White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis

Jitka Majovska, Igor Nestrasil, Amy Paulson, David R Nascene, Katarina Jurickova, Anna Hlavata, Troy Lund, Paul J Orchard, Manuela Vaneckova, Jiri Zeman, Martin Magner, Petr Dusek

Research output: Contribution to journalArticlepeer-review


Objective: Despite profound neurological symptomatology there are only few MRI studies focused on the brain abnormalities in alpha-mannosidosis (AM). Our aim was to characterize brain MRI findings in a large cohort of AM patients along with clinical manifestations. Methods: Twenty-two brain MRIs acquired in 13 untreated AM patients (8 M/5F; median age 17 years) were independently assessed by three experienced readers and compared to 16 controls. Results: Focal and/or diffuse hyperintense signals in the cerebral white matter were present in most (85%) patients. Cerebellar atrophy was common (62%), present from the age of 5 years. Progression was observed in two out of 6 patients with follow-up scans. Cortical atrophy (62%) and corpus callosum thinning (23%) were already present in a 13-month-old child. The presence of low T2 signal intensity in basal ganglia and thalami was excluded by the normalized signal intensity profiling. The enlargement of perivascular spaces in white matter (38%), widening of perioptic CSF spaces (62%), and enlargement of cisterna magna (85%) were also observed. Diploic space thickening (100%), mucosal thickening (69%) and sinus hypoplasia (54%) were the most frequent non-CNS abnormalities. Conclusion: White matter changes and cerebellar atrophy are proposed to be the characteristic brain MRI features of AM. The previously reported decreased T2 signal intensity in basal ganglia and thalami was not detected in this quantitative study. Rather, this relative MR appearance seems to be related to the diffuse high T2 signal in the adjacent white matter and not the gray matter iron deposition that has been hypothesized.

Original languageEnglish (US)
JournalMolecular Genetics and Metabolism
StateAccepted/In press - 2020

Bibliographical note

Funding Information:
The work was supported by the grants from the Ministry of the Health of the Czech Republic RVO-VFN-64165/2012 and the Ministry of Education, Youth and Sport of the Czech Republic PROGRES Q32/LF2 .

Funding Information:
IN was funded by the Lysosomal Disease Network ( U54NS065768 ) that is a part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), and NCATS . This consortium is funded through a collaboration between NCATS, NINDS, and NIDDK.

PubMed: MeSH publication types

  • Journal Article

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