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1.
Innov Aging ; 2(2): igy025, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30480142

RESUMO

In December 2017, the National Academy of Neuropsychology convened an interorganizational Summit on Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients in Denver, Colorado. The Summit brought together representatives of a broad range of stakeholders invested in the care of older adults to focus on the topic of cognitive health and aging. Summit participants specifically examined questions of who should be screened for cognitive impairment and how they should be screened in medical settings. This is important in the context of an acute illness given that the presence of cognitive impairment can have significant implications for care and for the management of concomitant diseases as well as pose a major risk factor for dementia. Participants arrived at general principles to guide future screening approaches in medical populations and identified knowledge gaps to direct future research. Key learning points of the summit included: recognizing the importance of educating patients and healthcare providers about the value of assessing current and baseline cognition;emphasizing that any screening tool must be appropriately normalized and validated in the population in which it is used to obtain accurate information, including considerations of language, cultural factors, and education; andrecognizing the great potential, with appropriate caveats, of electronic health records to augment cognitive screening and tracking of changes in cognitive health over time.

2.
Clin Neuropsychol ; 32(7): 1193-1225, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30396329

RESUMO

In December 2017, the National Academy of Neuropsychology convened an interorganizational Summit on Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients in Denver, Colorado. The Summit brought together representatives of a broad range of stakeholders invested in the care of older adults to focus on the topic of cognitive health and aging. Summit participants specifically examined questions of who should be screened for cognitive impairment and how they should be screened in medical settings. This is important in the context of an acute illness given that the presence of cognitive impairment can have significant implications for care and for the management of concomitant diseases as well as pose a major risk factor for dementia. Participants arrived at general principles to guide future screening approaches in medical populations and identified knowledge gaps to direct future research. Key learning points of the summit included: recognizing the importance of educating patients and healthcare providers about the value of assessing current and baseline cognition; emphasizing that any screening tool must be appropriately normalized and validated in the population in which it is used to obtain accurate information, including considerations of language, cultural factors, and education; and recognizing the great potential, with appropriate caveats, of electronic health records to augment cognitive screening and tracking of changes in cognitive health over time.


Assuntos
Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Testes Neuropsicológicos , Saúde da População , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/epidemiologia , Colorado , Congressos como Assunto/tendências , Assistência à Saúde/métodos , Demência/diagnóstico , Demência/epidemiologia , Demência/psicologia , Feminino , Humanos , Masculino
4.
Neurology ; 91(11): e1013-e1021, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30111549

RESUMO

OBJECTIVE: To study the effect of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease (PD) and moderate to severe restless legs syndrome (RLS) on their RLS symptoms. METHODS: Patients undergoing STN DBS surgery for PD completed the International RLS Study Group Rating Scale (IRLS) and RLS Quality of Life (QoL) questionnaires preoperatively and postoperatively at 6 months, 1 year, and 2 years. The primary outcome measure was IRLS sum score and subscales (severity and impact) and the secondary measure was RLS QoL scores. Differences among the mean scores over time were analyzed using mixed model regression. RESULTS: Twenty-two patients were enrolled. The preoperative IRLS sum scores were 19.59 ± 6.95, severity subscale 12.91 ± 4.33, impact subscale 4.45 ± 2.72, and transformed RLS QoL score 68.30 ± 20.26. The differences between preoperative and averaged postoperative scores were IRLS sum score -7.80, severity subscale -5.50, impact subscale -1.20, and RLS QoL 4.73. The overall F tests demonstrated differences among the times for the means of the IRLS sum and subscales: p < 0.05. There were no correlations between RLS symptoms improvement and PD motor symptoms improvement or reduction in PD medications. Half of the patients had at least 50% improvement and 27% had resolution of their RLS symptoms (IRLS = 0). CONCLUSIONS: STN DBS significantly decreased RLS symptoms in patients with PD despite a decrease in dopaminergic treatment. This improvement was sustained over a 2-year period. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with PD and moderate to severe RLS, STN DBS improves RLS symptoms.


Assuntos
Estimulação Encefálica Profunda , Síndrome das Pernas Inquietas/terapia , Núcleo Subtalâmico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Síndrome das Pernas Inquietas/complicações , Estudos Retrospectivos , Resultado do Tratamento
5.
J Neurol Neurosurg Psychiatry ; 88(5): 445-451, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27965397

RESUMO

Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterised by complex motor enactment of dreams and is a potential prodromal marker of Parkinson's disease (PD). Of note, patients with PD observed during RBD episodes exhibit improved motor function, relative to baseline states during wake periods. Here, we review recent epidemiological and mechanistic findings supporting the prodromal value of RBD for PD, incorporating clinical and electrophysiological studies. Explanations for the improved motor function during RBD episodes are evaluated in light of recent publications. In addition, we present preliminary findings describing changes in the activity of the basal ganglia across the sleep-wake cycle that contribute to our understanding of RBD.


