RESUMEN
INTRODUCTION: Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD) is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression. METHODS: Ninety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1) and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER) and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes. RESULTS: NIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss. DISCUSSION: The NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint.
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Progresión de la Enfermedad , Función Ejecutiva/fisiología , Demencia Frontotemporal , Pruebas Neuropsicológicas/estadística & datos numéricos , Biomarcadores , Proteína C9orf72/genética , Femenino , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/genética , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
INTRODUCTION: The Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial-frontotemporal lobar degeneration due to autosomal dominant mutations. METHODS: We examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non-mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia. RESULTS: Asymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes. Those with mild/questionable impairment showed decreased verbal recall, fluency, and Trail Making Test performance and impaired mood and self-monitoring. Dementia was associated with impairment in all measures. All MAPT carriers with dementia showed temporal atrophy, but otherwise, there was no single cognitive test or brain region that was abnormal in all subjects. DISCUSSION: Imaging changes appear to precede clinical changes in familial-frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.
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Atrofia/patología , Degeneración Lobar Frontotemporal , Predisposición Genética a la Enfermedad , Procesamiento de Imagen Asistido por Computador/estadística & datos numéricos , Pruebas Neuropsicológicas/estadística & datos numéricos , Proteína C9orf72/genética , Femenino , Degeneración Lobar Frontotemporal/genética , Degeneración Lobar Frontotemporal/patología , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Progranulinas/genética , Lóbulo Temporal/patología , Proteínas tau/genéticaRESUMEN
INTRODUCTION: Some models of therapy for neurodegenerative diseases envision starting treatment before symptoms develop. Demonstrating that such treatments are effective requires accurate knowledge of when symptoms would have started without treatment. Familial frontotemporal lobar degeneration offers a unique opportunity to develop predictors of symptom onset. METHODS: We created dementia risk scores in 268 familial frontotemporal lobar degeneration family members by entering covariate-adjusted standardized estimates of brain atrophy into a logistic regression to classify asymptomatic versus demented participants. The score's predictive value was tested in a separate group who were followed up longitudinally (stable vs. converted to dementia) using Cox proportional regressions with dementia risk score as the predictor. RESULTS: Cross-validated logistic regression achieved good separation of asymptomatic versus demented (accuracy = 90%, SE = 0.06). Atrophy scores predicted conversion from asymptomatic or mildly/questionably symptomatic to dementia (HR = 1.51, 95% CI: [1.16,1.98]). DISCUSSION: Individualized quantification of baseline brain atrophy is a promising predictor of progression in asymptomatic familial frontotemporal lobar degeneration mutation carriers.
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Atrofia/patología , Demencia Frontotemporal , Predisposición Genética a la Enfermedad , Mutación/genética , Pruebas Neuropsicológicas/estadística & datos numéricos , Encéfalo/patología , Proteína C9orf72/genética , Femenino , Demencia Frontotemporal/diagnóstico por imagen , Demencia Frontotemporal/genética , Humanos , Procesamiento de Imagen Asistido por Computador/estadística & datos numéricos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Progranulinas/genética , Proteínas tau/genéticaRESUMEN
We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo.
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Fiebre de Lassa/epidemiología , Fiebre de Lassa/virología , Virus Lassa/clasificación , Animales , Chlorocebus aethiops , Genes Virales , Historia del Siglo XXI , Humanos , Fiebre de Lassa/historia , Filogenia , Togo/epidemiología , Células VeroRESUMEN
Two patients with Lassa fever are described who are the first human cases treated with a combination of ribavirin and favipiravir. Both patients survived but developed transaminitis and had prolonged detectable virus RNA in blood and semen, suggesting that the possibility of sexual transmission of Lassa virus should be considered.
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Amidas/uso terapéutico , Antivirales/uso terapéutico , Fiebre de Lassa , Pirazinas/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Humanos , Fiebre de Lassa/tratamiento farmacológico , Fiebre de Lassa/fisiopatología , Fiebre de Lassa/virología , Virus Lassa/genética , Masculino , Reacción en Cadena de la Polimerasa , ARN Viral/análisis , ARN Viral/genética , TogoRESUMEN
This study investigated the effectiveness of simple-to-implement adjustments of phototherapy devices on irradiance levels in a cross-section of Nigerian hospitals. A total of 76 phototherapy devices were evaluated in 16 hospitals while adjustments were implemented for a subset of 25 devices for which consent was obtained. The mean irradiance level was 7.6 ± 5.9 µW/cm(2)/nm for all devices prior to adjustments. The average irradiance level improved from 9.0 µW/cm(2)/nm to 27.3 µW/cm(2)/nm for the adjusted group (n = 25) compared with 6.8 ± 5.4 µW/cm(2)/nm for the unadjusted group (n = 51). Simple, inexpensive adjustments to phototherapy devices with sub-optimal irradiance levels can significantly improve their effectiveness to acceptable international standards and should be widely promoted in resource-constrained settings.