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Idiopathic Basal Ganglia Calcifications and Parkinson's Disease

  • Xiaopeng Guo
    Affiliations
    Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng District, Beijing, China
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  • Honglin Hao
    Affiliations
    Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng District, Beijing, China
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  • Hao Xing
    Affiliations
    Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng District, Beijing, China
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  • Yi Guo
    Correspondence
    Requests for reprints should be addressed to Yi Guo, Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
    Affiliations
    Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng District, Beijing, China
    Search for articles by this author
      To the Editor:
      A 57-year-old man presented to the Neurology Clinic with a 6-year history of progressive bilateral static tremor, bradykinesia, and gait initiation difficulty. His non-motor manifestations included constipation and pollakiuria. Initial levodopa test revealed excellent responsiveness, with Unified Parkinson's Disease Rating Scale scores improving from 57 to 14 points (75%). No signs of atrophy in the cerebrum, cerebellum, or brain stem were found on the magnetic resonance imaging. Parkinson's disease was clinically diagnosed. Computerized tomography of the head showed bilateral, symmetric, dense calcifications in the basal ganglia and cerebellum (FigureA). His serum calcium level was normal, and he had normal parathyroid functions. Whole exome sequencing was then performed, and a heterozygous variant in the SLC20A2 gene, c.1784C>T (p.Thr595Met), was suspected as the disease-causing gene mutation. Therefore, the combination of bilateral brain calcifications, normal phosphate-calcium metabolic function, and SLC20A2 gene mutation contributed to the final diagnosis of idiopathic basal ganglia calcifications (iBGC), or Fahr's disease.
      Figure
      Figure(A) Bilateral, symmetric, dense calcifications located in the basal ganglia and cerebellum (not shown) in a patient presenting with Parkinson disease, and (B) successful deep brain stimulation surgery with electrodes targeting the bilateral subthalamic nucleus.
      Compared with secondary BGC that are caused mainly by endocrine abnormalities, cerebrum infections, or toxic exposures,
      • Donzuso G
      • Mostile G
      • Nicoletti A
      • Zappia M
      Basal ganglia calcifications (Fahr's syndrome): related conditions and clinical features.
      iBGC can be caused by gene mutations, with SCL20A2 gene mutations being the most commonly reported.
      • Nicolas G.
      • Pottier C.
      • Charbonnier C.
      • et al.
      Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification.
      The SLC20A2 gene on chromosome 8 encodes a sodium-dependent phosphate transporter, protein PiT-2, which is highly active in the neurons in the brain. SLC20A2 gene mutations cause impaired transport of inorganic phosphate across the cells and the subsequent calcium phosphate deposition mostly in deep brain structures, such as basal ganglia and thalamus, leading to neuronal degeneration and gliosis and thus resulting in movement disorders. Parkinson's disease is one of the most common movement disorders in the course of iBGC.
      • Hsu SC
      • Sears RL
      • Lemos RR
      • et al.
      Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification.
      However, iBGC can also present without any movement disorders.
      • Guo XX
      • Zou XH
      • Wang C
      • et al.
      Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification.
      • Zhan FX
      • Tian WT
      • Zhang C
      • et al.
      Primary familial brain calcification presenting as paroxysmal kinesigenic dyskinesia: genetic and functional analyses.
      Deep brain stimulation (DBS) is a well-established surgical option for Parkinson's disease.
      • Kogan M
      • McGuire M
      • Riley J
      Deep brain stimulation for Parkinson disease.
      However, research on its application in alleviating iBGC-related movement disorders is still lacking. Because the patient developed severe on-off episodes and dyskinesias despite optimal medical treatment, he was recommended for and accepted DBS surgery. The intracranial electrodes targeting the bilateral subthalamic nucleus were successfully positioned with the help of the carefully-designed trajectory plans avoiding being influenced by the dense calcifications (Figure B). At follow-up, 8 weeks after surgery, his dyskinesias and on-off complications as well as the Unified Parkinson's Disease Rating Scale scores significantly improved. The frequency and dose of the dopaminergic medication were also reduced compared with the preoperative level.

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