Cerebral perfusion and the burden of small vessel disease in patients referred to a memory clinic

Background: Cerebral small vessel disease (SVD) lesions on MRI are common in patients with cognitive impairment. It has been suggested that cerebral hypoperfusion is involved in the etiology of these lesions. Objective: The aim of the study was to determine the relationship between cerebral blood flow (CBF) and SVD burden in patients referred to a memory clinic with SVD on MRI. Method: We included 132 memory clinic patients (mean age 73 +/- 10, 56% male) with SVD on MRI. We excluded patients with large non-lacunar cortical infarcts. Global CBF (mL/min per 100 mL of brain tissue) was derived from 2-dimensional phase-contrast MRI focused on the internal carotid arteries and the basilar artery. SVD burden was defined as the sum of (each 1 point): white matter hyperintensities (WMHs) Fazekas 1 or more, lacunes, microbleeds (MBs), or enlarged perivascular spaces (PVS) presence, and each SVD feature separately. Linear regression analyses were performed to study the association between CBF and SVD burden, age- and sex-adjusted. Results: Median SVD burden score was 2, 36.4% of patients had MBs, 35.6% lacunar infarcts, 48.4% intermediate to severe enlarged PVS, and 57.6% a WMH Fazekas score 2 or more. Median WMH volume was 21.4 mL (25% quartile: 9.6 mL, 75% quartile: 32.5 mL). Mean CBF +/- SD was 44.0 +/- 11.9 mL/min per 100 mL brain. There was no relation between CBF and overall SVD burden (CBF difference per burden score point [95% CI]: -0.5 [-2.4; 1.4] mL/min/100 mL brain, p = 0.9). CBF did also not differ according to presence or absence or an high burden of any of the individual SVD features. Moreover, there was no significant relation between WMH volume and CBF (CBF difference per ml increase in WMH [95% CI] -0.6 [-1.5; 0.3] mL/min/100 mL brain p = 0.2). Conclusion: Global CBF was not related to overall SVD burden or with individual SVD features in this memory clinic cohort, indicating that in this setting these lesions were not primarily due to cerebral hypoperfusion.Neuro Imaging Researc

Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS

Neurotrophin treatment has so far failed to prolong the survival of individuals affected with amyotrophic lateral sclerosis (ALS), an incurable motoneuron degenerative disorder. Here we show that intracerebroventricular (i.c.v.) delivery of recombinant vascular endothelial growth factor (Vegf) in a SOD1(G93A) rat model of ALS delays onset of paralysis by 17 d, improves motor performance and prolongs survival by 22 d, representing the largest effects in animal models of ALS achieved by protein delivery. By protecting cervical motoneurons, i.c.v. delivery of Vegf is particularly effective in rats with the most severe form of ALS with forelimb onset. Vegf has direct neuroprotective effects on motoneurons in vivo, because neuronal expression of a transgene expressing the Vegf receptor prolongs the survival of SOD1(G93A) mice. On i.c.v. delivery, Vegf is anterogradely transported and preserves neuromuscular junctions in SOD1(G93A) rats. Our findings in preclinical rodent models of ALS may have implications for treatment of neurodegenerative disease in general.status: publishe