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BACKGROUND AND PURPOSE: Guidelines recommend screening stroke-survivors for cognitive impairments. We sought to collate published data on test accuracy of cognitive screening tools. METHODS: Index test was any direct, cognitive screening assessment compared against reference standard diagnosis of (undifferentiated) multidomain cognitive impairment/dementia. We used a sensitive search statement to search multiple, cross-disciplinary databases from inception to January 2014. Titles, abstracts, and articles were screened by independent researchers. We described risk of bias using Quality Assessment of Diagnostic Accuracy Studies tool and reporting quality using Standards for Reporting of Diagnostic Accuracy guidance. Where data allowed, we pooled test accuracy using bivariate methods. RESULTS: From 19 182 titles, we reviewed 241 articles, 35 suitable for inclusion. There was substantial heterogeneity: 25 differing screening tests; differing stroke settings (acute stroke, n=11 articles), and reference standards used (neuropsychological battery, n=21 articles). One article was graded low risk of bias; common issues were case-control methodology (n=7 articles) and missing data (n=22). We pooled data for 4 tests at various screen positive thresholds: Addenbrooke's Cognitive Examination-Revised (<88/100): sensitivity 0.96, specificity 0.70 (2 studies); Mini Mental State Examination (<27/30): sensitivity 0.71, specificity 0.85 (12 studies); Montreal Cognitive Assessment (<26/30): sensitivity 0.95, specificity 0.45 (4 studies); MoCA (<22/30): sensitivity 0.84, specificity 0.78 (6 studies); Rotterdam-CAMCOG (<33/49): sensitivity 0.57, specificity 0.92 (2 studies). CONCLUSIONS: Commonly used cognitive screening tools have similar accuracy for detection of dementia/multidomain impairment with no clearly superior test and no evidence that screening tools with longer administration times perform better. MoCA at usual threshold offers short assessment time with high sensitivity but at cost of specificity; adapted cutoffs have improved specificity without sacrificing sensitivity. Our results must be interpreted in the context of modest study numbers: heterogeneity and potential bias.
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Trastornos del Conocimiento/diagnóstico , Demencia/diagnóstico , Pruebas Neuropsicológicas , Accidente Cerebrovascular/psicología , Anciano , Humanos , Sensibilidad y Especificidad , Accidente Cerebrovascular/complicacionesRESUMEN
Phenylketonuria (PKU) is an inborn error of amino acid metabolism. If untreated, PKU can result in global developmental delay, learning difficulties or seizures. For that reason, PKU is included in the UK neonatal screening programme. We describe a patient in his sixth decade presenting with progressive cognitive decline and spasticity, in whom a diagnosis of PKU was eventually reached. We note that although we currently have a robust neonatal screening programme, this has not always been the case. Patients born before 1969 were not screened, and tests used in early screening programmes were less sensitive than those used today. This case serves as a reminder that inherited metabolic disorders may present in later life and may mimic the neurocognitive and radiological picture of other white matter syndromes.
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Fenilcetonurias , Recién Nacido , Humanos , Fenilcetonurias/diagnóstico , Tamizaje NeonatalRESUMEN
The histiocytoses are a rare but diverse group of disorders, ranging from localised, self-limiting lesions to disseminated, fulminant, multi-system disease. Some histiocytoses may cause or present with neurological disease and their recognition can be challenging. We illustrate this with a case, followed by a discussion of the clinical characteristics and management of the more common histiocytoses that may present to the neurologist.
