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1.
Ann Neurol ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31385358

RESUMO

OBJECTIVE: Spinal cord atrophy is a clinically relevant feature of multiple sclerosis (MS), but longitudinal assessments on magnetic resonance imaging using segmentation-based methods suffer from measurement variability, especially in multicenter studies. We compared the generalized boundary shift integral (GBSI), a registration-based method, with a standard segmentation-based method. METHODS: Baseline and 1-year spinal cord 3-dimensional T1-weighted images (1mm isotropic) were obtained from 282 patients (52 clinically isolated syndrome [CIS], 196 relapsing-remitting MS [RRMS], 34 progressive MS [PMS]), and 82 controls from 8 MAGNIMS (Magnetic Resonance Imaging in Multiple Sclerosis) sites on multimanufacturer and multi-field-strength scans. Spinal Cord Toolbox was used for C2-5 segmentation and cross-sectional area (CSA) calculation. After cord straightening and registration, GBSI measured atrophy based on the probabilistic boundary-shift region of interest. CSA and GBSI percentage annual volume change was calculated. RESULTS: GBSI provided similar rates of atrophy, but reduced measurement variability compared to CSA in all MS subtypes (CIS: -0.95 ± 2.11% vs -1.19 ± 3.67%; RRMS: -1.74 ± 2.57% vs -1.74 ± 4.02%; PMS: -2.29 ± 2.40% vs -1.29 ± 3.20%) and healthy controls (0.02 ± 2.39% vs -0.56 ± 3.77%). GBSI performed better than CSA in differentiating healthy controls from CIS (area under the curve [AUC] = 0.66 vs 0.53; p = 0.03), RRMS (AUC = 0.73 vs 0.59; p < 0.001), PMS (AUC = 0.77 vs 0.53; p < 0.001), and patients with disability progression from patients without progression (AUC = 0.59 vs 0.50; p = 0.04). Sample size to detect 60% treatment effect on spinal cord atrophy over 1 year was lower for GBSI than CSA (CIS: 106 vs 830; RRMS: 95 vs 335; PMS: 44 vs 215; power = 80%; alpha = 5%). INTERPRETATION: The registration-based method (GBSI) allowed better separation between MS patients and healthy controls and improved statistical power, when compared with a conventional segmentation-based method (CSA), although it is still far from perfect. ANN NEUROL 2019.

2.
Mult Scler ; : 1352458519865989, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31347448

RESUMO

BACKGROUND: Mechanisms associated with cervical spinal cord (CSC) and upper thoracic spinal cord (TSC) atrophy in multiple sclerosis (MS) are poorly understood. OBJECTIVE: To assess the influence of brain, CSC and TSC T2-hyperintense lesions on cord atrophy and disability in MS. METHODS: Thirty-four MS patients underwent 3T brain, cervical and thoracic cord magnetic resonance imaging (MRI) and Expanded Disability Status Scale (EDSS) score assessment. CSC/TSC lesion number and volume (LV), whole-brain and cortico-spinal tract (CST) LVs were obtained. Normalized whole CSC and upper TSC cross-sectional areas (CSAn) were also derived. Age- and sex-adjusted regression models assessed associations of brain/cord lesions with CSAn and EDSS and identified variables independently associated with CSAn and EDSS with a stepwise variable selection. RESULTS: CSC CSAn (ß = -0.36, p = 0.03) and TSC CSAn (ß = -0.60, p < 0.001) were associated with CSC T2 LV. EDSS (median = 3.0) was correlated with CSC T2 LV (ß = 0.42, p = 0.01), brain (ß = 0.34, p = 0.04) and CST LV (ß = 0.35, p = 0.03). The multivariate analysis retained CSC LV as significant predictor of CSC CSAn (R2 = 0.20, p = 0.023) and TSC CSAn (R2 = 0.51, p < 0.001) and retained CSC and CST LVs as significant predictors of EDSS (R2 = 0.55, p = 0.001). CONCLUSIONS: CSC LV is an independent predictor of cord atrophy. When neurological impairment is relatively mild, central nervous system (CNS) lesion burden is a better correlate of disability than atrophy.

3.
Mult Scler ; : 1352458519845109, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31079538

RESUMO

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.

4.
Mult Scler ; : 1352458519837707, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30887862

RESUMO

BACKGROUND:: In multiple sclerosis (MS), abnormalities of brain network dynamics and their relevance for cognitive impairment have never been investigated. OBJECTIVES:: The aim of this study was to assess the dynamic resting state (RS) functional connectivity (FC) on 62 relapsing-remitting MS patients and 65 sex-matched healthy controls enrolled at 7 European sites. METHODS:: MS patients underwent clinical and cognitive evaluation. Between-group network FC differences were evaluated using a dynamic approach (based on sliding-window correlation analysis) and grouping correlation matrices into recurrent FC states. RESULTS:: Dynamic FC analysis revealed, in healthy controls and MS patients, three recurrent FC states: two characterized by strong intra- and inter-network connectivity and one characterized by weak inter-network connectivity (State 3). A total of 23 MS patients were cognitively impaired (CI). Compared to cognitively preserved (CP), CI-MS patients had reduced RS-FC between subcortical and default-mode networks in the low-connectivity State 3 and lower dwell time (i.e. time spent in a given state) in the high-connectivity State 2. CI-MS patients also exhibited a lower number and a less frequent switching between meta-states, as well as a smaller distance traveled through connectivity states. CONCLUSION:: Time-varying RS-FC was markedly less dynamic in CI- versus CP-MS patients, suggesting that slow inter-network connectivity contributes to cognitive dysfunction in MS.

