title: The magnetic resonance imaging spectrum of Pelizaeus-Merzbacher disease: A multicenter study of 19 patients.
abstract: OBJECTIVE
  We retrospectively evaluated the imaging spectrum of Pelizaeus-Merzbacher disease (PMD) in correlation with the clinical course and genetic abnormality.
  
  
  METHODS
  We collected the magnetic resonance imaging (MRI) findings of 19 genetically proven PMD patients (all males, aged 0-29years old) using our integrated web-based MRI data collection system from 14 hospitals. The patterns of hypomyelination were determined mainly by the signals of the cerebrum, corticospinal tract, and brainstem on T2-weighted images (T2WI). We assessed the degree of myelination age on T1-weighted images (T1WI) and T2WI independently, and we evaluated cerebellar and callosal atrophy. The clinical severity and genetic abnormalities (causal mutations of the proteolipid protein gene PLP1) were analyzed together with the imaging findings.
  
  
  RESULTS
  The clinical stage tended to be more severe when the whole brainstem, or corticospinal tract in the internal capsule showed abnormally high intensity on T2WI. Diffuse T2-high signal of brainstem was observed only in the patients with PLP1 point mutation. Myelination age "before birth" on T1WI is a second manifestation correlated with the clinically severe phenotypes. On the other hand, eight patients whose myelination ages were > 4months on T1WI were associated with mild clinical phenotypes. Four of them showed almost complete myelination on T1WI with a discrepancy in myelination age between T1WI and T2WI. A random and patchy pattern of myelination on T2WI was noted in one patient with PLP1 point mutation. Advanced myelination was observed in three of the seven followed-up patients. Four patients had atrophy of the cerebellum, and 17 patients had atrophy of the corpus callosum.
  
  
  CONCLUSIONS
  Our multicenter study has demonstrated a wide variety of imaging findings of PMD. Signal intensity of brainstem and corticospinal tract of internal capsule would be the points to presume clinical severity in PMD patients. The spectrum of MRI findings should be kept in mind to diagnose PMD and to differentiate from other demyelinating leukodystrophies.
authors.affiliation: Department of Radiology, National Center Hospital of Neurology and Psychiatry, Kodaira, Tokyo, Japan; Department of Radiology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sumida
authors.affiliation: Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Chiba, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Takanashi
authors.affiliation: Department of Pediatrics, National Center Hospital of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Division of Pediatrics, Minami Kyushu National Hospital, Aira, Kagoshima, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Pediatric Neurology, Aichi Prefectural Colony Central Hospital, Kasugai, Aichi, Japan.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Pediatric Neurology, Aichi Prefectural Colony Central Hospital, Kasugai, Aichi, Japan; Department of Pediatric Neurology, Aichi Medical University Hospital, Nagakute, Aichi, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kurahashi
authors.affiliation: Division of Child Neurology, Chiba Children's Hospital, Midori-ku, Chiba, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Omata
authors.affiliation: Department of Neurology, Saitama Children's Medical Center, Iwatsuki-ku, Saitama, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Pediatrics, Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokochi
authors.affiliation: Department of Pediatrics, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Hyogo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Iio
authors.affiliation: Department of Pediatrics, Hiroshima City Hospital, Naka-ku, Hiroshima, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Iyoda
authors.affiliation: Department of Pediatrics, Seiai Rehabilitation Hospital, Onojo, Fukuoka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kurokawa
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Muneaki
authors.initials: M
authors.lastname: Matsuo
authors.affiliation: Department of Pediatrics, Kanazawa Disabled Children's Hospital, Kanazawa, Ishikawa, Japan.
authors.forename: Tamotu
authors.initials: T
authors.lastname: Sato
authors.affiliation: Medical Institute of Bioregulation, Kyusyu University, Higashi-ku, Fukuoka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwaki
authors.affiliation: Department of Pediatrics, Jichi Medical University, Shimotsuke, Tochigi, Japan; Division of Neurology, Kanagawa Children's Medical Center, Minami-ku, Yokohama, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.affiliation: Division of Genetics, Kanagawa Children's Medical Center, Minami-ku, Yokohama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.affiliation: Institute for Integrated Medical Science, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Norihide
authors.initials: N
authors.lastname: Maikusa
authors.affiliation: Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuda
authors.affiliation: Department of Radiology, National Center Hospital of Neurology and Psychiatry, Kodaira, Tokyo, Japan. Electronic address: snoriko@ncnp.go.jp.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D018991:Myelin Proteolipid Protein / Q000235:genetics; D020371:Pelizaeus-Merzbacher Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D011712:Pyramidal Tracts / Q000000981:diagnostic imaging; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human
keywords: Hypomyelination; Magnetic resonance imaging; PLP1 duplication; PLP1 point mutation; Pelizaeus–Merzbacher disease; Proteolipid protein