Multimodal MRI Longitudinal Assessment of White and Gray Matter in Different SPG Types of Hereditary Spastic Paraparesis

Abstract

Hereditary spastic paraplegias (HSP) are a group of genetically and clinically heterogeneous neurologic disorders. Hereby we describe a relatively large group of patients (pts) affected by HSP studied at baseline (31 pts) and at follow-up (mean period 28.9 ± 8.4 months; 23 pts) with multimodal advanced MRI: highresolution T1 images for voxel-based morphometry (VBM) analysis, magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI). An age-matched healthy control (HC) group underwent the same neuroimaging protocol in a time schedule matched with the HSP patients. At baseline, VBM showed gray matter (GM) reduction in HSP in the right pre-frontal cortex and bilaterally in the thalami. MRS at baseline depicted in HSP patients compared to the HC group reduction of NAA/Cr ratio in the right pre-frontal region, increase of Cho/Cr ratio in the right pre-central regions, and increase of mI/Cr ratio on the left pre-central area. At cross-sectional follow-up analysis and longitudinal evaluation, no VBM and MRS statistically significant results were obtained. Tract-based spatial statistics (TBSS) analysis showed widespread DTI brain white matter (WM) alterations in patients compared to HC at baseline, which are characterized by reduction of fractional anisotropy (FA) and increase of mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity, as confirmed on cross-analysis of the follow-up dataset. A longitudinal analysis with TBSS in HSP patients did not show significant variations, while upon applying region-based analysis we found increased FA and decreased MD and AD in specific brain WM fiber complex during follow-up. The changes were not correlated with the clinical presentation (pure vs complicated HSP), motor function, and motility indexes or history of specific treatments (botulinum toxin). In conclusion, the cross-sectional analysis of the multiparametric MRI data in our HSP patients confirmed the non-prominent involvement of the cortex in the primary motor regions but rather of other more associative areas. On the contrary, DTI demonstrated

Brain Damage and Gene Expression Across Hereditary Spastic Paraplegia Subtypes

“…Previous reports suggest that HSPs are not purely spinal diseases, 28,29 but in-depth investigation of cerebral and cerebellar damage in these diseases is lacking. In the present study, we took a step further in the characterization of brain damage in HSPs by stratifying it for specific genotypes SPG3A, SPG4, SPG7, SPG8, and SPG11.…”

Relationship between brain white matter damage and grey matter atrophy in hereditary spastic paraplegia types 4 and 5

“…Amongst these regions, PreCG and SMA were somatomotor cortex, whilst other regions were mainly overlapping with the frontoparietal network which is considered to be important for top–down information integration from motor networks to control motor output [26] and has been related to motor symptoms in neurodegenerative diseases [27]. In addition, non‐motor region involvement (thalamus, IPL and prefrontal cortex) in these components has also been linked with extra‐motor clinical manifestations such as cognitive impairment in HSP patients in previous studies [5, 7, 28].…”

Outcome Measures and Biomarkers for Clinical Trials in Hereditary Spastic Paraplegia: A Scoping Review

“…We recommend the SPRS as it was the most commonly used CROM in HSP-related studies, has undergone psychometric testing in a cohort of individuals with HSP [ 67 ], has demonstrated cross-cultural validity [ 68 ], has been tested for responsiveness in longitudinal and interventional studies [ 30 , 33 , 35 , 62 , 64 , 69 , 89 ], and is a disease-specific outcome measure. In addition, it includes an assessment of motor function, and therefore, a performance outcome measure (PerfOM) for motor function is not required.…”