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Sample records for acute neurological disorders

  1. Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E

    PubMed Central

    Perrin, H. Blasco; Cintas, P.; Abravanel, F.; Gérolami, R.; d'Alteroche, L.; Raynal, J.-N.; Alric, L.; Dupuis, E.; Prudhomme, L.; Vaucher, E.; Couzigou, P.; Liversain, J.-M.; Bureau, C.; Vinel, J.-P.; Kamar, N.; Izopet, J.

    2015-01-01

    Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage–Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection. PMID:26490255

  2. Neurological disorders and travel.

    PubMed

    Awada, Adnan; Kojan, Suleiman

    2003-02-01

    Travel is associated with a number of neurological disorders that can be divided into two categories: (1) Neurological infections including encephalitides, neurotuberculosis, neurobrucellosis, cysticercosis and trichinosis. Some of these disorders can be prevented by vaccinations, such as Japanese B encephalitis and rabies, some by the use of insect repellents and some by avoiding raw milk products and undercooked meat. (2) Non-infective neurological disorders, such as acute mountain sickness and high altitude cerebral oedema, problems occurring during air travel such as syncope, seizures, strokes, nerve compression, barotrauma and vertigo, motion sickness and foodborne neurotoxic disorders such as ciguatera, shellfish poisoning and intoxication by cassava. This group of diseases and disorders could be prevented if the traveller knows about them, applies simple physiological rules, takes some specific medications and knows how to avoid intoxications in certain geographical areas. Meningococcal meningitis, malaria and jet lag syndrome are extensively discussed in other articles of this issue. The discussion in this paper will be limited to the other disorders.

  3. Hippotherapy acute impact on heart rate variability non-linear dynamics in neurological disorders.

    PubMed

    Cabiddu, Ramona; Borghi-Silva, Audrey; Trimer, Renata; Trimer, Vitor; Ricci, Paula Angélica; Italiano Monteiro, Clara; Camargo Magalhães Maniglia, Marcela; Silva Pereira, Ana Maria; Rodrigues das Chagas, Gustavo; Carvalho, Eliane Maria

    2016-05-15

    Neurological disorders are associated with autonomic dysfunction. Hippotherapy (HT) is a therapy treatment strategy that utilizes a horse in an interdisciplinary approach for the physical and mental rehabilitation of people with physical, mental and/or psychological disabilities. However, no studies have been carried out which evaluated the effects of HT on the autonomic control in these patients. Therefore, the objective of the present study was to investigate the effects of a single HT session on cardiovascular autonomic control by time domain and non-linear analysis of heart rate variability (HRV). The HRV signal was recorded continuously in twelve children affected by neurological disorders during a HT session, consisting in a 10-minute sitting position rest (P1), a 15-minute preparatory phase sitting on the horse (P2), a 15-minute HT session (P3) and a final 10-minute sitting position recovery (P4). Time domain and non-linear HRV indices, including Sample Entropy (SampEn), Lempel-Ziv Complexity (LZC) and Detrended Fluctuation Analysis (DFA), were calculated for each treatment phase. We observed that SampEn increased during P3 (SampEn=0.56±0.10) with respect to P1 (SampEn=0.40±0.14, p<0.05), while DFA decreased during P3 (DFA=1.10±0.10) with respect to P1 (DFA=1.26±0.14, p<0.05). A significant SDRR increase (p<0.05) was observed during the recovery period P4 (SDRR=50±30ms) with respect to the HT session period P3 (SDRR=30±10ms). Our results suggest that HT might benefit children with disabilities attributable to neurological disorders by eliciting an acute autonomic response during the therapy and during the recovery period.

  4. Cardiomyopathy in neurological disorders.

    PubMed

    Finsterer, Josef; Stöllberger, Claudia; Wahbi, Karim

    2013-01-01

    According to the American Heart Association, cardiomyopathies are classified as primary (solely or predominantly confined to heart muscle), secondary (those showing pathological myocardial involvement as part of a neuromuscular disorder) and those in which cardiomyopathy is the first/predominant manifestation of a neuromuscular disorder. Cardiomyopathies may be further classified as hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, or unclassified cardiomyopathy (noncompaction, Takotsubo-cardiomyopathy). This review focuses on secondary cardiomyopathies and those in which cardiomyopathy is the predominant manifestation of a myopathy. Any of them may cause neurological disease, and any of them may be a manifestation of a neurological disorder. Neurological disease most frequently caused by cardiomyopathies is ischemic stroke, followed by transitory ischemic attack, syncope, or vertigo. Neurological disease, which most frequently manifests with cardiomyopathies are the neuromuscular disorders. Most commonly associated with cardiomyopathies are muscular dystrophies, myofibrillar myopathies, congenital myopathies and metabolic myopathies. Management of neurological disease caused by cardiomyopathies is not at variance from the same neurological disorders due to other causes. Management of secondary cardiomyopathies is not different from that of cardiomyopathies due to other causes either. Patients with neuromuscular disorders require early cardiologic investigations and close follow-ups, patients with cardiomyopathies require neurological investigation and avoidance of muscle toxic medication if a neuromuscular disorder is diagnosed. Which patients with cardiomyopathy profit most from primary stroke prevention is unsolved and requires further investigations.

  5. Genomics in neurological disorders.

    PubMed

    Han, Guangchun; Sun, Jiya; Wang, Jiajia; Bai, Zhouxian; Song, Fuhai; Lei, Hongxing

    2014-08-01

    Neurological disorders comprise a variety of complex diseases in the central nervous system, which can be roughly classified as neurodegenerative diseases and psychiatric disorders. The basic and translational research of neurological disorders has been hindered by the difficulty in accessing the pathological center (i.e., the brain) in live patients. The rapid advancement of sequencing and array technologies has made it possible to investigate the disease mechanism and biomarkers from a systems perspective. In this review, recent progresses in the discovery of novel risk genes, treatment targets and peripheral biomarkers employing genomic technologies will be discussed. Our major focus will be on two of the most heavily investigated neurological disorders, namely Alzheimer's disease and autism spectrum disorder.

  6. [Neurological sleep disorders].

    PubMed

    Khatami, Ramin

    2014-11-01

    Neurological sleep disorders are common in the general population and may have a strong impact on quality of life. General practitioners play a key role in recognizing and managing sleep disorders in the general population. They should therefore be familiar with the most important neurological sleep disorders. This review provides a comprehensive overview of the most prevalent and important neurological sleep disorders, including Restless legs syndrome (with and without periodic limb movements in sleep), narcolepsy, NREM- and REM-sleep parasomnias and the complex relationship between sleep and epilepsies. Although narcolepsy is considered as a rare disease, recent discoveries in narcolepsy research provided insight in the function of brain circuitries involved in sleep wake regulation. REM sleep behavioral parasomnia (RBD) is increasingly recognized to represent an early manifestation of neurodegenerative disorders, in particular evolving synucleinopathies. Early diagnosis may thus open new perspectives for developing novel treatment options by targeting neuroprotective substances.

  7. 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.

  8. Endocrine disorders and the neurologic manifestations

    PubMed Central

    2014-01-01

    The nervous system and the endocrine system are closely interrelated and both involved intimately in maintaining homeostasis. Endocrine dysfunctions may lead to various neurologic manifestations such as headache, myopathy, and acute encephalopathy including coma. It is important to recognize the neurologic signs and symptoms caused by the endocrine disorders while managing endocrine disorders. This article provides an overview of the neurologic manifestations found in various endocrine disorders that affect pediatric patients. It is valuable to think about 'endocrine disorder' as a cause of the neurologic manifestations. Early diagnosis and treatment of hormonal imbalance can rapidly relieve the neurologic symptoms. Better understanding of the interaction between the endocrine system and the nervous system, combined with the knowledge about the pathophysiology of the neurologic manifestations presented in the endocrine disorders might allow earlier diagnosis and better treatment of the endocrine disorders. PMID:25654063

  9. Key sleep neurologic disorders

    PubMed Central

    St. Louis, Erik K.

    2014-01-01

    Summary Sleep disorders are frequent comorbidities in neurologic patients. This review focuses on clinical aspects and prognosis of 3 neurologic sleep disorders: narcolepsy, restless legs syndrome/Willis-Ekbom disease (RLS/WED), and REM sleep behavior disorder (RBD). Narcolepsy causes pervasive, enduring excessive daytime sleepiness, adversely affecting patients' daily functioning. RLS/WED is characterized by an uncomfortable urge to move the legs before sleep, often evolving toward augmentation and resulting in daylong bothersome symptoms. RBD causes potentially injurious dream enactment behaviors that often signify future evolution of overt synucleinopathy neurodegeneration in as many as 81% of patients. Timely recognition, referral for polysomnography, and longitudinal follow-up of narcolepsy, RLS/WED, and RBD patients are imperatives for neurologists in providing quality comprehensive patient care. PMID:24605270

  10. [Neurological Disorders and Pregnancy].

    PubMed

    Berlit, P

    2016-02-01

    Neurological disorders caused by pregnancy and puerperium include the posterior reversible encephalopathy syndrome, the amniotic fluid embolism syndrome (AFES), the postpartum angiopathy due to reversible vasoconstriction syndrome, and the Sheehan syndrome. Hypertension and proteinuria are the hallmarks of preeclampsia, seizures define eclampsia. Hemolysis, elevated liver enzymes and low platelets constitute the HELLP syndrome. Vision disturbances including cortical blindness occur in the posterior reversible encephalopathy syndrome (PRES). The Sheehan syndrome presents with panhypopituitarism post partum due to apoplexia of the pituitary gland in severe peripartal blood loss leading to longstanding hypotension. Some neurological disorders occur during pregnancy and puerperium with an increased frequency. These include stroke, sinus thrombosis, the restless legs syndrome and peripheral nerve syndromes, especially the carpal tunnel syndrome. Chronic neurologic diseases need an interdisciplinary approach during pregnancy. Some anticonvulsants double the risk of birth defects. The highest risk exists for valproic acid, the lowest for lamotrigine and levetiracetam. For MS interval treatment, glatiramer acetate and interferones seem to be safe during pregnancy. All other drugs should be avoided.

  11. [Acute vertigo of neurological origin].

    PubMed

    Bruun, Marie; Højgaard, Joan L Sunnleyg; Kondziella, Daniel

    2013-11-04

    Acute vertigo of neurological origin may be caused by haemorrhages and tumours in the posterior fossa and, most frequently, by ischaemic infarction in the vertebrobasilar circulation. Urgent diagnosis is necessary to avoid further ischaemic episodes, herniation due to cerebellar oedema and/or fatal brainstem infarction. The history should focus on accompanying neurological symptoms. However, vertigo with cerebellar lesions may be monosymptomatic and then bedside evaluation of oculomotor function is the key to correct diagnosis. This paper discusses the pathophysiology, symptomatology and clinical evaluation of acute vertigo of neurological origin.

  12. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders.

    PubMed

    Masliah, E; Díez-Tejedor, E

    2012-04-01

    Neurotrophic factors are considered as part of the therapeutic strategy for neurological disorders like dementia, stroke and traumatic brain injury. Cerebrolysin is a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair. In dementia models, Cerebrolysin decreases β-amyloid deposition and microtubule-associated protein tau phosphorylation by regulating glycogen synthase kinase-3β and cyclin-dependent kinase 5 activity, increases synaptic density and restores neuronal cytoarchitecture. These effects protect integrity of the neuronal circuits and thus result in improved cognitive and behavioral performance. Furthermore, Cerebrolysin enhances neurogenesis in the dentate gyrus, the basis for neuronal replacement therapy in neurodegenerative diseases. Experimental studies in stroke animal models have shown that Cerebrolysin stabilizes the structural integrity of cells by inhibition of calpain and reduces the number of apoptotic cells after ischemic lesion. Cerebrolysin induces restorative processes, decreases infarct volume and edema formation and promotes functional recovery. Stroke-induced neurogenesis in the subventricular zone was also promoted by Cerebrolysin, thus supporting the brain's self-repair after stroke. Both, traumatic brain and spinal cord injury conditions stimulate the expression of natural neurotrophic factors to promote repair and regeneration processes -axonal regeneration, neuronal plasticity and neurogenesis- that is considered to be crucial for the future recovery. Neuroprotective effects of Cerebrolysin on experimentally induced traumatic spinal cord injury have shown that Cerebrolysin prevents apoptosis of lesioned motoneurons and promotes functional recovery. This section summarizes the most relevant data on the pharmacology of Cerebrolysin obtained from in vitro assays (biochemical and cell cultures) and in vivo animal models of acute and chronic neurological disorders.

  13. Neurologic disorder and criminal responsibility.

    PubMed

    Yaffe, Gideon

    2013-01-01

    Sufferers from neurologic and psychiatric disorders are not uncommonly defendants in criminal trials. This chapter surveys a variety of different ways in which neurologic disorder bears on criminal responsibility. It discusses the way in which a neurologic disorder might bear on the questions of whether or not the defendant acted voluntarily; whether or not he or she was in the mental state that is required for guilt for the crime; and whether or not he or she is deserving of an insanity defense. The discussion demonstrates that a just determination of whether a sufferer from a neurologic disorder is diminished in his or her criminal responsibility for harmful conduct requires equal appreciation of the nature of the relevant disorder and its impact on behavior, on the one hand, and of the legal import of facts about the psychologic mechanisms through which behavior is generated, on the other.

  14. The neurologic manifestations of the acute porphyrias.

    PubMed

    Simon, Neil G; Herkes, Geoffrey K

    2011-09-01

    The porphyrias are diseases characterised by accumulation of porphyrins and porphyrin precursors owing to enzymatic deficiencies of the haem synthetic pathway. In the acute hepatic porphyrias accumulation of porphyrin precursors, in particular delta-aminolaevulinic acid (ALA), cause dysfunction of the central, peripheral and autonomic nervous systems. This leads to the characteristic clinical findings of abdominal pain, neuropsychiatric symptoms and neuropathy. The exact pathogenic mechanism is not clear but evidence to date suggests both direct toxic effects of ALA and intracellular metabolic derangement contribute to the neurologic disorders. This review explores the mechanisms of neural dysfunction in the acute porphyrias and the resultant clinical features of an acute attack.

  15. Depressive syndromes in neurological disorders.

    PubMed

    Hellmann-Regen, Julian; Piber, Dominique; Hinkelmann, Kim; Gold, Stefan M; Heesen, Christoph; Spitzer, Carsten; Endres, Matthias; Otte, Christian

    2013-11-01

    Depressive syndromes represent a common and often characteristic feature in a number of neurological disorders. One prominent example is the development of post-stroke depression, which can be observed in more than one-third of stroke survivors in the aftermath of an ischemic stroke. Thus, post-stroke depression represents one of the most prevalent, disabling, and potentially devastating psychiatric post-stroke complications. On the other hand, depressive syndromes may also be considered as a risk factor for certain neurological disorders, as recently revealed by a meta-analysis of prospective cohort studies, which demonstrated an increased risk for ischemic events in depressed patients. Moreover, depressive syndromes represent common comorbidities in a number of other neurological disorders such as Parkinson's disease, multiple sclerosis, or epilepsy, in which depression has a strong impact on both quality of life and outcome of the primary neurological disorder.

  16. [Affective disorders and neurological comorbidities].

    PubMed

    Tassy, S; Belzeaux, R; Adida, M; Micoulaud Franchi, J-A; Azorin, J-M

    2014-12-01

    Mood disorders occupy a vast area in the field of psychiatry. Advances in the study of the brain, but also epidemiology and genetics allow us to make more solid connections between these disorders and neurological disorders, resuming a process of reconciliation between both specialties. The purpose of this short review is to draw the attention of the psychiatrist to these links, especially with a brief presentation of the psychiatric manifestations of a number of neurodegenerative diseases and more particularly frontotemporal dementia.

  17. Ion Channels in Neurological Disorders.

    PubMed

    Kumar, Pravir; Kumar, Dhiraj; Jha, Saurabh Kumar; Jha, Niraj Kumar; Ambasta, Rashmi K

    2016-01-01

    The convergent endeavors of the neuroscientist to establish a link between clinical neurology, genetics, loss of function of an important protein, and channelopathies behind neurological disorders are quite intriguing. Growing evidence reveals the impact of ion channels dysfunctioning in neurodegenerative disorders (NDDs). Many neurological/neuromuscular disorders, viz, Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, and age-related disorders are caused due to altered function or mutation in ion channels. To maintain cell homeostasis, ion channels are playing a crucial role which is a large transmembrane protein. Further, these channels are important as it determines the membrane potential and playing critically in the secretion of neurotransmitter. Behind NDDs, losses of pathological proteins and defective ion channels have been reported and are found to aggravate the disease symptoms. Moreover, ion channel dysfunctions are eliciting a range of symptoms, including memory loss, movement disabilities, neuromuscular sprains, and strokes. Since the possible mechanistic role played by aberrant ion channels, their receptor and associated factors in neurodegeneration remained elusive; therefore, it is a challenging task for the neuroscientist to implement the therapeutics for targeting NDDs. This chapter reviews the potential role of the ion channels in membrane physiology and brain homeostasis, where ion channels and their associated factors have been characterized with their functional consequences in neurological diseases. Moreover, mechanistic role of perturbed ion channels has been identified in various NDDs, and finally, ion channel modulators have been investigated for their therapeutic intervention in treating common NDDs.

  18. [Sleep disorders in neurology. Hypersomnia].

    PubMed

    Stepansky, R; Asenbaum, S; Saletu, B; Zeitlhofer, J

    1997-11-28

    Hypersomnia (excessive sleepiness) accompanies many diseases. 14% of the total Austrian population regularly have problems staying awake during the day or are prone to taking spontaneous naps. Hypersomnia is a symptom of the sleep apnea syndrome, which is a risk factor for cerebrovascular disorders. Daytime sleepiness is also a characteristic symptom of narcolepsy, idiopathic hypersomnia, episodic hypersomnia, and many more neurological or psychiatric disorders; it can also be drug induced. Involvement of brain structures which are essential for the regulation of the sleep wake cycle as a result of neurological disorders can likewise lead to hypersomnia. Symptomatic treatment is necessary when treatment of the causal factors is not possible or no improvement has been achieved.

  19. Molecular mechanisms in neurologic disorders.

    PubMed

    Cunniff, C

    2001-09-01

    Although many pediatric neurologic disorders, such as epilepsy and mental retardation, are the result of a combination of genetic and environmental factors, many others are the result of mutations of single genes. Most of these single gene traits are inherited in autosomal dominant, autosomal recessive, or X-linked fashion. The diversity of mutations that are responsible for these diseases produces variability in phenotypic expression. However, there are other important features of many neurologic disorders that cannot be explained by standard models of mendelian inheritance. This review focuses on recently described mechanisms, such as genomic imprinting, germline mosaicism, mitochondrial inheritance, and triplet repeat expansion. The diagnostic evaluation, prognostic significance, and recurrence risk for specific neurogenetic disorders is correlated with these underlying disease mechanisms.

  20. Update on Paraneoplastic Neurologic Disorders

    PubMed Central

    Rosenfeld, Myrna R.

    2010-01-01

    When patients with cancer develop neurologic symptoms, common causes include metastasis, infections, coagulopathy, metabolic or nutritional disturbances, and neurotoxicity from treatments. A thorough clinical history, temporal association with cancer therapies, and results of ancillary tests usually reveal one of these mechanisms as the etiology. When no etiology is identified, the diagnosis considered is often that of a paraneoplastic neurologic disorder (PND). With the recognition that PNDs are more frequent than previously thought, the availability of diagnostic tests, and the fact that, for some PNDs, treatment helps, PNDs should no longer be considered diagnostic zebras, and when appropriate should be included in the differential diagnosis early in the evaluation. PMID:20479279

  1. Medical Marijuana in Certain Neurological Disorders

    MedlinePlus

    ... Systematic Review for PATIENTS and their FAMILIES MEDICAL MARIJUANA IN CERTAIN NEUROLOGICAL DISORDERS This fact sheet presents the current research on medical marijuana (cannabis) for treating certain neurological disorders. The American ...

  2. HTLV-1 Associated Neurological Disorders.

    PubMed

    Khan, Muhammad Yasir; Khan, Ishaq Nasib; Farman, Muhammad; Al Karim, Saleh; Qadri, Ishtiaq; Kamal, Muhammad Amjad; Al Ghamdi, Khalid; Harakeh, Steve

    2016-12-22

    Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus which is endemic to certain regions of the world and infects around 10-20 million people. HTLV-1 is the etiologic agent of Adult T cell leukemia/lymphoma and HTLV-1 associated neurological disorders including mainly HTLV-1 associated myelopathy/Tropical spastic paraparesis. The involvement of the central nervous diseases occurs among: HTLV-1 infected patients from endemic areas, HIV positive individuals and drug users. The ability of HTLV-1 to cause associated neuropathies starts with the virus crossing the blood brain barrier (BBB), then entering and infecting the cells of the central nervous system. As a consequence, to the viral attack, HTLV-1 infected lymphocytes produce pro-inflammatory cytokines like tumor necrosis factor alpha, Interleukin 1 beta and interleukin 6 which further disrupts the BBB. Different serological tests have been used in the diagnosis of HTLV-1. These include: ELISA and Western Blotting (WB), Immunofluorescence, Particle Agglutination and Polymerase Chain Reaction which is used as a confirmatory test. Danazol, pentoxifylline, azathioprine and vitamin C have been used in the treatment of the HTLV-1 associated neurological disorders. Other antiviral drugs (lamivudine, zidovudine), monoclonal antibodies (Daclizumab) and therapeutic agents (valporic acid, interferons) have also been evaluated. No known drug, so far, has been shown to be efficacious. The aim of this review is to present the complexities of HTLV-1 associated neurological disorders and their current ongoing treatment. In addition to discussing future possible therapeutic strategies, by targeting HTVL-1 viral components and gene/s products, for the treatment of those neurological conditions.

  3. [Neurology of hysteria (conversion disorder)].

    PubMed

    Sonoo, Masahiro

    2014-07-01

    Hysteria has served as an important driving force in the development of both neurology and psychiatry. Jean Martin Charcot's devotion to mesmerism for treating hysterical patients evoked the invention of psychoanalysis by Sigmund Freud. Meanwhile, Joseph Babinski took over the challenge to discriminate between organic and hysterical patients from Charcot and found Babinski's sign, the greatest milestone in modern neurological symptomatology. Nowadays, the usage of the term hysteria is avoided. However, new terms and new classifications are complicated and inconsistent between the two representative taxonomies, the DSM-IV and ICD-10. In the ICD-10, even the alternative term conversion disorder, which was becoming familiar to neurologists, has also disappeared as a group name. The diagnosis of hysteria remains important in clinical neurology. Extensive exclusive diagnoses and over investigation, including various imaging studies, should be avoided because they may prolong the disease course and fix their symptoms. Psychological reasons that seem to explain the conversion are not considered reliable. Positive neurological signs suggesting nonorganic etiologies are the most reliable measures for diagnosing hysteria, as Babinski first argued. Hysterical paresis has several characteristics, such as giving-way weakness or peculiar distributions of weakness. Signs to uncover nonorganic paresis utilizing synergy include Hoover's test and the Sonoo abductor test.

  4. Child neurology practice and neurological disorders in East Africa.

    PubMed

    Idro, Richard; Newton, Charles; Kiguli, Sarah; Kakooza-Mwesige, Angelina

    2010-04-01

    Neurological disorders, including neurodevelopmental disorders, have been identified by the World Health Organization (WHO) as one of the greatest threats to global public health. It is generally believed that these conditions are more prevalent in the developing than the developed world because of multiple known risk factors such as infections, malnutrition, and limited resources for obstetric and neonatal management. In East Africa, few investigations have been conducted to obtain data on the magnitude and description of neurological disorders among children, and the practice of child neurology is faced with challenges cutting across areas of health personnel, patient diagnosis, management, and rehabilitation. This article reviews the burden, types, and causes of neurological disorders in the East African region. The challenges and successes in the practice of child neurology and recommendations for the future are discussed.

  5. Neurological disorders in complex humanitarian emergencies and natural disasters.

    PubMed

    Mateen, Farrah J

    2010-09-01

    Complex humanitarian emergencies include the relatively acute, severe, and overwhelming health consequences of armed conflict, food scarcity, mass displacement, and political strife. Neurological manifestations of complex humanitarian emergencies are important and underappreciated consequences of emergencies in populations worldwide. This review critically assesses the existing knowledge of the range of neurological disorders that accompany complex humanitarian emergencies and natural disasters in both the acute phase of crisis and the "long shadow" that follows.

  6. Dysphagia associated with neurological disorders.

    PubMed

    Buchholz, D W

    1994-01-01

    Neurogenic dysphagia results from sensorimotor impairment of the oral and pharyngeal phases of swallowing due to a neurologic disorder. The symptoms of neurogenic dysphagia include drooling, difficulty initiating swallowing, nasal regurgitation, difficulty managing secretions, choke/cough episodes while feeding, and food sticking in the throat. If unrecognized and untreated, neurogenic dysphagia can lead to dehydration, malnutrition, and respiratory complications. The symptoms of neurogenic dysphagia may be relatively inapparent on account of both compensation for swallowing impairment and diminution of the laryngeal cough reflex due to a variety of factors. Patients with symptoms of oropharyngeal dysphagia should undergo videofluoroscopy of swallowing, which in the case of neurogenic dysphagia typically reveals impairment of oropharyngeal motor performance and/or laryngeal protection. The many causes of neurogenic dysphagia include stroke, head trauma, Parkinson's disease, motor neuron disease and myopathy. Evaluation of the cause of unexplained neurogenic dysphagia should include consultation by a neurologist, magnetic resonance imaging of the brain, blood tests (routine studies plus muscle enzymes, thyroid screening, vitamin B12 and anti-acetylcholine receptor antibodies), electromyography/nerve conduction studies, and, in certain cases, muscle biopsy or cerebrospinal fluid examination. Treatment of neurogenic dysphagia involves treatment of the underlying neurologic disorder (if possible), swallowing therapy (if oral feeding is reasonably safe to attempt) and gastrostomy (if oral feeding is unsafe or inadequate).

  7. Practical approach to management of respiratory complications in neurological disorders

    PubMed Central

    Mangera, Zaheer; Panesar, Gurkirat; Makker, Himender

    2012-01-01

    Patients with certain neurological diseases are at increased risk of developing chest infections as well as respiratory failure due to muscular weakness. In particular, patients with certain neuromuscular disorders are at higher risk. These conditions are often associated with sleep disordered breathing. It is important to identify patients at risk of respiratory complications early in the course of their disease, although patients with neuromuscular disorders often present in the acute setting with respiratory involvement. This review of the respiratory complications of neurological disorders, with a particular focus on neuromuscular disorders, explores why this happens and looks at how to recognize, investigate, and manage these patients effectively. PMID:22505823

  8. Practical approach to management of respiratory complications in neurological disorders.

    PubMed

    Mangera, Zaheer; Panesar, Gurkirat; Makker, Himender

    2012-01-01

    Patients with certain neurological diseases are at increased risk of developing chest infections as well as respiratory failure due to muscular weakness. In particular, patients with certain neuromuscular disorders are at higher risk. These conditions are often associated with sleep disordered breathing. It is important to identify patients at risk of respiratory complications early in the course of their disease, although patients with neuromuscular disorders often present in the acute setting with respiratory involvement. This review of the respiratory complications of neurological disorders, with a particular focus on neuromuscular disorders, explores why this happens and looks at how to recognize, investigate, and manage these patients effectively.

  9. Neurological complications of acute multifocal placoid pigment epitheliopathy.

    PubMed

    Brownlee, W J; Anderson, N E; Sims, J; Pereira, J A

    2016-09-01

    Acute multifocal placoid pigment epitheliopathy (AMPPE) is an autoimmune chorioretinal disease that can be complicated by neurological involvement. There is limited information on this potentially treatable condition in the neurological literature. The objective of this patient series is to describe the neurological complications of AMPPE. We retrospectively identified patients with neurological complications of AMPPE seen at Auckland Hospital between 2008 and 2013 and summarised cases in the literature between 1976 and 2013. We identified five patients with neurological complications of AMPPE at Auckland Hospital and 47 reported patients. These patients demonstrated a spectrum of neurological involvement including isolated headache, stroke or transient ischaemic attack, seizures, venous sinus thrombosis, optic neuritis, sensorineural hearing loss and peripheral vestibular disorder. We propose criteria to define AMPPE with neurological complications. A cerebrospinal fluid (CSF) lymphocytosis in a patient with isolated headache may predict the development of cerebrovascular complications of AMPPE. Patients with cerebrovascular complications of AMPPE have a poor prognosis with high rates of death and neurological disability among survivors. Predictors of poor outcome in those who develop neurological complications of AMPPE are a relapsing course, generalised seizures and multifocal infarction on MRI. All patients with neurological complications of AMPPE, including headache alone, should be investigated with an MRI brain and CSF examination. Patients with focal neurological symptoms should receive intravenous (IV) methylprednisolone followed by a tapering course of oral steroids for at least 3months. Patients with AMPPE and an isolated headache with a CSF pleocytosis should be treated with oral steroids.

  10. Dissociation and functional neurologic disorders.

    PubMed

    Brown, R J

    2017-01-01

    Dissociation has been cited as a possible psychologic mechanism underpinning functional neurologic disorders (FND) since the 19th century. Since that time, changes in psychiatric classification have created confusion about what the term dissociation actually means. The available evidence suggests that it now refers to at least two qualitatively distinct types of phenomena: detachment (an altered state of consciousness characterized by a sense of separation from the self or world) and compartmentalization (a reversible loss of voluntary control over apparently intact processes and functions), as well as their underlying mechanisms. This chapter considers some of the problems with conflating these phenomena under a single heading as well as the relationship between detachment, compartmentalization, and FND. It is argued that FNDs are fundamentally compartmentalization disorders, but that detachment is often part of the clinical picture and may contribute to the development and maintenance of functional symptoms in many cases. By this view, understanding compartmentalization requires an appreciation of the mechanisms involved in controlling and accessing mental processes and contents. Two possible mechanisms in this regard are described and the evidence for these is considered, followed by a discussion of clinical and empiric implications.

  11. Comorbidity between neurological illness and psychiatric disorders.

    PubMed

    Hesdorffer, Dale C

    2016-06-01

    Psychiatric disorders are common in many neurological disorders, including epilepsy, migraine, Alzheimer's disease, Parkinson's disease, essential tremor, and stroke. These comorbidities increase disease burden and may complicate the treatment of the combined disorders. Initial studies of the comorbidity of psychiatric and neurological disorders were cross-sectional, and time order of the associations was impossible to elucidate. More recent work has clarified time associations between psychiatric disorders and neurological disorders, particularly in epilepsy and stroke where epidemiological evidence suggests that there is a bidirectional relationship. This article takes an epidemiological approach to understanding these relationships and focuses mostly on epilepsy. Although, these relationships are understood in many neurological disorders, routine screening for psychiatric disorders in neurological disorders is infrequent, mostly due to the lack of partnerships between psychiatrists and neurologists and the paucity of neuropsychiatrists. Much more needs to be done to improve the detection and treatment of patients affected by neurological and psychiatric disorders. Understanding the scope of this overlap may inspire collaborations to improve the lives of people affected by both disorders.

  12. Neurological Basis of Attention Deficit Hyperactivity Disorder.

    ERIC Educational Resources Information Center

    Riccio, Cynthia A.; And Others

    1993-01-01

    This article reviews various models in the neurological conceptualization of attention deficit disorder (ADD), with and without hyperactivity. It discusses neuroanatomical, neurochemical, and neurophysiological perspectives on ADD. (Author/DB)

  13. Paraneoplastic Neurologic Disorders: A Brief Overview

    PubMed Central

    Dalmau, Josep

    2012-01-01

    Immune-mediated paraneoplastic neurologic disorders (PND) may affect any part of the nervous system, and can mimic many non-cancer associated disorders. The availability of diagnostic tests based on the presence of specific anti-neuronal antibodies facilitates diagnosis and can suggest treatment strategies. Once thought to be poorly responsive to therapies, it is now recognized that there is a subgroup of PND, mostly associated with antibodies to antigens on the neuronal cell surface that are highly treatment responsive. For all PND, identification and treatment of the underlying tumor is the most effective step in the potential control or stabilization of the neurological disorder. PMID:23264806

  14. Targeting sonic hedgehog signaling in neurological disorders.

    PubMed

    Patel, Sita Sharan; Tomar, Sunil; Sharma, Diksha; Mahindroo, Neeraj; Udayabanu, Malairaman

    2017-03-01

    Sonic hedgehog (Shh) signaling influences neurogenesis and neural patterning during the development of central nervous system. Dysregulation of Shh signaling in brain leads to neurological disorders like autism spectrum disorder, depression, dementia, stroke, Parkinson's diseases, Huntington's disease, locomotor deficit, epilepsy, demyelinating disease, neuropathies as well as brain tumors. The synthesis, processing and transport of Shh ligand as well as the localization of its receptors and signal transduction in the central nervous system has been carefully reviewed. Further, we summarize the regulation of small molecule modulators of Shh pathway with potential in neurological disorders. In conclusion, further studies are warranted to demonstrate the potential of positive and negative regulators of the Shh pathway in neurological disorders.

  15. Neurological disorders presenting mainly in adolescence

    PubMed Central

    Macleod, S; Appleton, R E

    2007-01-01

    The aim of this review is to discuss some of the neurological diseases that present mainly in the adolescent period. The article focuses on the usual presentation and course of the more common, and some uncommon, epilepsies, neuromuscular disorders, neurodegenerative disorders, inflammatory disorders of the central nervous system and some other, miscellaneous conditions. The article ends with a very brief and general discussion about management issues in this age group. PMID:17264287

  16. Neurologic Disorders and Hepatitis E, France, 2010

    PubMed Central

    Despierres, Laura-Anne; Kaphan, Elsa; Attarian, Shahram; Cohen-Bacrie, Stephan; Pelletier, Jean; Pouget, Jean; Motte, Anne; Charrel, Rémi; Gerolami, René

    2011-01-01

    We report meningitis with diffuse neuralgic pain or polyradiculoneuropathy associated with PCR-documented acute hepatitis E in 2 adults. These observations suggest that diagnostic testing for hepatitis E virus should be conducted for patients who have neurologic symptoms and liver cytolysis. PMID:21801637

  17. Paraneoplastic Neurological Disorder in Nasopharyngeal Carcinoma

    PubMed Central

    Ng, Sze Yin; Kongg, Min Han; Yunus, Mohd Razif Mohamad

    2017-01-01

    Paraneoplastic neurological disorder (PND) is a condition due to immune cross-reactivity between the tumour cells and the normal tissue, whereby the “onconeural” antibodies attack the normal host nervous system. It can present within weeks to months before or after the diagnosis of malignancies. Nasopharyngeal carcinoma is associated with paraneoplastic syndrome, for example, dermatomyositis, and rarely with a neurological disorder. We report on a case of nasopharyngeal carcinoma with probable PND. Otolaryngologists, oncologists and neurologists need to be aware of this condition in order to make an accurate diagnosis and to provide prompt treatment. PMID:28381934

  18. Genetic testing for paediatric neurological disorders.

    PubMed

    Valente, Enza Maria; Ferraris, Alessandro; Dallapiccola, Bruno

    2008-12-01

    Paediatric neurological disorders encompass a large group of clinically heterogeneous diseases, of which some are known to have a genetic cause. Over the past few years, advances in nosological classifications and in strategies for molecular testing have substantially improved the diagnosis, genetic counselling, and clinical management of many patients, and have facilitated the possibility of prenatal diagnoses for future pregnancies. However, the increasing availability of genetic tests for paediatric neurological disorders is raising important questions with regard to the appropriateness, choice of protocols, interpretation of results, and ethical and social concerns of these services. In this Review, we discuss these topics and how these concerns affect genetic counselling.

  19. 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

  20. Glutamine Synthetase: Role in Neurological Disorders.

    PubMed

    Jayakumar, Arumugam R; Norenberg, Michael D

    2016-01-01

    Glutamine synthetase (GS) is an ATP-dependent enzyme found in most species that synthesizes glutamine from glutamate and ammonia. In brain, GS is exclusively located in astrocytes where it serves to maintain the glutamate-glutamine cycle, as well as nitrogen metabolism. Changes in the activity of GS, as well as its gene expression, along with excitotoxicity, have been identified in a number of neurological conditions. The literature describing alterations in the activation and gene expression of GS, as well as its involvement in different neurological disorders, however, is incomplete. This review summarizes changes in GS gene expression/activity and its potential contribution to the pathogenesis of several neurological disorders, including hepatic encephalopathy, ischemia, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's disease, and astroglial neoplasms. This review also explores the possibility of targeting GS in the therapy of these conditions.

  1. 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

  2. Imaging of Common Adult Neurologic Disorders

    PubMed Central

    McLennan, Michael K.; Marotta, Thomas R.; TerBrugge, Karel G.; Marotta, Joseph T.

    1991-01-01

    The family physician is often called upon to diagnose a range of adult neurologic disorders. Clinical history, physical examination, laboratory tests, and imaging studies are required to discover their cause. Various imaging modalities can be used to evaluate common adult disorders of the central nervous system. ImagesFigures 1-2Figure 3Figure 4Figures 5-6Figures 7-8Figures 9-11 PMID:21229013

  3. Neurological disorders in Gulf War veterans

    PubMed Central

    Rose, Michael R; Brix, Kelley Ann

    2006-01-01

    We present a review of neurological function in Gulf War veterans (GWV). Twenty-two studies were reviewed, including large hospitalization and registry studies, large population-based epidemiological studies, investigations of a single military unit, small uncontrolled studies of ill veterans and small controlled studies of veterans. In nearly all studies, neurological function was normal in most GWVs, except for a small proportion who were diagnosed with compression neuropathies (carpal tunnel syndrome or ulnar neuropathy). In the great majority of controlled studies, there were no differences in the rates of neurological abnormalities in GWVs and controls. In a national US study, the incidence of amyotrophic lateral sclerosis (ALS) seems to be significantly increased in GWVs, compared to the rate in controls. However, it is possible that military service, in general, might be associated with an increased risk of ALS, rather than Gulf War service in particular. Taken together, the conclusion is that if a neurological examination in a GWV is within normal limits, then extensive neurological testing is unlikely to diagnose occult neurological disorders. PMID:16687265

  4. Sleep disorders in children with neurologic diseases.

    PubMed

    Zucconi, M; Bruni, O

    2001-12-01

    Pediatric neurologic diseases are often associated with different kinds of sleep disruption (mainly insomnia, less frequently hypersomnia or parasomnias). Due to the key-role of sleep for development, the effort to ameliorate sleep patterns in these children could have important prognostic benefits. Study of sleep architecture and organization in neurologic disorders could lead to a better comprehension of the pathogenesis and a better treatment of the disorders. This article focuses on the following specific neurologic diseases: nocturnal frontal lobe epilepsy and abnormal motor behaviors of epileptic origin, evaluating differential diagnosis with parasomnias; achondroplasia, confirming the crucial role of craniofacial deformity in determining sleep-disordered breathing; neuromuscular diseases, mainly Duchenne's muscular dystrophy and myotonic dystrophy; cerebral palsy, evaluating either the features of sleep architecture and the importance of the respiratory problems associated; headaches, confirming the strict relationships with sleep in terms of neurochemical and neurobehavioral substrates; and finally a review on the effectiveness of melatonin for sleep problems in children with neurologic syndromes and mental retardation, blindness, and epilepsy.

  5. Protective effects of ginseng on neurological disorders

    PubMed Central

    Ong, Wei-Yi; Farooqui, Tahira; Koh, Hwee-Ling; Farooqui, Akhlaq A.; Ling, Eng-Ang

    2015-01-01

    Ginseng (Order: Apiales, Family: Araliaceae, Genus: Panax) has been used as a traditional herbal medicine for over 2000 years, and is recorded to have antianxiety, antidepressant and cognition enhancing properties. The protective effects of ginseng on neurological disorders are discussed in this review. Ginseng species and ginsenosides, and their intestinal metabolism and bioavailability are briefly introduced. This is followed by molecular mechanisms of effects of ginseng on the brain, including glutamatergic transmission, monoamine transmission, estrogen signaling, nitric oxide (NO) production, the Keap1/Nrf2 adaptive cellular stress pathway, neuronal survival, apoptosis, neural stem cells and neuroregeneration, microglia, astrocytes, oligodendrocytes and cerebral microvessels. The molecular mechanisms of the neuroprotective effects of ginseng in Alzheimer’s disease (AD) including β-amyloid (Aβ) formation, tau hyperphosphorylation and oxidative stress, major depression, stroke, Parkinson’s disease and multiple sclerosis are presented. It is hoped that this discussion will stimulate more studies on the use of ginseng in neurological disorders. PMID:26236231

  6. Diagnostic Exercise: Neurologic Disorder in a Cat

    DTIC Science & Technology

    1989-12-21

    dogs and a cat . Vet Pathol 1987;24:192-194. 4. Migaki G, Casey HW, Bayles WB. Cerebral phaeohyphomycosis in a dog . J Am Vet Med Assoc 1987;191(8):997...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

  7. Genetics of hereditary neurological disorders in children.

    PubMed

    Huang, Yue; Yu, Sui; Wu, Zhanhe; Tang, Beisha

    2014-04-01

    Hereditary neurological disorders (HNDs) are relatively common in children compared to those occurring in adulthood. Recognising clinical manifestations of HNDs is important for the selection of genetic testing, genetic testing results interpretation, and genetic consultation. Meanwhile, advances in next generation sequencing (NGS) technologies have significantly enabled the discovery of genetic causes of HNDs and also challenge paediatricians on applying genetic investigation. Combination of both clinical information and advanced technologies will enhance the genetic test yields in clinical setting. This review summarises the clinical presentations as well as genetic causes of paediatric neurological disorders in four major areas including movement disorders, neuropsychiatric disorders, neuron peripheral disorders and epilepsy. The aim of this review is to help paediatric neurologists not only to see the clinical features but also the complex genetic aspect of HNDs in order to utilise genetic investigation confidently in their clinical practice. A smooth transition from research based to clinical use of comprehensive genetic testing in HNDs in children could be foreseen in the near future while genetic testing, genetic counselling and genetic data interpretation are in place appropriately.

  8. Genetics of hereditary neurological disorders in children

    PubMed Central

    Yu, Sui; Wu, Zhanhe; Tang, Beisha

    2014-01-01

    Hereditary neurological disorders (HNDs) are relatively common in children compared to those occurring in adulthood. Recognising clinical manifestations of HNDs is important for the selection of genetic testing, genetic testing results interpretation, and genetic consultation. Meanwhile, advances in next generation sequencing (NGS) technologies have significantly enabled the discovery of genetic causes of HNDs and also challenge paediatricians on applying genetic investigation. Combination of both clinical information and advanced technologies will enhance the genetic test yields in clinical setting. This review summarises the clinical presentations as well as genetic causes of paediatric neurological disorders in four major areas including movement disorders, neuropsychiatric disorders, neuron peripheral disorders and epilepsy. The aim of this review is to help paediatric neurologists not only to see the clinical features but also the complex genetic aspect of HNDs in order to utilise genetic investigation confidently in their clinical practice. A smooth transition from research based to clinical use of comprehensive genetic testing in HNDs in children could be foreseen in the near future while genetic testing, genetic counselling and genetic data interpretation are in place appropriately. PMID:26835329

  9. NEUROLOGICAL ASPECTS OF HUMAN GLYCOSYLATION DISORDERS

    PubMed Central

    Freeze, Hudson H.; Eklund, Erik A.; Ng, Bobby G.; Patterson, Marc C.

    2016-01-01

    This review will present principles of glycosylation, describe the relevant glycosylation pathways and their related disorders, and highlight some of the neurological aspects and issues that continue to challenge researchers. Over 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. Most of these disorders impact the central and/or peripheral nervous systems. Patients typically have developmental delay/intellectual disability, hypotonia, seizures, neuropathy, and metabolic abnormalities in multiple organ systems. Between these disorders there is great clinical diversity because all cell types differentially glycosylate proteins and lipids. The patients have hundreds of mis-glycosylated products afflicting a myriad of processes including cell signaling, cell-cell interaction and cell migration. This vast complexity in glycan composition and function, along with limited analytic tools has impeded the identification of key glycosylated molecules that cause pathologies, and to date few critical target proteins have been pinpointed. PMID:25840006

  10. 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

  11. Complex I deficiencies in neurological disorders.

    PubMed

    Papa, Sergio; De Rasmo, Domenico

    2013-01-01

    Complex I is the point of entry in the mitochondrial electron transport chain for NADH reducing equivalents, and it behaves as a regulatable pacemaker of respiratory ATP production in human cells. Defects in complex I are associated with several human neurological disorders, including primary mitochondrial diseases, Parkinson disease (PD), and Down syndrome, and understanding the activity and regulation of complex I may reveal aspects of the underlying pathogenic mechanisms. Complex I is regulated by cyclic AMP (cAMP) and the protein kinase A (PKA) signal transduction pathway, and elucidating the role of the cAMP/PKA system in regulating complex I and oxygen free radical production provides new perspectives for devising therapeutic strategies for neurological diseases.

  12. Profile of neurological disorders in an adult neurology clinic in Kumasi, Ghana

    PubMed Central

    Sarfo, Fred Stephen; Akassi, John; Badu, Elizabeth; Okorozo, Aham; Ovbiagele, Bruce; Akpalu, Albert

    2016-01-01

    Background Although the burden of neurological disorders is highest among populations in developing countries there is a dearth of data on the clinical spectrum of these disorders. Objective To profile the frequency of neurologic disorders and basic demographic data in an adult neurology out-patient service commissioned in 2011 in Kumasi, Ghana. Methods The study was conducted at the neurology clinic of the Komfo Anokye Teaching Hospital in Kumasi, Ghana. Over a three year period, all medical records of patients enrolled at the out-patient neurology clinic was reviewed by a neurologist and neurological diagnoses classified according to ICD-10. Results 1812 adults enrolled for care in the neurology out-patient service between 2011 and 2013. This comprised of 882 males and 930 females (male: female ratio of 1.0: 1.1) with an overall median age of 54 (IQR, 39–69) years. The commonest primary neurological disorders seen were strokes, epilepsy and seizure disorders, and movement disorders at frequencies of 57.1%, 19.8%, and 8.2% respectively. Conclusions Cerebrovascular diseases, epilepsy and movement disorders were among the commonest neurological disorders and the major contributors to neurologic morbidity among Ghanaians in an urban neurology clinic. PMID:27110596

  13. Wilson's disease and other neurological copper disorders.

    PubMed

    Bandmann, Oliver; Weiss, Karl Heinz; Kaler, Stephen G

    2015-01-01

    The copper metabolism disorder Wilson's disease was first defined in 1912. Wilson's disease can present with hepatic and neurological deficits, including dystonia and parkinsonism. Early-onset presentations in infancy and late-onset manifestations in adults older than 70 years of age are now well recognised. Direct genetic testing for ATP7B mutations are increasingly available to confirm the clinical diagnosis of Wilson's disease, and results from biochemical and genetic prevalence studies suggest that Wilson's disease might be much more common than previously estimated. Early diagnosis of Wilson's disease is crucial to ensure that patients can be started on adequate treatment, but uncertainty remains about the best possible choice of medication. Furthermore, Wilson's disease needs to be differentiated from other conditions that also present clinically with hepatolenticular degeneration or share biochemical abnormalities with Wilson's disease, such as reduced serum ceruloplasmin concentrations. Disordered copper metabolism is also associated with other neurological conditions, including a subtype of axonal neuropathy due to ATP7A mutations and the late-onset neurodegenerative disorders Alzheimer's disease and Parkinson's disease.

  14. Integrins as Receptor Targets for Neurological Disorders

    PubMed Central

    Wu, Xin; Reddy, Doodipala Samba

    2012-01-01

    This review focuses on the neurobiology of integrins, pathophysiological roles of integrins in neuroplasticity and nervous system disorders, and therapeutic implications of integrins as potential drug targets and possible delivery pathways. Neuroplasticity is a central phenomenon in many neurological conditions such as seizures, trauma, and traumatic brain injury. During the course of many brain diseases, in addition to intracellular compartment changes, alterations in non-cell compartments such as extracellular matrix (ECM) are recognized as an essential process in forming and reorganizing neural connections. Integrins are heterodimeric transmembrane receptors that mediate cell–ECM and cell–cell adhesion events. Although the mechanisms of neuroplasticity remain unclear, it has been suggested that integrins undergo plasticity including clustering through interactions with ECM proteins, modulating ion channels, intracellular Ca2+ and protein kinases signaling, and reorganization of cytoskeletal filaments. As cell surface receptors, integrins are central to the pathophysiology of many brain diseases, such as epilepsy, and are potential targets for the development of new drugs for neurological disorders. PMID:22233753

  15. Community-Acquired Pneumonia Hospitalization among Children with Neurologic Disorders

    PubMed Central

    Millman, Alexander J.; Finelli, Lyn; Bramley, Anna M.; Peacock, Georgina; Williams, Derek J.; Arnold, Sandra R.; Grijalva, Carlos G.; Anderson, Evan J.; McCullers, Jonathan A.; Ampofo, Krow; Pavia, Andrew T.; Edwards, Kathryn M.; Jain, Seema

    2016-01-01

    Objective To describe and compare the clinical characteristics, outcomes, and etiology of pneumonia among children hospitalized with community-acquired pneumonia (CAP) with neurologic disorders, non-neurologic underlying conditions, and no underlying conditions. Study design Children <18 years old hospitalized with clinical and radiographic CAP were enrolled at 3 US children’s hospitals. Neurologic disorders included cerebral palsy, developmental delay, Down syndrome, epilepsy, non-Down syndrome chromosomal abnormalities, and spinal cord abnormalities. We compared the epidemiology, etiology, and clinical outcomes of CAP in children with neurologic disorders with those with non-neurologic underlying conditions, and those with no underlying conditions using bivariate, age-stratified, and multivariate logistic regression analyses. Results From January 2010–June 2012, 2358 children with radiographically confirmed CAP were enrolled; 280 (11.9%) had a neurologic disorder (52.1% of these individuals also had non-neurologic underlying conditions), 934 (39.6%) had non-neurologic underlying conditions only, and 1144 (48.5%) had no underlying conditions. Children with neurologic disorders were older and more likely to require intensive care unit (ICU) admission than children with non-neurologic underlying conditions and children with no underlying conditions; similar proportions were mechanically ventilated. In age-stratified analysis, children with neurologic disorders were less likely to have a pathogen detected than children with non-neurologic underlying conditions. In multivariate analysis, having a neurologic disorder was associated with ICU admission for children ≥2 years of age. Conclusions Children with neurologic disorders hospitalized with CAP were less likely to have a pathogen detected and more likely to be admitted to the ICU than children without neurologic disorders. PMID:27017483

  16. Drug treatment of vertigo in neurological disorders.

    PubMed

    Berisavac, Ivana I; Pavlović, Aleksandra M; Trajković, Jasna J Zidverc; Šternić, Nadežda M Čovičković; Bumbaširević, Ljiljana G Beslać

    2015-01-01

    Vertigo is a common symptom in everyday clinical practice. The treatment depends on the specific etiology. Vertigo may be secondary to inner ear pathology, or any existing brainstem or cerebellar lesion but may also be psychogenic. Central vertigo is a consequence of a central nervous system lesion. It is often associated with a focal neurological deficit. Peripheral vertigo is secondary to dysfunction of the peripheral vestibular system and is usually characterized by an acute vertigo with loss of balance, sensation of spinning in the space or around self, and is exaggerated with changes of the head and body position; no other neurological deficit is present. Some medications may also cause vertigo. Depending on the cause of the vertigo, drugs with different mechanisms of action, physical therapy, psychotherapy, as well as surgery may be used to combat this disabling malady. Symptomatic treatment has a particularly important role, regardless of the etiology of vertigo. We reviewed the current medications recommended for patients with vertigo, their mechanisms of action and their most frequent side effects.

