Genomic sequence interpretation can miss clinically relevant missense variants for several reasons. Rare missense variants are numerous in the exome and difficult to prioritise. Affected genes may also not have existing disease association. To improve variant prioritisation, we leverage population exome data to identify intragenic missense-depleted regions (MDRs) genome-wide that may be important in disease. We then use missense depletion analyses to help prioritise undiagnosed disease exome variants. We demonstrate application of this strategy to identify a novel gene association for human brain malformation. We identified de novo missense variants that affect the GDP/GTP-binding site of ARF1 in three unrelated patients. Corresponding functional analysis suggests ARF1 GDP/GTP-activation is affected by the specific missense mutations associated with heterotopia. These findings expand the genetic pathway underpinning neurologic disease that classically includes FLNA. ARF1 along with ARFGEF2 add further evidence implicating ARF/GEFs in the brain. Using functional ontology, top MDR-containing genes were highly enriched for nucleotide-binding function, suggesting these may be candidates for human disease. Routine consideration of MDR in the interpretation of exome data for rare diseases may help identify strong genetic factors for many severe conditions, infertility/reduction in reproductive capability, and embryonic conditions contributing to preterm loss. PMID:28868155

Rift valley Fever virus encephalitis is associated with an ineffective systemic immune response and activated T cell infiltration into the CNS in an immunocompetent mouse model.

PubMed

Dodd, Kimberly A; McElroy, Anita K; Jones, Tara L; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

2014-06-01

Rift Valley fever virus (RVFV) causes outbreaks of severe disease in livestock and humans throughout Africa and the Arabian Peninsula. In people, RVFV generally causes a self-limiting febrile illness but in a subset of individuals, it progresses to more serious disease. One manifestation is a delayed-onset encephalitis that can be fatal or leave the afflicted with long-term neurologic sequelae. In order to design targeted interventions, the basic pathogenesis of RVFV encephalitis must be better understood. To characterize the host immune responses and viral kinetics associated with fatal and nonfatal infections, mice were infected with an attenuated RVFV lacking NSs (ΔNSs) that causes lethal disease only when administered intranasally (IN). Following IN infection, C57BL/6 mice developed severe neurologic disease and succumbed 7-9 days post-infection. In contrast, inoculation of ΔNSs virus subcutaneously in the footpad (FP) resulted in a subclinical infection characterized by a robust immune response with rapid antibody production and strong T cell responses. IN-inoculated mice had delayed antibody responses and failed to clear virus from the periphery. Severe neurological signs and obtundation characterized end stage-disease in IN-inoculated mice, and within the CNS, the development of peak virus RNA loads coincided with strong proinflammatory responses and infiltration of activated T cells. Interestingly, depletion of T cells did not significantly alter survival, suggesting that neurologic disease is not a by-product of an aberrant immune response. Comparison of fatal (IN-inoculated) and nonfatal (FP-inoculated) ΔNSs RVFV infections in the mouse model highlighted the role of the host immune response in controlling viral replication and therefore determining clinical outcome. There was no evidence to suggest that neurologic disease is immune-mediated in RVFV infection. These results provide important insights for the future design of vaccines and therapeutic options.

Prediction of blood-brain barrier permeation of α-adrenergic and imidazoline receptor ligands using PAMPA technique and quantitative-structure permeability relationship analysis.

PubMed

Vucicevic, Jelica; Nikolic, Katarina; Dobričić, Vladimir; Agbaba, Danica

2015-02-20

Imidazoline receptor ligands are a numerous family of biologically active compounds known to produce central hypotensive effect by interaction with both α2-adrenoreceptors (α2-AR) and imidazoline receptors (IRs). Recent hypotheses connect those ligands with several neurological disorders. Therefore some IRs ligands are examined as novel centrally acting antihypertensives and drug candidates for treatment of various neurological diseases. Effective Blood-Brain Barrier (BBB) permeability (P(e)) of 18 IRs/α-ARs ligands and 22 Central Nervous System (CNS) drugs was experimentally determined using Parallel Artificial Membrane Permeability Assay (PAMPA) and studied by the Quantitative-Structure-Permeability Relationship (QSPR) methodology. The dominant molecules/cations species of compounds have been calculated at pH = 7.4. The analyzed ligands were optimized using Density Functional Theory (B3LYP/6-31G(d,p)) included in ChemBio3D Ultra 13.0 program and molecule descriptors for optimized compounds were calculated using ChemBio3D Ultra 13.0, Dragon 6.0 and ADMET predictor 6.5 software. Effective permeability of compounds was used as dependent variable (Y), while calculated molecular parametres were used as independent variables (X) in the QSPR study. SIMCA P+ 12.0 was used for Partial Least Square (PLS) analysis, while the stepwise Multiple Linear Regression (MLR) and Artificial Neural Networks (ANN) modeling were performed using STASTICA Neural Networks 4.0. Predictive potential of the formed models was confirmed by Leave-One-Out Cross- and external-validation and the most reliable models were selected. The descriptors that are important for model building are identified as well as their influence on BBB permeability. Results of the QSPR studies could be used as time and cost efficient screening tools for evaluation of BBB permeation of novel α-adrenergic/imidazoline receptor ligands, as promising drug candidates for treatment of hypertension or neurological diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Xeroderma pigmentosum is a definite cause of Huntington's disease-like syndrome.

PubMed

Garcia-Moreno, Hector; Fassihi, Hiva; Sarkany, Robert P E; Phukan, Julie; Warner, Thomas; Lehmann, Alan R; Giunti, Paola

2018-01-01

Xeroderma pigmentosum is characterized by cutaneous, ophthalmological, and neurological features. Although it is typical of childhood, late presentations can mimic different neurodegenerative conditions. We report two families presenting as Huntington's disease-like syndromes. The first case (group G) presented with neuropsychiatric features, cognitive decline and chorea. Typical lentigines were only noticed after the neurological disease started. The second case (group B) presented adult-onset chorea and neuropsychiatric symptoms after an aggressive ocular melanoma. Xeroderma pigmentosum can manifest as a Huntington's Disease-like syndrome. Classic dermatological and oncological features have to be investigated in choreic patients with negative genetic tests for Huntington's disease-like phenotypes.

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.

Brain transcriptome perturbations in the Hfe(-/-) mouse model of genetic iron loading.

PubMed

Johnstone, Daniel; Graham, Ross M; Trinder, Debbie; Delima, Roheeth D; Riveros, Carlos; Olynyk, John K; Scott, Rodney J; Moscato, Pablo; Milward, Elizabeth A

2012-04-11

Severe disruption of brain iron homeostasis can cause fatal neurodegenerative disease, however debate surrounds the neurologic effects of milder, more common iron loading disorders such as hereditary hemochromatosis, which is usually caused by loss-of-function polymorphisms in the HFE gene. There is evidence from both human and animal studies that HFE gene variants may affect brain function and modify risks of brain disease. To investigate how disruption of HFE influences brain transcript levels, we used microarray and real-time reverse transcription polymerase chain reaction to assess the brain transcriptome in Hfe(-/-) mice relative to wildtype AKR controls (age 10 weeks, n≥4/group). The Hfe(-/-) mouse brain showed numerous significant changes in transcript levels (p<0.05) although few of these related to proteins directly involved in iron homeostasis. There were robust changes of at least 2-fold in levels of transcripts for prominent genes relating to transcriptional regulation (FBJ osteosarcoma oncogene Fos, early growth response genes), neurotransmission (glutamate NMDA receptor Grin1, GABA receptor Gabbr1) and synaptic plasticity and memory (calcium/calmodulin-dependent protein kinase IIα Camk2a). As previously reported for dietary iron-supplemented mice, there were altered levels of transcripts for genes linked to neuronal ceroid lipofuscinosis, a disease characterized by excessive lipofuscin deposition. Labile iron is known to enhance lipofuscin generation which may accelerate brain aging. The findings provide evidence that iron loading disorders can considerably perturb levels of transcripts for genes essential for normal brain function and may help explain some of the neurologic signs and symptoms reported in hemochromatosis patients. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

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.

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.

Iron deposition quantification: Applications in the brain and liver.

PubMed

Yan, Fuhua; He, Naying; Lin, Huimin; Li, Ruokun

2018-06-13

Iron has long been implicated in many neurological and other organ diseases. It is known that over and above the normal increases in iron with age, in certain diseases there is an excessive iron accumulation in the brain and liver. MRI is a noninvasive means by which to image the various structures in the brain in three dimensions and quantify iron over the volume of the object of interest. The quantification of iron can provide information about the severity of iron-related diseases as well as quantify changes in iron for patient follow-up and treatment monitoring. This article provides an overview of current MRI-based methods for iron quantification, specifically for the brain and liver, including: signal intensity ratio, R 2 , R2*, R2', phase, susceptibility weighted imaging and quantitative susceptibility mapping (QSM). Although there are numerous approaches to measuring iron, R 2 and R2* are currently preferred methods in imaging the liver and QSM has become the preferred approach for imaging iron in the brain. 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Disability pension in Malmöhus county: aspects on long-term financial effects.

PubMed

Månsson, N O; Råstam, L; Adolfsson, A

1998-06-01

The purpose of this study was to estimate the financial costs of disability pension in order to compare the financial burden and the numerical distribution of disability pension by main diagnostic groups. During three months all new disability pensions (n = 944) granted in Malmöhus county were registered. During a follow-up of approximately two and a half years, 40 subjects died and 15 pensions expired. The predominating diagnoses were musculoskeletal diseases, mental disorders including alcohol dependence, cardiovascular and neurological diseases. To analyse whether these proportions changed when the extent of the pension, age at pension and the retirement allowance were considered, the present value of the total retirement allowances was calculated. The ranking of the four predominating diagnosis categories was not affected by the extent of the pension or the age at which the pension was granted. Thus, musculoskeletal diseases still predominated, although the proportion decreased. Among unemployed subjects, mental disorders made the largest contribution to the total expenditure. The results gained may be used in further research where alternatives to disability pension for different groups of patients and/or diagnoses are investigated.

Original footage of the Chilean miners with manganism published in Neurology in 1967.

PubMed

Miranda, Marcelo; Bustamante, M Leonor; Mena, Francisco; Lees, Andrew

2015-12-15

Manganism has captured the imagination of neurologists for more than a century because of its similarities to Parkinson disease and its indirect but seminal role in the "l-dopa miracle." We present unpublished footage of the original case series reported in Neurology® in 1967 by Mena and Cotzias depicting the typical neurologic signs of manganism in 4 Chilean miners and their response to high doses of l-dopa. © 2015 American Academy of Neurology.

Epilepsy and Other Neurological Diseases in the Parents of Children with Infantile Autism. A Case Control Study

ERIC Educational Resources Information Center

Mouridsen, Svend Erik; Rich, Bente; Isager, Torben

2008-01-01

In order to study the broader phenotype of infantile autism (IA) we compared the rates and types of epilepsy and other neurological diseases in the parents of 111 consecutively admitted patients with IA with a matched control group of parents of 330 children from the general population. All participants were screened through the nationwide Danish…

[Quality of life of neurological patients during therapy and rehabilitation].

PubMed

Musaev, A V; Guseĭnova, S G; Imamverdieva, S S; Mustafaeva, E E; Musaeva, I R

2006-01-01

A total of 198 neurological patients on physiotherapeutic rehabilitation participated in a questionnaire survey on their quality of life. The patients had diabetic polyneuropathy (n = 86), disorders in spinal blood circulation (n = 65), 47 patients were operated for discal hernia of the lumbar spine. It was found that all the responders suffer from physical, psychological, emotional and social sequelae of their diseases which deteriorate their quality of life. The severity of this deterioration depends on the form and stage of the disease, motor and sensitive disturbances. Rehabilitation improved subjective response, social, psychological and emotional parameters. Thus, the proposed questionnaires proved valid for assessment of physiotherapy efficacy in neurological patients.

Diagnostic Exercise: Neurologic Disorder in a Cat

DTIC Science & Technology

1989-12-21

IWORK UNIT ELEMENT NO. NO. NO. ACCESSION NO. 11. TITLE (Include Security Classification) Diagnostic Exercise - Neurologic Disorder in a Cat 12...and identify by block number) This report documents the fifth reported occurrance of cerebral phaeophyphomycosis in cats . Because mycotic...Exercise: Neurologic Disorder in a Cat Ronald C. Bell United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick

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

PubMed

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

2002-01-01

To establish a statistical diagnostic method to identify patients with Minamata disease (MD) considering factors of aging and sex, we analyzed the neurological findings in MD patients, inhabitants in a methylmercury polluted (MP) area, and inhabitants in a non-MP area. We compared the neurological findings in MD patients and inhabitants aged more than 40 years in the non-MP area. Based on the different frequencies of the neurological signs in the two groups, we devised the following formula to calculate the predicting index for MD: predicting index = 1/(1+e(-x)) x 100 (The value of x was calculated using the regression coefficients of each neurological finding obtained from logistic analysis. The index 100 indicated MD, and 0, non-MD). Using this method, we found that 100% of male and 98% of female patients with MD (95 cases) gave predicting indices higher than 95. Five percent of the aged inhabitants in the MP area (598 inhabitants) and 0.2% of those in the non-MP area (558 inhabitants) gave predicting indices of 50 or higher. Our statistical diagnostic method for MD was useful in distinguishing MD patients from healthy elders based on their neurological findings.

Advantages of Structure-Based Drug Design Approaches in Neurological Disorders

PubMed Central

Aarthy, Murali; Panwar, Umesh; Selvaraj, Chandrabose; Singh, Sanjeev Kumar

2017-01-01

Objective: The purpose of the review is to portray the theoretical concept on neurological disorders from research data. Background: The freak changes in chemical response of nerve impulse causes neurological disorders. The research evidence of the effort done in the older history suggests that the biological drug targets and their effective feature with responsive drugs could be valuable in promoting the future development of health statistics structure for improved treatment for curing the nervous disorders. Methods: In this review, we summarized the most iterative theoretical concept of structure based drug design approaches in various neurological disorders to unfathomable understanding of reported information for future drug design and development. Results: On the premise of reported information we analyzed the model of theoretical drug designing process for understanding the mechanism and pathology of the neurological diseases which covers the development of potentially effective inhibitors against the biological drug targets. Finally, it also suggests the management and implementation of the current treatment in improving the human health system behaviors. Conclusion: With the survey of reported information we concluded the development strategies of diagnosis and treatment against neurological diseases which leads to supportive progress in the drug discovery. PMID:28042767

[History of the Department of Neurology at the University of Buenos Aires (1887-2007)].

PubMed

Allegri, Ricardo F; Bartoloni, Leonardo; Sica, Roberto E

2016-07-01

In 1887, only five years after Jean-Martin Charcot was awarded the Head of Neurology at "La Salpetrière" in Paris, José María Ramos Mejía became the first professor of Neurology in South America, at the School of Medicine of the University of Buenos Aires. Ramos Mejía convoked three assistants, the neuropathologist Christofredo Jakob, the clinician José A. Esteves and José Ingenieros. Hence it followed that Neurology in Argentina took a stand based on a clinical neurology-neuropathology approach (1941-1987) followed by a clinical-semiological attitude, finally inserting itself within the modern times (1987-present) by creating subspecialties. Throughout its history, Argentina has made remarkable contributions to Neurology, such as the diagnosis and pathogenesis of the nervous system involvement occurring in some regional endemic disorders -for instance, Chagas' disease-, the clinical approach to the diagnosis of dementias, and the pathogenesis of extrapyramidal illnesses and other primary degenerative diseases of the central nervous system, mainly amyotrophic lateral sclerosis. On the other hand, in recent years globalization allowed neurologists to participate in international cooperative projects, favoring a swifter development in the practice of this discipline.

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

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.

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.

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

Excitotoxicity in the pathogenesis of neurological and psychiatric disorders: Therapeutic implications.