Assuntos
Doença de Parkinson/epidemiologia , Transtorno do Comportamento do Sono REM/epidemiologia , Sonhos/psicologia , Humanos , Polissonografia/métodos , Transtorno do Comportamento do Sono REM/diagnóstico , Índice de Gravidade de Doença
7.
J Neurol Sci ; 330(1-2): 119-20, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23628467

RESUMO

We describe a patient with zoster paresis and an MRI that revealed extensive spinal cord lesions from the upper cervical to the lower thoracic spinal cord. Importantly, the patient reported considerable spontaneous improvement in strength 2-3 weeks after zoster. This report reveals a previously undescribed remarkable preponderance of MRI lesions far beyond the site of zoster rash and focal lower motor neuron weakness.


Assuntos
Exantema/patologia , Herpes Zoster/patologia , Debilidade Muscular/patologia , Aciclovir/efeitos adversos , Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Idoso , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Feminino , Humanos , Imagem por Ressonância Magnética , Doença dos Neurônios Motores/patologia , Medula Espinal/patologia , Raízes Nervosas Espinhais/patologia , Valaciclovir , Valina/efeitos adversos , Valina/análogos & derivados , Valina/uso terapêutico
8.
J Neurol Sci ; 313(1-2): 193-5, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-21924743

RESUMO

We describe a 26-year-old man treated with azathioprine for myasthenia gravis who developed acute left-sided peripheral facial weakness. Brain magnetic resonance imaging (MRI) revealed enhancement in the left geniculate ganglion and in the intracanalicular and tympanic segments of the facial nerve. Analysis of cerebrospinal fluid (CSF) and serum revealed intrathecal synthesis of anti-varicella zoster virus (VZV) IgG antibody. Although previous analyses of saliva, blood mononuclear cells, serum antibodies, middle ear fluid, and auricular and geniculate zone skin scrapings have shown that a small but definite proportion of patients with idiopathic peripheral facial palsy ("Bell's palsy") have the Ramsay Hunt syndrome zoster sine herpete (RHS ZSH), this is the first confirmation of RHS ZSH by intrathecal synthesis of anti-VZV IgG antibody. In addition, herpes simplex virus (HSV)-1 DNA was found in saliva of the patient on 3 consecutive days. Simultaneous reactivation of two alphaherpesviruses (HSV-1 and VZV) in our immunosuppressed patient underscores the need to consider opportunistic infection as a cause of facial weakness.


Assuntos
Paralisia Facial/líquido cefalorraquidiano , Herpes Simples/líquido cefalorraquidiano , Herpes Zoster/líquido cefalorraquidiano , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 3/fisiologia , Hospedeiro Imunocomprometido , Doença Aguda , Adulto , Paralisia Facial/diagnóstico , Paralisia Facial/virologia , Herpes Simples/diagnóstico , Herpes Zoster/diagnóstico , Humanos , Masculino , Recidiva , Ativação Viral/fisiologia
9.
NeuroRehabilitation ; 26(1): 85-94, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20130357

RESUMO

Hypoxic-ischemic brain damage often results from a combination of cardiogenic and respiratory failure. Whether or not hypoxia in the absence of ischemia is injurious to the brain has been a topic of research. An example of hypoxia without ischemia is found in obstructive sleep apnea (OSA), which causes recurrent nocturnal oxygen desaturations. Furthermore, it is a pervasive problem in the general population, particularly in people with common disorders such as obesity or diabetes. Mounting evidence in the past decade indicates that cerebrovascular disease, specifically stroke, and neurobehavioral consequences, including excessive daytime sleepiness and cognitive deficits, are prevalent in people with OSA, at great costs to the individual well-being, public health, and the economy. Investigation of the two disease associations poses similar and unique challenges. Predictors of these sequelae need to be better defined. The apnea-hypopnea index, the most common measure of OSA, has proven to be variably related to stroke and cognitive impairment. The role of individual markers, whether they are comorbidities or differences in inherent cognitive reserve, also is incompletely understood. This review discusses the burgeoning literature on the neurological and neurobehavioral sequelae of OSA and highlights the future avenues of research in the field.


