title: MRI characteristics of globus pallidus infarcts in isolated methylmalonic acidemia.
abstract: BACKGROUND
  Bilateral infarcts confined to the globus pallidus are unusual and occur in conjunction with only a few disorders, including isolated methylmalonic acidemia, a heterogeneous inborn error of metabolism. On the basis of neuroradiographic features of metabolic strokes observed in a large cohort of patients with methylmalonic acidemia, we have devised a staging system for methylmalonic acidemia-related globus pallidus infarcts.
  
  
  METHODS
  Forty patients with isolated methylmalonic acidemia and neurologic symptoms underwent clinical brain MR imaging studies, which included 3D-T1WI. Infarcted globus pallidus segments were neuroanatomically characterized, and infarct volumes were measured.
  
  
  RESULTS
  Globus pallidus infarcts were present in 19 patients; all were bilateral, and most were left-dominant. A neuroanatomic scoring system based on the infarct patterns was devised; this revealed a 5-stage hierarchical susceptibility to metabolic infarct, with the posterior portion of the globus pallidus externa being the most vulnerable. Globus pallidus infarct prevalence by methylmalonic acidemia class was the following: cblA (5/7, 71%), cblB (3/7, 43%), mut(o) (10/22, 45%), and mut- (1/4, 25%). Tiny lacunar infarcts in the pars reticulata of the substantia nigra, previously unrecognized in methylmalonic acidemia, were found in 17 patients, 13 of whom also had a globus pallidus infarct.
  
  
  CONCLUSIONS
  The staged pattern of globus pallidus infarcts in isolated methylmalonic acidemia suggests a nonuniform, regionally specific cellular susceptibility to metabolic injury, even for patients having milder biochemical phenotypes. In support of this hypothesis, the delineation of lacunar infarcts in the pars reticulata of the substantia nigra, a tissue functionally and histologically identical to the globus pallidus interna, supports the concept of cell-specific pathology.
authors.affiliation: From the Department of Radiology and Imaging Sciences (E.H.B.), Clinical Center bakere@mail.nih.gov.
authors.forename: E H
authors.initials: EH
authors.lastname: Baker
authors.affiliation: Genetics and Molecular Biology Branch (J.L.S., I.M., C.P.V.).
authors.forename: J L
authors.initials: JL
authors.lastname: Sloan
authors.affiliation: Medical Genetics and Metabolism Department (N.S.H.), Children's Hospital Central California, Madera, California.
authors.forename: N S
authors.initials: NS
authors.lastname: Hauser
authors.affiliation: Department of Neurology (A.L.G.), Children's National Medical Center, Washington, DC.
authors.forename: A L
authors.initials: AL
authors.lastname: Gropman
authors.affiliation: Medical Genetics Branch (D.R.A.).
authors.forename: D R
authors.initials: DR
authors.lastname: Adams
authors.affiliation: Undiagnosed Diseases Program (C.T.), National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: C
authors.initials: C
authors.lastname: Toro
authors.affiliation: Genetics and Molecular Biology Branch (J.L.S., I.M., C.P.V.).
authors.forename: I
authors.initials: I
authors.lastname: Manoli
authors.affiliation: Genetics and Molecular Biology Branch (J.L.S., I.M., C.P.V.).
authors.forename: C P
authors.initials: CP
authors.lastname: Venditti
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications*; D020520:Brain Infarction / Q000209:etiology* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005917:Globus Pallidus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male