Metabolic Disorders Affecting Primarily White Matter



Metabolic Disorders Affecting Primarily White Matter


Bernadette L. Koch, MD



DIFFERENTIAL DIAGNOSIS


Common



  • Leukodystrophies



    • X-Linked Adrenoleukodystrophy (X-ALD)


    • Canavan Disease


    • Metachromatic Leukodystrophy (MLD)


    • Krabbe Disease (GLD)


    • Hypomyelination


    • Alexander Disease


    • Vanishing White Matter Disease


Less Common



  • Mucopolysaccharidoses


Rare but Important



  • Megaloencephalic Leukoencephalopathy with Cysts (MLC)


  • Merosin Deficient Congenital Muscular Dystrophy


  • Maple Syrup Urine Disease


  • Nonketotic Hyperglycinemia


  • Urea Cycle Disorders


  • Giant Axonal Neuropathy


  • Trichothiodystrophies


  • Oculocerebrorenal (Lowe) Syndrome


  • Hyperhomocysteinemia (Homocystinuria)


ESSENTIAL INFORMATION


Key Differential Diagnosis Issues



  • Leukodystrophy



    • Inborn errors of metabolism → abnormal growth or development of myelin sheath → progressive degeneration of WM


    • Symmetric subcortical or deep WM ± GM


  • Macrocephaly: Canavan, Alexander, & MLC


  • Initial PVWM involvement: MLD, Globoid-cell leukodystrophy (GLD), X-linked ALD


  • Initial subcortical WM involvement: MLC, vanishing white matter


  • Many → diffuse WM disease and atrophy


  • MRS: Majority → ↓ NAA; Canavan → ↑ NAA


Helpful Clues for Common Diagnoses



  • X-Linked Adrenoleukodystrophy (X-ALD)



    • Most common in males 5-12 years old


    • Immune-mediated inflammation at active zones of demyelination → enhancement



      • 80% splenium image peritrigonal WM image corticospinal tracts/fornix/commisural fibers/visual and auditory pathways


      • 15% frontal pattern, genu, anterior/genu internal capsule ± cerebellar (CB) WM


    • Spares subcortical U-fibers


    • ± Ca++


  • Canavan Disease



    • Macrocephaly


    • ↑ T2 subcortical U-fibers, thalami, and globi pallidi


    • MRS: ↑ NAA


  • Metachromatic Leukodystrophy (MLD)



    • Most common form is late infantile variant; presents in 2nd year of life


    • Frontal and posterior WM


    • Symmetric, confluent, nonenhancing ↑ T2 PVWM in “butterfly” pattern


    • ± radial stripes (relative sparing of myelin in perivenular regions)


    • Atrophy, subcortical U-fibers involved late


  • Krabbe Disease (GLD)



    • Globoid-cell leukodystrophy (GLD)


    • CT: Symmetric, bilateral high attenuation in thalami on early CT (3-6 months old)


    • ↑ T2: Thalami, basal ganglia, CB nuclei, PVWM, corticospinal and pyramidal tracts


    • ± optic nerve enlargement


    • ± enhancement at junction of normal and abnormal WM


    • ± lumbar nerve root enhancement


  • Hypomyelination



    • T2 hypointensity of myelin normally lags behind T1 hyperintensity by 4-8 months


    • Myelination on T2WI should be complete by 3 years, usually by 2 years of age


    • Primary hypomyelination syndromes 2° to chromosome deletions and mutations



      • Pelizaeus-Merzbacher disease (PMD)


      • Spastic paraplegia type 2 (SPG2)


      • Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC)


      • 18q-syndrome


      • Jacobsen syndrome (11q-)


      • Hypomyelination with congenital cataracts (DRCTNNB1A)


      • Hypomyelination + trichothiodystrophy


  • Alexander disease



    • Macrocephaly


    • Infantile form most common


    • ↑ T2 in bifrontal WM; caudate heads > putamina, thalami


    • Enhancement in periventricular frontal lobe white matter in infantile form



    • Enhancement in cerebellum and medulla in juvenile form


    • ± enhancement in thalami, brainstem, dentate nuclei, cerebellar cortex, optic chiasm, fornix


    • ± obstructive hydrocephalus 2° to periaqueductal disease


  • Vanishing White Matter Disease



    • Childhood ataxia with diffuse CNS hypomyelination, childhood ataxia with central hypomyelination (CASH)


    • WM ultimately becomes isointense to CSF, begins in central cerebral WM


Helpful Clues for Less Common Diagnoses



  • Mucopolysaccharidoses



    • Hunter & Hurler syndrome most common


    • Enlarged Virchow-Robin spaces, filled with glycosaminoglycans


    • Mild PVWM disease


Helpful Clues for Rare Diagnoses



  • Megaloencephalic Leukoencephalopathy with Cysts (MLC)



    • a.k.a. van der Knaap disease


    • Macrocephaly


    • Peripheral WM swollen with enlarged gyri


    • Less severe involvement of CB WM


    • Subcortical cysts in posterior frontal and anterior temporal lobes


  • Merosin Deficient Congenital Muscular Dystrophy



    • Hypomyelination of central cerebral WM


    • ± CB vermis and pontine hypoplasia


  • Maple Syrup Urine Disease



    • Acute phase: Edema and restricted diffusion in areas where normal neonatal WM should be myelinated



      • Deep CB and perirolandic WM, dorsal brainstem, cerebral peduncles, posterior limb internal capsule ± globi pallidi


  • Nonketotic Hyperglycinemia



    • Delayed myelination and edema in frontal cortex and subcortical WM


    • Long-echo MRS: Abnormal peak at 3.56 ppm probably represents glycine


  • Urea Cycle Disorders



    • Multiple different enzyme deficiencies


    • Severe edema in cortex, subcortical WM, and basal ganglia


  • Giant Axonal Neuropathy



    • ↑ T2 in cerebral and cerebellar WM, spares subcortical U-fibers


  • Trichothiodystrophies



    • Galactosemia: Delayed myelination in subcortical WM on T2WI, normal on T1WI; ± cerebral and CB atrophy


    • Cockayne syndrome: ↑ T2 periventricular WM, basal ganglia, CB dentate nuclei


  • Oculocerebrorenal (Lowe) Syndrome

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Aug 10, 2016 | Posted by in PEDIATRICS | Comments Off on Metabolic Disorders Affecting Primarily White Matter

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