PubMed

Olloquequi, Jordi; Cornejo-Córdova, Elizabeth; Verdaguer, Ester; Soriano, Francesc X; Binvignat, Octavio; Auladell, Carme; Camins, Antoni

2018-03-01

Neurological and psychiatric disorders are leading contributors to the global disease burden, having a serious impact on the quality of life of both patients and their relatives. Although the molecular events underlying these heterogeneous diseases remain poorly understood, some studies have raised the idea of common mechanisms involved. In excitotoxicity, there is an excessive activation of glutamate receptors by excitatory amino acids, leading to neuronal damage. Thus, the excessive release of glutamate can lead to a dysregulation of Ca 2+ homeostasis, triggering the production of free radicals and oxidative stress, mitochondrial dysfunction and eventually cell death. Although there is a consensus in considering excitotoxicity as a hallmark in most neurodegenerative diseases, increasing evidence points to the relevant role of this pathological mechanism in other illnesses affecting the central nervous system. Consequently, antagonists of glutamate receptors are used in current treatments or in clinical trials in both neurological and psychiatric disorders. However, drugs modulating other aspects of the excitotoxic mechanism could be more beneficial. This review discusses how excitotoxicity is involved in the pathogenesis of different neurological and psychiatric disorders and the promising strategies targeting the excitotoxic insult.

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.

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

Controlled population-based comparative study of USA and international adult [55-74] neurological deaths 1989-2014.

PubMed

Pritchard, C; Rosenorn-Lanng, E; Silk, A; Hansen, L

2017-12-01

A population-based controlled study to determine whether adult (55-74 years) neurological disease deaths are continuing to rise and are there significant differences between America and the twenty developed countries 1989-91 and 2012-14. Total Neurological Deaths (TND) rates contrasted against control Cancer and Circulatory Disease Deaths (CDD) extrapolated from WHO data. Confidence intervals compare USA and the other countries over the period. The Over-75's TND and population increases are examined as a context for the 55-74 outcomes. Male neurological deaths rose >10% in eleven countries, the other countries average rose 20% the USA 43% over the period. Female neurological deaths rose >10% in ten counties, averaging 14%, the USA up 68%. USA male and female neurological deaths increased significantly more than twelve and seventeen countries, respectively. USA over-75s population increased by 49%, other countries 56%. Other countries TND up 187% the USA rose fourfold. Male and female cancer and CDD fell in every country averaging 26% and 21%, respectively, and 64% and 67% for CDD. Male neurological rates rose significantly more than Cancer and CCD in every country; Female neurological deaths rose significantly more than cancer in 17 countries and every country for CDD. There was no significant correlation between increases in neurological deaths and decreases in control mortalities. There are substantial increases in neurological deaths in most countries, significantly so in America. Rises in the 55-74 and over-75's rates are not primarily due to demographic changes and are a matter of concern warranting further investigation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fisetin Acts on Multiple Pathways to Reduce the Impact of Age and Disease on CNS Function

PubMed Central

Maher, Pamela

2017-01-01

It is becoming increasingly clear that neurological diseases are multi-factorial involving disruptions in multiple cellular systems. Thus, while each disease has its own initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological diseases described to date. Thus, it is unlikely that modulating only a single factor will be effective at either preventing disease development or slowing disease progression. A better approach is to identify small (< 900 daltons) molecules that have multiple biological activities relevant to the maintenance of brain function. Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products. This wide range of actions suggests that fisetin has the ability to reduce the impact of age-related neurological diseases on brain function. PMID:25961687

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

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

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.

Gene expression patterns associated with neurological disease in human HIV infection

PubMed Central

Repunte-Canonigo, Vez; Masliah, Eliezer; Lefebvre, Celine

2017-01-01

The pathogenesis and nosology of HIV-associated neurological disease (HAND) remain incompletely understood. Here, to provide new insight into the molecular events leading to neurocognitive impairments (NCI) in HIV infection, we analyzed pathway dysregulations in gene expression profiles of HIV-infected patients with or without NCI and HIV encephalitis (HIVE) and control subjects. The Gene Set Enrichment Analysis (GSEA) algorithm was used for pathway analyses in conjunction with the Molecular Signatures Database collection of canonical pathways (MSigDb). We analyzed pathway dysregulations in gene expression profiles of patients from the National NeuroAIDS Tissue Consortium (NNTC), which consists of samples from 3 different brain regions, including white matter, basal ganglia and frontal cortex of HIV-infected and control patients. While HIVE is characterized by widespread, uncontrolled inflammation and tissue damage, substantial gene expression evidence of induction of interferon (IFN), cytokines and tissue injury is apparent in all brain regions studied, even in the absence of NCI. Various degrees of white matter changes were present in all HIV-infected subjects and were the primary manifestation in patients with NCI in the absence of HIVE. In particular, NCI in patients without HIVE in the NNTC sample is associated with white matter expression of chemokines, cytokines and β-defensins, without significant activation of IFN. Altogether, the results identified distinct pathways differentially regulated over the course of neurological disease in HIV infection and provide a new perspective on the dynamics of pathogenic processes in the course of HIV neurological disease in humans. These results also demonstrate the power of the systems biology analyses and indicate that the establishment of larger human gene expression profile datasets will have the potential to provide novel mechanistic insight into the pathogenesis of neurological disease in HIV infection and identify better therapeutic targets for NCI. PMID:28445538

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.

Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases.

PubMed

Yuan, Hongjie; Low, Chian-Ming; Moody, Olivia A; Jenkins, Andrew; Traynelis, Stephen F

2015-07-01

The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-d-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases

PubMed Central

Yuan, Hongjie; Low, Chian-Ming; Moody, Olivia A.; Jenkins, Andrew

2015-01-01

The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-d-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases. PMID:25904555

Women with Epilepsy: Drug Risks and Safety During Pregnancy

MedlinePlus

... the future. Neurologists from the American Academy of Neurology are doctors who identify and treat diseases of ... an educational service of the American Academy of Neurology. It is based on an assessment of current ...

Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentration in dystonia cases vs. controls.

PubMed

Louis, Elan D; Factor-Litvak, Pam; Michalec, Monika; Jiang, Wendy; Zheng, Wei

2014-09-01

Harmane (1-methyl-9H-pyrido[3,4-b]indole) (HA) is a potent neurotoxin that has been linked to two neurological diseases, essential tremor and Parkinson's disease. Blood harmane concentrations [HA] are elevated in patients with both diseases. An important question is whether HA is specifically linked with these diseases or alternatively, is a non-specific marker of neurological illness. We assessed whether blood [HA] was elevated in patients with a third neurological disease, dystonia, comparing them to controls. Blood [HA] was quantified by high performance liquid chromatography. Subjects comprised 104 dystonia cases and 107 controls. Mean log blood [HA] in dystonia cases was similar to that of controls (0.41±0.51g(-10)/ml vs. 0.38±0.61g(-10)/ml, t=0.42, p=0.68). In unadjusted and adjusted logistic regression analyses, log blood [HA] was not associated with the outcome (diagnosis of dystonia vs. control): odds ratio (OR)unadjusted=1.11, 95% confidence interval (CI)=0.69-1.79, p=0.68; ORadjusted=1.07, 95% CI=0.58-1.97, p=0.84. In contrast to the elevated blood [HA] that has been reported in patients with essential tremor and Parkinson's disease, our data demonstrate that blood [HA] was similar in patients with dystonia and controls. These findings provide the first support for the notion that an elevated blood [HA] is not a broad feature of neurological disease, and may be a specific feature of certain tremor disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Blood Harmane (1-methyl-9H-pyrido[3,4-b]indole) Concentration in Dystonia Cases vs. Controls

PubMed Central

Louis, Elan D.; Factor-Litvak, Pam; Michalec, Monika; Jiang, Wendy; Zheng, Wei

2014-01-01

Background Harmane (1-methyl-9H-pyrido[3,4-b]indole) (HA) is a potent neurotoxin that has been linked to two neurological diseases, essential tremor and Parkinson’s disease. Blood harmane concentrations [HA] are elevated in patients with both diseases. An important question is whether HA is specifically linked with these diseases or alternatively, is a non-specific marker of neurological illness. Objectives We assessed whether blood [HA] was elevated in patients with a third neurological disease, dystonia, comparing them to controls. Methods Blood [HA] were quantified by high performance liquid chromatography. Subjects comprised 104 dystonia cases and 107 controls. Results Mean log blood [HA] in dystonia cases was similar to that of controls (0.41 ± 0.51 g −10/ml vs. 0.38 ± 0.61 g−10/ml, t = 0.42, p = 0.68). In unadjusted and adjusted logistic regression analyses, log blood [HA] was not associated with the outcome (diagnosis of dystonia vs. control): odds ratio (OR) unadjusted = 1.11, 95% confidence interval (CI) = 0.69 – 1.79, p = 0.68; OR adjusted = 1.07, 95% CI = 0.58 – 1.97, p = 0.84. Conclusions In contrast to the elevated blood [HA] that has been reported in patients with essential tremor and Parkinson’s disease, our data demonstrate that blood [HA] was similar in patients with dystonia and controls. These findings provide the first support for the notion that an elevated blood [HA] is not a broad feature of neurological disease, and may be a specific feature of certain tremor disorders. PMID:24968164

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 onset appears to influence the prevalence of several non-cognitive manifestations in both groups, stroke being more prevalent at older ages of onset with motor symptoms being more prevalent at younger age of onset and at an older age of onset. Further, symptoms were overall more common in later clinical stages of disease. Interpretation Comparing the prevalence of non-amnestic and non-cognitive clinical features in DIAN with the published literature indicates that previous reports of non-cognitive features are likely overestimated whereas DIAN identifies higher non-amnestic cognitive symptoms in addition to memory impairment. The non-cognitive clinical manifestations of AD appear to be in a minor fraction of mild-moderate ADAD and is likely influenced by disease severity, environmental and genetic factors in addition to genetic status. The results of this work clarify the clinical presentations of ADAD including the effects of age and disease stage. Attention to these neurologic symptoms and screening for ADAD mutations are warranted if present. Future work is needed to determine the factors which cause these neurologic symptoms. PMID:27777020

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.

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.

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations

PubMed Central

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10–13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease. PMID:29201369

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations.

PubMed

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10-13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease.

Modeling human neurological disorders with induced pluripotent stem cells.

PubMed

Imaizumi, Yoichi; Okano, Hideyuki

2014-05-01

Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. The production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient-specific genetic information. Furthermore, innovations of gene-editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases-specific iPS cell research and described recently obtained knowledge in the form of actual examples. © 2013 International Society for Neurochemistry.

Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus.

PubMed

Cong, Yu; Lentz, Margaret R; Lara, Abigail; Alexander, Isis; Bartos, Christopher; Bohannon, J Kyle; Hammoud, Dima; Huzella, Louis; Jahrling, Peter B; Janosko, Krisztina; Jett, Catherine; Kollins, Erin; Lackemeyer, Matthew; Mollura, Daniel; Ragland, Dan; Rojas, Oscar; Solomon, Jeffrey; Xu, Ziyue; Munster, Vincent; Holbrook, Michael R

2017-04-01

Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition.

Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus

PubMed Central

Cong, Yu; Lentz, Margaret R.; Lara, Abigail; Alexander, Isis; Bartos, Christopher; Bohannon, J. Kyle; Hammoud, Dima; Huzella, Louis; Jahrling, Peter B.; Janosko, Krisztina; Jett, Catherine; Kollins, Erin; Lackemeyer, Matthew; Mollura, Daniel; Ragland, Dan; Rojas, Oscar; Solomon, Jeffrey; Xu, Ziyue; Munster, Vincent

2017-01-01

Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8–10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition. PMID:28388650

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.

[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.

[Pulmonary atelectasis in patients with neurological or muscular disease; gravity-related lung compression by the heart and intra-abdominal organs on persistent supine position].

PubMed

Toyoshima, Mitsuo; Maeoka, Yukinori; Kawahara, Hitoshi; Maegaki, Yoshihiro; Ohno, Kousaku

2006-11-01

We report 10 cases of pulmonary atelectasis diagnosed by chest computed tomography in patients with neurological or muscular disease. Atelectasis was frequently seen in hypotonic patients who could not roll over on their own. The atelectases located mostly in the dorsal bronchopulmonary segments, adjacent to the heart or diaphragm. Atelectasis diminished in two patients after they became able to roll themselves over. Gravity-related lung compression by the heart and intra-abdominal organs on persistent supine position can cause pulmonary atelectasis in patients with neurological or muscular disease who can not roll over by their own power. To confirm that the prone position reduces compression of the lungs, chest computed tomography was performed in both the supine and the prone position in three patients. Sagittal images with three-dimensional computed tomographic reconstruction revealed significant sternad displacements of the heart and caudal displacements of the dorsal portion of the diaphragm on prone position compared with supine position. The prone position, motor exercises for rolling over, and biphasic cuirass ventilation are effective in reducing gravity-related lung compression. Some patients with intellectual disabilities were also able to cooperate in chest physiotherapy. Chest physiotherapy is useful in preventing atelectasis in patients with neurological or muscular disease.

Impact of gut microbiota on neurological diseases: Diet composition and novel treatments.

PubMed

Larroya-García, Ana; Navas-Carrillo, Diana; Orenes-Piñero, Esteban

2018-06-05

Gut microbiota has significant effects on the structure and function of the enteric and central nervous system including human behaviour and brain regulation. Herein, we analyze the role of this intestinal ecosystem, the effects of dietary changes and the administration of nutritional supplements, such as probiotics, prebiotics, or fecal transplantation in neuropsychiatric disorders. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth delivery and environment. However, diet composition and nutritional status has been repeatedly shown to be one of the most critical modifiable factors of this ecosystem. A comprehensively analysis of the microbiome-intestine-brain axis has been performed, including the impact of intestinal bacteria in alterations in the nervous, immune and endocrine systems and their metabolites. Finally, we discuss the latest literature examining the effects of diet composition, nutritional status and microbiota alterations in several neuropsychiatric disorders, such as autism, anxiety, depression, Alzheimer's disease and anorexia nervosa.

Mimicking Neurotransmitter Release in Chemical Synapses via Hysteresis Engineering in MoS2 Transistors.

PubMed

Arnold, Andrew J; Razavieh, Ali; Nasr, Joseph R; Schulman, Daniel S; Eichfeld, Chad M; Das, Saptarshi

2017-03-28

Neurotransmitter release in chemical synapses is fundamental to diverse brain functions such as motor action, learning, cognition, emotion, perception, and consciousness. Moreover, improper functioning or abnormal release of neurotransmitter is associated with numerous neurological disorders such as epilepsy, sclerosis, schizophrenia, Alzheimer's disease, and Parkinson's disease. We have utilized hysteresis engineering in a back-gated MoS 2 field effect transistor (FET) in order to mimic such neurotransmitter release dynamics in chemical synapses. All three essential features, i.e., quantal, stochastic, and excitatory or inhibitory nature of neurotransmitter release, were accurately captured in our experimental demonstration. We also mimicked an important phenomenon called long-term potentiation (LTP), which forms the basis of human memory. Finally, we demonstrated how to engineer the LTP time by operating the MoS 2 FET in different regimes. Our findings could provide a critical component toward the design of next-generation smart and intelligent human-like machines and human-machine interfaces.

Teriflunomide for the treatment of relapsing-remitting multiple sclerosis: patient preference and adherence.

PubMed

Bayas, Antonios; Mäurer, Mathias

2015-01-01

Multiple sclerosis (MS), a chronic demyelinating neuroinflammatory disease of the central nervous system, is the most common neurological disorder leading to disability in young adulthood. In the last 2 decades, numerous treatments for relapsing-remitting MS have been approved with eleven treatment options available worldwide. One of the determinants in treatment selection is disease activity in the individual patient. However, patient preferences play an increasingly major role in treatment decision making. With teriflunomide, a reversible inhibitor of the enzyme dihydroorotate dehydrogenase, a new oral therapeutic option, given once daily, has been approved within the last 2 years by the regulatory agencies. The current review focuses on characteristics of the drug relevant for patients' preferences in the treatment decision process in the light of the available medications. Perceiving and considering patients' preferences will have an effect on treatment adherence, which is known to be often low in MS patients. Teriflunomide-related adherence issues will also be discussed regarding mode of application, dosing, and potential side effects.