  17. Etiology of Attention Disorders: A Neurological/Genetic Perspective.

    ERIC Educational Resources Information Center

    Grantham, Madeline Kay

    This paper explores the historical origins of attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD) as a neurological disorder, current neurological and genetic research concerning the etiology of ADD/ADHD, and implications for diagnosis and treatment. First, ADD/ADHD is defined and then the origins of ADD/ADHD as a…

  18. 76 FR 9587 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-18

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial Review...: National Institute of Neurological Disorders and Stroke Initial Review Group; Neurological Sciences...

  19. Wilson's disease and other neurological copper disorders.

    PubMed Central

    Bandmann, Oliver; Weiss, Karl Heinz; Kaler, Stephen G.

    2015-01-01

    Summary The classic copper metabolism disorder, Wilson disease (WD), was first defined in 1912. Both early onset presentations in infancy and late onset manifestations in adults > 70 years are now well recognized. Modern biochemical and genetic prevalence studies suggest that WD may be considerably more common than previously appreciated. Early diagnosis of WD is crucial to ensure that patients can be started on adequate treatment but uncertainty remains about the best possible choice of medication. Direct genetic testing for ATP7B mutations is increasingly available to confirm the clinical diagnosis of WD. WD needs to be differentiated from other conditions that present clinically with hepatolenticular degeneration or share biochemical abnormalities with WD, such as reduced serum cerulo plasmin levels. Disordered copper metabolism is also implied in an increasing number of other neurological conditions, including a subtype of axonal neuropathy due to ATP7A mutations, and the common late-onset neurodegenerative disorders Alzheimer’s disease and Parkinson’s disease. PMID:25496901

  20. Accommodation of workers with chronic neurologic disorders.

    PubMed

    Bleecker, Margit L; Barnes, Sheryl K

    2015-01-01

    The ability to work is important to those with chronic neurologic disorders (CND) and to the aging workforce. Many signs and symptoms are similar in those with CND and normal aging, but may interfere with the ability to work if not appropriately accommodated. This requires the healthcare provider to recognize the specific features of the CND that interferes with work and how it can be accommodated. Review of the American with Disabilities Act and the subsequent amendment informs the healthcare provider as to what is covered under the law and how the disability can be accommodated. Overall employers want to retain qualified employees and therefore accommodating workers is beneficial to both the employee with CND and the employer.

  1. Functional Neuroanatomy and Neurophysiology of Functional Neurological Disorders (Conversion Disorder).

    PubMed

    Voon, Valerie; Cavanna, Andrea E; Coburn, Kerry; Sampson, Shirlene; Reeve, Alya; LaFrance, W Curt

    2016-01-01

    Much is known regarding the physical characteristics, comorbid symptoms, psychological makeup, and neuropsychological performance of patients with functional neurological disorders (FNDs)/conversion disorders. Gross neurostructural deficits do not account for the patients' deficits or symptoms. This review describes the literature focusing on potential neurobiological (i.e. functional neuroanatomic/neurophysiological) findings among individuals with FND, examining neuroimaging and neurophysiological studies of patients with the various forms of motor and sensory FND. In summary, neural networks and neurophysiologic mechanisms may mediate "functional" symptoms, reflecting neurobiological and intrapsychic processes.

  2. Monogenic neurological disorders of sphingolipid metabolism.

    PubMed

    Sabourdy, Frédérique; Astudillo, Leonardo; Colacios, Céline; Dubot, Patricia; Mrad, Marguerite; Ségui, Bruno; Andrieu-Abadie, Nathalie; Levade, Thierry

    2015-08-01

    Sphingolipids comprise a wide variety of molecules containing a sphingoid long-chain base that can be N-acylated. These lipids are particularly abundant in the central nervous system, being membrane components of neurons as well as non-neuronal cells. Direct evidence that these brain lipids play critical functions in brain physiology is illustrated by the dramatic consequences of genetic disturbances of their metabolism. Inherited defects of both synthesis and catabolism of sphingolipids are now identified in humans. These monogenic disorders are due to mutations in the genes encoding for the enzymes that catalyze either the formation or degradation of simple sphingolipids such as ceramides, or complex sphingolipids like glycolipids. They cause varying degrees of central nervous system dysfunction, quite similarly to the neurological disorders induced in mice by gene disruption of the corresponding enzymes. Herein, the enzyme deficiencies and metabolic alterations that underlie these diseases are reviewed. Their possible pathophysiological mechanisms and the functions played by sphingolipids one can deduce from these conditions are discussed. This article is part of a Special Issue entitled Brain Lipids.

  3. Hyperhomocysteinemia and neurologic disorders: a review.

    PubMed

    Ansari, Ramin; Mahta, Ali; Mallack, Eric; Luo, Jin Jun

    2014-10-01

    Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. It has a physiologic role in DNA metabolism via methylation, a process governed by the presentation of folate, and vitamins B6 and B12. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy (eHcy) can be caused by deficiency of either vitamin B12 or folate, or a combination thereof. Certain genetic factors also cause eHcy, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase. eHcy has been observed in several medical conditions, such as cardiovascular disorders, atherosclerosis, myocardial infarction, stroke, minimal cognitive impairment, dementia, Parkinson's disease, multiple sclerosis, epilepsy, and eclampsia. There is evidence from laboratory and clinical studies that Hcy, and especially eHcy, exerts direct toxic effects on both the vascular and nervous systems. This article provides a review of the current literature on the possible roles of eHcy relevant to various neurologic disorders.

  4. Hyperhomocysteinemia and Neurologic Disorders: a Review

    PubMed Central

    Ansari, Ramin; Mallack, Eric; Luo, Jin Jun

    2014-01-01

    Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. It has a physiologic role in DNA metabolism via methylation, a process governed by the presentation of folate, and vitamins B6 and B12. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy (eHcy) can be caused by deficiency of either vitamin B12 or folate, or a combination thereof. Certain genetic factors also cause eHcy, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase. eHcy has been observed in several medical conditions, such as cardiovascular disorders, atherosclerosis, myocardial infarction, stroke, minimal cognitive impairment, dementia, Parkinson's disease, multiple sclerosis, epilepsy, and eclampsia. There is evidence from laboratory and clinical studies that Hcy, and especially eHcy, exerts direct toxic effects on both the vascular and nervous systems. This article provides a review of the current literature on the possible roles of eHcy relevant to various neurologic disorders. PMID:25324876

  5. Acute porphyric disorders.

    PubMed

    Moore, A W; Coke, J M

    2000-09-01

    Acute porphyrias are classified into 3 distinct groups of rare genetic disorders of metabolic enzyme biosynthesis. Acute porphyrias can significantly impact multiple organ systems, which often provides a challenge to the dentist presented with such a patient. A case of hereditary coproporphyria is reported in a patient with many of the classical signs and symptoms. The patient also had complex dental needs that required special medical and pharmacotherapeutic modifications. The acute porphyrias are reviewed by the authors with presentation of this challenging case. Recommendations for other dental health care professionals encountering these patients are then presented.

  6. Control of Abnormal Synchronization in Neurological Disorders

    PubMed Central

    Popovych, Oleksandr V.; Tass, Peter A.

    2014-01-01

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

  7. Microbiota and Neurological Disorders: A Gut Feeling

    PubMed Central

    Moos, Walter H.; Faller, Douglas V.; Harpp, David N.; Kanara, Iphigenia; Pernokas, Julie; Powers, Whitney R.; Steliou, Kosta

    2016-01-01

    Abstract In the past century, noncommunicable diseases have surpassed infectious diseases as the principal cause of sickness and death, worldwide. Trillions of commensal microbes live in and on our body, and constitute the human microbiome. The vast majority of these microorganisms are maternally derived and live in the gut, where they perform functions essential to our health and survival, including: digesting food, activating certain drugs, producing short-chain fatty acids (which help to modulate gene expression by inhibiting the deacetylation of histone proteins), generating anti-inflammatory substances, and playing a fundamental role in the induction, training, and function of our immune system. Among the many roles the microbiome ultimately plays, it mitigates against untoward effects from our exposure to the environment by forming a biotic shield between us and the outside world. The importance of physical activity coupled with a balanced and healthy diet in the maintenance of our well-being has been recognized since antiquity. However, it is only recently that characterization of the host–microbiome intermetabolic and crosstalk pathways has come to the forefront in studying therapeutic design. As reviewed in this report, synthetic biology shows potential in developing microorganisms for correcting pathogenic dysbiosis (gut microbiota–host maladaptation), although this has yet to be proven. However, the development and use of small molecule drugs have a long and successful history in the clinic, with small molecule histone deacetylase inhibitors representing one relevant example already approved to treat cancer and other disorders. Moreover, preclinical research suggests that epigenetic treatment of neurological conditions holds significant promise. With the mouth being an extension of the digestive tract, it presents a readily accessible diagnostic site for the early detection of potential unhealthy pathogens resident in the gut. Taken together, the

  8. 75 FR 5093 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

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  18. 75 FR 3475 - National Institute Of Neurological Disorders and Stroke; Notice of Meetings

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  1. 78 FR 22273 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

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  2. 77 FR 27239 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

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  3. 75 FR 42758 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

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  4. 76 FR 66732 - National Institute of Neurological Disorders and Stroke Notice of Closed Meetings

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  5. 78 FR 36201 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

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  6. Factitious disorders and malingering in relation to functional neurologic disorders.

    PubMed

    Bass, C; Halligan, P

    2017-01-01

    Interest in malingering has grown in recent years, and is reflected in the exponential increase in academic publications since 1990. Although malingering is more commonly detected in medicolegal practice, it is not an all-or-nothing presentation and moreover can vary in the extent of presentation. As a nonmedical disorder, the challenge for clinical practice remains that malingering by definition is intentional and deliberate. As such, clinical skills alone are often insufficient to detect it and we describe psychometric tests such as symptom validity tests and relevant nonmedical investigations. Finally, we describe those areas of neurologic practice where symptom exaggeration and deception are more likely to occur, e.g., postconcussional syndrome, psychogenic nonepileptic seizures, motor weakness and movement disorders, and chronic pain. Factitious disorders are rare in clinical practice and their detection depends largely on the level of clinical suspicion supported by the systematic collection of relevant information from a variety of sources. In this chapter we challenge the accepted DSM-5 definition of factitious disorder and suggest that the traditional glossaries have neglected the extent to which a person's reported symptoms can be considered a product of intentional choice or selective psychopathology largely beyond the subject's voluntary control, or more likely, both. We present evidence to suggest that neurologists preferentially diagnose factitious presentations in healthcare workers as "hysterical," possibly to avoid the stigma of simulated illness.

  7. Conversion disorder and mass psychogenic illness in child neurology.

    PubMed

    Mink, Jonathan W

    2013-11-01

    A common problem faced by neurologists is the existence of disorders that present with neurological symptoms but do not have identifiable neurological bases. Conversion disorder is the most common of these disorders. In some situations, members of a cohesive social group will develop the same or similar symptoms. This review discusses conversion disorder in children, with an emphasis on function movement disorders. It also reviews a recent occurrence of mass psychogenic illness in New York State with discussion of the key features of mass psychogenic illness.

  8. CSF hypocretin-1 assessment in sleep and neurological disorders.

    PubMed

    Bourgin, Patrice; Zeitzer, Jamie M; Mignot, Emmanuel

    2008-07-01

    Concentrations of CSF hypocretin-1 (formerly orexin A) have been measured in many patients with sleep or neurological conditions. Low CSF hypocretin-1 is most predictive of narcolepsy in patients positive for HLA allele DQB1*0602, most of whom have cataplexy. By contrast, the diagnostic significance of low CSF hypocretin-1 is unclear in the presence of acute CNS inflammation or trauma. The clinical usefulness of CSF testing in hypersomnia that is symptomatic of a neurological disorder remains to be evaluated. Determination of CSF hypocretin-1 concentration to diagnose narcolepsy might be most useful in ambulatory patients with cataplexy but with a normal multiple sleep latency test (MSLT) result, or if MSLT is not interpretable, conclusive, or feasible. Because 98% of patients with hypocretin-1 deficiency are positive for HLA DQB1*0602, we suggest that HLA typing is a useful screen before lumbar puncture. Although hypocretin-1 deficiency in narcolepsy might have therapeutic relevance, additional research is needed in this area.

  9. 78 FR 13359 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

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    2013-02-27

    ... invasion of personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke... Related to Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences,...

  10. Functional disorders in the Neurology section of ICD-11

    PubMed Central

    Hallett, Mark; Carson, Alan; Bergen, Donna; Shakir, Raad

    2014-01-01

    Functional disorders are one of the most common diagnoses in neurologic practice, but this is not reflected in current classification systems. The 11th revision of the World Health Organization's International Classification of Diseases (ICD-11) in 2017 offers an opportunity for these disorders to appear within both neurologic and psychiatric categories for the first time. We discuss the rationale for this proposal and highlight the potential benefits for health professionals and patients. PMID:25488992

  11. Bridging neuroanatomy, neuroradiology and neurology: three-dimensional interactive atlas of neurological disorders.

    PubMed

    Nowinski, W L; Chua, B C

    2013-06-01

    Understanding brain pathology along with the underlying neuroanatomy and the resulting neurological deficits is of vital importance in medical education and clinical practice. To facilitate and expedite this understanding, we created a three-dimensional (3D) interactive atlas of neurological disorders providing the correspondence between a brain lesion and the resulting disorder(s). The atlas contains a 3D highly parcellated atlas of normal neuroanatomy along with a brain pathology database. Normal neuroanatomy is divided into about 2,300 components, including the cerebrum, cerebellum, brainstem, spinal cord, arteries, veins, dural sinuses, tracts, cranial nerves (CN), white matter, deep gray nuclei, ventricles, visual system, muscles, glands and cervical vertebrae (C1-C5). The brain pathology database contains 144 focal and distributed synthesized lesions (70 vascular, 36 CN-related, and 38 regional anatomy-related), each lesion labeled with the resulting disorder and associated signs, symptoms, and/or syndromes compiled from materials reported in the literature. The initial view of each lesion was preset in terms of its location and size, surrounding surface and sectional (magnetic resonance) neuroanatomy, and labeling of lesion and neuroanatomy. In addition, a glossary of neurological disorders was compiled and for each disorder materials from textbooks were included to provide neurological description. This atlas of neurological disorders is potentially useful to a wide variety of users ranging from medical students, residents and nurses to general practitioners, neuroanatomists, neuroradiologists and neurologists, as it contains both normal (surface and sectional) brain anatomy and pathology correlated with neurological disorders presented in a visual and interactive way.

  12. Childhood organic neurological disease presenting as psychiatric disorder.

    PubMed Central

    Rivinus, T M; Jamison, D L; Graham, P J

    1975-01-01

    Over a period of one year 12 children with complaints which had been diagnosed as due to a psychiatric disorder presented to a paediatric neurological unit where neurological disease was diagnosed. The group was characterized by behavioural symptoms such as deteriorating school performance, visual loss, and postural disturbance, which are unusual in children attending child psychiatric departments. It is suggested that where there is diagnostic uncertainty the presence of these physical symptoms calls for periodic neurological reassessment, and attention is drawn to the rare but serious disorders which may thus be diagnosed. Making an organic diagnosis, however, should not preclude psychosocial management of emotional reactions in these families. PMID:1130816

  13. Neurological Manifestations of Acute Posterior Multifocal Placoid Pigment Epitheliopathy

    PubMed Central

    Alkhotani, Ashjan; Shirah, Bader

    2016-01-01

    Background and Purpose Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an immune-mediated chorioretinal disease that causes acute visual symptoms with characteristic ophthalmoscopic findings. Neurological complications are rarely reported in the literature. Here we report two new cases of APMPPE that presented with neurological manifestations, one of which was associated with peripheral neuropathy, which has not been described before. Methods A retrospective database review of all patients with a diagnosis of APMPPE was performed. Clinical, ophthalmological, and neurological data were analyzed, and only cases of APMPPE with neurological complications were included. A literature review of several databases was also performed, and previous case reports were reviewed and analyzed in detail. Results In total, 56 cases of APMPPE-associated neurological complications were included in the analyses: 54 from the literature and 2 from our own practice. The most common complication was cerebral vasculitis, which affected 28 patients (50%), followed by headaches in 15 patients (26.8%). The other complications include sixth-cranial-nerve palsy, transient hearing loss, meningoencephalitis, cavernous sinus thrombosis, and viral meningitis. Conclusions This report adds to the literature of a novel association of APMPPE with peripheral neuropathy, and comprehensively reviews the neurological manifestations of this disease. A high level of suspicion should be applied when dealing with a case of APMPPE. We recommend applying detailed clinical neurological examinations and magnetic resonance imaging to APMPPE patients, and then early steroid treatment if the examination is positive or even suspicious. Early treatment with steroids and long-term treatment with immunosuppressive azathioprine with interval neurological evaluations will contribute positively to the outcomes and avoid fatal complications, namely strokes. PMID:27819416

  14. Neuroelectronics and Biooptics: Closed-Loop Technologies in Neurological Disorders.

    PubMed

    Krook-Magnuson, Esther; Gelinas, Jennifer N; Soltesz, Ivan; Buzsáki, György

    2015-07-01

    Brain-implanted devices are no longer a futuristic idea. Traditionally, therapies for most neurological disorders are adjusted based on changes in clinical symptoms and diagnostic measures observed over time. These therapies are commonly pharmacological or surgical, requiring continuous or irreversible treatment regimens that cannot respond rapidly to fluctuations of symptoms or isolated episodes of dysfunction. In contrast, closed-loop systems provide intervention only when needed by detecting abnormal neurological signals and modulating them with instantaneous feedback. Closed-loop systems have been applied to several neurological conditions (most notably epilepsy and movement disorders), but widespread use is limited by conceptual and technical challenges. Herein, we discuss how advances in experimental closed-loop systems hold promise for improved clinical benefit in patients with neurological disorders.

  15. Early neurological stability predicts adverse outcome after acute ischemic stroke.

    PubMed

    Irvine, Hannah J; Battey, Thomas Wk; Ostwaldt, Ann-Christin; Campbell, Bruce Cv; Davis, Stephen M; Donnan, Geoffrey A; Sheth, Kevin N; Kimberly, W Taylor

    2016-10-01

    Background Deterioration in the National Institutes of Health Stroke Scale (NIHSS) in the early days after stroke is associated with progressive infarction, brain edema, and/or hemorrhage, leading to worse outcome. Aims We sought to determine whether a stable NIHSS score represents an adverse or favorable course. Methods Brain magnetic resonance images from a research cohort of acute ischemic stroke patients were analyzed. Using NIHSS scores at baseline and follow-up (day 3-5), patients were categorized into early neurological deterioration (ΔNIHSS ≥ 4), early neurological recovery (ΔNIHSS ≤ -4) or early neurological stability (ΔNIHSS between -3 and 3). The association between these categories and volume of infarct growth, volume of swelling, parenchymal hemorrhage, and 3-month modified Rankin Scale score were evaluated. Results Patients with early neurological deterioration or early neurological stability were less likely to be independent (modified Rankin Scale = 0-2) at 3 months compared to those with early neurological recovery ( P < 0.001). Patients with early neurological deterioration or early neurological stability were observed to have significantly greater infarct growth and swelling volumes than those with early neurological recovery ( P = 0.03; P < 0.001, respectively). Brain edema was more common than the other imaging markers investigated and was independently associated with a stable or worsening NIHSS score after adjustment for age, baseline stroke volume, infarct growth volume, presence of parenchymal hemorrhage, and reperfusion ( P < 0.0001). Conclusions Stable NIHSS score in the subacute period after ischemic stroke may not be benign and is associated with tissue injury, including infarct growth and brain edema. Early improvement is considerably more likely to occur in the absence of these factors.

  16. Neurological Disorders Complicating Pregnancy - Focus on Obstetric Outcome

    PubMed Central

    Renukesh, Sandya

    2016-01-01

    Introduction Neurological disorders in pregnancy can be pregnancy related or can be caused by exacerbation of a pre-existing neurological condition or sometimes may even be detected for the first time during pregnancy in which it might be an incidental finding. The diagnosis and management of the neurological disorders in pregnancy is always a challenging task due to varied symptomatology and risks to the fetus. The evaluation and management should be performed in a stepwise fashion and requires multidisciplinary approach. Aim The present study was conducted with the aim to study the influence of neurological disorders on outcome of pregnancy. Material and Methods This was a prospective observational study conduted over a period of 1 year (2013-2014) including 54 pregnant women with neurological manifestations. The spectrum of neurological manifestations was divided into-pregnancy specific, incidental and pre-existing neurological disorders for analysis. Five unusual cases with varied manifestations were studied in detail. Any pregnant woman presenting with neurological manifestation, irrespective of gestational age were included in the present study. The neurological manifestation and the obstetric outcome were analysed in the present study. Results There were 54 women with varied neurological manifestations, majority (74%) of them being primigravida. Seizure was the most common (63%) manifestation. The incidence of pregnancy specific disorder (eclampsia), pre-existing disease (epilepsy) and incidental causes were 40.8%, 37% and 22.2% respectively. Of the 22 women with eclampsia, 15(68%) had seizure during antepartum period and 7(32%) in the postpartum period. Three patients out of 22 who had eclampsia had intrauterine fetal demise on arrival itself, whereas the perinatal outcome was good in the other 19 patients who had live born babies. The most common incidental cause in the present study was tubercular meningitis (44%). There was however a maternal and

  17. 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

  18. [Neurological disorders associated with gluten sensitivity].

    PubMed

    Hernandez-Lahoz, C; Mauri-Capdevila, G; Vega-Villar, J; Rodrigo, L

    2011-09-01

    Gluten sensitivity is a systemic autoimmune disease that occurs in genetically susceptible individuals on ingesting gluten. It can appear at any age, then becoming a permanent condition. It is more frequent in women, as happens with other autoimmune diseases. Celiac disease is the intestinal form and the most important manifestation among a set of gluten-induced autoimmune pathologies that affect different systems. Neurological manifestations of gluten sensitivity, with or without enteropathy, are also frequent, their pathogenesis including an immunological attack on the central and peripheral nervous tissue accompanied by neurodegenerative changes. The clinical manifestations are varied, but the most common syndromes are cerebellar ataxia and peripheral neuropathy. Finally, gluten sensitivity is associated to a varying degree, with other complex diseases and could influence their evolution. The early detection of cases of gluten sensitivity with neurological manifestations and subsequent treatment with the gluten-free diet could provide remarkable benefits to the patients.

  19. 77 FR 49000 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

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  20. Acute Neurological Involvement in Diarrhea-Associated Hemolytic Uremic Syndrome

    PubMed Central

    Kwon, Thérésa; Elmaleh, Monique; Charbit, Marina; Launay, Emma Allain; Harambat, Jérôme; Brun, Muriel; Ranchin, Bruno; Bandin, Flavio; Cloarec, Sylvie; Bourdat-Michel, Guylhene; Piètrement, Christine; Champion, Gérard; Ulinski, Tim; Deschênes, Georges

    2010-01-01

    Background and objectives: Neurologic involvement is the most threatening complication of diarrhea-associated hemolytic uremic syndrome (D+HUS). Design, setting, participants, & measurements: We report a retrospective multicenter series of 52 patients with severe initial neurologic involvement that occurred in the course of D+HUS. Results: Verotoxigenic Escherichia coli infection was documented in 24. All except two patients had acute renal failure that required peritoneal dialysis, hemodialysis, or both techniques. A first group of eight patients remained with normal consciousness; five of them had protracted seizures. A second group of 23 patients had stuporous coma; five of these had protracted severe seizures, and 18 had a neurologic defect including pyramidal syndrome, hemiplegia or hemiparesia, and extrapyramidal syndrome. A third group of 21 patients had severe coma. Plasma exchanges were undertaken in 25 patients, 11 of whom were treated within 24 hours after the first neurologic sign; four died, two survived with severe sequelae, and five were alive without neurologic defect. Magnetic resonance imaging (MRI) for 29 patients showed that (1) every structure of the central nervous system was susceptible to involvement; (2) no correlation seemed to exist between special profile of localization on early MRI and the final prognosis; and (3) MRI did not exhibit any focal lesions in three patients. The overall prognosis of the series was marked by the death of nine patients and severe sequelae in 13. Conclusions: Neurologic involvement is associated with a severe renal disease but does not lead systematically to death or severe disability. PMID:20498239

  1. Progress in gene therapy for neurological disorders

    PubMed Central

    Simonato, Michele; Bennett, Jean; Boulis, Nicholas M.; Castro, Maria G.; Fink, David J.; Goins, William F.; Gray, Steven J.; Lowenstein, Pedro R.; Vandenberghe, Luk H.; Wilson, Thomas J.; Wolfe, John H.; Glorioso, Joseph C.

    2013-01-01

    Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy. PMID:23609618

  2. Temporal resolution in individuals with neurological disorders

    PubMed Central

    Rabelo, Camila Maia; Weihing, Jeffrey A; Schochat, Eliane

    2015-01-01

    OBJECTIVE: Temporal processing refers to the ability of the central auditory nervous system to encode and detect subtle changes in acoustic signals. This study aims to investigate the temporal resolution ability of individuals with mesial temporal sclerosis and to determine the sensitivity and specificity of the gaps-in-noise test in identifying this type of lesion. METHOD: This prospective study investigated differences in temporal resolution between 30 individuals with normal hearing and without neurological lesions (G1) and 16 individuals with both normal hearing and mesial temporal sclerosis (G2). Test performances were compared, and the sensitivity and specificity were calculated. RESULTS: There was no difference in gap detection thresholds between the two groups, although G1 revealed better average thresholds than G2 did. The sensitivity and specificity of the gaps-in-noise test for neurological lesions were 68% and 98%, respectively. CONCLUSIONS: Temporal resolution ability is compromised in individuals with neurological lesions caused by mesial temporal sclerosis. The gaps-in-noise test was shown to be a sensitive and specific measure of central auditory dysfunction in these patients. PMID:26375561

  3. Progress in gene therapy for neurological disorders.

    PubMed

    Simonato, Michele; Bennett, Jean; Boulis, Nicholas M; Castro, Maria G; Fink, David J; Goins, William F; Gray, Steven J; Lowenstein, Pedro R; Vandenberghe, Luk H; Wilson, Thomas J; Wolfe, John H; Glorioso, Joseph C

    2013-05-01

    Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy.

  4. 75 FR 51279 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-19

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke...: National Institute of Neurological Disorders and Stroke Initial Review Group, Neurological Sciences and... Disorders and Stroke Initial Review Group, Neurological Sciences and Disorders K. Date: October 28-29,...

  5. 77 FR 59939 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

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    2012-10-01

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  6. 78 FR 59041 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-25

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial Review... Neurological Disorders and Stroke Initial Review, Group Neurological Sciences and Disorders A. Date: October...

  7. 78 FR 4423 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-22

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke...@ninds.nih.gov . Name of Committee: National Institute of Neurological Disorders and Stroke Initial... Neurological Disorders and Stroke Initial Review Group; Neurological Sciences and Disorders C. Date:...

  8. Hypnosis as therapy for functional neurologic disorders.

    PubMed

    Deeley, Q

    2017-01-01

    Suggestion in hypnosis has been applied to the treatment of functional neurologic symptoms since the earliest descriptions of hypnosis in the 19th century. Suggestion in this sense refers to an intentional communication of beliefs or ideas, whether verbally or nonverbally, to produce subjectively convincing changes in experience and behavior. The recognition of suggestion as a psychologic process with therapeutic applications was closely linked to the derivation of hypnosis from earlier healing practices. Animal magnetism, the immediate precursor of hypnosis, arrived at a psychologic concept of suggestion along with other ideas and practices which were then incorporated into hypnosis. Before then, other forms of magnetism and ritual healing practices such as exorcism involved unintentionally suggestive verbal and nonverbal stimuli. We consider the derivation of hypnosis from these practices not only to illustrate the range of suggestive processes, but also the consistency with which suggestion has been applied to the production and removal of dissociative and functional neurologic symptoms over many centuries. Nineteenth-century practitioners treated functional symptoms with induction of hypnosis per se; imperative suggestions, or commands for specific effects; "medical clairvoyance" in hypnotic trance, in which patients diagnosed their own condition and predicted the time and manner of their recovery; and suggestion without prior hypnosis, known as "fascination" or "psychotherapeutics." Modern treatments largely involve different types of imperative suggestion with or without hypnosis. However, the therapeutic application of suggestion in hypnosis to functional and other symptoms waned in the first half of the 20th century under the separate pressures of behaviorism and psychoanalysis. In recent decades suggestion in hypnosis has been more widely applied to treating functional neurologic symptoms. Suggestion is typically applied within the context of other

  9. Neurological Disorders in Primary Sjögren's Syndrome

    PubMed Central

    Tobón, Gabriel J.; Pers, Jacques-Olivier; Devauchelle-Pensec, Valérie; Youinou, Pierre

    2012-01-01

    Sjögren's syndrome is an autoimmune disease characterized by an autoimmune exocrinopathy involving mainly salivary and lacrimal glands. The histopathological hallmark is periductal lymphocytic infiltration of the exocrine glands, resulting in loss of their secretory function. Several systemic manifestations may be found in patients with Sjögren's syndrome including neurological disorders. Neurological involvement ranges from 0 to 70% among various series and may present with central nervous system and/or peripheral nervous system involvement. This paper endeavors to review the main clinical neurological manifestations in Sjögren syndrome, the physiopathology, and their therapeutic response. PMID:22474573

  10. Endovascular treatment for acute pulmonary embolism in neurological patient

    PubMed Central

    Paul, Gunchan; Paul, Birinder S; Gautam, Parshotam L; Mohan, Bishav; Sharma, Shruti

    2015-01-01

    Among the spectrum of venous thrombo-embolic disease, acute pulmonary embolism accounts for the most life threatening manifestations with mortality exceeding 50%. It can affect many patient populations across various disciplines, hence immediate attention and aggressive treatment is crucial. With the advancement of technologies, various catheter-based devices are available to treat massive or submassive PE. In this paper we report two patients of acute pulmonary embolism with neurological issues where the life threatening emergency was successfully managed by utilizing endovascular directed thrombolytic reperfusion therapy. PMID:26609298

  11. Induced pluripotent stem cells for modeling of pediatric neurological disorders.

    PubMed

    Jang, Jiho; Quan, Zhejiu; Yum, Yunjin J; Song, Hyo Sook; Paek, Seonyeol; Kang, Hoon-Chul

    2014-07-01

    The pathophysiological mechanisms underlying childhood neurological disorders have remained obscure due to a lack of suitable disease models reflecting human pathogenesis. Using induced pluripotent stem cell (iPSC) technology, various neurological disorders can now be extensively modeled. Specifically, iPSC technology has aided the study and treatment of early-onset pediatric neurodegenerative diseases such as Rett syndrome, Down syndrome, Angelman syndrome. Prader-Willi syndrome, Friedreich's ataxia, spinal muscular atrophy (SMA), fragile X syndrome, X-linked adrenoleukodystrophy (ALD), and SCN1A gene-related epilepsies. In this paper, we provide an overview of various gene delivery systems for generating iPSCs, the current state of modeling early-onset neurological disorders and the ultimate application of these in vitro models in cell therapy through the correction of disease-specific mutations.

  12. Progress in stem cell therapy for major human neurological disorders.

    PubMed

    Martínez-Morales, P L; Revilla, A; Ocaña, I; González, C; Sainz, P; McGuire, D; Liste, I

    2013-10-01

    Human neurological disorders such as Alzheimer's disease (AD), Parkinson's disease, stroke or spinal cord injury are caused by the loss of neurons and glial cells in the brain or spinal cord in the Central Nervous System (CNS). Stem cell technology has become an attractive option to investigate and treat these diseases. Several types of neurons and glial cells have successfully been generated from stem cells, which in some cases, have ameliorated some dysfunctions both in animal models of neurological disorders and in patients at clinical level. Stem cell-based therapies can be beneficial by acting through several mechanisms such as cell replacement, modulation of inflammation and trophic actions. Here we review recent and current remarkable clinical studies involving stem cell-based therapy for AD and stroke and provide an overview of the different types of stem cells available nowadays, their main properties and how they are developing as a possible therapy for neurological disorders.

  13. Acute psychotic disorder and hypoglycemia.

    PubMed

    Singh, S K; Agrawal, J K; Srivastava, A S; Bhardwaj, V K; Bose, B S

    1994-04-01

    A variable array of neuroglycopenic symptoms are frequently encountered in the hypoglycemic stage, but acute psychotic disorders are quite rare. A fifty five year old female presented with an acute psychosis following oral sulfonylurea induced hypoglycemia without preceding features of adrenomedullary stimulation. This case report suggests that an acute and transient psychotic disorder may be an important neuroglycopenic feature and its early recognition protects the patient from severe hypoglycemic brain damage in a state of hypoglycemia unawareness.

  14. Large animal models of neurological disorders for gene therapy.

    PubMed

    Gagliardi, Christine; Bunnell, Bruce A

    2009-01-01

    he development of therapeutic interventions for genetic disorders and diseases that affect the central nervous system (CNS) has proven challenging. There has been significant progress in the development of gene therapy strategies in murine models of human disease, but gene therapy outcomes in these models do not always translate to the human setting. Therefore, large animal models are crucial to the development of diagnostics, treatments, and eventual cures for debilitating neurological disorders. This review focuses on the description of large animal models of neurological diseases such as lysosomal storage diseases, Parkinsons disease, Huntingtons disease, and neuroAIDS. The review also describes the contributions of these models to progress in gene therapy research.

  15. Genetic connections between neurological disorders and cholesterol metabolism

    PubMed Central

    Björkhem, Ingemar; Leoni, Valerio; Meaney, Steve

    2010-01-01

    Cholesterol is an essential component of both the peripheral and central nervous systems of mammals. Over the last decade, evidence has accumulated that disturbances in cholesterol metabolism are associated with the development of various neurological conditions. In addition to genetically defined defects in cholesterol synthesis, which will be covered in another review in this Thematic Series, defects in cholesterol metabolism (cerebrotendinous xanthomatosis) and intracellular transport (Niemann Pick Syndrome) lead to neurological disease. A subform of hereditary spastic paresis (type SPG5) and Huntington's disease are neurological diseases with mutations in genes that are of importance for cholesterol metabolism. Neurodegeneration is generally associated with disturbances in cholesterol metabolism, and presence of the E4 isoform of the cholesterol transporter apolipoprotein E as well as hypercholesterolemia are important risk factors for development of Alzheimer's disease. In the present review, we discuss the links between genetic disturbances in cholesterol metabolism and the above neurological disorders. PMID:20466796

  16. Hyperekplexia and stiff-baby syndrome: an identical neurological disorder?

    PubMed

    Cioni, G; Biagioni, E; Bottai, P; Castellacci, A M; Paolicelli, P B

    1993-03-01

    Hyperekplexia (startle disease) is an unusual, familial, neurological disorder characterized by abnormally enhanced startle response, followed in most cases by momentary generalized muscular stiffness. These attacks may cause the patients to fall rigidly, while remaining fully conscious. Startle symptomatology has generally an onset in infancy and is often accompanied, during the first years of life, by rigidity, sleep myoclonus, motor delay, regurgitation and apneic spells, which may cause sudden death. Stiff-baby syndrome is a familial disorder characterized by marked rigidity, with neonatal onset and gradual reduction during infancy, regurgitations, motor delay and attacks of stiffness. We report 4 new cases of hyperekplexia from two different families and another infant with stiff-baby syndrome discussing clinical, electrophysiological and genetic aspects of both neurological disorders in relation to other reported cases. We suggest a continuum between these familial syndromes, which are often misinterpreted as epilepsy or other disorders.

  17. Minor Neurological Dysfunction in Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

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

    2011-01-01

    Aim: The aim of this study was to improve the understanding of brain function in children with autism spectrum disorder (ASD) in relation to minor neurological dysfunctions (MNDs). Method: We studied MNDs in 122 children (93 males, 29 females; mean age 8y 1mo, SD 2y 6mo) who, among a total cohort of 705 children (513 males, 192 females; mean age…

  18. The Neurological Basis of Attention Deficit Hyperactivity Disorder.

    ERIC Educational Resources Information Center

    Ballard, Shirley; Bolan, Morna; Burton, Michael; Snyder, Sherry; Pasterczyk-Seabolt, Claire; Martin, Don

    1997-01-01

    Reviews research on attention deficit hyperactivity disorder (ADHD) and examines the role of neurochemical stimulation and signs of neurological deficits. Describes the chemical action of drugs used to treat ADHD, along with cognitive, affective, and behavioral effects, and side effects. Elaborates on drug treatment and basic behavior modification…

  19. Metabolic syndrome as a risk factor for neurological disorders.

    PubMed

    Farooqui, Akhlaq A; Farooqui, Tahira; Panza, Francesco; Frisardi, Vincenza

    2012-03-01

    The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the hypothalamic 'bodyweight/appetite/satiety set point,' resulting in the initiation and development of metabolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer's disease. The molecular mechanism underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However, it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders such as stroke, Alzheimer's disease and depression. The purpose of this review is not only to describe the involvement of brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical changes in stroke, Alzheimer's disease and depression to a wider audience of neuroscientists with the hope that this discussion will initiate more studies on the relationship between metabolic syndrome and neurological disorders.

  20. Secondary Abnormalities of Neurotransmitters in Infants with Neurological Disorders

    ERIC Educational Resources Information Center

    Garcia-Cazorla, A.; Serrano, M.; Perez-Duenas, B.; Gonzalez, V.; Ormazabal, A.; Pineda, M.; Fernandez-Alvarez, E.; Campistol, J. M. D.; Artuch, R. M. D.

    2007-01-01

    Neurotransmitters are essential in young children for differentiation and neuronal growth of the developing nervous system. We aimed to identify possible factors related to secondary neurotransmitter abnormalities in pediatric patients with neurological disorders. We analyzed cerebrospinal fluid (CSF) and biogenic amine metabolites in 56 infants…

  1. Notch: From Neural Development to Neurological Disorders

    PubMed Central

    Lathia, Justin D.; Mattson, Mark P.; Cheng, Aiwu

    2015-01-01

    Notch is an integral membrane protein that functions as receptor for ligands such as jagged and delta that are associated with the surface of neighboring cells. Upon ligand binding, notch is proteolytically cleaved within its transmembrane domain by presenilin-1 (the enzymatic component of the γ-secretase complex) resulting in the release of a notch intracellular domain (NICD) which translocates to the nucleus where it regulates gene expression. Notch signaling plays multiple roles in the development of the central nervous system (CNS) including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation. Notch is also present in postmitotic neurons in the adult CNS wherein its activation influences structural and functional plasticity including processes involved in learning and memory. Recent findings suggest that notch signaling in neurons, glia and NSCs may be involved in pathological changes that occur in disorders such as stroke, Alzheimer’s disease and CNS tumors. Studies of animal models suggest the potential of agents that target notch signaling as therapeutic interventions for several different CNS disorders. PMID:19094054

  2. 76 FR 61722 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-05

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial Review... Disorders and Stroke Initial Review Group, Neurological Sciences and Disorders A. Date: November 2-3,...

  3. Gene-targeting technologies for the study of neurological disorders.

    PubMed

    Beglopoulos, Vassilios; Shen, Jie

    2004-01-01

    Studies using genetic manipulations have proven invaluable in the research of neurological disorders. In the forefront of these approaches is the knockout technology that engineers a targeted gene mutation in mice resulting in inactivation of gene expression. In many cases, important roles of a particular gene in embryonic development have precluded the in vivo study of its function in the adult brain, which is usually the most relevant experimental context for the study of neurological disorders. The conditional knockout technology has provided a tool to overcome this restriction and has been used successfully to generate viable mouse models with gene inactivation patterns in certain regions or cell types of the postnatal brain. This review first describes the methodology of gene targeting in mice, detailing the aspects of designing a targeting vector, introducing it into embryonic stem cells in culture and screening for correct recombination events, and generating chimeric and null mutant mice from the positive clones. It then discusses the special issues and considerations for the generation of conditional knockout mice, including a section about approaches for inducible gene inactivation in the brain and some of their applications. An overview of gene-targeted mouse models that have been used in the study of several neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, seizure disorders, and schizophrenia, is also presented. The importance of the results obtained by these models for the understanding of the pathogenic mechanism underlying the disorders is discussed.

  4. Cerebrospinal fluid vasopressin in neurological and psychiatric disorders.

    PubMed Central

    Sørensen, P S; Gjerris, A; Hammer, M

    1985-01-01

    Vasopressin was determined in CSF and plasma of 243 patients with different neurological and psychiatric disorders, including control patients. CSF vasopressin was significantly higher in patients with high pressure hydrocephalus, intracranial tumour, benign intracranial hypertension, intracranial haemorrhage, ischaemic stroke, and craniocerebral trauma. In patients with primary degenerative dementia, CSF vasopressin was lower than in control patients. Among patients with psychiatric disorders, CSF vasopressin was increased in manic patients, while in patients with depression CSF concentration of this hormone did not differ from that found in controls. However, an increase in CSF vasopressin level was found in patients recovering from a depression. The clinical significance of changes in CSF vasopressin concentrations in groups of patients with neurological and psychiatric disorders is still unknown. PMID:3973621

  5. Mesenchymal Stem Cells as Cellular Vectors for Pediatric Neurological Disorders

    PubMed Central

    Phinney, Donald G.; Isakova, Iryna A.

    2014-01-01

    Lysosomal storage diseases are a heterogeneous group of hereditary disorders characterized by a deficiency in lysosomal function. Although these disorders differ in their etiology and phenotype those that affect the nervous system generally manifest as a profound deterioration in neurologic function with age. Over the past several decades implementation of various treatment regimens including bone marrow and cord blood cell transplantation, enzyme replacement, and substrate reduction therapy have proved effective for managing some clinical manifestations of these diseases but their ability to ameliorate neurologic complications remains unclear. Consequently, there exists a need to develop alternative therapies that more effectively target the central nervous system. Recently, direct intracranial transplantation of tissue-specific stem and progenitor cells has been explored as a means to reconstitute metabolic deficiencies in the CNS. In this chapter we discuss the merits of bone marrow-derived mesenchymal stem cells (MSCs) for this purpose. Originally identified as progenitors of connective tissue cell lineages, recent findings have revealed several novel aspects of MSC biology that make them attractive as therapeutic agents in the CNS. We relate these advances in MSC biology to their utility as cellular vectors for treating neurologic sequelae associated with pediatric neurologic disorders. PMID:24858930

  6. AMPA Receptors as Therapeutic Targets for Neurological Disorders.

    PubMed

    Lee, Kevin; Goodman, Lucy; Fourie, Chantelle; Schenk, Susan; Leitch, Beulah; Montgomery, Johanna M

    2016-01-01

    Almost every neurological disease directly or indirectly affects synapse function in the brain. However, these diseases alter synapses through different mechanisms, ultimately resulting in altered synaptic transmission and/or plasticity. Glutamate is the major neurotransmitter that mediates excitatory synaptic transmission in the brain through activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. These receptors have therefore been identified as a target for the development of therapeutic treatments for neurological disorders including epilepsy, neurodegenerative diseases, autism, and drug addiction. The fact that AMPA receptors play a dominant role throughout the brain raises the significant challenge of selectively targeting only those regions affected by disease, and clinical trials have raised doubt regarding the feasibility of specifically targeting AMPA receptors for new therapeutic options. Benzamide compounds that act as positive allosteric AMPA receptor modulators, known as AMPAkines, can act on specific brain regions and were initially proposed to revolutionize the treatment of cognitive deficits associated with neurological disorders. Their therapeutic potential has since declined due to inconsistent results in clinical trials. However, recent advances in basic biomedical research are significantly increasing our knowledge of AMPA receptor structure, binding sites, and interactions with auxiliary proteins. In particular, the large complex of postsynaptic proteins that interact with AMPA receptor subunits have been shown to control AMPA receptor insertion, location, pharmacology, synaptic transmission, and plasticity. These proteins are now being considered as alternative therapeutic target sites for modulating AMPA receptors in neurological disorders.

  7. [Brain-machine interface (BMI) - application to neurological disorders].

    PubMed

    Yoshimine, Toshiki; Yanagisawa, Takufumi; Hirata, Masayuki

    2013-01-01

    Brain-machine interface (BMI) is a new technology to receive input from the brain which is translated to operate a computer or other external device in real time. After significant progress during the recent 10 years, this technology is now very close to the clinical use to restore neural functions of patients with severe neurologic impairment. This technology is also a strong tool to investigate the mode of neuro-signal processing in the brain and to understand the mechanism of neural dysfunction which leads to the development of novel neurotechnology for the treatment of various sorts of neurological disorders.

  8. Neurological and psychiatric disorders as a neuroglial failure

    PubMed Central

    VERKHRATSKY, ALEXEI; PARPURA, VLADIMIR

    2014-01-01

    Neuroglia are a diverse non-neuronal population of cells in the central and peripheral nervous system. These cells have a variety of functions that can all be summed up as the maintenance of homeostasis of the nervous system. It is the loss of homeostasis that represents the culprit of all disorders. Thus, neuroglia can be envisioned as the pivotal element in all neural disorders, be that neurological or psychiatric. In this review, we discuss the role of glia in homeostasis and defence of the nervous system as well as changes in the morpho-functional characteristics of these cells in various disorders. PMID:25544781

  9. [Neurologic complications induced by the treatment of the acute renal allograft rejection with the monoclonal antibody OKT3].

    PubMed

    Fernández, O; Romero, F; Bravo, M; Burgos, D; Cabello, M; González-Molina, M

    1993-10-01

    The treatment of the acute renal allograft rejection with the monoclonal antibody orthoclone OKT3 produces both systemic and neurologic alterations. In a series of 21 patients with an acute renal allograft rejection treated with this monoclonal antibody, 20 with a renal allograft transplantation and one with a renal and pancreatic allograft transplantation, 29% referred headache associated with fever and vomiting, and 14.2% presented severe neurological alterations induced by the treatment. We stress the need to know these secondary effects to differentiate them from other central nervous system disorders, particularly those of infectious origin.

  10. Clinical perspectives on medical marijuana (cannabis) for neurologic disorders

    PubMed Central

    Fife, Terry D.; Moawad, Heidi; Moschonas, Constantine; Hammond, Nancy

    2015-01-01

    Summary The American Academy of Neurology published an evidence-based systematic review of randomized controlled trials using marijuana (Cannabis sativa) or cannabinoids in neurologic disorders. Several cannabinoids showed effectiveness or probable effectiveness for spasticity, central pain, and painful spasms in multiple sclerosis. The review justifies insurance coverage for dronabinol and nabilone for these indications. Many insurance companies already cover these medications for other indications. It is unlikely that the review will alter coverage for herbal marijuana. Currently, no payers cover the costs of herbal medical marijuana because it is illegal under federal law and in most states. Cannabinoid preparations currently available by prescription may have a role in other neurologic conditions, but quality scientific evidence is lacking at this time. PMID:26336632

  11. Clinical perspectives on medical marijuana (cannabis) for neurologic disorders.

    PubMed

    Fife, Terry D; Moawad, Heidi; Moschonas, Constantine; Shepard, Katie; Hammond, Nancy

    2015-08-01

    The American Academy of Neurology published an evidence-based systematic review of randomized controlled trials using marijuana (Cannabis sativa) or cannabinoids in neurologic disorders. Several cannabinoids showed effectiveness or probable effectiveness for spasticity, central pain, and painful spasms in multiple sclerosis. The review justifies insurance coverage for dronabinol and nabilone for these indications. Many insurance companies already cover these medications for other indications. It is unlikely that the review will alter coverage for herbal marijuana. Currently, no payers cover the costs of herbal medical marijuana because it is illegal under federal law and in most states. Cannabinoid preparations currently available by prescription may have a role in other neurologic conditions, but quality scientific evidence is lacking at this time.

