Brain Calcifications: Genetic, Molecular, and Clinical Aspects

Abstract

Many conditions can present with accumulation of calcium in the brain and manifest with a variety of neurological symptoms. Brain calcifications can be primary (idiopathic or genetic) or secondary to various pathological conditions (e.g., calcium–phosphate metabolism derangement, autoimmune disorders and infections, among others). A set of causative genes associated with primary familial brain calcification (PFBC) has now been identified, and include genes such as SLC20A2, PDGFB, PDGFRB, XPR1, MYORG, and JAM2. However, many more genes are known to be linked with complex syndromes characterized by brain calcifications and additional neurologic and systemic manifestations. Of note, many of these genes encode for proteins involved in cerebrovascular and blood–brain barrier functions, which both represent key anatomical structures related to these pathological phenomena. As a growing number of genes associated with brain calcifications is identified, pathways involved in these conditions are beginning to be understood. Our comprehensive review of the genetic, molecular, and clinical aspects of brain calcifications offers a framework for clinicians and researchers in the field.

Infectious Diseases and Basal Ganglia Calcifications: A Cross-Sectional Study in Patients with Fahr’s Disease and Systematic Review

“…During the last two decades, studies have reported associations between BGC and CMV, chronic active EBV, HIV, Mycobacterium tuberculosis, rubella virus, and Zika virus . Narrative reviews and textbooks have reported associations between BGC and Brucella sp., HSV, mumps virus, Neisseria meningitidis, Taenia solium, Toxoplasma gondii, and Treponema pallidum [2][3][4]6,7,17,38,41,[43][44][45][47][48][49][50][51][52][53][54][55][56][57][58][59][60]. Most original studies reported about congenital or perinatally acquired infectious diseases (CMV, HIV, rubella virus, Zika virus).…”

“…Narrative reviews and textbooks reported an additional seven pathogens, which included Brucella sp., HSV, mumps virus, Neisseria meningitidis, Taenia solium (a tapeworm causing cysticercosis), Toxoplasma gondii, and Treponema pallidum [2][3][4]6,7,17,38,41,[43][44][45][47][48][49][50][51][52][53][54][55][56][57][58][59][60]. The original articles, which were cited by the narrative reviews and textbooks, were published before 2002 and were therefore not retrieved.…”

Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities

“…Lastly, PET-MDCT is a practical and repeatable technique that combines the anatomical images of MDCT with the molecular images of PET, which is used to identify biomarkers of aortic valve biology and flow patterns [208,209]. PET-MDCT measurements of valvular 18 F-sodium fluoride ( 18 F-NaF) uptake serve as a marker of the active mineralization process taking place within the valve.…”

“…For example, the calcification of skin known as calcinosis cutis appears after patients with tuberculosis receive intravenous calcium gluconate, calcium chloride, and para-aminosalicylic acid [ 14 ]. Although pathological calcification can occur in almost all soft tissues of the body, the most prone areas are blood vessels, heart valves, brain, breast, kidneys, gastric mucosa, lungs, and tendons, and research has focused primarily on vascular calcification [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ] ( Figure 1 ).…”