Cerebral Vasoreactivity as an Indirect MRI Marker of White Matter Tracts Alterations in Multiple Sclerosis.

Patients with multiple sclerosis (MS) show a diffuse cerebral perfusion decrease, presumably related to multiple metabolism and vascular alterations. It is assumed that white matter fiber alterations cause a localized cerebral vasoreactivity (CVR) disruption through astrocytes metabolism alteration, leading to hypoperfusion. We proposed to (1) evaluate the CVR disruptions in MS, (2) in relation to white matter lesions and (3) compare CVR disruptions maps with standard imaging biomarkers. Thirty-five MS patients (10 progressive, 25 relapsing-remitting) and 22 controls underwent MRI with hypercapnic challenge, DTI imaging and neuropsychological assessment. Areas with disrupted CVR were assessed using a general linear model. Resulting maps were associated with clinical scores, compared between groups, and related to DTI metrics and white matter lesions. MS patients showed stronger disrupted CVR within supratentorial white matter, linking the left anterior insula to both the precentral gyrus and the right middle and superior frontal gyrus through the corpus callosum (P < 0.05, FWE corrected). Patient's verbal intellectual quotient was negatively associated with a pathway linking both hippocampi to the ispilateral prefrontal cortex (P < 0.05, FWE corrected). Disrupted CVR maps unrelated to DTI metrics and white matter lesions. We have demonstrated for the first time that white matter alterations can be indirectly identified through surrounding vessel alterations, and are related to clinical signs of MS. This offers a new, likely independent marker to monitor MS and supports a mediator role of the astrocytes in the fibers/vessels relationship.

Infantile-onset parkinsonism, dyskinesia, and developmental delay: do not forget polyglutamine defects!

We present the phenotype of an infant with the largest ATN1 CAG expansion reported to date (98 repeats). He presented at 4 months with developmental delay, poor eye contact, acquired microcephaly, failure to thrive. He progressively developed dystonia-parkinsonism with paroxysmal oromandibular and limbs dyskinesia and fatal outcome at 17 months. Cerebral MRI disclosed globus pallidus T2-WI hyperintensities and brain atrophy. Molecular analysis was performed post-mortem following the diagnosis of dentatorubral-pallidoluysian atrophy (DRPLA) in his symptomatic father. Polyglutamine expansion defects should be considered when neurodegenerative genetic disease is suspected even in infancy and parkinsonism can be a presentation of infantile-onset DRPLA.

Diffusion-weighted magnetic resonance imaging in early central retinal artery occlusion.

INTRODUCTION: Restricted retinal diffusion (RDR) has recently been recognized as a frequent finding on standard diffusion-weighted imaging (DWI) in central retinal artery occlusion (CRAO). However, data on early DWI signal evolution are missing. PATIENTS AND METHODS: Consecutive CRAO patients with DWI performed within 24 h after onset of visual impairment were included in a bicentric, retrospective cross-sectional study. Two blinded neuroradiologists assessed randomized DWI scans for the presence of retinal ischemia. RDR detection rates, false positive ratings, and interrater agreement were evaluated for predefined time groups. RESULTS: Sixty eight CRAO patients (68.4 ± 16.8 years; 25 female) with 72 DWI scans (76.4% 3 T, 23.6% 1.5 T) were included. Mean time-delay between onset of CRAO and DWI acquisition was 13.4 ± 7.0 h. Overall RDR detection rates ranged from 52.8% to 62.5% with false positive ratings in 4.2%-8.3% of cases. RDR detection rates were higher in DWI performed 12-24 h after onset, when compared with DWI acquired within the first 12 h (79.5%vs 39.3%, p < 0.001). The share of false positive ratings was highest for DWI performed within the first 6 h of symptom onset (up to 14.3%). Interrater reliability was "moderate" for DWI performed within the first 18 h (κ = 0.57-0.58), but improved for DWI acquired between 18 and 24 h (κ = 0.94). CONCLUSION: DWI-based detection of retinal ischemia in early CRAO is likely to be time-dependent with superior diagnostic accuracy for DWI performed 12-24 h after onset of visual impairment.

