Browsing by Author "Copetti, Massimiliano (24474249000)"

An overlap frequently occurs between major depression disorder (MDD) and generalized anxiety disorder (GAD). Aim of this study was to assess cortical and white matter (WM) alterations in MDD patients with or without GAD comorbidity. Seventy-one MDD patients and 71 controls were recruited. All subjects underwent T1-weighted and diffusion tensor (DT)/MRI. MRI metrics of cortical thickness and WM integrity were obtained from atlas-based cortical regions and the interhemispheric and major long association WM tracts. Between-group MRI comparisons and multiple regressions with clinical scale scores were performed. Compared to controls, both MDD and MDD-GAD patients showed a cortical thinning of the middle frontal cortex bilaterally, left medial frontal gyrus and frontal pole. Compared to controls and MDD patients, MDD-GAD cases also showed a thinning of the right medial orbitofrontal and fusiform gyri, and left temporal pole and lateral occipital cortices. Compared to controls, MDD patients showed DT MRI abnormalities of the right parahippocampal tract and superior longitudinal fasciculus bilaterally, while no WM alterations were found in MDD-GAD. In all patients, brain abnormalities were related with symptom severity. MDD and MDD-GAD share a common pattern of cortical alterations located in the frontal regions. However, while both the cortex and WM integrity are affected in MDD, only the former is affected in MDD-GAD. These findings support the notion of MDD-GAD as a distinct clinical entity, providing insights into patient vulnerability for specific networks as well as into patient resilience factors reflected by the integrity of other cerebral circuits. © 2015, Springer-Verlag Berlin Heidelberg.

An overlap frequently occurs between major depression disorder (MDD) and generalized anxiety disorder (GAD). Aim of this study was to assess cortical and white matter (WM) alterations in MDD patients with or without GAD comorbidity. Seventy-one MDD patients and 71 controls were recruited. All subjects underwent T1-weighted and diffusion tensor (DT)/MRI. MRI metrics of cortical thickness and WM integrity were obtained from atlas-based cortical regions and the interhemispheric and major long association WM tracts. Between-group MRI comparisons and multiple regressions with clinical scale scores were performed. Compared to controls, both MDD and MDD-GAD patients showed a cortical thinning of the middle frontal cortex bilaterally, left medial frontal gyrus and frontal pole. Compared to controls and MDD patients, MDD-GAD cases also showed a thinning of the right medial orbitofrontal and fusiform gyri, and left temporal pole and lateral occipital cortices. Compared to controls, MDD patients showed DT MRI abnormalities of the right parahippocampal tract and superior longitudinal fasciculus bilaterally, while no WM alterations were found in MDD-GAD. In all patients, brain abnormalities were related with symptom severity. MDD and MDD-GAD share a common pattern of cortical alterations located in the frontal regions. However, while both the cortex and WM integrity are affected in MDD, only the former is affected in MDD-GAD. These findings support the notion of MDD-GAD as a distinct clinical entity, providing insights into patient vulnerability for specific networks as well as into patient resilience factors reflected by the integrity of other cerebral circuits. © 2015, Springer-Verlag Berlin Heidelberg.

[No abstract available]

White matter (WM) tract alterations were assessed in patients with progressive supranuclear palsy (PSP) relative to healthy controls and patients with idiopathic Parkinson's disease (PD) to explore the relationship of WM tract damage with clinical disease severity, performance on cognitive tests, and apathy. 37 PSP patients, 41 PD patients, and 34 healthy controls underwent an MRI scan and clinical testing to evaluate physical disability, cognitive impairment, and apathy. In PSP, the contribution of WM tract damage to global disease severity and cognitive and behavioural disturbances was assessed using Random Forest analysis. Relative to controls, PSP patients showed diffusion tensor (DT) MRI abnormalities of the corpus callosum, superior cerebellar peduncle (SCP), cingulum and uncinate fasciculus bilaterally, and right inferior longitudinal fasciculus. Corpus callosum and SCP DT MRI measures distinguished PSP from PD patients with high accuracy (area under the curve ranging from 0.89 to 0.72). In PSP, DT MRI metrics of the corpus callosum and superior cerebellar peduncles were the best predictors of global disease severity scale scores. DT MRI metrics of the corpus callosum, right superior longitudinal and inferior longitudinal fasciculus, and left uncinate were the best predictors of executive dysfunction. In PSP, apathy severity was related to the damage to the corpus callosum, right superior longitudinal, and uncinate fasciculi. In conclusion, WM tract damage contributes to the motor, cognitive, and behavioural deficits in PSP. DT MRI offers markers for PSP diagnosis, assessment, and monitoring. © 2014 Springer-Verlag.

