Neurobehavioral Changes Associated with Rheumatic Fever and Rheumatic Heart Disease: A Narrative Review

Abstract

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are autoimmune conditions triggered by Group A Streptococcus skin or throat infections. If ARF/RHD is undetected, misdiagnosed or antibiotic treatment is not provided early, patients may develop cardiac failure, leading to premature death. Although it is an easily preventable disease, ARF/RHD remains the most significant cause of heart disease-associated deaths in people under 25 years old, both in low- and middle-income countries and among First Nations in high-income countries. Up to 30% of the patients with ARF/RHD present with a neurobehavioral condition – Sydenham’s chorea (SC). The clinical course of SC is mostly self-limiting and is characterized by the onset of involuntary choreiform movements and neuropsychiatric features such as obsessive-compulsive disorder, tics, depression and anxiety, psychosis, and attention-deficit hyperactivity disorder. While the precise mechanism as to why only a proportion of patients with ARF/RHD develop SC remains unknown, an impaired blood–brain barrier is considered to play a central role in its development. The most well-characterized neurobehavioral outcome is stroke which may occur in isolation or as part of systemic thromboembolism. Both infective endocarditis and mitral valve disease with or without aortic valve disease increase the embolic and ischemic stroke risk. ARF/RHD is known to significantly impact the quality of life with neuropsychiatric consequences. Another neurobehavioral syndrome which occurs in the absence of ARF/RHD is “pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections” (PANDAS). PANDAS has been categorized as a subset of pediatric acute-onset neuropsychiatric syndromes. However, establishing a diagnosis of PANDAS has been challenging. In this review, we discuss the current status of our understanding regarding the different manifestations of poststreptococcal neurobehavioral changes. Particular attention is given to ARF/RHD-associated SC, and we highlight the areas for further research to understand the association between poststreptococcal sequelae and neurobehavioral abnormalities.