5.
Mult Scler ; : 1352458519837704, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30887875

RESUMO

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.

6.
Brain ; 142(3): 633-646, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30715195

RESUMO

Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T2- and T2*-weighted axial and sagittal MRI scans acquired at 3 or 7 T. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P < 0.001), which was further confirmed by absolute and normalized lesion volumes (P < 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P < 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P < 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P < 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups.

7.
Mult Scler ; : 1352458518822145, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30657011

RESUMO

BACKGROUND:: Hand motor impairment has considerable effects on daily-life activities of patients with multiple sclerosis (pwMS). Understanding its anatomo-functional substrates is relevant to provide more specific therapeutic interventions. OBJECTIVES:: To investigate the association between hand motor performance and anatomo-functional magnetic resonance imaging (MRI) abnormalities in pwMS. METHODS:: A total of 134 healthy controls (HC) and 366 pwMS underwent the Nine-Hole-Peg-Test (9HPT), structural and resting state (RS) functional MRI. Multivariate analyses identified the independent predictors of hand motor performance. RESULTS:: PwMS versus HC showed widespread gray matter atrophy, microstructural white matter abnormalities, and decreased RS functional connectivity in motor and cognitive networks. Predictors of worse right-9HPT ( R2 = 0.52) were decreased right superior cerebellar peduncle and right lemniscus fractional anisotropy (FA) ( p ⩽ 0.02), left angular gyrus atrophy ( p < 0.003), decreased RS connectivity in left superior frontal gyrus, and left posterior cerebellum ( p < 0.001). Worse left 9HPT ( R2 = 0.56) was predicted by decreased right corticospinal FA ( p = 0.003), atrophy of left anterior cingulum and left cerebellum ( p ⩽ 0.02), decreased RS connectivity of left lingual gyrus and right posterior cerebellum in cerebellar and executive networks ( p ⩽ 0.02). CONCLUSION:: Structural and functional abnormalities of regions involved in motor functions contribute to explain motor disability in pwMS. The integration of clinical and advanced MRI measures contributes to improve our understanding of multiple sclerosis clinical manifestations.

8.
Neuroimage ; 184: 901-915, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30300751

RESUMO

The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in MS. Automating this operation eliminates inter-rater variability and increases the efficiency of large-throughput analysis pipelines. Robust and reliable segmentation across multi-site spinal cord data is challenging because of the large variability related to acquisition parameters and image artifacts. In particular, a precise delineation of lesions is hindered by a broad heterogeneity of lesion contrast, size, location, and shape. The goal of this study was to develop a fully-automatic framework - robust to variability in both image parameters and clinical condition - for segmentation of the spinal cord and intramedullary MS lesions from conventional MRI data of MS and non-MS cases. Scans of 1042 subjects (459 healthy controls, 471 MS patients, and 112 with other spinal pathologies) were included in this multi-site study (n = 30). Data spanned three contrasts (T1-, T2-, and T2∗-weighted) for a total of 1943 vol and featured large heterogeneity in terms of resolution, orientation, coverage, and clinical conditions. The proposed cord and lesion automatic segmentation approach is based on a sequence of two Convolutional Neural Networks (CNNs). To deal with the very small proportion of spinal cord and/or lesion voxels compared to the rest of the volume, a first CNN with 2D dilated convolutions detects the spinal cord centerline, followed by a second CNN with 3D convolutions that segments the spinal cord and/or lesions. CNNs were trained independently with the Dice loss. When compared against manual segmentation, our CNN-based approach showed a median Dice of 95% vs. 88% for PropSeg (p ≤ 0.05), a state-of-the-art spinal cord segmentation method. Regarding lesion segmentation on MS data, our framework provided a Dice of 60%, a relative volume difference of -15%, and a lesion-wise detection sensitivity and precision of 83% and 77%, respectively. In this study, we introduce a robust method to segment the spinal cord and intramedullary MS lesions on a variety of MRI contrasts. The proposed framework is open-source and readily available in the Spinal Cord Toolbox.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Redes Neurais (Computação) , Medula Espinal/patologia , Humanos , Imagem por Ressonância Magnética/métodos , Variações Dependentes do Observador , Reconhecimento Automatizado de Padrão , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Mult Scler ; : 1352458518787347, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30039746

RESUMO

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.

