Browsing by Author "Valsasina, Paola (6506051299)"

Introduction The pathophysiology of spasmodic dysphonia is poorly understood. This study evaluated patterns of cortical morphology, basal ganglia, and white matter microstructural alterations in patients with spasmodic dysphonia relative to healthy controls. Methods T1-weighted and diffusion tensor magnetic resonance imaging (MRI) scans were obtained from 13 spasmodic dysphonia patients and 30 controls. Tract-based spatial statistics was applied to compare diffusion tensor MRI indices (i.e., mean, radial and axial diffusivities, and fractional anisotropy) between groups on a voxel-by-voxel basis. Cortical measures were analyzed using surface-based morphometry. Basal ganglia were segmented on T1-weighted images, and volumes and diffusion tensor MRI metrics of nuclei were measured. Results Relative to controls, patients with spasmodic dysphonia showed increased cortical surface area of the primary somatosensory cortex bilaterally in a region consistent with the buccal sensory representation, as well as right primary motor cortex, left superior temporal, supramarginal and superior frontal gyri. A decreased cortical area was found in the rolandic operculum bilaterally, left superior/inferior parietal and lingual gyri, as well as in the right angular gyrus. Compared to controls, spasmodic dysphonia patients showed increased diffusivities and decreased fractional anisotropy of the corpus callosum and major white matter tracts, in the right hemisphere. Altered diffusion tensor MRI measures were found in the right caudate and putamen nuclei with no volumetric changes. Conclusions Multi-level alterations in voice-controlling networks, that included regions devoted not only to sensorimotor integration, motor preparation and motor execution, but also processing of auditory and visual information during speech, might have a role in the pathophysiology of spasmodic dysphonia. © 2016 Elsevier Ltd

Introduction The pathophysiology of spasmodic dysphonia is poorly understood. This study evaluated patterns of cortical morphology, basal ganglia, and white matter microstructural alterations in patients with spasmodic dysphonia relative to healthy controls. Methods T1-weighted and diffusion tensor magnetic resonance imaging (MRI) scans were obtained from 13 spasmodic dysphonia patients and 30 controls. Tract-based spatial statistics was applied to compare diffusion tensor MRI indices (i.e., mean, radial and axial diffusivities, and fractional anisotropy) between groups on a voxel-by-voxel basis. Cortical measures were analyzed using surface-based morphometry. Basal ganglia were segmented on T1-weighted images, and volumes and diffusion tensor MRI metrics of nuclei were measured. Results Relative to controls, patients with spasmodic dysphonia showed increased cortical surface area of the primary somatosensory cortex bilaterally in a region consistent with the buccal sensory representation, as well as right primary motor cortex, left superior temporal, supramarginal and superior frontal gyri. A decreased cortical area was found in the rolandic operculum bilaterally, left superior/inferior parietal and lingual gyri, as well as in the right angular gyrus. Compared to controls, spasmodic dysphonia patients showed increased diffusivities and decreased fractional anisotropy of the corpus callosum and major white matter tracts, in the right hemisphere. Altered diffusion tensor MRI measures were found in the right caudate and putamen nuclei with no volumetric changes. Conclusions Multi-level alterations in voice-controlling networks, that included regions devoted not only to sensorimotor integration, motor preparation and motor execution, but also processing of auditory and visual information during speech, might have a role in the pathophysiology of spasmodic dysphonia. © 2016 Elsevier Ltd

