Elevated Cerebral Blood Flow Velocities in Fabry Disease With Reversal After Enzyme Replacement

Background and Purpose — Fabry disease is an X-linked inherited disorder resulting from a deficiency of α-galactosidase A. Cerebrovascular disease in Fabry disease includes small-vessel disease and larger-vessel ectasia in a predominantly posterior distribution. We assessed transcranial Doppler (TCD) blood flow velocities in naive and enzyme-treated Fabry patients. Methods — TCD was used to noninvasively examine patients with Fabry disease for abnormal cerebral blood flow velocities. TCD measurements were also made during CO 2 retention by breathholding to examine cerebrovascular vessel reactivity. Twenty-six patients were enrolled in a 6-month, double-blind, placebo-controlled trial of enzyme replacement therapy consisting of biweekly intravenous α-galactosidase A infusions, with a subsequent 18-month follow-up in an open-label trial. Statistical analysis consisted of applying a mixed-effects ANOVA model for correlated outcomes. Results — Peak velocity, mean velocity, pulsatility index, and resistance index were found to be significantly higher in patients compared with control subjects. When the individual vessels were considered, elevated flow velocities were found in the middle cerebral M1 branch and the posterior cerebral artery. Enzyme replacement therapy significantly decreased peak, mean, and end-diastolic velocities and flow acceleration at the 18-month follow-up time point. Conclusions — Patients with Fabry disease have elevated cerebral blood flow velocities. These velocities significantly improved with enzyme replacement therapy

DARPA-funded efforts in the development of novel brain–computer interface technologies

•DARPA's programs foster multi-disciplinary collaborations.•DARPA's BCI programs span four major challenges: detect, emulate, restore, & improve.•Aims: restore function after injury; improve performance of healthy individuals. The Defense Advanced Research Projects Agency (DARPA) has funded innovative scientific research and technology developments in the field of brain–computer interfaces (BCI) since the 1970s. This review highlights some of DARPA's major advances in the field of BCI, particularly those made in recent years. Two broad categories of DARPA programs are presented with respect to the ultimate goals of supporting the nation's warfighters: (1) BCI efforts aimed at restoring neural and/or behavioral function, and (2) BCI efforts aimed at improving human training and performance. The programs discussed are synergistic and complementary to one another, and, moreover, promote interdisciplinary collaborations among researchers, engineers, and clinicians. Finally, this review includes a summary of some of the remaining challenges for the field of BCI, as well as the goals of new DARPA efforts in this domain