Dr. Chitnis, Director of the Deep Brain Stimulation Program at University of Texas Southwestern Medical Center, has no relevant financial relationships to disclose.)
Dr. Jankovic, Director of the Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine, has received research and/or training grants from Adamas, Allergan, Biotie, Civitas/Acorda, Hoffmann-La Roche, Medtronic, Merz, Neurocrine , Nuvelution, Pfizer, Prothena, Psyadon, Revance, and Teva; and has served as a consultant or as an advisory committee member for Adamas, Allergan, Merz, Prothena, Revance, and Teva.)
This article includes discussion of idiopathic basal ganglia calcification, primary familial basal ganglia calcification, primary familial brain calcification, Fahr disease, Fahr syndrome, symmetrical calcification of the basal ganglia, calcification of the striopallidodentate system, striopallidodentate calcification, pallido dentate calcification, calcification of the corpus striatum and dentate nucleus, idiopathic calcification of cerebral capillaries, familial idiopathic cerebral calcifications, familial calcific dentate-striatal degeneration, familial idiopathic striopallidodentate calcification, familial basal ganglionic calcification, familial idiopathic brain calcification, progressive idiopathic striopallidodentate calcinosis, idiopathic familial brain calcifications, and idiopathic nonarteriosclerotic cerebral calcification. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Idiopathic basal ganglia calcification (IBGC), previously referred to as Fahr disease, is an inherited neuropsychiatric disorder, characterized by bilateral and usually symmetrical basal ganglia calcifications that may extend to the cerebellum, thalamus, and subcortical white matter. Parkinsonism and other movement disorders appear to be the most common clinical manifestation, followed by psychiatric symptoms, cognitive impairment, and ataxia. CT scan is considered more sensitive than MRI for finding calcifications. In this article, the authors discuss the etiology, pathogenesis, genetics, classification, and clinical manifestations of idiopathic basal ganglia calcification. A comprehensive list of disorders causing secondary brain calcification is provided (hypoparathyroidism being the most common).
Historical note and terminology
Basal ganglia calcifications involving the striatum, pallidum, with or without deposits in dentate nucleus, thalamus, and white matter have been reported in asymptomatic individuals and in a variety of neurologic conditions (Oliveira et al 2004; Manyam 2005; Schmidt 2005). Many names are used in the literature to describe this imaging finding, which has added to the confusion regarding etiology and clinical manifestations of idiopathic basal ganglia calcification and other disorders with similar radiographic appearance.
When basal ganglia calcifications are thought to be idiopathic (after appropriate search for secondary causes), the term idiopathic basal ganglia calcification (IBGC) is used. This was previously referred to as Fahr disease, but this eponym went out of favor as Fahr was not the first to describe the disorder nor did he contribute significantly to its understanding (Manyam 2005). As genetic underpinnings of idiopathic basal ganglia calcification have been identified, many authors have started using term “primary familial” instead of “idiopathic” (Sobrido et al 2014; Keogh et al 2015; Taglia et al 2015). Idiopathic basal ganglia calcification is typically inherited in an autosomal-dominant fashion, but if family history or genetic testing cannot be obtained, the term idiopathic may still be appropriate. Of note, incidental finding of basal ganglia calcification is present in 1% to 20% of healthy people (these calcifications are typically smaller, confined to pallidum, and increase with age) (Yamada et al 2013), so the term idiopathic basal ganglia calcification should only be used if there are appropriate accompanying clinical symptoms, or the calcifications are large (genetic forms have variable phenotype so affected individuals can be asymptomatic), or relevant genetic mutation has been identified. Secondary brain calcification has been reported in a variety of genetic, developmental, metabolic, infectious, and other conditions (see Table 1) (Manyam 2005). This was previously referred to as Fahr syndrome, but to avoid confusion the term “secondary” should be used to differentiate it from idiopathic basal ganglia calcification (Savino et al 2016).
A historical description of basal ganglia calcification is provided by Manyam (Manyam 2005). Briefly, Delecour first described vascular calcifications of the basal ganglia in 1850 in a 56-year-old man who had stiffness and weakness of lower extremities with tremor. In 1855, Bamberger described the histopathologic entity of calcifications in a woman who had mental retardation and seizures (Bamberger 1855). Later, in 1930, Fahr described an 81-year-old man with a long history of dementia, “immobility without paralysis,” with pathologic findings of “rough granular cortex and calcifications in centrum semiovale and striatum” (Fahr 1930). Fritzsche gave the first roentgenographic description of the condition in 1935 (Manyam 2005).
Because the hallmark is involvement of the basal ganglia, the term “idiopathic basal ganglia calcification” is well established in the literature, and idiopathic basal ganglia calcification is used in the OMIM registry, we will use the term in this review.
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