Real-time imaging of Huntingtin aggregates diverting target search and gene transcription

PubMed Central

Li, Li; Liu, Hui; Dong, Peng; Li, Dong; Legant, Wesley R; Grimm, Jonathan B; Lavis, Luke D; Betzig, Eric; Tjian, Robert; Liu, Zhe

2016-01-01

The presumptive altered dynamics of transient molecular interactions in vivo contributing to neurodegenerative diseases have remained elusive. Here, using single-molecule localization microscopy, we show that disease-inducing Huntingtin (mHtt) protein fragments display three distinct dynamic states in living cells – 1) fast diffusion, 2) dynamic clustering and 3) stable aggregation. Large, stable aggregates of mHtt exclude chromatin and form 'sticky' decoy traps that impede target search processes of key regulators involved in neurological disorders. Functional domain mapping based on super-resolution imaging reveals an unexpected role of aromatic amino acids in promoting protein-mHtt aggregate interactions. Genome-wide expression analysis and numerical simulation experiments suggest mHtt aggregates reduce transcription factor target site sampling frequency and impair critical gene expression programs in striatal neurons. Together, our results provide insights into how mHtt dynamically forms aggregates and disrupts the finely-balanced gene control mechanisms in neuronal cells. DOI: http://dx.doi.org/10.7554/eLife.17056.001 PMID:27484239

Tuberculosis of the spine with severe angular kyphosis: mean 34-year post-operative follow-up shows that prevention is better than salvage.

PubMed

Wong, Y W; Samartzis, D; Cheung, K M C; Luk, K

2017-10-01

To address the natural history of severe post-tuberculous (TB) kyphosis, with focus upon the long-term neurological outcome, occurrence of restrictive lung disease, and the effect on life expectancy. This is a retrospective clinical review of prospectively collected imaging data based at a single institute. A total of 24 patients of Southern Chinese origin who presented with spinal TB with a mean of 113° of kyphosis (65° to 159°) who fulfilled inclusion criteria were reviewed. Plain radiographs were used to assess the degree of spinal deformity. Myelography, CT and MRI were used when available to assess the integrity of the spinal cord and canal. Patient demographics, age of onset of spinal TB and interventions, types of surgical procedure, intra- and post-operative complications, and neurological status were assessed. All except one of the 24 patients were treated with anti-TB chemotherapy when they were first diagnosed with spinal TB. They subsequently received surgery either for neurological deterioration, or deformity correction in later life. The mean follow-up was 34 years (11 to 59) since these surgical interventions. Some 16 patients (66.7%) suffered from late neurological deterioration at a mean of 26 years (8 to 49) after the initial drug treatment. The causes of neurological deterioration were healed disease in nine patients (56.2%), re-activation in six patients (37.5%) and adjacent level spinal stenosis in one patient (6.3%). The result of surgery was worse in healed disease. Eight patients without neurological deterioration received surgery to correct the kyphosis. The mean correction ranged from 97° to 72°. Three patients who were clinically quiescent with no neurological deterioration were found to have active TB of the spine. Solid fusion was achieved in all cases and no patient suffered from neurological deterioration after 42 years of follow-up. On final follow-up, six patients were noted to have deceased (age range: 47 years to 75 years). Our study presents one of the longest assessments of spinal TB with severe kyphosis. Severe post-TB kyphosis may lead to significant health problems many years following the initial drug treatment. Early surgical correction of the kyphosis, solid fusion and regular surveillance may avoid late complications. Paraplegia, restrictive lung disease and early onset kyphosis might relate to early death. Clinically quiescent disease does not mean cure. Cite this article: Bone Joint J 2017;99-B:1381-8. ©2017 The British Editorial Society of Bone & Joint Surgery.

Neurological risks associated with manganese exposure from welding operations--a literature review.

PubMed

Flynn, Michael R; Susi, Pam

2009-09-01

Exposure to manganese dusts and fumes may cause a clinical neurological syndrome called manganism. Welders are frequently exposed to manganese-containing fumes generated by electric arcs and thermal torches. This paper reviews studies on the association between exposure to such welding fumes and neurological disease. Using the IRSST expert panel criteria, 78 cases of probable/possible, and 19 additional cases of possible occupational manganism were identified in the literature among manganese-exposed workers involved in welding processes. Epidemiological evidence linking welding exposures to Parkinson's disease is still controversial. Although more research is needed to clarify the risks of neurological impairment from welding, control measures including ventilation and adequate respiratory protection, should be implemented to minimize welding fume exposures. The significance of fume transport into the central nervous system via the olfactory nerve, which by-passes the blood-brain barrier, also needs to be assessed.

Diagnosis of cysticercosis in endemic regions. The Cysticercosis Working Group in Peru.

PubMed

Garcia, H H; Martinez, M; Gilman, R; Herrera, G; Tsang, V C; Pilcher, J B; Diaz, F; Verastegui, M; Gallo, C; Porras, M

1991-08-31

Taenia solium cysticercosis is a frequent cause of neurological disease in developing countries. Specific diagnosis of cysticercosis is difficult. We obtained serum and/or CSF samples from 204 consecutive patients admitted to a neurological ward in Lima, Peru, and looked for antibodies specific for T solium with the enzyme-linked immunoelectrotransfer blot (EITB) assay. 21 (12%) of 173 serum samples from these patients were EITB-positive. In contrast, only 2 (1.5%) of 135 patients attending a public endoscopy clinic and 1 (1%) of 88 patients attending a private endoscopy clinic were seropositive. 1 (1%) of 98 pregnant women living in a Lima shanty town was EITB-positive. 15 (58%) of 26 neurology patients diagnosed clinically as having cysticercosis were seronegative. Routine screening by EITB of all patients with neurological symptoms from areas of endemic cysticercosis would avoid misdiagnosis of this common and treatable disease.

Diagnosis of cysticercosis in endemic regions

PubMed Central

Garcia, H. H.; Martinez, M.; Gilman, R.; Herrera, G.; Tsang, V. C. W.; Pilcher, J. B.; Diaz, F.; Verastegui, M.; Gallo, C.; Porras, M.; Alvarado, M.; Naranjo, J.; Miranda, E.

2010-01-01

Taenia solium cysticercosis is a frequent cause of neurological disease in developing countries. Specific diagnosis of cysticercosis is difficult. We obtained serum and/or CSF samples from 204 consecutive patients admitted to a neurological ward in Lima, Peru, and looked for antibodies specific for T solium with the enzyme-linked immunoelectrotransfer blot (EITB) assay. 21 (12%) of 173 serum samples from these patients were EITB-positive. In contrast only 2 (1·5%) of 135 patients attending a public endoscopy clinic and 1 (1%) of 88 patients attending a private endoscopy clinic were seropositive. 1 (1%) of 98 pregnant women living in a Lima shanty town was EITB-positive. 15 (58%) of 26 neurology patients diagnosed clinically as having cysticercosis were seronegative. Routine screening by EITB of all patients with neurological symptoms from areas of endemic cysticercosis would avoid misdiagnosis of this common and treatable disease. PMID:1678809

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.

Gut microbiota: Implications in Parkinson's disease.

PubMed

Parashar, Arun; Udayabanu, Malairaman

2017-05-01

Gut microbiota (GM) can influence various neurological outcomes, like cognition, learning, and memory. Commensal GM modulates brain development and behavior and has been implicated in several neurological disorders like Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, anxiety, stress and much more. A recent study has shown that Parkinson's disease patients suffer from GM dysbiosis, but whether it is a cause or an effect is yet to be understood. In this review, we try to connect the dots between GM and PD pathology using direct and indirect evidence. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Neuromuscular diseases were always difficult to diagnose].

PubMed

Claus, D

2013-06-01

The Deutsche Zeitschrift fuer Nervenheilkunde (German Journal for Neurology) was founded as a specifically neurological journal at the end of the nineteenth century and soon became a European platform for scientific discussion of neurological topics. Papers also came from the USA, Scandinavia and Russia. The difficulties of the diagnosis and definition of clinical entities are illustrated in cases of botulism, myotonic dystrophy and myasthenia gravis.

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.

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.

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

PubMed

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

2017-03-01

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

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease

PubMed Central

Nguyen, Tammy T.; Oh, Sang S.; Weaver, David; Lewandowska, Agnieszka; Maxfield, Dane; Schuler, Max-Hinderk; Smith, Nathan K.; Macfarlane, Jane; Saunders, Gerald; Palmer, Cheryl A.; Debattisti, Valentina; Koshiba, Takumi; Pulst, Stefan; Feldman, Eva L.; Hajnóczky, György; Shaw, Janet M.

2014-01-01

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease. PMID:25136135

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.

Structural and Genetic Studies Demonstrate Neurologic Dysfunction in Triosephosphate Isomerase Deficiency Is Associated with Impaired Synaptic Vesicle Dynamics

DOE PAGES

Roland, Bartholomew P.; Zeccola, Alison M.; Larsen, Samantha B.; ...

2016-03-31

Triosephosphate isomerase (TPI) deficiency is a poorly understood disease characterized by hemolytic anemia, cardiomyopathy, neurologic dysfunction, and early death. TPI deficiency is one of a group of diseases known as glycolytic enzymopathies, but is unique for its severe patient neuropathology and early mortality. The disease is caused by missense mutations and dysfunction in the glycolytic enzyme, TPI. Previous studies have detailed structural and catalytic changes elicited by disease-associated TPI substitutions, and samples of patient erythrocytes have yielded insight into patient hemolytic anemia; however, the neuropathophysiology of this disease remains a mystery. This study combines structural, biochemical, and genetic approaches tomore » demonstrate that perturbations of the TPI dimer interface are sufficient to elicit TPI deficiency neuropathogenesis. Also, the present study demonstrates that neurologic dysfunction resulting from TPI deficiency is characterized by synaptic vesicle dysfunction, and can be attenuated with catalytically inactive TPI. Collectively, our findings are the first to identify, to our knowledge, a functional synaptic defect in TPI deficiency derived from molecular changes in the TPI dimer interface.« less

Current Update on Synopsis of miRNA Dysregulation in Neurological Disorders

PubMed Central

Kamal, Mohammad A.; Mushtaq, Gohar; Greig, Nigel H.

2018-01-01

Aberrant expression of microRNAs (miRNAs) has been implicated in various neurological disorders (NDs) of the central nervous system such as Alzheimer disease, Parkinson’s disease, Huntington disease, amyotrophic lateral sclerosis, schizophrenia and autism. If dysregulated miRNAs are identified in patients suffering from NDs, this may serve as a biomarker for the earlier diagnosis and monitoring of disease progression. Identifying the role of miRNAs in normal cellular processes and understanding how dysregulated miRNA expression is responsible for their neurological effects is also critical in the development of new therapeutic strategies for NDs. miRNAs hold great promise from a therapeutic point of view especially if it can be proved that a single miRNA has the ability to influence several target genes, making it possible for the researchers to potentially modify a whole disease phenotype by modulating a single miRNA molecule. Hence, better understanding of the mechanisms by which miRNA play a role in the pathogenesis of NDs may provide novel targets to scientists and researchers for innovative therapies. PMID:25714967

Neurological outcome of patients with cryopyrin-associated periodic syndrome (CAPS).

PubMed

Mamoudjy, Nafissa; Maurey, Hélène; Marie, Isabelle; Koné-Paut, Isabelle; Deiva, Kumaran

2017-02-14

To assess the neurological involvement and outcome, including school and professional performances, of adults and children with cryopyrin-associated periodic syndrome (CAPS). In this observational study, patients with genetically proven CAPS and followed in the national referral centre for autoinflammatory diseases at Bicêtre hospital were assessed. Neurological manifestations, CSF data and MRI results at diagnosis and during follow-up were analyzed. Twenty-four patients (15 adults and 9 children at diagnosis) with CAPS were included. The median age at disease onset was 0 year (birth) [range 0-14], the median age at diagnosis was 20 years [range 0-53] and the mean duration of follow-up was 10.4 ± 2 years. Neurological involvement at diagnosis, mostly headaches and hearing loss, was noted in 17 patients (71%). Two patients of the same family had abnormal brain MRI. A439V mutation is frequently associated with a non-neurological phenotype while R260W mutation tends to be associated with neurological involvement. Eleven adult patients (61%) and 3 children (50%) underwent school difficulties. Neurological involvement is frequent in patients with CAPS and the majority of patients presented difficulties in school performances with consequences in the professional outcome during adulthood. Further studies in larger cohorts of children with CAPS focusing in intellectual efficiency and school performances are necessary.

Report by the Spanish Foundation for the Brain on the social impact of amyotrophic lateral sclerosis and other neuromuscular disorders.

PubMed

Camacho, A; Esteban, J; Paradas, C

A thorough knowledge of the socioeconomic scope of neuromuscular disease is essential for managing resources and raising social awareness. Our group reviewed current data on the epidemiology, mortality and dependence rates, and socioeconomic impact of amyotrophic lateral sclerosis and neuromuscular diseases in Spain. We also recorded how neurological care for these patients is organised. Neuromuscular disorders are a very heterogeneous group of diseases, and some are very rare. These disorders account for between 2.8% and 18% of the total motives for a neurological consultation. In Spain, prevalence and incidence figures for amyotrophic lateral sclerosis are similar to those in other countries; however, figures for patients with other neuromuscular diseases are not known. Since the diseases are chronic, progressive, and debilitating, they cause considerable disability and dependence, which in turn directly affects healthcare and social costs associated with the disease. The costs generated by one patient with amyotrophic lateral sclerosis or Duchenne disease have been calculated at about 50 000 euros per year. Neuromuscular disease shows aetiological, diagnostic, and prognostic complexity, and it requires multidisciplinary management. Follow-up for these patients should be entrusted to specialised units. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation of Imaging Methods in Tick-Borne Encephalitis.

PubMed

Zawadzki, Radosław; Garkowski, Adam; Kubas, Bożena; Zajkowska, Joanna; Hładuński, Marcin; Jurgilewicz, Dorota; Łebkowska, Urszula

2017-01-01

Tick-borne encephalitis (TBE) is caused by a virus that belongs to the Flaviviridae family and is transmitted by tick bites. The disease has a biphasic course. Diagnosis is based on laboratory examinations because of non-specific clinical features, which usually entails the detection of specific IgM antibodies in either blood or cerebrospinal fluid that appear in the second phase of the disease. Neurological symptoms, time course of the disease, and imaging findings are multifaceted. During the second phase of the disease, after the onset of neurological symptoms, magnetic resonance imaging (MRI) abnormalities are observed in a limited number of cases. However, imaging features may aid in predicting the prognosis of the disease.

Outcomes following severe hand foot and mouth disease: A systematic review and meta-analysis.

PubMed

Jones, Eben; Pillay, Timesh D; Liu, Fengfeng; Luo, Li; Bazo-Alvarez, Juan Carlos; Yuan, Chen; Zhao, Shanlu; Chen, Qi; Li, Yu; Liao, Qiaohong; Yu, Hongjie; Rogier van Doorn, H; Sabanathan, Saraswathy

2018-04-20

Hand, foot and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is associated with acute neurological disease in children. This study aimed to estimate the burden of long-term sequelae and death following severe HFMD. This systematic review and meta-analysis pooled all reports from English and Chinese databases including MEDLINE and Wangfang on outbreaks of clinically diagnosed HFMD and/or laboratory-confirmed EV-A71 with at least 7 days' follow-up published between 1st January 1966 and 19th October 2015. Two independent reviewers assessed the literature. We used a random effects meta-analysis to estimate cumulative incidence of neurological sequelae or death. Studies were assessed for methodological and reporting quality. PROSPERO registration number: 10.15124/CRD42015021981. 43 studies were included in the review, and 599 children from 9 studies were included in the primary analysis. Estimated cumulative incidence of death or neurological sequelae at maximum follow up was 19.8% (95% CI:10.2%, 31.3%). Heterogeneity (Iˆ2) was 88.57%, partly accounted for by year of data collection and reporting quality of studies. Incidence by acute disease severity was 0.00% (0.00, 0.00) for grade IIa; 17.0% (7.9, 28.2) for grade IIb/III; 81.6% (65.1, 94.5) for grade IV (p = 0.00) disease. HFMD with neurological involvement is associated with a substantial burden of long-term neurological sequelae. Grade of acute disease severity was a strong predictor of outcome. Strengths of this study include its bilingual approach and clinical applicability. Future prospective and interventional studies must use rigorous methodology to assess long-term outcomes in survivors. There was no specific funding for this study. See below for researcher funding. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Anticipating smallpox and monkeypox outbreaks: complications of the smallpox vaccine.