  12. Molecular mechanisms of long ncRNAs in neurological disorders

    PubMed Central

    Vučićević, Dubravka; Schrewe, Heinrich; Ørom, Ulf A.

    2014-01-01

    Long non-coding RNAs (ncRNAs) have added an unexpected layer of complexity in the regulation of gene expression. Mounting evidence now links long ncRNAs to fundamental biological processes such as development and differentiation, and recent research shows important involvement of long ncRNAs in a variety of diseases including neurodegenerative disorders, such as Parkinson’s, Alzheimer’s, spinocerebellar ataxia, and Huntington’s diseases. Furthermore, long ncRNAs are speculated to be implicated in development of psychiatric disorders such as schizophrenia and bipolar disorders. Long ncRNAs contribute to these disorders in diverse ways, from regulation of transcription to modulation of RNA processing and translation. In this review, we describe the diverse mechanisms reported for long ncRNAs, and discuss how they could mechanistically be involved in the development of neurological disorders. PMID:24624135

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

    PubMed

    Levenson, J L; Sharpe, M

    2017-01-01

    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.

  14. 76 FR 56772 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

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    2011-09-14

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    2012-12-26

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  16. 75 FR 11187 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

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  1. 76 FR 66730 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

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    2011-10-27

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  4. 76 FR 14979 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

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  9. 77 FR 35987 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

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  11. 77 FR 19024 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

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  12. 75 FR 4577 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

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  13. 77 FR 43343 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke...

  14. 76 FR 25702 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial...

  15. 75 FR 54162 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ... Institute of Neurological Disorders and Stroke; Notice of Closed Meeting Pursuant to section 10(d) of the... Neurological Disorders and Stroke Special Emphasis Panel; T32 Training Grants. Date: October 19-20, 2010....

  16. 77 FR 19025 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-29

    ... Institute of Neurological Disorders and Stroke; Notice of Closed Meeting Pursuant to section 10(d) of the... Neurological Disorders and Stroke Special Emphasis Panel; Translational Stroke SEP. Date: April 18, 2012....

  17. 75 FR 67380 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-02

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke...

  18. 75 FR 57043 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... invasion of personal privacy. Name of Committee: National Institute of Neurological Disorders and...

  19. 78 FR 48179 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-07

    ... Institute of Neurological Disorders and Stroke; Notice of Closed Meeting Pursuant to section 10(d) of the... Neurological Disorders and Stroke Special Emphasis Panel; Review Career Development Awards. Date: August...

  20. 78 FR 21615 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke...

  1. 78 FR 17420 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke...

  2. 78 FR 77476 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke...

  3. 77 FR 48999 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke...

  4. Facial Palsy, a Disorder Belonging to Influential Neurological Dynasty: Review of Literature

    PubMed Central

    Newadkar, Ujwala R.; Chaudhari, Lalit; Khalekar, Yogita K.

    2016-01-01

    Facial paralysis is one of the common problem leading to facial deformation. Bell's palsy (BP) is defined as a lower motor neuron palsy of acute onset and idiopathic origin. BP is regarded as a benign common neurological disorder of unknown cause. It has an acute onset and is almost always a mononeuritis. The facial nerve is a mixed cranial nerve with a predominant motor component, which supplies all muscles concerned with unilateral facial expression. Knowledge of its course is vital for anatomic localization and clinical correlation. BP accounts for approximately 72% of facial palsies. Almost a century later, the management and etiology of BP is still a subject of controversy. Here, we present a review of literature on this neurologically significant entity. PMID:27583233

  5. Virtual Reality in the Rehabilitation of Patients with Neurological Disorders.

    PubMed

    Kefaliakos, Antonios; Pliakos, Ioannis; Kiekkas, Panagiotis; Charalampidou, Martha; Diomidous, Marianna

    2016-01-01

    Neurological disorders affect the lifestyle and the living conditions of a patient. Virtual Reality is a technology that may be used to simulate various types of tasks in a computerized environment guiding the patient and help on rehabilitation. This review try to answer how Virtual Reality technologies can effect on the patients rehabilitation's results. Treatments which involves Virtual Reality applications offer new ways to make the patients more committed to their program and keeps them motivated. Another characteristic of a Virtual Reality treatment is that both patients and therapists can observe the mistakes made during a physiotherapy session. The insert of VR sessions in traditional rehabilitation therapy of patients with neurological disorders have produced positive results.

  6. Sex influences in neurological disorders: case studies and perspectives

    PubMed Central

    Clayton, Janine Austin

    2016-01-01

    Beginning in the late 1980s and early 1990s, scientists and the public alike recognized that, for too long, women had been underrepresented in clinical trials. While much progress was made in the following decades, preclinical research still often ignores sex as a fundamental biological variable. Many neurological disorders, including multiple sclerosis and migraine, show strong sex differences in incidence and disease manifestation. In this commentary, we highlight case studies of neurological disorders affecting men and women to demonstrate the need for more such studies. Research conducted in these areas so far has shed light on the underlying mechanisms of the disease and offers the promise to help develop more personalized treatments for both men and women. PMID:28179807

  7. Sex influences in neurological disorders: case studies and perspectives.

    PubMed

    Clayton, Janine Austin

    2016-12-01

    Beginning in the late 1980s and early 1990s, scientists and the public alike recognized that, for too long, women had been underrepresented in clinical trials. While much progress was made in the following decades, preclinical research still often ignores sex as a fundamental biological variable. Many neurological disorders, including multiple sclerosis and migraine, show strong sex differences in incidence and disease manifestation. In this commentary, we highlight case studies of neurological disorders affecting men and women to demonstrate the need for more such studies. Research conducted in these areas so far has shed light on the underlying mechanisms of the disease and offers the promise to help develop more personalized treatments for both men and women.

  8. Large Animal Models of Neurological Disorders for Gene Therapy

    PubMed Central

    Gagliardi, Christine; Bunnell, Bruce A.

    2009-01-01

    The development of therapeutic interventions for genetic disorders and diseases that affect the central nervous system (CNS) has proven challenging. There has been significant progress in the development of gene therapy strategies in murine models of human disease, but gene therapy outcomes in these models do not always translate to the human setting. Therefore, large animal models are crucial to the development of diagnostics, treatments, and eventual cures for debilitating neurological disorders. This review focuses on the description of large animal models of neurological diseases such as lysosomal storage diseases, Parkinson’s disease, Huntington’s disease, and neuroAIDS. The review also describes the contributions of these models to progress in gene therapy research. PMID:19293458

  9. Acupressure for treating neurological disorders: a systematic review.

    PubMed

    Lee, Jeong-Sook; Lee, Myeong Soo; Min, Kyungyoon; Lew, Jae-Hwan; Lee, Beom-Joon

    2011-08-01

    The objective of this review is to assess the clinical evidence for or against acupressure as a treatment for neurological disorders. We searched the literature from 12 databases from their inception to July 2010. We included any type of controlled clinical trial (CCT) in which patients with neurological disorders were treated with acupressure. The methodological quality of all clinical trials was assessed using the Cochrane risk of bias analysis. In total, two randomized clinical trials (RCTs) and four CCTs were included. Four studies (one RCT and three CCTs) compared the effects of acupressure with routine care or no treatment in patients with stroke and showed significant effects of acupressure on improving patient function and symptoms. One RCT, which compared acupressure with sham acupressure and no treatment in patients with headache, also showed that acupressure significantly reduced headache severity and pain. However, all trials were open to methodological limitations and a high risk of bias. In conclusion, current evidence showing that acupressure is an effective treatment for improving function and symptoms in patients with stroke is limited. However, the evidence is insufficient to draw conclusions concerning the effects of acupressure on other neurological disorders. More rigorous studies are warranted.

  10. Pathogens and chronic or long-term neurologic disorders.

    PubMed

    Starakis, Ioannis; Panos, George; Koutras, Angelos; Mazokopakis, Elias E

    2011-03-01

    Infections of the central nervous system may provoke glial and autoimmune responses but a definitive linkage between these infections and the pathogenesis of chronic neurologic disorders is still elusive. There are controversial reports implicating infectious agents in the pathogenetic mechanisms of chronic or long-term neurologic disorders, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease and autistic spectrum disorders, but the specific role of bacterial or viral infections in the pathogenesis of these medical entities has not been fully elucidated. Up till now, the evidence is distant from definite, but certain cases may be attributed to infections in the millieu of multiple toxic events such as trauma, nutritional deficits, immune dysregulation and excitotoxicity in genetically vulnerable indiniduals. There is an ongoing debate concering the direct involvement of various infectious agents in the neurodegenerative and neurobehavioral diseases pathogenesis and/or their contribution to the deterioration of the disease or co-morbidity in these patients. These patients are exceptionally difficult to be treated by using single therapeutic modalities, because their disese is multifocal and treatment is aimed to control signs and symptoms rather than the true causes of the disease and its progressive course. Furthermore, even if these causative links were indetifiable, our therapeutic interventions would come too late due to the irreversible damages at the time of the initiation of treatment. Our aim is to comprehensively review all available data suggesting that infections could be common antecedent events of progressive neurologic degenerative or behavioural diseases.

  11. 77 FR 6570 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-08

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial Review Group; Neurological Sciences and Disorders C. Date: March 1-2, 2012. Time: 8 a.m. to 5 p.m. Agenda:...

  12. 76 FR 20695 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial Review...-9223, saavedrr@ninds.nih.gov . Name of Committee: National Institute of Neurological Disorders...

  13. 77 FR 43097 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-23

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Special... Program Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological...

  14. 76 FR 20691 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial Review Group; Neurological Sciences and Disorders C. Date: June 9-10, 2011. Time: 8 a.m. to 5 p.m. Agenda:...

  15. 77 FR 24971 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-26

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial Review Group; Neurological Sciences and Disorders C. Date: June 18-19, 2012 Time: 8 a.m. to 6 p.m. Agenda:...

  16. 75 FR 64316 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-19

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial Review Group, Neurological Sciences and Disorders B. Date: October 28-29, 2010. Time: 8 a.m. to 6 p.m....

  17. 78 FR 45932 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-30

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of the National Advisory Neurological Disorders and Stroke Council. The... Neurological Disorders and Stroke Council. Date: September 12-13, 2013. Open: September 12, 2013, 8:00 a.m....

  18. 75 FR 2149 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-14

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of a meeting of the National Advisory Neurological Disorders and Stroke... personal privacy. Name of Committee: National Advisory Neurological Disorders and Stroke Council,...

  19. 75 FR 22607 - National Institute of Neurological Disorders and Stroke; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of meetings of the National Advisory Neurological Disorders and Stroke... Neurological Disorders and Stroke Council, Clinical Trials Subcommittee. Date: May 26-27, 2010. Closed: May...

  20. 75 FR 992 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-07

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of a meeting of the National Advisory Neurological Disorders and Stroke... Neurological Disorders and Stroke Council. Date: February 4-5, 2010. Open: February 4, 2010, 10:30 a.m. to...

  1. 75 FR 52010 - National Institute of Neurological Disorders and Stroke; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-24

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of meetings of the National Advisory Neurological Disorders and Stroke... Neurological Disorders and Stroke Council; Clinical Trials Subcommittee. Date: September 22-23, 2010....

  2. 76 FR 2129 - National Institute of Neurological Disorders And Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-12

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders And Stroke.... App.), notice is hereby given of a meeting of the National Advisory Neurological Disorders and Stroke... Neurological Disorders and Stroke Council Clinical Trials Subcommittee. Date: February 2-3, 2011....

  3. 76 FR 28054 - National Institute of Neurological Disorders and Stroke; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-13

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of meetings of the National Advisory Neurological Disorders and Stroke... Neurological Disorders and Stroke Council, Clinical Trials Subcommittee. Date: May 25, 2011. Closed: 6:30...

  4. 76 FR 57062 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-15

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial Review... Neurological Disorders and Stroke Initial Review Group, NST-2 Subcommittee. Date: October 31-November 1,...

  5. 75 FR 9421 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-02

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Special... Neurological Disorders and Stroke Special Emphasis Panel; 2010 EUREKA Review. Date: March 24, 2010. Time: 8...

  6. 76 FR 64360 - National Institute of Neurological Disorders and Stroke Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-18

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial Review... Stroke Initial Review Group; Neurological Sciences and Disorders K. Date: November 4, 2011. Time: 8...

  7. 76 FR 28440 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-17

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Special...-0635, Rc218u@nih.gov . Name of Committee: National Institute of Neurological Disorders and...

  8. 75 FR 21643 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... privacy. Name of Committee: National Advisory Neurological Disorders and Stroke Council. Date: May 27..., National Institute of Neurological Disorders and Stroke, NIH, 6001 Executive Blvd., Suite 3309, MSC...

  9. The social brain in psychiatric and neurological disorders

    PubMed Central

    Kennedy, Daniel P.; Adolphs, Ralph

    2013-01-01

    Psychiatric and neurological disorders have historically provided key insights into the structure-function relationships that subserve human social cognition and behavior, informing the concept of the ‘social brain’. In this review, we take stock of the current status of this concept, retaining a focus on disorders that impact social behavior. We discuss how the social brain, social cognition, and social behavior are interdependent, and emphasize the important role of development and compensation. We suggest that the social brain, and its dysfunction and recovery, must be understood not in terms of specific structures, but rather in terms of their interaction in large-scale networks. PMID:23047070

  10. Gene Therapy for the Treatment of Neurological Disorders: Metabolic Disorders

    PubMed Central

    Gessler, Dominic J.; Gao, Guangping

    2016-01-01

    Metabolic disorders comprise a large group of heterogeneous diseases ranging from very prevalent diseases such as diabetes mellitus to rare genetic disorders like Canavan Disease. Whether either of these diseases is amendable by gene therapy depends to a large degree on the knowledge of their pathomechanism, availability of the therapeutic gene, vector selection, and availability of suitable animal models. In this book chapter, we review three metabolic disorders of the central nervous system (CNS; Canavan Disease, Niemann–Pick disease and Phenylketonuria) to give examples for primary and secondary metabolic disorders of the brain and the attempts that have been made to use adeno-associated virus (AAV) based gene therapy for treatment. Finally, we highlight commonalities and obstacles in the development of gene therapy for metabolic disorders of the CNS exemplified by those three diseases. PMID:26611604

  11. Gene Therapy for the Treatment of Neurological Disorders: Metabolic Disorders.

    PubMed

    Gessler, Dominic J; Gao, Guangping

    2016-01-01

    Metabolic disorders comprise a large group of heterogeneous diseases ranging from very prevalent diseases such as diabetes mellitus to rare genetic disorders like Canavan Disease. Whether either of these diseases is amendable by gene therapy depends to a large degree on the knowledge of their pathomechanism, availability of the therapeutic gene, vector selection, and availability of suitable animal models. In this book chapter, we review three metabolic disorders of the central nervous system (CNS; Canavan Disease, Niemann-Pick disease and Phenylketonuria) to give examples for primary and secondary metabolic disorders of the brain and the attempts that have been made to use adeno-associated virus (AAV) based gene therapy for treatment. Finally, we highlight commonalities and obstacles in the development of gene therapy for metabolic disorders of the CNS exemplified by those three diseases.

  12. Factors Related to Social Support in Neurological and Mental Disorders.

    PubMed

    Kamenov, Kaloyan; Cabello, Maria; Caballero, Francisco Félix; Cieza, Alarcos; Sabariego, Carla; Raggi, Alberto; Anczewska, Marta; Pitkänen, Tuuli; Ayuso-Mateos, Jose Luis

    2016-01-01

    Despite the huge body of research on social support, literature has been primarily focused on its beneficial role for both physical and mental health. It is still unclear why people with mental and neurological disorders experience low levels of social support. The main objective of this study was to explore what are the strongest factors related to social support and how do they interact with each other in neuropsychiatric disorders. The study used cross-sectional data from 722 persons suffering from dementia, depression, epilepsy, migraine, multiple sclerosis, Parkinson's disease, schizophrenia, stroke, and substance use disorders. Multiple linear regressions showed that disability was the strongest factor for social support. Extraversion and agreeableness were significant personality variables, but when the interaction terms between personality traits and disability were included, disability remained the only significant variable. Moreover, level of disability mediated the relationship between personality (extraversion and agreeableness) and level of social support. Moderation analysis revealed that people that had mental disorders experienced lower levels of support when being highly disabled compared to people with neurological disorders. Unlike previous literature, focused on increasing social support as the origin of improving disability, this study suggested that interventions improving day-to-day functioning or maladaptive personality styles might also have an effect on the way people perceive social support. Future longitudinal research, however, is warranted to explore causality.

  13. Neurologic complications of disorders of the adrenal glands.

    PubMed

    Bertorini, Tulio E; Perez, Angel

    2014-01-01

    Disorders of the adrenal glands frequently have secondary neurological manifestations, while some diseases that involve the central nervous system are accompanied by adrenal gland dysfunction. Excessive corticosteroid secretions in primary or secondary Cushing's syndrome causes muscle weakness and behavioral disturbances, such as emotional lability and sometimes depression, while adrenal insufficiency may cause fatigue, weakness, and depression. Adrenoleukodystrophy and adrenoneuromyelopathy are X-linked recessive disorders of the metabolism of very long chain fatty acids that manifest with white matter abnormalities of the brain, myelopathy and/or neuropathy, as well as adrenal insufficiency. Other disorders of the adrenal glands include hyperaldosteroidism, which may cause weakness from hypokalemia. Dysfunction of the adrenal medulla causes excessive or deficient secretion of catecholamines, primarily causing cardiovascular symptoms. This chapter reviews the clinical manifestations and diagnostic aspects and treatment of the various disorders of the adrenal glands. Some of the congenital adrenal diseases are also discussed.

  14. Brain insulin dysregulation: implication for neurological and neuropsychiatric disorders.

    PubMed

    Ghasemi, Rasoul; Dargahi, Leila; Haeri, Ali; Moosavi, Maryam; Mohamed, Zahurin; Ahmadiani, Abolhassan

    2013-06-01

    Arduous efforts have been made in the last three decades to elucidate the role of insulin in the brain. A growing number of evidences show that insulin is involved in several physiological function of the brain such as food intake and weight control, reproduction, learning and memory, neuromodulation and neuroprotection. In addition, it is now clear that insulin and insulin disturbances particularly diabetes mellitus may contribute or in some cases play the main role in development and progression of neurodegenerative and neuropsychiatric disorders. Focusing on the molecular mechanisms, this review summarizes the recent findings on the involvement of insulin dysfunction in neurological disorders like Alzheimer's disease, Parkinson's disease and Huntington's disease and also mental disorders like depression and psychosis sharing features of neuroinflammation and neurodegeneration.

  15. Induced pluripotent stem cells for modeling neurological disorders.

    PubMed

    Russo, Fabiele B; Cugola, Fernanda R; Fernandes, Isabella R; Pignatari, Graciela C; Beltrão-Braga, Patricia C B

    2015-12-24

    Several diseases have been successfully modeled since the development of induced pluripotent stem cell (iPSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines. Neurological disorders have benefited the most from iPSC-disease modeling for its capability for generating disease-relevant cell types in vitro from the central nervous system, such as neurons and glial cells, otherwise only available from post-mortem samples. Patient-specific iPSC-derived neural cells can recapitulate the phenotypes of these diseases and therefore, considerably enrich our understanding of pathogenesis, disease mechanism and facilitate the development of drug screening platforms for novel therapeutic targets. Here, we review the accomplishments and the current progress in human neurological disorders by using iPSC modeling for Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy, amyotrophic lateral sclerosis, duchenne muscular dystrophy, schizophrenia and autism spectrum disorders, which include Timothy syndrome, Fragile X syndrome, Angelman syndrome, Prader-Willi syndrome, Phelan-McDermid, Rett syndrome as well as Nonsyndromic Autism.

  16. Connectivity Analysis is Essential to Understand Neurological Disorders

    PubMed Central

    Rowe, James B.

    2010-01-01

    Neurological and neuropsychiatric disorders are major causes of morbidity worldwide. A systems level analysis including functional and structural neuroimaging is particularly useful when the pathology leads to disorders of higher order cognitive functions in human patients. However, an analysis that is restricted to regional effects is impoverished and insensitive, compared to the analysis of distributed brain networks. We discuss the issues to consider when choosing an appropriate connectivity method, and compare the results from several different methods that are relevant to fMRI and PET data. These include psychophysiological interactions in general linear models, structural equation modeling, dynamic causal modeling, and independent components analysis. The advantages of connectivity analysis are illustrated with a range of structural and neurodegenerative brain disorders. We illustrate the sensitivity of these methods to the presence or severity of disease and/or treatment, even where analyses of voxel-wise activations are insensitive. However, functional and structural connectivity methods should be seen as complementary to, not a substitute for, other imaging and behavioral approaches. The functional relevance of changes in connectivity, to motor or cognitive performance, are considered alongside the complex relationship between structural and functional changes and neuropathology. Finally some of the problems associated with connectivity analysis are discussed. We suggest that the analysis of brain connectivity is an essential complement to the analysis of regionally specific dysfunction, in order to understand neurological and neuropsychiatric disease, and to evaluate the mechanisms of effective therapies. PMID:20948582

  17. Telerehabilitation, Virtual Therapists, and Acquired Neurologic Speech and Language Disorders

    PubMed Central

    Cherney, Leora R.; van Vuuren, Sarel

    2013-01-01

    Telerehabilitation (telererehab) offers cost effective services that potentially can improve access to care for those with acquired neurologic communication disorders. However, regulatory issues including licensure, reimbursement, and threats to privacy and confidentiality hinder the routine implementation of telerehab services into the clinical setting. Despite these barriers, rapid technological advances and a growing body of research regarding the use of telerehab applications support its use. This article reviews the evidence related to acquired neurologic speech and language disorders in adults, focusing on studies that have been published since 2000. Research studies have used telerehab systems to assess and treat disorders including dysarthria, apraxia of speech, aphasia, and mild Alzheimer’s disease. They show that telerehab is a valid and reliable vehicle for delivering speech and language services. The studies represent a progression of technological advances in computing, Internet, and mobile technologies. They range on a continuum from working synchronously (in real-time) with a speech-language pathologist to working asynchronously (offline) with a stand-in virtual therapist. One such system that uses a virtual therapist for the treatment of aphasia, the Web-ORLA™ (Rehabilitation Institute of Chicago, Chicago, IL) system, is described in detail. Future directions for the advancement of telerehab for clinical practice are discussed. PMID:22851346

  18. Induced pluripotent stem cells for modeling neurological disorders

    PubMed Central

    Russo, Fabiele B; Cugola, Fernanda R; Fernandes, Isabella R; Pignatari, Graciela C; Beltrão-Braga, Patricia C B

    2015-01-01

    Several diseases have been successfully modeled since the development of induced pluripotent stem cell (iPSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines. Neurological disorders have benefited the most from iPSC-disease modeling for its capability for generating disease-relevant cell types in vitro from the central nervous system, such as neurons and glial cells, otherwise only available from post-mortem samples. Patient-specific iPSC-derived neural cells can recapitulate the phenotypes of these diseases and therefore, considerably enrich our understanding of pathogenesis, disease mechanism and facilitate the development of drug screening platforms for novel therapeutic targets. Here, we review the accomplishments and the current progress in human neurological disorders by using iPSC modeling for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, spinal muscular atrophy, amyotrophic lateral sclerosis, duchenne muscular dystrophy, schizophrenia and autism spectrum disorders, which include Timothy syndrome, Fragile X syndrome, Angelman syndrome, Prader-Willi syndrome, Phelan-McDermid, Rett syndrome as well as Nonsyndromic Autism. PMID:26722648

  19. Telerehabilitation, virtual therapists, and acquired neurologic speech and language disorders.

    PubMed

    Cherney, Leora R; van Vuuren, Sarel

    2012-08-01

    Telerehabilitation (telerehab) offers cost-effective services that potentially can improve access to care for those with acquired neurologic communication disorders. However, regulatory issues including licensure, reimbursement, and threats to privacy and confidentiality hinder the routine implementation of telerehab services into the clinical setting. Despite these barriers, rapid technological advances and a growing body of research regarding the use of telerehab applications support its use. This article reviews the evidence related to acquired neurologic speech and language disorders in adults, focusing on studies that have been published since 2000. Research studies have used telerehab systems to assess and treat disorders including dysarthria, apraxia of speech, aphasia, and mild Alzheimer disease. They show that telerehab is a valid and reliable vehicle for delivering speech and language services. The studies represent a progression of technological advances in computing, Internet, and mobile technologies. They range on a continuum from working synchronously (in real-time) with a speech-language pathologist to working asynchronously (offline) with a stand-in virtual therapist. One such system that uses a virtual therapist for the treatment of aphasia, the Web-ORLA™ (Rehabilitation Institute of Chicago, Chicago, IL) system, is described in detail. Future directions for the advancement of telerehab for clinical practice are discussed.

  20. Pathology of neurologic disorders of raccoons (Procyon lotor).

    PubMed

    Hamir, Amir N

    2011-09-01

    The raccoon (Procyon lotor) is almost ubiquitous in North America. In recent times, it was introduced in many parts of the world where it has now become largely feral. Since the outbreak of raccoon rabies epizootic in eastern United States and Canada, most diagnostic laboratories have had increased numbers of raccoon carcasses or raccoon brain submissions for diagnosis of rabies. However, since a number of other diseases that affect the central nervous system and have similar clinical signs as rabies have been documented in this species, the current review attempts to bring together the published information on neurologic disorders of raccoons.

  1. Cerebrospinal fluid ascorbic acid levels in neurological disorders.

    PubMed

    Brau, R H; García-Castiñeiras, S; Rifkinson, N

    1984-02-01

    The ascorbic acid/dehydroascorbic acid system was analyzed in the cerebrospinal fluid (CSF) of 41 patients with different neurological disorders. The chi-square test of covariance analysis revealed in this sample significant differences in the CSF levels of total ascorbic acid when patients were classified by diagnostic categories. The population analyzed contained a group of 18 patients (back pain/sciatica group) in whom no overt neurological abnormalities were disclosed upon evaluation. Taking the CSF levels of total ascorbic acid and dehydroascorbic acid in these patients as the reference (3.57 +/- 0.87 (SD)/100 ml and 0.53 +/- 0.19 mg/100 ml, respectively), it was found that head-traumatized patients showed a significant reduction in the concentration of total ascorbic acid in the CSF. CSF ascorbic acid levels were also significantly lower in patients with increased intracranial pressure (noninfected hydrocephalus group) and in patients with cerebral tumors. Although the CSF concentration of dehydroascorbic acid did not correspondingly increase over the reference values in these three groups of patients, the tendency existed for dehydroascorbic acid to represent in them a higher percentage of total ascorbic acid. After examining different alternatives, it is concluded that the hypothesis of free radical damage to the central nervous system after certain types of injury (trauma, ischemia, and tumors) may provide a satisfactory explanation of our findings. A rationale for the use of vitamin C in the management of some neurological patients is also derived from this work.

  2. Severe neurologic manifestations in acute intermittent porphyria developed after spine surgery under general anesthesia: a case report

    PubMed Central

    Park, Eun Young; Kim, Yi Seul; Lim, Kyung-Jee; Lee, Hye Kyoung; Lee, Soo Kyung; Choi, Hyun

    2014-01-01

    Porphyrias are inherited metabolic disorders resulting from a specific enzyme defect in the heme biosynthetic pathway. Porphyrias are induced by various precipitants. Clinical features include abdominal pain, neurologic manifestations, autonomic neuropathy, and mental disturbance. Diagnosis may be delayed because of variable symptoms that mimic other diseases and because of the rarity of of porphyrias. Although most patients with known porphyria can complete anesthesia and surgery safely, undiagnosed porphyric patients are in danger of porphyric crisis due to inadvertent exposure to precipitating drugs and environment. We report a case of a patient who experienced delayed emergence with neurological disturbance after general anesthesia, ultimately diagnosed as acute intermittent porphyria. PMID:25302100

  3. 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

  4. Gene therapy for the neurological manifestations in lysosomal storage disorders.

    PubMed

    Cheng, Seng H

    2014-09-01

    Over the past several years, considerable progress has been made in the development of gene therapy as a therapeutic strategy for a variety of inherited metabolic diseases, including neuropathic lysosomal storage disorders (LSDs). The premise of gene therapy for this group of diseases is borne of findings that genetic modification of a subset of cells can provide a more global benefit by virtue of the ability of the secreted lysosomal enzymes to effect cross-correction of adjacent and distal cells. Preclinical studies in small and large animal models of these disorders support the application of either a direct in vivo approach using recombinant adeno-associated viral vectors or an ex vivo strategy using lentiviral vector-modified hematopoietic stem cells to correct the neurological component of these diseases. Early clinical studies utilizing both approaches have begun or are in late-stage planning for a small number of neuropathic LSDs. Although initial indications from these studies are encouraging, it is evident that second-generation vectors that exhibit a greater safety profile and transduction activity may be required before this optimism can be fully realized. Here, I review recent progress and the remaining challenges to treat the neurological aspects of various LSDs using this therapeutic paradigm.

  5. Acute neurological symptoms during hypobaric exposure: consider cerebral air embolism.

    PubMed

    Weenink, Robert P; Hollmann, Markus W; van Hulst, Robert A

    2012-11-01

    Cerebral arterial gas embolism (CAGE) is well known as a complication of invasive medical procedures and as a risk in diving and submarine escape. In the underwater environment, CAGE is caused by trapped air, which expands and leads to lung vessel rupture when ambient pressure decreases during ascent. Pressure decrease also occurs during hypobaric activities such as flying and, therefore, CAGE may theoretically be a risk in hypobaric exposure. We reviewed the available literature on this subject. Identified were 12 cases of CAGE due to hypobaric exposure. Based on these cases, we discuss pathophysiology, diagnosis, and treatment of CAGE due to hypobaric exposure. The low and slow pressure decrease during most hypobaric activities (as opposed to diving) account for the low incidence of CAGE during these exposures and suggest that severe air trapping must be present to cause barotrauma. This is also suggested by the large prevalence of air filled cysts in the case reports reviewed. We recommend considering CAGE in all patients presenting with acute central neurological injury during or shortly after pressure decrease such as flying. A CT scan of head and chest should be performed in these patients. Treatment with hyperbaric oxygen therapy should be initiated as soon as possible in cases of proven or probable CAGE.

  6. Neurological soft signs in homicidal men with antisocial personality disorder.

    PubMed

    Lindberg, Nina; Tani, Pekka; Stenberg, Jan-Henry; Appelberg, Björn; Porkka-Heiskanen, Tarja; Virkkunen, Matti

    2004-11-01

    Neurological soft signs (NSS) are characterized by abnormalities in motor, sensory, and integrative functions. NSS have been regarded as a result of neurodevelopmental dysfunction, and as evidence of a central nervous system defect, resulting in considerable sociopsychological dysfunction. During the last decade there has been growing evidence of brain dysfunction in severe aggressive behavior. As a symptom, aggression overlaps a number of psychiatric disorders, but it is commonly associated with antisocial personality disorder. The aim of the present study was to examine NSS in an adult criminal population using the scale by Rossi et al. [29]. Subjects comprised 14 homicidal men with antisocial personality disorder recruited from a forensic psychiatric examination. Ten age- and gender-matched healthy volunteers as well as eight patients with schizophrenia, but no history of physical aggression, served as controls. The NSS scores of antisocial offenders were significantly increased compared with those of the healthy controls, whereas no significant differences were observed between the scores of offenders and those of patients with schizophrenia. It can be speculated that NSS indicate a nonspecific vulnerability factor in several psychiatric syndromes, which are further influenced by a variety of genetic and environmental components. One of these syndromes may be antisocial personality disorder with severe aggression.

  7. 77 FR 72872 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-06

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of the National Advisory Neurological Disorders and Stroke Council. The... Disorders and Stroke Council. Date: January 31-February 1, 2013. Open: January 31, 2013, 8:00 a.m. to 2:45...

  8. 76 FR 20691 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of the National Advisory Neurological Disorders and Stroke Council. The... Disorders and Stroke Council. Date: May 26-27, 2011. Open: May 26, 2011, 10:45 a.m. to 4:45 p.m....

  9. 77 FR 1702 - National Institute of Neurological Disorders and Stroke Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of the National Advisory Neurological Disorders and Stroke Council. The... Disorders and Stroke Council. Date: February 16-17, 2012. Open: February 16, 2012, 8 a.m. to 2:30...

  10. 77 FR 48999 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of the National Advisory Neurological Disorders and Stroke Council. The... Disorders and Stroke Council. Date: September 20-21, 2012. Open: September 20, 2012, 8 a.m. to 2:15...

  11. 77 FR 24725 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of the National Advisory Neurological Disorders and Stroke Council. The... Disorders and Stroke Council. Date: May 24-25, 2012. Open: May 24, 2012, 8 a.m. to 2:15 p.m. Agenda:...

  12. 76 FR 51043 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of the National Advisory Neurological Disorders and Stroke Council. The... Disorders and Stroke Council. Date: September 15-16, 2011. Open: September 15, 2011, 8:30 a.m. to 2...

  13. 75 FR 80510 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-22

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... privacy. Name of Committee: National Advisory Neurological Disorders and Stroke Council. Date: February 3... Disorders and Stroke, NIH, 6001 Executive Blvd., Suite 3309, MSC 9531, Bethesda, MD 20892, (301)...

  14. 78 FR 76633 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-18

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of the National Advisory Neurological Disorders and Stroke Council. The... Disorders and Stroke Council. Date: January 30-31, 2014. Open: January 30, 2014, 8:00 a.m. to 3:00...

  15. 78 FR 22274 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke.... App.), notice is hereby given of the National Advisory Neurological Disorders and Stroke Council. The... Disorders and Stroke Council. Date: May 23-24, 2013. Open: May 23, 2013, 8:00 a.m. to 2:45 p.m....

  16. Mild neurological impairment may indicate a psychomotor endophenotype in patients with borderline personality disorder.

    PubMed

    Arbabi, Mohammad; Paast, Negin; Karim, Hamid Reza; Faghfori, Sara; Memari, Amir Hossein

    2016-11-30

    The aim of the present study was to determine whether patients with borderline personality disorder (BPD) show any neurological soft signs compared to healthy controls. Furthermore we sought to examine the role of common symptoms related to BPD, such as depression, anxiety or impulsivity, in association with neurological soft signs. Thirty patients with borderline personality disorder and thirty hospital-based controls were examined for neurological soft signs. The total score of neurological soft signs in BPD was significantly higher than controls. In terms of subscales, patients had higher scores in Sensory Integration and Motor Coordination and other neurological soft signs compared to control group. Multiple regression analysis showed that the impulsivity score was the best significant predictor of neurological soft signs in BPD. The increase of neurological soft signs in patients with BPD may address a non-focal neurological dysfunction in borderline personality disorder.

  17. [Assessment and treatment of conversion disorder: the most fascinating borderline of psychiatry and neurology].

    PubMed

    Vataja, Risto; Leppävuori, Antero

    2012-01-01

    Conversion disorder or functional neurological disorder is a neurological symptom complex originating from psychological factors, which manifests in voluntary motor and sensory functions or as unexplained epilepsy-like seizures. Until the 1980's the disorder was called hysterical neurosis. Later on, various general terms, such as unexplained somatic symptoms, pseudoneurological, somatoformic, psychogenic, or psychosomatic symptoms, have been applied. The latest phrase, functional neurological symptoms, emphasizes the change in the functioning of the nervous system rather than in its structure.

  18. Construction of standardized Arabic questionnaires for screening neurological disorders (dementia, stroke, epilepsy, movement disorders, muscle and neuromuscular junction disorders)

    PubMed Central

    El Tallawy, Hamdy N; Farghaly, Wafaa MA; Rageh, Tarek A; Saleh, Ahmed O; Mestekawy, Taha AH; Darwish, Manal MM; Abd El Hamed, Mohamed A; Ali, Anwar M; Mahmoud, Doaa M

    2016-01-01

    A screening questionnaire is an important tool for early diagnosis of neurological disorders, and for epidemiological research. This screening instrument must be both feasible and valid. It must be accepted by the community and must be sensitive enough. So, the aim of this study was to prepare different Arabic screening questionnaires for screening different neurological disorders. This study was carried out in three stages. During the first stage, construction of separate questionnaires designed for screening the five major neurological disorders: cerebrovascular stroke, dementias, epilepsy, movement disorders, and muscle and neuromuscular disorders were done. Validation of the screening questionnaires was carried out in the second stage. Finally, questionnaire preparation was done in the third stage. Questions with the accepted sensitivity and specificity in each questionnaire formed the refined separate questionnaires. PMID:27621635

  19. 78 FR 15727 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-12

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Related to Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences,...

  20. 76 FR 59414 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ... clearly unwarranted invasion of personal privacy. Name of Committee: Board of Scientific Counselors... Program Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological...

  1. 76 FR 73653 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Related to Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences,...

  2. 76 FR 81951 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... clearly unwarranted invasion of personal privacy. Name of Committee: Board of Scientific Counselors... Program Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological...

  3. 76 FR 41273 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-13

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Related to Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences,...

  4. Synaptic Plasticity and Neurological Disorders in Neurotropic Viral Infections

    PubMed Central

    Atluri, Venkata Subba Rao; Hidalgo, Melissa; Samikkannu, Thangavel; Kurapati, Kesava Rao Venkata; Nair, Madhavan

    2015-01-01

    Based on the type of cells or tissues they tend to harbor or attack, many of the viruses are characterized. But, in case of neurotropic viruses, it is not possible to classify them based on their tropism because many of them are not primarily neurotropic. While rabies and poliovirus are considered as strictly neurotropic, other neurotropic viruses involve nervous tissue only secondarily. Since the AIDS pandemic, the interest in neurotropic viral infections has become essential for all clinical neurologists. Although these neurotropic viruses are able to be harbored in or infect the nervous system, not all the neurotropic viruses have been reported to cause disrupted synaptic plasticity and impaired cognitive functions. In this review, we have discussed the neurotropic viruses, which play a major role in altered synaptic plasticity and neurological disorders. PMID:26649202

  5. The therapeutic value of yoga in neurological disorders

    PubMed Central

    Mishra, Shri K.; Singh, Parampreet; Bunch, Steven J.; Zhang, Ray

    2012-01-01

    Background: The ancient mind and body healing methods of yoga recently sparked fervor in the scientific community as an alternative and complementary means of therapy. Since the World Health Organization officially began promoting yoga in developing countries in 1978, yoga has been cited for its therapeutic potential and has been widely recognized in Western culture. However, as an increasing number of people practice yoga for remedial purposes, researchers raise two important questions: 1) Is yoga a valid complementary management and rehabilitation treatment modality? 2) What conditions show promise of treatment with this intervention?. Objective: This review article uses comprehensive scientific, evidence-based studies to analyze the efficacy of various basic and applied aspects of yoga in disease prevention and health promotion. It specifically intends to expose the effects of yoga in neurological disorders, particularly epilepsy, stroke, multiple sclerosis, Alzheimer's disease, peripheral nervous system disease, and fibromyalgia. Materials and Methods: Information was gathered from various resources including PubMed, Ovid, MD-Consult, USC, and U.C.L.A. libraries. Studies were selected and reviewed on the basis of sample size, control, randomization, double-blinding, and statistical analysis of results. Results: The pratice of yoga and meditation demonstrates statistically encouraging physiological and psychological improvements in the aforementioned neurological disorders. However, there were certain flaws and inadequacies in the study designs employed to evaluate the same. A critical analysis of these studies is presented. Conclusions: With the aim to focus attention on this widespread yet largely unexamined treatment modality, this paper seeks to provide direction and support for further research necessary to validate yoga as an integrative, alternative, and complementary therapy. PMID:23349587

  6. Common mechanisms of compensatory respiratory plasticity in spinal neurological disorders

    PubMed Central

    Johnson, Rebecca A.; Mitchell, Gordon S.

    2013-01-01

    In many neurological disorders that disrupt spinal function and compromise breathing (e.g. ALS, cervical spinal injury, MS), patients often maintain ventilatory capacity well after the onset of severe CNS pathology. In progressive neurodegenerative diseases, patients ultimately reach a point where compensation is no longer possible, leading to catastrophic ventilatory failure. In this brief review, we consider evidence that common mechanisms of compensatory respiratory plasticity preserve breathing capacity in diverse clinical disorders, despite the onset of severe pathology (e.g. respiratory motor neuron denervation and/or death). We propose that a suite of mechanisms, operating at distinct sites in the respiratory control system, underlies compensatory respiratory plasticity, including: 1) increased (descending) central respiratory drive, 2) motor neuron plasticity, 3) plasticity at the neuromuscular junction or spared respiratory motor neurons, and 4) shifts in the balance from more to less severely compromised respiratory muscles. To establish this framework, we contrast three rodent models of neural dysfunction, each posing unique problems for the generation of adequate inspiratory motor output: 1) respiratory motor neuron death, 2) de- or dysmyelination of cervical spinal pathways, and 3) cervical spinal cord injury, a neuropathology with components of demyelination and motor neuron death. Through this contrast, we hope to understand the multilayered strategies used to “fight” for adequate breathing in the face of mounting pathology. PMID:23727226

  7. Organic vs. functional neurological disorders: The role of childhood psychological trauma.

    PubMed

    Karatzias, Thanos; Howard, Ruth; Power, Kevin; Socherel, Florentina; Heath, Craig; Livingstone, Alison

    2017-01-01

    Although the relationship between psychological trauma and medically unexplained symptoms (MUS) is well established, this relationship is less well understood in people with medically unexplained neurological symptoms. In the present study, we set out to compare people with functional neurological disorders, and organic neurological disorders, in terms of childhood and adulthood traumatic events, traumatic stress, emotional dysregulation and symptoms of depression and anxiety. We have hypothesised that those with functional neurological disorders would be more likely to report childhood and adulthood traumatic life events, traumatic symptomatology, emotional dysregulation and symptoms of anxiety and depression, compared to those with organic neurological disorders. Sample consisted of a consecutive series of people with functional neurological disorders and with organic neurological disorders (n=82) recruited from a hospital in Scotland. Participants completed measures of life events, traumatic stress, emotional regulation, anxiety and depression. The two groups were found to significantly differ in relation to all measures, with the MUS group being more likely to report childhood and adulthood life events, more severe emotional dysregulation, traumatic stress and symptoms of anxiety and stress. Logistic regression analysis revealed that exposure to childhood traumatic life events, specifically childhood sexual abuse, and childhood physical neglect, were the only factors which were significantly associated with membership of the medically unexplained neurological symptoms group. Although further research is required to confirm our findings, our results suggest that identifying and addressing the impact of childhood trauma, may alleviate distress and aid recovery from functional neurological disorders.

  8. 76 FR 47218 - National Institute of Neurological Disorders and Stroke Amended; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... Neurological Disorders and Stroke Special Emphasis Panel, August 2, 2011, 9 a.m. to August 2, 2011, 3...

  9. 77 FR 27783 - National Institute of Neurological Disorders and Stroke Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Special... 20892-9529, 301-594-0635, Rc218u@nih.gov . Name of Committee: National Institute of...

  10. 75 FR 51278 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-19

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... privacy. Name of Committee: National Advisory Neurological Disorders and Stroke Council. Date: September... Stroke, NIH, 6001 Executive Blvd., Suite 3309, MSC 9531, Bethesda, MD 20892, (301) 496-9248....

  11. 76 FR 10382 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Special Emphasis Panel; Stroke Clinical Trials. Date: March 25, 2011. Time: 10 a.m. to 3 p.m. Agenda: To review...

  12. 75 FR 22818 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke Initial Review... Stroke Initial Review Group, NST-1 Subcommittee. Date: June 3-4, 2010. Time: 8 a.m. to 6 p.m. Agenda:...

  13. 78 FR 72683 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-03

    ... HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... personal privacy. Name of Committee: National Institute of Neurological Disorders and Stroke, Special Emphasis Panel, Stroke Trials Network-NDMC. Date: December 18, 2013. Time: 9:00 a.m. to 2:30 p.m....

  14. 78 FR 19498 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... Stroke Initial Review Group; Neurological Sciences and Disorders C. Date: June 20-21, 2013. Time: 8:00...

  15. 76 FR 23613 - National Institute of Neurological Disorders and Stroke; Amended Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-27

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke... Neurological Disorders and Stroke Special Emphasis Panel, April 19, 2011, 3:15 p.m. to April 19, 2011, 7:15...

  16. 78 FR 29144 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke..., neuhuber@ninds.nih.gov . Name of Committee: National Institute of Neurological Disorders and Stroke...

  17. Clinical assessment of social cognitive function in neurological disorders.

    PubMed

    Henry, Julie D; von Hippel, William; Molenberghs, Pascal; Lee, Teresa; Sachdev, Perminder S

    2016-01-01

    Social cognition broadly refers to the processing of social information in the brain that underlies abilities such as the detection of others' emotions and responding appropriately to these emotions. Social cognitive skills are critical for successful communication and, consequently, mental health and wellbeing. Disturbances of social cognition are early and salient features of many neuropsychiatric, neurodevelopmental and neurodegenerative disorders, and often occur after acute brain injury. Its assessment in the clinic is, therefore, of paramount importance. Indeed, the most recent edition of the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5) introduced social cognition as one of six core components of neurocognitive function, alongside memory and executive control. Failures of social cognition most often present as poor theory of mind, reduced affective empathy, impaired social perception or abnormal social behaviour. Standard neuropsychological assessments lack the precision and sensitivity needed to adequately inform treatment of these failures. In this Review, we present appropriate methods of assessment for each of the four domains, using an example disorder to illustrate the value of these approaches. We discuss the clinical applications of testing for social cognitive function, and finally suggest a five-step algorithm for the evaluation and treatment of impairments, providing quantitative evidence to guide the selection of social cognitive measures in clinical practice.

  18. The dawn of the yawn: is yawning a warning? Linking neurological disorders.

    PubMed

    Thompson, Simon B N

    2010-12-01

    Yawning continues to pose as a scientist's conundrum. Evidence is presented of yawning and contagious yawning in a number of different neurological disorders. Explanations are discussed in the context of disparate neurological disorders together with proposals for how theses findings may be linked. Thus, greater understanding of yawning and of neurological disorders may be achieved by exploring common neuro-chemical pathways and the involvement of neurotransmitters that are implicated in these different disorders. Finally, contagious yawning is discussed in the context of the susceptibility of persons and the similarity this presents with our understanding of the mechanisms involved in hypnosis.

  19. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies

    PubMed Central

    Hove, Michael J.; Keller, Peter E.

    2014-01-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson’s disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients’ gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient’s walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with Parkinson patients’ footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. PMID:25773624

  20. Therapeutic effects of progesterone in animal models of neurological disorders.

    PubMed

    De Nicola, Alejandro F; Coronel, Florencia; Garay, Laura I; Gargiulo-Monachelli, Gisella; Gonzalez Deniselle, Maria Claudia; Gonzalez, Susana L; Labombarda, Florencia; Meyer, Maria; Guennoun, Rachida; Schumacher, Michael

    2013-12-01

    Substantial evidence supports that progesterone exerts many functions in the central and peripheral nervous system unrelated to its classical role in reproduction. In this review we first discussed progesterone effects following binding to the classical intracellular progesterone receptors A and B and several forms of membrane progesterone receptors, the modulation of intracellular signalling cascades and the interaction of progesterone reduced metabolites with neurotransmitter receptors. We next described our results involving animal models of human neuropathologies to elucidate the protective roles of progesterone. We described: (a) the protective and promyelinating effects of progesterone in experimental spinal cord injury; (b) the progesterone protective effects exerted upon motoneurons in the degenerating spinal cord of Wobbler mouse model of amyotropic lateral sclerosis; (c) the protective and anti-inflammatory effects of progesterone in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis and after lysolecithin demyelination; (d) the progesterone prevention of nociception and neuropathic pain which follow spinal cord injury; and (e) the protective effect of progesterone in experimental ischemic stroke. Whenever available, the molecular mechanisms involved in these progesterone effects were examined. The multiplicity of progesterone beneficial effects has opened new venues of research for neurological disorders. In this way, results obtained in animal models could provide the basis for novel therapeutic strategies and pre-clinical studies.

  1. The Therapeutic Effects of Singing in Neurological Disorders

    PubMed Central

    Wan, Catherine Y.; Rüber, Theodor; Hohmann, Anja; Schlaug, Gottfried

    2010-01-01

    Music making (playing an instrument or singing) is a multimodal activity that involves the integration of auditory and sensorimotor processes. The ability to sing in humans is evident from infancy, and does not depend on formal vocal training but can be enhanced by training. Given the behavioral similarities between singing and speaking, as well as the shared and distinct neural correlates of both, researchers have begun to examine whether singing can be used to treat some of the speech-motor abnormalities associated with various neurological conditions. This paper reviews recent evidence on the therapeutic effects of singing, and how it can potentially ameliorate some of the speech deficits associated with conditions such as stuttering, Parkinson's disease, acquired brain lesions, and autism. By reviewing the status quo, it is hoped that future research can help to disentangle the relative contribution of factors to why singing works. This may ultimately lead to the development of specialized or “gold-standard” treatments for these disorders, and to an improvement in the quality of life for patients. PMID:21152359

  2. Perspectives for computational modeling of cell replacement for neurological disorders

    SciTech Connect

    Aimone, James B.; Weick, Jason P.

    2013-01-01

    Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.

  3. Perspectives for computational modeling of cell replacement for neurological disorders

    SciTech Connect

    Aimone, James B.; Weick, Jason P.

    2013-01-01

    In mathematical modeling of anatomically-constrained neural networks we provide significant insights regarding the response of networks to neurological disorders or injury. Furthermore, a logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.

  4. Carriers in Cell-Based Therapies for Neurological Disorders

    PubMed Central

    Wong, Francisca S. Y.; Chan, Barbara P.; Lo, Amy C. Y.

