Abstract
Despite improvement in the specific treatment, clinical and anatomo-functional central nervous system (CNS) abnormalities of various severities are still observed in cystinosis patients. Patients who develop CNS complications today have a worse compliance to cysteamine treatment. Radiological studies have shown that cortical or central (ventriculomegaly) atrophy is observed in more than two thirds of cystinosis patients’ magnetic resonance imaging (MRI) and correlates with the intelligence quotient score. Half of cystinosis patients have marked aspecific white matter hyperintensities. The development of advanced neuroimaging techniques provides new tools to further investigate CNS complications. A recent neuroimaging study using a voxel-based morphometry approach showed that cystinosis patients present a decreased grey matter volume in the left middle frontal gyrus. Diffusion tensor imaging studies have shown white matter microstructure abnormalities in children and adults with cystinosis, respectively in areas of the dorsal visual pathway and within the corpus callosum’s body. Finally, leucocyte cystine levels are associated with decreased resting cerebral blood flow, measured by arterial spin labelling, in the frontal cortex, which could be associated with the neurocognitive deficits described in these patients. These results reinforce the relevance of neuroimaging studies to further understand the mechanisms that underline CNS impairments.
Highlights
Cystinosis is a rare autosomal recessive disease caused by intracellular cystine accumulation [1,2]
Three clinical forms have been described based on the severity of symptoms and the age of onset: infantile cystinosis characterized by renal proximal tubulopathy and early progression to end-stage renal disease (ESRD), a juvenile form with a markedly slower rate of progression and an adult form with mainly, but, ocular abnormalities [3]
Our results showed a significantly decreased fractional anisotropy in cystinosis patients compared to healthy controls in clusters within the corpus callosum’s body, indicating a white matter microarchitecture abnormality, which suggests disruption in white matter maturation, there might be a secondary progressive effect cystine accumulation on white matter organization and connectivity [43]
Summary
Cystinosis is a rare autosomal recessive disease caused by intracellular cystine accumulation [1,2]. In historical cohorts, central nervous system complications (CNS) were observed in adolescents and young adults not fully treated with cysteamine, as this treatment became available only in the 1990s [5–7]. In the era of early specific treatment with cysteamine, a high prevalence of mild to severe clinical and radiological CNS impairments is still observed in adult patients. Such complications may affect quality of life, academic function, and professional insertion. The cause of death was linked to neurological reason in one-third of cases in that series and in two patients out of thirty-three (6%) in the series of Gahl et al [16] These data further reinforce the relevance of investigating CNS complications in this disease. Mini-mental state examination, which screens for cognitive function deficit, was assessed in twelve patients, and the median score was twenty-seven out of thirty, with four patients having a decreased score below twenty-five
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