PubMed

Abrahams, Brian C; Kaufman, David M

2004-09-01

The recent outbreak in the Midwest of monkeypox, as well as the continued fears of a terrorist-induced epidemic of smallpox, prompted the authors' review of the literature regarding past and current experiences with smallpox vaccination. The smallpox vaccine, which is highly effective in preventing the spread of both these orthopoxvirus infectious illnesses, might be administered to numerous health care workers and, in the event of a smallpox attack, millions of other citizens. However, vaccinees would be at risk for several vaccine-related neurologic complications. According to prior reports, neurologic complications have occurred in 2.5 per million US individuals, with the most common being postvaccinal encephalomyelitis (PVEM). In older children and adults, PVEM causes stupor and coma, seizures, paraparesis, and other neurologic and mental abnormalities, and, in 16% of cases, permanent neurologic sequelae. The overall mortality rate of neurologic complications is approximately 1.5 per million vaccinees. Risk factors for PVEM were age younger than 1 year and no previous smallpox vaccination, but not a prior episode of PVEM or other preexisting neurologic illnesses. Neither the current smallpox vaccination campaigns in Israel nor the one in the United States has had comparable complications, but the US campaign has been associated with myocarditis and myopericarditis. Although the potential neurologic complications of the smallpox vaccine must be weighed against the threat of monkeypox and smallpox, current experience with vaccination suggests it carries a very low risk of neurologic complications and does not lead to exacerbations of chronic neurologic illnesses.

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.

Effect of Chinese Herbal Medicine on Molecular Imaging of Neurological Disorders.

PubMed

Yao, Yao; Chen, Ting; Huang, Jing; Zhang, Hong; Tian, Mei

2017-01-01

Chinese herbal medicine has been used to treat a wide variety of neurological disorders including stroke, Alzheimer's disease, and Parkinson's disease. However, its mechanism behind the effectiveness remains unclear. Recently, molecular imaging technology has been applied for this purpose, since it can assess the cellular or molecular function in a living subject by using specific imaging probes and/or radioactive tracers, which enable efficient analysis and monitoring the therapeutic response repetitively. This chapter reviews the in vivo functional and metabolic changes after administration of Chinese herbal medicine in various neurological disorders and provides perspectives on the future evaluations of therapeutic response of Chinese herbal medicine. © 2017 Elsevier Inc. All rights reserved.

Astrogliopathology in neurological, neurodevelopmental and psychiatric disorders

PubMed Central

Verkhratsky, Alexei; Parpura, Vladimir

2015-01-01

Astroglial cells represent a main element in the maintenance of homeostasis and providing defense to the brain. Consequently, their dysfunction underlies many, if not all, neurological, neuropsychiatric and neurodegenerative disorders. General astrogliopathy is evident in diametrically opposing morpho-functional changes in astrocytes, i.e. their hypertrophy along with reactivity or atrophy with asthenia. Neurological disorders with astroglial participation can be genetic, of which Alexander disease is a primary sporadic astrogliopathy, environmentally caused, such as heavy metal encephalopathies, or neurodevelopmental in origin. Astroglia also play a role in major neuropsychiatric disorders, ranging from schizophrenia to depression, as well as in additive disorders. Furthermore, astroglia contribute to neurodegenerative processes seen in amyotrophic lateral sclerosis, Alzheimer’s and Huntington’s diseases. PMID:25843667

The neurological complications of chikungunya virus: A systematic review

PubMed Central

Gerardin, Patrick; de Brito, Carlos Alexandre Antunes; Soares, Cristiane Nascimento; Ferreira, Maria Lucia Brito

2018-01-01

Summary We performed a systematic review on the neurological complications of chikungunya virus. Such complications are being reported increasingly, owing primarily to the scale of recent epidemics but also to a growing understanding of the virus' neurovirulence. We performed a thorough literature search using PubMed and Scopus databases, summating the data on all published reports of neurological disease associated with chikungunya virus. We appraised the data for each major condition in adults, children, and neonates, as well as evaluating the latest evidence on disease pathogenesis and management strategies. The review provides a comprehensive summary for clinicians, public health officials, and researchers tackling the challenges associated with this important emerging pathogen. PMID:29671914

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system.

PubMed

Kim, Hee Jin; Kim, Pitna; Shin, Chan Young

2013-03-01

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng's therapeutic effects. These include Alzheimer's disease, Parkinson's disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng.

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system

PubMed Central

Kim, Hee Jin; Kim, Pitna; Shin, Chan Young

2013-01-01

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng’s therapeutic effects. These include Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng. PMID:23717153

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

The neurologic significance of celiac disease biomarkers

PubMed Central

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

2014-01-01

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

Parkinson disease - resources

MedlinePlus

Resources - Parkinson disease ... The following organizations are good resources for information on Parkinson disease : The Michael J. Fox Foundation -- www.michaeljfox.org National Institute of Neurological Disorders and Stroke -- www. ...

Validity and Inter-Rater Reliability of a Novel Bedside Referral Tool for Spasticity

ClinicalTrials.gov

2018-02-20

Spasticity, Muscle; Muscular Diseases; Musculoskeletal Disease; Muscle Hypertonia; Muscle Spasticity; Neuromuscular Manifestations; Signs and Symptoms; Nervous System Diseases; Neurologic Manifestations

Metabotropic glutamatergic receptors and their ligands in drug addiction.

PubMed

Pomierny-Chamioło, Lucyna; Rup, Kinga; Pomierny, Bartosz; Niedzielska, Ewa; Kalivas, Peter W; Filip, Małgorzata

2014-06-01

Glutamatergic excitatory transmission is implicated in physiological and pathological conditions like learning, memory, neuronal plasticity and emotions, while glutamatergic abnormalities are reported in numerous neurological and psychiatric disorders, including neurodegenerative diseases, epilepsy, stroke, traumatic brain injury, depression, anxiety, schizophrenia and pain. Also, several lines of evidence have accumulated indicating a pivotal role for glutamatergic neurotransmission in mediating addictive behaviors. Among the proteins regulating glutamatergic transmission, the metabotropic glutamate receptors (mGluR) are being developed as pharmacological targets for treating many neuropsychiatric disorders, including drug addiction. In this review we describe the molecular structure of mGluRs and their distribution, physiology and pharmacology in the central nervous system, as well as their use as targets in preclinical studies of drug addiction. Copyright © 2013 Elsevier Inc. All rights reserved.

The role of infections in Behçet disease and neuro-Behçet syndrome.

PubMed

Marta, Monica; Santos, Ernestina; Coutinho, Ester; Silva, Ana Martins; Correia, João; Vasconcelos, Carlos; Giovannoni, Gavin

2015-07-01

Infections are considered an environmental trigger for exacerbations of immune-mediated diseases. We aimed to establish if common viral infections could be identified as a precipitant of Behçet disease (BD) with or without neurological involvement and to assess the variability of the immune response to common viruses. We also investigated whether cytokines and chemokines could be markers of neurological involvement. Finally, we explored if anti-basal ganglia antibodies (ABGAs) would be associated with neurological involvement in BD. Our study included 14 individuals with BD with neurological involvement (neuroBehçet syndrome - NBS), 16 individuals with BD without neurological involvement and 18 healthy controls (HC). Overall we found a tendency for increased levels of anti-viral IgG antibody levels in BD, more evident in NBS patients versus HC. Epstein-Barr viral-capsid antigen IgG titres were increased in NBS patients versus other BD patients (p=0.032). Anti-measles antibody titres induced by vaccination were similarly elevated. ABGAs were not detected in the serum of our cohort. Raised levels of serum IL-8 in some BD patients did not reflect clinical activity or severity. In conclusion, there was evidence for a polyclonal immune activation rather than a specific virus effect in the sera of individuals with BD or NBS. Copyright © 2015 Elsevier B.V. All rights reserved.

The burden of mental, neurological, and substance use disorders in China and India: a systematic analysis of community representative epidemiological studies.

PubMed

Charlson, Fiona J; Baxter, Amanda J; Cheng, Hui G; Shidhaye, Rahul; Whiteford, Harvey A

2016-07-23

China and India jointly account for 38% of the world population, so understanding the burden attributed to mental, neurological, and substance use disorders within these two countries is essential. As part of the Lancet/Lancet Psychiatry China-India Mental Health Alliance Series, we aim to provide estimates of the burden of mental, neurological, and substance use disorders for China and India from the Global Burden of Disease Study 2013 (GBD 2013). In this systematic analysis for community representative epidemiological studies, we conducted systematic reviews in line with PRISMA guidelines for community representative epidemiological studies. We extracted estimates of prevalence, incidence, remission and duration, and mortality along with associated uncertainty intervals from GBD 2013. Using these data as primary inputs, DisMod-MR 2.0, a Bayesian meta-regression instrument, used a log rate and incidence-prevalence-mortality mathematical model to develop internally consistent epidemiological models. Disability-adjusted life-year (DALY) changes between 1990 and 2013 were decomposed to quantify change attributable to population growth and ageing. We projected DALYs from 2013 to 2025 for mental, neurological, and substance use disorders using United Nations population data. Around a third of global DALYs attributable to mental, neurological, and substance use disorders were found in China and India (66 million DALYs), a number greater than all developed countries combined (50 million DALYs). Disease burden profiles differed; India showed similarities with other developing countries (around 50% of DALYs attributable to non-communicable disease), whereas China more closely resembled developed countries (around 80% of DALYs attributable to non-communicable disease). The overall population growth in India explains a greater proportion of the increase in mental, neurological, and substance use disorder burden from 1990 to 2013 (44%) than in China (20%). The burden of mental, neurological, and substance use disorders is estimated to increase by 10% in China and 23% in India between 2013 and 2025. The current and projected burden of mental, neurological, and substance use disorders in China and India warrants the urgent prioritisation of programmes focused on targeted prevention, early identification, and effective treatment. China Medical Board, Bill & Melinda Gates Foundation. Copyright © 2016 Elsevier Ltd. All rights reserved.

CNS imaging findings associated with Parry-Romberg syndrome and en coup de sabre: correlation to dermatologic and neurologic abnormalities.

PubMed

Doolittle, Derrick A; Lehman, Vance T; Schwartz, Kara M; Wong-Kisiel, Lily C; Lehman, Julia S; Tollefson, Megha M

2015-01-01

Parry-Romberg syndrome (PRS) and en coup de sabre (ECS) are variants of morphea. Although numerous findings on central nervous system (CNS) imaging of PRS and ECS have been reported, the spectrum and frequency of CNS imaging findings and relation to cutaneous and neurologic abnormalities have not been fully characterized. We retrospectively reviewed patients younger than 50 years at our institution over a 16-year interval who had clinical diagnosis of PRS and ECS by a skin or facial subspecialist. Two neuroradiologists evaluated available imaging and characterized CNS imaging findings. Eighty-eight patients with PRS or ECS were identified (62 women [70.4 %]; mean age 28.8 years). Of the 43 patients with CNS imaging, 19 (44 %) had abnormal findings. The only finding in 1 of these 19 patients was lateral ventricle asymmetry; of the other 18, findings were bilateral in 11 (61 %), ipsilateral to the side of facial involvement in 6 (33 %), and contralateral in 1 (6 %). Sixteen patients had serial imaging examinations over an average of 632 days; 13 (81 %) had stable imaging findings, and 3 (19 %) had change over time. Of six patients with progressive cutaneous findings, five (83 %) had stable imaging findings over time. Among the 23 patients with clinical neurologic abnormality and imaging, 12 (52 %) had abnormal imaging findings. All seven patients with seizures (100 %) had abnormal imaging studies. In PRS and ECS, imaging findings often are bilateral and often do not progress, regardless of cutaneous disease activity. Findings are inconsistently associated with clinical abnormalities.

Are BDNF and glucocorticoid activities calibrated?

PubMed Central

Jeanneteau, Freddy; Chao, Moses V.

2012-01-01

One hypothesis to account for the onset and severity of neurological disorders is the loss of trophic support. Indeed, changes in the levels and activities of brain-derived neurotrophic factor (BDNF) occur in numerous neurodegenerative and neuropsychiatric diseases. A deficit promotes vulnerability whereas a gain of function facilitates recovery by enhancing survival, synapse formation and synaptic plasticity. Implementation of ‘BDNF therapies’, however, faces numerous methodological and pharmacokinetic issues. Identifying BDNF mimetics that activate the BDNF receptor or downstream targets of BDNF signaling represent an alternative approach. One mechanism that shows great promise is to study the interplay of BDNF and glucocorticoid hormones, a major class of natural steroid secreted during stress reactions and in synchrony with circadian rhythms. While small amounts of glucocorticoids support normal brain function, excess stimulation by these steroid hormones precipitate stress-related affective disorders. To date, however, because of the paucity of knowledge of underlying cellular mechanisms, deleterious effects of glucocorticoids are not prevented following extreme stress. In the present review, we will discuss the complementary roles share by BDNF and glucocorticoids in synaptic plasticity, and delineate possible signaling mechanisms mediating these effects. PMID:23022538

[The possibility of using music therapy in neurology on the example of multiple sclerosis].

PubMed

Boiko, E A; Ivanchuk, E V; Gunchenko, M M; Batysheva, T T

2016-01-01

Currently music therapy plays an important role in the drug-free treatment and rehabilitation of children and adults with acute and chronic neurological and somatic diseases including demyelinating diseases. Existing studies show the effectiveness of music therapy in the improvement of social skills, cognitive function and sleep as well as in the reduction in the severity of depression, anxiety and pain in patients with multiple sclerosis.

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.

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.

The Emergence of Single Neurons in Clinical Neurology

PubMed Central

Cash, Sydney S.; Hochberg, Leigh R.

2015-01-01

Summary Single neuron actions and interactions are the sine qua non of brain function, and nearly all diseases and injuries of the central nervous system trace their clinical sequelae to neuronal dysfunction or failure. Remarkably, discussion of neuronal activity is largely absent in clinical neuroscience. Advances in neurotechnology and computational capabilities, accompanied by shifts in theoretical frameworks, have led to renewed interest in the information represented by single neurons. Using direct interfaces with the nervous system, millisecond-scale information will soon be extracted from single neurons in clinical environments, supporting personalized treatment of neurologic and psychiatric disease. In this review we focus on single neuronal activity in restoring communication and motor control in patients suffering from devastating neurological injuries. We also explore the single neuron's role in epilepsy and movement disorders, surgical anesthesia, and in cognitive processes disrupted in neurodegenerative and neuropsychiatric disease. Finally, we speculate on how technological advances will revolutionize neurotherapeutics. PMID:25856488

The emergence of single neurons in clinical neurology.

PubMed

Cash, Sydney S; Hochberg, Leigh R

2015-04-08

Single neuron actions and interactions are the sine qua non of brain function, and nearly all diseases and injuries of the CNS trace their clinical sequelae to neuronal dysfunction or failure. Remarkably, discussion of neuronal activity is largely absent in clinical neuroscience. Advances in neurotechnology and computational capabilities, accompanied by shifts in theoretical frameworks, have led to renewed interest in the information represented by single neurons. Using direct interfaces with the nervous system, millisecond-scale information will soon be extracted from single neurons in clinical environments, supporting personalized treatment of neurologic and psychiatric disease. In this Perspective, we focus on single-neuronal activity in restoring communication and motor control in patients suffering from devastating neurological injuries. We also explore the single neuron's role in epilepsy and movement disorders, surgical anesthesia, and in cognitive processes disrupted in neurodegenerative and neuropsychiatric disease. Finally, we speculate on how technological advances will revolutionize neurotherapeutics. Copyright © 2015 Elsevier Inc. All rights reserved.

Eliminating barriers to personalized medicine: learning from neurofibromatosis type 1.