    2014-01-01

    There is a pressing need for long-term neuroprotective and neuroregenerative therapies to promote full function recovery of injuries in the human nervous system resulting from trauma, stroke or degenerative diseases. Although cell-based therapies are promising in supporting repair and regeneration, direct introduction to the injury site is plagued by problems such as low transplanted cell survival rate, limited graft integration, immunorejection, and tumor formation. Neural tissue engineering offers an integrative and multifaceted approach to tackle these complex neurological disorders. Synergistic therapeutic effects can be obtained from combining customized biomaterial scaffolds with cell-based therapies. Current scaffold-facilitated cell transplantation strategies aim to achieve structural and functional rescue via offering a three-dimensional permissive and instructive environment for sustainable neuroactive factor production for prolonged periods and/or cell replacement at the target site. In this review, we intend to highlight important considerations in biomaterial selection and to review major biodegradable or non-biodegradable scaffolds used for cell transplantation to the central and peripheral nervous system in preclinical and clinical trials. Expanded knowledge in biomaterial properties and their prolonged interaction with transplanted and host cells have greatly expanded the possibilities for designing suitable carrier systems and the potential of cell therapies in the nervous system. PMID:24933636

  5. Dynamic regulation of aquaporin-4 water channels in neurological disorders

    PubMed Central

    Hsu, Ying; Tran, Minh; Linninger, Andreas A.

    2015-01-01

    Aquaporin-4 water channels play a central role in brain water regulation in neurological disorders. Aquaporin-4 is abundantly expressed at the astroglial endfeet facing the cerebral vasculature and the pial membrane, and both its expression level and subcellular localization significantly influence brain water transport. However, measurements of aquaporin-4 levels in animal models of brain injury often report opposite trends of change at the injury core and the penumbra. Furthermore, aquaporin-4 channels play a beneficial role in brain water clearance in vasogenic edema, but a detrimental role in cytotoxic edema and exacerbate cell swelling. In light of current evidence, we still do not have a complete understanding of the role of aquaporin-4 in brain water transport. In this review, we propose that the regulatory mechanisms of aquaporin-4 at the transcriptional, translational, and post-translational levels jointly regulate water permeability in the short and long time scale after injury. Furthermore, in order to understand why aquaporin-4 channels play opposing roles in cytotoxic and vasogenic edema, we discuss experimental evidence on the dynamically changing osmotic gradients between blood, extracellular space, and the cytosol during the formation of cytotoxic and vasogenic edema. We conclude with an emerging picture of the distinct osmotic environments in cytotoxic and vasogenic edema, and propose that the directions of aquaporin-4-mediated water clearance in these two types of edema are distinct. The difference in water clearance pathways may provide an explanation for the conflicting observations of the roles of aquaporin-4 in edema resolution. PMID:26526878

  6. Cognitive-analytical therapy for a patient with functional neurological symptom disorder-conversion disorder (psychogenic myopia): A case study.

    PubMed

    Nasiri, Hamid; Ebrahimi, Amrollah; Zahed, Arash; Arab, Mostafa; Samouei, Rahele

    2015-05-01

    Functional neurological symptom disorder commonly presents with symptoms and defects of sensory and motor functions. Therefore, it is often mistaken for a medical condition. It is well known that functional neurological symptom disorder more often caused by psychological factors. There are three main approaches namely analytical, cognitive and biological to manage conversion disorder. Any of such approaches can be applied through short-term treatment programs. In this case, study a 12-year-old boy with the diagnosed functional neurological symptom disorder (psychogenic myopia) was put under a cognitive-analytical treatment. The outcome of this treatment modality was proved successful.

  7. ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

    PubMed Central

    Hayreh, Sohan Singh

    2011-01-01

    The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual

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

    PubMed

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

    2016-04-01

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

  9. Predation as a cause of neurologic signs and acute mortality in a pheasant flock.

    PubMed

    Martin, M P; Anderson, C M; Johnson, B; Wakenell, P S

    2006-09-01

    A flock of approximately 15,000 ring-necked pheasants (Phasianus colchicus) was evaluated for a sudden increase in mortality and acute neurological signs after having been previously diagnosed 3 wk earlier with a chronic respiratory disease of undetermined etiology. Approximately 25 live birds were displaying neurological signs including circling, ataxia, and obtunded behavior and 50 birds were dead. Three birds with neurological signs were submitted for evaluation. Extensive subcutaneous hemorrhage over the head and penetrating puncture wounds through the skull and into the brain were found. Trauma from a wild predatory mammal, most likely the long-tailed weasel (Mustela frenata) that had invaded the pheasant house and expressed surplus killing behavior was determined to be the cause of the acute neurological signs and mortality. The relationship of the chronic respiratory disease to the predation episode was not determined but it is possible that pheasants with severe respiratory disease may have had increased susceptibility to predation.

  10. Therapeutic potential of human adipose-derived stem cells in neurological disorders.

    PubMed

    Chang, Keun-A; Lee, Jun-Ho; Suh, Yoo-Hun

    2014-01-01

    Stem cell therapy has been noted as a novel strategy to various diseases including neurological disorders such as Alzheimer's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and Huntington's disease that have no effective treatment available to date. The adipose-derived stem cells (ASCs), mesenchymal stem cells (MSCs) isolated from adipose tissue, are well known for their pluripotency with the ability to differentiate into various types of cells and immuno-modulatory property. These biological features make ASCs a promising source for regenerative cell therapy in neurological disorders. Here we discuss the recent progress of regenerative therapies in various neurological disorders utilizing ASCs.

  11. Central Venous Line and Acute Neurological Deficit: A Case Series

    PubMed Central

    Ahmadi, Seyed Hossein; Shirzad, Mahmood; Zeraatian, Sam; Salehiomran, Abbas; Abbasi, Seyed Hesameddin; Ghiasi, Atefeh

    2014-01-01

    Abstract Central venous catheter (CVC) insertion is a practical way to assess patients hemodynamic specially in cardiovascular surgery but this relatively simple junior level procedure is not risk free and its common reported complications include; pneumothorax, hydrothorax, hemothorax, local hematoma, cardiac tamponade, vascular injury, thrombosis, embolism, and catheter disruption. Here in this article we are going to present 6 patients with very unusual presentation of CVC complication which was neurological deficit presented by agitation, unconsciousness, disorientation to time and place and hemiparesis. All patients undergone neurologic consult and brain computed tomography. Final diagnosis was brain ischemic damage and finally we kept them on conservative management; fortunately we did not have any permanent damage. PMID:25870645

  12. 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.

  13. Stem cells as promising therapeutic options for neurological disorders.

    PubMed

    Yoo, Jongman; Kim, Han-Soo; Hwang, Dong-Youn

    2013-04-01

    Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell-mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed.

  14. William Shakespeare's neurology.

    PubMed

    Paciaroni, Maurizio; Bogousslavsky, Julien

    2013-01-01

    Many of Shakespeare's plays contain characters who appear to be afflicted by neurological or psychiatric disorders. Shakespeare, in his descriptive analysis of his protagonists, was contributing to the understanding of these disorders. In fact, Charcot frequently used Shakespearean references in his neurological teaching sessions, stressing how acute objective insight is essential to achieving expert clinical diagnosis. Charcot found in Shakespeare the same rigorous observational techniques for which he himself became famous. This chapter describes many of Shakespearean characters suffering from varied neurological disorders, including Parkinsonism, epilepsy, sleeping disturbances, dementia, headache, prion disease, and paralyses.

  15. Neurological Soft Signs in Indian Children with Specific Developmental Disorders of Scholastic Skills

    ERIC Educational Resources Information Center

    Sadhu, Raja; Mehta, Manju; Kalra, Veena; Sagar, Rajesh; Mongia, Monica

    2008-01-01

    Aim: To compare the occurrence of neurological soft signs (NSS) in children with specific developmental disorders of scholastic skills (SDDSS) and normal children. Methods: 36 cases of SDDSS were compared with 30 control children regarding sociodemographic and clinical variables and neurological soft signs. Results: Children with SDDSS had…

  16. [Neurological disorders after cardiac surgery: Diagnosis of cerebral tumors in the postoperative period].

    PubMed

    López Álvarez, A; Rodríguez Fernández, P; Román Fernández, A; Filgueira Dávila, E; Gálvez Gómez, D; González Monzón, V

    2014-11-01

    The incidence of neurologic disorders in the postoperative period of cardiac surgery is high and usually due to a combination of pre- and intraoperative factors. We present 2 patients with brain tumors diagnosed in the immediate postoperative period after sudden onset of neurologic dysfunction. Image studies yielded clinically useful information in these 2 cases.

  17. 78 FR 64227 - National Institute of Neurological Disorders and Stroke; Amended Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-28

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the Neurological...

  18. 78 FR 64223 - National Institute of Neurological Disorders and Stroke Amended Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-28

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke Amended Notice of Meeting Notice is hereby given of a change in the meeting of the Neurological...

  19. Abnormalities on the Neurological Examination and EEG in Young Children with Pervasive Developmental Disorders

    ERIC Educational Resources Information Center

    Akshoomoff, Natacha; Farid, Nikdokht; Courchesne, Eric; Haas, Richard

    2007-01-01

    This study examined the nature and frequency of neurological and EEG abnormalities in 60 young children (ages 2-6 years) with pervasive developmental disorders. A number of standard neurological functions could not be adequately assessed due to the young age of the children and/or limited comprehension and cooperation. The most common neurological…

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

    PubMed

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

    2015-01-01

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

  1. 77 FR 72362 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-05

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of..., Clinical Research Related to Neurological Disorders; 93.854, Biological Basis Research in the...

  2. 77 FR 52337 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-29

    ... clearly unwarranted invasion of personal privacy. Name of Committee: Board of Scientific Counselors.... 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological Basis Research in...

  3. 77 FR 65896 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-31

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Assistance Program Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological...

  4. 76 FR 16432 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ... review and evaluate grant applications. Place: National Institutes of Health, Neuroscience Center, 6001... Review Officer, Scientific Review Branch, Division of Extramural Research, NINDS/ NIH/DHHS/Neuroscience... to Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences,...

  5. 75 FR 64315 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-19

    ... Executive Boulevard, MSC 9529, Neuroscience Center, Room 3203, Bethesda, MD 20892-9529. 301- 496-5388... Related to Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences,...

  6. 75 FR 65497 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-25

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Assistance Program Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological...

  7. 75 FR 3475 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-21

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological Basis Research...

  8. 76 FR 369 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of..., Clinical Research Related to Neurological Disorders; 93.854, Biological Basis Research in the...

  9. 76 FR 52961 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-24

    ... with the contract proposals, the disclosure of which would constitute a clearly unwarranted invasion of... Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences, National Institutes of...

  10. 75 FR 49501 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-13

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Program Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological...

  11. 78 FR 42528 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-16

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological Basis Research...

  12. 77 FR 45644 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-01

    ... constitute a clearly unwarranted invasion of personal privacy. Name of Committee: National Institute of... Assistance Program Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological...

  13. 78 FR 66372 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-05

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Assistance Program Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological...

  14. 76 FR 10038 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-23

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of..., Clinical Research Related to Neurological Disorders; 93.854, Biological Basis Research in the...

  15. 78 FR 45933 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-30

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Assistance Program Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological...

  16. 75 FR 30409 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-01

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of..., Clinical Research Related to Neurological Disorders; 93.854, Biological Basis Research in the...

  17. Pertussis immunisation and serious acute neurological illness in children.

    PubMed Central

    Miller, D L; Ross, E M; Alderslade, R; Bellman, M H; Rawson, N S

    1981-01-01

    The first 1000 cases notified to the National Childhood Encephalopathy Study were analysed. The diagnoses included encephalitis/encephalopathy, prolonged convulsions, infantile spasms, and Reye's syndrome. Eighty-eight of the children had had a recent infectious disease, including 19 with pertussis. Only 35 of the notified children (3.5%) had received pertussis antigen within seven days before becoming ill. Of 1955 control children matched for age, sex, and area of residence, 34 (1.7%) had been immunised with pertussis vaccine within the seven days before the date on which they became of the same age as the corresponding notified child. The relative risk of a notified child having had pertussis immunisation within that time interval was 2.4 (p less than 0.001). Of the 35 notified children, 32 had no previous neurological abnormality. A year later two had died, nine had developmental retardation, and 21 were normal. A significance association was shown between serious neurological illness and pertussis vaccine, though cases were few and most children recovered completely. PMID:6786580

  18. Functional disorders in the Neurology section of ICD-11: A landmark opportunity.

    PubMed

    Stone, Jon; Hallett, Mark; Carson, Alan; Bergen, Donna; Shakir, Raad

    2014-12-09

    Functional disorders are one of the most common diagnoses in neurologic practice, but this is not reflected in current classification systems. The 11th revision of the World Health Organization's International Classification of Diseases (ICD-11) in 2017 offers an opportunity for these disorders to appear within both neurologic and psychiatric categories for the first time. We discuss the rationale for this proposal and highlight the potential benefits for health professionals and patients.

  19. A Population-Based Study of the Association Between Bullous Pemphigoid and Neurologic Disorders

    PubMed Central

    Brick, Katherine E.; Weaver, Chad H.; Savica, Rodolfo; Lohse, Christine M.; Pittelkow, Mark R.; Boeve, Bradley F.; Gibson, Lawrence E.; Camilleri, Michael J.; Wieland, Carilyn N.

    2015-01-01

    Background Bullous pemphigoid has been reported in association with neurologic disorders. Objective To analyze the association between bullous pemphigoid and neurologic disorders. Methods We retrospectively identified residents of Olmsted County, Minnesota, with a first lifetime diagnosis of bullous pemphigoid between January 1, 1960, and December 31, 2009. Three age- and sex-matched Olmsted County residents without bullous pemphigoid were selected as controls for each patient. We compared history of or development of neurologic disorders (dementia, Alzheimer disease, Parkinson disease, multiple sclerosis, cerebrovascular disease, and seizures) between groups using case-control and cohort designs. Results A total of 87 patients with bullous pemphigoid were identified and matched to 261 controls. The odds of a previous diagnosis of any neurologic disorder or a history of dementia were significantly increased among cases compared with controls (odds ratios: 6.85 (3.00–15.64); P<.001, and 6.75 (2.08–21.92); P=.002, respectively). Both Parkinson disease (hazard ratio, 8.56 (1.55–47.25); P=.01) and any type of neurologic disorder (hazard ratio, 2.02 (1.17–3.49); P=.01) were significantly more likely to develop during follow-up in patients with bullous pemphigoid than in those without bullous pemphigoid. Limitations Small geographic area; retrospective study design. Conclusion Our study confirmed an association of bullous pemphigoid with neurologic disorders, especially dementia and Parkinson disease. PMID:25174542

  20. Yoga as an ancillary treatment for neurological and psychiatric disorders: a review.

    PubMed

    Meyer, Hilary B; Katsman, Alina; Sones, Alexander C; Auerbach, Daniel E; Ames, Donna; Rubin, Robert T

    2012-01-01

    Yoga is gaining acceptance as an ancillary medical treatment, but there have been few studies evaluating its therapeutic benefits in neurological and major psychiatric conditions. The authors reviewed the literature in English on the efficacy of yoga for these disorders. Only randomized, controlled trials were included, with the exception of the only study of yoga for bipolar disorder, which was observational. Trials were excluded if yoga was not the central component of the intervention. Of seven randomized, controlled trials of yoga in patients with neurological disorders, six found significant, positive effects. Of 13 randomized, controlled trials of yoga in patients with psychiatric disorders, 10 found significant, positive effects. These results, although encouraging, indicate that additional randomized, controlled studies are needed to critically define the benefits of yoga for both neurological and psychiatric disorders.

  1. Uncommon acute neurologic presentation of canine distemper in 4 adult dogs

    PubMed Central

    Galán, Alba; Gamito, Araceli; Carletti, Beatrice E.; Guisado, Alicia; de las Mulas, Juana Martín; Pérez, José; Martín, Eva M.

    2014-01-01

    Four uncommon cases of canine distemper (CD) were diagnosed in vaccinated adult dogs. All dogs had acute onset of neurologic signs, including seizures, abnormal mentation, ataxia, and proprioceptive deficits. Polymerase chain reaction for CD virus was positive on cerebrospinal fluid in 2 cases. Due to rapid deterioration the dogs were euthanized and CD was confirmed by postmortem examination. PMID:24688139

  2. Uncommon acute neurologic presentation of canine distemper in 4 adult dogs.

    PubMed

    Galán, Alba; Gamito, Araceli; Carletti, Beatrice E; Guisado, Alicia; de las Mulas, Juana Martín; Pérez, José; Martín, Eva M

    2014-04-01

    Four uncommon cases of canine distemper (CD) were diagnosed in vaccinated adult dogs. All dogs had acute onset of neurologic signs, including seizures, abnormal mentation, ataxia, and proprioceptive deficits. Polymerase chain reaction for CD virus was positive on cerebrospinal fluid in 2 cases. Due to rapid deterioration the dogs were euthanized and CD was confirmed by postmortem examination.

  3. Neurological disorders in Iraqi refugees in Jordan: data from the United Nations Refugee Assistance Information System.

    PubMed

    Mateen, Farrah J; Carone, Marco; Nyce, Sayre; Ghosn, Jad; Mutuerandu, Timothy; Al-Saedy, Huda; Lowenstein, Daniel H; Burnham, Gilbert

    2012-04-01

    The United Nations High Commissioner for Refugees (UNHCR) recognizes 43.7 million forcibly displaced persons and asylum seekers due to conflict and persecution worldwide. Neurological disorders have rarely been described in displaced persons but likely pose a significant burden of disease. We describe the disease spectrum and health service utilization of Iraqi refugees and asylum seekers with neurological disorders using an information system developed by the UNHCR. Neurological disorders were actively monitored among the 7,642 UNHCR-registered Iraqi refugees and asylum seekers who received health and humanitarian assistance using a pilot, centralized, database called the Refugee Assistance Information System (RAIS) in the Kingdom of Jordan in 2010. There were 122 neurological diagnoses reported in 1,328 refugees (mean age 41 years, 49% female, 10% disabled, 43% with pending resettlement applications) in 2,659 health visits, accounting for 17% of all refugees who sought health assistance in RAIS. Referral to a neurologist occurred in 178 cases (13.4%). The most frequent ICD-10 neurological diagnoses were dorsalgia (back pain) (29.7% of individuals with neurological disorders), headache (13.1%), and epilepsy (12.6%). Approximately 1 in 20 Iraqi refugees with a neurological diagnosis self-reported a history of torture, which was higher than Iraqi refugees without a history of torture [66/1,328 versus 196/6,314, odds ratio (OR) = 1.63, 95% confidence interval (CI) 1.21-2.18]. Neurological disease affects a high proportion of Iraqi refugees, including victims of torture and the disabled. Refugees require dedicated care for treatment of neurological disease with a focus on pain disorders and epilepsy.

  4. Evidence-based review of therapeutic plasma exchange in neurological disorders.

    PubMed

    Chhibber, Vishesh; Weinstein, Robert

    2012-01-01

    Several neurologic disorders have been treated with therapeutic plasma exchange (TPE). Case reports, case series, and clinical trials have published results regarding the outcomes in such patients. The data gathered have been used to formulate evidence-based guidelines, which can be used to guide therapy in patients with these neurological disorders. Adequately designed and powered randomized controlled trials have proven the efficacy of TPE in some disease entities, while other diseases are lacking such data. In the latter, decisions for the use of TPE must be made using the limited published data available. In this review, we discuss the published evidence regarding the use of TPE in neurological disorders, focusing on the most recent guidelines published by the American Society of Apheresis in 2010 and the American Academy of Neurology in 2011.

  5. Medical and Nonstroke Neurologic Causes of Acute, Continuous Vestibular Symptoms.

    PubMed

    Edlow, Jonathan A; Newman-Toker, David E

    2015-08-01

    Most patients with the acute vestibular syndrome (AVS) have vestibular neuritis or stroke or, in the setting of trauma, a posttraumatic vestibular cause. Some medical and nonstroke causes of the AVS must also be considered. Multiple sclerosis is the most common diagnosis in this group. Other less common causes include cerebellar masses, inflammation and infection, mal de debarquement, various toxins, Wernicke disease, celiac-related dizziness, and bilateral vestibulopathy. Finally, there may be unmasking of prior posterior circulation events by various physiologic alterations such as alterations of temperature, blood pressure, electrolytes, or various medications, especially sedating agents.

  6. Distinct neurological disorders with ATP1A3 mutations

    PubMed Central

    Heinzen, Erin L.; Arzimanoglou, Alexis; Brashear, Allison; Clapcote, Steven J.; Gurrieri, Fiorella; Goldstein, David B.; Jóhannesson, Sigurður H.; Mikati, Mohamad A.; Neville, Brian; Nicole, Sophie; Ozelius, Laurie J.; Poulsen, Hanne; Schyns, Tsveta; Sweadner, Kathleen J.; van den Maagdenberg, Arn; Vilsen, Bente

    2014-01-01

    Genetic research has shown that mutations that modify the protein-coding sequence of ATP1A3, the gene encoding the α3 subunit of Na+/K+-ATPase, cause both rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood. These discoveries link two clinically distinct neurological diseases to the same gene, however, ATP1A3 mutations are, with one exception, disease-specific. Although the exact mechanism of how these mutations lead to disease is still unknown, much knowledge has been gained about functional consequences of ATP1A3 mutations using a range of in vitro and animal model systems, and the role of Na+/K+-ATPases in the brain. Researchers and clinicians are attempting to further characterise neurological manifestations associated with mutations in ATP1A3, and to build on the existing molecular knowledge to understand how specific mutations can lead to different diseases. PMID:24739246

  7. Mutational consequences of aberrant ion channels in neurological disorders.

    PubMed

    Kumar, Dhiraj; Ambasta, Rashmi K; Kumar, Pravir

    2014-11-01

    Neurological channelopathies are attributed to aberrant ion channels affecting CNS, PNS, cardiac, and skeletal muscles. To maintain the homeostasis of excitable tissues, functional ion channels are necessary to rely electrical signals, whereas any malfunctioning serves as an intrinsic factor to develop neurological channelopathies. Molecular basis of these disease is studied based on genetic and biophysical approaches, e.g., loci positional cloning, whereas pathogenesis and bio-behavioral analysis revealed the dependency on genetic mutations and inter-current triggering factors. Although electrophysiological studies revealed the possible mechanisms of diseases, analytical study of ion channels remained unsettled and therefore underlying mechanism in channelopathies is necessary for better clinical application. Herein, we demonstrated (i) structural and functional role of various ion channels (Na(+), K(+), Ca(2+),Cl(-)), (ii) pathophysiology involved in the onset of their associated channelopathies, and (iii) comparative sequence and phylogenetic analysis of diversified sodium, potassium, calcium, and chloride ion channel subtypes.

  8. Torsade de pointes indicates early neurologic damage in acute ischemic stroke.

    PubMed

    Huang, Li-Yen; Lin, Wei-Shiang; Lin, Wen-Yu; Cheng, Cheng-Chung; Cheng, Shu-Meng; Tsai, Tsung-Neng

    2013-12-01

    Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia that is related to QT prolongation. Although QT prolongation is commonly seen in acute stroke, TdP is rare. We report the case of a 78-year-old woman with ischemic stroke who presented with TdP as the initial manifestation of early neurologic deterioration. We hypothesized that an increase in intracranial pressure may result in neurohormonal activation, QT prolongation, and then myocardial damage, leading to TdP. We highlight that new onset of TdP in a patient with stroke may reflect neurologic deterioration, requiring further evaluation and specific intervention.

  9. Acute neurologic disease in Porcine rubulavirus experimentally infected piglets.

    PubMed

    Herrera, Jenifer; Gómez-Núñez, Luis; Lara-Romero, Rocío; Diosdado, Fernando; Martínez-Lara, Atalo; Jasso, Miguel; Ramírez-Mendoza, Humberto; Pérez-Torres, Armando; Rivera-Benítez, José Francisco

    2017-02-15

    The objective of this study was to evaluate the clinical disease, humoral response and viral distribution of recent Porcine rubulavirus (PorPV) isolates in experimentally infected pigs. Four, 6-piglet (5-days old) groups were employed (G1-84, G2-93, G3-147, and G4-T). Three viral strains were used for the experimental infection: the reference strain LPMV-1984 (Michoacán 1984) and two other strains isolated in 2013, one in Queretaro (Qro/93/2013) and the other in Michoacán (Mich/147/2013). Each strain was genetically characterized by amplification and sequencing of the gene encoding hemagglutinin-neuroamidase (HN). The inoculation was performed through the oronasal and ocular routes, at a dose of 1×10(6)TCID50/ml. Subsequently, the signs were evaluated daily and necropsies were performed on 3 different days post infection (dpi). We recorded all micro- and macroscopic lesions. Organs from the nervous, lymphatic, and respiratory system were analyzed by quantifying the viral RNA load and the presence of the infectious virus. The presence of the viral antigen in organs was evidenced through immunohistochemistry. Seroconversion was evaluated through the use of a hemagglutination inhibition test. In the characterization of gene HN, only three substitutions were identified in strain Mich/147/2013, two in strain LPMV/1984 (fourth passage) and one in strain Qro/93/2013, with respect to reference strain LPMV-84, these changes had not been identified as virulence factors in previously reported strains. Neurological alterations associated with the infection were found in all three experimental groups starting from 3dpi. Groups G1-84 and G3-147 presented the most exacerbated nervous signs. Group G2-93 only presented milder signs including slight motor incoordination, and an increased rectal temperature starting from day 5 post infection (PI). The main histopathological findings were the presence of a mononuclear inflammatory infiltrate (lymphocytic/monocytic) surrounding the

  10. Gait variability in people with neurological disorders: A systematic review and meta-analysis.

    PubMed

    Moon, Yaejin; Sung, JongHun; An, Ruopeng; Hernandez, Manuel E; Sosnoff, Jacob J

    2016-06-01

    There has been growing evidence showing gait variability provides unique information about gait characteristics in neurological disorders. This study systemically reviewed and quantitatively synthesized (via meta-analysis) existing evidence on gait variability in various neurological diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), cerebellar ataxia (CA), Huntington's disease (HD), multiple sclerosis (MS), and Parkinson's disease (PD). Keyword search were conducted in PubMed, Web of science, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library. Meta-analysis was performed to estimate the pooled effect size for gait variability for each neurological group. Meta-regression was performed to compare gait variability across multiple groups with neurological diseases. Gait variability of 777 patients with AD, ALS, CA, HD, MS, or PD participating in 25 studies was included in meta-analysis. All pathological groups had increased amount of gait variability and loss of fractal structure of gait dynamics compared to healthy controls, and gait variability differentiated distinctive neurological conditions. The HD groups had the highest alterations in gait variability among all pathological groups, whereas the PD, AD and MS groups had the lowest. Interventions that aim to improve gait function in patients with neurological disorders should consider the heterogeneous relationship between gait variability and neurological conditions.

  11. Male sexual dysfunction and infertility associated with neurological disorders

    PubMed Central

    Fode, Mikkel; Krogh-Jespersen, Sheila; Brackett, Nancy L; Ohl, Dana A; Lynne, Charles M; Sønksen, Jens

    2012-01-01

    Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic and retroperitoneal surgery, diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord injury. Erectile dysfunction can be managed by an increasingly invasive range of treatments including medications, injection therapy and the surgical insertion of a penile implant. Retrograde ejaculation is managed by medications to reverse the condition in mild cases and in bladder harvest of semen after ejaculation in more severe cases. Anejaculation might also be managed by medication in mild cases while assisted ejaculatory techniques including penile vibratory stimulation and electroejaculation are used in more severe cases. If these measures fail, surgical sperm retrieval can be attempted. Ejaculation with penile vibratory stimulation can be done by some spinal cord injured men and their partners at home, followed by in-home insemination if circumstances and sperm quality are adequate. The other options always require assisted reproductive techniques including intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection. The method of choice depends largely on the number of motile sperm in the ejaculate. PMID:22138899

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

    PubMed

    Thomas, Jaya; Seo, Dongmin; Sael, Lee

    2016-06-01

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

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

    PubMed Central

    Thomas, Jaya; Seo, Dongmin; Sael, Lee

    2016-01-01

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

  14. Acute infantile motor unit disorder. Infantile botulism?

    PubMed

    Clay, S A; Ramseyer, J C; Fishman, L S; Sedgwick, R P

    1977-04-01

    Eight infants with an acute reversible motor unit disorder are described, including two infants from whom Clostridum botulinum type A was isolated from stool specimens. The clinical spectrum includes constipation, cranial nerve deficits, pupillary involvement, and generalized hypotonic weakness. There were no deaths, and all infants have had complete clinical recovery. A characteristic electromyographic (EMG) pattern was present in part until clinical recovery. This distinctive pattern consisted of brief, small, abundant for power exerted motor unit potentials. This EMG pattern in the context of the clinical syndrome may well be diagnostic for acute infantile motor unit disorder.

  15. Current therapeutic techniques and rehabilitation from neurological disorders

    NASA Technical Reports Server (NTRS)

    Nickel, V. L.; Hsu, J. D.

    1974-01-01

    Rancho Los Amigos Hospital is a 1100-bed teaching hospital that is primarily oriented toward rehabilitation. The individual services that deal with neuromuscular disorders are categorically disease entity oriented: They are directed toward the major problems, such as spinal cord injuries, amputations, stroke, cerebral palsy, and rheumatoid arthritis. The services at Rancho cross many traditional medical specialty barriers.

  16. Deep brain stimulation for movement and other neurologic disorders.

    PubMed

    DeLong, Mahlon; Wichmann, Thomas

    2012-08-01

    Deep brain stimulation (DBS) was introduced as a treatment for patients with parkinsonism and other movement disorders in the early 1990s. The technique rapidly became the treatment of choice for these conditions, and is now also being explored for other diseases, including Tourette syndrome, gait disorders, epilepsy, obsessive-compulsive disorder, and depression. Although the mechanism of action of DBS remains unclear, it is recognized that DBS works through focal modulation of functionally specific circuits. The fact that the same DBS parameters and targets can be used in multiple diseases suggests that DBS does not counteract the pathophysiology of any specific disorder, but acts to replace pathologic activities in disease-affected brain circuits with activity that is more easily tolerated. Despite the progress made in the use of DBS, much remains to be done to fully realize the potential of this therapy. We describe some of the most active areas of research in this field, both in terms of exploration of new targets and stimulation parameters, and in terms of new electrode or stimulator designs.

  17. Neurological soft signs in children with attention deficit hyperactivity disorder: Their relationship to executive function and parental neurological soft signs.

    PubMed

    Gong, Jingbo; Xie, Jingtao; Chen, Gui; Zhang, Yajie; Wang, Suhong

    2015-07-30

    The correlations between neurological soft signs (NSS) in children with attention deficit hyperactivity disorder (ADHD) and their executive function, symptoms of inattention, and hyperactivity-impulsivity and the NSS of their parents remain unclear. This study aimed to examine: (1) the prevalence of NSS in children with ADHD and their parents; (2) the correlation between the NSS of children with ADHD and the NSS of their parents; and (3) the correlation between the NSS of children with ADHD and their executive function and symptoms. NSS were assessed with the Cambridge Neurological Inventory (CNI) in 57 children with ADHD (and 80 parents) and 60 healthy children (and 75 parents). Executive function was measured with the Behavioral Rating Inventory of Executive Function (BRIEF). Children with ADHD and their parents had significantly higher NSS than normal children and their parents, respectively, and the NSS of children with ADHD were correlated more strongly with the NSS of their fathers than their mothers. No correlation was found between NSS and BRIEF executive function, but Disinhibition in children with ADHD was significantly correlated with hyperactivity-impulsivity symptoms. Paternal and maternal NSS provided different predictions for child NSS. It may be that NSS are more likely to be genetically transmitted by fathers.

  18. Hypnosis as a model of functional neurologic disorders.

    PubMed

    Deeley, Q

    2017-01-01

    In the 19th century it was recognized that neurologic symptoms could be caused by "morbid ideation" as well as organic lesions. The subsequent observation that hysteric (now called "functional") symptoms could be produced and removed by hypnotic suggestion led Charcot to hypothesize that suggestion mediated the effects of ideas on hysteric symptoms through as yet unknown effects on brain activity. The advent of neuroimaging 100 years later revealed strikingly similar neural correlates in experiments matching functional symptoms with clinical analogs created by suggestion. Integrative models of suggested and functional symptoms regard these alterations in brain function as the endpoint of a broader set of changes in information processing due to suggestion. These accounts consider that suggestions alter experience by mobilizing representations from memory systems, and altering causal attributions, during preconscious processing which alters the content of what is provided to our highly edited subjective version of the world. Hypnosis as a model for functional symptoms draws attention to how radical alterations in experience and behavior can conform to the content of mental representations through effects on cognition and brain function. Experimental study of functional symptoms and their suggested counterparts in hypnosis reveals the distinct and shared processes through which this can occur.

  19. Advances in reprogramming-based study of neurologic disorders.

    PubMed

    Nityanandam, Anjana; Baldwin, Kristin K

    2015-06-01

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

  20. Advances in Reprogramming-Based Study of Neurologic Disorders

    PubMed Central

    Baldwin, Kristin K.

    2015-01-01

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

  1. Neurologic approaches to hysteria, psychogenic and functional disorders from the late 19th century onwards.

    PubMed

    Stone, J

    2017-01-01

    The history of functional neurologic disorders in the 20th century from the point of view of the neurologist is U-shaped. A flurry of interest between the 1880s and early 1920s gave way to lack of interest, skepticism, and concern about misdiagnosis. This was mirrored by increasing professional and geographic divisions between neurology and psychiatry after the First World War. In the 1990s the advent of imaging and other technology highlighted the positive nature of a functional diagnosis. Having been closer in the early 20th century but later more separate, these disorders are now once again the subject of academic and clinical interest, although arguably still very much on the fringes of neurology and neuropsychiatry. Revisiting older material provides a rich source of ideas and data for today's clinical researcher, but also offers cautionary tales of theories and treatments that led to stagnation rather than advancement of the field. Patterns of treatment do have a habit of repeating themselves, for example, the current enthusiasm for transcranial magnetic stimulation compared to the excitement about electrotherapy in the 19th century. For these reasons, an understanding of the history of functional disorders in neurology is arguably more important than it is for other areas of neurologic practice.

  2. Growth associated protein (GAP-43): cloning and the development of a sensitive ELISA for neurological disorders.

    PubMed

    Gnanapavan, Sharmilee; Yousaf, Nasim; Heywood, Wendy; Grant, Donna; Mills, Kevin; Chernajovsky, Yuti; Keir, Geoff; Giovannoni, Gavin

    2014-11-15

    GAP-43 has been studied in the rodent and mammalian brain and shown to be present specifically in areas undergoing axonal elongation and synapse formation. GAP-43 was cloned using the baculovirus expression system and purified. A sandwich ELISA was developed using the recombinant GAP-43 as standard and validated. CSF GAP-43 levels were analysed in benign intracranial hypertension, movement disorders, multiple sclerosis, neuropathy, CNS infections, motor neuron disease, and headache (neurological controls). GAP-43 levels were low in all disorders analysed (in particular motor neuron disease; p=0.001, and movement disorders and multiple sclerosis; p<0.0001) compared to controls, aside from CNS infections. GAP-43 is preferentially reduced in the CSF of neurological disorders associated with neurodegeneration.

  3. The Significance of the Default Mode Network (DMN) in Neurological and Neuropsychiatric Disorders: A Review

    PubMed Central

    Mohan, Akansha; Roberto, Aaron J.; Mohan, Abhishek; Lorenzo, Aileen; Jones, Kathryn; Carney, Martin J.; Liogier-Weyback, Luis; Hwang, Soonjo; Lapidus, Kyle A.B.

    2016-01-01

    The relationship of cortical structure and specific neuronal circuitry to global brain function, particularly its perturbations related to the development and progression of neuropathology, is an area of great interest in neurobehavioral science. Disruption of these neural networks can be associated with a wide range of neurological and neuropsychiatric disorders. Herein we review activity of the Default Mode Network (DMN) in neurological and neuropsychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, Epilepsy (Temporal Lobe Epilepsy - TLE), attention deficit hyperactivity disorder (ADHD), and mood disorders. We discuss the implications of DMN disruptions and their relationship to the neurocognitive model of each disease entity, the utility of DMN assessment in clinical evaluation, and the changes of the DMN following treatment. PMID:27505016

  4. Current perspectives on deep brain stimulation for severe neurological and psychiatric disorders

    PubMed Central

    Kocabicak, Ersoy; Temel, Yasin; Höllig, Anke; Falkenburger, Björn; Tan, Sonny KH

    2015-01-01

    Deep brain stimulation (DBS) has become a well-accepted therapy to treat movement disorders, including Parkinson’s disease, essential tremor, and dystonia. Long-term follow-up studies have demonstrated sustained improvement in motor symptoms and quality of life. DBS offers the opportunity to selectively modulate the targeted brain regions and related networks. Moreover, stimulation can be adjusted according to individual patients’ demands, and stimulation is reversible. This has led to the introduction of DBS as a treatment for further neurological and psychiatric disorders and many clinical studies investigating the efficacy of stimulating various brain regions in order to alleviate severe neurological or psychiatric disorders including epilepsy, major depression, and obsessive–compulsive disorder. In this review, we provide an overview of accepted and experimental indications for DBS therapy and the corresponding anatomical targets. PMID:25914538

  5. Quantitative Evaluation System of Soft Neurological Signs for Children with Attention Deficit Hyperactivity Disorder.

    PubMed

    Kaneko, Miki; Yamashita, Yushiro; Iramina, Keiji

    2016-01-18

    Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity. Soft neurological signs (SNS) are minor neurological abnormalities in motor performance, and are used as one evaluation method for neurodevelopmental delays in children with ADHD. Our aim is to establish a quantitative evaluation system for children with ADHD. We focused on the arm movement called pronation and supination, which is one such soft neurological sign. Thirty three children with ADHD aged 7-11 years (27 males, six females) and twenty five adults participants aged 21-29 years old (19 males, six females) participated in our experiments. Our results suggested that the pronation and supination function in children with ADHD has a tendency to lag behind that of typically developing children by several years. From these results, our system has a possibility to objectively evaluate the neurodevelopmental delay of children with ADHD.

  6. [Effect of work conditions on the development of vertebral neurologic disorders].

    PubMed

    Lagutina, G N; Tarasova, L A; Suvorov, G A; Shardakova, E F

    1994-01-01

    Clinical and hygienic studies covered agricultural machine operators, bulldozer operators, truck drivers, excavator and boring machine operators, display terminal controllers, electronic miniature device assemblers. The studies proved that occupational hazards (general vibration, sitting posture) result in formation of vertebral neurologic disorders in the examinees. The localization and clinical manifestations appeared to depend on intensity and site of the acting hazard.

  7. 75 FR 39548 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-09

    ... and evaluate grant applications. Place: National Institutes of Health, Neuroscience Center, 6001.../Neuroscience Center, 6001 Executive Blvd., Suite 3208, Msc 9529, Bethesda, MD 20852, 301-435-6033, rajarams... to Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences,...

  8. 75 FR 64315 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-19

    ... grant applications. Place: National Institutes of Health, Neuroscience Center, 6001 Executive Boulevard..., Neuroscience Center, 6001 Executive Blvd., Room 3208, MSC 9529, Bethesda, MD 20892-9529. 301-496-0635. Rc218u... Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences, National Institutes of...

  9. 78 FR 51196 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5...

  10. 78 FR 59945 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as ] amended...

  11. 77 FR 24727 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5...

  12. 75 FR 2146 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as ] amended...

  13. 77 FR 15112 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-14

    ... review and evaluate contract proposals. Place: National Institutes of Health, Neuroscience Center, 6001.../Neuroscience Center, 6001 Executive Blvd., Suite 3208, MSC 9529, Bethesda, MD 20892, 301-496-5324, mcconnej... to Neurological Disorders; 93.854, Biological Basis Research in the ] Neurosciences,...

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

    PubMed

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

    2013-10-01

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

  15. A Unique Team Approach to the Total Education of the Student with a Neurological Disorder.

    ERIC Educational Resources Information Center

    Cant, Malcolm J.

    The paper outlines the program of services provided by a multidisciplinary professional team for the neurologically disordered child from preschool to young adulthood. Noted among the services offered are the following: an infant stimulation program, preschool prep program, group sensory integration program, special educational assistance, summer…

  16. Specific protein profile in cerebrospinal fluid from HIV-1-positive cART-treated patients affected by neurological disorders.

    PubMed

    Zanin, Valentina; Delbue, Serena; Marcuzzi, Annalisa; Tavazzi, Eleonora; Del Savio, Rossella; Crovella, Sergio; Marchioni, Enrico; Ferrante, Pasquale; Comar, Manola

    2012-10-01

    Cytokines/chemokines are involved in the immune response of infections, including HIV-1. We defined the profile of 48 cytokines/chemokines in cerebrospinal fluid from 18 cART patients with chronic HIV-1 infection by Luminex technology. Nine patients were affected with leukoencephalopathies: five with John Cunningham virus (JCV) + progressive multifocal leukoencephalopathy (PML) and four with JCV-not determined leukoencephalopathy (NDLE). In addition, nine HIV-1-positive patients with no neurological signs (NND) and five HIV-1-negative patients affected with acute disseminated encephalomyelitis (ADEM) were enrolled. Ten cytokines (IL-15, IL-3, IL-16, IL-18, CTACK, GRO1, SCF, MCP-1, MIF, SDF) were highly expressed in HIV-1-positive patients while IL-1Ra and IL-17 were present at a lower level. In addition, the levels of IL-17, IL-9, FGF-basic, MIP-1β, and MCP-1 were significantly higher (p < 0.05) in patients with neurological diseases (PML, NDLE, ADEM) with respect to NND. Focusing the attention to the cytokine profile in JCV + PML patients with respect to JCV-NDLE patients, only TNF-β was significantly downregulated (p < 0.05) in JCV + PML patients. This pilot study emphasized the role of immunoregulation in HIV-1-related neurological disorders during cART treatment.

  17. Marathon Runner with Acute Hyponatremia: A Neurological Disorder

    PubMed Central

    Kormann, R.; Philippart, F.; Hubert, S.; Bruel, C.

    2012-01-01

    We report the case of an athletic 49-year-old female who has run the 2011 Marathon of Paris and was addressed to the hospital for a confusion. The investigations revealed a cerebral edema complicating a severe hyponatremia secondary to an exercise-associated hyponatremia (EAH). Using 3% hypertonic saline solution, the evolution the patient rapidly improve allowing discharge after 7 days. We then discuss the importance of EAH in long-term efforts. PMID:23326709

  18. Miscellaneous neurologic, cardiac, pulmonary, and metabolic disorders with rheumatic manifestations.

    PubMed

    Larkin, J G

    1993-01-01

    Problems both old and new are featured in this year's selection of rheumatologic aspects of miscellaneous diseases. Paralysis of one or more limbs can lead to many musculoskeletal complications, and the approach of Auguste Dejerine-Klumpke in 1918 can be compared with that of the present-day physician. The reappearance of rheumatic fever continues to excite interest. The specificity of the modified Jones criteria has been questioned, as have the benefits of long-term antibiotic prophylaxis following an attack of the disease. Meanwhile, metabolic disorders may be the first diseases to come under novel scrutiny using the techniques of genetic engineering, with outstanding possibilities for advancing both understanding and treatment. Dermatologic diseases other than psoriasis may be associated with arthropathy. Many of these symptom complexes may be variants of the recently described SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome.

  19. Worse Neurological State During Acute Ischemic Stroke is Associated with a Decrease in Serum Albumin Levels.

    PubMed

    Bielewicz, Joanna; Kurzepa, Jacek; Czekajska-Chehab, Elżbieta; Kamieniak, Piotr; Daniluk, Beata; Bartosik-Psujek, Halina; Rejdak, Konrad

    2016-04-01

    High serum albumin levels during ischemic stroke (IS) decrease the risk of a poor outcome. This study aimed to determine whether serum albumin levels within the first days after IS correlate with radiological and biochemical markers of brain tissue damage. Fifty-six IS patients were enrolled into the study. Neurological examinations were based on the National Institute of Health Stroke Scale. Serum albumin levels and S100BB were evaluated using commercially available ELISA kits. The albumin decrease index (ADI) was calculated as the difference between serum albumin levels measured on days 1 and 10 of IS. All parameters were estimated on the 1st, 3rd, 5th, and 10th days of IS, and the volume of ischemic focus was measured on the 10th day. Mean serum albumin levels were decreased during acute IS. There were correlations between the ADI and mean S100BB serum levels (r = 0.36, p < 0.05), the volume of ischemic focus (r = 0.39, p < 0.05), and the patients' neurological state when measured on day 10 of IS (r = 0.59, p < 0.001). A decrease in serum albumin levels during the acute phase of IS corresponds to a worse neurological state as a result of a large ischemic focus with intense catabolic processes.

  20. Acute Acquired Comitant Esotropia in Adults: Is It Neurologic or Not?

    PubMed Central

    Kansu, Tulay

    2016-01-01

    Objectives. Acute acquired comitant esotropia (AACE) can be a diagnostic challenge for ophthalmologists and neurologists because of its association with neurological pathologies. Our study describes a series of adult patients with AACE of undetermined etiology. Methods. Data on the clinical findings of patients presented with AACE of undetermined etiology with a minimum follow-up of 1 year were retrieved from the medical records and the results analyzed. Results. A series of 9 esotropia cases (age range: 20–43 years) was reviewed. All patients had full duction and versions, without an A-pattern or V-pattern. All patients had esotropia for distance and near. Neurological evaluation in all cases was normal. Among patients, 3 were treated with prisms, 4 were treated with strabismus surgery, and 1 was treated with botulinum toxin injections; 1 patient declined treatment. In treated patients posttreatment sensory testing indicated restoration of binocularity that remained stable throughout follow-up of 1–9 years. The patient that declined treatment had binocular function with base-out prisms. Conclusion. Acute onset esotropia may be seen without a neurological pathology in adults. Good motor and sensory outcomes can be achieved in these patients with AACE of undetermined etiology via surgical and nonsurgical methods. PMID:28018672

  1. Translational Meta-analytical Methods to Localize the Regulatory Patterns of Neurological Disorders in the Human Brain

    PubMed Central

    Sochat, Vanessa; David, Maude; Wall, Dennis P

    2015-01-01

    The task of mapping neurological disorders in the human brain must be informed by multiple measurements of an individual’s phenotype - neuroimaging, genomics, and behavior. We developed a novel meta-analytical approach to integrate disparate resources and generated transcriptional maps of neurological disorders in the human brain yielding a purely computational procedure to pinpoint the brain location of transcribed genes likely to be involved in either onset or maintenance of the neurological condition. PMID:26958307

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

    ERIC Educational Resources Information Center

    Gilger, Jeffrey W.

    2001-01-01

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

  3. Practical considerations on the use of rituximab in autoimmune neurological disorders

    PubMed Central

    Kosmidis, Mixalis L.; Dalakas, Marinos C.

    2010-01-01

    Rituximab (Mabthera, Rituxan) is a chimeric human/murine monoclonal antibody against CD-20 surface antigen expressed on B-cells. Rituximab, by causing B-cell depletion, appears to be effective in several autoimmune disorders; it has been approved for rheumatoid arthritis and is a promising new agent in the treatment of several autoimmune neurological disorders. A controlled study in patients with relapsing remitting multiple sclerosis has shown that rituximab significantly reduces the number of new MRI lesions and improves clinical outcome; it also showed some promise in a subset of patients with primary progressive MS. The drug is also effective in a number of patients with Devic’s disease, myasthenia gravis, autoimmune neuropathies, and inflammatory myopathies. The apparent effectiveness of rituximab has moved B-cells into the center stage of clinical and laboratory investigation of autoimmune neurological disorders. We review the evidence-based effectiveness of rituximab in neurological disorders based on controlled trials and anecdotal reports, including our own experience, and address the immunobiology of B-cells in autoimmune central nervous system (CNS) and peripheral nervous system (PNS) disorders. In addition, we provide practical guidelines on how best to use this drug in clinical practice and highlight its potential toxicity. PMID:21179602

  4. Psychiatric and neurological disorders are associated with bullous pemphigoid – a nationwide Finnish Care Register study

    PubMed Central

    Försti, Anna-Kaisa; Jokelainen, Jari; Ansakorpi, Hanna; Seppänen, Allan; Majamaa, Kari; Timonen, Markku; Tasanen, Kaisa

    2016-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering skin disease with increasing incidence. BP is associated with neurological disorders, but it has not been established, what subtypes of dementia and stroke are associated with BP, and what is the temporal relation between these diseases. Also, the association between BP and psychiatric disorders is controversial. We conducted a retrospective nationwide study, using the Finnish Care Register for Health Care diagnoses between 1987 and 2013. The study population of 4524 BP patients were compared with 66138 patients with basocellular carcinoma (BCC), neurological and psychiatric comorbid disorders were evaluated for both groups, and associations were estimated by Cox regression and logistic regression analyses. The strongest risk of developing BP was found after diagnosis of multiple sclerosis (MS) (OR=5.9, 95% CI 3.9–8.5). Among psychiatric diseases, the corresponding risk was strongest in schizophrenia (OR=2.7, 95% CI 2.0–3.5), and as a novel finding, also personality disorders (OR=2.2, 95% CI 1.3–3.3) preceded BP. In conclusion, many psychiatric disorders, especially schizophrenia, carry heightened risk for BP. Furthermore, several neurological diseases which cause central nervous system inflammation or degeneration were related to BP, and the association was strongest between MS and BP. PMID:27845416

  5. Neurological disorders and therapeutics targeted to surmount the blood–brain barrier

    PubMed Central

    Kanwar, Jagat R; Sriramoju, Bhasker; Kanwar, Rupinder K

    2012-01-01

    We are now in an aging population, so neurological disorders, particularly the neurodegenerative diseases, are becoming more prevalent in society. As per the epidemiological studies, Europe alone suffers 35% of the burden, indicating an alarming rate of disease progression. Further, treatment for these disorders is a challenging area due to the presence of the tightly regulated blood–brain barrier and its unique ability to protect the brain from xenobiotics. Conventional therapeutics, although effective, remain critically below levels of optimum therapeutic efficacy. Hence, methods to overcome the blood–brain barrier are currently a focus of research. Nanotechnological applications are gaining paramount importance in addressing this question, and yielding some promising results. This review addresses the pathophysiology of the more common neurological disorders and novel drug candidates, along with targeted nanoparticle applications for brain delivery. PMID:22848160

  6. Neuro-archaeology: pre-symptomatic architecture and signature of neurological disorders.

    PubMed

    Ben-Ari, Yehezkel

    2008-12-01

    During brain development cells divide, differentiate and migrate to their assigned targets to form synapses and active cell assemblies. This sequence is controlled both by genetic programs and environmental factors. Alterations of this sequence by mutations or environmental insults leads to the formation of misconnected circuits endowed with a 'pre-symptomatic signature'. I propose here that early- and late-onset neurological disorders as diverse as infantile epilepsies, mental retardation, dyslexia or, in certain conditions, even Huntington's and Alzheimer's disease might be, in part, born at early developmental stages before symptoms appear. The core of this working hypothesis is that imaging or non-invasive recordings might unravel signatures of disorders to come, thereby permitting earlier diagnosis and potential treatment of neurological disorders.

