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Diffusion-Weighted MR Imaging in Leukodystrophies

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Diffusion-Weighted MR Imaging in Leukodystrophies Eur Radiol (2005) 15: 2284–2303 DOI 10.1007/s00330-005-2846-2 NEURO Zoltan Patay Diffusion-weighted MR imaging in leukodystrophies Abstract Leukodystrophies are pending on the nature of histopathol- Received: 2 February 2005 Revised: 23 May 2005 genetically determined metabolic dis- ogical changes, stage and progression Accepted: 31 May 2005 eases, in which the underlying bio- gradient of diseases, various diffusion- Published online: 15 July 2005 chemical abnormality interferes weighted imaging patterns may be # Springer-Verlag 2005 with the normal build-up and/or seen in leukodystrophies. Absent or maintenance of myelin, which leads low-grade myelin edema is found to hypo- (or arrested) myelination, or in mucopolysaccharidoses, GM dysmyelination with resultant demy- gangliosidoses, Zellweger disease, elination. Although conventional adrenomyeloneuropathy, L-2-hy- magnetic resonance imaging has sig- droxyglutaric aciduria, non-ketotic nificantly contributed to recent prog- hyperglycinemia, classical phenylke- ress in the diagnostic work-up of tonuria, Van der Knaap disease and the these diseases, diffusion-weighted vanishing white matter, medium grade imaging has the potential to further myelin edema in metachromatic leu- improve our understanding of under- kodystrophy, X-linked adrenoleuko- lying pathological processes and their dystrophy and HMG coenzyme lyase dynamics through the assessment deficiency and high grade edema in of normal and abnormal diffusion Krabbe disease, Canavan disease, properties of cerebral white matter. hyperhomocystinemias, maple syrup Z. Patay (*) Department of Radiology, MBC 28, Evaluation of conventional diffusion- urine disease and leukodystrophy with King Faisal Specialist Hospital weighted and ADC map images brainstem and spinal cord involve- and Research Centre, allows the detection of major diffusion ment and high lactate. P.O. Box 3354, 11211 Riyadh, abnormalities and the identification of Kingdom of Saudi Arabia . e-mail: [email protected] various edema types, of which the so- Keywords Magnetic resonance Tel.: +966-1-4423089 called myelin edema is particularly Diffusion study . Metabolism . Fax: +966-1-4427796 relevant to leukodystrophies. De- Leukodystrophy Introduction Goutière syndrome, vanishing white matter disease, leuko- dystrophy with brainstem and spinal cord involvement and The term leukodystrophy refers to a pathological process, high lactate and others have been described. Furthermore, most commonly of metabolic origin, involving the cerebral since the advent of MR imaging, a large number of addi- white matter exclusively or dominantly [1]. The so-called tional metabolic diseases (organic and amino acidopathies, classical leukodystrophies (e.g., metachromatic leukodys- etc.) have been identified that also present with dominant- trophy, globoid cell leukodystrophy, Canavan disease and ly white matter lesions, but have never been regarded as X-linked adrenoleukodystrophy) are genetically determined leukodystrophies. diseases that adversely affect the normal myelin turnover. Indeed, leukodystrophies are essentially histopatholog- More recently, several additional entities, such as megalen- ical and radiological entities, but the term is justified from cephalic leukoencephalopathy with subcortical cysts, Aicardi- the clinical point of view, too. Leukodystrophies usually 2285 present with cortical-spinal tract, in particular with pyra- weighted MR imaging in leukodystrophies has not been midal signs. This is in contrast to diseases affecting grey assessed systematically to date. matter structures, the so-called poliodystrophies, the clas- sical presentation of which is typically seizures and/or ex- trapyramidal movement disorders [1–3]. It is nevertheless Classification of leukodystrophies noteworthy that in poliodystrophies some degree of white matter involvement is often present, and conversely, many Leukodystrophies are difficult to classify because of the leukodystrophies present with clinical and radiological diversity of biochemical derangements potentially leading evidence of grey matter involvement. to white matter abnormalities. Possible metabolic errors may In leukodystrophies or leukodystrophy-like conditions, include peroxisomal disorders, lysosomal storage disorders, the underlying pathological processes may be diverse, organic acidurias, aminoacidemias and other relatively rare notably delayed myelination, dysmyelination or demyelin- disorders. In some of them, however, the underlying met- ation, or quite frequently a combination of them [4–6]. In abolic abnormality is not known at all (Table 1). delayed myelination the composition of the produced my- elin is normal; it is only