Here, we explored trajectories of sub-regional thalamic resting state (RS) functional connectivity (FC) modifications occurring in clinically isolated syndrome (CIS) patients early after their first clinical episode, and assessed their relationship with disability over 7 years. RS fMRI and clinical data were prospectively acquired from 59 CIS patients and 13 healthy controls (HC) over 2 years. A clinical re-assessment was performed in 53 (89%) patients after 7 years. Using a structural connectivity-based atlas, five thalamic sub-regions (frontal, motor, postcentral, occipital, and temporal) were used for seed-based RS FC. Thalamic RS FC abnormalities and their longitudinal changes were correlated with disability. Thirty-nine (66.1%) patients suffered a second clinical relapse, but the median EDSS remained stable over time. At baseline, CIS patients vs HC showed reduced RS FC (p < 0.001, uncorrected) with: (1) frontal cortices, for the whole thalamus, occipital, postcentral, and temporal thalamic sub-regions, (2) occipital cortices, for the occipital thalamic sub-region. In CIS, the longitudinal analysis revealed at year 2 vs baseline: (1) no significant whole-thalamic RS FC changes; (2) reduction of motor, postcentral, and temporal sub-regional RS FC with occipital cortices (p < 0.05, corrected); (3) an increase (p < 0.001, uncorrected) of postcentral and occipital sub-regional thalamic RS FC with frontal cortices, left putamen, and ipsi- and contralateral thalamus, this latter correlating with less severe clinical disability at year 7. Thalamo-cortical disconnections were present in CIS mainly in thalamic sub-regions closer to the third ventricle early after the demyelinating event, evolved in the subsequent 2 years, and were associated with long-term clinical disability. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Here, we explored trajectories of sub-regional thalamic resting state (RS) functional connectivity (FC) modifications occurring in clinically isolated syndrome (CIS) patients early after their first clinical episode, and assessed their relationship with disability over 7 years. RS fMRI and clinical data were prospectively acquired from 59 CIS patients and 13 healthy controls (HC) over 2 years. A clinical re-assessment was performed in 53 (89%) patients after 7 years. Using a structural connectivity-based atlas, five thalamic sub-regions (frontal, motor, postcentral, occipital, and temporal) were used for seed-based RS FC. Thalamic RS FC abnormalities and their longitudinal changes were correlated with disability. Thirty-nine (66.1%) patients suffered a second clinical relapse, but the median EDSS remained stable over time. At baseline, CIS patients vs HC showed reduced RS FC (p < 0.001, uncorrected) with: (1) frontal cortices, for the whole thalamus, occipital, postcentral, and temporal thalamic sub-regions, (2) occipital cortices, for the occipital thalamic sub-region. In CIS, the longitudinal analysis revealed at year 2 vs baseline: (1) no significant whole-thalamic RS FC changes; (2) reduction of motor, postcentral, and temporal sub-regional RS FC with occipital cortices (p < 0.05, corrected); (3) an increase (p < 0.001, uncorrected) of postcentral and occipital sub-regional thalamic RS FC with frontal cortices, left putamen, and ipsi- and contralateral thalamus, this latter correlating with less severe clinical disability at year 7. Thalamo-cortical disconnections were present in CIS mainly in thalamic sub-regions closer to the third ventricle early after the demyelinating event, evolved in the subsequent 2 years, and were associated with long-term clinical disability. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Purpose: To study the concomitant use of structural and functional magnetic resonance (MR) imaging correlates to explain information processing speed (IPS) and executive function (EF) in multiple sclerosis (MS). Materials and Methods: Local ethics committee approval was obtained at all sites for this prospective, multicenter study. All subjects provided written informed consent. Twenty-six patients with relapsing-remitting MS and 32 healthy control subjects from four centers underwent structural and functional MR imaging, including a go/no-go task and neuropsychological assessment. Subtests of the Brief Repeatable Battery of Neuropsychological Tests, the Wisconsin Card Sorting Test, and the performance with the functional MR imaging paradigm were used as estimates of IPS and EF. Activation of the thalamus and the inferior frontal gyrus (pars triangularis), thalamic volume, T2 lesion load, and age were used to explain IPS and EF in regression models. Results: Compared with control subjects, patients showed increased activation in a frontoparietal network, including both thalami, during the execution of the go/no-go task. Patients had decreased thalamic volume (P , .001). Among tested variables, thalamic volume (b = 0.606, P = .001), together with thalamic activation (b = 20.410, P = .022), were the best predictors of IPS and EF and helped explain 52.7% of the variance in IPS and EF. Conclusion: This study highlights the potential of the combined use of functional and morphologic parameters to explain IPS and EF in patients with relapsing-remitting MS and confirms the central role of the thalamus as a relay station in executive functioning. © RSNA, 2016.

Background: Different subregional patterns of hippocampal involvement have been observed in diverse multiple sclerosis (MS) phenotypes. Objective: To evaluate the occurrence of regional hippocampal variations in clinically isolated syndrome (CIS) patients, their relationships with focal white matter (WM) lesions, and their prognostic implications. Methods: Brain dual-echo and three-dimensional (3D) T1-weighted scans were acquired from 14 healthy controls and 36 CIS patients within 2 months from clinical onset and after 3, 12, and 24 months. Radial distance distribution was assessed using 3D parametric surface mesh models. A cognitive screening was also performed. Results: Patients showed clusters of reduced radial distance in the Cornu Ammonis 1 from month 3, progressively extending to the subiculum, negatively correlated with ipsilateral T2 and T1 lesion volume. Increased radial distance appeared in the right dentate gyrus after 3 (p < 0.05), 12, and 24 (p < 0.001) months, and in the left one after 3 and 24 months (p < 0.001), positively correlated with lesional measures. Hippocampal volume variations were more pronounced in patients converting to MS after 24 months and did not correlate with cognitive performance. Conclusion: Regional hippocampal changes occur in CIS, are more pronounced in patients converting to MS, and are modulated by focal WM lesions. © The Author(s), 2018.