  7. The challenge of managing headache disorders in a tertiary referral neurology clinic in Rwanda

    PubMed Central

    Kaputu-Kalala-Malu, Célestin; Walker, Timothy D.; Ntumba-Tshitenge, Olga; Mafuta, Eric M.; Tugirimana, Pierrot L.; Misson, Jean P.

    2016-01-01

    Objective: To determine the pattern, management, and outcome of headaches among patients treated at Outpatient Neurology Clinic. Methods: A retrospective study was conducted at the Out-Patient Neurology Clinic of the Butare University Teaching Hospital, University of Rwanda, Butare, Rwanda between February and May 2015. We extracted the demographic data, headache characteristics, and associated conditions, prior pain-relieving medication use, waiting time before consultation, the results of paraclinical investigations, final diagnosis according to the International Classification of Headache Disorders, management, and 3-month clinical outcome from the medical records of all patients who consulted for headache over 36-month period. Epi Data and Statistical package for Social sciences software version 21.0 (SPSS Inc, Chicago, IL, USA) software were used for data processing. Results: Headache disorders represent a quarter of all neurological consultations. Patients were predominantly female (67%) and young (78% <45 years old). One-third (34%) presented with chronic tension-type headache. Neuroimaging demonstrated an abnormality in a significant minority (14%). Amitriptyline was the most commonly used drug (60%) in management. Forty percent of those patients followed for 3 months did not experience any clinical improvement. Conclusion: Headache is among the most common medical complaints in the Outpatient Neurology Clinic, with a wide array of underlying diagnoses, and a significant yield on neuroimaging. A significant proportion of those suffering from headache disorders have poor short-term outcomes. Novel approaches, such as headache support groups and alternative pharmacological agents, should be investigated for these patients. PMID:27094526

  8. 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

  9. Motor-Cognitive Dual-Task Training in Neurologic Disorders: A Systematic Review

    PubMed Central

    Fritz, NE; Cheek, FM; Nichols-Larsen, DS

    2015-01-01

    Background and Purpose Deficits in motor-cognitive dual-tasks (e.g., walking while talking) are common in individuals with neurological conditions. This review was conducted to determine the effectiveness of motor-cognitive dual-task training (DTT) compared to usual care on mobility and cognition in individuals with neurologic disorders. Methods Databases searched were Biosis, CINAHL, ERIC, PsychInfo, EBSCO Psychological & Behavioral, PubMed, Scopus, and Web of Knowledge. Eligibility criteria were studies of adults with neurologic disorders that included DTT and outcomes of gait or balance were included. Fourteen studies met inclusion criteria. Participants were individuals with brain injury, Parkinson’s disease (PD) and Alzheimer’s disease (AD). Intervention protocols included cued walking, cognitive tasks paired with gait, balance, and strength training and virtual reality or gaming. Quality of the included trials was evaluated with a standardized rating scale of clinical relevance. Results Results show that DTT improves single-task gait velocity and stride length in PD and AD, dual-task gait velocity and stride length in PD, AD and brain injury, and may improve balance and cognition in PD and AD. The inclusion criteria limited the diagnostic groups included. Discussion and Conclusions The range of training protocols and outcome assessments in available studies limited comparison of the results across studies. Improvement of dual-task ability in individuals with neurologic disorders holds potential for improving gait, balance and cognition. Motor-cognitive dual-task deficits in individuals with neurologic disorders may be amenable to training. Video Abstract available for additional insights from the authors (See Supplemental Digital Content). PMID:26079569

  10. Urodynamic profile in acute transverse myelitis patients: Its correlation with neurological outcome

    PubMed Central

    Gupta, Anupam; Kumar, Sushruth Nagesh; Taly, Arun B.

    2017-01-01

    Objective: The objective of this study was to observe urodynamic profile of acute transverse myelitis (ATM) patients and its correlation with neurological outcome. Patients and Methods: This prospective study was conducted in the neurorehabilitation unit of a tertiary university research hospital from July 2012 to June 2014. Forty-three patients (19 men) with ATM with bladder dysfunction, admitted in the rehabilitation unit, were included in this study. Urodynamic study (UDS) was performed in all the patients. Their neurological status was assessed using ASIA impairment scale and functional status was assessed using spinal cord independence measure. Bladder management was based on UDS findings. Results: In total, 17 patients had tetraplegia and 26 had paraplegia. Thirty-six patients (83.7%) had complaints of increased frequency and urgency of urine with 26 patients reported at least one episode of urge incontinence. Seven patients reported obstructive urinary complaints in the form of straining to void with 13 patients reported both urgency and straining to void and 3 also had stress incontinence. Thirty-seven (86.1%) patients had neurogenic overactive detrusor with or without sphincter dyssynergia and five patients had acontractile detrusor on UDS. No definitive pattern was observed between neurological status and bladder characteristics. All patients showed significant neurological and functional recovery with inpatient rehabilitation (P < 0.05 and P < 0.001, respectively). Conclusions: The problem of neurogenic bladder dysfunction is integral to ATM. Bladder management in these patients should be based on UDS findings. Bladder characteristics have no definitive pattern consistent with the neurological status. PMID:28149080

  11. Transverse Myelitis in Acute Hepatitis A Infection: The Rare Co-Occurrence of Hepatology and Neurology

    PubMed Central

    Chonmaitree, Piyanant; Methawasin, Kulthida

    2016-01-01

    Transverse myelitis refers to the inflammatory process involving the spinal cord. Clinical features can be either acute or subacute onset that results in neurological deficits such as weakness and/or numbness of extremities as well as autonomic dysfunctions. While there are some etiologies related, a viral infection is common. However, the hepatitis A virus rarely causes myelitis. This report provides details of a hepatitis A infectious patient who developed myelitis as comorbidity. Although, the disability was initially severe, the patient successfully recovered with corticosteroid treatment. PMID:27403101

  12. Fibromyalgia and arachnoiditis presented as an acute spinal disorder

    PubMed Central

    Idris, Zamzuri; Ghazali, Faizul H.; Abdullah, Jafri M.

    2014-01-01

    Background: Adhesive arachnoiditis is a chronic, insidious condition that causes debilitating intractable pain and a range of other neurological problems. Its pathophysiology is not well understood. This manuscript discusses its presentations, which can mimic an acute spinal disorder, its hypothetical pathophysiology, treatment, and its relationship with fibromyalgia. Case Description: The authors present a case of a 47-year-old female who presented with clinical features mimicking an acute spinal disorder but later found to have an adhesive arachnoiditis. She was admitted following a trauma with complaints of back pain and paraplegia. On examination, there was marked tenderness over thoracolumbar spine with lower limbs upper motor neuron weakness. An urgent magnetic resonance imaging (MRI) of the spine revealed multiple lesions at her thoracic and lumbar spinal canals, which did not compress the spinal cord. Therefore, conservative management was initiated. Despite on regular therapies, her back and body pain worsened and little improvement in her limbs power was noted. Laminectomy was pursued and found to have spinal cord arachnoiditis. Subsequently, she was operated by other team members for multiple pelvic masses, which later proved to be benign. After gathering all the clinical information obtained at surgery and after taking detailed history inclusive of cognitive functions, diagnosis of an adhesive arachnoiditis syndrome was made. Currently, she is managed by neuropsychologist and pain specialist. Conclusion: This case report highlights the importance of knowing an adhesive arachnoiditis syndrome – a rarely discussed pathology by the neurosurgeon, which discloses a significant relationship between immune and nervous systems. PMID:25396073

  13. The Early Use of Blinding in Therapeutic Clinical Research of Neurological Disorders

    PubMed Central

    Jensen, Matthew B.; Janik, Erika L.; Waclawik, Andrew J.

    2016-01-01

    We sought to identify early uses of blinding in therapeutic clinical trials of neurological disorders by multiple search methods. A 1784 report by Benjamin Franklin and others described the evaluation of the use of Mesmerism to treat neurological and other syndromes including headache and epilepsy, using blindfolds and screens. This report demonstrated the usefulness of blinding to reduce bias in clinical research, yet despite this early discovery, blinding was not widely accepted or routinely used until the 20th century. Blinded clinical trials began to be used for various neurological syndromes in the 1950s, sporadically at first and then increasing in frequency in subsequent years. The reason for this delay is unclear, but we propose several hypotheses. PMID:27617324

  14. Robotic gait rehabilitation and substitution devices in neurological disorders: where are we now?

    PubMed

    Calabrò, Rocco Salvatore; Cacciola, Alberto; Bertè, Francesco; Manuli, Alfredo; Leo, Antonino; Bramanti, Alessia; Naro, Antonino; Milardi, Demetrio; Bramanti, Placido

    2016-04-01

    Gait abnormalities following neurological disorders are often disabling, negatively affecting patients' quality of life. Therefore, regaining of walking is considered one of the primary objectives of the rehabilitation process. To overcome problems related to conventional physical therapy, in the last years there has been an intense technological development of robotic devices, and robotic rehabilitation has proved to play a major role in improving one's ability to walk. The robotic rehabilitation systems can be classified into stationary and overground walking systems, and several studies have demonstrated their usefulness in patients after severe acquired brain injury, spinal cord injury and other neurological diseases, including Parkinson's disease, multiple sclerosis and cerebral palsy. In this review, we want to highlight which are the most widely used devices today for gait neurological rehabilitation, focusing on their functioning, effectiveness and challenges. Novel and promising rehabilitation tools, including the use of virtual reality, are also discussed.

  15. Patient heal thyself: modeling and treating neurological disorders using patient-derived stem cells.

    PubMed

    Ess, Kevin C

    2013-03-01

    Disorders of the brain and spinal cord are common worldwide problems but have remained very difficult to treat. As a group they have diverse etiologies and can be due to trauma, infection, tumors, genetic mutations and environmental insults. Though distinct in etiology, neurological disorders share an overall intractability as current therapies are largely limited to treatment of symptoms. Improved outcomes are further constrained by the minimal endogenous capacity of the brain and spinal cord for repair. Spectacular recent scientific advances, however, suggest that new stem cell-based approaches may change this undesirable situation. In this review, I will broadly outline the challenges of studying and treating disorders of the brain and spinal cord. I will review ongoing attempts to use stem cell-based therapies to both model and treat neurological disorders. While this field is in its infancy, expected advances and needed breakthroughs point to a future where patient-derived stem cells will be the basis for the emerging discipline of regenerative neurology.

  16. Patient heal thyself: modeling and treating neurological disorders using patient-derived stem cells

    PubMed Central

    Ess, Kevin C

    2013-01-01

    Disorders of the brain and spinal cord are common worldwide problems but have remained very difficult to treat. As a group they have diverse etiologies and can be due to trauma, infection, tumors, genetic mutations and environmental insults. Though distinct in etiology, neurological disorders share an overall intractability as current therapies are largely limited to treatment of symptoms. Improved outcomes are further constrained by the minimal endogenous capacity of the brain and spinal cord for repair. Spectacular recent scientific advances, however, suggest that new stem cell-based approaches may change this undesirable situation. In this review, I will broadly outline the challenges of studying and treating disorders of the brain and spinal cord. I will review ongoing attempts to use stem cell-based therapies to both model and treat neurological disorders. While this field is in its infancy, expected advances and needed breakthroughs point to a future where patient-derived stem cells will be the basis for the emerging discipline of regenerative neurology. PMID:23598977

  17. Computerized neuropsychological testing to rapidly evaluate cognition in pediatric patients with neurologic disorders.

    PubMed

    Brooks, Brian L; Sherman, Elisabeth M S

    2012-08-01

    Computerized neuropsychological tests represent a viable method for rapidly screening cognition. The purpose of this study was to explore performance on the CNS Vital Signs in a large pediatric neurology sample. Participants included 166 neurology patients (mean age, 13.0 years; standard deviation, 3.2) and 281 controls (mean age, 13.2 years; standard deviation, 3.2) between 7 and 19 years. The neurology sample performed significantly worse on all domain scores and nearly all subtest scores. Cohen d effect sizes were small to medium for verbal memory (d= 0.44), visual memory (d= 0.40), and reaction time (d= 0.48) and very large for psychomotor speed (d= 1.19), complex attention (d = 0.94), cognitive flexibility (d = 0.94), and the overall composite score (d = 1.08). Using the criterion for cognitive impairment of 2 or more scores ≤5th percentile, 36.6% of the neurology sample was identified as having an uncommon cognitive profile. This is the first study to demonstrate the performance of pediatric patients with neurologic disorders on CNS Vital Signs.

  18. Pharmacological targeting of the PDGF-CC signaling pathway for blood-brain barrier restoration in neurological disorders.

    PubMed

    Lewandowski, Sebastian A; Fredriksson, Linda; Lawrence, Daniel A; Eriksson, Ulf

    2016-11-01

    Neurological disorders account for a majority of non-malignant disability in humans and are often associated with dysfunction of the blood-brain barrier (BBB). Recent evidence shows that despite apparent variation in the origin of neural damage, the central nervous system has a common injury response mechanism involving platelet-derived growth factor (PDGF)-CC activation in the neurovascular unit and subsequent dysfunction of BBB integrity. Inhibition of PDGF-CC signaling with imatinib in mice has been shown to prevent BBB dysfunction and have neuroprotective effects in acute damage conditions, including traumatic brain injury, seizures or stroke, as well as in neurodegenerative diseases that develop over time, including multiple sclerosis and amyotrophic lateral sclerosis. Stroke and traumatic injuries are major risk factors for age-associated neurodegenerative disorders and we speculate that restoring BBB properties through PDGF-CC inhibition might provide a common therapeutic opportunity for treatment of both acute and progressive neuropathology in humans. In this review we will summarize what is known about the role of PDGF-CC in neurovascular signaling events and the variety of seemingly different neuropathologies it is involved in. We will also discuss the pharmacological means of therapeutic interventions for anti-PDGF-CC therapy and ongoing clinical trials. In summary: inhibition of PDGF-CC signaling can be protective for immediate injury and decrease the long-term neurodegenerative consequences.

  19. Architects of the genome: CHD dysfunction in cancer, developmental disorders and neurological syndromes.

    PubMed

    Li, Wangzhi; Mills, Alea A

    2014-01-01

    Chromatin is vital to normal cells, and its deregulation contributes to a spectrum of human ailments. An emerging concept is that aberrant chromatin regulation culminates in gene expression programs that set the stage for the seemingly diverse pathologies of cancer, developmental disorders and neurological syndromes. However, the mechanisms responsible for such common etiology have been elusive. Recent evidence has implicated lesions affecting chromatin-remodeling proteins in cancer, developmental disorders and neurological syndromes, suggesting a common source for these different pathologies. Here, we focus on the chromodomain helicase DNA binding chromatin-remodeling family and the recent evidence for its deregulation in diverse pathological conditions, providing a new perspective on the underlying mechanisms and their implications for these prevalent human diseases.

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

    PubMed Central

    Maia, Tiago V.; Frank, Michael J.

    2013-01-01

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

  1. Acute hydrogen sulfide-induced neuropathology and neurological sequelae: challenges for translational neuroprotective research.

    PubMed

    Rumbeiha, Wilson; Whitley, Elizabeth; Anantharam, Poojya; Kim, Dong-Suk; Kanthasamy, Arthi

    2016-08-01

    Hydrogen sulfide (H2 S), the gas with the odor of rotten eggs, was formally discovered in 1777, over 239 years ago. For many years, it was considered an environmental pollutant and a health concern only in occupational settings. Recently, however, it was discovered that H2 S is produced endogenously and plays critical physiological roles as a gasotransmitter. Although at low physiological concentrations it is physiologically beneficial, exposure to high concentrations of H2 S is known to cause brain damage, leading to neurodegeneration and long-term neurological sequelae or death. Neurological sequelae include motor, behavioral, and cognitive deficits, which are incapacitating. Currently, there are concerns about accidental or malicious acute mass civilian exposure to H2 S. There is a major unmet need for an ideal neuroprotective treatment, for use in the field, in the event of mass civilian exposure to high H2 S concentrations. This review focuses on the neuropathology of high acute H2 S exposure, knowledge gaps, and the challenges associated with development of effective neuroprotective therapy to counteract H2 S-induced neurodegeneration.

  2. Acute hydrogen sulfide–induced neuropathology and neurological sequelae: challenges for translational neuroprotective research

    PubMed Central

    Whitley, Elizabeth; Anantharam, Poojya; Kim, Dong‐Suk; Kanthasamy, Arthi

    2016-01-01

    Hydrogen sulfide (H2S), the gas with the odor of rotten eggs, was formally discovered in 1777, over 239 years ago. For many years, it was considered an environmental pollutant and a health concern only in occupational settings. Recently, however, it was discovered that H2S is produced endogenously and plays critical physiological roles as a gasotransmitter. Although at low physiological concentrations it is physiologically beneficial, exposure to high concentrations of H2S is known to cause brain damage, leading to neurodegeneration and long‐term neurological sequelae or death. Neurological sequelae include motor, behavioral, and cognitive deficits, which are incapacitating. Currently, there are concerns about accidental or malicious acute mass civilian exposure to H2S. There is a major unmet need for an ideal neuroprotective treatment, for use in the field, in the event of mass civilian exposure to high H2S concentrations. This review focuses on the neuropathology of high acute H2S exposure, knowledge gaps, and the challenges associated with development of effective neuroprotective therapy to counteract H2S‐induced neurodegeneration. PMID:27442775

  3. Repetitive transcranial magnetic stimulation for clinical applications in neurological and psychiatric disorders: an overview.

    PubMed

    Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Vieira, Renata Teles; Caixeta, Leonardo; Novaes, Felipe; Marinho, Tamires; Almada, Leonardo Ferreira; Silva, Adriana Cardoso; Nardi, Antonio Egidio

    2013-10-01

    Neurological and psychiatric disorders are characterized by several disabling symptoms for which effective, mechanism-based treatments remain elusive. Consequently, more advanced non-invasive therapeutic methods are required. A method that may modulate brain activity and be viable for use in clinical practice is repetitive transcranial magnetic stimulation (rTMS). It is a non-invasive procedure whereby a pulsed magnetic field stimulates electrical activity in the brain. Here, we focus on the basic foundation of rTMS, the main stimulation parametters, the factors that influence individual responses to rTMS and the experimental advances of rTMS that may become a viable clinical application to treat neurological and psychiatric disorders. The findings showed that rTMS can improve some symptoms associated with these conditions and might be useful for promoting cortical plasticity in patients with neurological and psychiatric disorders. However, these changes are transient and it is premature to propose these applications as realistic therapeutic options, even though the rTMS technique has been evidenced as a potential modulator of sensorimotor integration and neuroplasticity. Functional imaging of the region of interest could highlight the capacity of rTMS to bring about plastic changes of the cortical circuitry and hint at future novel clinical interventions. Thus, we recommend that further studies clearly determine the role of rTMS in the treatment of these conditions. Finally, we must remember that however exciting the neurobiological mechanisms might be, the clinical usefulness of rTMS will be determined by its ability to provide patients with neurological and psychiatric disorders with safe, long-lasting and substantial improvements in quality of life.

  4. Repetitive Transcranial Magnetic Stimulation for Clinical Applications in Neurological and Psychiatric Disorders: An Overview

    PubMed Central

    Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Vieira, Renata Teles; Caixeta, Leonardo; Novaes, Felipe; Marinho, Tamires; Almada, Leonardo Ferreira; Silva, Adriana Cardoso; Nardi, Antonio Egidio

    2013-01-01

    Neurological and psychiatric disorders are characterized by several disabling symptoms for which effective, mechanism-based treatments remain elusive. Consequently, more advanced non-invasive therapeutic methods are required. A method that may modulate brain activity and be viable for use in clinical practice is repetitive transcranial magnetic stimulation (rTMS). It is a non-invasive procedure whereby a pulsed magnetic field stimulates electrical activity in the brain. Here, we focus on the basic foundation of rTMS, the main stimulation parametters, the factors that influence individual responses to rTMS and the experimental advances of rTMS that may become a viable clinical application to treat neurological and psychiatric disorders. The findings showed that rTMS can improve some symptoms associated with these conditions and might be useful for promoting cortical plasticity in patients with neurological and psychiatric disorders. However, these changes are transient and it is premature to propose these applications as realistic therapeutic options, even though the rTMS technique has been evidenced as a potential modulator of sensorimotor integration and neuroplasticity. Functional imaging of the region of interest could highlight the capacity of rTMS to bring about plastic changes of the cortical circuitry and hint at future novel clinical interventions. Thus, we recommend that further studies clearly determine the role of rTMS in the treatment of these conditions. Finally, we must remember that however exciting the neurobiological mechanisms might be, the clinical usefulness of rTMS will be determined by its ability to provide patients with neurological and psychiatric disorders with safe, long-lasting and substantial improvements in quality of life. PMID:25610279

  5. Cerebrolysin effects on neurological outcomes and cerebral blood flow in acute ischemic stroke

    PubMed Central

    Amiri-Nikpour, Mohammad Reza; Nazarbaghi, Surena; Ahmadi-Salmasi, Babak; Mokari, Tayebeh; Tahamtan, Urya; Rezaei, Yousef

    2014-01-01

    Background Cerebrolysin, a brain-derived neuropeptide, has been shown to improve the neurological outcomes of stroke, but no study has demonstrated its effect on cerebral blood flow. This study aimed to determine the cerebrolysin impact on the neurological outcomes and cerebral blood flow. Methods In a randomized, double-blinded, placebo-controlled trial, 46 patients who had acute focal ischemic stroke were randomly assigned into two groups to receive intravenously either 30 mL of cerebrolysin diluted in normal saline daily for 10 days (n=23) or normal saline alone (n=23) adjunct to 100 mg of aspirin daily. All patients were examined using the National Institutes of Health Stroke Scale and transcranial Doppler to measure the mean flow velocity and pulsatility index (PI) of their cerebral arteries at baseline as well as on days 30, 60, and 90. Results The patients’ mean age was 60±9.7 years, and 51.2% of patients were male. The National Institutes of Health Stroke Scale was significantly lower in the cerebrolysin group compared with the placebo group on day 60 (median 10, interquartile range 9–11, P=0.008) and day 90 (median 11, interquartile range 10–13.5, P=0.001). The median of PI in the right middle cerebral artery was significantly lower in the cerebrolysin group compared with the placebo group on days 30, 60, and 90 (P<0.05). One patient in the cerebrolysin group and two patients in the placebo group died before day 30 (4.3% versus 8.7%). Conclusion Cerebrolysin can be useful to improve the neurological outcomes and the PI of middle cerebral artery in patients with acute focal ischemic stroke. PMID:25516711

  6. Mouse models in neurological disorders: applications of non-invasive imaging.

    PubMed

    Waerzeggers, Yannic; Monfared, Parisa; Viel, Thomas; Winkeler, Alexandra; Jacobs, Andreas H

    2010-10-01

    Neuroimaging techniques represent powerful tools to assess disease-specific cellular, biochemical and molecular processes non-invasively in vivo. Besides providing precise anatomical localisation and quantification, the most exciting advantage of non-invasive imaging techniques is the opportunity to investigate the spatial and temporal dynamics of disease-specific functional and molecular events longitudinally in intact living organisms, so called molecular imaging (MI). Combining neuroimaging technologies with in vivo models of neurological disorders provides unique opportunities to understand the aetiology and pathophysiology of human neurological disorders. In this way, neuroimaging in mouse models of neurological disorders not only can be used for phenotyping specific diseases and monitoring disease progression but also plays an essential role in the development and evaluation of disease-specific treatment approaches. In this way MI is a key technology in translational research, helping to design improved disease models as well as experimental treatment protocols that may afterwards be implemented into clinical routine. The most widely used imaging modalities in animal models to assess in vivo anatomical, functional and molecular events are positron emission tomography (PET), magnetic resonance imaging (MRI) and optical imaging (OI). Here, we review the application of neuroimaging in mouse models of neurodegeneration (Parkinson's disease, PD, and Alzheimer's disease, AD) and brain cancer (glioma).

  7. 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

  8. Neurological disorders associated with cassava diet: a review of putative etiological mechanisms.

    PubMed

    Adamolekun, Bola

    2011-03-01

    Tropical ataxic neuropathy (TAN) and epidemic spastic paraparesis (konzo) are two neurological disorders associated with the consumption of cassava (Manihot esculenta) in several African countries. TAN is characterized by sensory polyneuropathy, sensory ataxia, bilateral optic atrophy and bilateral sensori-neural deafness. It occurs in elderly individuals subsisting on a monotonous cassava diet with minimal protein supplementation. Konzo is a syndrome of symmetrical spastic paraparesis with a predilection for children and young women and invariably associated with consumption of inadequately processed bitter cassava roots with minimal protein supplementation. Despite numerous epidemiological, clinical and biochemical studies aimed at elucidating the etiological mechanisms of these disorders, their etiologies remain unknown, and there is no known treatment. The diseases continue to be prevalent in endemic areas, causing significant disability and increased mortality. A fresh appraisal of the putative etiologic mechanisms proposed for these intriguing and enigmatic syndromes is presented in this paper. Evidences against a causal role for cyanide intoxication are discussed, and evidences implicating thiamine deficiency as a unifying etiological mechanism for these neurological syndromes are presented. It is concluded that urgent research is needed to evaluate thiamine status and implement a therapeutic trial of thiamine in these debilitating neurological disorders.

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

    PubMed Central

    Venkataraman, Archana; Kubicki, Marek; Golland, Polina

    2014-01-01

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

  10. Semantic Pattern Analysis for Verbal Fluency Based Assessment of Neurological Disorders

    SciTech Connect

    Sukumar, Sreenivas R; Ainsworth, Keela C; Brown, Tyler C

    2014-01-01

    In this paper, we present preliminary results of semantic pattern analysis of verbal fluency tests used for assessing cognitive psychological and neuropsychological disorders. We posit that recent advances in semantic reasoning and artificial intelligence can be combined to create a standardized computer-aided diagnosis tool to automatically evaluate and interpret verbal fluency tests. Towards that goal, we derive novel semantic similarity (phonetic, phonemic and conceptual) metrics and present the predictive capability of these metrics on a de-identified dataset of participants with and without neurological disorders.

  11. Involuntary emotional expression disorder - new/old disease in psychiatry and neurology.

    PubMed

    Presecki, Paola; Mimica, Ninoslav

    2007-09-01

    Involuntary emotional expression disorder (IEED) is underrecognized by clinicians, misdiagnosed as depression or bipolar disorder and undertreated, because clinicians are unfamiliar with the disorder. An important clinical consideration for IEED is that of distinguishing mood from affect. IEED describes a syndrome of relatively stereotypical episodes of uncontrollable crying and/or laughing, resulting from lesions of multiple types, in multiple brain regions, without an apparent stimulus to trigger such responses. This syndrome is common among a number of neurological diseases like patients with a stroke or traumatic brain injury (TBI), patients with amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), as well as dementias such as Alzheimer;s disease (AD), and motor disorders such as Parkinson;s disease (PD). The neuropathological cause and neurochemistry of the disorder remains unclear. There is general agreement that IEED is the result of an injury to the neurological pathways that control the expression of emotions. Adequate treatment can reduce the frequency and improve the quality of life of patients and caregivers.

  12. Chronic hepatitis C virus infection and neurological and psychiatric disorders: An overview

    PubMed Central

    Adinolfi, Luigi Elio; Nevola, Riccardo; Lus, Giacomo; Restivo, Luciano; Guerrera, Barbara; Romano, Ciro; Zampino, Rosa; Rinaldi, Luca; Sellitto, Ausilia; Giordano, Mauro; Marrone, Aldo

    2015-01-01

    Hepatitis C virus (HCV) infection is considered a systemic disease because of involvement of other organs and tissues concomitantly with liver disease. Among the extrahepatic manifestations, neuropsychiatric disorders have been reported in up to 50% of chronic HCV infected patients. Both the central and peripheral nervous system may be involved with a wide variety of clinical manifestations. Main HCV-associated neurological conditions include cerebrovascular events, encephalopathy, myelitis, encephalomyelitis, and cognitive impairment, whereas “brain fog”, depression, anxiety, and fatigue are at the top of the list of psychiatric disorders. Moreover, HCV infection is known to cause both motor and sensory peripheral neuropathy in the context of mixed cryoglobulinemia, and has also been recently recognized as an independent risk factor for stroke. These extrahepatic manifestations are independent of severity of the underlying chronic liver disease and hepatic encephalopathy. The brain is a suitable site for HCV replication, where the virus may directly exert neurotoxicity; other mechanisms proposed to explain the pathogenesis of neuropsychiatric disorders in chronic HCV infection include derangement of metabolic pathways of infected cells, alterations in neurotransmitter circuits, autoimmune disorders, and cerebral or systemic inflammation. A pathogenic role for HCV is also suggested by improvement of neurological and psychiatric symptoms in patients achieving a sustained virologic response following interferon treatment; however, further ad hoc trials are needed to fully assess the impact of HCV infection and specific antiviral treatments on associated neuropsychiatric disorders. PMID:25741133

  13. Urine specific gravity as a predictor of early neurological deterioration in acute ischemic stroke.

    PubMed

    Lin, L C; Fann, W C; Chou, M H; Chen, H W; Su, Y C; Chen, J C

    2011-07-01

    We previously found that a blood urea nitrogen/creatinine (BUN/Cr) ratio>15 is an independent predictor of early neurological deterioration after acute ischemic stroke, which suggests that dehydration may be a cause of early deterioration. The aim of this study was to determine whether urine specific gravity, which is another indicator of hydration status and one that is more easily obtained, is also an independent predictor of early deterioration or stroke-in-evolution (SIE). Demographic and clinical data were recorded at admission from patients with acute ischemic stroke who were prospectively enrolled from October 2007 to June 2010. We compared patients with and without stroke-in-evolution (based on an increase of 3 points or more points on the National Institutes of Health Stroke Scale within 3 days). Univariate and multivariate statistical analyses were carried out. A total of 317 patients (43 SIE and 274 non-SIE) were enrolled; the first 196 patients comprised the cohort of our previous study. The only two independent predictors of early deterioration or SIE were BUN/Cr>15 and urine specific gravity>1.010. After adjusting for age and gender, patients with a urine specific gravity>1.010 were 2.78 times more likely to develop SIE (95% CI=1.11-6.96; P=0.030). Urine specific gravity may be useful as an early predictor of early deterioration in patients with acute ischemic stroke. Patients with urine specific gravity ≤ 1.010 therefore may have a reduced likelihood of early neurological deterioration.

  14. Removal kinetics of antibodies against glutamic acid decarboxylase by various plasmapheresis modalities in the treatment of neurological disorders.

    PubMed

    Ohkubo, Atsushi; Okado, Tomokazu; Kurashima, Naoki; Maeda, Takuma; Miyamoto, Satoko; Nakamura, Ayako; Seshima, Hiroshi; Iimori, Soichiro; Sohara, Eisei; Uchida, Shinichi; Rai, Tatemitsu

    2014-06-01

    Plasmapheresis is one of the acute treatment modalities for neurological disorders associated with antibodies against glutamic acid decarboxylase (anti-GAD). However, there is little information about the removal kinetics of anti-GAD by various plasmapheresis modalities. Here, we investigated the removal rate of anti-GAD and fibrinogen (Fib) by immunoadsorption (IA), plasma exchange using a conventional plasma separator (OP-PE), and plasma exchange using a high cut-off selective membrane plasma separator (EC-PE) in two cases of anti-GAD-associated neurological diseases. In case 1, IA and OP-PE were used, and the percent reductions were as follows: anti-GAD: 38.2% and 69.1% and Fib: 67.7% and 68.2%, respectively. In case 2, OP-PE and EC-PE were used, and the percent reductions were as follows: anti-GAD: 65.8% and 48.5% and Fib: 68.5% and 19.8%, respectively. OP-PE could remove anti-GAD more efficiently than IA. Further, EC-PE could maintain coagulation factors such as Fib better than IA and OP-PE. It is important to select the appropriate plasmapheresis modality on the basis of the removal kinetics.

  15. Bile Acid Signaling Is Involved in the Neurological Decline in a Murine Model of Acute Liver Failure

    PubMed Central

    McMillin, Matthew; Frampton, Gabriel; Quinn, Matthew; Ashfaq, Samir; de los Santos, Mario; Grant, Stephanie; DeMorrow, Sharon

    2017-01-01

    Hepatic encephalopathy is a serious neurological complication of liver failure. Serum bile acids are elevated after liver damage and may disrupt the blood-brain barrier and enter the brain. Our aim was to assess the role of serum bile acids in the neurological complications after acute liver failure. C57Bl/6 or cytochrome p450 7A1 knockout (Cyp7A1−/−) mice were fed a control, cholestyramine-containing, or bile acid–containing diet before azoxymethane (AOM)-induced acute liver failure. In parallel, mice were given an intracerebroventricular infusion of farnesoid X receptor (FXR) Vivo-morpholino before AOM injection. Liver damage, neurological decline, and molecular analyses of bile acid signaling were performed. Total bile acid levels were increased in the cortex of AOM-treated mice. Reducing serum bile acids via cholestyramine feeding or using Cyp7A1−/− mice reduced bile acid levels and delayed AOM-induced neurological decline, whereas cholic acid or deoxycholic acid feeding worsened AOM-induced neurological decline. The expression of bile acid signaling machinery apical sodium-dependent bile acid transporter, FXR, and small heterodimer partner increased in the frontal cortex, and blocking FXR signaling delayed AOM-induced neurological decline. In conclusion, circulating bile acids may play a pathological role during hepatic encephalopathy, although precisely how they dysregulate normal brain function is unknown. Strategies to minimize serum bile acid concentrations may reduce the severity of neurological complications associated with liver failure. PMID:26683664

  16. Increased Blood Pressure Variability Is Associated with Worse Neurologic Outcome in Acute Anterior Circulation Ischemic Stroke

    PubMed Central

    Bennett, Alicia; Stoddard, Gregory J.; Smith, Gordon; Wang, Haimei; Wold, Jana; Chung, Lee; Tirschwell, David L.; Majersik, Jennifer J.

    2016-01-01

    Background. Although research suggests that blood pressure variability (BPV) is detrimental in the weeks to months after acute ischemic stroke, it has not been adequately studied in the acute setting. Methods. We reviewed acute ischemic stroke patients from 2007 to 2014 with anterior circulation stroke. Mean blood pressure and three BPV indices (standard deviation, coefficient of variation, and successive variation) for the intervals 0–24, 0–72, and 0–120 hours after admission were correlated with follow-up modified Rankin Scale (mRS) in ordinal logistic regression models. The correlation between BPV and mRS was further analyzed by terciles of clinically informative stratifications. Results. Two hundred and fifteen patients met inclusion criteria. At all time intervals, increased systolic BPV was associated with higher mRS, but the relationship was not significant for diastolic BPV or mean blood pressure. This association was strongest in patients with proximal stroke parent artery vessel occlusion and lower mean blood pressure. Conclusion. Increased early systolic BPV is associated with worse neurologic outcome after ischemic stroke. This association is strongest in patients with lower mean blood pressure and proximal vessel occlusion, often despite endovascular or thrombolytic therapy. This hypothesis-generating dataset suggests potential benefit for interventions aimed at reducing BPV in this patient population. PMID:27974991

  17. [Somatoform disorders in neurology visits: history and circumstances: retrospective study of 124 cases].

    PubMed

    Dubas, F; Thomas-Antérion, C

    2012-12-01

    We report 124 cases of somatoform disorders, considering psychogenic disorders at the same level as neurological disorders. We noted any psychic, somatic or social condition (history taking) and facilitating circumstances. The patients were aged 16 to 84 years old; 71.7% were women. We observed pain (35.4%), psychogenic headache (25%), sensorimotor loss (27.4%), gait and psychogenic tremor (17.7%), cognitive disorders (11.8%), ocular symptoms (7.2%), and urogenital symptoms (2.4%). Delay to consultation ranged from a few days to 20 years. Psychiatric comorbidity was noted in 30.6% of the cases. In 55.6% of 124 cases, we observed a psychological background. It was a childhood trauma in 15.3% of these cases. In one-third of the 124 situations, we noted an underlying somatic or social condition. Facilitation conditions were frequently mixed. Somatic and/or psychological conditions were noted in one-third of the 124 cases and social conditions in half of them. The neurologist is faced with the challenge of naming the symptom (most often labelled a functional disorder) and of making the decision to stop or limit investigations. Visits by patients with psychogenic disorders make up a significant percentage of neurology speciality appointments. The neurologist should not limit the consultation to differentiating "real" symptoms from psychogenic somatoform disorders, but should also propose a straightforward compassionate approach for effective therapeutic care. By carefully listening to the patient's dialogue, the neurologist can help the patient give meaning to the symptoms, and progress towards improved well-being.

  18. Zinc in gut-brain interaction in autism and neurological disorders.

    PubMed

    Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M

    2015-01-01

    A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life.

  19. A decade from discovery to therapy: Lingo-1, the dark horse in neurological and psychiatric disorders.

    PubMed

    Andrews, Jessica L; Fernandez-Enright, Francesca

    2015-09-01

    Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) is a potent negative regulator of neuron and oligodendrocyte survival, neurite extension, axon regeneration, oligodendrocyte differentiation, axonal myelination and functional recovery; all processes highly implicated in numerous brain-related functions. Although playing a major role in developmental brain functions, the potential application of Lingo-1 as a therapeutic target for the treatment of neurological disorders has so far been under-estimated. A number of preclinical studies have shown that various methods of antagonizing Lingo-1 results in neuronal and oligodendroglial survival, axonal growth and remyelination; however to date literature has only detailed applications of Lingo-1 targeted therapeutics with a focus primarily on myelination disorders such as multiple sclerosis and spinal cord injury; omitting important information regarding Lingo-1 signaling co-factors. Here, we provide for the first time a complete and thorough review of the implications of Lingo-1 signaling in a wide range of neurological and psychiatric disorders, and critically examine its potential as a novel therapeutic target for these disorders.

  20. Zinc in Gut-Brain Interaction in Autism and Neurological Disorders

    PubMed Central

    Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M.

    2015-01-01

    A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life. PMID:25878905

  1. The prospect of molecular therapy for Angelman syndrome and other monogenic neurologic disorders

    PubMed Central

    2014-01-01

    Background Angelman syndrome is a monogenic neurologic disorder that affects 1 in 15,000 children, and is characterized by ataxia, intellectual disability, speech impairment, sleep disorders, and seizures. The disorder is caused by loss of central nervous system expression of UBE3A, a gene encoding a ubiquitin ligase. Current treatments focus on the management of symptoms, as there have not been therapies to treat the underlying molecular cause of the disease. However, this outlook is evolving with advances in molecular therapies, including artificial transcription factors a class of engineered DNA-binding proteins that have the potential to target a specific site in the genome. Results Here we review the recent progress and prospect of targeted gene expression therapies. Three main issues that must be addressed to advance toward human clinical trials are specificity, toxicity, and delivery. Conclusions Artificial transcription factors have the potential to address these concerns on a level that meets and in some cases exceeds current small molecule therapies. We examine the possibilities of such approaches in the context of Angelman syndrome, as a template for other single-gene, neurologic disorders. PMID:24946931

  2. Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase

    PubMed Central

    Puppala, Anupama K.; French, Rachel L.; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Simonović, Miljan

    2016-01-01

    Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS–Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*–induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders. PMID:27576344

  3. Mouse models of neurological disorders--a comparison of heritable and acquired traits.

    PubMed

    Harper, Alex

    2010-10-01

    Human neurological disorders include a wide range of illnesses which have a disproportionately high prevalence in the increasingly populous geriatric community. Any research effort directed at discovering the aetiology of neurological disease is greatly enhanced with in vivo models of the disease of interest. Scientific research incorporating the use of mice has advanced rapidly in the last three decades. Relatively simple to breed, maintain and train, mice have many advantages over other species for use in research. More than a century of selective breeding has provided investigators with a rich gene pool and sub-strain diversity from which to choose for their research. Thus the dramatic increase in genetic screening and gene engineering that has occurred in research in recent decades has enabled the generation of a multitude of mouse models. This review discusses the relative utility of mouse models in which a heritable or non-heritable (acquired) manipulation has been used to model a specified trait of a human neurological disorder. The techniques used in deriving useful genetic alterations or modifications and in generating acquired mouse models are outlined with examples of each provided.

  4. Exploring the role of BCHE in the onset of Diabetes, Obesity and Neurological Disorders.

    PubMed

    Rao, Allam Appa; Jyothsna, Gundlapally; Shalini, Pulipati; Kumar, Amit; Bhattacharya, Anupam; Kashyap, Amita

    2012-01-01

    Diabetes, Obesity and Neurological disturbances, most often show co-occurrence. There has been an extensive research in this domain, but the exact mechanism underlying the co-occurrence of the three conditions is still an enigma. The current paper is an approach to establish the role of Butyryl cholinesterase (BCHE) in Diabetes, Obesity and Neurological disorders by performing a comparative analysis with Neuroligin (NLGN2) a protein belonging to the same family. BCHE has its role in glucose regulation, Lipid metabolism and nerve signaling. Emphasis is laid on BCHE's diverse functions whose impediment affects the above mentioned metabolic pathways. Insilco techniques were employed to analyze the sequence, structural and functional similarities of the two proteins. A point mutation is focused which is common to both BCHE and Neuroligin. The mutation occurs at the homologous position in both the proteins making them deficient. This affects the three metabolic pathways leading to the respective disorders. The work describes the pathway that describes the role of BCHE in the onset of obesity mediated diabetes. The pathway further explains the association between Diabetes, Obesity and neurological disturbances.

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

    PubMed

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

    2009-01-01

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

  6. Anti-cardiolipin antibodies in neurological disorders: cross-reaction with anti-single stranded DNA activity.

    PubMed Central

    Colaço, C B; Scadding, G K; Lockhart, S

    1987-01-01

    Antiphospholipid (PL) antibodies have been detected in sera from patients with chronic neurological diseases associated with disorders of immunity. In an isotype specific radioimmunoassay for anti-cardiolipin (CL) antibodies, we found IgM anti-CL (greater than 2 s.d. above mean of controls) in 17/25 (68%) patients with myasthenia gravis (MG), 8/25 (32%) with the Lambert-Eaton myasthenic syndrome (LEMS), 5/17 (29%) with multiple sclerosis and 3/11 (27%) cases of migraine. IgG anti-CL was only found in low titres in sera from 10 patients with MG and three with LEMS. Significant anti-CL activity could not be detected in sera from nine patients with acute Guillain-Barré Syndrome (GBS), 12 chronic cases of epilepsy, 8/9 with oat cell carcinoma and 9/10 with acute stroke. Further tests on 39 sera with the highest anti-CL activity, from all of the above disease groups, showed a significant correlation between IgM anti-CL and IgM anti-ss DNA activities. In a series of competitive inhibition assays six sera from patients with MG were shown to have a proportion of both specific and cross-reactive IgM anti-CL and IgM anti-ss DNA antibodies. Anti-phospholipid antibodies occur in certain neurological diseases, at lower titres than seen in SLE, yet their cross-reactive binding to ss DNA suggests similar antibacterial origins as have been proposed for lupus auto-antibodies. In the absence of overt infection they might reflect a breakdown of tolerance for non-organ specific membrane antigens in diseases with predominantly organ specific membrane bound putative autoimmunogens. PMID:3498571

  7. Beta-blockers in the treatment of neurological and psychiatric disorders.

    PubMed

    Peet, M; Yates, R A

    1981-09-01

    Beta-blockers, originally introduced into clinical practice for the treatment of cardiovascular disorders, are being increasingly advocated in the treatment of diverse neurological and psychiatric conditions. Thus, propranolol and certain other beta-blockers have been shown to be effective, and may be the drugs of choice, in the treatment of benign essential tremor and the prevention of recurrent migraine attacks. These drugs also have a useful role to play in the treatment of anxiety and alcohol withdrawal states, although beta-blockers have not come into general use in these conditions. The action of propranolol and related drugs in these neurological and psychiatric conditions is generally considered to be mediated by blockade of peripheral beta-adrenergic receptors, although other effects, either central or peripheral, may also be involved. The use of beta-blockers in the treatment of psychosis remains controversial. Current evidence does not support the use of propranolol in schizophrenia, but further studies in mania are warranted.

  8. Hepatic encephalopathy with reversible focal neurologic signs resembling acute stroke: case report.

    PubMed

    Yamamoto, Yoshiya; Nishiyama, Yasuhiro; Katsura, Ken-Ichiro; Yamazaki, Mineo; Katayama, Yasuo

    2011-01-01

    A 64-year-old female with a history of primary biliary cirrhosis and esophageal varices starting at age 39 was brought to our Stroke Care Unit by ambulance with right-side weakness and speech difficulty. Physical examination revealed right hemiparesis (including the face), sensory disturbances, pathological reflexes, and slightly decreased consciousness, with a Glasgow Coma Scale rating of E3V4M6. Flapping tremors and speech disturbance, as well as anarithmia, construction apraxia, and ideomotor apraxia, were noted, and her National Institutes of Health Stroke Scale score was 13. Initially, the patient was diagnosed with acute stroke and treated accordingly; however, subsequent findings from clinical images and electroencephalography led to a diagnosis of focal neurologic signs due to hepatic encephalopathy (HE). The patient had significantly reduced cerebral blood flow in the left side of the brain, probably due to microsurgical repair of an aneurysm done 2 years earlier. HE with exaggerated chronic liver damage might have made the previously silent ischemia clinically apparent. This interpretation is supported by the fact that the patient's neurologic deficits resolved once HE was adequately controlled. This case illustrates the need for careful assessment of background pathophysiology when diagnosing patients with stroke-like symptoms.

  9. Aging potentiates the acute and chronic neurological symptoms of pyrithiamine-induced thiamine deficiency in the rodent.

    PubMed

    Pitkin, S R; Savage, L M

    2001-03-15

    The present study aimed to assess the role of advanced age in the development and manifestation of thiamine deficiency using an animal model of Wernicke-Korsakoff syndrome (WKS). Interactions between pyrithiamine-induced thiamine deficiency (PTD) and age were examined relative to working memory impairment and neuropathology in Fischer 344 rats. Young (2-3 months) and aged (22-23 months) F344 rats were assigned to one of two treatment conditions: PTD or pair-fed control (PF). Rats in the former group were further divided into three groups according to duration of PTD treatment. Working memory was assessed with an operant matching-to-position (MTP) task; after testing, animals were sacrificed and both gross and immunocytochemical measures of brain pathology were obtained. Aged rats exhibited acute neurological disturbances during the PTD treatment regime earlier than did young rats, and also developed more extensive neuropathology with a shorter duration of PTD. Aged rats displayed increased brain shrinkage (smaller frontal cortical and callosal thickness) as well as enhanced astrocytic activity in the thalamus and a decrease in ChAT-positive cell numbers in the medial septum; the latter two measures of neuropathology were potentiated by PTD. In both young and aged rats, and to a greater degree in the latter group, PTD reduced thalamic volume. Behaviorally, aged rats displayed impaired choice accuracy on the delayed MTP task. Regardless of age, rats with lesions centered on the internal medullary lamina of the thalamus also displayed impaired choice accuracy. Moreover, increased PTD treatment duration led to increased response times on the delayed MTP task. These results suggest that aging does indeed potentiate the neuropathology associated with experimental thiamine deficiency, supporting an age coupling hypothesis of alcohol-related neurological disorders.

  10. Acute stroke care in a neurologically underserved state: lessons learned from the Iowa Stroke Survey.

    PubMed

    Albright, Karen C; Schott, Todd C; Boland, Debbie F; George, Leslie; Boland, Kevin P; Wohlford-Wessels, Mary Pat; Finnerty, Edward P; Jacoby, Michael R K

    2009-01-01

    Prior studies have suggested that stroke care is more fragmented in rural or neurologically underserved areas. The purpose of this study was to determine the availability of diagnostic and treatment services for acute stroke care in Iowa and to identify factors influencing care. Each of the 118 facilities in Iowa with emergency departments was surveyed by telephone. This survey consisted of 10 questions, focusing on the existence of pre-hospital and emergency room acute stroke protocols and the availability of essential personnel and diagnostic and treatment modalities essential for acute stroke care. Of the 118 hospitals with emergency departments, 109 (92.4%) had CT available. Within the subset having CT capabilities, 89.9% (98/109) had intravenous tissue plasminogen activator (IV t-PA) available. Of those facilities with both CT and IV t-PA, 46% (45/98) had around-the-clock in-house physician coverage. Further, 31% (14/45) of sites with CT, t-PA, and an in-house physician had a radiology technician on site. Only 12% (14/118) of centers could offer all essential components. Despite 88% of Iowa hospitals not providing all of these components, only 31% of these hospitals reported protocols for stabilization and immediate transfer of acute stroke patients. These findings indicate that the development of a stroke system is still in its infancy in Iowa. Collaborative efforts are needed to address barriers in rural Iowa and to assist facilities in providing the best possible care. Creativity will be paramount in establishing a functional statewide system to ensure optimum care for all Iowans.