Assuntos
Transtornos Cognitivos/etiologia , Transtornos Mentais/etiologia , Doenças do Sistema Nervoso/etiologia , Apneia Obstrutiva do Sono/complicações , Transtornos Cerebrovasculares/complicações , Progressão da Doença , Humanos , Apneia Obstrutiva do Sono/etiologia
10.
J Autoimmun ; 34(4): 453-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20036106

RESUMO

The C-terminal domain of the fibrinogen gamma chain (gammaC) has been shown to bind to the integrins alphaIIbbeta3, alphaMbeta2 and alphaVbeta3. It has also been reported that a peptide derived from the alphaMbeta2-binding site of gammaC can suppress an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Here we have truncated gammaC at position 399 to remove the prothrombotic alphaIIbbeta3-binding site. We show that this truncated version of gammaC, termed gammaC399tr, can bind to activated T cells. In addition, T cells incubated with gammaC399tr secreted less IFN-gamma when stimulated with antigen and APC; however, cytokine secretion was unaltered when T cells were stimulated non-specifically with a mixture of anti-CD3 and anti-CD28 antibodies. Thus, only antigen-dependent T cell activation is inhibited by gammaC399tr. When administered intraperitoneally, gammaC399tr potently inhibited actively induced EAE and reversed ongoing disease. We hypothesize that the ability of gammaC399tr to inhibit autoreactive immune responses is a result of its ability to bind integrins. This activity was not solely dependent on the alphaMbeta2 integrin-binding site. When polyalanine was substituted for the alphaMbeta2-binding site, the resulting gammaC390polyA was still able to inhibit EAE. To our knowledge, this is the first demonstration that T cells can bind to fibrin (ogen), an important extracellular matrix protein that is deposited at sites of inflammation. Our results also identify gammaC399tr as a novel therapeutic molecule.


Assuntos
Encefalomielite Autoimune Experimental/prevenção & controle , Fibrinogênio/química , Fragmentos de Peptídeos/farmacologia , Linfócitos T/metabolismo , Animais , Autoimunidade/efeitos dos fármacos , Sítios de Ligação , Encefalomielite Autoimune Experimental/tratamento farmacológico , Fibrinogênio/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Fragmentos de Peptídeos/administração & dosagem , Ligação Proteica
11.
Am J Ophthalmol ; 140(1): 142-4, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16038662

RESUMO

PURPOSE: To report the ophthalmic findings and response to treatment in a patient with glutamic-acid decarboxylase antibodies. DESIGN: Case report. METHODS: A 55-year-old woman developed progressive, painful, low back muscle spasms, vertical diplopia, downbeating nystagmus, and asymmetric appendicular ataxia. RESULTS: Downbeating nystagmus was present in primary gaze with an alternating skew deviation in lateral gaze. Serum and cerebrospinal fluid GAD antibodies were detected. Treatment with diazepam led to resolution of spasticity, whereas repeated courses of intravenous immunoglobulin improved cerebellar function, including appendicular ataxia and downbeating nystagmus. CONCLUSIONS: Patients with GAD antibodies may have elements of both Stiff-person syndrome (muscle rigidity and spasms) and prominent cerebellar dysfunction. Treatment with diazepam rapidly improved Stiff-person symptoms, whereas IVIg was partially effective at the early stage of cerebellar dysfunction.


Assuntos
Autoanticorpos/sangue , Glutamato Descarboxilase/imunologia , Músculo Esquelético/patologia , Nistagmo Patológico/complicações , Espasmo/complicações , Rigidez Muscular Espasmódica/complicações , Autoanticorpos/líquido cefalorraquidiano , Diazepam/uso terapêutico , Diplopia/complicações , Diplopia/diagnóstico , Diplopia/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Relaxantes Musculares Centrais/uso terapêutico , Rigidez Muscular/complicações , Rigidez Muscular/diagnóstico , Rigidez Muscular/tratamento farmacológico , Nistagmo Patológico/diagnóstico , Nistagmo Patológico/tratamento farmacológico , Espasmo/diagnóstico , Espasmo/tratamento farmacológico , Rigidez Muscular Espasmódica/diagnóstico , Rigidez Muscular Espasmódica/tratamento farmacológico
12.
Virology ; 312(2): 369-80, 2003 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-12919742

RESUMO

Targeted recombination was carried out to select mouse hepatitis viruses (MHVs) in a defined genetic background, containing an MHV-JHM spike gene encoding either three heptad repeat 1 (HR1) substitutions (Q1067H, Q1094H, and L1114R) or L1114R alone. The recombinant virus, which expresses spike with the three substitutions, was nonfusogenic at neutral pH. Its replication was significantly inhibited by lysosomotropic agents, and it was highly neuroattenuated in vivo. In contrast, the recombinant expressing spike with L1114R alone mediated cell-to-cell fusion at neutral pH and replicated efficiently despite the presence of lysosomotropic agents; however, it still caused only subclinical morbidity and no mortality in animals. Thus, both recombinant viruses were highly attenuated and expressed viral antigen which was restricted to the olfactory bulbs and was markedly absent from other regions of the brains at 5 days postinfection. These data demonstrate that amino acid substitutions, in particular L1114R, within HR1 of the JHM spike reduced the ability of MHV to spread in the central nervous system. Furthermore, the requirements for low pH for fusion and viral entry are not prerequisites for the highly attenuated phenotype.


