title: Alexander disease: ventricular garlands and abnormalities of the medulla and spinal cord.
abstract: BACKGROUND
  Alexander disease is most commonly associated with macrocephaly and, on MRI, a leukoencephalopathy with frontal preponderance. The disease is caused by mutation of the GFAP gene. Clinical and MRI phenotypic variation have been increasingly recognized.
  
  
  METHODS
  The authors studied seven patients with Alexander disease, diagnosed based on mutations in the GFAP gene, who presented unusual MRI findings. The authors reviewed clinical history, MRI abnormalities, and GFAP mutations.
  
  
  RESULTS
  All patients had juvenile disease onset with signs of brainstem or spinal cord dysfunction. None of the patients had a macrocephaly. The MRI abnormalities were dominated by medulla and spinal cord abnormalities, either signal abnormalities or atrophy. One patient had only minor cerebral white matter abnormalities. A peculiar finding was the presence of a kind of garland along the ventricular wall in four patients. Three patients had an unusual GFAP mutation, one of which was a duplication mutation of two amino acids, and one an insertion deletion.
  
  
  CONCLUSIONS
  Signal abnormalities or atrophy of the medulla or spinal cord on MRI are sufficient to warrant DNA analysis for Alexander disease. Ventricular garlands constitute a new sign of the disease. Unusual phenotypes of Alexander disease are found among patients with late onset and protracted disease course.
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands. ms.vanderknaap@vumc.nl
authors.forename: M S
authors.initials: MS
authors.lastname: van der Knaap
authors.forename: V
authors.initials: V
authors.lastname: Ramesh
authors.forename: R
authors.initials: R
authors.lastname: Schiffmann
authors.forename: S
authors.initials: S
authors.lastname: Blaser
authors.forename: M
authors.initials: M
authors.lastname: Kyllerman
authors.forename: A
authors.initials: A
authors.lastname: Gholkar
authors.forename: D W
authors.initials: DW
authors.lastname: Ellison
authors.forename: J P
authors.initials: JP
authors.lastname: van der Voorn
authors.forename: S J M
authors.initials: SJ
authors.lastname: van Dooren
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: G S
authors.initials: GS
authors.lastname: Salomons
mesh_terms: D000293:Adolescent; D000328:Adult; D038261:Alexander Disease / Q000235:genetics / Q000473:pathology*; D001921:Brain / Q000002:abnormalities*; D002552:Cerebral Ventricles / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008526:Medulla Oblongata / Q000002:abnormalities* / Q000473:pathology; D009154:Mutation; D013116:Spinal Cord / Q000002:abnormalities* / Q000473:pathology
chemical_list: D005904:Glial Fibrillary Acidic Protein