TBC1D32 variants disrupt retinal ciliogenesis and cause retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common inherited retinal disease (IRD) and is characterized by photoreceptor degeneration and progressive vision loss. We report 4 patients presenting with RP from 3 unrelated families with variants in TBC1D32, which to date has never been associated with an IRD. To validate TBC1D32 as a putative RP causative gene, we combined Xenopus in vivo approaches and human induced pluripotent stem cell-derived (iPSC-derived) retinal models. Our data showed that TBC1D32 was expressed during retinal development and that it played an important role in retinal pigment epithelium (RPE) differentiation. Furthermore, we identified a role for TBC1D32 in ciliogenesis of the RPE. We demonstrated elongated ciliary defects that resulted in disrupted apical tight junctions, loss of functionality (delayed retinoid cycling and altered secretion balance), and the onset of an epithelial-mesenchymal transition-like phenotype. Last, our results suggested photoreceptor differentiation defects, including connecting cilium anomalies, that resulted in impaired trafficking to the outer segment in cones and rods in TBC1D32 iPSC-derived retinal organoids. Overall, our data highlight a critical role for TBC1D32 in the retina and demonstrate that TBC1D32 mutations lead to RP. We thus identify TBC1D32 as an IRD-causative gene.

Homotopic redistribution of functional connectivity in insula-centered diffuse low-grade glioma.

OBJECTIVE: In the event of neural injury, the homologous contralateral brain areas may play a compensatory role to avoid or limit the functional loss. However, this dynamic strategy of functional redistribution is not clearly established, especially in the pathophysiological context of diffuse low-grade glioma. Our aim here was to assess the extent to which unilateral tumor infiltration of the insula dynamically modulates the functional connectivity of the contralesional one. METHODS: Using resting-state functional connectivity MRI, a seed-to-ROI approach was employed in 52 insula-centered glioma patients (n = 30 left and 22 right) compared with 19 age-matched healthy controls. RESULTS: Unsurprisingly, a significant decrease of the inter-insular connectivity was observed in both patient groups. More importantly, the analyses revealed a significant increase of the contralesional insular connectivity towards both cerebral hemispheres, especially in cortical areas forming the visual and the sensorimotor networks. This functional redistribution was not identified when the analyses were performed on three control regions for which the homologous area was not impaired by the tumor. This overall pattern of results indicates that massive infiltration of the insular cortex causes a significant redeployment of the contralesional functional connectivity. CONCLUSION: This general finding suggests that the undamaged insula plays a role in the functional compensation usually observed in this patient population, and thus provides compelling support for the concept of homotopic functional plasticity in brain-damaged patients.

Transient immediate postoperative homotopic functional disconnectivity in low-grade glioma patients.

Background and purpose: The aim of this longitudinal study is to evaluate large-scale perioperative resting state networks reorganization in patients with diffuse low-grade gliomas following awake surgery. Materials and methods: Eighty-two patients with diffuse low-grade gliomas were prospectively enrolled and underwent awake surgical resection. Resting-state functional images were acquired at three time points: preoperative (MRI-1), immediate postoperative (MRI-2) and three months after surgery (MRI-3). We simultaneously performed perfusion-weighted imaging. Results: Comparing functional connectivity between MRI-1 and MRI-2, we observed a statistically significant functional homotopy decrease in cortical and subcortical supratentorial structures (P < 0.05). A functional homotopy increase was observed between MRI-2 and MRI-3 in parietal lobes, cingulum and putamen (P < 0.05). No significant functional connectivity modification was noticed between MRI-1 and MRI-3. Regional cerebral blood flow appeared transiently reduced on MRI-2 (P < 0.05). No correlation between neurological deficit and interhemispheric connectivity results was found. Conclusion/interpretation: We found a supratentorial widely distributed functional homotopy disruption between preoperative and immediate postoperative time points with a complete restitution three months after surgery with simultaneous variation of regional cerebral blood flow.