Neuroradiological Findings (MRS, MRI, SPECT) in Infantile Neuronal Ceroid-Lipofuscinosis (Infantile CLN1) at Different Stages of the Disease

Abstract

Infantile neuronal ceroid-lipofuscinosis (infantile CLN1) is a progressive and uniformly fatal lysosomal storage disease of the nervous system. The purpose of this study was to compare the findings of various radiological examinations of the brain in the course of infantile CLN1 in order to evaluate the relative usefulness of the methods and their potential for monitoring therapeutic interventions. We examined eight infantile CLN1 patients, 51 studies, in various stages of the disease--preclinical to late stage--with proton magnetic resonance spectroscopy (1H-MRS), MRI, and perfusion SPECT, and in addition three benzodiazepine (BZ) receptor ligand SPECT studies. Both 1H-MRS and MRI showed abnormal findings before clinical manifestations of the disease. Cortical hypoperfusion and loss of cortical BZ receptors revealed by SPECT appeared simultaneously with clinical signs. After the age of 4 years MRI and SPECT alterations progressed minimally, whereas 1H-MRS showed progressive deterioration of neurometabolism. Of the four methods used in this study, MRI proved to be the most practicable for diagnosing infantile CLN1; the final diagnosis of infantile CLN1 is confirmed by the characteristic clinical picture and DNA or PPT enzyme analysis. The combination of 1H- MRS and MRI could be most useful for monitoring therapeutic interventions.

Infantile neuronal ceroid lipofuscinosis: Follow-up on a Spanish series

“…Regarding brain MRI, our patients showed similar findings to what has previously been reported by other authors (Santavuori et al, 1992(Santavuori et al, , 2000Vanhanen et al, 1995Vanhanen et al, , 2004.…”

MRI Brain Volume Measurements in Infantile Neuronal Ceroid Lipofuscinosis

“…Extrapolation of our previously published measurements of NAA in the thalamus 11 suggest that NAA in the thalamus may be in the normal range for a few months after birth; previous measurements 22 on very young children with INCL demonstrated normal NAA in the thalamus of a 2 month old child and a slight deficit of NAA in the thalamus of a 4 month old child. Thus, the relative order of volume loss (cerebrum before thalamus) that we report in this study is concordant with the order of previously reported MRS changes in humans.…”

“…Extrapolation of the cerebellum-to-cerebrum volume ratio suggests that the cerebral volume may never have been normal, not even in the fetus. A previous MRS study 22 found low NAA in the cerebral white matter of a patient at the age of 4 months; in the separately-reported MRS component of the current study 11 , we found that extrapolation of cerebral NAA levels beyond the age of our youngest patient does not appear to intersect the normal curve. NAA is produced mainly (or perhaps exclusively) by healthy neurons 23, 24 , and a decline in the level of NAA indicates loss or injury of neurons; logically, loss or injury of neurons should precede atrophy, and therefore the timing of our cerebral atrophy observations is consistent with the timing of NAA decline observed in the previous MRS reports.…”

Assessing Disease Severity in Late Infantile Neuronal Ceroid Lipofuscinosis Using Quantitative MR Diffusion-Weighted Imaging

“…Conventional MR imaging and CT have been used to demonstrate the presence of cerebral atrophy in multiple forms of neuronal ceroid lipofuscinosis. [13][14][15][16] However, atrophic grading using conventional MR imaging is only a subjective measure of disease severity. A diffuse hyperintensity of cerebral white matter has been reported in LINCL patients.…”