  11. Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders.

    PubMed

    Mantegazza, Massimo; Curia, Giulia; Biagini, Giuseppe; Ragsdale, David S; Avoli, Massimo

    2010-04-01

    Voltage-gated sodium channels (VGSCs) are key mediators of intrinsic neuronal and muscle excitability. Abnormal VGSC activity is central to the pathophysiology of epileptic seizures, and many of the most widely used antiepileptic drugs, including phenytoin, carbamazepine, and lamotrigine, are inhibitors of VGSC function. These antiepileptic drugs might also be efficacious in the treatment of other nervous system disorders, such as migraine, multiple sclerosis, neurodegenerative diseases, and neuropathic pain. In this Review, we summarise the structure and function of VGSCs and their involvement in the pathophysiology of several neurological disorders. We also describe the biophysical and molecular bases for the mechanisms of action of antiepileptic VGSC blockers and discuss the efficacy of these drugs in the treatment of epileptic and non-epileptic disorders. Overall, clinical and experimental data indicate that these drugs are efficacious for a range of diseases, and that the development of drugs with enhanced selectivity for specific VGSC isoforms might be an effective and novel approach for the treatment of several neurological diseases.

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

    PubMed

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

    2017-03-01

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

  13. DISC1 and Huntington's Disease – Overlapping Pathways of Vulnerability to Neurological Disorder?

    PubMed Central

    Boxall, Ruth; Porteous, David J.; Thomson, Pippa A.

    2011-01-01

    We re-annotated the interacting partners of the neuronal scaffold protein DISC1 using a knowledge-based approach that incorporated recent protein interaction data and published literature to. This revealed two highly connected networks. These networks feature cellular function and maintenance, and cell signaling. Of potentially greatest interest was the novel finding of a high degree of connectivity between the DISC1 scaffold protein, linked to psychiatric illness, and huntingtin, the protein which is mutated in Huntington's disease. The potential link between DISC1, huntingtin and their interacting partners may open new areas of research into the effects of pathway dysregulation in severe neurological disorders. PMID:21298101

  14. National Institute of Neurological Disorders and Stroke support for brain-machine interface technology.

    PubMed

    Pancrazio, Joseph J

    2009-07-01

    Brain-machine interfaces (BMIs) offer the promise of restoring communication, enabling control of assistive devices, and allowing volitional control of extremities in paralyzed individuals. Working in multidisciplinary teams, neurosurgeons can play an invaluable role in the design, development, and demonstration of novel BMI technology. At the National Institutes of Health, the National Institute of Neurological Disorders and Stroke has a long history of supporting neural engineering and prosthetics efforts including BMI, and these research opportunities continue today. The author provides a brief overview of the opportunities and programs currently available to support BMI projects.

  15. The use of pluripotent stem cell for personalized cell therapies against neurological disorders.

    PubMed

    Ha, Hye-Yeong; Jang, Si-Hyong; Jung, Ji-Won

    2011-01-01

    Although there are a number of weaknesses for clinical use, pluripotent stem cells are valuable sources for patient-specific cell therapies against various diseases. Backed-up by a huge number of basic researches, neuronal differentiation mechanism is well established and pluripotent stem cell therapies against neurological disorders are getting closer to clinical application. However, there are increasing needs for standardization of the sourcing pluripotent stem cells by establishing stem cell registries and banking. Global harmonization will accelerate practical use of personalized therapies using pluripotent stem cells.

  16. Direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders

    PubMed Central

    Hou, Shaoping; Lu, Paul

    2016-01-01

    Direct reprogramming of somatic cells into neurons or neural stem cells is one of the most important frontier fields in current neuroscience research. Without undergoing the pluripotency stage, induced neurons or induced neural stem cells are a safer and timelier manner resource in comparison to those derived from induced pluripotent stem cells. In this prospective, we review the recent advances in generation of induced neurons and induced neural stem cells in vitro and in vivo and their potential treatments of neurological disorders. PMID:26981072

  17. Efficient and versatile CRISPR engineering of human neurons in culture to model neurological disorders.

    PubMed

    Shah, Ruth R; Cholewa-Waclaw, Justyna; Davies, Faith C J; Paton, Katie M; Chaligne, Ronan; Heard, Edith; Abbott, Catherine M; Bird, Adrian P

    2016-11-15

    The recent identification of multiple new genetic causes of neurological disorders highlights the need for model systems that give experimental access to the underlying biology. In particular, the ability to couple disease-causing mutations with human neuronal differentiation systems would be beneficial. Gene targeting is a well-known approach for dissecting gene function, but low rates of homologous recombination in somatic cells (including neuronal cells) have traditionally impeded the development of robust cellular models of neurological disorders. Recently, however, CRISPR/Cas9 gene editing technologies have expanded the number of systems within which gene targeting is possible. Here we adopt as a model system LUHMES cells, a commercially available diploid human female mesencephalic cell line that differentiates into homogeneous mature neurons in 1-2 weeks. We describe optimised methods for transfection and selection of neuronal progenitor cells carrying targeted genomic alterations using CRISPR/Cas9 technology. By targeting the endogenous X-linked MECP2 locus, we introduced four independent missense mutations that cause the autism spectrum disorder Rett syndrome and observed the desired genetic structure in 3-26% of selected clones, including gene targeting of the inactive X chromosome. Similar efficiencies were achieved by introducing neurodevelopmental disorder-causing mutations at the autosomal EEF1A2 locus on chromosome 20. Our results indicate that efficiency of genetic "knock-in" is determined by the location of the mutation within the donor DNA molecule. Furthermore, we successfully introduced an mCherry tag at the MECP2 locus to yield a fusion protein, demonstrating that larger insertions are also straightforward in this system. We suggest that our optimised methods for altering the genome of LUHMES cells make them an attractive model for the study of neurogenetic disorders.

  18. Synaptopathies: synaptic dysfunction in neurological disorders - A review from students to students.

    PubMed

    Lepeta, Katarzyna; Lourenco, Mychael V; Schweitzer, Barbara C; Martino Adami, Pamela V; Banerjee, Priyanjalee; Catuara-Solarz, Silvina; de La Fuente Revenga, Mario; Guillem, Alain Marc; Haidar, Mouna; Ijomone, Omamuyovwi M; Nadorp, Bettina; Qi, Lin; Perera, Nirma D; Refsgaard, Louise K; Reid, Kimberley M; Sabbar, Mariam; Sahoo, Arghyadip; Schaefer, Natascha; Sheean, Rebecca K; Suska, Anna; Verma, Rajkumar; Vicidomini, Cinzia; Wright, Dean; Zhang, Xing-Ding; Seidenbecher, Constanze

    2016-09-01

    Synapses are essential components of neurons and allow information to travel coordinately throughout the nervous system to adjust behavior to environmental stimuli and to control body functions, memories, and emotions. Thus, optimal synaptic communication is required for proper brain physiology, and slight perturbations of synapse function can lead to brain disorders. In fact, increasing evidence has demonstrated the relevance of synapse dysfunction as a major determinant of many neurological diseases. This notion has led to the concept of synaptopathies as brain diseases with synapse defects as shared pathogenic features. In this review, which was initiated at the 13th International Society for Neurochemistry Advanced School, we discuss basic concepts of synapse structure and function, and provide a critical view of how aberrant synapse physiology may contribute to neurodevelopmental disorders (autism, Down syndrome, startle disease, and epilepsy) as well as neurodegenerative disorders (Alzheimer and Parkinson disease). We finally discuss the appropriateness and potential implications of gathering synapse diseases under a single term. Understanding common causes and intrinsic differences in disease-associated synaptic dysfunction could offer novel clues toward synapse-based therapeutic intervention for neurological and neuropsychiatric disorders. In this Review, which was initiated at the 13th International Society for Neurochemistry (ISN) Advanced School, we discuss basic concepts of synapse structure and function, and provide a critical view of how aberrant synapse physiology may contribute to neurodevelopmental (autism, Down syndrome, startle disease, and epilepsy) as well as neurodegenerative disorders (Alzheimer's and Parkinson's diseases), gathered together under the term of synaptopathies. Read the Editorial Highlight for this article on page 783.

  19. Efficient and versatile CRISPR engineering of human neurons in culture to model neurological disorders

    PubMed Central

    2016-01-01

    The recent identification of multiple new genetic causes of neurological disorders highlights the need for model systems that give experimental access to the underlying biology. In particular, the ability to couple disease-causing mutations with human neuronal differentiation systems would be beneficial. Gene targeting is a well-known approach for dissecting gene function, but low rates of homologous recombination in somatic cells (including neuronal cells) have traditionally impeded the development of robust cellular models of neurological disorders. Recently, however, CRISPR/Cas9 gene editing technologies have expanded the number of systems within which gene targeting is possible. Here we adopt as a model system LUHMES cells, a commercially available diploid human female mesencephalic cell line that differentiates into homogeneous mature neurons in 1-2 weeks. We describe optimised methods for transfection and selection of neuronal progenitor cells carrying targeted genomic alterations using CRISPR/Cas9 technology. By targeting the endogenous X-linked MECP2 locus, we introduced four independent missense mutations that cause the autism spectrum disorder Rett syndrome and observed the desired genetic structure in 3-26% of selected clones, including gene targeting of the inactive X chromosome. Similar efficiencies were achieved by introducing neurodevelopmental disorder-causing mutations at the autosomal EEF1A2 locus on chromosome 20. Our results indicate that efficiency of genetic “knock-in” is determined by the location of the mutation within the donor DNA molecule. Furthermore, we successfully introduced an mCherry tag at the MECP2 locus to yield a fusion protein, demonstrating that larger insertions are also straightforward in this system. We suggest that our optimised methods for altering the genome of LUHMES cells make them an attractive model for the study of neurogenetic disorders. PMID:27976757

  20. Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders

    PubMed Central

    Koppel, Barbara S.; Brust, John C.M.; Fife, Terry; Bronstein, Jeff; Youssof, Sarah; Gronseth, Gary; Gloss, David

    2014-01-01

    Objective: To determine the efficacy of medical marijuana in several neurologic conditions. Methods: We performed a systematic review of medical marijuana (1948–November 2013) to address treatment of symptoms of multiple sclerosis (MS), epilepsy, and movement disorders. We graded the studies according to the American Academy of Neurology classification scheme for therapeutic articles. Results: Thirty-four studies met inclusion criteria; 8 were rated as Class I. Conclusions: The following were studied in patients with MS: (1) Spasticity: oral cannabis extract (OCE) is effective, and nabiximols and tetrahydrocannabinol (THC) are probably effective, for reducing patient-centered measures; it is possible both OCE and THC are effective for reducing both patient-centered and objective measures at 1 year. (2) Central pain or painful spasms (including spasticity-related pain, excluding neuropathic pain): OCE is effective; THC and nabiximols are probably effective. (3) Urinary dysfunction: nabiximols is probably effective for reducing bladder voids/day; THC and OCE are probably ineffective for reducing bladder complaints. (4) Tremor: THC and OCE are probably ineffective; nabiximols is possibly ineffective. (5) Other neurologic conditions: OCE is probably ineffective for treating levodopa-induced dyskinesias in patients with Parkinson disease. Oral cannabinoids are of unknown efficacy in non–chorea-related symptoms of Huntington disease, Tourette syndrome, cervical dystonia, and epilepsy. The risks and benefits of medical marijuana should be weighed carefully. Risk of serious adverse psychopathologic effects was nearly 1%. Comparative effectiveness of medical marijuana vs other therapies is unknown for these indications. PMID:24778283

  1. Soft Neurological Signs and Cognitive Function in Obsessive-compulsive Disorder Patients

    PubMed Central

    Dhuri, Chetali Vijay; Parkar, Shubhangi R.

    2016-01-01

    Objective: Modern research on obsessive-compulsive disorder (OCD) indicates that the primary cause of OCD, which was earlier explained only on basis of psychoanalytical theories, is biological. Our study attempts to investigate the neurobiological signs in form of soft neurological signs and cognitive function in OCD. Methods: A cross sectional study was conducted at psychiatric facility of Seth G.S. Medical College and KEM Hospital. Materials and Method: 50 OCD patients and age- and education-matched controls were selected for the study. Established instruments were used to assess the neurological soft signs (NSS) and the cognitive deficits. Results: OCD patients had significant more NSS in tests for motor coordination, sensory integration, complex motor tasks, hard signs, and right/left and spatial orientation. Cognitive deficits in the domains of visuospatial ability, executive function, attention, and working memory were significantly more in OCD patients compared to controls. Conclusion: Our study highlights the role of biological factors in form of soft neurological signs and cognitive dysfunction in the development of the OCD. PMID:27570338

  2. Learning Disorders as a School Health Problem—Neurological and Psychiatric Aspects

    PubMed Central

    Whitsell, Leon J.

    1969-01-01

    Broadened concepts of intellectual functions have shown that many varieties of mental subnormality may be preventable or subject to improvement with proper treatment. Many types of neurologic dysfunction are accompanied by learning disorders based on specific intellectual deficits. A more refined delineation of the higher cerebral functions of each child with a learning disorder provides the basis for improved specific remedial educational techniques. Such detailed assessment of higher functions of the nervous system can be greatly enhanced by the appropriate special evaluations carried out by well trained psychologists, speech pathologists and educational consultants, working in cooperation with physicians. The varieties of adjustment problems of children and emotional impact of a learning disorder should be recognized as early as possible and treated appropriately. Motor and perceptual-motor therapies may have limited value in some cases but may be harmful if indiscriminately applied. Psychotropic drugs have a relatively limited place in the management of learning disorders but may be immensely valuable in some cases by helping to control specific behavior problems which interfere with learning processes. Physicians have a major responsibility to provide help and leadership in dealing with learning disorders. PMID:4902291

  3. Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases.

    PubMed

    Zeliger, Harold I

    2013-09-01

    Many studies have associated environmental exposure to chemicals with neurological impairments (NIs) including neuropathies, cognitive, motor and sensory impairments; neurodevelopmental disorders (NDDs) including autism and attention deficit hyperactivity disorder (ADHD); neurodegenerative diseases (NDGs) including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS). The environmental chemicals shown to induce all these diseases include persistent organic pollutants (POPs), the plastic exudates bisphenol A and phthalates, low molecular weight hydrocarbons (LMWHCs) and polynuclear aromatic hydrocarbons (PAHs). It is reported here that though these chemicals differ widely in their chemical properties, reactivities and known points of attack in humans, a common link does exist between them. All are lipophilic species found in serum and they promote the sequential absorption of otherwise non-absorbed toxic hydrophilic species causing these diseases.

  4. Functional Neurological Symptom Disorder: Mismanagement, Misdiagnosis, Chronic Cough Following Sexual Abuse: A Rare Case Report

    PubMed Central

    BIDAKI, Reza; ZAREPUR, Ehsan; AKRAMI, Maryam; Mohammad, Mohammad

    2016-01-01

    Objective Conversion disorder (CD) is a mental disorder in which patient displays neurological symptoms such as blindness, mutism, paralysis and seizure. It starts when our mind converts our mental stress into a physical symptom. A 15-year-old single white female with chronic cough, which had begun 5 months ago, was brought to our clinic. She had no history of hospitalization. His daily cough was without sputum production or fever, rhinorrhea and stopped during sleep. There was no recent exposure to tobacco smoke or a person with a chronic productive cough. Laboratory tests were normal. She had engaged 4 months ago. Doing sex during engagement is prohibited in her culture but and had anal sex, because of her spouse’s trend. Psychotherapy was done and complete recovery was accomplished. PMID:27247590

  5. Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases

    PubMed Central

    2013-01-01

    Many studies have associated environmental exposure to chemicals with neurological impairments (NIs) including neuropathies, cognitive, motor and sensory impairments; neurodevelopmental disorders (NDDs) including autism and attention deficit hyperactivity disorder (ADHD); neurodegenerative diseases (NDGs) including Alzheimer′s disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS). The environmental chemicals shown to induce all these diseases include persistent organic pollutants (POPs), the plastic exudates bisphenol A and phthalates, low molecular weight hydrocarbons (LMWHCs) and polynuclear aromatic hydrocarbons (PAHs). It is reported here that though these chemicals differ widely in their chemical properties, reactivities and known points of attack in humans, a common link does exist between them. All are lipophilic species found in serum and they promote the sequential absorption of otherwise non-absorbed toxic hydrophilic species causing these diseases. PMID:24678247

  6. Stiff Person syndrome and other anti-GAD-associated neurologic disorders.

    PubMed

    Dayalu, Praveen; Teener, James W

    2012-11-01

    Antibodies directed against glutamic acid decarboxylase (GAD) are present in many patients with stiff person syndrome and increasingly found in patients with other symptoms indicative of central nervous system (CNS) dysfunction, such as ataxia. The classic clinical features of stiff person syndrome include muscular stiffness with superimposed painful muscular spasms. Gait is often impaired. Other CNS disorders associated with GAD antibodies include progressive encephalomyelitis with rigidity and myoclonus (PERM), limbic encephalitis, and even epilepsy. Glutamic acid decarboxylase is the rate-limiting enzyme in the production of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter. Presumably, antibodies directed against GAD impair GABA production, but the precise pathogenic mechanism of GAD-antibody-related neurologic disorders is uncertain. Many patients respond to treatment with immunomodulating therapy. Symptomatic treatment with agents that enhance GABA activity, such as benzodiazepines and baclofen, is also helpful for many patients.

  7. Frontiers in therapeutic development of allopregnanolone for Alzheimer’s disease and other neurological disorders

    PubMed Central

    Irwin, Ronald W.; Solinsky, Christine M.; Brinton, Roberta Diaz

    2014-01-01

    Allopregnanolone (Allo), a neurosteroid, has emerged as a promising promoter of endogenous regeneration in brain. In a mouse model of Alzheimer’s disease, Allo induced neurogenesis, oligodendrogenesis, white matter generation and cholesterol homeostasis while simultaneously reducing β-amyloid and neuroinflammatory burden. Allo activates signaling pathways and gene expression required for regeneration of neural stem cells and their differentiation into neurons. In parallel, Allo activates systems to sustain cholesterol homeostasis and reduce β-amyloid generation. To advance Allo into studies for chronic human neurological conditions, we examined translational and clinical parameters: dose, regimen, route, formulation, outcome measures, and safety regulations. A treatment regimen of once per week at sub-sedative doses of Allo was optimal for regeneration and reduction in Alzheimer’s pathology. This regimen had a high safety profile following chronic exposure in aged normal and Alzheimer’s mice. Formulation of Allo for multiple routes of administration has been developed for both preclinical and clinical testing. Preclinical evidence for therapeutic efficacy of Allo spans multiple neurological diseases including Alzheimer’s, Parkinson’s, multiple sclerosis, Niemann-Pick, diabetic neuropathy, status epilepticus, and traumatic brain injury. To successfully translate Allo as a therapeutic for multiple neurological disorders, it will be necessary to tailor dose and regimen to the targeted therapeutic mechanisms and disease etiology. Treatment paradigms conducted in accelerated disease models in young animals have a low probability of successful translation to chronic diseases in adult and aged humans. Gender, genetic risks, stage and burden of disease are critical determinants of efficacy. This review focuses on recent advances in development of Allo for Alzheimer’s disease (AD) that have the potential to accelerate therapeutic translation for multiple unmet

  8. Role of histaminergic system in blood-brain barrier dysfunction associated with neurological disorders.

    PubMed

    Bañuelos-Cabrera, Ivette; Valle-Dorado, María Guadalupe; Aldana, Blanca Irene; Orozco-Suárez, Sandra Adela; Rocha, Luisa

    2014-11-01

    Blood-brain barrier (BBB) disruption has been associated with several acute and chronic brain disorders such as Alzheimer's disease, Parkinson's disease and epilepsy. This represents a critical situation because damaged integrity of the BBB is related to the influx of immune mediators, plasma proteins and other outside elements from blood to the central nervous system (CNS) that may trigger a cascade of events that leads to neuroinflammation. In this review, evidence that mast cells and the release of factors such as histamine play an important role in the neuroinflammatory process associated with brain disorders such as Alzheimer's disease, Parkinson's disease and epilepsy is presented.

  9. Cerebrospinal fluid arginine vasopressin in degenerative disorders and other neurological diseases.

    PubMed Central

    Sundquist, J; Forsling, M L; Olsson, J E; Akerlund, M

    1983-01-01

    Arginine vasopressin (AVP) was determined in plasma and lumbar CSF from 46 patients with Parkinson's disease, dementia, cerebrovascular disease, multiple sclerosis and other, mostly peripheral neurological disorders. The mean plasma concentration of AVP was 1.62 microU/ml, the CSF concentration 1.14 microU/ml and the gradient CSF/plasma 0.72. There was a good correlation between the plasma and the CSF values in most patients. No sex difference could be found. A slight decrease of the CSF values could be found with increasing age. Significantly higher CSF-AVP values were found in patients with cerebrovascular disease, whereas lower CSF values were found in patients with dementia and Parkinson's disease. However there were decreased CSF/plasma gradients in patients with dementia and Parkinson's disease to about 0.30 compared to 0.98 in patients with peripheral neurological disorders. Patients with multiple sclerosis had an increased IgG index indicating an intrathecal IgG production but there was no obvious correlation between this and the AVP concentrations in plasma and CSF, nor with the total CSF protein content, nor with the albumin and IgG concentrations in plasma and CSF. PMID:6842195

  10. Current understanding of the circadian clock and the clinical implications for neurological disorders.

    PubMed

    Turek, F W; Dugovic, C; Zee, P C

    2001-11-01

    The changes in behavior that occur on a 24-hour basis to match the 24-hour changes in the physical environment due to the rotation of the earth on its axis are a hallmark of life on the planet Earth. The nervous system of both lower and higher organisms has evolved over millions of years to meet the demands of the dramatic changes in the physical environment that occur in relation to the changes in the light-dark cycle, optimizing the survival and reproductive success of the organism. During the past 50 years, it has been clearly established that the 24-hour nature of life was not simply a response to the 24-hour changes in the physical environment imposed by celestial mechanics, but instead was due to an internal time-keeping system in the brain. Many neurological disorders are associated with abnormal 24-hour rhythms, including the sleep-wake cycle. The recent discovery of the molecular basis of the neural clock in animals offers neurologists new avenues for studying the pathophysiology of neurological disorders.

  11. The bowel and beyond: the enteric nervous system in neurological disorders.

    PubMed

    Rao, Meenakshi; Gershon, Michael D

    2016-09-01

    The enteric nervous system (ENS) is large, complex and uniquely able to orchestrate gastrointestinal behaviour independently of the central nervous system (CNS). An intact ENS is essential for life and ENS dysfunction is often linked to digestive disorders. The part the ENS plays in neurological disorders, as a portal or participant, has also become increasingly evident. ENS structure and neurochemistry resemble that of the CNS, therefore pathogenic mechanisms that give rise to CNS disorders might also lead to ENS dysfunction, and nerves that interconnect the ENS and CNS can be conduits for disease spread. We review evidence for ENS dysfunction in the aetiopathogenesis of autism spectrum disorder, amyotrophic lateral sclerosis, transmissible spongiform encephalopathies, Parkinson disease and Alzheimer disease. Animal models suggest that common pathophysiological mechanisms account for the frequency of gastrointestinal comorbidity in these conditions. Moreover, the neurotropic pathogen, varicella zoster virus (VZV), unexpectedly establishes latency in enteric and other autonomic neurons that do not innervate skin. VZV reactivation in these neurons produces no rash and is therefore a clandestine cause of gastrointestinal disease, meningitis and strokes. The gut-brain alliance has raised consciousness as a contributor to health, but a gut-brain axis that contributes to disease merits equal attention.

  12. The bowel and beyond: the enteric nervous system in neurological disorders

    PubMed Central

    Rao, Meenakshi; Gershon, Michael D.

    2016-01-01

    The enteric nervous system (ENS) is large, complex and uniquely able to orchestrate gastrointestinal behaviour independently of the central nervous system (CNS). An intact ENS is essential for life and ENS dysfunction is often linked to digestive disorders. The part the ENS plays in neurological disorders, as a portal or participant, has also become increasingly evident. ENS structure and neurochemistry resemble that of the CNS, therefore pathogenic mechanisms that give rise to CNS disorders might also lead to ENS dysfunction, and nerves that interconnect the ENS and CNS can be conduits for disease spread. We review evidence for ENS dysfunction in the aetiopathogenesis of autism spectrum disorder, amyotrophic lateral sclerosis, transmissible spongiform encephalopathies, Parkinson disease and Alzheimer disease. Animal models suggest that common pathophysiological mechanisms account for the frequency of gastrointestinal comorbidity in these conditions. Moreover, the neurotropic pathogen, varicella zoster virus (VZV), unexpectedly establishes latency in enteric and other autonomic neurons that do not innervate skin. VZV reactivation in these neurons produces no rash and is therefore a clandestine cause of gastrointestinal disease, meningitis and strokes. The gut–brain alliance has raised consciousness as a contributor to health, but a gut–brain axis that contributes to disease merits equal attention. PMID:27435372

  13. Clinical Utility and Lifespan Profiling of Neurological Soft Signs in Schizophrenia Spectrum Disorders.

    PubMed

    Chan, Raymond C K; Xie, Weizhen; Geng, Fu-lei; Wang, Ya; Lui, Simon S Y; Wang, Chuan-yue; Yu, Xin; Cheung, Eric F C; Rosenthal, Robert

    2016-05-01

    Neurological soft signs (NSSs) bear the promise for early detection of schizophrenia spectrum disorders. Nonetheless, the sensitivity and specificity of NSSs in the psychosis continuum remains a topic of controversy. It is also unknown how NSSs reveal neurodevelopmental abnormality in schizophrenia. We investigated the effect sizes of NSSs in differentiating individuals with schizophrenia spectrum disorders from individuals with other psychiatric conditions and from covariate-matched healthy subjects. We also investigated the partitioned age-related variations of NSSs in both schizophrenia and healthy individuals. NSSs were assessed by the abridged version of the Cambridge Neurological Inventory (CNI) in 3105 participants, consisting of healthy individuals (n=1577), unaffected first-degree relatives of schizophrenia patients (n= 155), individuals with schizotypal personality disorder (n= 256), schizophrenia patients (n= 738), and other psychiatric patients (n= 379). Exact matching and propensity score matching procedures were performed to control for covariates. Multiple regression was used to partition age-related variations. Individuals along the schizophrenia continuum showed elevated levels of NSSs, with moderate effect sizes, in contrast to other psychiatric patients who had minimal NSSs, as well as matched healthy controls. Furthermore, the age-and-NSS relationship in schizophrenia patients was represented by a flat but overall elevated pattern, in contrast to a U-shaped pattern in healthy individuals. In sum, NSSs capture a moderate portion of psychosis proneness with reasonable specificity. Lifespan profiling reveals an abnormal developmental trajectory of NSSs in schizophrenia patients, which supports the endophenotype hypothesis of NSSs by associating it with the neurodevelopmental model of schizophrenia.

  14. Neurologic Evaluation of Acute Lacrimomimetic Effect of Cyclosporine in an Experimental Rabbit Dry Eye Model

    PubMed Central

    Toshida, Hiroshi; Nguyen, Doan H.; Beuerman, Roger W.; Murakami, Akira

    2010-01-01

    PURPOSE To evaluate neurologically acute lacrimation caused by cyclosporine (CsA) eyedrops in rabbit. METHODS Normal adult male New Zealand White rabbits and those that underwent parasympathectomy each received a single instillation of 0.1% CsA or vehicle eyedrops. Schirmer tear test (STT) results, flow rate of lacrimal gland (LG) fluid from the excretory lacrimal duct of the main LG, and blink rate (over a 3-minute period) were measured before and after instillation of CsA or vehicle. Light microscopy was performed to examine the main LG in vitro. Protein release from LG fragments was assessed after incubation with CsA for 30 minutes. RESULTS In normal rabbits, the STT value and the flow rate of LG fluid were significantly increased after treatment with CsA compared with vehicle (P < 0.05). In contrast, no changes were found in denervated eyes. The blink rate of CsA-treated eyes was significantly higher than that of vehicle- treated eyes in normal rabbits (P < 0.005), whereas that of denervated eyes decreased significantly after CsA instillation compared with before administration (P < 0.005). Light microscopy showed that the cytoplasm of acinar cells was packed with secretory granules in denervated LG tissue 7 days after parasympathectomy. The same finding was observed 3 hours after CsA instillation. CsA had no stimulatory effect on protein release by acinar cells in LG fragments at all concentrations tested. CONCLUSIONS These results suggest that CsA has no direct effect on tear fluid secretion from the LG in an acute model. Instead, CsA increases reflex tear flow. PMID:19218606

  15. Acute disseminated encephalomyelitis with severe neurological outcomes following virosomal seasonal influenza vaccine.

    PubMed

    Alicino, Cristiano; Infante, Maria Teresa; Gandoglia, Ilaria; Miolo, Nadia; Mancardi, Gian Luigi; Zappettini, Simona; Capello, Elisabetta; Orsi, Andrea; Tamburini, Tiziano; Grandis, Marina

    2014-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory, usually monophasic, immune mediate, demyelinating disease of the central nervous system which involves the white matter. ADEM is more frequent in children and usually occurs after viral infections, but may follow vaccinations, bacterial infections, or may occur without previous events. Only 5% of cases of ADEM are preceded by vaccination within one month prior to symptoms onset. The diagnosis of ADEM requires both multifocal involvement and encephalopathy and specific demyelinating lesions of white matter. Overall prognosis of ADEM patients is often favorable, with full recovery reported in 23% to 100% of patients from pediatric cohorts, and more severe outcome in adult patients. We describe the first case of ADEM occurred few days after administration of virosomal seasonal influenza vaccine. The patient, a 59-year-old caucasic man with unremarkable past medical history presented at admission decreased alertness, 10 days after flu vaccination. During the 2 days following hospitalization, his clinical conditions deteriorated with drowsiness and fever until coma. The magnetic resonance imaging of the brain showed multiple and symmetrical white matter lesions in both cerebellar and cerebral hemispheres, suggesting demyelinating disease with inflammatory activity, compatible with ADEM. The patient was treated with high dose of steroids and intravenous immunoglobulin with relevant sequelae and severe neurological outcomes.

  16. The use of ketogenic diet in special situations: expanding use in intractable epilepsy and other neurologic disorders

    PubMed Central

    2012-01-01

    The ketogenic diet has been widely used and proved to be effective for intractable epilepsy. Although the mechanisms underlying its anti-epileptic effects remain to be proven, there are increasing experimental evidences for its neuroprotective effects along with many researches about expanding use of the diet in other neurologic disorders. The first success was reported in glucose transporter type 1 deficiency syndrome, in which the diet served as an alternative metabolic source. Many neurologic disorders share some of the common pathologic mechanisms such as mitochondrial dysfunction, altered neurotransmitter function and synaptic transmission, or abnormal regulation of reactive oxygen species, and the role of the ketogenic diet has been postulated in these mechanisms. In this article, we introduce an overview about the expanding use and emerging trials of the ketogenic diet in various neurologic disorders excluding intractable epilepsy and provide explanations of the mechanisms in that usage. PMID:23049588

  17. Accelerating discovery for complex neurological and behavioral disorders through systems genetics and integrative genomics in the laboratory mouse.

    PubMed

    Bubier, Jason A; Chesler, Elissa J

    2012-04-01

    Recent advances in systems genetics and integrative functional genomics have greatly improved the study of complex neurological and behavioral traits. The methods developed for the integrated characterization of new, high-resolution mouse genetic reference populations and systems genetics enable behavioral geneticists an unprecedented opportunity to address questions of the molecular basis of neurological and psychiatric disorders and their comorbidities. Integrative genomics augment these strategies by enabling rapid informatics-assisted candidate gene prioritization, cross-species translation, and mechanistic comparison across related disorders from a wealth of existing data in mouse and other model organisms. Ultimately, through these complementary approaches, finding the mechanisms and sources of genetic variation underlying complex neurobehavioral disease related traits is becoming tractable. Furthermore, these methods enable categorization of neurobehavioral disorders through their underlying biological basis. Together, these model organism-based approaches can lead to a refinement of diagnostic categories and targeted treatment of neurological and psychiatric disease.

  18. Mammalian Target of Rapamycin: Hitting the Bull's-Eye for Neurological Disorders

    PubMed Central

    Chong, Zhao Zhong; Shang, Yan Chen; Zhang, Lijie; Wang, Shaohui; Maiese, Kenneth

    2010-01-01

    The mammalian target of rapamycin (mTOR) and its associated cell signaling pathways have garnered significant attention for their roles in cell biology and oncology. Interestingly,the explosion of information in this field has linked mTOR to neurological diseases with promising initial studies. mTOR, a 289 kDa serine/threonine protein kinase, plays an important role in cell growth and proliferation and is activated through phosphorylation in response to growth factors, mitogens and hormones. Growth factors, amino acids, cellular nutrients and oxygen deficiency can downregulate mTOR activity. The function of mTOR signaling is mediated primarily through two mTOR complexes: mTORC1 and mTORC2. mTORC1 initiates cap-dependent protein translation, a rate-limiting step of protein synthesis, through the phosphorylation of the targets eukaryotic initiation factor 4E-binding protein 1 (4EBP1) and p70 ribosomal S6 kinase (p70S6K). In contrast, mTORC2 regulates development of the cytoskeleton and also controls cell survival. Although closely tied to tumorigenesis, mTOR and the downstream signaling pathways are significantly involved in the central nervous system (CNS) with synaptic plasticity, memory retention, neuroendocrine regulation associated with food intake and puberty and modulation of neuronal repair following injury. The signaling pathways of mTOR also are believed to be a significant component in a number of neurological diseases, such as Alzheimer disease, Parkinson disease and Huntington disease, tuberous sclerosis, neurofibromatosis, fragile X syndrome, epilepsy, traumatic brain injury and ischemic stroke. Here we describe the role of mTOR in the CNS and illustrate the potential for new strategies directed against neurological disorders. PMID:21307646

  19. A systematic review of self-reported swallowing assessments in progressive neurological disorders.

    PubMed

    Keage, Megan; Delatycki, Martin; Corben, Louise; Vogel, Adam

    2015-02-01

    Dysphagia experienced as a consequence of neurodegenerative disease can have severe consequences on a patient's health and well-being. Regular assessment of swallowing function can assist to achieve adequate nutrition and hydration. Here we review subjective swallowing assessments currently available are suitable for use in people with neurodegenerative disease. Measurement properties were reviewed for each tool and coverage of the World Health Organization's International Classification of Functioning, Disability and Health (WHO ICF) was considered. Assessments were identified following a review of the published literature Instruments were reviewed on the basis of reliability and validity, as well as administrative properties, such an interpretability, acceptability, and feasibility. Tools were also evaluated according to the WHO ICF framework. In total, 19 studies were identified for full-text review from 13,315 abstracts. Nine self-reported dysphagia assessment tools suitable for use in progressive neurological disorders were identified. The Swallowing Quality of Life Questionnaire (SWAL-QOL) yields the strongest combination of reliability (including internal consistency and test-retest reliability) and convergent validity while simultaneously covering all WHO ICF domains. Lengthy administration time was identified as a limitation of the SWAL-QOL. The review highlights a relative lack of well-validated self-report questionnaires in dysphagia for people with progressive neurological disease. Additional validation and evaluation of the clinical utility of the tools currently available is required to further promote an informed selection of available assessments.

  20. Effectiveness of music therapy as an aid to neurorestoration of children with severe neurological disorders

    PubMed Central

    Bringas, Maria L.; Zaldivar, Marilyn; Rojas, Pedro A.; Martinez-Montes, Karelia; Chongo, Dora M.; Ortega, Maria A.; Galvizu, Reynaldo; Perez, Alba E.; Morales, Lilia M.; Maragoto, Carlos; Vera, Hector; Galan, Lidice; Besson, Mireille; Valdes-Sosa, Pedro A.

    2015-01-01

    This study was a two-armed parallel group design aimed at testing real world effectiveness of a music therapy (MT) intervention for children with severe neurological disorders. The control group received only the standard neurorestoration program and the experimental group received an additional MT “Auditory Attention plus Communication protocol” just before the usual occupational and speech therapy. Multivariate Item Response Theory (MIRT) identified a neuropsychological status-latent variable manifested in all children and which exhibited highly significant changes only in the experimental group. Changes in brain plasticity also occurred in the experimental group, as evidenced using a Mismatch Event Related paradigm which revealed significant post intervention positive responses in the latency range between 308 and 400 ms in frontal regions. LORETA EEG source analysis identified prefrontal and midcingulate regions as differentially activated by the MT in the experimental group. Taken together, our results showing improved attention and communication as well as changes in brain plasticity in children with severe neurological impairments, confirm the importance of MT for the rehabilitation of patients across a wide range of dysfunctions. PMID:26582974

  1. The GABA excitatory/inhibitory shift in brain maturation and neurological disorders.

    PubMed

    Ben-Ari, Yehezkel; Khalilov, Ilgam; Kahle, Kristopher T; Cherubini, Enrico

    2012-10-01

    Ionic currents and the network-driven patterns they generate differ in immature and adult neurons: The developing brain is not a "small adult brain." One of the most investigated examples is the developmentally regulated shift of actions of the transmitter GABA that inhibit adult neurons but excite immature ones because of an initially higher intracellular chloride concentration [Cl(-)](i), leading to depolarizing and often excitatory actions of GABA instead of hyperpolarizing and inhibitory actions. The levels of [Cl(-)](i) are also highly labile, being readily altered transiently or persistently by enhanced episodes of activity in relation to synaptic plasticity or a variety of pathological conditions, including seizures and brain insults. Among the plethora of channels, transporters, and other devices involved in controlling [Cl(-)](i), two have emerged as playing a particularly important role: the chloride importer NKCC1 and the chloride exporter KCC2. Here, the authors stress the importance of determining how [Cl(-)](i) is dynamically regulated and how this affects brain operation in health and disease. In a clinical perspective, agents that control [Cl(-)](i) and reinstate inhibitory actions of GABA open novel therapeutic perspectives in many neurological disorders, including infantile epilepsies, autism spectrum disorders, and other developmental disorders.

  2. Neurological disorders and the potential role for stem cells as a therapy.

    PubMed

    Sanberg, Paul R; Eve, David J; Cruz, L Eduardo; Borlongan, Cesar V

    2012-01-01

    Introduction Neurological disorders are routinely characterized by loss of cells in response to an injury or a progressive insult. Stem cells could therefore be useful to treat these disorders. Sources of data Pubmed searches of recent literature. Areas of agreement Stem cells exhibit proliferative capacity making them ideally suited for replacing dying cells. However, instead of cell replacement therapy stem cell transplants frequently appear to work via neurotrophic factor release, immunomodulation and upregulation of endogenous stem cells. Areas of controversy and areas timely for developing research Many questions remain with respect to the use of stem cells as a therapy, the answers to which will vary depending on the disorder to be treated and mode of action. Whereas the potential tumorigenic capability of stem cells is a concern, most studies do not support this notion. Further determination of the optimal cell type, and whether to perform allogeneic or autologous transplants warrant investigation before the full potential of stem cells can be realized. In addition, the use of stem cells to develop disease models should not be overlooked.

  3. Accuracy of WISC-III and WAIS-IV short forms in patients with neurological disorders.

    PubMed

    van Ool, Jans S; Hurks, Petra P M; Snoeijen-Schouwenaars, Francesca M; Tan, In Y; Schelhaas, Helenius J; Klinkenberg, Sylvia; Aldenkamp, Albert P; Hendriksen, Jos G M

    2017-02-02

    The assessment of intellectual abilities is intensive, time-consuming, and might be considered burdensome for patients. We examined psychometric qualities of short forms (SFs) of the Wechsler Intelligence Scales for Children (WISC-third edition) and for adults (WAIS-fourth edition), in children (n = 986; Mage = 10.9) and adults (n = 324; Mage = 40.9) with neurological disorders. SF estimates were compared with Full Scale IQ (FSIQ), obtained by a complete administration, for the entire sample and for the subgroups FSIQ < 80 and FSIQ ≥ 80. The FSIQ was correctly identified within ± 7 points in 86% of children and 87% of adults. There were, however, some differences regarding the optimal SF subtest combination between subgroups. Although clinical inferences should not be made, SFs may be useful in research settings to obtain a global estimate of intelligence, and in clinical settings to screen periodically for possible intellectual deterioration.

  4. Current Perspectives on the Beneficial Role of Ginkgo biloba in Neurological and Cerebrovascular Disorders

    PubMed Central

    Nash, Kevin M.; Shah, Zahoor A.

    2015-01-01

    Ginkgo biloba extract is an alternative medicine available as a standardized formulation, EGb 761®, which consists of ginkgolides, bilobalide, and flavonoids. The individual constituents have varying therapeutic mechanisms that contribute to the pharmacological activity of the extract as a whole. Recent studies show anxiolytic properties of ginkgolide A, migraine with aura treatment by ginkgolide B, a reduction in ischemia-induced glutamate excitotoxicity by bilobalide, and an alternative antihypertensive property of quercetin, among others. These findings have been observed in EGb 761 as well and have led to clinical investigation into its use as a therapeutic for conditions such as cognition, dementia, cardiovascular, and cerebrovascular diseases. This review explores the therapeutic mechanisms of the individual EGb 761 constituents to explain the pharmacology as a whole and its clinical application to cardiovascular and neurological disorders, in particular ischemic stroke. PMID:26604665

  5. CK2—An Emerging Target for Neurological and Psychiatric Disorders

    PubMed Central

    Castello, Julia; Ragnauth, Andre; Friedman, Eitan; Rebholz, Heike

    2017-01-01

    Protein kinase CK2 has received a surge of attention in recent years due to the evidence of its overexpression in a variety of solid tumors and multiple myelomas as well as its participation in cell survival pathways. CK2 is also upregulated in the most prevalent and aggressive cancer of brain tissue, glioblastoma multiforme, and in preclinical models, pharmacological inhibition of the kinase has proven successful in reducing tumor size and animal mortality. CK2 is highly expressed in the mammalian brain and has many bona fide substrates that are crucial in neuronal or glial homeostasis and signaling processes across synapses. Full and conditional CK2 knockout mice have further elucidated the importance of CK2 in brain development, neuronal activity, and behavior. This review will discuss recent advances in the field that point to CK2 as a regulator of neuronal functions and as a potential novel target to treat neurological and psychiatric disorders. PMID:28067771

  6. Psychiatric illness in inpatients with neurological disorders: patients' views on discussion of emotional problems with neurologists.

    PubMed Central

    Bridges, K W; Goldberg, D P

    1984-01-01

    The prevalence of psychiatric morbidity in inpatients with neurological disorders and the extent to which it is detected by neurologists were measured by using a two stage model of psychiatric assessment and from information recorded in the patients' medical notes. The prevalence of psychiatric morbidity was estimated as 39%, of which 72% was unrecognised by the neurologists. Only a minority of patients with an uncertain physical diagnosis had a psychiatric illness, showing the error in assuming that a patient's physical symptoms arise from a psychological disturbance if an organic aetiology cannot be determined. When the patients were interviewed on their discharge from hospital they were divided on whether they had wished to discuss their mood with neurologists while they were in hospital. The reasons that they gave suggested that interactions between patients and doctors and the lack of ward facilities for private consultations with doctors are important determinants of hidden psychiatric morbidity in medical inpatients. PMID:6434026

  7. Regulated protein expression for in vivo gene therapy for neurological disorders: progress, strategies, and issues.

    PubMed

    Manfredsson, Fredric P; Bloom, David C; Mandel, Ronald J

    2012-11-01

    The field of in vivo gene therapy has matured to the point where there are numerous clinical trials underway including late-stage clinical trials. Several viral vectors are especially efficient and support lifetime protein expression in the brain and a number of clinical trials are underway for various progressive or chronic neurological disorders including Parkinson's disease, Alzheimer's disease, and Batten's disease. To date, however, none of the vectors in clinical use have any direct way to reverse or control their transgene product in the event continued protein expression should become problematic. Several schemes that use elements within the vector design have been developed that allow an external drug or pro-drug to alter ongoing protein expression after in vivo gene transfer. The most promising and most studied regulated protein expression methods for in vivo gene transfer are reviewed. In addition, potential scientific and clinical advantages of transgene regulation for gene therapy are discussed.

  8. Parents do matter: genomic imprinting and parental sex effects in neurological disorders.

    PubMed

    Chatkupt, S; Antonowicz, M; Johnson, W G

    1995-05-01

    Genomic imprinting is a recently recognized phenomenon of differential expression of genetic material depending upon whether the genetic material has come from the male or female parent. This process of differential phenotypic expression involves mammalian development both in the normal and abnormal situations, resulting in parental sex effects. However, some parental sex effects may be due to other mechanisms such as mitochondrial inheritance. In the following article, evidence for genomic imprinting in experimental animals and in diseases are summarized. Relevant human neurological disorders manifesting parental sex effects discussed here include myotonic dystrophy, Huntington's disease, fragile X syndrome, spinocerebellar ataxia type 1, and neurofibromatosis type 1 and 2. A possible mechanism of imprinting involves the processes of methylation imprint and replication imprint. The knowledge of imprinting is helpful in clinical practice particularly in the areas of genetic counseling, prenatal diagnosis, and possible future gene therapy.

  9. [Stiff-person syndrome and other neurological disorders associated with anti-GAD antibodies].

    PubMed

    Hijazi, J; Bedat-Millet, A-L; Hannequin, D

    2010-01-01

    Autoantibodies to glutamic acid decarboxylase (GAD), originally identified in the stiff-person syndrome, are also associated with rare cases of therapy-resistant epilepsy and sporadic cerebellar ataxia. The association of GAD antibodies with these three syndromes and other auto-immune diseases, particularly type 1 diabetes mellitus, argues for their auto-immune origin. Anti-GAD antibodies inhibit GABAergic circuits inducing a neuronal hyper-excitability that seems to be responsible for these three syndromes. However, an additional mechanism seems to be involved in the degenerative component of the cerebellar ataxia associated with anti-GAD antibodies. A more accurate diagnosis and the study of neuropathological cases are necessary to document the different mechanisms implicated in these neurological disorders.

  10. Imbalance between nitric oxide and dopamine may underly aggression in acute neurological patients.

    PubMed

    Ramírez-Bermudez, J; Perez-Neri, I; Montes, S; Ramirez-Abascal, M; Nente, F; Abundes-Corona, A; Soto-Hernandez, J L; Rios, C

    2010-10-01

    The neurochemical basis of aggressive behavior in humans is not fully understood. In this study we explored the relationship between aggressiveness (as measured by the Overt Aggression Scale), cognitive performance (as measured by the Mini Mental State Examination), and biochemical markers of dopamine neurotransmission (homovanillic acid, HVA) and nitric oxide synthesis (nitrite plus nitrate, NO(x)) in cerebrospinal fluid from 70 patients with acute brain disorders, mainly brain infections. Aggressive behavior and cognitive performance showed an inverse correlation. NO(x)/HVA ratio was inversely correlated to aggressive behavior, and positively correlated to cognitive performance. A subanalysis with antipsychotic-naïve patients confirmed those results. The balance between nitric oxide and dopamine could be related to the cognitive control of aggressive impulse.

  11. Neurologic complications of immunizations.

    PubMed

    Rutledge, S L; Snead, O C

    1986-12-01

    Although there does appear to be at least a temporal relationship between pertussis immunization and serious acute neurologic illness, data to suggest that children with stable preexisting neurologic disease or positive family history of neurologic disease are at increased risk for complications of pertussis immunizations are inconclusive. Furthermore, there are no firm statistical data concerning the incidence of pertussis vaccine-related encephalopathy. Rather, the literature on pertussis vaccine complications is replete with anecdotal reports and retrospective studies with a number of questionable conclusions drawn from this inadequate data base. Unfortunately, these conclusions have been sensationalized and exploited with litigious fervor to the point that the practice of pertussis immunization is being questioned in the United States. A number of points should be reiterated: pertussis is a dangerous and deadly disease, as seen in the epidemic in Great Britain; pertussis immunization is effective in protecting against the disease; and there is no conclusive proof that the incidence of complications from pertussis vaccination of children with seizure disorders or other preexisting stable neurologic abnormalities is higher, because appropriate studies have not been done to define such a risk. We would do well to keep these facts in mind in order to avoid a disaster similar to the pertussis epidemic in Great Britain. Pertussis vaccination should be given to all children except those with allergic hypersensitivity, a progressive neurologic disorder, or an adverse reaction to a previous pertussis dose.