PubMed

Gutmann, David H

2014-07-29

With the emergence of high-throughput discovery platforms, robust preclinical small-animal models, and efficient clinical trial pipelines, it is becoming possible to envision a time when the treatment of human neurologic diseases will become personalized. The emergence of precision medicine will require the identification of subgroups of patients most likely to respond to specific biologically based therapies. This stratification only becomes possible when the determinants that contribute to disease heterogeneity become more fully elucidated. This review discusses the defining factors that underlie disease heterogeneity relevant to the potential for individualized brain tumor (optic pathway glioma) treatments arising in the common single-gene cancer predisposition syndrome, neurofibromatosis type 1 (NF1). In this regard, NF1 is posited as a model genetic condition to establish a workable paradigm for actualizing precision therapeutics for other neurologic disorders. © 2014 American Academy of Neurology.

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.

[Dopamine neurotransmission of peripheral blood lymphocytes is a potential biomarker of psychiatric and neurological disorders].

PubMed

Taraskina, A E; Nasyrova, R F; Grunina, M N; Zabotina, A M; Ivashchenko, D V; Ershov, E E; Sosin, D N; Kirnichnaya, K A; Ivanov, M V; Krupitsky, E M

2015-01-01

Current literature on a role of dopamine in the development of mental and neurological disorders suggests that the discovery of endogenous dopamine in peripheral blood lymphocytes gave rise to a new line of research. Dopamine receptors are not only found on cells of the innate immune response (nonspecific), but also on cells of adaptive immune response (specific): T and B lymphocytes. These facts bring a new evidence of interrelationships between the peripheral immune system, neuroinflammation and neurodegeneration and suggest new ways for investigation of the pathogenesis of different mental and neurological disorders, in particular Parkinson's disease, Alzheimer's disease and schizophrenia. There is strong evidence that ligands of dopamine receptors can change the expression of coding genes both in central neurons and in peripheral cells. Thus, peripheral blood lymphocytes may prove a cellular tool to identify dopamine transmission disturbances in neuropsychiatric diseases, as well as to monitor the effects of pharmacological treatment.

Thyroid disease and the nervous system.

PubMed

Wood-Allum, Clare A; Shaw, Pamela J

2014-01-01

Thyroid disorders are common in the general population and in hospitalized patients. Thyroid disease may present first with neurological complications or else may occur concurrently in patients suffering other neurological disorders, particularly those with an autoimmune etiology. For this reason neurologists will commonly encounter patients with thyroid disease. This chapter provides an overview of the neurological complications and associations of disorders of the thyroid gland. Particular emphasis is placed on conditions such as thyrotoxic periodic paralysis and myxedema coma in which the underlying thyroid disorder may be occult leading to a first, often emergency, presentation to a neurologist. Information about clinical features, diagnosis, pathogenesis, therapy, and prognosis is provided. Emphasis is placed on those aspects most likely to be relevant to the practicing neurologist and the interested reader is directed to references to good, recent review articles for further information. © 2014 Elsevier B.V. All rights reserved.

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

Tay-Sachs Disease

MedlinePlus

... better understanding of how neurological deficits arise in lipid storage diseases and on the development of new treatments targeting disease mechanisms. Specific research on the gangliodisoses including expanding the use of ...

Evaluating Hospital-Based Surveillance for Outbreak Detection in Bangladesh: Analysis of Healthcare Utilization Data

PubMed Central

Nikolay, Birgit; Salje, Henrik; Sturm-Ramirez, Katharine; Azziz-Baumgartner, Eduardo; Homaira, Nusrat; Iuliano, A. Danielle; Paul, Repon C.; Hossain, M. Jahangir; Cauchemez, Simon; Gurley, Emily S.

2017-01-01

Background The International Health Regulations outline core requirements to ensure the detection of public health threats of international concern. Assessing the capacity of surveillance systems to detect these threats is crucial for evaluating a country’s ability to meet these requirements. Methods and Findings We propose a framework to evaluate the sensitivity and representativeness of hospital-based surveillance and apply it to severe neurological infectious diseases and fatal respiratory infectious diseases in Bangladesh. We identified cases in selected communities within surveillance hospital catchment areas using key informant and house-to-house surveys and ascertained where cases had sought care. We estimated the probability of surveillance detecting different sized outbreaks by distance from the surveillance hospital and compared characteristics of cases identified in the community and cases attending surveillance hospitals. We estimated that surveillance detected 26% (95% CI 18%–33%) of severe neurological disease cases and 18% (95% CI 16%–21%) of fatal respiratory disease cases residing at 10 km distance from a surveillance hospital. Detection probabilities decreased markedly with distance. The probability of detecting small outbreaks (three cases) dropped below 50% at distances greater than 26 km for severe neurological disease and at distances greater than 7 km for fatal respiratory disease. Characteristics of cases attending surveillance hospitals were largely representative of all cases; however, neurological disease cases aged <5 y or from the lowest socioeconomic group and fatal respiratory disease cases aged ≥60 y were underrepresented. Our estimates of outbreak detection rely on suspected cases that attend a surveillance hospital receiving laboratory confirmation of disease and being reported to the surveillance system. The extent to which this occurs will depend on disease characteristics (e.g., severity and symptom specificity) and surveillance resources. Conclusion We present a new approach to evaluating the sensitivity and representativeness of hospital-based surveillance, making it possible to predict its ability to detect emerging threats. PMID:28095468

Recommendations for the diagnosis and management of Niemann-Pick disease type C: an update.

PubMed

Patterson, Marc C; Hendriksz, Christian J; Walterfang, Mark; Sedel, Frederic; Vanier, Marie T; Wijburg, Frits

2012-07-01

Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease caused by mutations in either the NPC1 (in 95% of cases) or the NPC2 gene (in around 5% of cases), which lead to impaired intracellular lipid trafficking and accumulation of cholesterol and glycosphingolipids in the brain and other tissues. Characteristic neurological manifestations of NP-C include saccadic eye movement (SEM) abnormalities or vertical supranuclear gaze palsy (VSGP), cerebellar signs (ataxia, dystonia/dysmetria, dysarthria and dysphagia) and gelastic cataplexy. Epileptic seizures are also common in affected patients. Typically, neurological disease onset occurs during childhood, although an increasing number of cases are being detected and diagnosed during adulthood based on late-onset neurological signs and psychiatric manifestations. Categorization of patients according to age at onset of neurological manifestations (i.e. early-infantile, late-infantile, juvenile and adolescent/adult-onset) can be useful for the evaluation of disease course and treatment responses. The first international guidelines for the clinical management of NP-C in children and adults were published in 2009. Since that time a significant amount of data regarding the epidemiology, detection/diagnosis, and treatment of NP-C has been published. Here, we report points of consensus among experts in the diagnosis and treatment of NP-C based on a follow-up meeting in Paris, France in September 2011. This article serves as an update to the original guidelines providing, among other things, further information on detection/diagnostic methods, potential new methods of monitoring disease progression, and therapy. Treatment goals and the application of disease-specific therapy with miglustat are also re-evaluated. Copyright © 2012 Elsevier Inc. All rights reserved.

Oxygen radicals as key mediators in neurological disease: fact or fiction?

PubMed

Halliwell, B

1992-01-01

A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radicals and other reactive oxygen species are frequently proposed to be involved in the pathology of several neurological disorders. Criteria for establishing such involvement are presented. Development of new methods for measuring oxidative damage should enable elucidation of the precise role of reactive oxygen species in neurological disorders.

Cryptococcus gattii in North American Pacific Northwest: whole-population genome analysis provides insights into species evolution and dispersal.

PubMed

Engelthaler, David M; Hicks, Nathan D; Gillece, John D; Roe, Chandler C; Schupp, James M; Driebe, Elizabeth M; Gilgado, Felix; Carriconde, Fabian; Trilles, Luciana; Firacative, Carolina; Ngamskulrungroj, Popchai; Castañeda, Elizabeth; Lazera, Marcia dos Santos; Melhem, Marcia S C; Pérez-Bercoff, Asa; Huttley, Gavin; Sorrell, Tania C; Voelz, Kerstin; May, Robin C; Fisher, Matthew C; Thompson, George R; Lockhart, Shawn R; Keim, Paul; Meyer, Wieland

2014-07-15

The emergence of distinct populations of Cryptococcus gattii in the temperate North American Pacific Northwest (PNW) was surprising, as this species was previously thought to be confined to tropical and semitropical regions. Beyond a new habitat niche, the dominant emergent population displayed increased virulence and caused primary pulmonary disease, as opposed to the predominantly neurologic disease seen previously elsewhere. Whole-genome sequencing was performed on 118 C. gattii isolates, including the PNW subtypes and the global diversity of molecular type VGII, to better ascertain the natural source and genomic adaptations leading to the emergence of infection in the PNW. Overall, the VGII population was highly diverse, demonstrating large numbers of mutational and recombinational events; however, the three dominant subtypes from the PNW were of low diversity and were completely clonal. Although strains of VGII were found on at least five continents, all genetic subpopulations were represented or were most closely related to strains from South America. The phylogenetic data are consistent with multiple dispersal events from South America to North America and elsewhere. Numerous gene content differences were identified between the emergent clones and other VGII lineages, including genes potentially related to habitat adaptation, virulence, and pathology. Evidence was also found for possible gene introgression from Cryptococcus neoformans var. grubii that is rarely seen in global C. gattii but that was present in all PNW populations. These findings provide greater understanding of C. gattii evolution in North America and support extensive evolution in, and dispersal from, South America. Importance: Cryptococcus gattii emerged in the temperate North American Pacific Northwest (PNW) in the late 1990s. Beyond a new environmental niche, these emergent populations displayed increased virulence and resulted in a different pattern of clinical disease. In particular, severe pulmonary infections predominated in contrast to presentation with neurologic disease as seen previously elsewhere. We employed population-level whole-genome sequencing and analysis to explore the genetic relationships and gene content of the PNW C. gattii populations. We provide evidence that the PNW strains originated from South America and identified numerous genes potentially related to habitat adaptation, virulence expression, and clinical presentation. Characterization of these genetic features may lead to improved diagnostics and therapies for such fungal infections. The data indicate that there were multiple recent introductions of C. gattii into the PNW. Public health vigilance is warranted for emergence in regions where C. gattii is not thought to be endemic. Copyright © 2014 Engelthaler et al.

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

Education Research: Neurology resident education: Trending skills, confidence, and professional preparation.

PubMed

Jordan, Justin T; Mayans, David; Schneider, Logan; Adams, Nellie; Khawaja, Ayaz M; Engstrom, John

2016-03-15

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. An electronic survey was sent to all American Academy of Neurology members graduating from US neurology residency programs in the Spring of 2014. 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. 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. © 2016 American Academy of Neurology.

NATIONAL COLLABORATIVE PERINATAL PROJECT (AAD - HEALTH AND SOCIAL SERVICES BRANCH)

EPA Science Inventory

Study was conducted by NIH's National Institute of Neurological Diseases and Stroke. Biomedical and behavioral research in many areas of obstetrics, perinatology, pediatrics, and developmental psychology. The data also provide a prospective base for examining neurological and neu...

Progress in Paralysis | NIH MedlinePlus the Magazine

MedlinePlus

... benefits from this research flowing to people with Parkinson's disease or other neurological disorders? The mechanism of dysfunction in spinal cord injury is not completely understood but is believed to be ... Parkinson's and some of the other neurological disorders. Consequently, ...

Protothecal granulomatous meningoencephalitis in a dog.

PubMed

Salvadori, C; Gandini, G; Ballarini, A; Cantile, C

2008-10-01

A case of central nervous system protothecosis in a dog is reported. A three-year-old male Maremma sheepdog was referred with a two month history of diarrhoea associated with progressive tetraparesis, depression and right circling. Stupor, severe proprioceptive deficits, bilateral decreased thoracic limb flexor reflexes and bilateral deficit of the menace reaction were detected on neurological examination and a multi-focal neurological localisation was suspected. Histopathological evaluation revealed multi-focal granulomatous foci in the thalamus, hippocampus and caudal brainstem containing numerous oval-rounded organisms with a thick, periodic acid-Schiff-positive and Gomori's methenamine silver-positive cell wall, a basophilic cytoplasm and one nucleus. Scattered sporangia containing two to four endospores were also observed. Morphological features were consistent with Prototheca species. Ultrastructurally, numerous degenerated algae were present within macrophages mainly lacking nuclei and cytoplasmic organelles. Generally, protothecosis in dogs is characterised by systemic signs because of a multi-organ involvement, and haemorrhagic colitis or ophthalmologic signs are the most frequent presenting signs. However, protothecosis should be added, also in Europe, to the list of the differential diagnoses in adult dogs with a multi-focal neurological localisation even in absence of other clinical signs.

Recent advances in the diagnosis and treatment of niemann-pick disease type C in children: a guide to early diagnosis for the general pediatrician.

PubMed

Alobaidy, Hanna

2015-01-01

Niemann-Pick disease (NP-C) is a lysosomal storage disease in which impaired intracellular lipid transport leads to accumulation of cholesterol and glycosphingolipids in various neurovisceral tissues. It is an autosomal recessive disorder, caused by mutations in the NPC1 or NPC2 genes. The clinical spectrum is grouped by the age of onset and onset of neurological manifestation: pre/perinatal; early infantile; late infantile; and juvenile periods. The NP-C Suspicion Index (SI) screening tool was developed to identify suspected patients with this disease. It is especially good at recognizing the disease in patients older than four years of age. Biochemical tests involving genetic markers and Filipin staining of skin fibroblast are being employed to assist diagnosis. Therapy is mostly supportive and since 2009, the first specific therapy approved for use was Miglustat (Zavesca) aimed at stabilizing the rate of progression of neurological manifestation. The prognosis correlates with age at onset of neurological signs; patients with early onset form progress faster. The NP-C disease has heterogeneous neurovisceral manifestations. A SI is a screening tool that helps in diagnostic process. Filipin staining test is a specific biomarker diagnostic test. Miglustat is the first disease-specific therapy.

Prevalence of Comorbid Spasticity and Urinary Incontinence in Residents of a Long-Term Care Facility

ClinicalTrials.gov

2018-02-20

Spasticity, Muscle; Muscular Diseases; Musculoskeletal Disease; Muscle Hypertonia; Muscle Spasticity; Neuromuscular Manifestations; Signs and Symptoms; Nervous System Diseases; Neurologic Manifestations

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

Neurologic disorders associated with anti-glutamic acid decarboxylase antibodies: A comparison of anti-GAD antibody titers and time-dependent changes between neurologic disease and type I diabetes mellitus.

PubMed

Nakajima, Hideto; Nakamura, Yoshitsugu; Inaba, Yuiko; Tsutsumi, Chiharu; Unoda, Kiichi; Hosokawa, Takafumi; Kimura, Fumiharu; Hanafusa, Toshiaki; Date, Masamichi; Kitaoka, Haruko

2018-04-15

To determine clinical features of neurologic disorders associated with anti-glutamic acid decarboxylase antibodies (anti-GAD-Ab), we examined titers and time-dependent changes of anti-GAD-Ab. Six patients, stiff person syndrome (2), cerebellar ataxia (1), limbic encephalitis (1), epilepsy (1), brainstem encephalitis (1), were compared with 87 type I diabetes mellitus (T1DM) patients without neurologic disorders. Anti-GAD-Ab titers and index were higher in neurologic disorders than in T1DM, suggesting intrathecal antibody synthesis. Anti-GAD-Ab titers in T1DM decreased over time, whereas they remained high in neurologic disorders. Immunotherapy improved neurological disorders and anti-GAD-Ab titers and index provide clinically meaningful information about their diagnostic accuracy. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Guillain-Barre syndrome caused by hepatitis E infection: case report and literature review.

PubMed

Zheng, Xiaoqin; Yu, Liang; Xu, Qiaomai; Gu, Silan; Tang, Lingling

2018-01-23

Hepatitis E infection is a global disorder that causes substantial morbidity. Numerous neurologic illnesses, including Guillain-Barre syndrome (GBS), have occurred in patients with hepatitis E virus (HEV) infection. We report a 58 year-old non-immunocompromised man who presented with progressive muscle weakness in all extremities during an episode of acute HEV infection, which was confirmed by measuring the anti-HEV IgM antibodies in the serum. Both cerebrospinal fluid examination and electrophysiological study were in agreement with the diagnosis of HEV-associated GBS. Following the treatment with intravenous immunoglobulin, the patient's neurological condition improved rapidly. HEV infection should be strongly considered in patients with neurological symptoms, especially those with elevated levels of liver enzymes.