White matter (WM) tract alterations were assessed in patients with progressive supranuclear palsy (PSP) relative to healthy controls and patients with idiopathic Parkinson's disease (PD) to explore the relationship of WM tract damage with clinical disease severity, performance on cognitive tests, and apathy. 37 PSP patients, 41 PD patients, and 34 healthy controls underwent an MRI scan and clinical testing to evaluate physical disability, cognitive impairment, and apathy. In PSP, the contribution of WM tract damage to global disease severity and cognitive and behavioural disturbances was assessed using Random Forest analysis. Relative to controls, PSP patients showed diffusion tensor (DT) MRI abnormalities of the corpus callosum, superior cerebellar peduncle (SCP), cingulum and uncinate fasciculus bilaterally, and right inferior longitudinal fasciculus. Corpus callosum and SCP DT MRI measures distinguished PSP from PD patients with high accuracy (area under the curve ranging from 0.89 to 0.72). In PSP, DT MRI metrics of the corpus callosum and superior cerebellar peduncles were the best predictors of global disease severity scale scores. DT MRI metrics of the corpus callosum, right superior longitudinal and inferior longitudinal fasciculus, and left uncinate were the best predictors of executive dysfunction. In PSP, apathy severity was related to the damage to the corpus callosum, right superior longitudinal, and uncinate fasciculi. In conclusion, WM tract damage contributes to the motor, cognitive, and behavioural deficits in PSP. DT MRI offers markers for PSP diagnosis, assessment, and monitoring. © 2014 Springer-Verlag.

This study investigated the regional distribution of white matter (WM) damage in Richardson's syndrome (PSP-RS) and progressive supranuclear palsy-Parkinsonism (PSP-P) using diffusion tensor (DT) magnetic resonance imaging (MRI). The DT MRI classificatory ability in diagnosing progressive supranuclear palsy (PSP) syndromes, when used in combination with infratentorial volumetry, was also quantified. In 37 PSP (21 PSP-RS, 16 PSP-P) and 42 controls, the program Tract-Based Spatial Statistics (TBSS; www.fmrib.ox.ac.uk/fsl/tbss) was applied. DT MRI metrics were derived from supratentorial, thalamic, and infratentorial tracts. The magnetic resonance parkinsonism index (MRPI) was calculated. All PSP harbored diffusivity abnormalities in the corpus callosum, frontoparietal, and frontotemporo-occipital tracts. Infratentorial WM and thalamic radiations were severely affected in PSP-RS and relatively spared in PSP-P. When MRPI and DT MRI measures were combined, the discriminatory power increased for each comparison. Distinct patterns of WM alterations occur in PSP-RS and PSP-P. Adding DT MRI measures to MRPI improves the diagnostic accuracy in differentiating each PSP syndrome from healthy individuals and each other. © 2012 Elsevier Inc..

