Background: Primary angiitis of the central nervous system (PACNS) is a rare form of single-organ vasculitis, as classified by the 2012 Chapel Hill Consensus Conference. It affects small- and medium-sized vessels within the brain and spinal cord, arises independently of systemic disease, manifests with heterogeneous clinical features, and remains without definitive diagnostic biomarkers.

Objectives: This review aims to provide an updated overview of the literature on this complex condition, highlighting the diagnostic challenges it presents. Given its insidious onset and nonspecific clinical presentation, early recognition is crucial to prevent diagnostic delays and minimize the risk of irreversible neurological damage.

Methods: An online single-database search was done targeting literature published between 2000 and 2024. Only English-language articles focusing on clinical presentations and mimics in adult patients were included. Four manual screening stages were performed independently by two authors. Of 447 identified articles, 233 were selected after initial screening, and 95 underwent further review and were read in full. Ultimately, 31 articles were included in the final analysis. Data extraction included demographics, clinical presentation, misdiagnoses, cerebrospinal fluid and blood biomarkers, imaging findings, histopathological results, and reported epidemiologic or environmental risk factors.

Results: Across all populations, the most frequent clinical manifestations were stroke, headache, and seizures, in that order. Neurological deficits occurred in more than half of patients, often accompanied or preceded by headache. One study reported a higher prevalence of seizures in cases with small-vessel involvement. Cognitive impairment was observed but appeared less common compared with other vasculitis syndromes. Rare complications included unruptured intracranial aneurysms, pseudoaneurysms, and subcortical hemorrhage. No sex predilection was observed. PACNS was often misdiagnosed. Mimickers included systemic vasculitides, infectious vasculitides, vascular disorders, neoplastic conditions, and demyelinating diseases.

Conclusions: PACNS manifests with a broad clinical spectrum, most commonly stroke, headache, or seizures. Given its overlap with numerous mimicking conditions and its association with significant morbidity and mortality, a high index of suspicion and timely diagnosis are essential.

Brain vasculitis, Primary CNS angiitis, Adult CNS vasculitis, Primary central nervous system vasculitis, Mimics, Clinical manifestations