Wavelet-based characterization of gait signal for neurological abnormalities.

PubMed

Baratin, E; Sugavaneswaran, L; Umapathy, K; Ioana, C; Krishnan, S

2015-02-01

Studies conducted by the World Health Organization (WHO) indicate that over one billion suffer from neurological disorders worldwide, and lack of efficient diagnosis procedures affects their therapeutic interventions. Characterizing certain pathologies of motor control for facilitating their diagnosis can be useful in quantitatively monitoring disease progression and efficient treatment planning. As a suitable directive, we introduce a wavelet-based scheme for effective characterization of gait associated with certain neurological disorders. In addition, since the data were recorded from a dynamic process, this work also investigates the need for gait signal re-sampling prior to identification of signal markers in the presence of pathologies. To benefit automated discrimination of gait data, certain characteristic features are extracted from the wavelet-transformed signals. The performance of the proposed approach was evaluated using a database consisting of 15 Parkinson's disease (PD), 20 Huntington's disease (HD), 13 Amyotrophic lateral sclerosis (ALS) and 16 healthy control subjects, and an average classification accuracy of 85% is achieved using an unbiased cross-validation strategy. The obtained results demonstrate the potential of the proposed methodology for computer-aided diagnosis and automatic characterization of certain neurological disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

[Cerebral ischemia in Rendu-Osler-Weber disease].

PubMed

Delgado Reyes, S; García de la Rocha, M L; Fernández-Armayor Ajo, V; Sierra Sierra, I; Martín Araguz, A; Moreno Martínez, J M

2000-02-01

Neurologic manifestations occur in 8-12% of the patients with Rendu-Osler-Weber disease or hereditary hemorrhagic telangiectasia (HHT), principally infectious and hemorrhagic and, less frequently, ischemic ones. More than a half of these neurologic complications are associated with pulmonary arterio-venous malformations (PAVM). The diagnosis of HHT is based on the presence of telangiectases, hemorrhagic events and a family history with an autosomal dominant pattern. We report a case of a patient diagnosed as having HHT with transient ischemic attacks and a PAVM, which was occluded by the use of embolotherapy. Cerebral ischemia in HHT is related to the existence of a PAVM and results from three mechanisms: 1) secondary poliglobulia and hyperviscosity because of the hypoxemia due to a right-left shunt; 2) communication between the airway and the pulmonary circulation during cough access, which produces gas embolism and hemoptysis; 3) and, finally, paradoxical embolism trough the PAVM, the same mechanism proposed to the infectious neurologic manifestations of the disease. When the diagnosis of HHT is suspected, early search and treatment of PAVM, with embolotherapy or surgery, are necessary in order to avoid respiratory problems (hemoptysis, exertional dyspnea, cianosis, clubbing) and neurologic complications.

Leptomeningeal metastases: a RANO proposal for response criteria

PubMed Central

Junck, Larry; Brandsma, Dieta; Soffietti, Riccardo; Rudà, Roberta; Raizer, Jeffrey; Boogerd, Willem; Taillibert, Sophie; Groves, Morris D.; Rhun, Emilie Le; Walker, Julie; van den Bent, Martin; Wen, Patrick Y.; Jaeckle, Kurt A.

2017-01-01

Abstract Leptomeningeal metastases (LM) currently lack standardization with respect to response assessment. A Response Assessment in Neuro-Oncology (RANO) working group with expertise in LM developed a consensus proposal for evaluating patients treated for this disease. Three basic elements in assessing response in LM are proposed: a standardized neurological examination, cerebral spinal fluid (CSF) cytology or flow cytometry, and radiographic evaluation. The group recommends that all patients enrolling in clinical trials undergo CSF analysis (cytology in all cancers; flow cytometry in hematologic cancers), complete contrast-enhanced neuraxis MRI, and in instances of planned intra-CSF therapy, radioisotope CSF flow studies. In conjunction with the RANO Neurological Assessment working group, a standardized instrument was created for assessing the neurological exam in patients with LM. Considering that most lesions in LM are nonmeasurable and that assessment of neuroimaging in LM is subjective, neuroimaging is graded as stable, progressive, or improved using a novel radiological LM response scorecard. Radiographic disease progression in isolation (ie, negative CSF cytology/flow cytometry and stable neurological assessment) would be defined as LM disease progression. The RANO LM working group has proposed a method of response evaluation for patients with LM that will require further testing, validation, and likely refinement with use. PMID:28039364

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.

A national case-crossover analysis of the short-term effect of PM2.5 on hospitalizations and mortality in subjects with diabetes and neurological disorders.

PubMed

Zanobetti, Antonella; Dominici, Francesca; Wang, Yun; Schwartz, Joel D

2014-05-22

Diabetes and neurological disorders are a growing burden among the elderly, and may also make them more susceptible to particulate air matter with aerodynamic diameter less than 2.5 μg (PM2.5). The same biological responses thought to effect cardiovascular disease through air pollution-mediated systemic oxidative stress, inflammation and cerebrovascular dysfunction could also be relevant for diabetes and neurodegenerative diseases. We conducted multi-site case-crossover analyses of all-cause deaths and of hospitalizations for diabetes or neurological disorders among Medicare enrollees (>65 years) during the period 1999 to 2010 in 121 US communities. We examined whether 1) short-term exposure to PM2.5 increases the risk of hospitalization for diabetes or neurological disorders, and 2) the association between short-term exposure to PM2.5 and all-cause mortality is modified by having a previous hospitalization of diabetes or neurological disorders. We found that short term exposure to PM2.5 is significantly associated with an increase in hospitalization risks for diabetes (1.14% increase, 95% CI: 0.56, 1.73 for a 10 μg/m3 increase in the 2 days average), and for Parkinson's disease (3.23%, 1.08, 5.43); we also found an increase in all-cause mortality risks (0.64%, 95% CI: 0.42, 0.85), but we didn't find that hospitalization for diabetes and neurodegenerative diseases modifies the association between short term exposure to PM2.5 and all-cause mortality. We found that short-term exposure to fine particles increased the risk of hospitalizations for Parkinson's disease and diabetes, and of all-cause mortality. While the association between short term exposure to PM2.5 and mortality was higher among Medicare enrollees that had a previous admission for diabetes and neurological disorders than among Medicare enrollees that did not had a prior admission for these diseases, the effect modification was not statistically significant. We believe that these results provide useful insights regarding the mechanisms by which particles may affect the brain. A better understanding of the mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system.

Numeracy Skills in Patients With Degenerative Disorders and Focal Brain Lesions

PubMed Central

Cappelletti, Marinella; Butterworth, Brian; Kopelman, Michael

2012-01-01

Objective: To characterize the numerical profile of patients with acquired brain disorders. Method: We investigated numeracy skills in 76 participants—40 healthy controls and 36 patients with neurodegenerative disorders (Alzheimer dementia, frontotemporal dementia, semantic dementia, progressive aphasia) and with focal brain lesions affecting parietal, frontal, and temporal areas as in herpes simplex encephalitis (HSE). All patients were tested with the same comprehensive battery of paper-and-pencil and computerized tasks assessing numerical abilities and calculation. Degenerative and HSE patients also performed nonnumerical semantic tasks. Results: Our results, based on nonparametric group statistics as well as on the analysis of individual patients, and all highly significant, show that: (a) all patients, including those with parietal lesions—a key brain area for numeracy processing—had intact processing of number quantity; (b) patients with impaired semantic knowledge had much better preserved numerical knowledge; and (c) most patients showed impaired calculation skills, with the exception of most semantic dementia and HSE patients. Conclusion: Our results allow us, for the first time, to characterize the numeracy skills in patients with a variety of neurological conditions and to suggest that the pattern of numerical performance can vary considerably across different neurological populations. Moreover, the selective sparing of calculation skills in most semantic dementia and HSE suggest that numerical abilities are an independent component of the semantic system. Finally, our data suggest that, besides the parietal areas, other brain regions might be critical to the understanding and processing of numerical concepts. PMID:22122516

77 FR 32975 - AHRQ Workgroups on ICD-10-CM/PCS Conversion of Quality Indicators (QIs)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-04

... relevant clinical expertise (e.g., cardiovascular disease, neurologic disease, orthopedic and musculoskeletal disease, obstetrics and gynecologic disease, surgery, critical care and pulmonary disease... measurement using administrative data in specific, relevant clinical domains (e.g., cardiovascular disease...

[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.

Case for diagnosis. Riga-Fede disease.

PubMed

Calistru, Ana Maria; Lisboa, Carmen; Bettencourt, Herberto; Azevedo, Filomena

2012-01-01

Riga-Fede disease is a rare, benign disorder characterized by reactive ulceration of the oral mucosa associated with repetitive dental traumatism. It was first described in children with neurologic disorders and is very rare in adults. This case report describes the occurrence of a large ulcer of the tongue, resembling squamous cell carcinoma, in an adult with hemiparesis. The lesion cleared after neurologic recovery. This case highlights the importance of considering this disorder in the differential diagnosis of oral mucosal ulcerations.

The Madrid School of Neurology (1885-1939).

PubMed

Giménez-Roldán, S

2015-01-01

The emergence of neurology in Madrid between 1885 and 1939 had well-defined characteristics. On foundations laid by Cajal and Río-Hortega, pioneers combined clinical practice with cutting-edge neurohistology and neuropathology research. Luis Simarro, trained in Paris, taught many talented students including Gayarre, Achúcarro and Lafora. The untimely death of Nicolás Achúcarro curtailed his promising career, but he still completed the clinicopathological study of the first American case of Alzheimer's disease. On returning to Spain, he studied glial cells, including rod cells. Rodríguez Lafora described progressive myoclonus epilepsy and completed experimental studies of corpus callosum lesions and clinical and neuropathology studies of senile dementia. He fled to Mexico at the end of the Spanish Civil War (1936-1939). Sanchís Banús, a sterling clinical neurologist, described the first cluster of Huntington's disease in Spain, and he and Río-Hortega joined efforts to determine that pallidal degeneration underlies rigidity in advanced stages of the disease. Just after the war, Alberca Llorente eruditely described inflammatory diseases of the neuraxis. Manuel Peraita studied "the neurology of hunger" with data collected during the siege of Madrid. Dionisio Nieto, like many exiled intellectuals, settled in Mexico DF, where he taught neurohistological methods and neuropsychiatry in the tradition of the Madrid School of Neurology. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Laryngotracheal Stenosis in Children and Infants With Neurological Disorders: Management and Outcome.

PubMed

Nicollas, Richard; Moreddu, Eric; Le Treut-Gay, Claire; Roman, Stéphane; Mancini, Julien; Triglia, Jean-Michel

2016-12-01

The goal of this retrospective study is to compare the management and outcome of surgical treatment of laryngotracheal stenosis in children and infants with and without an associated neurological disorder. In a series of children operated on for subglottic stenosis (SGS), patients with an associated neurological disorder were identified. The following criteria were compared in children with and without neurological disease: grade of stenosis, age, technique (Crico-Tracheal Resection (CTR), Laryngo-Tracheo-Plasty (LTP) in single and 2 stage, laser), analyzing duration, preoperative tracheostomy, decannulation rate, preoperative gastrostomy, and number of days in intensive care unit and in hospital. Two hundred twenty-three children were operated on for subglottic stenosis, of whom 68 (30.5%) had an associated neurological disorder. Some criteria were found to be statistically different between the 2 populations: mean age of 43 months in neurological population versus 13 months (P < .001). The distribution of the grades of SGS appeared similar in the 2 groups (P = .088), and the mean duration of stay in hospital and in ICU were not statistically different (respectively, P = .186 and P = .056) between the 2 groups; a 2-stage procedure was performed more frequently than 1-stage in the cases with associated neurological disorder-66.6% versus 36.5% (P = .013); the median duration of stenting was 20 days in those with neurological disease versus 12 (P = .021). Preoperative tracheotomy was noted in 75% of neurological patients versus 47.7% of the others (P < .001). The outcome was considered to be good (decannulation and no further treatment) following a single procedure in 82.4% of patients with neurological disorder, as against 86.5% of neurologically unimpaired subjects. The difference in outcome of surgery was not statistically different (P = .392) between the 2 groups. It appears that subglottic stenosis in children with associated neurological disorder is not more severe than in neurologically normal patients. In three-quarters of the neurologically impaired cases, a preoperative tracheostomy was needed, but the rates of failure of postoperative decannulation are not statistically significant between the 2 groups. In our experience, 2-stage techniques are more often performed than single stage in this population in order to allow airway safety, for example after feeding. If properly managed, the final results are similar in the 2 populations. © The Author(s) 2016.

A Review of Neurogenic Stunned Myocardium

PubMed Central

Wongrakpanich, Supakanya; Agrawal, Akanksha; Yadlapati, Sujani; Kishlyansky, Marina; Figueredo, Vincent

2017-01-01

Neurologic stunned myocardium (NSM) is a phenomenon where neurologic events give rise to cardiac abnormalities. Neurologic events like stroke and seizures cause sympathetic storm and autonomic dysregulation that result in myocardial injury. The clinical presentation can involve troponin elevation, left ventricular dysfunction, and ECG changes. These findings are similar to Takotsubo cardiomyopathy and acute coronary syndrome. It is difficult to distinguish NSM from acute coronary syndrome based on clinical presentation alone. Because of this difficulty, a patient with NSM who is at high risk for coronary heart disease may undergo cardiac catheterization to rule out coronary artery disease. The objective of this review of literature is to enhance physician's awareness of NSM and its features to help tailor management according to the patient's clinical profile. PMID:28875040

Measles, mumps, rubella, and human parvovirus B19 infections and neurologic disease.

PubMed

Bale, James F

2014-01-01

While the systemic disorders associated with measles, mumps, and rubella viruses and human parvovirus B19 tend to be mild, each virus can produce potentially life-threatening neurologic disease in human hosts, especially when these viruses infect young children. Two of the viruses, rubella and parvovirus B19, can be vertically transmitted to fetuses during maternal infection and cause congenital infection. Neurologic complications are common after intrauterine infection with the rubella virus, a condition known as the congenital rubella syndrome. Two, measles and rubella viruses, can induce "slow viral" infections, serious, disorders that can occur several years after the initial exposure to the virus and typically have fatal outcomes. © 2014 Elsevier B.V. All rights reserved.

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.

Therapeutic approaches to preventing cell death in Huntington disease

PubMed Central

Kaplan, Anna; Stockwell, Brent R.

2012-01-01

Neurodegenerative diseases affect the lives of millions of patients and their families. Due to the complexity of these diseases and our limited understanding of their pathogenesis, the design of therapeutic agents that can effectively treat these diseases has been challenging. Huntington disease (HD) is one of several neurological disorders with few therapeutic options. HD, like numerous other neurodegenerative diseases, involves extensive neuronal cell loss. One potential strategy to combat HD and other neurodegenerative disorders is to intervene in the execution of neuronal cell death. Inhibiting neuronal cell death pathways may slow the development of neurodegeneration. However, discovering small molecule inhibitors of neuronal cell death remains a significant challenge. Here, we review candidate therapeutic targets controlling cell death mechanisms that have been the focus of research in HD, as well as an emerging strategy that has been applied to developing small molecule inhibitors—fragment-based drug discovery (FBDD). FBDD has been successfully used in both industry and academia to identify selective and potent small molecule inhibitors, with a focus on challenging proteins that are not amenable to traditional high-throughput screening approaches. FBDD has been used to generate potent leads, pre-clinical candidates, and has led to the development of an FDA approved drug. This approach can be valuable for identifying modulators of cell-death-regulating proteins; such compounds may prove to be the key to halting the progression of HD and other neurodegenerative disorders. PMID:22967354

Neurology of the H1N1 pandemic in Singapore: a nationwide case series of children and adults.