the pattern and extent of the mye- lination that is inappropriate for the age. The absence or The principles of diffusion-weighted MR imaging abnormality of one or more of the essential constituents of and its relevance to the diagnostic imaging myelin (e.g., the incorporation of abnormally large quanti- work-up of leukodystrophies ties of very long chain fatty acids in peroxisomal disorders) leads to dysmyelination (abnormal histochemical structure Diffusion-weighted imaging (DWI) is a functional imaging of myelin), which may be associated with hypomyelina- technique at the cellular level. In homogeneous media tion. The produced myelin is sparse, fragile and prone to (such as water), the phenomenon of diffusion is the net breakdown, potentially leading to partial or complete de- movement of molecules due to a concentration gradient. myelination (loss of myelin) after a variable length of time. In biological specimens, however, diffusion is more com- The term demyelination may therefore refer to loss of either plex. Besides concentration gradients, pressure and ther- primarily normal or abnormal myelin. Possible causes of mal gradients, available volume fractions, space tortuosity, demyelination include a wide range of pathologies, notably as well as ionic interactions also play some role. Hence, it inflammatory, toxic, ischemic, etc. In leukodystrophies is actually referred to as apparent diffusion. dysmyelination is a frequent, perhaps the most common Diffusion-weighted imaging in biological specimens cause of demyelination, but a direct toxic effect or even relies on the detection of differences in water diffusion (in- reactive inflammatory changes may also play a role in travoxel incoherent motion) properties of various tissues. some entities. The process of demyelination may be rather The normal or abnormal diffusion properties of a biologi- rapid in some white matter diseases and quite slow in oth- cal specimen can be quantified; the two most commonly ers, and the triggering factor is often unknown. used parameters are the apparent diffusion coefficient (ADC) All of the above necessitate the redefinition of the term and the so-called tensor fractional anisotropy (FA) values. leukodystrophy. Indeed, leukodystrophies comprise any While the apparent diffusion coefficient describes only the inborn error of metabolism that interferes with the normal overall gross mobility of the water molecules in a given build-up and/or maintenance of myelin and hence has the tissue environment, determining fractional anisotropy pro- potential to cause hypo- (or arrested) myelination, or dys- vides additional information about the magnitude of an- myelination with resultant demyelination. isotropy of diffusion, hence, indirectly, about the integrity On conventional MR imaging, delayed myelination is of white matter tracts and cellular microstructure [7]. The often easy to identify, but occasionally it may be difficult latter, however, requires the availability of diffusion tensor to differentiate from a coexisting demyelinating process imaging (DTI), which is not the subject of the present of early onset. Dysmyelination may, but in most cases review. does not have conventional imaging manifestations until Diffusion information may be displayed in a conven- it leads to demyelination. Advanced MR techniques, such tional, image-based fashion. On these so-called conven- as proton MR spectroscopy and in particular diffusion- tional diffusion-weighted images, the signal is the product weighted imaging seem to further enhance the diagnostic of a T2-weighted echo planar background image, modified sensitivity and specificity of the MR imaging work-up by (typically attenuated) by the rate of apparent diffusion in more accurately identifying and differentiating the above the direction of the applied diffusion gradient. As a result, pathological processes. For instance, in proton MR spec- decreased water diffusion presents with hypersignal and, troscopy, increased choline content in normal appearing conversely, increased water diffusion with hyposignal on white matter—reflecting increased myelin turnover—can diffusion-weighted images. be an early indicator of demyelination. Despite its great However, because of the rather heavily T2-weighted potential and widespread use, the value of diffusion- echo-planar background image, diffusion-weighted images 2286 Table 1 Classification of the inherited metabolic diseases of the central nervous system presenting with leukodystrophy or leukodystrophy- like appearance on imaging (entities in bold are illustrated later in this paper) Lysosomal disorders Peroxisomal disorders Organic acidemias Amino acidurias Miscellaneous Unknown Mucopolysaccharidoses Zellweger disease L-2 hydroxyglutaric Maple syrup urine Galactosemia Van der Knaap aciduria disease disease Metachromatic Neonatal
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