Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy of Megalencephaly and Dilated Virchow-Robin Spaces Samuel Groeschel*, Knut Brockmann, MD*, Peter Dechent, PhD † , Ekkehard Wilichowski, MD*, Jens Frahm, PhD ‡ , and Folker Hanefeld, MD* Megalencephaly with dilated Virchow-Robin spaces has been suggested to represent a new clinical entity. This report describes two males and a female who have been monitored from pregnancy. The patients manifest a relatively normal psychomotor development with some minor neurologic symptoms such as mild muscle hypotonia and clumsy motor performance. Biochemi- cal and electrophysiologic tests were normal. In the white matter of the brain, a prominent dilatation of the Virchow-Robin spaces with some adjacent signal alter- ations could be demonstrated by magnetic resonance imaging. Magnetic resonance spectroscopy revealed normal metabolite concentrations in the cortical and deep gray matter and normal-appearing white matter. Affected white matter was characterized by mildly reduced to normal levels of myo-inositol and a decrease of all other metabolites including total N-acetyl moi- eties, choline-containing compounds, and total cre- atine. These data indicate that the dilatation of Vir- chow-Robin spaces reflects an underlying brain pa- thology causing neuroaxonal damage. Possible differ- ential diagnoses are discussed. © 2006 by Elsevier Inc. All rights reserved. Groeschel S, Brockmann K, Dechent P, Wilichowski E, Frahm J, Hanefeld F. Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy of Megalen- cephaly and Dilated Virchow-Robin Spaces. Pediatr Neu- rol 2006;34:35-40. Introduction Macrocephaly is frequently noticed during the first years of life and has a wide range of differential diagnoses. It can be the result of an external or internal hydrocephalus (or both) or an enlargement of the brain itself (megalen- cephaly) [1,2]. Apart from familial macrocephaly, an ever-increasing number of syndromes has been reported, characterized by macrocephaly combined with other ab- normalities that affect different organs and tissues. The Online Mendelian Inheritance in Man currently lists 138 entries under “macrocephaly” and 64 under “familial macrocephaly”. Two recent publications describe children with mega- lencephaly and dilated Virchow-Robin spaces. Artigas et al. [3] reported two children with a normal development, whereas the two affected siblings reported by Härtel et al. [4] presented with psychomotor retardation. Virchow [5] and Robin [6] described perivascular spaces that surround arteries and arterioles as they perforate the surface of the brain and extend into the brain tissue [7]. Despite the fact that dilated Virchow-Robin spaces is a frequent radiologic finding, their exact nature and function are largely unknown. In this study, three further patients, two males and a female, are reported. They have been monitored for 5 years with a detailed diagnostic evaluation including magnetic resonance imaging and localized proton mag- netic resonance spectroscopy. Besides the clinical and radiologic description of these patients, differential diag- noses are reviewed and possible disease mechanisms are discussed. From the *Department of Pediatrics and Neuropediatrics and † MR Research in Neurology and Psychiatry, Georg-August-Universität, Göttingen, Germany; and ‡ Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany. Communications should be addressed to: Dr. Hanefeld; Department of Pediatrics and Neuropediatrics; Children=s Hospital; Robert-Koch-Str. 40; 37075 Göttingen, Germany. E-mail: hanefeld@med.uni-goettingen.de Received February 22, 2005; accepted May 23, 2005. 35 © 2006 by Elsevier Inc. All rights reserved. Groeschel et al: Megalencephaly and Virchow-Robin Spaces doi:10.1016/j.pediatrneurol.2005.05.012 ● 0887-8994/06/$—see front matter