This study investigated the regional distribution of white matter (WM) damage in Richardson's syndrome (PSP-RS) and progressive supranuclear palsy-Parkinsonism (PSP-P) using diffusion tensor (DT) magnetic resonance imaging (MRI). The DT MRI classificatory ability in diagnosing progressive supranuclear palsy (PSP) syndromes, when used in combination with infratentorial volumetry, was also quantified. In 37 PSP (21 PSP-RS, 16 PSP-P) and 42 controls, the program Tract-Based Spatial Statistics (TBSS; www.fmrib.ox.ac.uk/fsl/tbss) was applied. DT MRI metrics were derived from supratentorial, thalamic, and infratentorial tracts. The magnetic resonance parkinsonism index (MRPI) was calculated. All PSP harbored diffusivity abnormalities in the corpus callosum, frontoparietal, and frontotemporo-occipital tracts. Infratentorial WM and thalamic radiations were severely affected in PSP-RS and relatively spared in PSP-P. When MRPI and DT MRI measures were combined, the discriminatory power increased for each comparison. Distinct patterns of WM alterations occur in PSP-RS and PSP-P. Adding DT MRI measures to MRPI improves the diagnostic accuracy in differentiating each PSP syndrome from healthy individuals and each other. © 2012 Elsevier Inc..

Background and Purpose: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. Methods: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients-Intervention-Comparator-Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score >6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. Results: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. Conclusions: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs. © Alessandra Solari et al., 2020; Published by Mary Ann Liebert, Inc. 2020.

Background and Purpose: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. Methods: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients-Intervention-Comparator-Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score >6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. Results: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. Conclusions: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs. © Alessandra Solari et al., 2020; Published by Mary Ann Liebert, Inc. 2020.

This prospective study explored whether an approach combining structural [cortical thickness and white matter (WM) microstructure] and resting state functional MRI can aid differentiation between 62 early onset Alzheimer's disease (EOAD) and 27 behavioural variant of frontotemporal dementia (bvFTD) patients. Random forest and receiver operator characteristic curve analyses assessed the ability of MRI in classifying the two clinical syndromes. All patients showed a distributed pattern of brain alterations relative to controls. Compared to bvFTD, EOAD patients showed bilateral inferior parietal cortical thinning and decreased default mode network functional connectivity. Compared to EOAD, bvFTD patients showed bilateral orbitofrontal and temporal cortical thinning, and WM damage of the corpus callosum, bilateral uncinate fasciculus, and left superior longitudinal fasciculus. Random forest analysis revealed that left inferior parietal cortical thickness (accuracy 0.78, specificity 0.76, sensitivity 0.83) and WM integrity of the right uncinate fasciculus (accuracy 0.81, specificity 0.96, sensitivity 0.43) were the best predictors of clinical diagnosis. The combination of cortical thickness and DT MRI measures was able to distinguish patients with EOAD and bvFTD with accuracy 0.82, specificity 0.76, and sensitivity 0.96. The diagnostic ability of MRI models was confirmed in a subsample of patients with biomarker-based clinical diagnosis. Multiparametric MRI is useful to identify brain alterations which are specific to EOAD and bvFTD. A severe cortical involvement is suggestive of EOAD, while a prominent WM damage is indicative of bvFTD. © 2017 The Authors

This prospective study explored whether an approach combining structural [cortical thickness and white matter (WM) microstructure] and resting state functional MRI can aid differentiation between 62 early onset Alzheimer's disease (EOAD) and 27 behavioural variant of frontotemporal dementia (bvFTD) patients. Random forest and receiver operator characteristic curve analyses assessed the ability of MRI in classifying the two clinical syndromes. All patients showed a distributed pattern of brain alterations relative to controls. Compared to bvFTD, EOAD patients showed bilateral inferior parietal cortical thinning and decreased default mode network functional connectivity. Compared to EOAD, bvFTD patients showed bilateral orbitofrontal and temporal cortical thinning, and WM damage of the corpus callosum, bilateral uncinate fasciculus, and left superior longitudinal fasciculus. Random forest analysis revealed that left inferior parietal cortical thickness (accuracy 0.78, specificity 0.76, sensitivity 0.83) and WM integrity of the right uncinate fasciculus (accuracy 0.81, specificity 0.96, sensitivity 0.43) were the best predictors of clinical diagnosis. The combination of cortical thickness and DT MRI measures was able to distinguish patients with EOAD and bvFTD with accuracy 0.82, specificity 0.76, and sensitivity 0.96. The diagnostic ability of MRI models was confirmed in a subsample of patients with biomarker-based clinical diagnosis. Multiparametric MRI is useful to identify brain alterations which are specific to EOAD and bvFTD. A severe cortical involvement is suggestive of EOAD, while a prominent WM damage is indicative of bvFTD. © 2017 The Authors

