Congenital Cerebrovascular Disorders- From Clinic To Bench and Back

Emerging targeted treatments for congenital cerebrovascular disorders- Current State and Future Directions
Moran Hausman-Kedem

Recent advancements in genetic analysis have facilitated the identification of specific genes and genetic variants responsible for different types of congenital cerebrovascular disorders and have opened the door to the development of targeted therapies aimed at addressing underlying genetic abnormalities. In recent years, several targeted therapies have been developed and studied for the treatment of vascular malformations, including arteriovenous malformations (AVMs) and cavernous malformations (CMs), and have shown positive results in early clinical trials. Current targeted treatments for congenital cerebrovascular disorders include gene therapy, pharmacological treatments, and neuro-interventional procedures. Studies have shown that MEK inhibitors can effectively shrink AVMs and reduce the risk of bleeding. For CMs, beta-blockers such as propranolol have shown promise in reducing the frequency and severity of headaches associated with these malformations. Additionally, REC-194 is a monoclonal antibody that has been developed specifically to target and remove abnormal blood vessels associated with CMs and has shown positive results in early clinical trials.
This lecture will review emerging targeted treatments for a spectrum of congenital cerebrovascular disorders and discuss advancement in their management.

Clinical and radiological phenotype-genotype correlation of congenital vasculopathies
Nomazulu Dlamini

Pediatric cerebrovascular diseases have significant impacts on health and economics. These disorders, which can begin in utero and extend into adulthood, affect various age ranges. A significant number of congenital cerebral vasculopathies are caused by genetic factors, and recent genetic discoveries have led to an increased understanding of the underlying pathogenesis of these conditions. This presentation will provide an overview of monogenic cerebrovascular disorders, including arteriopathies, their clinical and radiological phenotypes, natural history, and diagnosis. Arteriopathies, which are the most common cause of childhood ischemic stroke, will be discussed in detail, including their clinical presentations, pathogenesis, and genetic basis. The presentation will also cover the advances in imaging techniques and how they have improved the diagnosis and management of these disorders. Furthermore, the potential impact of genetic testing and counseling on the management of these diseases will be highlighted. The presentation will conclude by discussing the current state of knowledge in this field and the future directions for research and development. The ultimate goal is to improve the diagnosis, treatment, and outcomes for children affected by cerebrovascular diseases.

Advancement in neurointerventional therapies for congenital vasculopathies
Gabrielle DeVeber

In recent years, neuro-interventional therapies have advanced rapidly, offering new minimally invasive treatment options for a variety of congenital vasculopathies. These procedures use imaging guidance to deliver therapeutic agents or devices directly to the affected blood vessels. Novel neuro-interventional therapies are continuously being developed and studied. One promising technique is the use of flow diverters, which are stent-like devices that redirect blood flow away from vascular malformations and promote the growth of a new vessel lining. This approach has shown potential in treating complex and high-risk AVMs and aneurysms. Another emerging therapy is laser interstitial thermal therapy (LITT), which uses laser energy to heat and destroy abnormal blood vessels. LITT has shown effectiveness in treating cerebral cavernous malformations (CCMs) and other vascular malformations. Additionally, newer therapies such as the percutaneous transuterine fetal cerebral embolization technique have been introduced for treating vein of Galen malformations. These techniques and others will be reviewed in this talk, providing an overview of the latest advancements in the treatment of congenital cerebrovascular disorders through neuro-interventional approaches.

Cerebral vasculopathies in resource-limited settings – Genetic Clues from the Clinic
Alvin Ndondo
Arteriopathies are the commonest risk factor for childhood arterial ischaemic stroke globally.Underlying mechanisms involve genetic and inflammatory components in variable proportion. Thepathophysiology of many genetic vasculopathies in children (including moyamoya disease - MMD) remains unknown. Mutations of a variety of genes could be involved in the development of these vasculopathies. The anatomical site for these mutations will be found in the different components of the blood vessel. Mutations may be found in genes that affect the extracellular matrix, smooth muscle, and angiogenetic pathways, amongst others. The expression and clinical manifestations of these will likely vary in different ethnic groups. In resource-limited settings the emphasis of study has mostly been directed at the infective contributors to the burden of vasculopathies and stroke inchildren. Outside of sickle cell disease, t here is paucity of data regarding the other genetic vasculopathies, including MMD. Access to tools for the genetic understanding of vasculopathies (including DNA sequencing, genetic linkage, and genetic association studies) in these settings is lacking. The genetic variants are likely to differ depending on et nicity. This talk will reflect on thetranslation of clinical experience from a resource-limited clinic, with interesting case-based examples. Questions regarding the pathophysiological basis of vasculopathies and thoughts abouttiming, arterial segmental identity and vulnerability will be explored.