Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI

A 37-year-old macrocephalic woman was investigated for increasing gait disturbance due to longstanding spasticity and ataxia. MRI showed widespread bilateral increase in signal from cerebral white matter on T2-weighted images. Numerous subcortical cysts were visible in anterior-temporal and parietal regions. These clinical and neuroradiological features are those of megalencephalic leukoencephalopathy with subcortical cysts (MLC), a recently delineated white-matter disease with onset in childhood. Quantitative localised proton MR spectroscopy of white matter revealed marked reduction of N-acetylaspartate, creatine, and choline with normal values for myo-inositol, consistent with axonal loss and astrocytic proliferation. Diffusion tensor imaging showed an increased apparent diffusion coefficient and reduced anisotropy in affected white matter pointing to reduced cell density with an increased extracellular space. These findings are in line with histological changes alterations known to occur in MLC.

[1]  B. Ben-Zeev,et al.  Vacuolating Megalencephalic Leukoencephalopathy in 12 Israeli Patients , 2001, Journal of child neurology.

[2]  J. Frahm,et al.  Localized Proton Magnetic Resonance Spectroscopy of Cerebral Metabolites , 1996, Neuropediatrics.

[3]  J. Frahm,et al.  Improvements in localized proton NMR spectroscopy of human brain. Water suppression, short echo times, and 1 ml resolution , 1990 .

[4]  William H. Oldendorf,et al.  N-Acetyl-L-Aspartic acid: A literature review of a compound prominent in 1H-NMR spectroscopic studies of brain , 1989, Neuroscience & Biobehavioral Reviews.

[5]  D Matthaei,et al.  Rapid three-dimensional MR imaging using the FLASH technique. , 1986, Journal of computer assisted tomography.

[6]  J. Valk,et al.  Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children , 1995, Annals of neurology.

[7]  J. Beckmann,et al.  Vacuoliting megalencephalic leukoencephalopathy with subcortical cysts, mapped to chromosome 22qtel. , 2000, American journal of human genetics.

[8]  D. Leibfritz,et al.  Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. , 1993, Developmental neuroscience.

[9]  N. De Stefano,et al.  Severe metabolic abnormalities in the white matter of patients with vacuolating megalencephalic leukoencephalopathy with subcortical cysts. A proton MR spectroscopic imaging study , 2001, Journal of Neurology.

[10]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

[11]  R. Schutgens,et al.  Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts. , 2001, American journal of human genetics.

[12]  B. Singhal,et al.  Megalencephalic leukodystrophy in an Asian Indian ethnic group. , 1996, Pediatric neurology.

[13]  B. Engelen,et al.  Leukoencephalopathy with swelling in children and adolescents: MRI patterns and differential diagnosis , 1995, Neuroradiology.

[14]  J. Aicardi,et al.  Leukoencephalopathy, Megalencephaly, and Mild Clinical Course. A Recently Individualized Familial Leukodystrophy. Report on Five New Cases , 1996, Journal of child neurology.

[15]  B. Trapp,et al.  N‐acetylaspartate is an axon‐specific marker of mature white matter in vivo: A biochemical and immunohistochemical study on the rat optic nerve , 2002, Annals of neurology.

[16]  J. Griffin,et al.  Choline containing metabolites during cell transfection: an insight into magnetic resonance spectroscopy detectable changes , 2001, FEBS letters.

[17]  J. Finsterbusch,et al.  Rapid isotropic diffusion mapping without susceptibility artifacts: Whole brain studies using diffusion‐weighted single‐shot STEAM MR imaging , 2000, Magnetic resonance in medicine.

[18]  J. Valk,et al.  Histopathology of an infantile-onset spongiform leukoencephalopathy with a discrepantly mild clinical course , 1996, Acta Neuropathologica.

[19]  Jens Frahm,et al.  Regional Age Dependence of Human Brain Metabolites from Infancy to Adulthood as Detected by Quantitative Localized Proton MRS , 1999, Pediatric Research.

[20]  J. Frahm,et al.  Cystic leukoencephalopathy in a megalencephalic child: clinical and magnetic resonance imaging/magnetic resonance spectroscopy findings. , 1997, Pediatric neurology.

[21]  I. Saatci,et al.  Megalencephaly and leukodystrophy with mild clinical course: a report on 12 new cases , 1998, Brain and Development.