  12. Neurological, psychological, and cognitive disorders in patients with chronic kidney disease on conservative and replacement therapy

    PubMed Central

    Lai, Silvia; Mecarelli, Oriano; Pulitano, Patrizia; Romanello, Roberto; Davi, Leonardo; Zarabla, Alessia; Mariotti, Amalia; Carta, Maria; Tasso, Giorgia; Poli, Luca; Mitterhofer, Anna Paola; Testorio, Massimo; Frassetti, Nicla; Aceto, Paola; Galani, Alessandro; Lai, Carlo

    2016-01-01

    Abstract Chronic kidney disease (CKD) is a highly prevalent condition in the world. Neurological, psychological, and cognitive disorders, related to CKD, could contribute to the morbidity, mortality, and poor quality of life of these patients. The aim of this study was to assess the neurological, psychological, and cognitive imbalance in patients with CKD on conservative and replacement therapy. Seventy-four clinically stable patients affected by CKD on conservative therapy, replacement therapy (hemodialysis (HD), peritoneal dialysis (PD)), or with kidney transplantation (KT) and 25 healthy controls (HC), matched for age and sex were enrolled. Clinical, laboratory, and instrumental examinations, as renal function, inflammation and mineral metabolism indexes, electroencephalogram (EEG), psychological (MMPI-2, Sat P), and cognitive tests (neuropsychological tests, NPZ5) were carried out. The results showed a significant differences in the absolute and relative power of delta band and relative power of theta band of EEG (P = 0.008, P < 0.001, P = 0.051), a positive correlation between relative power of delta band and C-reactive protein (CRP) (P < 0.001) and a negative correlation between estimated glomerular filtration rate (eGFR) (P < 0.001) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) (P < 0.001), in all the samples. Qualitative analysis of EEG showed alterations of Grade 2 (according to Parsons–Smith classification) in patients on conservative therapy, and Grade 2–3 in KT patients. The scales of MMPI-2 hysteria and paranoia, are significantly correlated with creatinine, eGFR, serum nitrogen, CRP, 1,25-(OH)2D3, intact parathyroid hormone (iPTH), phosphorus, and cynical and hysterical personality, are correlated with higher relative power of delta (P = 0.016) and theta band (P = 0.016). Moreover, all NPZ5 scores showed a significant difference between the means of nephropathic patients and the means of the HC, and a positive

  13. Neurological, psychological, and cognitive disorders in patients with chronic kidney disease on conservative and replacement therapy.

    PubMed

    Lai, Silvia; Mecarelli, Oriano; Pulitano, Patrizia; Romanello, Roberto; Davi, Leonardo; Zarabla, Alessia; Mariotti, Amalia; Carta, Maria; Tasso, Giorgia; Poli, Luca; Mitterhofer, Anna Paola; Testorio, Massimo; Frassetti, Nicla; Aceto, Paola; Galani, Alessandro; Lai, Carlo

    2016-11-01

    Chronic kidney disease (CKD) is a highly prevalent condition in the world. Neurological, psychological, and cognitive disorders, related to CKD, could contribute to the morbidity, mortality, and poor quality of life of these patients. The aim of this study was to assess the neurological, psychological, and cognitive imbalance in patients with CKD on conservative and replacement therapy.Seventy-four clinically stable patients affected by CKD on conservative therapy, replacement therapy (hemodialysis (HD), peritoneal dialysis (PD)), or with kidney transplantation (KT) and 25 healthy controls (HC), matched for age and sex were enrolled. Clinical, laboratory, and instrumental examinations, as renal function, inflammation and mineral metabolism indexes, electroencephalogram (EEG), psychological (MMPI-2, Sat P), and cognitive tests (neuropsychological tests, NPZ5) were carried out.The results showed a significant differences in the absolute and relative power of delta band and relative power of theta band of EEG (P = 0.008, P < 0.001, P = 0.051), a positive correlation between relative power of delta band and C-reactive protein (CRP) (P < 0.001) and a negative correlation between estimated glomerular filtration rate (eGFR) (P < 0.001) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) (P < 0.001), in all the samples. Qualitative analysis of EEG showed alterations of Grade 2 (according to Parsons-Smith classification) in patients on conservative therapy, and Grade 2-3 in KT patients. The scales of MMPI-2 hysteria and paranoia, are significantly correlated with creatinine, eGFR, serum nitrogen, CRP, 1,25-(OH)2D3, intact parathyroid hormone (iPTH), phosphorus, and cynical and hysterical personality, are correlated with higher relative power of delta (P = 0.016) and theta band (P = 0.016). Moreover, all NPZ5 scores showed a significant difference between the means of nephropathic patients and the means of the HC, and a positive correlation with e

  14. Acute movement disorders in children: experience from a developing country.

    PubMed

    Goraya, Jatinder Singh

    2015-03-01

    We describe acute movement disorders in 92 children, aged 5 days to 15 years, from an Indian tertiary hospital. Eighty-nine children had hyperkinetic movement disorders, with myoclonus in 25, dystonia in 21, choreoathetosis in 19, tremors in 15, and tics in 2. Tetany and tetanus were seen in 5 and 2 children, respectively. Hypokinetic movement disorders included acute parkinsonism in 3 children. Noninflammatory and inflammatory etiology were present in 60 and 32 children, respectively. Benign neonatal sleep myoclonus in 16 and opsoclonus myoclonus syndrome in 7 accounted for the majority of myoclonus cases. Vitamin B12 deficiency in 13 infants was the most common cause of tremors. Rheumatic fever and encephalitis were the most common causes of acute choreoathetosis. Acute dystonia had metabolic etiology in 6 and encephalitis and drugs in 3 each. Psychogenic movement disorders were seen in 4 cases only, although these patients may be underreported.

  15. Self-Reported Acute and Chronic Voice Disorders in Teachers.

    PubMed

    Rossi-Barbosa, Luiza Augusta Rosa; Barbosa, Mirna Rossi; Morais, Renata Martins; de Sousa, Kamilla Ferreira; Silveira, Marise Fagundes; Gama, Ana Cristina Côrtes; Caldeira, Antônio Prates

    2016-11-01

    The present study aimed to identify factors associated with self-reported acute and chronic voice disorders among municipal elementary school teachers in the city of Montes Claros, in the State of Minas Gerais, Brazil.

  16. Clinical correlates of neurological change in posttraumatic stress disorder: an overview of critical systems.

    PubMed

    Kimble, Matthew; Kaufman, Milissa

    2004-03-01

    Knowledge about the biological basis of psychological trauma is changing at an exponential rate. A PsychlNFO search on the search terms "locus coeruleus" and "PTSD" revealed one peer-reviewed journal article between 1982 and 1992 and 51 in the subsequent decade. A similar search revealed zero articles on "hippocampus" and "PTSD" between 1982 and 1992 and 170 in the past decade. As clinicians, it is important to become increasingly familiar with this growing literature to use that knowledge to treat and educate patients. Imagine the relief that can be provided to survivors of trauma if clinicians can tell them that they have a good idea about what causes their symptoms and even clearer ideas about how to treat them.One ancillary but invaluable outcome to this work is the fact that understanding the neurological underpinnings of PTSD will go a long way to establishing a necessary equilibrium in nature and nurture's role in the etiology and maintenance of the disorder. In its early conceptualization, PTSD was thought by many to be an ordinary reaction to an extraordinary event, thus placing responsibility for the disorder firmly in the hands of environmental factors. A subsequent emphasis on vulnerability and resiliency factors in the disorder, however, gave the impression that genetic and potentially hard-wired neurological factors were dominant in the expression of the disorder. Appreciating the balance between nature and nurture in the development of stress disorders like PTSD will allow clinicians and patients alike to appreciate the role of personal responsibility in the process of recovery. A parallel, albeit more mature process, has occurred in the area of schizophrenia in the past four decades. Early conceptualizations of schizophrenia placed a heavy burden on parenting and behavioral factors, leaving the patients angry at their parents and parents with unnecessary guilt. The later dominance of genetic and biological theories in the disorder allayed parents of

  17. Highly automated computer-aided diagnosis of neurological disorders using functional brain imaging

    NASA Astrophysics Data System (ADS)

    Spetsieris, P. G.; Ma, Y.; Dhawan, V.; Moeller, J. R.; Eidelberg, D.

    2006-03-01

    We have implemented a highly automated analytical method for computer aided diagnosis (CAD) of neurological disorders using functional brain imaging that is based on the Scaled Subprofile Model (SSM). Accurate diagnosis of functional brain disorders such as Parkinson's disease is often difficult clinically, particularly in early stages. Using principal component analysis (PCA) in conjunction with SSM on brain images of patients and normals, we can identify characteristic abnormal network covariance patterns which provide a subject dependent scalar score that not only discriminates a particular disease but also correlates with independent measures of disease severity. These patterns represent disease-specific brain networks that have been shown to be highly reproducible in distinct groups of patients. Topographic Profile Rating (TPR) is a reverse SSM computational algorithm that can be used to determine subject scores for new patients on a prospective basis. In our implementation, reference values for a full range of patients and controls are automatically accessed for comparison. We also implemented an automated recalibration step to produce reference scores for images generated in a different imaging environment from that used in the initial network derivation. New subjects under the same setting can then be evaluated individually and a simple report is generated indicating the subject's classification. For scores near the normal limits, additional criteria are used to make a definitive diagnosis. With further refinement, automated TPR can be used to efficiently assess disease severity, monitor disease progression and evaluate treatment efficacy.

  18. Measurement, evaluation, and assessment of peripheral neurological disorders caused by hand-transmitted vibration.

    PubMed

    Griffin, Michael J

    2008-04-01

    Regular exposure to hand-transmitted vibration can result in symptoms and signs of peripheral vascular, neurological and other disorders collectively known as the hand-arm vibration syndrome. The measurement of the effects of hand-transmitted vibration involves converting the evidence of disorder (symptoms and signs) into information that can be stored. Evaluation requires the use of scales on which to indicate the severity of the various symptoms and signs. Assessment involves a judgement of severity relative to a criterion, usually for a specific purpose (e.g. to decide on removal from work or compensation). The measurement and evaluation of symptoms and signs is necessary when monitoring patient health and when performing epidemiological studies for research. The assessment of the severity of the hand-arm vibration syndrome is currently performed with staging systems, but the criteria are not clear and not related to defined methods for measuring or evaluating the symptoms and signs. Recognizing that similar symptoms can occur without injury from occupational exposures to hand-transmitted vibration, this paper attempts to define significant peripheral neurological symptoms caused by hand-transmitted vibration (i.e. 'unusual symptoms') and how these symptoms and related signs may be measured. Scales for evaluating the symptoms (e.g. their extent) and the related signs (e.g. their probability relative to the probability of the sign being present in persons not exposed to vibration) are defined. A method of relating unusual symptoms to both the signs of disorder and the pattern of vibration exposure is illustrated. Assessments of severity will vary according to the reasons for assessing the health effects of vibration, and will depend on local practice and convenience, but a way of combining evaluations of symptoms and signs is demonstrated in a staging system. Although inherently complex, the methods may assist the collection of data required to improve

  19. Next generation sequencing for molecular diagnosis of neurological disorders using ataxias as a model.

    PubMed

    Németh, Andrea H; Kwasniewska, Alexandra C; Lise, Stefano; Parolin Schnekenberg, Ricardo; Becker, Esther B E; Bera, Katarzyna D; Shanks, Morag E; Gregory, Lorna; Buck, David; Zameel Cader, M; Talbot, Kevin; de Silva, Rajith; Fletcher, Nicholas; Hastings, Rob; Jayawant, Sandeep; Morrison, Patrick J; Worth, Paul; Taylor, Malcolm; Tolmie, John; O'Regan, Mary; Valentine, Ruth; Packham, Emily; Evans, Julie; Seller, Anneke; Ragoussis, Jiannis

    2013-10-01

    Many neurological conditions are caused by immensely heterogeneous gene mutations. The diagnostic process is often long and complex with most patients undergoing multiple invasive and costly investigations without ever reaching a conclusive molecular diagnosis. The advent of massively parallel, next-generation sequencing promises to revolutionize genetic testing and shorten the 'diagnostic odyssey' for many of these patients. We performed a pilot study using heterogeneous ataxias as a model neurogenetic disorder to assess the introduction of next-generation sequencing into clinical practice. We captured 58 known human ataxia genes followed by Illumina Next-Generation Sequencing in 50 highly heterogeneous patients with ataxia who had been extensively investigated and were refractory to diagnosis. All cases had been tested for spinocerebellar ataxia 1-3, 6, 7 and Friedrich's ataxia and had multiple other biochemical, genetic and invasive tests. In those cases where we identified the genetic mutation, we determined the time to diagnosis. Pathogenicity was assessed using a bioinformatics pipeline and novel variants were validated using functional experiments. The overall detection rate in our heterogeneous cohort was 18% and varied from 8.3% in those with an adult onset progressive disorder to 40% in those with a childhood or adolescent onset progressive disorder. The highest detection rate was in those with an adolescent onset and a family history (75%). The majority of cases with detectable mutations had a childhood onset but most are now adults, reflecting the long delay in diagnosis. The delays were primarily related to lack of easily available clinical testing, but other factors included the presence of atypical phenotypes and the use of indirect testing. In the cases where we made an eventual diagnosis, the delay was 3-35 years (mean 18.1 years). Alignment and coverage metrics indicated that the capture and sequencing was highly efficient and the consumable cost

  20. Acute aseptic meningitis and diffuse myelitis as the presenting features of neurological Behcet disease.

    PubMed

    Mullins, G M; Elamin, M; Saidha, S; Ali, E; Jennings, L; Counihan, T J; Hennessy, M

    2009-12-01

    We report an explosive presentation of neurological Behcet disease, in an Irish male patient. We present the clinical and radiological findings in our patient and discuss a novel and effective therapeutic approach. We review other treatment modalities of patients with neurological involvement.

  1. An Overview of Multiple Sclerosis: Medical, Psychosocial, and Vocational Aspects of a Chronic and Unpredictable Neurological Disorder

    ERIC Educational Resources Information Center

    Rumrill, Phillip D., Jr.; Roessler, Richard T.

    2015-01-01

    This article presents an overview of multiple sclerosis (MS), one of the most common neurological disorders in the western hemisphere. Medical and psychosocial aspects of the disease such as causes and risk factors, diagnosis, incidence and prevalence, symptoms, courses, and treatment are described. Existing research regarding the employment…

  2. Autistic Traits, ADHD Symptoms, Neurological Soft Signs and Regional Cerebral Blood Flow in Adults with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Manouilenko, Irina; Pagani, Marco; Stone-Elander, Sharon; Odh, Richard; Brolin, Fredrik; Hatherly, Robert; Jacobsson, Hans; Larsson, Stig A.; Bejerot, Susanne

    2013-01-01

    The resting regional cerebral blood flow (rCBF) patterns related to co-occurring symptoms such as inattention, hyperactivity, neurological soft signs and motor problems have not yet been disclosed in autism spectrum disorders (ASD). In this study thirteen adults with ASD and ten matched neurotypical controls underwent PET. The scores of rating…

  3. Rey's 15-Item Visual Memory Test for the Detection of Malingering: Normative Observations on Patients with Neurological Disorders.

    ERIC Educational Resources Information Center

    Lee, Gregory P.; And Others

    1992-01-01

    To gather normative observations on a visual memory test developed by A. Rey (1964), it was administered to 100 temporal-lobe epilepsy patients with memory deficits and 56 outpatients with neurological disorders. Results suggest a cutoff score of 7 on the memory test may alert the clinician to possible factitious memory complaints. (SLD)

  4. Acute Neurological Illness in a Kidney Transplant Recipient Following Infection With Enterovirus-D68: An Emerging Infection?

    PubMed

    Wali, R K; Lee, A H; Kam, J C; Jonsson, J; Thatcher, A; Poretz, D; Ambardar, S; Piper, J; Lynch, C; Kulkarni, S; Cochran, J; Djurkovic, S

    2015-12-01

    We report the first case of enterovirus-D68 infection in an adult living-donor kidney transplant recipient who developed rapidly progressive bulbar weakness and acute flaccid limb paralysis following an upper respiratory infection. We present a 45-year-old gentleman who underwent pre-emptive living-donor kidney transplantation for IgA nephropathy. Eight weeks following transplantation, he developed an acute respiratory illness from enterovirus/rhinovirus that was detectable in nasopharyngeal (NP) swabs. Within 24 h of onset of respiratory symptoms, the patient developed binocular diplopia which rapidly progressed to multiple cranial nerve dysfunctions (acute bulbar syndrome) over the next 24 h. Within the next 48 h, asymmetric flaccid paralysis of the left arm and urinary retention developed. While his neurological symptoms were evolving, the Centers for Disease Control reported that the enterovirus strain from the NP swabs was, in fact, Enterovirus-D68 (EV-D68). Magnetic resonance imaging of the brain demonstrated unique gray matter and anterior horn cell changes in the midbrain and spinal cord, respectively. Constellation of these neurological symptoms and signs was suggestive for postinfectious encephalomyelitis (acute disseminated encephalomyelitis [ADEM]) from EV-D68. Treatment based on the principles of ADEM included intensive physical therapy and other supportive measures, which resulted in a steady albeit slow improvement in his left arm and bulbar weakness, while maintaining stable allograft function.

  5. [Some neurological and psychiatric complications of the disorders of the hypothalamo-hypophyseal system].

    PubMed

    Aszalós, Zsuzsa

    2007-04-22

    Connection between the central nervous system and the endocrine system is extremely complex. The hypothalamus serves as a crucial centre for the integration and coordination of autonomic functions by neuronal and hormonal pathways. It plays a central role in the homeostatic regulation of internal physiological conditions. It controls growth and reproduction, stress reactions, and determines rhythmicity, periodicity and timing of physiological processes. Beside its well-known functions, antidiuretic hormone has a role in social behavior as it enhances aggression via vasopressin receptor 1A. Oxitocin is affected in the formation of maternal behavior, and in other social interactions, like the pair bounding, as well as in analgesia and pain modulation. The corticotrop-releasing hormone acts as a neurotransmitter, it has a special role in stress-behavior, anxiety, and depression, and it blocks deep sleeping. Among the neurotransmitters and neuropeptids of the hypothalamus, serotonin, norepinephrine, GABA, cholecystokinin, neuropeptide-Y, Agouti-related protein, alpha-MSH and ghrelin have essential importance in the eating disorders. The levels of leptin and galanin determine whether formation of anabolic or catabolic neurotransmitters should take place. In the thermoregulation the central thermoreceptors play role, and suprachiasmatic nucleus is responsible for circadian rhythm, through "timing genes". The diseases of the hypothalamus cause most frequently bulimia or anorexia, hypersomnia, impotency, and attacks of anxiety. The most common expansive process of the hypothalamus is craniopharyngioma. The lack or diminution of vasopressin causes diabetes insipidus, while inappropriate antidiuretic hormone secretion induces Schwartz-Barter syndrome. Fröhlich-, Kleine-Levin- or Prader-Willi syndromes have characteristic neuropsychiatric features. The main psychiatric symptom of hypopituitarism is a combination of dementia and delirium. The most characteristic neurological

  6. Impact of endocrine-disrupting chemicals on neural development and the onset of neurological disorders.

    PubMed

    Kajta, Małgorzata; Wójtowicz, Anna K

    2013-01-01

    Even though high doses of organic pollutants are toxic, relatively low concentrations have been reported to cause long-term alterations in functioning of individual organisms, populations and even next generations. Among these pollutants are dioxins, polychlorinated biphenyls, pesticides, brominated flame retardants, plasticizers (bisphenol A, nonylphenol, and phthalates) as well as personal care products and drugs. In addition to toxic effects, they are able to interfere with hormone receptors, hormone synthesis or hormone conversion. Because these chemicals alter hormone-dependent processes and disrupt functioning of the endocrine glands, they have been classified as endocrine-disrupting chemicals (EDCs). Because certain EDCs are able to alter neural transmission and the formation of neural networks, the term neural-disrupting chemicals has been introduced, thus implicating EDCs in the etiology of neurological disorders. Recently, public concern has been focused on the effects of EDCs on brain function, concomitantly with an increase in neuropsychiatric disorders, including autism, attention deficit and hyperactivity disorder as well as learning disabilities and aggressiveness. Several lines of evidence suggest that exposure to EDCs is associated with depression and could result in neural degeneration. EDCs act via several classes of receptors with the best documented mechanisms being reported for nuclear steroid and xenobiotic receptors. Low doses of EDCs have been postulated to cause incomplete methylation of specific gene regions in the young brain and to impair neural development and brain functions across generations. Efforts are needed to develop systematic epidemiological studies and to investigate the mechanisms of action of EDCs in order to fully understand their effects on wildlife and humans.

  7. Peritraumatic versus persistent dissociation in acute stress disorder.

    PubMed

    Panasetis, Paula; Bryant, Richard A

    2003-12-01

    The DSM-IV definition of acute stress disorder (ASD) regards dissociation that occurs during a trauma (peritraumatic dissociation) comparably to persistent dissociation. This study investigated the relative contributions of peritraumatic dissociation and persistent dissociation to acute posttraumatic stress reactions. Civilian trauma (N = 53) survivors with either acute stress disorder (ASD), subclinical ASD, or no ASD were administered modified versions of the Peritraumatic Dissociative Experiences Questionnaire that indexed both dissociation during the trauma and dissociation at the time of assessment. Persistent dissociation was more strongly associated with ASD severity and intrusive symptoms than peritraumatic dissociation. These results are consistent with the proposition that persistent, rather than peritraumatic, dissociation is associated with posttraumatic psychopathology.

  8. Acute and post-traumatic stress disorder after spontaneous abortion.

    PubMed

    Bowles, S V; James, L C; Solursh, D S; Yancey, M K; Epperly, T D; Folen, R A; Masone, M

    2000-03-15

    When a spontaneous abortion is followed by complicated bereavement, the primary care physician may not consider the diagnosis of acute stress disorder or post-traumatic stress disorder. The major difference between these two conditions is that, in acute stress disorder, symptoms such as dissociation, reliving the trauma, avoiding stimuli associated with the trauma and increased arousal are present for at least two days but not longer than four weeks. When the symptoms persist beyond four weeks, the patient may have post-traumatic stress disorder. The symptoms of distress response after spontaneous abortion include psychologic, physical, cognitive and behavioral effects; however, patients with distress response after spontaneous abortion often do not meet the criteria for acute or post-traumatic stress disorder. After spontaneous abortion, as many as 10 percent of women may have acute stress disorder and up to 1 percent may have post-traumatic stress disorder. Critical incident stress debriefing, which may be administered by trained family physicians or mental health practitioners, may help patients who are having a stress disorder after a spontaneous abortion.

  9. Epigenetics of cell fate reprogramming and its implications for neurological disorders modelling.

    PubMed

    Grzybek, Maciej; Golonko, Aleksandra; Walczak, Marta; Lisowski, Pawel

    2017-03-01

    The reprogramming of human induced pluripotent stem cells (hiPSCs) proceeds in a stepwise manner with reprogramming factors binding and epigenetic composition changes during transition to maintain the epigenetic landscape, important for pluripotency. There arises a question as to whether the aberrant epigenetic state after reprogramming leads to epigenetic defects in induced stem cells causing unpredictable long term effects in differentiated cells. In this review, we present a comprehensive view of epigenetic alterations accompanying reprogramming, cell maintenance and differentiation as factors that influence applications of hiPSCs in stem cell based technologies. We conclude that sample heterogeneity masks DNA methylation signatures in subpopulations of cells and thus believe that beside a genetic evaluation, extensive epigenomic screening should become a standard procedure to ensure hiPSCs state before they are used for genome editing and differentiation into neurons of interest. In particular, we suggest that exploitation of the single-cell composition of the epigenome will provide important insights into heterogeneity within hiPSCs subpopulations to fast forward development of reliable hiPSC-based analytical platforms in neurological disorders modelling and before completed hiPSC technology will be implemented in clinical approaches.

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

    PubMed Central

    Ognjenović, Jana; Wu, Jiang; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Ling, Jiqiang; Simonović, Miljan

    2016-01-01

    Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggest that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. This report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. PMID:26869582

  11. Intrathecal baclofen therapy for neurological disorders: a sound knowledge base but many challenges remain.

    PubMed

    Brennan, P M; Whittle, I R

    2008-08-01

    Continuous infusion of intrathecal baclofen (ITB) via a subcutaneously implanted pump has developed over the last 20 years as a powerful tool in the management of spasticity in various adult and paediatric neurological conditions. Acting more focally on spinal GABA receptors, ITB causes fewer systemic side effects than orally administered baclofen. The result is facilitation of daily caring, and symptomatic relief from painful spasm. With increasing experience of ITB use, novel applications and indications are emerging. These include the management of dystonia and chronic neuropathic pain. However, despite some recent authoritative reviews, there is still uncertainty about optimal use and evaluation of this therapy. Many challenges remain. How can efficacy of therapy best be assessed both at primary testing and after pump implantation? What is the precise mechanism of baclofen action in different brain and spinal disorders associated with spasticity and dystonia? Does placement of the spinal catheter tip influence efficacy? What is the cranio-caudal gradient of CSF baclofen levels at given pump flow rates and does this matter? What CSF baclofen levels are efficacious in various conditions? Why do some patients with the same primary condition require large differences in ITB dose? What are the relative merits of programmable versus constant infusion rate pumps? What are the implications of setting up multidisciplinary teams for long term follow up? This review evaluates these questions and highlights other areas for further investigation.

  12. Identification of neuron-related genes for cell therapy of neurological disorders by network analysis* #

    PubMed Central

    Su, Li-ning; Song, Xiao-qing; Wei, Hui-ping; Yin, Hai-feng

    2017-01-01

    Bone mesenchymal stem cells (BMSCs) differentiated into neurons have been widely proposed for use in cell therapy of many neurological disorders. It is therefore important to understand the molecular mechanisms underlying this differentiation. We screened differentially expressed genes between immature neural tissues and untreated BMSCs to identify the genes responsible for neuronal differentiation from BMSCs. GSE68243 gene microarray data of rat BMSCs and GSE18860 gene microarray data of rat neurons were received from the Gene Expression Omnibus database. Transcriptome Analysis Console software showed that 1248 genes were up-regulated and 1273 were down-regulated in neurons compared with BMSCs. Gene Ontology functional enrichment, protein-protein interaction networks, functional modules, and hub genes were analyzed using DAVID, STRING 10, BiNGO tool, and Network Analyzer software, revealing that nine hub genes, Nrcam, Sema3a, Mapk8, Dlg4, Slit1, Creb1, Ntrk2, Cntn2, and Pax6, may play a pivotal role in neuronal differentiation from BMSCs. Seven genes, Dcx, Nrcam, Sema3a, Cntn2, Slit1, Ephb1, and Pax6, were shown to be hub nodes within the neuronal development network, while six genes, Fgf2, Tgfβ1, Vegfa, Serpine1, Il6, and Stat1, appeared to play an important role in suppressing neuronal differentiation. However, additional studies are required to confirm these results. PMID:28124845

  13. Vocal acoustic analysis as a biometric indicator of information processing: Implications for neurological and psychiatric disorders

    PubMed Central

    Cohen, Alex S.; Dinzeo, Thomas J.; Donovan, Neila J.; Brown, Caitlin E.; Morrison, Sean C.

    2015-01-01

    Vocal expression reflects an integral component of communication that varies considerably within individuals across contexts and is disrupted in a range of neurological and psychiatric disorders. There is reason to suspect that variability in vocal expression reflects, in part, the availability of “on-line” resources (e.g., working memory, attention). Thus, understanding vocal expression is a potentially important biometric index of information processing, not only across but within individuals over time. A first step in this line of research involves establishing a link between vocal expression and information processing systems in healthy adults. The present study employed a dual attention experimental task where participants provided natural speech while simultaneously engaged in a baseline, medium or high nonverbal processing-load task. Objective, automated, computerized analysis was employed to measure vocal expression in 226 adults. Increased processing load resulted in longer pauses, fewer utterances, greater silence overall and less variability in frequency and intensity levels. These results provide compelling evidence of a link between information processing resources and vocal expression, and provide important information for the development of an automated, inexpensive and uninvasive biometric measure of information processing. PMID:25656172

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

    DOE PAGES

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

    2016-02-10

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

  15. Targeting neuronal nitric oxide synthase as a valuable strategy for the therapy of neurological disorders

    PubMed Central

    Maccallini, Cristina; Amoroso, Rosa

    2016-01-01

    The management of neurological disorders have huge and increasing human and economic costs. Despite this, there is a scarcity of effective therapeutics, and there is an extreme urgency for new and real treatments. In this short review we analyze some promising advancements in the search of new bioactive molecules targeting neuronal nitric oxide synthase (nNOS), an enzyme deputed to the biosynthesis of nitric oxide (NO). In different conditions of neuronal damages, this molecule is overproduced, contributing to the pathogenesis and progression of neuronal diseases. Two main approaches to modulate nNOS are discussed: a first one consisting in the direct inhibition of the enzyme by means of small organic molecules, which can be also active against other different targets involved in such diseases. A second section is dedicated to molecules able to prevent the formation of the ternary complex N-methyl-D-aspartate (NMDA)-type glutamate receptors, postsynaptic density-95 (PSD95) protein-nNOS, which is necessary to activate the latter for the biosynthesis of NO. PMID:28123402

  16. Model-driven therapeutic treatment of neurological disorders: reshaping brain rhythms with neuromodulation

    PubMed Central

    Modolo, Julien; Legros, Alexandre; Thomas, Alex W.; Beuter, Anne

    2011-01-01

    Electric stimulation has been investigated for several decades to treat, with various degrees of success, a broad spectrum of neurological disorders. Historically, the development of these methods has been largely empirical but has led to a remarkably efficient, yet invasive treatment: deep brain stimulation (DBS). However, the efficiency of DBS is limited by our lack of understanding of the underlying physiological mechanisms and by the complex relationship existing between brain processing and behaviour. Biophysical modelling of brain activity, describing multi-scale spatio-temporal patterns of neuronal activity using a mathematical model and taking into account the physical properties of brain tissue, represents one way to fill this gap. In this review, we illustrate how biophysical modelling is beginning to emerge as a driving force orienting the development of innovative brain stimulation methods that may move DBS forward. We present examples of modelling works that have provided fruitful insights in regards to DBS underlying mechanisms, and others that also suggest potential improvements for this neurosurgical procedure. The reviewed literature emphasizes that biophysical modelling is a valuable tool to assist a rational development of electrical and/or magnetic brain stimulation methods tailored to both the disease and the patient's characteristics. PMID:22419974

  17. Identification of neuron-related genes for cell therapy of neurological disorders by network analysis.

    PubMed

    Su, Li-Ning; Song, Xiao-Qing; Wei, Hui-Ping; Yin, Hai-Feng

    Bone mesenchymal stem cells (BMSCs) differentiated into neurons have been widely proposed for use in cell therapy of many neurological disorders. It is therefore important to understand the molecular mechanisms underlying this differentiation. We screened differentially expressed genes between immature neural tissues and untreated BMSCs to identify the genes responsible for neuronal differentiation from BMSCs. GSE68243 gene microarray data of rat BMSCs and GSE18860 gene microarray data of rat neurons were received from the Gene Expression Omnibus database. Transcriptome Analysis Console software showed that 1248 genes were up-regulated and 1273 were down-regulated in neurons compared with BMSCs. Gene Ontology functional enrichment, protein-protein interaction networks, functional modules, and hub genes were analyzed using DAVID, STRING 10, BiNGO tool, and Network Analyzer software, revealing that nine hub genes, Nrcam, Sema3a, Mapk8, Dlg4, Slit1, Creb1, Ntrk2, Cntn2, and Pax6, may play a pivotal role in neuronal differentiation from BMSCs. Seven genes, Dcx, Nrcam, sema3a, Cntn2, Slit1, Ephb1, and Pax6, were shown to be hub nodes within the neuronal development network, while six genes, Fgf2, Tgfβ1, Vegfa, Serpine1, Il6, and Stat1, appeared to play an important role in suppressing neuronal differentiation. However, additional studies are required to confirm these results.

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

    SciTech Connect

    Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Ling, Jiqiang; Simonovic, Miljan

    2016-02-10

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

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

    PubMed Central

    Meng, Xiangling; Wang, Wei; Lu, Hui; He, Ling-jie; Chen, Wu; Chao, Eugene S; Fiorotto, Marta L; Tang, Bin; Herrera, Jose A; Seymour, Michelle L; Neul, Jeffrey L; Pereira, Fred A; Tang, Jianrong; Xue, Mingshan; Zoghbi, Huda Y

    2016-01-01

    Many postnatal onset neurological disorders such as autism spectrum disorders (ASDs) and intellectual disability are thought to arise largely from disruption of excitatory/inhibitory homeostasis. Although mouse models of Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-function mutations in MECP2, display impaired excitatory neurotransmission, the RTT phenotype can be largely reproduced in mice simply by removing MeCP2 from inhibitory GABAergic neurons. To determine what role excitatory signaling impairment might play in RTT pathogenesis, we generated conditional mouse models with Mecp2 either removed from or expressed solely in glutamatergic neurons. MeCP2 deficiency in glutamatergic neurons leads to early lethality, obesity, tremor, altered anxiety-like behaviors, and impaired acoustic startle response, which is distinct from the phenotype of mice lacking MeCP2 only in inhibitory neurons. These findings reveal a role for excitatory signaling impairment in specific neurobehavioral abnormalities shared by RTT and other postnatal neurological disorders. DOI: http://dx.doi.org/10.7554/eLife.14199.001 PMID:27328325

  20. [CHARACTERIZATION OF VESTIBULAR DISORDERS IN THE INJURED PERSONS WITH THE BRAIN CONCUSSION IN ACUTE PERIOD].

    PubMed

    Skobska, O E; Kadzhaya, N V; Andreyev, O A; Potapov, E V

    2015-04-01

    There were examined 32 injured persons, ageing (34.1 ± 1.3) yrs at average, for the brain commotion (BC). The adopted protocol SCAT-3 (Standardized Concussion Assessment Tool, 3rd ed.), DHI (Dizziness Handicap Inventory questionnaire), computer stabilography (KS) were applied for the vestibular disorders diagnosis. There was established, that in acute period of BC a dyssociation between regression of objective neurological symptoms and permanence of the BC indices occurs, what confirms a latent disorder of the balance function. Changes of basic indices of statokinesiography, including increase of the vibration amplitude enhancement in general centre of pressure in a saggital square and the BC square (235.3 ± 13.7) mm2 in a modified functional test of Romberg with the closed eyes is possible to apply as objective criteria for the BC diagnosis.

  1. Mental, neurological, and substance use disorders in people living with HIV/AIDS in low- and middle-income countries.

    PubMed

    Chibanda, Dixon; Benjamin, Laura; Weiss, Helen A; Abas, Melanie

    2014-09-01

    Depression, alcohol use disorders (AUD), and neurocognitive disorders are the 3 most prevalent mental, neurological, and substance use disorders in people living with HIV infection in low- and middle-income countries (LMICs). Importantly, they have an impact on everyday functions and on HIV outcomes. Many LMICs have validated tools to screen for and diagnose depression and AUD in the general population that can be used among people living with HIV infection. Current screening and diagnostic methods for HIV-associated neurocognitive disorders in the era of antiretroviral therapy are suboptimal and require further research. In our view, 2 research priorities are most critical. One is the development of an integrated screening approach for depression, AUD, and neurocognitive disorders that can be used by nonspecialists in LMICs. Second, research is needed on interventions for depression and AUD that also target behavior change, as these could impact on adherence to antiretroviral therapy and improve mental symptoms. Mentorship and fellowship schemes at an individual and institutional level need to be further supported to build capacity and provide platforms for research on HIV and mental, neurological, and substance use disorders in LMICs.

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

    PubMed

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

    2016-09-01

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

  3. Computerized Functional Reach Test to Measure Balance Stability in Elderly Patients With Neurological Disorders

    PubMed Central

    Scena, Silvio; Steindler, Roberto; Ceci, Moira; Zuccaro, Stefano Maria; Carmeli, Eli

    2016-01-01

    Background The ability to maintain static and dynamic balance is a prerequisite for safe walking and for obtaining functional mobility. For this reason, a reliable and valid means of screening for risk of falls is needed. The functional reach test (FRT) is used in many countries, yet it does not provide some kinematic parameters such as shoulder or pelvic girdles translation. The purpose was to analyze video records measuring of distance, velocity, time length, arm direction and girdles translation while doing FRT. Methods A cross-sectional, descriptive study was conducted where the above variables were correlated to the mini-mental state examination (MMSE) for mental status and the Tinetti balance assessment test, which have been validated, in order to computerize the FRT (cFRT) for elderly patients with neurological disorders. Eighty patients were tested and 54 were eligible to serve as experimental group. The patients underwent the MMSE, the Tinetti test and the FRT. LAB view software was used to record the FRT performances and to process the videos. The control group consisted of 51 healthy subjects who had been previously tested. Results The experimental group was not able to perform the tests as well as the healthy control subjects. The video camera provided valuable kinematic results such as bending down while performing the forward reach test. Conclusions Instead of manual measurement, we proposed to use a cheap with fair resolution web camera to accurately estimate the FRT. The kinematic parameters were correlated with Tinetti and MMSE scores. The performance values established in this study indicate that the cFRT is a reliable and valid assessment, which provides more accurate data than “manual” test about functional reach. PMID:27635176

  4. A case of acute paraneoplastic neurological syndrome in BRAF mutant metastatic melanoma.

    PubMed

    Lee, Shu F; Atkinson, Victoria

    2016-08-01

    A 58-year-old man with indolent metastatic BRAF mutant melanoma presented with several days' history of progressive ataxia and dysdiadochokinesia. His PET/computed tomography restaging scan indicated two new fluorine-18-fluorodeoxyglucose-avid mesenteric lymph nodes. Meanwhile, his MRI brain and whole spine were within normal limits. A lumbar puncture indicated an elevated protein level with a normal cell count and negative paraneoplastic antibodies. Because of the lack of an alternative differential, the diagnosis of paraneoplastic syndrome was made. He was started on high-dose corticosteroids as well as dabrafenib and trametinib. Despite this, his neurological symptoms continued to progress. Consequently, he was trialed on a course of intravenous immunoglobulin, which stabilized his symptoms. He continued to improve over several weeks, with near-complete resolution of all his neurological symptoms, and showed a complete radiological response of his disease. To our knowledge, this is the first reported case of paraneoplastic neurological syndrome with mixed neurology associated with BRAF mutant cutaneous melanoma that responded to BRAF targeted therapy.

  5. Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross-sectional study

    PubMed Central

    Khan, Raja B.; Hudson, Melissa M.; Ledet, Davonna S.; Morris, E. Brannon; Pui, Ching-Hon; Howard, Scott C.; Krull, Kevin R.; Hinds, Pamela S.; Crom, Debbie; Browne, Emily; Zhu, Liang; Rai, Shesh; Srivastava, Deokumar; Ness, Kirsten K.

    2014-01-01

    Purpose Childhood acute lymphoblastic leukemia (ALL) is treated with potentially neurotoxic drugs and neurologic complications in long-term survivors are inadequately studied. This study investigated neurologic morbidity and its effect on quality of life in long-term survivors of childhood ALL. Methods Prospective, single institution, cross-sectional, institutional review board-approved study of long-term ALL survivors. Participants were recruited from institutional clinics. Participants answered an investigator-administered questionnaire followed by evaluation by a neurologist. Quality of life (QOL) was also assessed. Results Of the 162 participants recruited over a 3-year period, 83.3 % reported at least one neurologic symptom of interest, 16.7 % had single symptom, 11.1 % had two symptoms, and 55.6 % had three or more symptoms. Symptoms were mild and disability was low in the majority of participants with neurologic symptoms. Median age at ALL diagnosis was 3.9 years (0.4–18.6), median age at study enrollment was 15.7 years (6.9–28.9), and median time from completion of ALL therapy was 7.4 years (1.9–20.3). On multivariable analyses, female sex correlated with presence of dizziness, urinary incontinence, constipation, and neuropathy; use of≥10 doses of triple intrathecal chemotherapy correlated with uri-nary incontinence, back pain, and neuropathy; cranial radiation with ataxia; history of ALL relapse with fatigue; and CNS leukemia at diagnosis with seizures. Decline in mental QOL was associated with migraine and tension type headaches, while physical QOL was impaired by presence of dizziness and falls. Overall, good QOL and physical function was maintained by a majority of participants. Conclusions Neurologic symptoms were present in 83 % long-term ALL survivors. Symptoms related morbidity and QOL impairment is low in majority of survivors. Female sex, ≥10 doses of intrathecal chemotherapy, and history of ALL relapse predispose to impaired QOL

  6. Beyond Neural Cubism: Promoting a Multidimensional View of Brain Disorders by Enhancing the Integration of Neurology and Psychiatry in Education

    PubMed Central

    Taylor, Joseph J.; Williams, Nolan R.; George, Mark S.

    2014-01-01

    Cubism was an influential early 20th century art movement characterized by angular, disjointed imagery. The two-dimensional appearance of Cubist figures and objects is created through juxtaposition of angles. The authors posit that the constrained perspectives found in Cubism may also be found in the clinical classification of brain disorders. Neurological disorders are often separated from psychiatric disorders as if they stem from different organ systems. Maintaining two isolated clinical disciplines fractionalizes the brain in the same way that Pablo Picasso fractionalized figures and objects in his Cubist art. This Neural Cubism perpetuates a clinical divide that does not reflect the scope and depth of neuroscience. All brain disorders are complex and multidimensional, with aberrant circuitry and resultant psychopharmacology manifesting as altered behavior, affect, mood or cognition. Trainees should receive a multidimensional education based on modern neuroscience, not a partial education based on clinical precedent. The authors briefly outline the rationale for increasing the integration of neurology and psychiatry and discuss a nested model with which clinical neuroscientists (neurologists and psychiatrists) can approach and treat brain disorders. PMID:25340364

  7. Beyond neural cubism: promoting a multidimensional view of brain disorders by enhancing the integration of neurology and psychiatry in education.

    PubMed

    Taylor, Joseph J; Williams, Nolan R; George, Mark S

    2015-05-01

    Cubism was an influential early-20th-century art movement characterized by angular, disjointed imagery. The two-dimensional appearance of Cubist figures and objects is created through juxtaposition of angles. The authors posit that the constrained perspectives found in Cubism may also be found in the clinical classification of brain disorders. Neurological disorders are often separated from psychiatric disorders as if they stemmed from different organ systems. Maintaining two isolated clinical disciplines fractionalizes the brain in the same way that Pablo Picasso fractionalized figures and objects in his Cubist art. This Neural Cubism perpetuates a clinical divide that does not reflect the scope and depth of neuroscience. All brain disorders are complex and multidimensional, with aberrant circuitry and resultant psychopharmacology manifesting as altered behavior, affect, mood, or cognition. Trainees should receive a multidimensional education based on modern neuroscience, not a partial education based on clinical precedent. The authors briefly outline the rationale for increasing the integration of neurology and psychiatry and discuss a nested model with which clinical neuroscientists (neurologists and psychiatrists) can approach and treat brain disorders.

  8. Acute Stress Disorder as a Predictor of Post-Traumatic Stress Disorder in Physical Assault Victims

    ERIC Educational Resources Information Center

    Elklit, Ask; Brink, Ole

    2004-01-01

    The authors' objective was to examine the ability of acute stress disorder (ASD) and other trauma-related factors in a group of physical assault victims in predicting post-traumatic stress disorder (PTSD) 6 months later. Subjects included 214 victims of violence who completed a questionnaire 1 to 2 weeks after the assault, with 128 participating…

  9. Does Acute Stress Disorder Predict Posttraumatic Stress Disorder Following Bank Robbery?

    ERIC Educational Resources Information Center

    Hansen, Maj; Elklit, Ask

    2013-01-01

    Unfortunately, the number of bank robberies is increasing and little is known about the subsequent risk of posttraumatic stress disorder (PTSD). Several studies have investigated the prediction of PTSD through the presence of acute stress disorder (ASD). However, there have only been a few studies following nonsexual assault. The present study…

  10. The Relationship between Acute Stress Disorder and Posttraumatic Stress Disorder Following Cancer

    ERIC Educational Resources Information Center

    Kangas, Maria; Henry, Jane L.; Bryant, Richard A.

    2005-01-01

    In this study, the authors investigated the relationship between acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) following cancer diagnosis. Patients who were recently diagnosed with 1st onset head and neck or lung malignancy (N = 82) were assessed for ASD within the initial month following their diagnosis and reassessed (n =…

  11. Diagnosis of Attention-Deficit/Hyperactivity Disorder and Its Behavioral, Neurological, and Genetic Roots

    ERIC Educational Resources Information Center

    Mueller, Kathryn L.; Tomblin, J. Bruce

    2012-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common developmental disorder often associated with other developmental disorders including speech, language, and reading disorders. Here, we review the principal features of ADHD and current diagnostic standards for the disorder. We outline the ADHD subtypes, which are based upon the dimensions…

  12. A review of acute stress disorder in DSM-5.

    PubMed

    Bryant, Richard A; Friedman, Matthew J; Spiegel, David; Ursano, Robert; Strain, James

    2011-09-01

    Acute stress disorder (ASD) was introduced into DSM-IV to describe acute stress reactions (ASRs) that occur in the initial month after exposure to a traumatic event and before the possibility of diagnosing posttraumatic stress disorder (PTSD), and to identify trauma survivors in the acute phase who are high risk for PTSD. This review considers ASD in relation to other diagnostic approaches to acute stress responses, critiques the evidence of the predictive power of ASD, and discusses ASD in relation to Adjustment Disorder. The evidence suggests that ASD does not adequately identify most people who develop PTSD. This review presents a number of options and preliminary considerations to be considered for DSM-5. It is proposed that ASD be limited to describing severe ASRs (that are not necessarily precursors of PTSD). The evidence suggests that the current emphasis on dissociation may be overly restrictive and does not recognize the heterogeneity of early posttraumatic stress responses. It is proposed that ASD may be better conceptualized as the severity of acute stress responses that does not require specific clusters to be present.

  13. [Some neurologic and psychiatric complications in endocrine disorders: the thyroid gland].

    PubMed

    Aszalós, Zsuzsa

    2007-02-18

    Thyroid hormones are of primary importance for the perinatal development of the central nervous system, and for normal function of the adult brain. These hormones primarily regulate the transcription of specific target genes. They increase the cortical serotonergic neurotransmission, and play an important role in regulating central noradrenergic and GABA function. Thyroid deficiency during the perinatal period results in mental retardation. Hypothyroidism of the adults causes most frequently dementia and depression. Other less common clinical pictures include myxoedema coma, dysfunction of cerebellum and cranial nerves. Hypothyroidism also increases predisposition of stroke. Peripheral diseases frequently include polyneuropathy, carpal tunnel syndrome, myalgic state, and rarely myokymia. Nearly all the hyperthyroid patients show minor psychiatric signs, and infrequently psychosis, dementia, confusion state, depression, apathetic thyrotoxicosis, thyrotoxic crisis, seizures, pyramidal signs, or chorea occur. The peripheral complications may be indicated by chronic thyrotoxic myopathy, infiltrative ophthalmopathy, myasthenia gravis, periodic hypokalemic paralysis and polyneuropathy. Generalized resistance to thyroid hormone was confirmed in a number of patients with attention deficit-hyperactivity disorder. Significantly elevated antithyroid antibody titers characterize Hashimoto's encephalopathy. This condition is a rare, acute - subacute, serious, life threatening, but steroid-responsive, relapsing-remitting, autoimmune disease.

  14. Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders

    PubMed Central

    Barral, Serena; Kurian, Manju A.

    2016-01-01

    The study of neurological disorders often presents with significant challenges due to the inaccessibility of human neuronal cells for further investigation. Advances in cellular reprogramming techniques, have however provided a new source of human cells for laboratory-based research. Patient-derived induced pluripotent stem cells (iPSCs) can now be robustly differentiated into specific neural subtypes, including dopaminergic, inhibitory GABAergic, motorneurons and cortical neurons. These neurons can then be utilized for in vitro studies to elucidate molecular causes underpinning neurological disease. Although human iPSC-derived neuronal models are increasingly regarded as a useful tool in cell biology, there are a number of limitations, including the relatively early, fetal stage of differentiated cells and the mainly two dimensional, simple nature of the in vitro system. Furthermore, clonal variation is a well-described phenomenon in iPSC lines. In order to account for this, robust baseline data from multiple control lines is necessary to determine whether a particular gene defect leads to a specific cellular phenotype. Over the last few years patient-derived neural cells have proven very useful in addressing several mechanistic questions related to central nervous system diseases, including early-onset neurological disorders of childhood. Many studies report the clinical utility of human-derived neural cells for testing known drugs with repurposing potential, novel compounds and gene therapies, which then can be translated to clinical reality. iPSCs derived neural cells, therefore provide great promise and potential to gain insight into, and treat early-onset neurological disorders. PMID:27656126

  15. Acute Stress Disorder: Conceptual Issues and Treatment Outcomes

    ERIC Educational Resources Information Center

    Koucky, Ellen M.; Galovski, Tara E.; Nixon, Reginald D. V.

    2012-01-01

    Acute stress disorder (ASD) was included as a diagnosis to the 4th edition of the "Diagnostic and Statistical Manual" (American Psychiatric Association, 1994) as a way of describing pathological reactions in the first month following a trauma. Since that time, ASD has been the focus of some controversy, particularly regarding the theoretical basis…

  16. Communication Disorders and Treatment in the Acute Trauma Center Setting.

    ERIC Educational Resources Information Center

    Schwartz-Cowley, Roberta; Stepanik, Mark J.

    1989-01-01

    The Shock Trauma Center of the Maryland Institute for Emergency Medical Services Systems instituted a comprehensive speech-language pathology program to provide acute intervention for communicative disorders in a critical/intensive care environment. This article provides a profile of the Center, a review of communicative impairments, and examples…

  17. Acute auditory agnosia as the presenting hearing disorder in MELAS.

    PubMed

    Miceli, Gabriele; Conti, Guido; Cianfoni, Alessandro; Di Giacopo, Raffaella; Zampetti, Patrizia; Servidei, Serenella

    2008-12-01

    MELAS is commonly associated with peripheral hearing loss. Auditory agnosia is a rare cortical auditory impairment, usually due to bilateral temporal damage. We document, for the first time, auditory agnosia as the presenting hearing disorder in MELAS. A young woman with MELAS (A3243G mtDNA mutation) suffered from acute cortical hearing damage following a single stroke-like episode, in the absence of previous hearing deficits. Audiometric testing showed marked central hearing impairment and very mild sensorineural hearing loss. MRI documented bilateral, acute lesions to superior temporal regions. Neuropsychological tests demonstrated auditory agnosia without aphasia. Our data and a review of published reports show that cortical auditory disorders are relatively frequent in MELAS, probably due to the strikingly high incidence of bilateral and symmetric damage following stroke-like episodes. Acute auditory agnosia can be the presenting hearing deficit in MELAS and, conversely, MELAS should be suspected in young adults with sudden hearing loss.

