Hyperattenuated intracerebral lesions after mechanical recanalization in acute stroke.

BACKGROUND AND PURPOSE: Following mechanical recanalization of an acute intracranial vessel occlusion, hyperattenuated lesions are frequently found on postinterventional cranial CT. They represent either blood or-more frequently-enhancement of contrast agent. Here, we aimed to evaluate the prognostic value of these hyperattenuated intracerebral lesions. MATERIALS AND METHODS: One hundred one consecutive patients with acute stroke in the anterior circulation who underwent mechanical recanalization were included. Risk factors for hyperattenuated intracerebral lesions were assessed, and lesion volume was compared with the volume of final infarction. Clinical outcome and relative risk of secondary hemorrhage were determined in patients with and without any hyperattenuated lesions and compared. RESULTS: The frequency of hyperattenuated lesions was 84.2%. Risk factors for hyperattenuated lesions were female sex, higher NIHSS score on admission, and higher amount of contrast agent applied. On follow-up, 3 patients showed no infarction; 53 patients, an ischemic infarction; and 45 patients, a hemorrhagic infarction. In all except 1 case, final volume of infarction (median = 92.4 mL) exceeded the volume of hyperattenuated intracerebral lesions (median = 5.6 mL). Patients with hyperattenuated lesions were at a 4 times higher relative risk for hemorrhagic transformation but had no significantly worse clinical outcome. CONCLUSIONS: Our data show that the extent of postinterventional hyperattenuated intracerebral lesions underestimates the volume of final infarction. Although hyperattenuated lesions indicate a higher risk of secondary hemorrhagic transformation, their presence seems not to be of any prognostic value regarding clinical outcome.

Verbal memory impairment in subcortical ischemic vascular disease: a descriptive analysis in CADASIL.

In the elderly, the high prevalence of Alzheimer's disease neuropathology presents a major challenge to the investigation of memory decline in common diseases such as small vessel disease. CADASIL represents a unique clinical model to determine the spectrum of memory impairment in subcortical ischemic vascular dementia (SIVD). One hundred and forty CADASIL patients underwent detailed clinical, neuropsychological and imaging analyses. The Free and Cued Selective Reminding Test was used as a measure of verbal memory. Forty-four out of 140 CADASIL patients (31.4%) presented with memory impairment according to this test. Eight out of 44 (18.2%) subjects with memory impairment matched the definition of the amnestic syndrome of hippocampal type. While alterations in spontaneous recall were related to the severity of subcortical ischemic lesions, the profile of memory impairment, particularly the sensitivity to cueing was found related to other factors such as hippocampal atrophy.

[Vasculitis and hereditary small vessel diseases]. / Vaskulitis und genetisch bedingte Mikroangiopathien.

In younger patients with stroke, cerebral vasculitis and hereditary small vessel diseases should be considered as important differential diagnoses. Since the clinical course of cerebral vasculitis is highly variable, diagnostic workup, which includes laboratory tests, CSF analysis, cranial magnetic resonance imaging and biopsy, is often challenging. Therapy should be initiated on an interdisciplinary basis and includes immunosuppressive induction and maintenance regimes. Hereditary small vessel diseases, e.g. CADASIL or Fabry's disease, can mimic clinical features of cerebral vasculitis. Their diagnosis which is based on family history, typical clinical features and genetic analysis often has implications for treatment and genetic counselling.

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.

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.

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.