Purpose: To assess whether a structural disconnection between the cerebellum and the cerebral hemispheres contributes to cerebellar and brainstem symptoms in multiple sclerosis (MS). Materials and Methods: This study was approved by the local ethics committee, and written informed consent was obtained from each participant. Brain T2 lesion load, cerebellar white matter and gray matter volumes, and tract-specific measures of the middle and superior cerebellar peduncles were derived from 172 patients with MS and 46 control subjects. Predictors of clinical impairment, which was determined at ambulation and with cerebellar and brainstem functional system scores, were identified by using random forest analysis. Results: Of the 172 patients, 112 (65%) had middle cerebellar peduncle T2 lesions and 74 (43%) had superior cerebellar peduncle T2 lesions. T2 lesions in the middle and superior cerebellar peduncles were more common in clinically impaired patients than in unimpaired patients (P =.05 to <.0001). Most conventional magnetic resonance imaging metrics were more abnormal in impaired patients than in unimpaired patients (P =.03 to <.0001). Except for axial diffusivity, diffusivity abnormalities of the middle and superior cerebellar peduncles were more severe in clinically impaired patients than in unimpaired patients (P =.04 to <.0001). A minimal overlap was found between diffusivity abnormalities and T2 lesions. Compared with volumetric measures of T2 lesions or cerebellar atrophy, diffusivity measures of middle or superior cerebellar peduncle damage enabled better differentiation between clinically impaired and unimpaired patients (C statistics: 61%-70%). Conclusion: The assessment of middle and superior cerebellar peduncle damage contributes to the explanation of cerebellar and/or brainstem symptoms and ambulatory impairment in MS. © 2014 RSNA.

Purpose: To investigate the structural brain connectome in patients with Parkinson disease (PD) and mild cognitive impairment (MCI) and in patients with PD without MCI. Materials and Methods: This prospective study was approved by the local ethics committees, and written informed consent was obtained from all subjects prior to enrollment. The individual structural brain connectome of 170 patients with PD (54 with MCI, 116 without MCI) and 41 healthy control subjects was obtained by using deterministic diffusion-tensor tractography. A network-based statistic was used to assess structural connectivity differences among groups. Results: Patients with PD and MCI had global network alterations when compared with both control subjects and patients with PD without MCI (range, P = .004 to P = .048). Relative to control subjects, patients with PD and MCI had a large basal ganglia and frontoparietal network with decreased fractional anisotropy (FA) in the right hemisphere and a subnetwork with increased mean diffusivity (MD) involving similar regions bilaterally (P <.01). When compared with patients with PD without MCI, those with PD and MCI had a network with decreased FA, including basal ganglia and frontotemporoparietal regions bilaterally (P, .05). Similar findings were obtained by adjusting for motor disability (P <.05, permutation-corrected P = .06). At P <.01, patients with PD and MCI did not show network alterations relative to patients with PD without MCI. Network FA and MD values were used to differentiate patients with PD and MCI from healthy control subjects and patients with PD without MCI with fair to good accuracy (cross-validated area under the receiver operating characteristic curve [principal + secondary connected components] range, 0.75-0.85). Conclusion: A disruption of structural connections between brain areas forming a network contributes to determine an altered information integration and organization and thus cognitive deficits in patients with PD. These results provide novel information concerning the structural substrates of MCI in patients with PD and may offer markers that can be used to differentiate between patients with PD and MCI and patients with PD without MCI. © RSNA, 2016.

