Systemic Lupus Erythematosus (SLE) is an autoimmune disease that causes damage to multiple organs. Neuropsychiatric systemic lupus erythematosus (NPSLE) is the term used when SLE affects the brain and other parts of the nervous system. NPSLE is often severe and can occur in both children and adults. In childhood-onset SLE (cSLE) in particular, NPSLE is a top priority research area. One of the most severe and devastating complications of NPSLE is cerebrovascular accidents (CVA), also known as Strokes. Approximately 15% of children with SLE experience strokes. However, despite the significant proportion of patients affected, the specific risk factors, comparative severity, and outcomes of strokes in cSLE are still poorly understood.

Currently, the field relies on studies from adult-onset SLE to care for cSLE patients with stroke. But there is insufficient evidence from adult studies to fully inform the impact of stroke on the developing childhood brain and the comprehensive care needs of a child with neurologic deficits from a stroke. Especially as severe symptoms of SLE are more often found in children than in adult-onset SLE. Also, studies from children with non-SLE-related stroke are also limited in their application to cSLE as patients with cSLE could potentially have higher stroke recurrence and poorer outcomes than children with non-SLE-related stroke.

Dr. Ogbu’s research will address these issues. Dr. Ogbu’s research will identify potential blood biomarkers of abnormal blood vessel wall functioning and abnormal clotting predisposition, which will serve as more accurate early indicators of a higher risk of stroke in cSLE and enhance surveillance measures to prevent this devastating complication. To further understand the burden of strokes in cSLE, Dr. Ogbu will compare stroke severity and outcomes in cSLE with other populations. Dr. Ogbu’s study aims to provide long-term comparative outcome data of stroke in cSLE, to determine at-risk sub populations, inform management approaches, and support the development of targeted therapies.

What this study means for people with lupus:

Strokes are severe, and devastating complications of cSLE that are poorly understood. The results of Dr. Ogbu’s study will impact the care of patients with cSLE by identifying blood biomarkers and other factors that could serve as early indicators of increased stroke risk. The results will also shed more light on short and long-term stroke outcomes in cSLE and factors that could result in and improve poorer outcomes. Early intervention is critical for mitigating the risk of stroke and improving the overall outcome. Therefore, the results of Dr. Ogbu’s study will be important in supporting the development of effective and targeted interventions that could improve outcomes for patients with cSLE.

Cerebrovascular accidents (CVA) are the most devastating neuropsychiatric manifestations of childhood-onset systemic lupus erythematosus (cSLE). CVA occur in up to 15% of patients with cSLE. Despite the frequency of CVA in cSLE (CVA-cSLE), the associated high mortality risk and potentially disabling consequences, risk factors and prognosis of CVA-cSLE have not been well delineated. Therefore, a critical scientific gap remains in our understanding of CVA-cSLE which hinders primary prevention of CVA, and provision of early targeted therapies and comprehensive care specific to CVA-cSLE.

Unfortunately, current knowledge on CVA-cSLE has had to rely on extrapolation from adult-onset systemic lupus erythematosus (aSLE) which may not be appropriate as cSLE tends to have a more severe disease course than aSLE. Furthermore, aSLE studies are limited in explaining the impact of CVA on the developing brain and the care needs of a growing child with neurologic devastation. Traditional risk factors of CVA in aSLE (CVA-aSLE) such as atherosclerosis do not fully explain the risk of CVA-cSLE. Similarly, extrapolation of CVA outcomes from other non-cSLE pediatric populations are limited in their applicability to cSLE. While many pediatric patients end up with long-term neurologic, motor and cognitive deficits following CVA, it is thought that children with chronic underlying diseases such as cSLE could have higher CVA recurrence rates and poorer outcomes. Therefore, our study will address the crucial need to understand risk factors and outcomes of CVA-cSLE. Our specific aims are:

Aim 1: To delineate candidate biomarkers that discriminate children with CVA-cSLE from other children who experience CVA. We will establish a longitudinal bioregistry (CVA-Bioregistry) to evaluate promising candidate blood-based biomarkers of vascular endothelial dysfunction and thrombosis proposed in the literature. These include vascular endothelial growth factor, angiopoetin1& 2, von Willebrand factor antigen, anti-endothelial antibodies and platelet factor 4.

Aim 2: To test whether the severity of CVA-cSLE is higher than that of CVA-aSLE. Severity will be measured by rates of all-cause mortality, 90-day re-admission, and discharge to in-patient rehabilitation.

Aim 3: To establish the functional outcome of CVA-cSLE and compared to other types of pediatric CVA. Functional outcomes will be assessed using the Pediatric Stroke Outcome Measure.

Our study is relevant as it will provide scientific data to support the development of targeted interventions toward improving outcomes for CVA-cSLE, and cSLE overall. Our results would promote earlier intervention by aiding the ability to identify cSLE sub­populations at higher risk of CVA. The long-term objective of our application is to improve outcomes for CVA-cSLE. Establishing the CVA-Bioregistry would enable further studies on the trajectory and mechanisms of CVA-cSLE in order to inform clinical care considerations.