MR imaging and proton MR spectroscopic studies in Sjögren-Larsson syndrome: characterization of the leukoencephalopathy

Abstract

Background and purpose: Sjögren-Larsson syndrome (SLS) is a neurocutaneous syndrome caused by a genetic enzyme deficiency in lipid metabolism. Our purpose was to characterize the nature of the cerebral involvement in SLS.

Methods: MR imaging was performed in 18 patients (aged 5 months to 45 years) and repeated in 14. Single-voxel proton MR spectra were acquired from cerebral white matter and gray matter in 16 patients, with follow-up studies in 11. LCModel fits were used to determine brain metabolite levels.

Results: MR imaging showed retardation of myelination and a mild persistent myelin deficit. A zone of increased signal intensity was seen in the periventricular white matter on T2-weighted images. Proton MR spectroscopy of white matter revealed a prominent peak at 1.3 ppm, normal levels of N-acetylaspartate, and elevated levels of creatine (+14%), choline (+18%), and myo-inositol (+54%). MR imaging and proton MR spectroscopy of gray matter were normal. In the two patients examined during the first years of life, abnormalities on MR imaging and proton MR spectroscopy gradually emerged and then stabilized, as in all other patients.

Conclusion: Abnormalities on MR imaging and proton MR spectroscopy emerge during the first years of life and are similar in all patients with SLS, but the severity varies. The changes are confined to cerebral white matter and suggest an accumulation of lipids, periventricular gliosis, delayed myelination, and a mild permanent myelin deficit.

Fig 1.

FALDH catalyzes the oxidation of long-chain fatty aldehydes (here, octadecanal) to the corresponding carboxylic acid.

Fig 2.

Patient 13 at 16 years of age. T2-weighted MR images (3100/98 [TR/TE]). A and B, Severe signal-intensity changes of the periventricular white matter with predominant involvement of the frontal trigones. C, Small areas of unmyelinated subcortical association fibers.

Fig 3.

Patient 6 at 9 years of age. T2-weighted MR images (3100/98 [TR/TE]). A and B, Mild signal-intensity changes of the periventricular white matter with predominant involvement of the occipital trigones. C, Small areas of unmyelinated subcortical association fibers.

Fig 4.

Patient 2. T2-weighted MR images (3100/98 [TR/TE]). There is a delay in the maturation of the white matter on all three images. A, At 5 months of age, the unmyelinated periventricular white matter shows no abnormal signal intensities. B and C, Images obtained at 16 (B) and 35 (C) months of age show nonprogressive, slight signal-intensity abnormalities in the periventricular white matter that mainly involve the occipital trigones.

Fig 5.

Patient 3 at 5 years of age. A, Image shows voxel locations in the occipital trigone (box A) and in the central occipital gray matter (box B). B, Proton MR spectra (TE = 20 msec) obtained from cerebral white matter (spectrum A) and gray matter (spectrum B). Note the presence of the high, sharp lipid peak at 1.3 ppm and a small peak at 0.8–0.9 ppm in the spectrum obtained from the white matter.

Fig 6.

Serial proton MR spectra (TE = 20 msec) from cerebral white matter of patients 1 and 2 demonstrate a gradual emergence of the lipid peak at 1.3 ppm during the first years of life.

Fig 7.

Metabolite map derived from MRSI data of patient 13 shows the spatial distribution of the lipid peak over the cerebral white matter. The peak has its maximum height around the anterior and posterior trigones.