Table 1.
Demographic data of the patients studied.
Fig 1.
Examples of ROIs manually positioned along the cortico-spinal tracts (squared colored dots) for analysis of the diffusion values.
Examples of displayed: on FA colored map superimposed to b = 0 image of the DTI acquisition (A1, B1, C1); on FA map (A2); on FA colored maps alone (B2, C2, D2, E2, F2). Anatomical ROIs positions: A1 and A2, vertex of sub-cortical pre-central and pre-motor WM and corresponding GM; B1 and B2, cranial portion of the internal capsule, close to centrum semiovale and corona radiata; C1 and C2, anterior and posterior limb, and genu of internal capsule; D1 and D2, cerebral peduncles; E1 and E2, pons; F1 and F2 bulbar pyramids. DTI acquisitions parameters: TR 10.000 ms, TE 69 ms; IR 2400 ms; EPI factor 55; acquisition matrix 104x102; voxel 2x2x2,03mm; b-value 0–1.000 s/mm; 102 contiguous slices. A 32 different gradient directions acquisition was applied and tensor reconstruction was obtained to create isotropic and anisotropic maps.
Fig 2.
The disease duration and age at onset for the various SPG forms.
(A) Dot-plot illustrates the disease duration and age at onset size-scaled by the magnitude of SPRS score for patients in different HSP forms. (B) Faceted scatter-plot with a matrix of panels. Each panel shows correlation between age of onset and disease duration and SPRS for different SPG forms. Abbreviations of Fig 2: SPRS, Spastic Paraplegia Rating Scale.
Table 2.
Additional clinical signs in the various SPG forms.
Fig 3.
MCA analysis of additional signs reported in HSP patients.
In the space defined by the first two dimensions emerge three different profiles: bottom left (SPG3a, SPG4, SPG5, SPG10 and SPG31) absence of all the reported variables; bottom right (SPG11 and SPG15) presence of muscle atrophy, axonal neuropathy, ataxia, dysarthria, dysphagia and cognitive impairment; cloud between the first and second group (SPG7) presence of muscle atrophy, axonal neuropathy and ataxia. Top right (SPG35) cannot be considered significant as including only two individual with cognitive impairment. The genotypes are represented by black dots, arrows link to the specific SPG type. IDD: intellectual disability impairment. Abbreviations of Fig 3: IDD, Intellectual Developmental Disorder; SPG, Spastic Paraplegia Gene.
Table 3.
Findings on the standard MRI examinations.
Fig 4.
DTI values in controls and HSP patients for FA (A) and MD (B).
Only anatomical areas with statistically significant differences are reported (ANOVA, p-values not adjusted for multiple comparisons ranged between 0.002 and 0.048). Abbreviations: of Fig 4: WM, White Matter; GM, Gray Matter; R, Right; L, Left.
Fig 5.
Discriminant analysis: Area under the ROC curve (AUC) expressed as percent (abscises axis), reported for fractional anisotropy (FA), mean diffusivity (MD) and FA+MD.
Anatomical subdivision of cortico-spinal tract (CST) from pre-central and pre-motor grey matter (GM) to bulb: A, pre-central GM; B, sub-cortical pre-central white matter (WM); C, Deep supra-tentorial CST, from corona radiata to internal capsule; D, brain-stem CST tract, from cerebral peduncle to bulb; E, CST from sub-cortical pre-central WM to Cerebral Peduncles, throughout deep supra-tentorial WM; F, CST from sub-cortical pre-central WM to pons, throughout deep supra-tentorial WM; G, CST from corona radiata to cerebral peduncles; H, CST from corona radiata to pons; I, CST from corona radiata to bulb; L, Pre-motor GM; M, Pre-motor sub-cortical WM. X-axis: Combinations of the anatomical subdivision: A + B = pre-central GM and WM; B + C = Sub-cortical Pre-central WM and deep supra-tentorial CST; B + C + D = CST from sub-cortical pre-central WM to bulb, throughout deep supra-tentorial WM; A + B + C = Pre-central GM, more sub-cortical pre-central WM and deep supra-tentorial CST; A + E = Pre-central GM, more CST from sub-cortical pre-central WM to Cerebral Peduncles, throughout deep supra-tentorial; A + F = Pre-central GM, more CST from sub-cortical pre-central WM to pons, throughout deep supra-tentorial; A + B + C + D = Pre-central GM, more CST from sub-cortical pre-central WM to bulb, throughout deep supra-tentorial; L + M = Pre-motor GM and WM; A + L = Pre-central and pre-motor GM; B + M = Pre-central and pre-motor WM; A + B + L + M = Pre-central and pre-motor GM and WM; M + C = Pre-motor sub-cortical WM, more deep supra-tentorial CST, from corona radiata to internal capsule; L + M + C = Pre-motor GM, more Pre-motor sub-cortical WM and deep supra-tentorial CST, from corona radiata to internal capsule; M + C + D = Pre-motor sub-cortical WM, more deep CST, from corona radiata to bulb; L + M +C + D = Pre-motor GM and WM, more deep CST, from corona radiata to bulb.
Table 4.
Recommendations on the assessment tools for clinical use in HSP patients.