RESUMEN
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: high-resolution 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 a widespread involvement of the brain WM, including the primary motor regions, which was confirmed at follow-up. The longitudinal analysis revealed an apparent inversion of tendency when considering the expected evolution of a neurodegenerative process: we detected an increase of FA and a decrease of MD and AD. These time-related modifications may suggest a repair attempt by the residual central WM fibers, which requires confirmation with a larger group of patients and with a longer time interval.
RESUMEN
In adults, partial damage to V1 or optic radiations abolishes perception in the corresponding part of the visual field, causing a scotoma. However, it is widely accepted that the developing cortex has superior capacities to reorganize following an early lesion to endorse adaptive plasticity. Here we report a single patient case (G.S.) with near normal central field vision despite a massive unilateral lesion to the optic radiations acquired early in life. The patient underwent surgical removal of a right hemisphere parieto-temporal-occipital atypical choroid plexus papilloma of the right lateral ventricle at four months of age, which presumably altered the visual pathways during in utero development. Both the tumor and surgery severely compromised the optic radiations. Residual vision of G.S. was tested psychophysically when the patient was 7 years old. We found a close-to-normal visual acuity and contrast sensitivity within the central 25° and a great impairment in form and contrast vision in the far periphery (40-50°) of the left visual hemifield. BOLD response to full field luminance flicker was recorded from the primary visual cortex (V1) and in a region in the residual temporal-occipital region, presumably corresponding to the middle temporal complex (MT+), of the lesioned (right) hemisphere. A population receptive field analysis of the BOLD responses to contrast modulated stimuli revealed a retinotopic organization just for the MT+ region but not for the calcarine regions. Interestingly, consistent islands of ipsilateral activity were found in MT+ and in the parieto-occipital sulcus (POS) of the intact hemisphere. Probabilistic tractography revealed that optic radiations between LGN and V1 were very sparse in the lesioned hemisphere consistently with the post-surgery cerebral resection, while normal in the intact hemisphere. On the other hand, strong structural connections between MT+ and LGN were found in the lesioned hemisphere, while the equivalent tract in the spared hemisphere showed minimal structural connectivity. These results suggest that during development of the pathological brain, abnormal thalamic projections can lead to functional cortical changes, which may mediate functional recovery of vision.
Asunto(s)
Plasticidad Neuronal , Corteza Visual/lesiones , Adolescente , Mapeo Encefálico , Neoplasias del Plexo Coroideo/cirugía , Sensibilidad de Contraste , Imagen de Difusión Tensora , Femenino , Humanos , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Papiloma del Plexo Coroideo/cirugía , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/psicología , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/lesiones , Corteza Visual/diagnóstico por imagen , Pruebas del Campo Visual , Vías Visuales/diagnóstico por imagen , Vías Visuales/lesionesRESUMEN
BACKGROUND AND PURPOSE: The hereditary spastic paraplegias are a group of genetically heterogeneous neurodegenerative disorders, characterized by progressive spasticity and weakness of the lower limbs. Although conventional brain MR imaging findings are normal in patients with pure hereditary spastic paraplegia, microstructural alteration in the cerebral WM can be revealed with DTI. Concomitant investigation of multiple intrinsic diffusivities may shed light on the neurobiologic substrate of the WM degeneration pattern in patients with pure hereditary spastic paraplegia across the whole brain. MATERIALS AND METHODS: Tract-based spatial statistics analysis was performed to compare fractional anisotropy and mean, axial, and radial diffusivities of the WM skeleton in a group of 12 patients with pure hereditary spastic paraplegia and 12 healthy volunteers. Data were analyzed counting age and sex as nuisance covariates. The threshold-free cluster-enhancement option was applied, and the family-wise error rate was controlled by using permutation tests for nonparametric statistics. RESULTS: In pure hereditary spastic paraplegia, group widespread fractional anisotropy decreases and radial diffusivity and mean diffusivity increases (P < .05, corrected) were found. No voxelwise difference was observed for the axial diffusivity map. Percentage of voxels within the WM skeleton that passed the significance threshold were 51%, 41.6%, and 11.9%, respectively, for radial diffusivity, fractional anisotropy, and mean diffusivity clusters. An anteroposterior pattern with preferential decrease of fractional anisotropy in the frontal circuitry was detected. CONCLUSIONS: In patients with pure hereditary spastic paraplegia, alterations in multiple DTI indices were found. Radial diffusivity seems more sensitive to hereditary spastic paraplegia-related WM pathology and, in line with the lack of axial diffusivity changes, might indicate a widespread loss of myelin integrity. A decrease of fractional anisotropy alone in the frontal circuitry may reflect subtle disruption of the frontal connections.