Advances in robotic technology have been adopted in various subspecialties of both open and minimally invasive surgery, offering benefits such as enhanced surgical precision and accuracy with reduced fatigue of the surgeon. Despite the advantages, robotic applications to endovascular neurosurgery have remained largely unexplored because of technical challenges such as the miniaturization of robotic devices that can reach the complex and tortuous vasculature of the brain. Although some commercial systems enable robotic manipulation of conventional guidewires for coronary and peripheral vascular interventions, they remain unsuited for neurovascular applications because of the considerably smaller and more tortuous anatomy of cerebral arteries. Here, we present a teleoperated robotic neurointerventional platform based on magnetic manipulation. Our system consists of a magnetically controlled guidewire, a robot arm with an actuating magnet to steer the guidewire, a set of motorized linear drives to advance or retract the guidewire and a microcatheter, and a remote-control console to operate the system under real-time fluoroscopy. We demonstrate our system’s capability to navigate narrow and winding pathways both in vitro with realistic neurovascular phantoms representing the human anatomy and in vivo in the porcine brachial artery with accentuated tortuosity for preclinical evaluation. We further demonstrate telerobotically assisted therapeutic procedures including coil embolization and clot retrieval thrombectomy for treating cerebral aneurysms and ischemic stroke, respectively. Our system could enable safer and quicker access to hard-to-reach lesions while minimizing the radiation exposure to physicians and open the possibility of remote procedural services to address challenges in current stroke systems of care.

Significance: α-Synuclein (αS) inclusions are a hallmark of many progressive neurodegenerative disorders. Previously, intracerebral injection of exogenous preformed fibrillar αS in mouse models was shown to induce neuronal αS aggregation—a finding that has been interpreted as a prion-like mechanism. We now show that αS inclusion pathology can be induced in the brain and spinal cord of αS transgenic mice by a single peripheral intramuscular injection of αS. The formation of αS inclusions occurred concurrently with the presentation of a motor impairment in mice expressing mutant Ala53Thr human αS. This new model of robust and predictable induction of αS pathology will be especially valuable to further study the pathogenic mechanisms and assessment of therapeutic interventions.

Importance Stroke is the second leading cause of death in the world, and nearly one-third of ischemic strokes are lacunar strokes (LSs) or small subcortical infarcts. Although smaller in size, they create large problems, leaving many patients with intellectual and physical disabilities. Because there are limitations in understanding the underlying pathophysiology of LS, the development of novel therapies has been slow. Observations When the termlacunewas described in the 1800s, its underlying pathophysiological basis was obscure. In the 1960s, C. Miller Fisher, MD, performed autopsy studies that showed that vessels supplying lacunes displayed segmental arteriolar disorganization, characterized by vessel enlargement, hemorrhage, and fibrinoid deposition. For these pathologic changes, he coined the termlipohyalinosis. Since that time, few attempts have been made to reconcile this pathologic description with modern mechanisms of cerebral small vessel disease (CSVD). During the past 6 years, progress has been made in understanding the clinical mechanisms, imaging characteristics, and genetic basis of LS. Conclusions and Relevance Questions persist regarding the order of events related to the initiation and progression of CSVD, how LS is related to other sequelae of CSVD, and whether LS is part of a systemic disease process. The relative roles of aging, oxidative stress, mechanical stress, genetic predisposition, and other vascular risk factors should be further studied, especially in the era of widespread antihypertensive use. Although understanding of endothelial dysfunction has increased, future work on the role of media and adventitial dysfunction should be explored. Recent advances in mapping the brain vasculome may generate new hypotheses. The investigation of new therapeutic targets, aimed at reversing CSVD processes and promoting neural repair after LS, depends upon further understanding these basic mechanisms.

Activation of angiotensin‐converting enzyme 2 (ACE2), production of angiotensin‐(1–7) [Ang‐(1–7)] and stimulation of the Ang‐(1–7) receptor Mas exert beneficial actions in various peripheral cardiova...

Cerebral small vessel disease (CSVD) is a common group of neurological conditions that confer a significant burden of morbidity and mortality worldwide. In most cases, CSVD is only recognized in its advanced stages once its symptomatic sequelae develop. However, its significance in asymptomatic healthy populations remains poorly defined. In population-based studies of presumed healthy elderly individuals, CSVD neuroimaging markers including white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, cortical superficial siderosis, and cerebral microinfarcts are frequently detected. While the presence of these imaging markers may reflect unique mechanisms at play, there are likely shared pathways underlying CSVD. Herein, we aim to assess the etiology and significance of these individual biomarkers by focusing in asymptomatic populations at an epidemiological level. By primarily examining population-based studies, we explore the risk factors that are involved in the formation and progression of these biomarkers. Through a critical semi-systematic review, we aim to characterize "asymptomatic" CSVD, review screening modalities, and draw associations from observational studies in clinical populations. Lastly, we highlight areas of research (including therapeutic approaches) in which further investigation is needed to better understand asymptomatic CSVD.

Cerebral amyloid angiopathy–related inflammation (CAA-ri), also referred to as inflammatory cerebral amyloid angiopathy and Aß-related angiitis, is a distinct subset of cerebral amyloid angiopathy (CAA) characterized by an autoimmune reaction to cerebrovascular β-amyloid deposits.^1-6 It differs from more common noninflammatory forms of CAA in its clinical presentation, with subacute cognitive changes and vasogenic edema rather than acute intracerebral hemorrhage.^7-10 Quiz Ref ID Neuroimaging results often show multiple lobar microhemorrhages characteristic of CAA as well as patchy or confluent asymmetric white matter hyperintensities (WMHs) suggestive of subcortical edema, which may regress in response to treatment, as reported in small case studies.^4,11 Neuropathologic examination of brain biopsy samples has shown a spectrum of inflammatory changes associated with amyloid-laden blood vessel segments, ranging from perivascular accumulation of inflammatory cells¹ to true vasculitis with transmural vessel wall destructive changes.¹² Clinical and imaging criteria have been described for the diagnosis of probable CAA-ri, demonstrating high sensitivity (82%) and specificity (97%) in a small validation study.¹¹ Disease flares are associated with elevated cerebrospinal fluid (CSF) titers of anti–β-amyloid autoantibodies,³ but assays for the CSF autoantibodies are not commercially available and have not been validated as a diagnostic test for this disorder.