Third Ventricle Width Assessed by Transcranial Sonography as Predictor of Long-Term Cognitive Impairment.

BACKGROUND: Non-invasive biomarkers of cognitive impairment are needed. We aim to evaluate transcranial sonographic markers as predictors of cognitive impairment in a prospective cohort. OBJECTIVE: To study the changes in the third ventricle diameter and the SN echogenicity between the baseline and the control visit, as well as its association with cognitive performance and the diagnosis of cognitive impairment in a prospective cohort. METHODS: From the longitudinal population-based Asymptomatic Intracranial Atherosclerosis Study, we selected those subjects that received a complete transcranial sonography (TCS) and extensive cognitive testing, both at baseline and follow-up. We evaluated third ventricle (IIIv) width, echogenicity of substantia nigra (SN), and temporal changes of these parameters. RESULTS: We included 289 participants with a median follow-up time of 7.16 years. Those subjects who developed cognitive decline (n = 23, 7.96%) had a larger IIIv at baseline than those who did not (0.54±0.14 cm versus 0.41±0.15 cm; p = 0.001). A cut-off point of 0.465 cm for the IIIv width was identified as an independent predictor of long-term cognitive impairment after adjustment for age, gender, educational level, and vascular risk score. Change in IIIv diameter after follow-up was not associated with diagnosis of cognitive impairment. The area of SN and the presence of hyperechogenicity of the SN remained stable over time and was not associated with the diagnosis of cognitive impairment. CONCLUSION: IIIv width assessed by TCS emerged as an independent predictor of long-term cognitive impairment.

Features of speech and swallowing dysfunction in pre-ataxic spinocerebellar ataxia type 2.

OBJECTIVE: To determine whether objective and quantitative assessment of dysarthria and dysphagia in spinocerebellar ataxia type 2 (SCA2), specifically at pre-ataxic and early disease phases, can act as sensitive disease markers. METHODS: Forty-six individuals (16 with pre-ataxic SCA2, 14 with early-stage ataxic SCA2, and 16 healthy controls) were recruited in Holguin, Cuba. All participants underwent a comprehensive battery of assessments including objective acoustic analysis, clinician-derived ratings of speech function and swallowing, and quality of life assessments of swallowing. RESULTS: Reduced speech agility manifest at the pre-ataxic stage was observed during diadochokinetic tasks, with the magnitude of speech deficit augmented in the early ataxic stage. Speech rate was slower in early-stage ataxic SCA2 compared with pre-ataxic SCA2 and healthy controls. Reduced speech agility and speech rate correlated with disease severity and time to ataxia onset, verifying that speech deficits occur prior to ataxia onset and increase in severity as the disease progresses. Whereas dysphagia was observed in both pre-ataxic and ataxic SCA2, it was not associated with swallowing-related quality of life, disease severity, or time to ataxia onset. CONCLUSIONS: Speech and swallowing deficits appear sensitive to disease progression in early-stage SCA2, with syllabic rate a viable marker. Findings provide insight into mechanisms of disease progression in early-stage SCA2, signaling an opportunity for stratifying early-stage SCA2 and identifying salient markers of disease onset as well as outcome measures in future early-stage therapeutic studies.

The Barcelona-Asymptomatic Intracranial Atherosclerosis study: Subclinical intracranial atherosclerosis as predictor of long-term vascular events.

BACKGROUND AND AIMS: Symptomatic intracranial atherosclerosis (ICAS) is associated with a high risk of stroke recurrence and occurrence of other vascular events. However, ICAS has been poorly studied from its asymptomatic stage. The objective of our study was to determine if subclinical intracranial atherosclerosis is associated with long-term incident vascular events in Caucasians. METHODS: The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) Study is a population-based study that enrolled 933 subjects with a moderate-high vascular risk and without history of stroke or coronary disease, and determined the prevalence of asymptomatic ICAS and associated risk factors. At baseline visit, carotid atherosclerosis and ICAS were screened by color-coded duplex ultrasound, and moderate-severe stenosis was confirmed by magnetic resonance angiography. At baseline, 8.9% of subjects had asymptomatic ICAS, of whom 3.3% were moderate-severe. In the longitudinal phase, subjects were prospectively followed-up to assess the incidence of a combined primary endpoint of vascular events (stroke, acute coronary syndrome and/or vascular death). RESULTS: After 7.17 years of follow-up, there were 51 incident cerebrovascular events (16 transient ischemic attacks, 27 ischemic, 8 hemorrhagic strokes), 63 incident coronary events and 23 vascular deaths. After multivariate Cox regression analyses adjusted by age, sex, vascular risk and presence of carotid plaques, ICAS was an independent predictor for overall vascular events (HR 1.83 [1.10-3.03], p = 0.020), and moderate-severe intracranial stenosis was also an independent predictor for cerebrovascular events (HR 2.66 [1.02-6.94], p = 0.046). CONCLUSIONS: Asymptomatic ICAS is independently associated with the incidence of future vascular events in our population. These findings might have implications for the development of primary prevention strategies.

Progressive multifocal leukoencephalopathy associated to natalizumab extended dosing regimen.

A risk for developing progressive multifocal leukoencephalopathy is a major barrier to natalizumab use. Extended dosing intervals have been proposed as a way to maintain therapeutic efficacy and reduce progressive multifocal leukoencephalopathy incidence. This is the first reported case of progressive multifocal leukoencephalopathy in a patient using an extended dosing regimen (300 mg/6 weeks). A close clinical and imaging monitoring allowed early detection, which is a major prognostic factor. A favorable outcome was seen with a therapy comprising plasma exchange therapy, mirtazapine, mefloquine and cidofovir. Further studies will be needed to assess the potential role of extended dosing intervals to improve prognosis in patients receiving natalizumab and also to measure its impact clinically and/or radiologically.