PubMed

Prerna, Asha; Lim, Jocelyn Y X; Tan, Natalie W H; Isa, Mas Suhaila; Oh, Helen May-Lin; Yassin, Norazieda; Low, Chian-Yong; Chan, Derrick W S; Chong, Chia-Yin; Leo, Yee-Sin; Chow, Angela Li-Ping; Tambyah, Paul Ananth; Tan, Kevin

2015-10-01

Neurologic complications have long been associated with influenza. A novel strain of influenza A (H1N1) first described in humans to have outbreak potential in 2009 in Mexico went on to become the first influenza pandemic of this century. We evaluated the neurologic complications of the novel influenza A (H1N1) 2009 in children and adults admitted to all public hospitals in Singapore during the influenza A (H1N1) 2009 pandemic between May 2009 and March 2010. All patients were positive for novel H1N1 infection and presented with neurologic symptoms prior to oseltamivir treatment. Ninety-eight patients (median age 6.6 years, range 0.4-62.6) were identified; 90 % were younger than 18 years; 32 % suffered from preexisting neurological, respiratory, or cardiac disease; and 66 % presented with seizures. Of those presenting with seizures, new onset seizures were the most common manifestation (n = 40, 61.5 %), followed by breakthrough seizures (n = 18, 27.7 %) and status epilepticus (n = 7, 10.8 %). Influenza-associated encephalopathy occurred in 20 %. The majority of children (n = 88) presented with seizures (n = 63, 71.6 %), encephalopathy (n = 19, 21.6 %), and syncope (n = 4, 4.5 %). Among adults, a wider range of neurological conditions were seen, with half of them presenting with an exacerbation of their underlying neurological disease. The neurological symptoms developed at a median of 2 days after the onset of systemic symptoms. The median length of hospital stay was 3 days, and 79 % were monitored in general wards. Neurologic complications associated with the novel influenza A (H1N1) 2009 strain were generally mild and had a good outcome. They occurred more frequently in patients with underlying neurological disorders. Seizures and encephalopathy were the most common manifestations, similar to other influenza virus strains.

Therapeutics for Equine Protozoal Myeloencephalitis.

PubMed

Pusterla, Nicola; Tobin, Thomas

2017-04-01

Equine protozoal myeloencephalitis is an infectious disease of the central nervous system caused by Sarcocystis neurona or Neospora hughesi. Affected horses routinely present with progressive and asymmetrical neurologic deficits. The diagnosis relies on the presence of neurologic signs, ruling out other neurologic disorders, and the detection of intrathecally derived antibodies to either S neurona and/or N hughesi. Recommended treatment is use of an FDA-approved anticoccidial drug formulation. Medical and supportive treatment is provided based on the severity of neurologic deficits and complications. This article focuses on recent data related to diagnosis, pharmacologic treatment, and prevention. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Risk of neurological, eye and ear disease in offspring to parents with schizophrenia or depression compared with offspring to healthy parents.

PubMed

Gunnarsdóttir, Elin Dianna; Hällgren, Jonas; Hultman, Christina M; McNeil, Thomas F; Crisby, Milita; Sandin, Sven

2018-04-19

Neurological, visual and hearing deviations have been observed in the offspring of parents with schizophrenia. This study test whether children to parents hospitalized with schizophrenia have increased the likelihood of childhood neurological disorder. Among all parents in Sweden born 1950-1985 and with offspring born 1968-2002: 7107 children with a parent hospitalized for schizophrenia were compared to 172 982 children with no parents hospitalized for schizophrenia or major depression, as well as to 32 494 children with a parent hospitalized for major depression as a control population with another severe psychiatric outcome. We estimated relative risks (RR) and two-sided 95% confidence intervals calculated from Poisson regression. Children to parents with schizophrenia were more likely than controls to have been hospitalized before the age of 10 with a diagnosis of cerebral palsy, RR = 1.76 (95% CI: 1.15-2.69); epilepsy, RR = 1.78 (95% CI: 1.33-2.40), combined neurological disease, RR = 1.33 (95% CI: 1.11-1.60) and certain diseases of the eye, RR = 1.92 (95% CI: 1.17-3.15) and ear, RR = 1.18 (95% CI: 1.05-1.32). Similar disease-risk-pattern was found for children to parents hospitalized with a diagnosis of major depression. A specific risk increase for strabismus RR = 1.21 (95%CI: 1.05-1.40) was found for off-spring with parental depression. Compared with children to healthy parents, children to parents with schizophrenia have increased risk of a variety of neurological disorders as well as visual and hearing disorders at an early age. The risk increase was not specific to schizophrenia but was also seen in children to parents with a diagnosis of major depression.

Inertial Sensors to Assess Gait Quality in Patients with Neurological Disorders: A Systematic Review of Technical and Analytical Challenges

PubMed Central

Vienne, Aliénor; Barrois, Rémi P.; Buffat, Stéphane; Ricard, Damien; Vidal, Pierre-Paul

2017-01-01

Gait disorders are major causes of falls in patients with neurological diseases. Understanding these disorders allows prevention and better insights into underlying diseases. InertiaLocoGraphy (ILG) –the quantification of gait by using inertial measurement units (IMUs) –shows great potential to address this public health challenge, but protocols vary widely and normative values of gait parameters are still unavailable. This systematic review critically compares ILG protocols, questions features extracted from inertial signals and proposes a semeiological analysis of clinimetric characteristics for use in neurological clinical routine. For this systematic review, PubMed, Cochrane and EMBASE were searched for articles assessing gait quality by using IMUs that were published from January 1, 2014 to August 31, 2016. ILG was used to assess gait in a wide range of neurological disorders – including Parkinson disease, mild cognitive impairment, Alzheimer disease, cerebral palsy, and cerebellar atrophy – as well as in the faller or frail older population and in people presenting rheumatological pathologies. However, results have not yet been driving changes in clinical practice. One reason could be that studies mainly aimed at comparing pathological gait to healthy gait, but there is stronger need for semiological descriptions of gait perturbation, severity or prognostic assessment. Furthermore, protocols used to assess gait using IMUs are too many. Likely, outcomes are highly heterogeneous and difficult to compare across large panels of studies. Therefore, homogenization is needed to foster the use of ILG to assess gait quality in neurological routine practice. The pros and cons of each protocol are emphasized so that a compromise can be reached. As well, analysis of seven complementary clinical criteria (springiness, sturdiness, smoothness, steadiness, stability, symmetry, synchronization) is advocated. PMID:28572784

Oscillatory Activities in Neurological Disorders of Elderly: Biomarkers to Target for Neuromodulation.

PubMed

Giovanni, Assenza; Capone, Fioravante; di Biase, Lazzaro; Ferreri, Florinda; Florio, Lucia; Guerra, Andrea; Marano, Massimo; Paolucci, Matteo; Ranieri, Federico; Salomone, Gaetano; Tombini, Mario; Thut, Gregor; Di Lazzaro, Vincenzo

2017-01-01

Non-invasive brain stimulation (NIBS) has been under investigation as adjunct treatment of various neurological disorders with variable success. One challenge is the limited knowledge on what would be effective neuronal targets for an intervention, combined with limited knowledge on the neuronal mechanisms of NIBS. Motivated on the one hand by recent evidence that oscillatory activities in neural systems play a role in orchestrating brain functions and dysfunctions, in particular those of neurological disorders specific of elderly patients, and on the other hand that NIBS techniques may be used to interact with these brain oscillations in a controlled way, we here explore the potential of modulating brain oscillations as an effective strategy for clinical NIBS interventions. We first review the evidence for abnormal oscillatory profiles to be associated with a range of neurological disorders of elderly (e.g., Parkinson's disease (PD), Alzheimer's disease (AD), stroke, epilepsy), and for these signals of abnormal network activity to normalize with treatment, and/or to be predictive of disease progression or recovery. We then ask the question to what extent existing NIBS protocols have been tailored to interact with these oscillations and possibly associated dysfunctions. Our review shows that, despite evidence for both reliable neurophysiological markers of specific oscillatory dis-functionalities in neurological disorders and NIBS protocols potentially able to interact with them, there are few applications of NIBS aiming to explore clinical outcomes of this interaction. Our review article aims to point out oscillatory markers of neurological, which are also suitable targets for modification by NIBS, in order to facilitate in future studies the matching of technical application to clinical targets.

Management and outcome of mechanically ventilated neurologic patients.

PubMed

Pelosi, Paolo; Ferguson, Niall D; Frutos-Vivar, Fernando; Anzueto, Antonio; Putensen, Christian; Raymondos, Konstantinos; Apezteguia, Carlos; Desmery, Pablo; Hurtado, Javier; Abroug, Fekri; Elizalde, José; Tomicic, Vinko; Cakar, Nahit; Gonzalez, Marco; Arabi, Yaseen; Moreno, Rui; Esteban, Andres

2011-06-01

To describe and compare characteristics, ventilatory practices, and associated outcomes among mechanically ventilated patients with different types of brain injury and between neurologic and nonneurologic patients. Secondary analysis of a prospective, observational, and multicenter study on mechanical ventilation. Three hundred forty-nine intensive care units from 23 countries. We included 552 mechanically ventilated neurologic patients (362 patients with stroke and 190 patients with brain trauma). For comparison we used a control group of 4,030 mixed patients who were ventilated for nonneurologic reasons. None. We collected demographics, ventilatory settings, organ failures, and complications arising during ventilation and outcomes. Multivariate logistic regression analysis was performed with intensive care unit mortality as the dependent variable. At admission, a Glasgow Coma Scale score ≤8 was observed in 68% of the stroke, 77% of the brain trauma, and 29% of the nonneurologic patients. Modes of ventilation and use of a lung-protective strategy within the first week of mechanical ventilation were similar between groups. In comparison with nonneurologic patients, patients with neurologic disease developed fewer complications over the course of mechanical ventilation with the exception of a higher rate of ventilator-associated pneumonia in the brain trauma cohort. Neurologic patients showed higher rates of tracheotomy and longer duration of mechanical ventilation. Mortality in the intensive care unit was significantly (p < .001) higher in patients with stroke (45%) than in brain trauma (29%) and nonneurologic disease (30%). Factors associated with mortality were: stroke (in comparison to brain trauma), Glasgow Coma Scale score on day 1, and severity at admission in the intensive care unit. In our study, one of every five mechanically ventilated patients received this therapy as a result of a neurologic disease. This cohort of patients showed a higher mortality rate than nonneurologic patients despite a lower incidence of extracerebral organ dysfunction.

Oscillatory Activities in Neurological Disorders of Elderly: Biomarkers to Target for Neuromodulation

PubMed Central

Assenza, Giovanni; Capone, Fioravante; di Biase, Lazzaro; Ferreri, Florinda; Florio, Lucia; Guerra, Andrea; Marano, Massimo; Paolucci, Matteo; Ranieri, Federico; Salomone, Gaetano; Tombini, Mario; Thut, Gregor; Di Lazzaro, Vincenzo

2017-01-01

Non-invasive brain stimulation (NIBS) has been under investigation as adjunct treatment of various neurological disorders with variable success. One challenge is the limited knowledge on what would be effective neuronal targets for an intervention, combined with limited knowledge on the neuronal mechanisms of NIBS. Motivated on the one hand by recent evidence that oscillatory activities in neural systems play a role in orchestrating brain functions and dysfunctions, in particular those of neurological disorders specific of elderly patients, and on the other hand that NIBS techniques may be used to interact with these brain oscillations in a controlled way, we here explore the potential of modulating brain oscillations as an effective strategy for clinical NIBS interventions. We first review the evidence for abnormal oscillatory profiles to be associated with a range of neurological disorders of elderly (e.g., Parkinson’s disease (PD), Alzheimer’s disease (AD), stroke, epilepsy), and for these signals of abnormal network activity to normalize with treatment, and/or to be predictive of disease progression or recovery. We then ask the question to what extent existing NIBS protocols have been tailored to interact with these oscillations and possibly associated dysfunctions. Our review shows that, despite evidence for both reliable neurophysiological markers of specific oscillatory dis-functionalities in neurological disorders and NIBS protocols potentially able to interact with them, there are few applications of NIBS aiming to explore clinical outcomes of this interaction. Our review article aims to point out oscillatory markers of neurological, which are also suitable targets for modification by NIBS, in order to facilitate in future studies the matching of technical application to clinical targets. PMID:28659788

ATP7A-related copper transport diseases-emerging concepts and future trends.

PubMed

Kaler, Stephen G

2011-01-01

This Review summarizes recent advances in understanding copper-transporting ATPase 1 (ATP7A), and examines the neurological phenotypes associated with dysfunction of this protein. Involvement of ATP7A in axonal outgrowth, synapse integrity and neuronal activation underscores the fundamental importance of copper metabolism to neurological function. Defects in ATP7A cause Menkes disease, an infantile-onset, lethal condition. Neonatal diagnosis and early treatment with copper injections enhance survival in patients with this disease, and can normalize clinical outcomes if mutant ATP7A molecules retain small amounts of residual activity. Gene replacement rescues a mouse model of Menkes disease, suggesting a potential therapeutic approach for patients with complete loss-of-function ATP7A mutations. Remarkably, a newly discovered ATP7A disorder-isolated distal motor neuropathy-has none of the characteristic clinical or biochemical abnormalities of Menkes disease or its milder allelic variant occipital horn syndrome (OHS), instead resembling Charcot-Marie-Tooth disease type 2. These findings indicate that ATP7A has a crucial but previously unappreciated role in motor neuron maintenance, and that the mechanism underlying ATP7A-related distal motor neuropathy is distinct from Menkes disease and OHS pathophysiology. Collectively, these insights refine our knowledge of the neurology of ATP7A-related copper transport diseases and pave the way for further progress in understanding ATP7A function.

Molecular genetics in neurology.

PubMed

Martin, J B

1993-12-01

There has been remarkable progress in the identification of mutations in genes that cause inherited neurological disorders. Abnormalities in the genes for Huntington disease, neurofibromatosis types 1 and 2, one form of familial amyotrophic lateral sclerosis, fragile X syndrome, myotonic dystrophy, Kennedy syndrome, Menkes disease, and several forms of retinitis pigmentosa have been elucidated. Rare disorders of neuronal migration such as Kallmann syndrome, Miller-Dieker syndrome, and Norrie disease have been shown to be due to specific gene defects. Several muscle disorders characterized by abnormal membrane excitability have been defined as mutations of the muscle sodium or chloride channels. These advances provide opportunity for accurate molecular diagnosis of at-risk individuals and are the harbinger of new approaches to therapy of these diseases.

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 results than others (one trial). Different time schedules for administration of rectal medication may produce different bowel responses (one trial). Mechanical evacuation may be more effective than oral or rectal medication (one trial). There appears to be a benefit to patients in one-off educational interventions from nurses. The clinical significance of any of these results is difficult to interpret. There is still remarkably little research on this common and, to patients, very significant condition. It is not possible to draw any recommendation for bowel care in people with neurological diseases from the trials included in this review. Bowel management for these people must remain empirical until well-designed controlled trials with adequate numbers and clinically relevant outcome measures become available.

Parkinson's Disease Research at NIH | NIH MedlinePlus the Magazine

MedlinePlus

... turn JavaScript on. Feature: Parkinson's Disease Parkinson's Disease Research at NIH Past Issues / Winter 2014 Table of ... Disorders/All-Disorders/Parkinsons-Disease-Information-Page What Research Is Being Done? The National Institute of Neurological ...

Parkinson's disease (PD) in the elderly: an example of geriatric syndrome (GS)?

PubMed

Lauretani, Fulvio; Maggio, Marcello; Silvestrini, Claudio; Nardelli, Anna; Saccavini, Marsilio; Ceda, Gian Paolo

2012-01-01

PD is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. In the latest decade, the approach to PD was dramatically changed. In fact, although for many years PD has been considered only "a disease that affects walking", with a key role of the neurotransmitter dopamine, recently the neurological approach has been substantially modified. The approach for this disease is not only a neurological issue. Given the complexity of its clinical aspects, such as depression, anxiety, dementia, sleep disorder, pneumonia dysfagia-related and malnutrition, a multidisciplinary evaluation and not just a neurological evaluation is needed. We suggest a n multidisciplinary approach for this old actor, underlying a subtle link between neurophatological stages of the disease (Braak's classification) and clinical aspects (Braak's stages 1 and 2 associated with the premotor phase; Braak's stages 3-4 associated with the motor symptoms and Braak's stages 5-6 associated with cognitive impairment). In addition, we emphasize the usefulness of geriatric evaluation for the identification of frail "in situ", frail, and disable status for improving care and treatment in this multifaceted disease. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Consensus document on spasticity in patients with multiple sclerosis. Grupo de Enfermedades Desmielinizantes de la Sociedad Española de Neurología].

