Primary Brain Calcification: An International Consensus on Nomenclature, Diagnosis, Evaluation, and Management

Our understanding of primary brain calcification (PBC) has accelerated with the identification of seven causative genes over the past 13 years, vastly expanding knowledge of the molecular underpinnings of this disorder. Despite this progress, a lack of standardized clinical definitions, variable presentations, and heterogeneous calcification patterns has perpetuated inconsistencies in diagnosis and patient care. To address these challenges, an international expert panel undertook a comprehensive process—combining systematic literature review, virtual and in-person expert discussions, and iterative Delphi consensus questionnaires—to develop unified recommendations. These consensus guidelines encompass terminology, diagnostic criteria, neuroimaging protocols, clinical evaluation standards, genetic testing approaches, and management strategies. Notably, PBC is recommended as the clinical standard, with new diagnostic criteria, including the use of a computed tomography–based total calcification score and a three-tiered diagnostic algorithm (possible, probable, definite PBC). A systematic review of 27 symptoms and signs identified 19 as most closely linked with PBC, guiding more focused clinical assessment. Recommendations strongly support comprehensive next-generation sequencing for genetic testing, favoring whole genome over exome or targeted panels to maximize diagnostic yield. Multidisciplinary management priorities are outlined in four key principles centering on individualized care, symptom relief, genetic counseling, and ongoing monitoring. Widespread adoption of these unified guidelines will facilitate consistent diagnosis, enable comparative international data collection, and lay the groundwork for large-scale collaborative research—including future randomized controlled trials of symptomatic and disease-modifying PBC therapies. This consensus fosters clarity and consistency, creating a framework for improved patient care and scientific discovery.