Background: Different subregional patterns of hippocampal involvement have been observed in diverse multiple sclerosis (MS) phenotypes. Objective: To evaluate the occurrence of regional hippocampal variations in clinically isolated syndrome (CIS) patients, their relationships with focal white matter (WM) lesions, and their prognostic implications. Methods: Brain dual-echo and three-dimensional (3D) T1-weighted scans were acquired from 14 healthy controls and 36 CIS patients within 2 months from clinical onset and after 3, 12, and 24 months. Radial distance distribution was assessed using 3D parametric surface mesh models. A cognitive screening was also performed. Results: Patients showed clusters of reduced radial distance in the Cornu Ammonis 1 from month 3, progressively extending to the subiculum, negatively correlated with ipsilateral T2 and T1 lesion volume. Increased radial distance appeared in the right dentate gyrus after 3 (p < 0.05), 12, and 24 (p < 0.001) months, and in the left one after 3 and 24 months (p < 0.001), positively correlated with lesional measures. Hippocampal volume variations were more pronounced in patients converting to MS after 24 months and did not correlate with cognitive performance. Conclusion: Regional hippocampal changes occur in CIS, are more pronounced in patients converting to MS, and are modulated by focal WM lesions. © The Author(s), 2018.

Background: Functional magnetic resonance imaging (fMRI) correlates of cognitive deficits have not been thoroughly studied in patients with neuromyelitis optica spectrum disorders (NMOSDs). Objective: To investigate resting state (RS) functional connectivity (FC) abnormalities within the main cognitive networks in NMOSD patients and their correlation with cognitive performance. Methods: We acquired RS fMRI from 25 NMOSD patients and 30 healthy controls (HC). Patients underwent an extensive neuropsychological evaluation. Between-group RS FC comparisons and correlations with cognitive performance were assessed on the main cognitive RS networks identified by independent component analysis. Results: NMOSD patients showed higher RS FC versus HC in the precuneus of the default mode network (DMN) and right working memory network (WMN), as well as in several frontoparietal regions of the salience network (SN) and bilateral WMNs. Reduced frontal RS FC in NMOSD versus HC was detected in the left WMN. Increased RS FC in the DMN and right WMN was correlated with better cognitive performance, while decreased RS FC in the left WMN was associated with worse cognitive performance. Conclusion: Cognitive-network reorganization occurs in NMOSD. Clinico-imaging correlations suggest an adaptive role of increased RS FC. Conversely, reduced RS FC seems to be a maladaptive mechanism associated with a worse cognitive performance. © The Author(s), 2019.

Background: Functional magnetic resonance imaging (fMRI) correlates of cognitive deficits have not been thoroughly studied in patients with neuromyelitis optica spectrum disorders (NMOSDs). Objective: To investigate resting state (RS) functional connectivity (FC) abnormalities within the main cognitive networks in NMOSD patients and their correlation with cognitive performance. Methods: We acquired RS fMRI from 25 NMOSD patients and 30 healthy controls (HC). Patients underwent an extensive neuropsychological evaluation. Between-group RS FC comparisons and correlations with cognitive performance were assessed on the main cognitive RS networks identified by independent component analysis. Results: NMOSD patients showed higher RS FC versus HC in the precuneus of the default mode network (DMN) and right working memory network (WMN), as well as in several frontoparietal regions of the salience network (SN) and bilateral WMNs. Reduced frontal RS FC in NMOSD versus HC was detected in the left WMN. Increased RS FC in the DMN and right WMN was correlated with better cognitive performance, while decreased RS FC in the left WMN was associated with worse cognitive performance. Conclusion: Cognitive-network reorganization occurs in NMOSD. Clinico-imaging correlations suggest an adaptive role of increased RS FC. Conversely, reduced RS FC seems to be a maladaptive mechanism associated with a worse cognitive performance. © The Author(s), 2019.