PubMed

Oreja-Guevara, Celia; Montalban, Xavier; de Andrés, Clara; Casanova-Estruch, Bonaventura; Muñoz-García, Delicias; García, Inmaculada; Fernández, Óscar

2013-10-16

Multiple sclerosis is a chronic neurological inflammatory demyelinating disease. Specialists involved in the symptomatic treatment of this disease tend to apply heterogeneous diagnostic and treatment criteria. To establish homogeneous criteria for treating spasticity based on available scientific knowledge, facilitating decision-making in regular clinical practice. A group of multiple sclerosis specialists from the Spanish Neurological Society demyelinating diseases working group met to review aspects related to spasticity in this disease and draw up the consensus. After an exhaustive bibliographic search and following a metaplan technique, a number of preliminary recommendations were established to incorporate into the document. Finally, each argument was classified depending on the degree of recommendation according to the SIGN (Scottish Intercollegiate Guidelines Network) system. The resulting text was submitted for review by the demyelinating disease group. An experts' consensus was reached regarding spasticity triggering factors, related symptoms, diagnostic criteria, assessment methods, quality of life and therapeutic management (drug and non-drug) criteria. The recommendations included in this consensus can be a useful tool for improving the quality of life of multiple sclerosis patients, as they enable improved diagnosis and treatment of spasticity.

Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry.

PubMed

Levy, R; Gérard, L; Kuemmerle-Deschner, J; Lachmann, H J; Koné-Paut, I; Cantarini, L; Woo, P; Naselli, A; Bader-Meunier, B; Insalaco, A; Al-Mayouf, S M; Ozen, S; Hofer, M; Frenkel, J; Modesto, C; Nikishina, I; Schwarz, T; Martino, S; Meini, A; Quartier, P; Martini, A; Ruperto, N; Neven, B; Gattorno, M

2015-11-01

To evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers. A web-based registry retrospectively collected data on patients with CAPS. Experts in the disease independently validated all cases. Patients carrying NLRP3 variants and germline-mutation-negative patients were included. 136 patients were analysed. The median age at disease onset was 9 months, and the median duration of follow-up was 15 years. Skin rash, musculoskeletal involvement and fever were the most prevalent features. Neurological involvement (including severe complications) was noted in 40% and 12% of the patients, respectively, with ophthalmological involvement in 71%, and neurosensory hearing loss in 42%. 133 patients carried a heterozygous, germline mutation, and 3 patients were mutation-negative (despite complete NLRP3 gene screening). Thirty-one different NLRP3 mutations were recorded; 7 accounted for 78% of the patients, whereas 24 rare variants were found in 27 cases. The latter were significantly associated with early disease onset, neurological complications (including severe complications) and severe musculoskeletal involvement. The T348M variant was associated with early disease onset, chronic course and hearing loss. Neurological involvement was less strongly associated with V198M, E311 K and A439 V alleles. Early onset was predictive of severe neurological complications and hearing loss. Patients carrying rare NLRP3 variants are at risk of severe CAPS; onset before the age of 6 months is associated with more severe neurological involvement and hearing loss. These findings may have an impact on treatment decisions. 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.

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.

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

Powassan meningoencephalitis, New York, New York, USA.

PubMed

Sung, Simon; Wurcel, Alysse G; Whittier, Susan; Kulas, Karen; Kramer, Laura D; Flam, Robin; Roberts, James Kirkland; Tsiouris, Simon

2013-01-01

Disease caused by Powassan virus (POWV), a tick-borne flavivirus, ranges from asymptomatic to severe neurologic compromise and death. Two cases of POWV meningoencephalitis in New York, USA, highlight diagnostic techniques, neurologic outcomes, and the effect of POWV on communities to which it is endemic.

Oculomotor abnormalities in children with Niemann-Pick type C.

PubMed

Blundell, James; Frisson, Steven; Chakrapani, Anupam; Gissen, Paul; Hendriksz, Chris; Vijay, Suresh; Olson, Andrew

2018-02-01

Niemann-Pick type C (NP-C) is a rare recessive disorder associated with progressive supranuclear gaze palsy. Degeneration occurs initially for vertical saccades and later for horizontal saccades. There are studies of oculomotor degeneration in adult NP-C patients [1, 2] but no comparable studies in children. We used high-resolution video-based eye tracking to record monocular vertical and horizontal eye movements in 2 neurological NP-C patients (children with clinically observable oculomotor abnormalities) and 3 pre-neurological NP-C patients (children without clinically observable oculomotor abnormalities). Saccade onset latency, saccade peak velocity and saccade curvature were compared to healthy controls (N=77). NP-C patients had selective impairments of vertical saccade peak velocity and vertical saccade curvature, with slower peak velocities and greater curvature. Changes were more pronounced in neurological than pre-neurological patients, showing that these measures are sensitive to disease progress, but abnormal curvature and slowed downward saccades were present in both groups, showing that eye-tracking can register disease-related changes before these are evident in a clinical exam. Both slowing, curvature and the detailed characteristics of the curvature we observed are predicted by the detailed characteristics of RIMLF population codes. Onset latencies were not different from healthy controls. High-resolution video-based eye tracking is a promising sensitive and objective method to measure NP-C disease severity and neurological onset. It may also help evaluate responses to therapeutic interventions. Copyright © 2017. Published by Elsevier Inc.

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.

[Social-medical significance of the concept of salutogenesis in neurology and psychiatry].

PubMed

Glazinski, R

2007-03-01

The so-called "sense of coherence" (SOC) is the central idea of Antonovsky's concept of salutogenesis. The structure and the meaning of SOC for a person's ability to cope with stress are discussed as well as the overall health-promoting effect of SOC. At the end of the study's first part the question of proving the SOC empirically and of the SOC's construct validity are critically discussed. The second part of the article demonstrates the relevance of salutogenic mechanisms for psychiatry and neurology, especially regarding the social aspects of both disciplines. Health promotion and disease prevention are already important issues in the Mental Health Community. But also in neurology, which is much more grounded in the physical medicine than psychiatry, the concept of salutogenesis can help patients to prevent illness or to cope better with the consequences of diseases. Finally, the necessity to supply the current health care system in psychiatry and neurology with much more salutogenic input is questioned.

Pediatric neurocritical care.

PubMed

Murphy, Sarah

2012-01-01

Pediatric neurocritical care is an emerging multidisciplinary field of medicine and a new frontier in pediatric critical care and pediatric neurology. Central to pediatric neurocritical care is the goal of improving outcomes in critically ill pediatric patients with neurological illness or injury and limiting secondary brain injury through optimal critical care delivery and the support of brain function. There is a pressing need for evidence based guidelines in pediatric neurocritical care, notably in pediatric traumatic brain injury and pediatric stroke. These diseases have distinct clinical and pathophysiological features that distinguish them from their adult counterparts and prevent the direct translation of the adult experience to pediatric patients. Increased attention is also being paid to the broader application of neuromonitoring and neuroprotective strategies in the pediatric intensive care unit, in both primary neurological and primary non-neurological disease states. Although much can be learned from the adult experience, there are important differences in the critically ill pediatric population and in the circumstances that surround the emergence of neurocritical care in pediatrics.

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.

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.

A qualitative study in neurological physiotherapy and hope: beyond physical improvement.

PubMed

Soundy, Andy; Smith, Brett; Butler, Miriam; Minns Lowe, Catherine; Helen, Dawes; Winward, Charlie H

2010-02-01

Drawing on data from a qualitative study of a small group of physiotherapists, this article explores the meaning of hope in neurological physiotherapy practice. Nine female physiotherapists (43.2 +/- 8.5 years) each took part in a one-off semistructured interview. The most common kinds of hope used and offered by the physiotherapists in the process of working with people with neurological disease were evident in five themes. These are termed 1) Realistic Hope, 2) False Hope, 3) Accepting Hope and No Need to Hope, 4) Hope in Faith, and 5) No Hope. Neurological experience with patients in physiotherapy provides stories that relate to hope and this informs the way they understand it. It is important that when considering therapeutic outcome, the physiotherapists recognised the need for having a realistic hope and the danger of having a false hope. However, both were balanced with the need to accept that the unknown was possible and not limiting this or losing their dream. Where hope in relation to recovery was not possible, hope in other areas of life was emphasised. The implications of this dynamic process of working with different kinds of hope in relation to people with neurological disease are considered.

Neurological Disorders in Medical Use of Cannabis: An Update.

PubMed

Solimini, Renata; Rotolo, Maria Concetta; Pichini, Simona; Pacifici, Roberta

2017-01-01

Medical cannabis is increasingly used as a treatment or adjunct treatment with different levels of efficacy in several neurological disorders or related symptoms (such as multiple sclerosis, autism, Parkinson and Alzheimer disease, Tourette's syndrome, Huntington's disease, neuropathic pain, epilepsy, headache), as well as in other medical conditions (e.g. nausea and vomiting, glaucoma, appetite stimulation, cancer, inflammatory conditions, asthma). Nevertheless, a number of neurological adverse effects from use of medical cannabis on the short- and on the longterm have been reported, in addition to other adverse health events. It has been noticed that the use of medical cannabis can lead to a paradoxical effects depending on the amount of delta-9-tetrahydrocannabinol (THC) -like cannabinoids the preparation contain. Accordingly, some neurological disorders or symptoms (e.g. multiple sclerosis, seizures, epilepsy, headache) may be caused or exacerbated by the same treatment supposed to cure them. The current review presents an update of the neurological adverse effects resulting from the use of cannabis for medical purposes, highlighting the need to weigh the benefits and risks, when using cannabinoidbased treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

GM2 gangliosidosis in a UK study of children with progressive neurodegeneration: 73 cases reviewed.

PubMed

Smith, Nicholas J; Winstone, Anne Marie; Stellitano, Lesley; Cox, Timothy M; Verity, Christopher M

2012-02-01

To report the demographic, phenotypic, and time-to-diagnosis characteristics of children with GM2 gangliosidosis referred to the UK study of Progressive Intellectual and Neurological Deterioration. Case notification is made via monthly surveillance card, administered by the British Paediatric Surveillance Unit to all UK-based paediatricians; children with GM2 gangliosidosis were identified from cases satisfying inclusion in the UK study of Progressive Intellectual and Neurological Deterioration and analysed according to phenotypic and biochemical categories. Between May 1997 and January 2010, 73 individuals with GM2 gangliosidoses were reported: 40 with Tay-Sachs disease, 31 with Sandhoff disease, and two with GM2 activator protein deficiency. Together they account for 6% (73/1164) of all diagnosed cases of progressive intellectual and neurological deterioration. The majority (62/73) were sporadic index cases with no family history. Children of Pakistani ancestry were overrepresented in all subtypes, particularly juvenile Sandhoff disease, accounting for 10 of 11 notified cases. Infantile-onset variants predominated (55/73); the mean age at onset of symptoms was 6.2 and 4.7 months for infantile-onset Tay-Sachs and Sandhoff disease respectively, and 26.2 and 34.7 months for the corresponding juvenile-onset variants. Time to diagnosis averaged 7.4 months and 28.0 months in infantile- and juvenile-onset disease respectively. GM2 gangliosidosis is a significant cause of childhood neurodegenerative disease; timely diagnosis relies upon improved clinical recognition, which may be increasingly important as specific therapies become available. There is a potential benefit from the introduction of screening programmes for high-risk ethnic groups. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

Brain magnetic resonance imaging screening is not useful for HIV-1-infected patients without neurological symptoms.

PubMed

Nishijima, Takeshi; Gatanaga, Hiroyuki; Teruya, Katsuji; Tajima, Tsuyoshi; Kikuchi, Yoshimi; Hasuo, Kanehiro; Oka, Shinichi

2014-10-01

We investigated the diagnostic usefulness of brain magnetic resonance imaging (MRI) screening in HIV-1-infected patients without neurological symptoms in detecting intracranial diseases at early stages. In this retrospective analysis, the study patients were HIV-1-infected patients who underwent brain MRI scan in clinical practice between 2001 and 2013. We excluded patients with MRI for (1) follow-up examination for prediagnosed intracranial diseases, (2) cancer staging, (3) screening mycobacterium/bacteria/fungi disease proliferation in the brain, and (4) evaluation for meningitis/encephalitis. The study patients (n=485) were classified into two groups: those who underwent brain MRI scan without any neurological symptoms/signs (asymptomatic patients, n=158) and those who underwent MRI due to such symptoms (symptomatic patients, n=327). Asymptomatic patients had lower CD4 counts than symptomatic patients (median 78 versus 241/μl). Intracranial diseases were detected in three (2%) of the asymptomatic patients [two toxoplasmosis and one progressive multifocal leukoencephalopathy (PML)] compared to 58 (19%) of the symptomatic patients (the χ(2) test, p<0.01). The latter included toxoplasmosis (n=10), PML (n=7), cytomegalovirus encephalitis (n=3), primary central nervous system lymphoma (n=3), cryptococcoma/meningitis (n=3), and HIV-associated dementia (n=17). Among symptomatic patients, intracranial diseases were common in those with slurred speech (3/6, 50%), seizure (4/10, 40%), eyesight/vision abnormality (5/16, 31%), altered mental status (8/31, 26%), and hemiplegia/numbness (13/50, 26%). For patients with CD4 count <200/μl, intracranial diseases were detected in only 3 (3%) of 144 asymptomatic patients, compared with 46 (32%) of 113 symptomatic patients (p<0.01). Brain MRI screening for HIV-1-infected patients without neurological symptoms is of little value.

[Neurological evaluation of the leper king Baldwin IV of Jerusalem].

PubMed

Guerrero-Peral, A L

In the medieval period, physicians became more aware of leprosy symptoms and differentiated it from other similar diseases. Baldwin, the leper king of Jerusalem (1161-1185), probably contributed to an increasing interest and tolerance to this disease in medieval Christian states. We review historical descriptions of the neurological manifestations he developed. William of Tyre gives us a description of first symptoms experienced by the prince when aged nine. He notices that half of his right arm and hand were partially numb. No skin or nervous lesions are described. By his early twenties, muscle weakness makes him unable to walk. He gets blinded, probably due to keratopathy related to facial nerves involvement. Repeated attacks of fever lead to progressive worsening of his disease. He finally dies in Jerusalem, aged twenty-five, probably due to a septicaemia from infected sores. The earliest sign of Baldwin's disease is anaesthesia. Though skin lesions are not described, it is likely that at this point he had a tuberculoid form of leprosy. As his disease finally takes a lepromatous form, we suspect that it began as a borderline, immunologically unstable form. Leper king Baldwin biography gives us interesting descriptions of neurological clinical features of leprosy. Besides, it helps us to discover twelfth century medicine knowledge about this disease.

Old friends in new constellations--the hematopoetic growth factors G-CSF, GM-CSF, and EPO for the treatment of neurological diseases.

PubMed

Maurer, M H; Schäbitz, W-R; Schneider, A

2008-01-01

Currently, growth factors which have been identified in hematopoiesis and angiogenesis are re-considered as therapeutical agents in a number of neurological diseases, mainly neurodegenerative disorders like Parkinson's Disease, amyotrophic lateral sclerosis (ALS), or cerebrovascular events such as stroke. Among these growth factors, erythropoietin (EPO) and granulocyte colony-stimulating growth factor (G-CSF) are the most prominent. With regard to neurological disease, EPO has been tested in clinical trials for potential use in stroke, schizophrenia, and addiction, G-CSF is currently under clinical investigation for stroke treatment. The major advantage of these growth factors is their well-described pharmacological behavior and their clinical use over several years. A number of mechanisms of action in the CNS have been identified that are probably important for the beneficial action of these factors in animal models of disease, the most relevant relating to neuroprotection, neuroplasticity and stem cell growth and differentiation. In this review, we will discuss the current efforts and prerequisites of novel growth factor therapies for neurodegenerative diseases with regard to their possible mechanism of action on the molecular level and their effects on brain-derived stem cell populations. Additionally, we will describe the necessities for future research before such therapies can be envisioned.