This study investigated gray matter (GM) and white matter (WM) damage in 89 patients at different clinical stages of Parkinson's disease (PD) (17 early, 46 mild, 14 moderate, and 12 severe) to differentiate the trajectories of tissue injury in this condition. PD patients had a very little GM atrophy even at the more advanced stages of the disease. Microstructural damage to the WM occurs with increasing PD severity and involves the brainstem, thalamocortical pathways, olfactory tracts, as well as the major interhemispheric, limbic, and extramotor association tracts. The most marked WM damage was found in moderate vs. mild cases. WM damage correlated with the degree of global cognitive deficits. WM abnormalities beyond the nigrostriatal system accumulate with increasing PD severity. WM damage is likely to contribute to the more severe motor and nonmotor dysfunctions occurring in patients at the later stages. © 2012 Wiley Periodicals, Inc.

This study investigated gray matter (GM) and white matter (WM) damage in 89 patients at different clinical stages of Parkinson's disease (PD) (17 early, 46 mild, 14 moderate, and 12 severe) to differentiate the trajectories of tissue injury in this condition. PD patients had a very little GM atrophy even at the more advanced stages of the disease. Microstructural damage to the WM occurs with increasing PD severity and involves the brainstem, thalamocortical pathways, olfactory tracts, as well as the major interhemispheric, limbic, and extramotor association tracts. The most marked WM damage was found in moderate vs. mild cases. WM damage correlated with the degree of global cognitive deficits. WM abnormalities beyond the nigrostriatal system accumulate with increasing PD severity. WM damage is likely to contribute to the more severe motor and nonmotor dysfunctions occurring in patients at the later stages. © 2012 Wiley Periodicals, Inc.

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.

Objective To assess brain white matter tract alterations in patients with Parkinson's disease and punding (PD-punding) compared with controls and PD cases without any impulsive-compulsive behaviour. Methods Forty-nine PD patients (21 PD-punding and 28 PD with no impulsive-compulsive behaviours) and 28 controls were consecutively recruited. Clinical, cognitive and psychopathological evaluations were performed. Diffusion tensor MRI metrics of the main white matter tracts were assessed using a tractography approach. Results Compared with controls, both PD groups showed white matter microstructural alterations of the left pedunculopontine tract and splenium of the corpus callosum. PD-punding patients showed a further damage to the right pedunculopontine tract and uncinate fasciculus, genu of the corpus callosum, and left parahippocampal tract relative to controls. When adjusting for depression and/or apathy severity, a greater damage of the genu of the corpus callosum and the left pedunculopontine tract was found in PD-punding compared with patients with no impulsive-compulsive behaviours. Conclusions PD-punding is associated with a disconnection between midbrain, limbic and white matter tracts projecting to the frontal cortices. These alterations are at least partially independent of their psychopathological changes. Diffusion tensor MRI is a powerful tool for understanding the neural substrates underlying punding in PD. © 2017 Elsevier Ltd

Objective To assess brain white matter tract alterations in patients with Parkinson's disease and punding (PD-punding) compared with controls and PD cases without any impulsive-compulsive behaviour. Methods Forty-nine PD patients (21 PD-punding and 28 PD with no impulsive-compulsive behaviours) and 28 controls were consecutively recruited. Clinical, cognitive and psychopathological evaluations were performed. Diffusion tensor MRI metrics of the main white matter tracts were assessed using a tractography approach. Results Compared with controls, both PD groups showed white matter microstructural alterations of the left pedunculopontine tract and splenium of the corpus callosum. PD-punding patients showed a further damage to the right pedunculopontine tract and uncinate fasciculus, genu of the corpus callosum, and left parahippocampal tract relative to controls. When adjusting for depression and/or apathy severity, a greater damage of the genu of the corpus callosum and the left pedunculopontine tract was found in PD-punding compared with patients with no impulsive-compulsive behaviours. Conclusions PD-punding is associated with a disconnection between midbrain, limbic and white matter tracts projecting to the frontal cortices. These alterations are at least partially independent of their psychopathological changes. Diffusion tensor MRI is a powerful tool for understanding the neural substrates underlying punding in PD. © 2017 Elsevier Ltd