Background: The spinal cord is commonly involved in patients with neuromyelitis optica spectrum disorders (NMOSDs). However, the relationship between inflammation and atrophy remains unclear. Purpose: To characterize the spatial distribution of T1-hypointense lesions in the spinal cord at MRI, its association with cord atrophy, and its correlation with disability in participants with NMOSDs. Materials and Methods: This prospective study evaluated three-dimensional T1-weighted spinal cord MRI scans in seropositive participants with NMOSDs and in age-matched healthy control participants acquired between February 2010 and July 2018. Binary masks of T1-hypointense lesions and lesion probability maps were produced. Cross-sectional area of the cervical and upper thoracic cord (down to T3 level) was calculated with the active-surface method. Full factorial models were used to assess cord atrophy in participants with NMOSDs. Correlations between cord atrophy and clinical and brain MRI measures were investigated with multiple regression models. Results: A total of 52 participants with NMOSDs (mean age 6 standard deviation, 44 years 6 15; 45 women) and 28 age-matched healthy control participants (mean age, 44 years 6 13; 16 women) were evaluated. Thirty-eight of 52 (73%) participants with NMOSDs had T1-hypointense cord lesions. No cord lesions were detected in the healthy control participants. Lesion probability maps showed a predominant involvement of the upper cervical (C2–C4) and upper thoracic (T1–T3 level) cord. The greater involvement of C1–C4 survived Bonferroni correction (P value range, .007–.04), with a higher percentage lesion extent in the gray matter (P , .001). Atrophy colocalized with focal cord lesions and correlated with pyramidal subscore (r ranging from 20.53 to 20.40; P , .001) and sensitive subscore (r ranging from 20.48 to 20.46; P = .001) of the Expanded Disability Status Scale. Participants without cord lesions had no cord atrophy. Conclusion: In participants with neuromyelitis optica spectrum disorders, focal areas of spinal cord atrophy at MRI were topographically associated with lesions and correlated to motor and sensory disability. Participants without visible cord lesions had no atrophy. © RSNA, 2020.

Objectives: In this prospective, longitudinal, multiparametric MRI study, we investigated clinical as well as brain grey matter and white matter (WM) regional changes in patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). Methods: Twenty-one patients with PSP-RS were evaluated at baseline relative to 36 healthy controls and after a mean follow-up of 1.4 years with clinical rating scales, neuropsychological tests and MRI scans. Results: Relative to controls, patients with PSP-RS showed at baseline a typical pattern of brain damage, including midbrain atrophy, frontal cortical thinning and widespread WM involvement of the main infratentorial and supratentorial tracts that exceeded cortical damage. Longitudinal study showed that PSP-RS exhibited no further changes in cortical thinning, which remained relatively focal, while midbrain atrophy and WM damage significantly progressed. Corpus callosum and frontal WM tract changes correlated with the progression of both disease severity and behavioural dysfunction. Conclusions: This study demonstrated the feasibility of carrying out longitudinal diffusion tensor MRI in patients with PSP-RS and its sensitivity to identifying the progression of pathology. Longitudinal midbrain volume loss and WM changes are associated with PSP disease course. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved.

Background: The features of functional network connectivity reorganization at the earliest stages of MS have not been investigated yet. Objective: To combine static and dynamic analysis of resting state (RS) functional connectivity (FC) to identify mechanisms of clinical dysfunction and recovery occurring in clinically isolated syndrome (CIS) patients. Methods: RS functional magnetic resonance imaging (fMRI) and clinical data were prospectively acquired from 50 CIS patients and 13 healthy controls (HC) at baseline, month 12 and month 24. Between-group differences and longitudinal evolution of network FC were analysed across 41 functionally relevant networks. Results: At follow-up, 47 patients developed MS. Disability remained stable (and relatively low). CIS and HC exhibited two recurring RS FC states (states 1 and 2, showing low and high internetwork connectivity, respectively). At baseline, patients showed reduced state 2 connectivity strength in the default-mode and cerebellar networks, and no differences in global dynamism versus HC. A selective FC reduction in networks affected by the clinical attack was also detected. At follow-up, increased state 2 connectivity strength and global connectivity dynamism was observed in patients versus HC. Conclusion: Longitudinal FC modifications occurring relatively early in the course of multiple sclerosis may represent a protective mechanism contributing to preserve clinical function over time. © The Author(s), 2019.