  18. [Hyponatremia in acute intracranial disorders: cerebral salt wasting].

    PubMed

    Betjes, M G; Koopmans, R P

    2000-03-18

    Hyponatraemia is a frequent finding in the course of an acute intracranial disease, especially after a subarachnoid haemorrhage. The fall in plasma sodium concentration is usually mild and not below 124 mmol/l but may reach dangerously low levels with serious neurological complications. In the early 1950s the cause of the hyponatraemia was believed to be primarily excessive natriuresis and therefore named 'cerebral salt wasting'. After the description of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) this was favoured as the most likely explanation. Only in recent years has it become evident that many hyponatraemic patients with acute brain disease are actually hypovolaemic. This is compatible with the original diagnosis of cerebral salt wasting. The increased plasma concentrations of natriuretic peptides are likely to mediate the increased natriuresis. Cerebral salt wasting can be treated with a simple regimen of water and salt suppletion. If needed a mineralocorticoid like fludrocortisone can be given to increase renal tubular sodium reabsorption.

  19. Self-management in neurological disorders: systematic review of the literature and potential interventions in multiple sclerosis care.

    PubMed

    Rae-Grant, Alex D; Turner, Aaron P; Sloan, Alicia; Miller, Deborah; Hunziker, James; Haselkorn, Jodie K

    2011-01-01

    Our objective was to review the current body of evidence supporting the efficacy of self-management programs in individuals with multiple sclerosis (MS) and other chronic neurological conditions. We reviewed published literature using standardized search terms; examined self-management interventions in a variety of chronic neurological disorders, including MS; and classified studies using the evidence classification established by the American Academy of Neurology. We reviewed 527 abstracts, of which 39 met our inclusion criteria for evaluation. Of the 39 studies, 3 provided class I evidence assessing the efficacy of self-management interventions: a randomized controlled trial of a telephone counseling program for health promotion in MS, a home-based exercise program for reducing falls in people with Parkinson disease, and the comparison of a fitness center program versus a home-based exercise program for people with traumatic brain injury. The remaining studies provided additional support for self-management interventions with a lesser degree of methodologic rigor (class II, class III, or class IV evidence). We concluded that self-management strategies are applicable to chronic neurological diseases, but a need exists for more rigorous studies in this area. We provide recommendations for future intervention study methodologies with a specific emphasis on MS care.

  20. Acute and subacute drug-induced movement disorders.

    PubMed

    Burkhard, Pierre R

    2014-01-01

    Many pharmacological agents may induce a variety of movement disorders, including dystonia, tremor, parkinsonism, myoclonus and dyskinesia, with an acute, subacute or more chronic time course. Motor symptoms may be isolated or part of a more extensive cerebral or systemic condition, such as the neuroleptic malignant syndrome or the serotonin syndrome. Drug-induced movement disorders share a number of features that should make them easy to identify, including a clear temporal relationship between medication initiation and symptom onset, a dose-effect, and, with the exception of tardive syndromes, complete resolution after discontinuation of the offending agent. Diagnosis relies on a thorough medication history. Medications commonly involved include dopamine receptor blockers, antidepressants and anti-epileptics, among many others. Mechanisms underlying drug-induced movement disorders involve blockade, facilitation or imbalance of dopamine, serotonin, noradrenaline and cholinergic neurotransmission in the basal ganglia. The present review focuses on drug-induced movement disorders that typically develop as an acute (hours to days) or subacute (days to weeks) event, including acute dystonic reactions, akathisia, drug-induced parkinsonism, neuroleptic malignant syndrome, serotonin syndrome, parkinsonism-hyperpyrexia syndrome, drug-induced tremor, drug-induced hyperkinesias and movement disorders associated with the use of recreational drugs.

  1. Diagnosis and Treatment of Neurological Disorders by Millimeter-Wave Stimulation

    NASA Technical Reports Server (NTRS)

    Siegel, Peter H.; Pikov, Victor

    2011-01-01

    Increasingly, millimeter waves are being employed for telecomm, radar, and imaging applications. To date in the U.S, however, very few investigations on the impact of this radiation on biological systems at the cellular level have been undertaken. In the beginning, to examine the impact of millimeter waves on cellular processes, researchers discovered that cell membrane depolarization may be triggered by low levels of integrated power at these high frequencies. Such a situation could be used to advantage in the direct stimulation of neuronal cells for applications in neuroprosthetics and diagnosing or treating neurological disorders. An experimental system was set up to directly monitor cell response on exposure to continuous-wave, fixed-frequency, millimeter-wave radiation at low and modest power levels (0.1 to 100 safe exposure standards) between 50 and 100 GHz. Two immortalized cell lines derived from lung and neuronal tissue were transfected with green fluorescent protein (GFP) that locates on the inside of the cell membrane lipid bi-layer. Oxonol dye was added to the cell medium. When membrane depolarization occurs, the oxonal bound to the outer wall of the lipid bi-layer can penetrate close to the inner wall where the GFP resides. Under fluorescent excitation (488 nm), the normally green GFP (520 nm) optical signal quenches and gives rise to a red output when the oxonol comes close enough to the GFP to excite a fluorescence resonance energy transfer (FRET) with an output at 620 nm. The presence of a strong FRET signature upon exposures of 30 seconds to 2 minutes at 5-10 milliwatts per square centimeter RF power at 50 GHz, followed by a return to the normal 520-nm GFP signal after a few minutes indicating repolarization of the membrane, indicates that low levels of RF energy may be able to trigger non-destructive membrane depolarization without direct cell contact. Such a mechanism could be used to stimulate neuronal cells in the cortex without the need for

  2. Acute Necrotizing Encephalopathy: An Underrecognized Clinicoradiologic Disorder

    PubMed Central

    Wu, Xiujuan; Wu, Wei; Pan, Wei; Wu, Limin; Liu, Kangding; Zhang, Hong-Liang

    2015-01-01

    Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration. However, the causal relationship between viral infections and ANE and the exact pathogenesis of ANE remain unclear; both environmental and host factors might be involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or sporadic ANE; however, few cases are recurrent and with familial episodes. The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant. Further the missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) were identified. Although the clinical course and the prognosis of ANE are diverse, the hallmark of neuroradiologic manifestation of ANE is multifocal symmetric brain lesions which are demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI). The treatment of ANE is still under investigation. We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease. PMID:25873770

  3. Dissociative disorders in acute psychiatric inpatients in Taiwan.

    PubMed

    Chiu, Chui-De; Meg Tseng, Mei-Chih; Chien, Yi-Ling; Liao, Shih-Cheng; Liu, Chih-Min; Yeh, Yei-Yu; Hwu, Hai-Gwo; Ross, Colin A

    2017-04-01

    Dissociative disorders have been documented to be common psychiatric disorders which can be detected reliably with standardized diagnostic instruments in North American and European psychiatric inpatients and outpatients (20.6% and 18.4%, respectively). However, there are concerns about their cross-cultural manifestations as an apparently low prevalence rate has been reported in East Asian inpatients and outpatients (1.7% and 4.9%, respectively). It is unknown whether the clinical profile of dissociative disorders in terms of their core symptomatic clusters, associated comorbid disorders, and environmental risk factors that has emerged in western clinical populations can also be found in non-western clinical populations. A standardized structured interview for DSM-IV dissociative disorders, post-traumatic stress disorder, and a history of interpersonal victimization was administered in a sample of Taiwanese acute psychiatric inpatients. Our results showed that 19.5% of our participants met criteria for a DSM-IV dissociative disorder, mostly dissociative disorder not otherwise specified. More importantly, the western clinical profile of dissociative disorders also characterized our patients, including a poly-symptomatic presentation and a history of interpersonal trauma in both childhood and adulthood. Our results lend support to the conclusion that cross-cultural manifestations of dissociative pathology in East Asia are similar to those in North America and Europe.

  4. Splenic hematoma in acute pancreatitis. Role of coagulation disorders.

    PubMed

    Clavé, P; Guillaumes, S; Blanco, I; Martínez de Hurtado, J; Esquius, J; Marruecos, L; Fontcuberta, J; Pérez, C; Farré, A; Lluís, F

    1992-08-01

    Splenic hematomas are infrequent complications of acute pancreatitis. In some cases, local factors that may play a role in the pathogenesis of the hematoma (thrombosis of the splenic artery or veins, intrasplenic pseudocysts, perisplenic adhesions, enzymatic digestion) are found. In the absence of local factors, the etiology of splenic hemorrhage remains unknown. We report two cases of splenic hematoma occurring during an acute necro-hemorrhagic pancreatitis associated with renal failure that required renal replacement therapy (hemodialysis and continuous arteriovenous hemodialysis). In both cases, more than half of splenic parenchyma was affected by multiple infarctions. No local factors responsible for the splenic abnormalities were detected in either case. Thrombosis of the splenic arterial microcirculation and a coagulation disorder consistent with disseminated intravascular coagulation was detected in one patient. In the second patient, coagulation disorders secondary to either liver disease, pancreatitis and its septic complications, or extracorporeal circuit heparinization for renal replacement therapy were present. Coagulation disorders should be considered whenever a splenic hematoma is found in a patient with acute pancreatitis. Disseminated intravascular coagulation may be the etiology of a splenic hematoma in acute pancreatitis.

  5. An observational study on electrolyte disorders in the acute phase of ischemic stroke and their prognostic value.

    PubMed

    Fofi, Luisa; Dall'armi, Valentina; Durastanti, Laura; Valenza, Alessandro; Lorenzano, Svetlana; Prencipe, Massimiliano; Toni, Danilo

    2012-04-01

    Data on electrolyte disorders in neurological conditions and in acute stroke are somewhat scanty and not easily compared. In our Stroke Unit we studied patients hospitalized within six hours of the onset of an acute ischemic stroke and recorded their demographic and clinical data. Blood test results were recorded before any pharmacological therapy. A total of 475 individuals (256 M, 219 F; range: 14-96 years) treated over a period of 18 consecutive months, were selected. According to multiple logistic regression analysis, the baseline National Institute of Health Stroke Scale (NIHSS) score (odds ratio [OR]=1.33; 95% confidence interval [CI]: 1.22-1.44) and natremia alterations (OR=6.89; 95% CI=1.94-24.40) were associated with higher odds of death. Based on the ordinal logistic regression analysis, the baseline NIHSS score (OR=1.07; 95% CI=1.03-1.10) and baseline hypernatremia (OR=9.69; 95% CI=1.55-60.69) were related to early neurological worsening. Our work suggests an association between serum sodium alterations and mortality, and between high sodium levels and neurological clinical impairment, in the acute phase of an ischemic stroke.

  6. REM Sleep Behavior Disorder and REM Sleep Without Atonia as an Early Manifestation of Degenerative Neurological Disease

    PubMed Central

    McCarter, Stuart J.; St Louis, Erik K.

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by repeated episodes of dream enactment behavior and REM sleep without atonia (RSWA) during polysomnography recording. RSWA is characterized by increased phasic or tonic muscle activity seen on polysomnographic electromyogram channels. RSWA is a requisite diagnostic feature of RBD, but may also be seen in patients without clinical symptoms or signs of dream enactment as an incidental finding in neurologically normal individuals, especially in patients receiving antidepressant therapy. RBD may be idiopathic or symptomatic. Patients with idiopathic RBD often later develop other neurological features including parkinsonism, orthostatic hypotension, anosmia, or cognitive impairment. RSWA without clinical symptoms as well as clinically overt RBD also often occurs concomitantly with the α-synucleinopathy family of neurodegenerative disorders, which includes idiopathic Parkinson disease, Lewy body dementia, and multiple system atrophy. This review article considers the epidemiology of RBD, clinical and polysomnographic diagnostic standards for both RBD and RSWA, previously reported associations of RSWA and RBD with neurodegenerative disorders and other potential causes, the pathophysiology of which brain structures and networks mediate dysregulation of REM sleep muscle atonia, and considerations for the effective and safe management of RBD. PMID:22328094

  7. REM sleep behavior disorder and REM sleep without atonia as an early manifestation of degenerative neurological disease.

    PubMed

    McCarter, Stuart J; St Louis, Erik K; Boeve, Bradley F

    2012-04-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by repeated episodes of dream enactment behavior and REM sleep without atonia (RSWA) during polysomnography recording. RSWA is characterized by increased phasic or tonic muscle activity seen on polysomnographic electromyogram channels. RSWA is a requisite diagnostic feature of RBD, but may also be seen in patients without clinical symptoms or signs of dream enactment as an incidental finding in neurologically normal individuals, especially in patients receiving antidepressant therapy. RBD may be idiopathic or symptomatic. Patients with idiopathic RBD often later develop other neurological features including parkinsonism, orthostatic hypotension, anosmia, or cognitive impairment. RSWA without clinical symptoms as well as clinically overt RBD also often occurs concomitantly with the α-synucleinopathy family of neurodegenerative disorders, which includes idiopathic Parkinson disease, Lewy body dementia, and multiple system atrophy. This review article considers the epidemiology of RBD, clinical and polysomnographic diagnostic standards for both RBD and RSWA, previously reported associations of RSWA and RBD with neurodegenerative disorders and other potential causes, the pathophysiology of which brain structures and networks mediate dysregulation of REM sleep muscle atonia, and considerations for the effective and safe management of RBD.

  8. Peptide regulation of cofilin activity in the CNS: A novel therapeutic approach for treatment of multiple neurological disorders.

    PubMed

    Shaw, Alisa E; Bamburg, James R

    2017-02-20

    Cofilin is a ubiquitous protein which cooperates with many other actin-binding proteins in regulating actin dynamics. Cofilin has essential functions in nervous system development including neuritogenesis, neurite elongation, growth cone pathfinding, dendritic spine formation, and the regulation of neurotransmission and spine function, components of synaptic plasticity essential for learning and memory. Cofilin's phosphoregulation is a downstream target of many transmembrane signaling processes, and its misregulation in neurons has been linked in rodent models to many different neurodegenerative and neurological disorders including Alzheimer disease (AD), aggression due to neonatal isolation, autism, manic/bipolar disorder, and sleep deprivation. Cognitive and behavioral deficits of these rodent models have been largely abrogated by modulation of cofilin activity using viral-mediated, genetic, and/or small molecule or peptide therapeutic approaches. Neuropathic pain in rats from sciatic nerve compression has also been reduced by modulating the cofilin pathway within neurons of the dorsal root ganglia. Neuroinflammation, which occurs following cerebral ischemia/reperfusion, but which also accompanies many other neurodegenerative syndromes, is markedly reduced by peptides targeting specific chemokine receptors, which also modulate cofilin activity. Thus, peptide therapeutics offer potential for cost-effective treatment of a wide variety of neurological disorders. Here we discuss some recent results from rodent models using therapeutic peptides with a surprising ability to cross the rodent blood brain barrier and alter cofilin activity in brain. We also offer suggestions as to how neuronal-specific cofilin regulation might be achieved.

  9. 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…

  10. CT findings of a thoracic vertebral hemangioma presenting with acute neurological symptoms.

    PubMed

    Tan, Sinan; Kurt, Aydın; Okutan, Ozerk; Keskin, Suat

    2011-01-01

    Vertebral body hemangiomas are benign lesions and account for 4% of all spinal tumors. The most common histological type is cavernous hemangioma. These tumors generally locate in the vertebral body as a solitary lesion. Multiple lesions are seen in approximately 25-30% of vertebral hemangiomas. Mostly they are asymptomatic and incidentally found with radiological studies. Symptomatic vertebral hemangiomas are rare and represent < 1% of all hemangiomas; however, if untreated, they may cause local or radicular pain and neurological deficits ranging from myeloradiculopathy to paralysis. In this case we aim to present preoperative and postoperative Computed Tomography findings of a cavernous hemangioma that caused sudden motor deficit and was localised to the thoracic vertebra corpus and posterior elements.

  11. Tourette's Disorder: Genetic Update, Neurological Correlates, and Evidence-Based Interventions

    ERIC Educational Resources Information Center

    Phelps, LeAdelle

    2008-01-01

    This article provides an update of the search for genetic markers related to Tourette's Disorder. The probable neurophysiology of the disorder is reviewed. Frequently prescribed medications are related to the probable biological bases of the disorder. Behavioral interventions and assessment tools are examined. It is concluded that evidence based…

  12. Resilience as a correlate of acute stress disorder symptoms in patients with acute myocardial infarction

    PubMed Central

    Meister, Rebecca E; Weber, Tania; Princip, Mary; Schnyder, Ulrich; Barth, Jürgen; Znoj, Hansjörg; Schmid, Jean-Paul; von Känel, Roland

    2015-01-01

    Objectives Myocardial infarction (MI) may be experienced as a traumatic event causing acute stress disorder (ASD). This mental disorder has an impact on the daily life of patients and is associated with the development of post-traumatic stress disorder. Trait resilience has been shown to be a protective factor for post-traumatic stress disorder, but its association with ASD in patients with MI is elusive and was examined in this study. Methods We investigated 71 consecutive patients with acute MI within 48 h of having stable haemodynamic conditions established and for 3 months thereafter. All patients completed the Acute Stress Disorder Scale and the Resilience Scale to self-rate the severity of ASD symptoms and trait resilience, respectively. Results Hierarchical regression analysis showed that greater resilience was associated with lower symptoms of ASD independent of covariates (b=−0.22, p<0.05). Post hoc analysis revealed resilience level to be inversely associated with the ASD symptom clusters of re-experiencing (b=−0.05, p<0.05) and arousal (b=−0.09, p<0.05), but not with dissociation and avoidance. Conclusions The findings suggest that patients with acute MI with higher trait resilience experience relatively fewer symptoms of ASD during MI. Resilience was particularly associated with re-experiencing and arousal symptoms. Our findings contribute to a better understanding of resilience as a potentially important correlate of ASD in the context of traumatic situations such as acute MI. These results emphasise the importance of identifying patients with low resilience in medical settings and to offer them adequate support. PMID:26568834

  13. Risk Factors for Delirium During Acute and Subacute Stages of Various Disorders in Patients Admitted to Rehabilitation Units

    PubMed Central

    2016-01-01

    Objective To assess the risk factors for delirium in patients admitted to a rehabilitation unit for acute or subacute neurological or musculoskeletal disorders. Methods We reviewed the medical records of 537 patients admitted to a rehabilitation unit and selected 398 patients in the acute or subacute stage of various neurological or musculoskeletal disorders. Among them, patients who had suffered from delirium were categorized into the delirium group (n=65), and the other patients were categorized into the non-delirium group (n=333). As potential risk factors for delirium, the patients' diagnosis, underlying disease, demographic data, hospital stay duration, surgery, and laboratory findings were reviewed, and the differences between the two groups with respect to independent risk factors were analyzed. Results The average age in the delirium group was higher; the hospital stay and pre-transfer periods were longer. A large proportion of the patients were admitted for musculoskeletal disorders, and many patients had diabetes mellitus, dementia, and depression as underlying diseases. Laboratory tests revealed increases in the white blood cells (WBC), glucose, blood urea nitrogen (BUN), total bilirubin, aspartate transaminase (AST), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels in the delirium group, while the hemoglobin, calcium, phosphorus, protein, albumin, and potassium levels were decreased. Depression, musculoskeletal disorders, traumatic brain injury, elevated WBC, BUN, AST, and CRP levels, and decreased potassium and phosphorus levels were identified as independent risk factors for delirium. Conclusion Risk factors treatable before delirium onset were identified in rehabilitation patients in acute and subacute stages of various disorders. Early diagnosis and prevention of these risk factors could decrease delirium occurrence and increase rehabilitation effectiveness. PMID:28119839

  14. Next-gen sequencing identifies non-coding variation disrupting miRNA-binding sites in neurological disorders.

    PubMed

    Devanna, P; Chen, X S; Ho, J; Gajewski, D; Smith, S D; Gialluisi, A; Francks, C; Fisher, S E; Newbury, D F; Vernes, S C

    2017-03-14

    Understanding the genetic factors underlying neurodevelopmental and neuropsychiatric disorders is a major challenge given their prevalence and potential severity for quality of life. While large-scale genomic screens have made major advances in this area, for many disorders the genetic underpinnings are complex and poorly understood. To date the field has focused predominantly on protein coding variation, but given the importance of tightly controlled gene expression for normal brain development and disorder, variation that affects non-coding regulatory regions of the genome is likely to play an important role in these phenotypes. Herein we show the importance of 3 prime untranslated region (3'UTR) non-coding regulatory variants across neurodevelopmental and neuropsychiatric disorders. We devised a pipeline for identifying and functionally validating putatively pathogenic variants from next generation sequencing (NGS) data. We applied this pipeline to a cohort of children with severe specific language impairment (SLI) and identified a functional, SLI-associated variant affecting gene regulation in cells and post-mortem human brain. This variant and the affected gene (ARHGEF39) represent new putative risk factors for SLI. Furthermore, we identified 3'UTR regulatory variants across autism, schizophrenia and bipolar disorder NGS cohorts demonstrating their impact on neurodevelopmental and neuropsychiatric disorders. Our findings show the importance of investigating non-coding regulatory variants when determining risk factors contributing to neurodevelopmental and neuropsychiatric disorders. In the future, integration of such regulatory variation with protein coding changes will be essential for uncovering the genetic causes of complex neurological disorders and the fundamental mechanisms underlying health and disease.Molecular Psychiatry advance online publication, 14 March 2017; doi:10.1038/mp.2017.30.

  15. Alternate centromere inactivation in a pseudodicentric (15;20)(pter;pter) associated with a progressive neurological disorder.

    PubMed Central

    Rivera, H; Zuffardi, O; Maraschio, P; Caiulo, A; Anichini, C; Scarinci, R; Vivarelli, R

    1989-01-01

    A 13 year old male with a severe progressive neurological disorder was found to have a pseudodicentric chromosome resulting from a telomeric fusion 15p;20p. In lymphocytes, the centromeric constriction of the abnormal chromosome was always that of the chromosome 20, while in fibroblasts both centromeres were alternately constricted. Cd staining was positive only at the active centromere, but a weak anticentromere immunofluorescence was present at the inactive one. We suggest that centromere inactivation results from a modified conformation of the functional DNA sequences preventing normal binding to centromere specific proteins. We also postulate that the patient's disorder, reminiscent of a spongy glioneuronal dystrophy as seen in Alper's and Creutzfeldt-Jakob diseases, may be secondary to the presence of the pathogenic isoform of the prion protein encoded by a gene mapped to 20p12----pter. Images PMID:2685311

  16. Integral Characterization of Defective BDNF/TrkB Signalling in Neurological and Psychiatric Disorders Leads the Way to New Therapies

    PubMed Central

    Tejeda, Gonzalo S.; Díaz-Guerra, Margarita

    2017-01-01

    Enhancement of brain-derived neurotrophic factor (BDNF) signalling has great potential in therapy for neurological and psychiatric disorders. This neurotrophin not only attenuates cell death but also promotes neuronal plasticity and function. However, an important challenge to this approach is the persistence of aberrant neurotrophic signalling due to a defective function of the BDNF high-affinity receptor, tropomyosin-related kinase B (TrkB), or downstream effectors. Such changes have been already described in several disorders, but their importance as pathological mechanisms has been frequently underestimated. This review highlights the relevance of an integrative characterization of aberrant BDNF/TrkB pathways for the rational design of therapies that by combining BDNF and TrkB targets could efficiently promote neurotrophic signalling. PMID:28134845

  17. Bedside screening to detect oropharyngeal dysphagia in patients with neurological disorders: an updated systematic review.

    PubMed

    Kertscher, Berit; Speyer, Renée; Palmieri, Maria; Plant, Chris

    2014-04-01

    Oropharyngeal dysphagia is a highly prevalent comorbidity in neurological patients and presents a serious health threat, which may le to outcomes of aspiration pneumonia ranging from hospitalization to death. Therefore, an early identification of risk followed by an accurate diagnosis of oropharyngeal dysphagia is fundamental. This systematic review provides an update of currently available bedside screenings to identify oropharyngeal dysphagia in neurological patients. An electronic search was carried out in the databases PubMed, Embase, CINAHL, and PsychInfo (formerly PsychLit), and all hits from 2008 up to December 2012 were included in the review. Only studies with sufficient methodological quality were considered, after which the psychometric characteristics of the screening tools were determined. Two relevant bedside screenings were identified, with a minimum sensitivity and specificity of ≥70 and ≥60 %, respectively.

  18. Systems biological approach on neurological disorders: a novel molecular connectivity to aging and psychiatric diseases

    PubMed Central

    2011-01-01

    Background Systems biological approach of molecular connectivity map has reached to a great interest to understand the gene functional similarities between the diseases. In this study, we developed a computational framework to build molecular connectivity maps by integrating mutated and differentially expressed genes of neurological and psychiatric diseases to determine its relationship with aging. Results The systematic large-scale analyses of 124 human diseases create three classes of molecular connectivity maps. First, molecular interaction of disease protein network generates 3632 proteins with 6172 interactions, which determines the common genes/proteins between diseases. Second, Disease-disease network includes 4845 positively scored disease-disease relationships. The comparison of these disease-disease pairs with Medical Subject Headings (MeSH) classification tree suggests 25% of the disease-disease pairs were in same disease area. The remaining can be a novel disease-disease relationship based on gene/protein similarity. Inclusion of aging genes set showed 79 neurological and 20 psychiatric diseases have the strong association with aging. Third and lastly, a curated disease biomarker network was created by relating the proteins/genes in specific disease contexts, such analysis showed 73 markers for 24 diseases. Further, the overall quality of the results was achieved by a series of statistical methods, to avoid insignificant data in biological networks. Conclusions This study improves the understanding of the complex interactions that occur between neurological and psychiatric diseases with aging, which lead to determine the diagnostic markers. Also, the disease-disease association results could be helpful to determine the symptom relationships between neurological and psychiatric diseases. Together, our study presents many research opportunities in post-genomic biomarkers development. PMID:21226925

  19. [Acute hemiplegia and hemianesthesia together with decreased tendon reflexes mimicking acute stroke representing a conversion disorder].

    PubMed

    Schif, Aharon; Ravid, Sarit; Hafner, Hava; Shahar, Eli

    2010-01-01

    Acute hemiplegia and hemianesthesia is commonly caused by obstruction of major cortical arteries. Such a presentation secondary to a conversion reaction is very rare, especially in the pediatric age group. The authors report an adolescent presenting with acute complete left-sided hemiplegia and sensory loss together with decreased tendon reflexes mimicking an acute arterial stroke. Examination revealed Hoover's sign was present and the patient was oblivious to his stern neurological state. Movement of his paralytic limbs was observed during sleep. Cortical and spinal CT, cortical MRI, motor and somatosensory evoked potentials and a PET study were all normal. As such, the diagnosis of psychogenic hemiplegia was established, apparently within a period that the patient had experienced severe emotional stress while questioning his gender identity. After three days, the adolescent began to move the paralytic limbs along gradual resolution of sensory deficit, leading to complete clinical recovering within two months. Although extremely rare, a conversion reaction should be taken into account in children presenting with acute hemiplegia and anaesthesia, even accompanied with decreased tendon reflexes, when the patient is oblivious to his alleged grave state, and when clinical observations such as Hoover's sign remain intact, substantiated by normal extensive radiological and neurophysiological investigation. Intact motor evoked potentials serve as a key for the diagnosis of psychogenic hemiplegia and, should therefore be performed in suspected cases.

  20. Comparison of admission random glucose, fasting glucose, and glycated hemoglobin in predicting the neurological outcome of acute ischemic stroke: a retrospective study

    PubMed Central

    Sung, Jia-Ying; Chen, Chin-I; Hsieh, Yi-Chen; Chen, Yih-Ru; Wu, Hsin-Chiao; Chan, Lung; Hu, Chaur-Jong; Hu, Han-Hwa; Chiou, Hung-Yi

    2017-01-01

    Background Hyperglycemia is a known predictor of negative outcomes in stroke. Several glycemic measures, including admission random glucose, fasting glucose, and glycated hemoglobin (HbA1c), have been associated with bad neurological outcomes in acute ischemic stroke, particularly in nondiabetic patients. However, the predictive power of these glycemic measures is yet to be investigated. Methods This retrospective study enrolled 484 patients with acute ischemic stroke from January 2009 to March 2013, and complete records of initial stroke severity, neurological outcomes at three months, and glycemic measures were evaluated. We examined the predictive power of admission random glucose, fasting glucose, and HbA1c for neurological outcomes in acute ischemic stroke. Furthermore, subgroup analyses of nondiabetic patients and patients with diabetes were performed separately. Results Receiver operating characteristic (ROC) analysis revealed that admission random glucose and fasting glucose were significant predictors of poor neurological outcomes, whereas HbA1c was not (areas under the ROC curve (AUCs): admission random glucose = 0.564, p = 0.026; fasting glucose = 0.598, p = 0.001; HbA1c = 0.510, p = 0.742). Subgroup analyses of nondiabetic patients and those with diabetes revealed that only fasting glucose predicts neurological outcomes in patients with diabetes, and the AUCs of these three glycemic measures did not differ between the two groups. A multivariate logistic regression analysis of the study patients indicated that only age, initial stroke severity, and fasting glucose were independent predictors of poor neurological outcomes, whereas admission random glucose and HbA1c were not (adjusted odds ratio: admission random glucose = 1.002, p = 0.228; fasting glucose = 1.005, p = 0.039; HbA1c = 1.160, p = 0.076). Furthermore, subgroup multivariate logistic regression analyses of nondiabetic patients and those with diabetes indicated that none of the three glycemic

  1. Neurology and psychiatry in Babylon.

    PubMed

    Reynolds, Edward H; Wilson, James V Kinnier

    2014-09-01

    We here review Babylonian descriptions of neurological and psychiatric disorders, including epilepsy, stroke, psychoses, obsessive compulsive disorder, phobias, psychopathic behaviour, depression and anxiety. Most of these accounts date from the first Babylonian dynasty of the first half of the second millennium BC, within a millennium and a half of the origin of writing. The Babylonians were remarkably acute and objective observers of medical disorders and human behaviour. Their detailed descriptions are surprisingly similar to modern 19th and 20th century AD textbook accounts, with the exception of subjective thoughts and feelings which are more modern fields of enquiry. They had no knowledge of brain or psychological function. Some neuropsychiatric disorders, e.g. stroke or facial palsy, had a physical basis requiring the attention of a physician or asû, using a plant and mineral based pharmacology; some disorders such as epilepsy, psychoses, depression and anxiety were regarded as supernatural due to evil demons or spirits, or the anger of personal gods, and thus required the intervention of the priest or ašipu; other disorders such as obsessive compulsive disorder and psychopathic behaviour were regarded as a mystery. The Babylonians were the first to describe the clinical foundations of neurology and psychiatry. We discuss these accounts in relation to subsequent and more modern clinical descriptions.

  2. [Heterogeneity of cognitive disorders in the acute stage of the first ischemic carotid stroke].

    PubMed

    Kulesh, A A; Shestakov, V V

    2012-01-01

    We studied 116 patients in the acute stage of the first ischemic carotid stroke. The patients had no cognitive disorders before the disease. All patients underwent a neuropsychological examination in 3-4th week after stroke. The severity of neurological deficit was evaluated with the NIHSS in 4-7th day. To study cognitive disturbances in depth, we divided the neuropsychological tests into 5 integral characteristics in accordance with the cognitive domains: attention, executive functioning, memory, speech, visual-spatial functions. Most of patients performed best on the memory index and worst on the attention index. Four groups of cognitive disturbances were singled out: "typical" that was characterized by the combination of intact memory with impaired attention (31% of patients); "atypical" with the prevalence of memory disturbances (19%); "typical transitive" (42%) and "atypical transitive" (8%). The greater severity of stroke as assessed by the NIHSS was associated with the "typical" variant of cognitive disturbances. Therefore, the neurodynamic disturbances represent basic neurological deficit in stroke but every fifth patient demonstrates the amnestic profile of cognitive disturbances that suggests the presence of the concomitant neurodegenerative process.

  3. Plasma copeptin as a predictor of intoxication severity and delayed neurological sequelae in acute carbon monoxide poisoning.

    PubMed

    Pang, Li; Wang, He-Lei; Wang, Zhi-Hao; Wu, Yang; Dong, Ning; Xu, Da-Hai; Wang, Da-Wei; Xu, Hong; Zhang, Nan

    2014-09-01

    The present study was designed to assess the usefulness of measuring plasma levels of copeptin (a peptide co-released with the hypothalamic stress hormone vasopressin) as a biomarker for the severity of carbon monoxide (CO) poisoning and for predicting delayed neurological sequelae (DNS). Seventy-two patients with CO poisoning and 72 sex and age matched healthy individuals were recruited. Plasma copeptin levels were measured on admission from CO poisoning patients and for healthy individuals at study entry by using a sandwich immunoassay. The CO poisoning patients were divided into two groups according to severity (unconscious and conscious) and occurrence of DNS. The mean plasma copeptin levels (52.5±18.5 pmol/L) in the unconscious group were significantly higher than in the conscious group (26.3±12.7 pmol/L) (P<0.001). Plasma copeptin levels of more than 39.0 pmol/L detected CO poisoning with severe neurological symptoms e.g. unconsciousness (sensitivity 84.6% and specificity 81.4%). The plasma copeptin levels were higher in patients with DNS compared to patients without DNS (52.2±20.6 pmol/L vs. 27.9±14.8 pmol/L, P<0.001). Plasma copeptin levels higher than 40.5 pmol/L predicted the development of DNS (sensitivity 77.8%, specificity 82.1%). Plasma copeptin levels were identified as an independent predictor for intoxication severity [odds ratio (OR) 1.261, 95% confidence interval (CI) 1.112-1.638, P=0.002] and DNS (OR 1.313, 95% CI 1.106-1.859, P=0.001). Thus, plasma copeptin levels independently related to intoxication severity and were identified as a novel biomarker for predicting DNS after acute CO poisoning.

  4. Hysteria, conversion and functional disorders: a neurological contribution to classification issues.

    PubMed

    Reynolds, Edward H

    2012-10-01

    Proposals by psychiatrists to reclassify conversion disorder in DSM-5 and ICD-11 are proving difficult and controversial. Patients with conversion disorder usually present initially to neurologists, who often use different concepts and terminology. History and clinical practice suggest that the way forward is to seek agreed principles and a common understanding between the two disciplines, preferably in a single universal classification.

  5. GABAB receptor antibodies in limbic encephalitis and anti-GAD–associated neurologic disorders

    PubMed Central

    Boronat, A.; Sabater, L.; Saiz, A.; Dalmau, J.

    2011-01-01

    Background: γ-Aminobutyric acid-B receptor antibodies (GABABR-ab) were recently described in 15 patients with limbic encephalitis (LE), associated with small-cell lung cancer (SCLC) or with concurrent glutamic acid decarboxylase (GAD) antibodies. We analyzed the frequency of GABABR-ab in 147 patients with LE or neurologic syndromes associated with GAD-ab. Methods: We examined the presence of GABABR-ab in 70 patients with LE (33 paraneoplastic with onconeural antibodies, 18 paraneoplastic without onconeural antibodies [5 with Gad-ab], and 19 idiopathic with either GAD-ab [5 patients] or seronegative) and 77 patients with GAD-ab-associated neurologic syndromes other than LE (29 stiff-person syndrome, 28 cerebellar ataxia, 14 epilepsy, and 6 with diverse paraneoplastic neurologic syndromes). GABABR-ab were analyzed in serum or CSF by indirect immunofluorescence on HEK293 cells transfected with GABAB1 and GABAB2 receptor subunits. Results: GABABR-ab were detected in 10 of the 70 patients with LE (14%). Eight had SCLC and 2 were idiopathic. One of the 8 patients with LE with SCLC had an additional onconeural antibody (Hu) and 2 GAD-ab. GABABR-ab were identified in 7 (70%) of the 10 patients with LE and SCLC without onconeural antibodies. GABABR-ab antibodies were not found in patients with GAD-ab and stiff-person syndrome, idiopathic cerebellar ataxia, or epilepsy. However, one patient with GAD-ab, paraneoplastic cerebellar ataxia, and anaplastic carcinoid of the thymus also presented GABABR-ab. Conclusions: GABABR-ab are the most common antibodies found in LE associated with SCLC previously considered “seronegative.” In patients with GAD-ab, the frequency of GABABR-ab is low and only observed in the context of cancer. PMID:21357831

  6. Nose-to-brain drug delivery by nanoparticles in the treatment of neurological disorders.

    PubMed

    Ong, Wei-Yi; Shalini, Suku-Maran; Costantino, Luca

    2014-01-01

    Many potential drugs for the treatment of neurological diseases are unable to reach the brain in sufficient enough concentrations to be therapeutic because of the blood brain barrier. On the other hand, direct delivery of drugs to the brain provides the possibility of a greater therapeutic-toxic ratio than with systemic drug delivery. The use of intranasal delivery of therapeutic agents to the brain provides a means of bypassing the blood brain barrier in a non-invasive manner. In this respect, nanosized drug carriers were shown to enhance the delivery of drugs to CNS compared to equivalent drug solution formulations. Neurological conditions that have been studied in animal models that could benefit from nose-to-brain delivery of nanotherapeutics include pain, epilepsy, neurodegenerative disease and infectious diseases. The delivery of drugs to the brain via the nose-to-brain route holds great promise, on the basis of preclinical research by means of drug delivery systems such as polymeric nanoparticles and clinical data related to intranasal delivery to CNS of large molecular weight biologics administered in solution, but safety issues about toxicity on nasal mucosa, Np transport into the brain, delivery only to specific brain regions and variability in the adsorbed dose still represent research topics that need to be considered, with a view of clinical translation of these delivery systems.

  7. Regulation of ABC Efflux Transporters at Blood-Brain Barrier in Health and Neurological Disorders

    PubMed Central

    Qosa, Hisham; Miller, David S.; Pasinelli, Piera; Trotti, Davide

    2015-01-01

    The strength of the blood-brain barrier (BBB) in providing protection to the central nervous system from exposure to circulating chemicals is maintained by tight junctions between endothelial cells and by a broad range of transporter proteins that regulate exchange between CNS and blood. The most important transporters that restrict the permeability of large number of toxins as well as therapeutic agents are the ABC transporters. Among them, P-gp, BCRP, MRP1 and MRP2 are the utmost studied. These efflux transporters are neuroprotective, limiting the brain entry of neurotoxins; however, they could also restrict the entry of many therapeutics and contribute to CNS pharmacoresistance. Characterization of several regulatory pathways that govern expression and activity of ABC efflux transporters in the endothelium of brain capillaries have led to an emerging consensus that these processes are complex and contain several cellular and molecular elements. Alterations in ABC efflux transporters expression and/or activity occur in several neurological diseases. Here, we review the signaling pathways that regulate expression and transport activity of P-gp, BCRP, MRP1 and MRP2 as well as how their expression/activity changes in neurological diseases. PMID:26187753

  8. Neurology and orthopaedics

    PubMed Central

    Houlden, Henry; Charlton, Paul; Singh, Dishan

    2007-01-01

    Neurology encompasses all aspects of medicine and surgery, but is closer to orthopaedic surgery than many other specialities. Both neurological deficits and bone disorders lead to locomotor system abnormalities, joint complications and limb problems. The main neurological conditions that require the attention of an orthopaedic surgeon are disorders that affect the lower motor neurones. The most common disorders in this group include neuromuscular disorders and traumatic peripheral nerve lesions. Upper motor neurone disorders such as cerebral palsy and stroke are also frequently seen and discussed, as are chronic conditions such as poliomyelitis. The management of these neurological problems is often coordinated in the neurology clinic, and this group, probably more than any other, requires a multidisciplinary team approach. PMID:17308288

  9. 78 FR 39299 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... Disorders and Stroke Special, Emphasis Panel, International Traumatic Brain Injury Research Initiative. Date... Traumatic Encephalopathy and Delayed Effects of Traumatic Brain Injury. Date: July 19, 2013. Time: 1:30...

  10. 78 FR 18996 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-28

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Disorders; 93.854, Biological Basis Research in the Neurosciences, National Institutes of Health,...

  11. 75 FR 42758 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-22

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion... Disorders; 93.854, Biological Basis Research in the Neurosciences, National Institutes of Health, HHS)...

  12. 75 FR 70014 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Disorders; 93.854, Biological Basis Research in the Neurosciences, National Institutes of Health, HHS)...

  13. 75 FR 57971 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-23

    ... with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of... Disorders; 93.854, Biological Basis Research in the Neurosciences, National Institutes of Health,...

  14. Manic depressive psychosis and schizophrenia are neurological disorders at the extremes of CNS maturation and nutritional disorders associated with a deficit in marine fat.

    PubMed

    Saugstad, L F

    2001-12-01

    The maturational theory of brain development comprises manic depressive psychosis and schizophrenia. It holds that the disorders are part of human diversity in growth and maturation, which explains their ubiquity, shared susceptibility genes and multifactorial inheritance. Rate of maturation and age at puberty are the genotype; the disorders are localized at the extremes with normality in between. This is based on the association between onset of puberty and the final regressive event, with pruning of 40% of excitatory synapses leaving the inhibitory ones fairly unchanged. This makes excitability, a fundamental property of nervous tissue, a distinguishing factor: the earlier puberty, the greater excitability--the later puberty, the greater deficit. Biological treatment supports deviation from the norm: neuroleptics are convulsant; antidepressives are anti-epiletogenic. There is an association between onset of puberty and body-build: early maturers are pyknic broad-built, late ones linearly leptosomic. This discrepancy is similar to that in the two disorders, supporting the theory that body-build is the phenotype. Standard of living is the environmental factor, which affects pubertal age and shifts the panorama of mental illness accordingly. Unnatural death has increased with antipsychotics. Other treatment is needed. PUFA deficit has been observed in RBC in both disorders and striking improvements with addition of minor amounts of PUFA. This supports that dietary deficit might cause psychotic development and that prevention is possible. Other neurological disorders also profit from PUFA, underlining a general deficit in the diet.

  15. Insights into the Pathology of the α3 Na+/K+-ATPase Ion Pump in Neurological Disorders; Lessons from Animal Models

    PubMed Central

    Holm, Thomas H.; Lykke-Hartmann, Karin

    2016-01-01

    The transmembrane Na+-/K+ ATPase is located at the plasma membrane of all mammalian cells. The Na+-/K+ ATPase utilizes energy from ATP hydrolysis to extrude three Na+ cations and import two K+ cations into the cell. The minimum constellation for an active Na+-/K+ ATPase is one alpha (α) and one beta (β) subunit. Mammals express four α isoforms (α1−4), encoded by the ATP1A1-4 genes, respectively. The α1 isoform is ubiquitously expressed in the adult central nervous system (CNS) whereas α2 primarily is expressed in astrocytes and α3 in neurons. Na+ and K+ are the principal ions involved in action potential propagation during neuronal depolarization. The α1 and α3 Na+-/K+ ATPases are therefore prime candidates for restoring neuronal membrane potential after depolarization and for maintaining neuronal excitability. The α3 isoform has approximately four-fold lower Na+ affinity compared to α1 and is specifically required for rapid restoration of large transient increases in [Na+]i. Conditions associated with α3 deficiency are therefore likely aggravated by suprathreshold neuronal activity. The α3 isoform been suggested to support re-uptake of neurotransmitters. These processes are required for normal brain activity, and in fact autosomal dominant de novo mutations in ATP1A3 encoding the α3 isoform has been found to cause the three neurological diseases Rapid Onset Dystonia Parkinsonism (RDP), Alternating Hemiplegia of Childhood (AHC), and Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS). All three diseases cause acute onset of neurological symptoms, but the predominant neurological manifestations differ with particularly early onset of hemiplegic/dystonic episodes and mental decline in AHC, ataxic encephalopathy and impairment of vision and hearing in CAPOS syndrome and late onset of dystonia/parkinsonism in RDP. Several mouse models have been generated to study the in vivo consequences of Atp1a3 modulation

  16. Development of a Kinect-based exergaming system for motor rehabilitation in neurological disorders

    NASA Astrophysics Data System (ADS)

    Estepa, A.; Sponton Piriz, S.; Albornoz, E.; Martínez, C.

    2016-04-01

    The development of videogames for physical therapy, known as exergames, has gained much interest in the last years. In this work, a sytem for rehabilitation and clinical evaluation of neurological patients is presented. The Microsoft Kinect device is used to track the full body of patients, and three games were developed to exercise and assess different aspects of balance and gait rehabilitation. The system provides visual feedback by means of an avatar that follows the movements of the patients, and sound and visual stimuli for giving orders during the experience. Also, the system includes a database and management tools for further analysis and monitoring of therapies. The results obtained show, on the one side, a great reception and interest of patients to use the system. On the other side, the specialists considered very useful the data collected and the quantitative analysis provided by the system, which was then adopted for the clinical routine.

  17. Apotemnophilia, body integrity identity disorder or xenomelia? Psychiatric and neurologic etiologies face each other

    PubMed Central

    Sedda, Anna; Bottini, Gabriella

    2014-01-01

    This review summarizes the available studies of a rare condition in which individuals seek the amputation of a healthy limb or desire to be paraplegic. Since 1977, case reports and group studies have been produced, trying to understand the cause of this unusual desire. The main etiological hypotheses are presented, from the psychological/psychiatric to the most recent neurologic explanation. The paradigms adopted and the clinical features are compared across studies and analyzed in detail. Finally, future directions and ethical implications are discussed. A proposal is made to adopt a multidisciplinary approach that comprises state-of-the-art technologies and a variety of theoretical models, including both body representation and psychological and sexual components. PMID:25045269

  18. Aicardi-Goutieres syndrome, a rare neurological disease in children: a new autoimmune disorder?

    PubMed

    Fazzi, Elisa; Cattalini, Marco; Orcesi, Simona; Tincani, Angela; Andreoli, L; Balottin, U; De Simone, M; Fredi, M; Facchetti, F; Galli, J; Giliani, S; Izzotti, A; Meini, A; Olivieri, I; Plebani, A

    2013-02-01

    Aicardi-Goutieres syndrome (AGS), described by J. Aicardi and F. Goutieres in 1984, is a rare neurological disease with onset in infancy. It is often misdiagnosed as a sequela of congenital infection or recognized later. Nowadays almost 200 cases are reported all over the world, most of them collected by the International Aicardi-Goutieres Syndrome Association (IAGSA), founded in Pavia (Italy) in 2000. AGS (MIM 225750) is a genetically-determined encephalopathy characterized by severe neurological dysfunction, acquired microcephaly associated with severe prognosis quoad valetudinem, and less frequently also quoad vitam. Some AGS children also develop some symptoms overlapping with systemic lupus erythematosus (SLE). Intracranial calcification, white matter involvement and brain atrophy revealed on MRI, lymphocytosis and elevated levels of interferon alpha (IFN-α) in the cerebrospinal fluid (CSF) are features of both AGS and congenital viral infection. No evidence of congenital infection at serological exams has ever been found. A genetic etiology was hypothesized since the first descriptions, because of the recurrence in families, and demonstrated some years ago. Nowadays five genes (AGS1-5), if mutated, can be responsible for 90% of the cases. The transmission is autosomal recessive but there are also rare "de novo" autosomal dominant cases. Even if pathogenesis is still almost unknown, it seems that responsible genes are involved in nucleic acid reparation mechanisms and consequently in a secondary activation of innate autoimmunity. The relative lack of precise information on pathogenesis and on the evolution of the disease over time has not yet allowed the creation of codified diagnostic and therapeutic models and programs.

  19. Genetic dys-regulation of astrocytic glutamate transporter EAAT2 and its implications in neurological disorders and manganese toxicity

    PubMed Central

    Karki, Pratap; Smith, Keisha; Johnson, James; Aschner, Michael; Lee, Eunsook

    2014-01-01

    Astrocytic glutamate transporters, the excitatory amino acid transporter (EAAT) 2 and EAAT1 [glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST) in rodents, respectively], are the main transporters for maintaining optimal glutamate levels in the synaptic clefts by taking up more than 90% of glutamate from extracellular space thus preventing excitotoxic neuronal death. Reduced expression and function of these transporters, especially EAAT2, has been reported in numerous neurological disorders, including amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease, schizophrenia and epilepsy. The mechanism of down-regulation of EAAT2 in these diseases has yet to be fully established. Genetic as well as transcriptional dys-regulation of these transporters by various modes, such as single nucleotide polymorphisms (SNPs) and epigenetics, resulting in impairment of their functions, might play an important role in the etiology of neurological diseases. Consequently, there has been an extensive effort to identify molecular targets for enhancement of EAAT2 expression as a potential therapeutic approach. Several pharmacological agents increase expression of EAAT2 via NF-κB and CREB at the transcriptional level. However, the negative regulatory mechanisms of EAAT2 have yet to be identified. Recent studies, including those from our laboratory, suggest that the transcriptional factor yin yang 1 (YY1) plays a critical role in the repressive effects of various neurotoxins, such as manganese (Mn), on EAAT2 expression. In this review, we will focus on transcriptional epigenetics, and translational regulation of EAAT2. PMID:25064045

  20. Treatment of Neuromyelitis Optica Spectrum Disorder: Acute, Preventive, and Symptomatic

    PubMed Central

    Kessler, Remi A.; Mealy, Maureen A.; Levy, Michael

    2016-01-01

    Opinion statement Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that primarily attacks the optic nerves and spinal cord leading to blindness and paralysis. The spectrum of the disease has expanded based on the specificity of the autoimmune response to the aquaporin-4 water channel on astrocytes. With wider recognition of NMOSD, a standard of care for treatment of this condition has condition based on a growing series of retrospective and prospective studies. This review covers the present state of the field in the treatment of acute relapses, preventive approaches, and therapies for symptoms of NMOSD. PMID:26705758