title: Brain calcifications induce neurological dysfunction that can be reversed by a bone drug.
abstract: Perivascular calcifications within the brain form in response to a variety of insults. While considered by many to be benign, these calcium phosphate deposits or "brain stones" can become large and are associated with neurological symptoms that range from seizures to parkinsonian symptoms. Here we hypothesize that the high concentrations of calcium in these deposits produce reversible, toxic effects on neurons that can be overcome with "bone" drugs that chelate solid phase calcium phosphates. We present preliminary findings that suggest a direct association between progressive neurological symptoms and brain calcification and the symptomatic improvement of seizures, headaches, and parkinsonian symptoms in patients treated with the bisphosphonate drug disodium etidronate, normally used to treat bone diseases. Future, longitudinal epidemiological studies and randomized trials will be needed to determine the true relationship between brain stones and neurological disorders as well as the utility of bisphosphonates in their prevention and treatment.
authors.affiliation: Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA. jloeb@med.wayne.edu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Loeb
authors.forename: Sayyed A
authors.initials: SA
authors.lastname: Sohrab
authors.forename: Mabubul
authors.initials: M
authors.lastname: Huq
authors.forename: Darren R
authors.initials: DR
authors.lastname: Fuerst
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D001927:Brain Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D002114:Calcinosis / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D002130:Calcium Phosphates / Q000378:metabolism; D002648:Child; D004311:Double-Blind Method; D012968:Etidronic Acid / Q000627:therapeutic use*; D005260:Female; D006392:Hemangioma, Cavernous / Q000150:complications; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D012640:Seizures / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D002130:Calcium Phosphates; C020243:calcium phosphate; D012968:Etidronic Acid