Assuntos
Substituição de Aminoácidos , Antígenos Virais/metabolismo , Encéfalo/metabolismo , Coronavirus/genética , Coronavirus/metabolismo , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/metabolismo , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/metabolismo , Animais , Antígenos Virais/química , Antígenos Virais/genética , Antígenos Virais/imunologia , Encéfalo/imunologia , Fusão Celular , Coronavirus/imunologia , DNA Recombinante/genética , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Fenótipo , Estrutura Terciária de Proteína , Glicoproteína da Espícula de Coronavírus , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Replicação Viral
13.
J Virol ; 77(2): 841-50, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12502800

RESUMO

Using isogenic recombinant murine coronaviruses expressing wild-type murine hepatitis virus strain 4 (MHV-4) or MHV-A59 spike glycoproteins or chimeric MHV-4/MHV-A59 spike glycoproteins, we have demonstrated the biological functionality of the N-terminus of the spike, encompassing the receptor binding domain (RBD). We have used two assays, one an in vitro liposome binding assay and the other a tissue culture replication assay. The liposome binding assay shows that interaction of the receptor with spikes on virions at 37 degrees C causes a conformational change that makes the virions hydrophobic so that they bind to liposomes (B. D. Zelus, J. H. Schickli, D. M. Blau, S. R. Weiss, and K. V. Holmes, J. Virol. 77: 830-840, 2003). Recombinant viruses with spikes containing the RBD of either MHV-A59 or MHV-4 readily associated with liposomes at 37 degrees C in the presence of soluble mCEACAM1(a), except for S(4)R, which expresses the entire wild-type MHV-4 spike and associated only inefficiently with liposomes following incubation with soluble mCEACAM1(a). In contrast, soluble mCEACAM1(b) allowed viruses with the MHV-A59 RBD to associate with liposomes more efficiently than did viruses with the MHV-4 RBD. In the second assay, which requires virus entry and replication, all recombinant viruses replicated efficiently in BHK cells expressing mCEACAM1(a). In BHK cells expressing mCEACAM1(b), only viruses expressing chimeric spikes with the MHV-A59 RBD could replicate, while replication of viruses expressing chimeric spikes with the MHV-4 RBD was undetectable. Despite having the MHV-4 RBD, S(4)R replicated in BHK cells expressing mCEACAM1(b); this is most probably due to spread via CEACAM1 receptor-independent cell-to-cell fusion, an activity displayed only by S(4)R among the recombinant viruses studied here. These data suggest that the RBD domain and the rest of the spike must coevolve to optimize function in viral entry and spread.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação/metabolismo , Coronavirus/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas do Envelope Viral/metabolismo , Animais , Sequência de Bases , Antígeno Carcinoembrionário , Moléculas de Adesão Celular , Linhagem Celular , Cricetinae , Primers do DNA , Lipossomos , Glicoproteínas de Membrana/química , Camundongos , Ligação Proteica , Conformação Proteica , Glicoproteína da Espícula de Coronavírus , Proteínas do Envelope Viral/química
14.
J Neurovirol ; 8(5): 400-10, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12402166

RESUMO

The cleavage and fusion properties of recombinant murine hepatitis viruses (MHV) were examined to assess the role of the cleavage signal in determining the extent of S protein cleavage, and the correlation between cleavage and induction of cell-to-cell fusion. Targeted recombination was used to introduce amino acid substitutions into the cleavage signal of the fusion glycoprotein (spike or S protein) of MHV strain A59. The recombinants were then used to address the question of the importance of S protein cleavage and viral-mediated cell-to-cell fusion on pathogenicity. Our data indicate that cleavage of spike is not solely determined by the amino acid sequence at the cleavage site, but may also depend on sequences removed from the cleavage site. In addition, efficient cell-to-cell fusion is not necessary for virulence.


Assuntos
Infecções do Sistema Nervoso Central/virologia , Infecções por Coronavirus/virologia , Glicoproteínas de Membrana/metabolismo , Vírus da Hepatite Murina/patogenicidade , Proteínas do Envelope Viral/metabolismo , Substituição de Aminoácidos , Animais , Encéfalo/virologia , Modelos Animais de Doenças , Células Gigantes/fisiologia , Glicoproteínas de Membrana/química , Camundongos , Camundongos Endogâmicos C57BL , Vírus da Hepatite Murina/genética , Recombinação Genética , Glicoproteína da Espícula de Coronavírus , Fatores de Tempo , Proteínas do Envelope Viral/química , Virulência
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