Novel Hypomyelinating Leukoencephalopathy Affecting Early Myelinating Structures | Neurology | JAMA Neurology | JAMA Network
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Jan 2012

Novel Hypomyelinating Leukoencephalopathy Affecting Early Myelinating Structures

Author Affiliations

Author Affiliations: Departments of Child Neurology (Drs Steenweg, Wolf, and van der Knaap), Radiology (Dr Barkhof), and Physics and Medical Technology (Dr Pouwels), VU University Medical Center, Amsterdam, and Department of Child Neurology, Radboud University Nijmegen Medical Center, Nijmegen (Dr Schieving), the Netherlands; Department of Pediatric Neurology, Hamad Medical Corp, Doha, Qatar (Dr Fawzi Elsaid); Pediatric Subspecialty Services, The Permanente Medical Group, Sacramento, California (Dr Friederich); and Department of Paediatrics, Aarhus University Hospital, Skejby, Denmark (Dr Østergaard).

Arch Neurol. 2012;69(1):125-128. doi:10.1001/archneurol.2011.1030

Objective To describe 4 children with a novel hypomyelinating leukoencephalopathy, defined by a distinct pattern of magnetic resonance imaging (MRI) abnormalities.

Design In our ongoing study on leukoencephalopathies of unknown origin, MRIs of patients are rated in a standardized manner. Patients are grouped according to their MRI abnormalities. The clinical and laboratory data are retrospectively reviewed.

Subjects The MRIs of approximately 3000 patients with a leukoencephalopathy of unknown origin were initially evaluated. Four unrelated patients (all male, aged 1.8-7.4 years) displayed similar MRI alterations.

Results Patients displayed mild T2 hyperintensity of the medulla oblongata, caudal part of the pons, hilus of the dentate nucleus, peridentate white matter, subcortical cerebellar white matter, optic radiation, and frontoparietal periventricular white matter. The posterior limb of the internal capsule showed alternating T2 hyperintense-hypointense-hyperintense stripes in 3 patients. The T1-weighted images showed hyperintensity, isointensity, or mild hypointensity of T2 hyperintense structures. The thalamus had a neonatal appearance with a mildly hyperintense signal except for a darker lateral part. Clinically, patients presented with nystagmus between ages 6 and 20 months. Over time, cerebellar ataxia and mild spasticity developed. All achieved unsupported walking. Cognition and language were normal. Known causes of hypomyelination were excluded.

Conclusions The patients share a striking pattern of MRI abnormalities and have a similar clinical picture, suggesting that they have the same disorder. The hypomyelination in this disorder specifically occurs in structures that normally myelinate early. We hypothesize that the disease is caused by a defect in a gene involved in early myelination.