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Introduction: Cerebral small vessel disease (SVD) is an important cause of dementia that lacks effective treatment. We evaluated the efficacy and safety of cilostazol, an antiplatelet agent with potential neurovascular protective effects, in slowing the progression of white matter hyperintensities (WMHs) in stroke- and dementia-free subjects harboring confluent WMH on magnetic resonance imaging (MRI). Methods: In this single-center, randomized, double-blind, placebo-controlled study, we randomized stroke- and dementia-free subjects with confluent WMHs to receive cilostazol or placebo for 2 years in a 1:1 ratio. The primary outcome was change in WMH volume over 2 years. Secondary outcomes were changes in brain volumes, lacunes, cerebral microbleeds, perivascular space, and alterations in white matter microstructural integrity, cognition, motor function, and mood. Results: We recruited 120 subjects from October 27, 2014, to January 21, 2019. A total of 55 subjects in the cilostazol group and 54 subjects in the control group were included for intention-to-treat analysis. At 2-year follow-up, the changes in WMH volume were not statistically different between cilostazol treatment and placebo (0.3±1.0 mL vs -0.1±0.8 mL, p = 0.167). Secondary outcomes, bleeding and vascular events, were also not statistically different between the two groups. Discussion: In this trial with stroke- and dementia-free subjects with confluent WMHs, cilostazol did not impact WMH progression but demonstrated an acceptable safety profile. Future studies should address the treatment effects of cilostazol on subjects at different clinical stages of SVD.
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OBJECTIVES: Elderly persons harbouring severe white matter hyperintensity (WMH), a radiological manifestation of cerebral small vessel disease (SVD), have an increased risk of dementia, stroke and poor functional outcomes. A simple screening tool will enhance their recruitment into preventive trials for SVD. We explored the clinical utility of the pulsatility index (PI) of the middle cerebral artery (MCA), obtained from transcranial Doppler ultrasound (TCD), in identifying severe WMH among community elderly persons with vascular risk factors. METHODS: Three hundred and thirty-one dementia- and stroke-free community elderly subjects with hypertension and/or diabetes mellitus underwent TCD to obtain the MCA PI. The WMH volume on 3.0 Tesla MRI was quantified and normalized to each subject's brain volume. The normalized WMH volumes were classified as low (<14.5â¯ml, 1 standard deviation [SD] above the mean, 84th percentile) or high (≥14.5â¯ml). The severity of WMH was also rated visually with the Fazekas score. Logistic regression and receiver-operator characteristics (ROC) analysis were performed to evaluate the association between the MCA PI and the severity of WMH. RESULTS: The MCA PI was not an independent predictor of severe WMH. An MCA PI ≥1.095 detected high normalized WMH volumes with an area under the curve (AUC) of 0.553 (95% CI 0.473-0.633), sensitivity of 0.556, and specificity of 0.523. ROC analysis of the MCA PI in predicting high Fazekas scores yielded similar findings. CONCLUSION: In stroke- and dementia-free elderly persons with vascular risk factors, the MCA PI was unable to identify severe WMH. (Word count: 260).
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Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Vida Independente , Programas de Rastreamento/métodos , Ultrassonografia Doppler Transcraniana/métodos , Idoso , Estudos Transversais , Feminino , Hong Kong/epidemiologia , Humanos , MasculinoRESUMO
We evaluated the safety and efficacy of rituximab in seven Chinese patients with neuromyelitis optica (NMO) or neuromyelitis optica syndrome disorders (NMOSD) in a tertiary medical center in Hong Kong. After rituximab induction, five patients became relapse-free and two had 50% reduction of relapses over a median follow-up of 24 months. No further deterioration of functional status, measured by the Expanded Disability Status Scale, was observed in all patients. Infusions were well tolerated except in two patients who developed transient hypotension. Rituximab reduced clinical relapse and prevented neurological deterioration in a small cohort of Chinese patients with NMO or NMOSD.