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Encéfalo/patología , Enfermedad de Erdheim-Chester/diagnóstico , Enfermedad de Erdheim-Chester/terapia , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Médula Ósea/patología , Encéfalo/diagnóstico por imagen , Diagnóstico Diferencial , Enfermedad de Erdheim-Chester/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Chronic systemic inflammatory conditions, such as atherosclerosis, diabetes and obesity are associated with increased risk of stroke, which suggests that systemic inflammation may contribute to the development of stroke in humans. The hypothesis that systemic inflammation may induce brain pathology can be tested in animals, and this was the key objective of the present study. First, we assessed inflammatory changes in the brain in rodent models of chronic, systemic inflammation. PET imaging revealed increased microglia activation in the brain of JCR-LA (corpulent) rats, which develop atherosclerosis and obesity, compared to the control lean strain. Immunostaining against Iba1 confirmed reactive microgliosis in these animals. An atherogenic diet in apolipoprotein E knock-out (ApoE(-/-)) mice induced microglial activation in the brain parenchyma within 8 weeks and increased expression of vascular adhesion molecules. Focal lipid deposition and neuroinflammation in periventricular and cortical areas and profound recruitment of activated myeloid phagocytes, T cells and granulocytes into the choroid plexus were also observed. In a small, preliminary study, patients at risk of stroke (multiple risk factors for stroke, with chronically elevated C-reactive protein, but negative MRI for brain pathology) exhibited increased inflammation in the brain, as indicated by PET imaging. These findings show that brain inflammation occurs in animals, and tentatively in humans, harbouring risk factors for stroke associated with elevated systemic inflammation. Thus a "primed" inflammatory environment in the brain may exist in individuals at risk of stroke and this can be adequately recapitulated in appropriate co-morbid animal models.
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Encefalitis/epidemiología , Accidente Cerebrovascular/epidemiología , Anciano , Animales , Apolipoproteínas E/deficiencia , Aterosclerosis/epidemiología , Aterosclerosis/etiología , Aterosclerosis/patología , Química Encefálica , Proteína C-Reactiva/análisis , Comorbilidad , Dieta Aterogénica , Encefalitis/diagnóstico por imagen , Encefalitis/patología , Femenino , Humanos , Interleucina-6/sangre , Lípidos/análisis , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/patología , Persona de Mediana Edad , Obesidad/epidemiología , Obesidad/genética , Fagocitos/patología , Tomografía de Emisión de Positrones , Ratas , Ratas Mutantes , Factores de RiesgoRESUMEN
Cerebral microvascular angiopathy (MVA) is associated with clinical vascular risk factors and is characterised by histological changes, including thickening of the walls of arterial vessels and dilatation of the Virchow-Robin spaces (VRS). We have previously described two novel biomarkers of MVA based on magnetic resonance imaging (MRI), VRS dilatation and abnormalities in the transfer of systolic arterial pulsation to the ventricular CSF, which occur as a result of decreased cerebral arterial compliance. These are associated with vascular dementia and treatment-resistant late onset depression. We studied a group of normal subjects at risk of cerebrovascular disease to determine if these biomarkers are present in patients who have no evidence of symptomatic vascular disease. We studied 31 subjects, 16 with three or more vascular risk factors and 15 with one or less significant risk factors. We measured arterial blood flow and CSF flow in the cerebral aqueduct, white matter lesion load, and the distribution and number of VRS. There were significant differences in CSF pulsatility and in VRS in the basal ganglia between the two groups, but no differences in white matter lesion load. We conclude that asymptomatic subjects at risk of stroke have MRI evidence of MVA before white matter lesions become apparent.
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Accidente Cerebrovascular/diagnóstico , Enfermedades Vasculares/diagnóstico , Anciano , Biomarcadores , Arterias Cerebrales/patología , Demencia Vascular/complicaciones , Demencia Vascular/patología , Diagnóstico por Imagen/métodos , Femenino , Humanos , Masculino , Microcirculación , Microscopía de Contraste de Fase , Persona de Mediana Edad , Factores de Riesgo , Accidente Cerebrovascular/patología , Enfermedades Vasculares/terapiaRESUMEN
BACKGROUND: The Oxfordshire Community Stroke Project (OCSP) and Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classifications are widely used for the assessment of major ischaemic stroke. We explored their intra- and inter-observer reliability in the classification of outpatient minor stroke. METHODS: Four physicians of differing seniority and training backgrounds classified minor stroke using clinical data from 90 patients. RESULTS: For both the OCSP and TOAST classifications, the intra-observer reliability varied from moderate to excellent (kappa = 0.48-0.83). The inter-observer reliability was good (kappa = 0.64) for the OCSP and moderate (kappa = 0.42) for the TOAST. Thus, neither classification was consistently reliable. CONCLUSIONS: Our results may reflect the limited validity of these classifications in a typical minor stroke outpatient population and variable observer expertise.