Background: The features of functional network connectivity reorganization at the earliest stages of MS have not been investigated yet. Objective: To combine static and dynamic analysis of resting state (RS) functional connectivity (FC) to identify mechanisms of clinical dysfunction and recovery occurring in clinically isolated syndrome (CIS) patients. Methods: RS functional magnetic resonance imaging (fMRI) and clinical data were prospectively acquired from 50 CIS patients and 13 healthy controls (HC) at baseline, month 12 and month 24. Between-group differences and longitudinal evolution of network FC were analysed across 41 functionally relevant networks. Results: At follow-up, 47 patients developed MS. Disability remained stable (and relatively low). CIS and HC exhibited two recurring RS FC states (states 1 and 2, showing low and high internetwork connectivity, respectively). At baseline, patients showed reduced state 2 connectivity strength in the default-mode and cerebellar networks, and no differences in global dynamism versus HC. A selective FC reduction in networks affected by the clinical attack was also detected. At follow-up, increased state 2 connectivity strength and global connectivity dynamism was observed in patients versus HC. Conclusion: Longitudinal FC modifications occurring relatively early in the course of multiple sclerosis may represent a protective mechanism contributing to preserve clinical function over time. © The Author(s), 2019.

OBJECTIVE: To explore structural and functional changes of the brain and cervical cord in patients with amyotrophic lateral sclerosis (ALS) due to mutation in the superoxide dismutase (SOD1) gene compared with sporadic ALS. METHODS: Twenty patients with SOD1 ALS, 11 with sporadic ALS, and 33 healthy controls underwent clinical evaluation and brain MRI. Cortical thickness analysis, diffusion tensor MRI of the corticospinal tracts (CST) and corpus callosum, and resting-state functional connectivity were performed. Patients with ALS also underwent cervical cord MRI to evaluate cord cross-sectional area and magnetization transfer ratio (MTR). RESULTS: Patients with SOD1 ALS showed longer disease duration and slower rate of functional decline relative to those with sporadic ALS. No cortical thickness abnormalities were found in patients with ALS compared with controls. Fractional anisotropy showed that sporadic ALS patients had significant CST damage relative to both healthy controls (p = 0.001-0.02) and SOD1-related ALS (p = 0.05), although the latter showed alterations that were intermediate between controls and sporadic ALS. Functional hyperconnectivity of the motor cortex in the sensorimotor network was observed in patients with sporadic ALS relative to controls. Conversely, patients with SOD1 ALS showed lower cord cross-sectional area along the whole cervical cord relative to those with sporadic ALS (p < 0.001). No cord MTR differences were found between patient groups. CONCLUSIONS: Patients with SOD1 ALS showed cervical cord atrophy relative to those with sporadic ALS and a relative preservation of brain motor structural and functional networks. Neurodegeneration in SOD1 ALS is likely to occur primarily in the spinal cord. An objective and accurate estimate of spinal cord damage has potential in the future assessment of preventive SOD1 ALS therapies. © 2018 American Academy of Neurology.

Objective: To apply voxel-based methods to map the regional distribution of atrophy and T2 hyperintense lesions in the cervical cord of multiple sclerosis (MS) patients with different clinical phenotypes. Methods: Brain and cervical cord 3D T1-weighted and T2-weighted scans were acquired from 31 healthy controls (HC) and 77 MS patients (15 clinically isolated syndromes (CIS), 15 relapsing-remitting (RR), 19 benign (B), 15 primary progressive (PP) and 13 secondary progressive (SP) MS). Hyperintense cord lesions were outlined on T2-weighted scans. The T2- and 3D T1-weighted cord images were then analysed using an active surface method which created output images reformatted in planes perpendicular to the estimated cord centre line. These unfolded cervical cord images were co-registered into a common space; then smoothed binary cord masks and lesion masks underwent spatial statistic analysis (SPM8). Results: No cord atrophy was found in CIS patients versus HC, while PPMS had significant cord atrophy. Clusters of cord atrophy were found in BMS versus RRMS, and in SPMS versus RRMS, BMS and PPMS patients, mainly involving the posterior and lateral cord segments. Cord lesion probability maps showed a significantly greater likelihood of abnormalities in RRMS, PPMS and SPMS than in CIS and BMS patients. The spatial distributions of cord atrophy and cord lesions were not correlated. In progressive MS, regional cord atrophy was correlated with clinical disability and impairment in the pyramidal system. Conclusions: Voxel-based assessment of cervical cord damage is feasible and may contribute to a better characterisation of the clinical heterogeneity of MS patients.