giovedì 23 aprile 2009

Adrenal leukodystrophy


Figure 1: Axial non contrast CT demonstrates symmetric low attenuation in the temporal-parietal white matter. Note involvement of the splenium of the corpus callosum.
Figure 2 and Figure 3: Axial T1 and T2 images demonstrate symmetric T1 hypointensity and T2 hyperintensity in the temporal-parietal white matter corresponding to the low attenuation on CT. Note relative sparing of the subcortical U-fibers.
Figure 4: Axial post gadolinium T1 weighted image demonstrates abnormal hypointensity involving the temporal-parietal white matter, with enhancement of the leading edge which represents active demyelination.
Figure 5: MR spectroscopy demonstrates increased choline and decreased NAA, findings that are non specific but consistent with adrenal leukodystrophy. Note the presence of lactate an indicator of necrosis.

Diagnosis: Adrenal leukodystrophy

Adrenal leukodystrophy is a hereditary disorder caused by impaired beta-oxidation of very long chain fatty acids (VLCFA). Various forms exist, each named according to the age of presentation, including neonatal, childhood, adolescent and adulthood. Another variant, in which there is severe involvement of the spinal cord rather than the cerebrum, is termed adrenomyeloneuropathy (AMN).

The disease is caused by a mutation of the ALD gene which codes for a peroxisomal membrane protein. Transport of very long chain fatty acids into the peroxisome is consequently restricted. This results in reduced supply of shorter chain fatty acids within the peroxisome available for synthesis of complex lipids and proteins, which are myelin components.

The defective myelin is more easily broken down by the body’s normal physiologic functioning and the resulting pathophysiologic processes which include a severe inflammatory demyelination that predominates in the cerebral white matter and axonal degeneration that predominates in the posterior fossa and spinal cord.
These processes manifest radiologically as three zones in the cerebral white matter:
- Zone A, a central burned out zone containing only astrogliosis
- Zone B, an inflammatory zone peripheral to the central zone containing perivascular inflammatory cells and demyelination where axons are preserved
- Zone C, site of demyelination without inflammation.

Clinically, patients suffering from the childhood variant of ALD develop normally initially, but then present with behavioral changes and progressive visual, auditory and motor dysfunction between the ages of 4-10. Diagnosis is usually made by laboratory evaluation of very long chain fatty acid levels once there is clinical suspicion. Treatment options are limited and aimed at lowering levels of VLCFA’s through dietary restriction, consumption of Lorenzo’s oil and lovastatin therapy. Bone marrow transplantation has also shown to be of benefit in some cases. Imaging is helpful as an adjunctive tool to evaluate the extent of disease at presentation and to assess for evolution of the disease during treatment.

The classic picture of ALD is that of confluent, bilateral periatrial (parietal-occipital) deep white matter signal abnormality with sparing of the subcortical u-fibers. The pathological basis for the signal abnormality is a combination of demyelination and gliosis. The signal abnormality demonstrates a “leading edge” of enhancement which reflects blood brain barrier breakdown at sites of active demyelination at the margins of the signal abnormality. Calcifications along the trigone have also been noted as late sequelae.

Loes et al. have described five patterns of involvement, which when considered in the context of patient age at presentation, may give a clue to prognosis:
- Pattern 1 describes involvement of the parietal-occipital white matter and splenium and is associated with rapid progression with younger age of presentation and with enhancement.
- Pattern 2 is that of frontal white matter and genu involvement, and has a similar prognosis to that of Pattern 1.
- Pattern 3 is that of corticospinal tract involvement, usually seen in adults and demonstrates slower progression.
- Pattern 4 is that of corticospinal tract involvement associated with abnormality of the cerebellar white matter, which is seen in adolescents and is also associated with slower progression.
- Pattern 5 is that of concomitant frontal and parietal-occipital white matter abnormality, seen mostly in children and having a rapidly progressive course.

Proton MR spectroscopy demonstrates decreased NAA and myo-inositol and increased choline, glutamine, glutamate and lactate. Decreased NAA/Cr and NAA/Ch ratios and increased Ch/Cr ratios are characteristic. The classic imaging findings are virtually pathognomonic with limited differential diagnosis. Another peroxisomal disorder, acyl CoA oxidase deficiency, has similar imaging findings, but the clinical presentation is much different.

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