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Accidente Cerebrovascular/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Competencia Clínica , Inglaterra , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Pacientes Ambulatorios , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/clasificaciónRESUMEN
BACKGROUND: Inter-observer variability in stroke aetiological classification may have an effect on trial power and estimation of treatment effect. We modelled the effect of misclassification on required sample size in a hypothetical cardioembolic (CE) stroke trial. METHODS: We performed a systematic review to quantify the reliability (inter-observer variability) of various stroke aetiological classification systems. We then modelled the effect of this misclassification in a hypothetical trial of anticoagulant in CE stroke contaminated by patients with non-cardioembolic (non-CE) stroke aetiology. Rates of misclassification were based on the summary reliability estimates from our systematic review. We randomly sampled data from previous acute trials in CE and non-CE participants, using the Virtual International Stroke Trials Archive. We used bootstrapping to model the effect of varying misclassification rates on sample size required to detect a between-group treatment effect across 5000 permutations. We described outcomes in terms of survival and stroke recurrence censored at 90 days. RESULTS: From 4655 titles, we found 14 articles describing three stroke classification systems. The inter-observer reliability of the classification systems varied from 'fair' to 'very good' and suggested misclassification rates of 5% and 20% for our modelling. The hypothetical trial, with 80% power and alpha 0.05, was able to show a difference in survival between anticoagulant and antiplatelet in CE with a sample size of 198 in both trial arms. Contamination of both arms with 5% misclassified participants inflated the required sample size to 237 and with 20% misclassification inflated the required sample size to 352, for equivalent trial power. For an outcome of stroke recurrence using the same data, base-case estimated sample size for 80% power and alpha 0.05 was n = 502 in each arm, increasing to 605 at 5% contamination and 973 at 20% contamination. CONCLUSIONS: Stroke aetiological classification systems suffer from inter-observer variability, and the resulting misclassification may limit trial power. TRIAL REGISTRATION: Protocol available at reviewregistry540 .
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Ensayos Clínicos como Asunto/métodos , Embolia/complicaciones , Cardiopatías/complicaciones , Modelos Estadísticos , Tamaño de la Muestra , Accidente Cerebrovascular/etiología , Terminología como Asunto , Anticoagulantes/uso terapéutico , Ensayos Clínicos como Asunto/estadística & datos numéricos , Interpretación Estadística de Datos , Embolia/diagnóstico , Embolia/tratamiento farmacológico , Cardiopatías/diagnóstico , Cardiopatías/tratamiento farmacológico , Humanos , Variaciones Dependientes del Observador , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores de Riesgo , Accidente Cerebrovascular/clasificación , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND AND HYPOTHESIS: Inflammation is implicated in the pathogenesis and outcome of ischaemic injury. Poststroke inflammation is associated with outcome but it remains unclear whether such inflammation precedes or results from ischaemic injury. We hypothesised that inflammatory markers are associated with an increased risk of recurrent vascular events soon after transient ischaemic attack and minor stroke. METHODS: This was a multicentre, prospective, nested case-control study. Plasma concentrations of C-reactive protein, interleukin-6, interleukin-1-receptor antagonist and fibrinogen, leucocyte counts, erythrocyte sedimentation rate and inflammatory gene allele frequencies were analysed in 711 patients with recent transient ischaemic attack or minor stroke. Cases were defined by the incidence of one or more recurrent vascular events during the three-month follow-up. Association of inflammatory markers with case-status was determined using conditional logistic regression. RESULTS: Plasma concentrations of C-reactive protein, interleukin-1-receptor antagonist and interleukin-6 were not associated with case-status. In secondary analyses, only erythrocyte sedimentation rate was significantly associated with case-status (odds ratio 1·39, 95% confidence interval 1·03-1·85; P=0·03), but this effect did not persist after adjustment for smoking and past history of transient ischaemic attack or stroke. Single nucleotide polymorphisms in four inflammatory genes (interleukin-6, fibrinogen, P-selectin and vascular cell adhesion molecule-1) were nominally associated with case-status. CONCLUSIONS: Circulating inflammatory markers were not associated with recurrent vascular events. Nominally significant associations between genetic markers and case-status will require replication. These data provide little evidence for an inflammatory state predisposing to stroke and other vascular events in a susceptible population.