This comprehensive review synthesizes the latest advancements in understanding inflammatory disorders affecting cerebral small vessels, a distinct yet understudied category within cerebral small vessel diseases (SVD). Unlike classical SVD, these inflammatory conditions exhibit unique clinical presentations, imaging patterns, and pathophysiological mechanisms, posing significant diagnostic and therapeutic challenges. Highlighting their heterogeneity, this review spans primary angiitis of the central nervous system, cerebral amyloid angiopathy-related inflammation, systemic vasculitis, secondary vasculitis, and vasculitis in autoinflammatory diseases. Key discussions focus on emerging insights into immune-mediated processes, neuroimaging characteristics, and histopathological distinctions. Furthermore, this review underscores the importance of standardized diagnostic frameworks, individualized immunomodulation approaches, and novel targeted therapies to address unmet clinical demands.
Humans ; Cerebral Small Vessel Diseases/pathology* ; Inflammation/pathology* ; Cerebral Amyloid Angiopathy/pathology* ; Vasculitis, Central Nervous System/pathology* ; Vasculitis/pathology*

Cerebral small vessel disease (SVD) is a common global brain disease that causes cognitive impairment, ischemic or hemorrhagic stroke, problems with mobility, and neuropsychiatric symptoms. The brain damage, seen as focal white and deep grey matter lesions on brain magnetic resonance imaging (MRI) or computed tomography (CT), typically accumulates "covertly" and may reach an advanced state before being detected incidentally on brain scanning or causing symptoms. Patients have typically presented to different clinical services or been recruited into research focused on one clinical manifestation, perhaps explaining a lack of awareness, until recently, of the full range and complexity of SVD.In this review, we discuss the varied clinical presentations, established and emerging risk factors, relationship to SVD features on MRI or CT, and the current state of knowledge on the effectiveness of a wide range of pharmacological and lifestyle interventions. The core message is that effective assessment and clinical management of patients with SVD, as well as future advances in diagnosis, care, and treatment, will require a more "joined-up" ’ approach. This approach should integrate clinical expertise in stroke neurology, cognitive, and physical dysfunctions. It requires more clinical trials in order to improve pharmacological interventions, lifestyle and dietary modifications. A deeper understanding of the pathophysiology of SVD is required to steer the identification of novel interventions. An essential prerequisite to accelerating clinical trials is to improve the consistency, and standardization of clinical, cognitive and neuroimaging endpoints.