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C Opherk

Publications and source records attributed to C Opherk.

6 recordsLinked to original sources
PubMed2006

Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease causing stroke and subcortical vascular dementia. Recent studies in sporadic subcortical ischemic vascular disease have drawn attention to brain atrophy as a clinically important marker of disease progression. However, little is known about the role of brain atrophy and its clinical correlates in CADASIL. METHOD: The authors determined the normalized brain volume (NBV) and percent brain volume change (PBVC) over 2 years in 76 CADASIL subjects (45.1 +/- 9.7 years) using the SIENA (structural image evaluation using normalization of atrophy) software and its adaptation for cross-sectional measurements (SIENAX). Baseline assessments included systolic blood pressure (SBP), homocysteine levels, BMI, and APOE genotyping. T2-lesion volumes and clinical scales were assessed at both time points. RESULTS: The NBV significantly correlated with all clinical scores (Rankin, NIH Stroke Scale, Barthel, structured interview for the diagnosis of Alzheimer dementia and multi-infarct dementia, Mattis dementia rating scale) at both time points independently of age and sex. PBVC correlated with changes of all clinical scores (all p < 0.01) except for the Mattis dementia rating scale (p = 0.10). In a linear regression model, age (p < 0.001), male sex (p < 0.01), and SBP (p = 0.07) were the main risk factors for a lower NBV at baseline. Age (p < 0.001) and SBP (p = 0.01) were risk factors for brain volume loss during follow-up. Sample size estimates showed that the number of individuals needed to demonstrate a treatment effect in a trial can be reduced when PBVC is used as an endpoint. CONCLUSIONS: This study identifies brain atrophy as an important aspect of the disease process in CADASIL and establishes significant correlations with multiple clinical aspects including cognition. Age and systolic blood pressure are risk factors for brain volume loss during follow-up. Percent brain volume change seems promising as an adjunct outcome measure in future interventional trials.

Adult↗
PubMed2004

Retinal vascular abnormalities in CADASIL.

To assess retinal vascular alterations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the authors examined 10 affected individuals with ophthalmologic evaluation including fluorescence angiography. Findings included bilateral peripapillary arteriolar sheathing (30%), arteriolar narrowing (80%), and arteriovenous nicking (90%). No retinal infarcts, vascular occlusions, exudation, or hypoperfusion of affected vessels were found.

Adult↗
PubMed1999

Inducible site-specific recombination in the brain.

The Cre/loxP recombination system allows the generation of tissue-specific somatic mutations in mice. Additional temporal control of somatic mutagenesis is highly desirable, as this would permit a more precise analysis of gene function in complex systems such as the central nervous system. Extending our previous studies, we compared several ligand-regulated recombinases, in which the ligand-binding domain (LBD) of the progesterone receptor or the estrogen receptor was fused to the Cre recombinase. A fusion protein between the Cre recombinase and a truncated LBD of the progesterone receptor was chosen to obtain inducible recombination in the brain. This fusion protein can be activated by the synthetic steroid RU486, but not by the physiological hormone progesterone. Its expression was targeted to the brain using regulatory sequences of the calcium-calmodulin-dependent kinase IIalpha or the Thy-1 gene. Application of RU486 to the mice induced Cre-mediated recombination of a lacZ reporter transgene in the cortex and hippocampus, showing that spatially and temporally controlled gene targeting can be mediated in the brain.

Animals↗