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. 2018 Jun 25:12:379.
doi: 10.3389/fnins.2018.00379. eCollection 2018.

Middle Cerebellar Peduncle Width-A Novel MRI Biomarker for FXTAS?

Annie L Shelton  1   2   3 , Jun Y Wang  1   2   4 , Emily Fourie  1   2   3 , Flora Tassone  1   4 , Anna Chen  3 , Lauren Frizzi  3 , Randi J Hagerman  1   5 , Emilio Ferrer  3 , David Hessl  1   6 , Susan M Rivera  1   2   3
Affiliations

Middle Cerebellar Peduncle Width-A Novel MRI Biomarker for FXTAS?

Annie L Shelton et al. Front Neurosci. .

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a severe neurodegenerative movement disorder affecting over 40% of male and 16% of female FMR1 premutation carriers over the age of 50. However, there is a lack of prognostic biomarkers to aid early diagnosis and treatment planning. Therefore, this study aimed to assess the utility of the Magnetic Resonance Parkinson Index (MRPI) as a potential MRI biomarker for FXTAS. The four measurements required for the MRPI were assessed in 45 male premutation carriers at risk of developing FXTAS (Mean age = 59.54 years), 53 male patients with FXTAS (Mean age = 66.16 years) and 61 male controls (Mean age = 60.75 years), of which 73 participants had follow-up visits on average 1.96 years later. Middle cerebellar peduncle (MCP) width as well as midbrain and pons cross-sectional area were reduced in patients with FXTAS compared to both premutation carriers without FXTAS and controls. While these measurements were not found to change over time in the three-group analysis, age was an important predictor of midbrain cross-sectional area and pons/midbrain ratio. MCP width was initially reduced in a subset of premutation carriers who developed FXTAS symptoms between their initial and follow-up visits, which also decreased between visits, compared to age-matched premutation carriers who did not show any FXTAS symptom development over time. Therefore, while the MPRI may not be a useful biomarker for FXTAS, decreased MCP width may be one of the first notable signs of FXTAS, and therefore the first biomarker with the potential to identify those most at risk for the disorder.

Keywords: FXTAS; MRI; biomarkers; fragile X; middle cerebellar peduncle.

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Figures

Figure 1
Figure 1
Schematic diagram showing the four MRPI measurements. Panel (A) shows the horizontal lines of the superior pontine notch which divides the midbrain (green) and pons (red) cross-sectional areas. Panel (B) shows the line drawn to define the MCP width, which is the linear distance between the peripeduncular cerebrospinal fluid spaces of pontocerebellar cisterns. The white arrow points to the white matter connecting the cerebellar tonsil to the deep white matter of the cerebellum. Panel (C) shows the horizontal lines which delineate the SCP width, at the coronal slice where the SCP first separates from the inferior colliculi.
Figure 2
Figure 2
Cross-sectional analysis of MRPI measurements at time 1, with age as a covariate. Brackets represents group differences where p < 0.05 using post-hoc Bonferroni correction.
Figure 3
Figure 3
Converter and non-converter group comparison of MCP width over time. Solid lines represent p < 0.007 and surviving Bonferroni correction for multiple comparisons, while the dotted line represents p < 0.05 and not surviving Bonferroni correction.
See this image and copyright information in PMC

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