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Alexander disease

Ventricular garlands and abnormalities of the medulla and spinal cord

From the Departments of Child Neurology (M.S.v.d.K., J.P.v.d.V.), Pathology (J.P.v.d.V.), and Radiology (F.B.), Metabolic Unit of the Department of Clinical Chemistry (S.J.M.v.D., C.J., G.S.S.), VU University Medical Center, Amsterdam, The Netherlands; Departments of Pediatric Neurology (V.R.), Neuroradiology (A.G.), and Neuropathology (D.W.E.), Newcastle General Hospital, Newcastle-upon-Tyne, UK; Developmental and Metabolic Neurology Branch (R.S.), National Institutes of Health, Bethesda, MD; Department of Radiology (S.B.), The Hospital for Sick Children, Toronto, Canada; and Department of Pediatric Neurology (M.K.), Queen Silvia Children's Hospital, University of Gothenburg, Sweden.

Address correspondence and reprint requests to Dr. Marjo S. van der Knaap, Department of Child Neurology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; e-mail: ms.vanderknaap{at}vumc.nl

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.

Conclusion: 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.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the February 28 issue to find the title link for this article.

Editorial, see page 468

Disclosure: The authors report no conflicts of interest.

Received August 10, 2005. Accepted in final form November 20, 2005.

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