10.
Mult Scler ; : 1352458518778008, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29771186

RESUMO

OBJECTIVE: To explore resting-state (RS) functional connectivity (FC) of the main sensory/motor networks of patients with neuromyelitis optica spectrum disorders (NMOSDs), clinically isolated optic neuritis (ON), and myelitis. METHODS: Clinical evaluation and RS fMRI were obtained from 28 NMOSD, 11 recurrent ON, and 12 recurrent myelitis patients and 30 healthy controls. Between-group RS FC comparisons and correlations with motor performance were assessed (SPM12) on the main sensory/motor RS networks (RSNs) identified by independent component analysis. Functional network connectivity analysis estimated inter-network connectivity. RESULTS: Intra- and inter-network RS FCs were reduced in RSNs associated to somatosensory modalities affected by pathology: regions of the primary visual network in ON patients, of the sensorimotor networks in myelitis patients, and of the sensorimotor and secondary visual networks in NMOSD patients. The opposite trend was observed in regions of RSNs spared by pathology: the auditory and part of visual networks in NMOSD, the secondary visual and sensorimotor networks in ON, and the primary visual network in myelitis patients. Better motor performance correlated with higher RS FC of spared RSNs. CONCLUSION: Sensory and motor RSN abnormalities occur in NMOSD. Loss of function within disease-target networks may elicit cross-modal plasticity across sensory networks potentially preserving clinical function.

11.
Radiology ; 288(1): 234-244, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29664341

RESUMO

Purpose To characterize the spatial distribution of cervical cord T1-weighted hypointense lesions in patients with multiple sclerosis (MS) and analyze their association with cord atrophy and disability. Materials and Methods For this prospective study that took place between 2014 and 2016, 3.0-T high-resolution T1-weighted cervical cord magnetic resonance (MR) images and clinical evaluations were obtained from 82 patients with relapsing-remitting MS (RRMS), 33 patients with secondary progressive MS (SPMS), 25 patients with primary progressive MS (PPMS), and 35 sex-matched healthy control participants. Hypointense cord lesions on T1-weighted imaging were identified and corresponding lesion masks were produced. A semiautomatic method on the basis of active surfaces was used to perform voxel-wise assessment (by using statistical parametric mapping and full factorial models) of T1-weighted hypointense lesion distribution and cord atrophy. Results T1-weighted hypointense cervical cord lesions were detected in 122 of 140 (87.1%) patients with MS. Lesions were preferentially located in the posterior (P = .01) and upper (P < .001) cervical cord. Lesion extent at C1/C2 and C5 was higher in patient with SPMS versus RRMS, and patients with PPMS versus RRMS and SPMS (P value range, <.001 to .05). Cord atrophy at upper cervical levels was found in patients with MS compared with control participants, especially in progressive MS (P value range, <.001 to .04). Partial overlap (r = 0.66; P < .001) occurred between regions with T1-weighted hypointense cord lesions and atrophy. Cord atrophy (r value range, -0.24 to -0.48; P < .001) and T1-weighted hypointense cord lesion extent (r value range, 0.36-0.42; P < .001) were correlated with clinical disability. Conclusion Hypointense lesions at T1-weighted imaging were observed in the cervical spinal cord of the majority of patients with MS and more widespread in progressive than in relapsing MS phenotypes. Both T1-weighted hypointense cord lesions and atrophy correlated with patient clinical disability.


Assuntos
Medula Cervical/diagnóstico por imagem , Medula Cervical/patologia , Avaliação da Deficiência , Imagem por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Adulto , Idoso , Atrofia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
12.
Neurology ; 90(8): e707-e716, 2018 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-29367447

RESUMO

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.

13.
J Neurol Neurosurg Psychiatry ; 89(7): 696-701, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29348302

RESUMO

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.

14.
Mult Scler ; 24(4): 459-471, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28294693

RESUMO

OBJECTIVE: To investigate resting state (RS) functional connectivity (FC) abnormalities within the principal brain networks in a large cohort of multiple sclerosis (MS) patients, to define the trajectory of FC changes over disease stages and their relation with clinical and structural magnetic resonance imaging (MRI) measures. METHODS: RS functional magnetic resonance imaging (fMRI), clinical, and neuropsychological evaluation were obtained from 215 MS patients and 98 healthy controls. Connectivity abnormalities and correlations with clinical/neuropsychological/imaging measures were evaluated. We analyzed seed-voxel FC with seven major hubs, producing one visual/sensory, one motor, two cognitive, one cerebellar, and two subcortical networks. RESULTS: MS patients showed reduced network average RS FC versus controls in the default-mode network. At regional level, a complex pattern of decreased and increased RS FC was found. Reduced RS FC mainly involved sensorimotor, cognitive, thalamic, and cerebellar networks, whereas increased RS FC involved visual/sensory and subcortical networks. Reduced RS FC correlated with T2 lesions. Reduced thalamic RS FC correlated with better neuropsychological performance, whereas for all remaining networks reduced FC correlated with more severe clinical/cognitive impairment. CONCLUSION: Increased and decreased RS FC occurs in MS and contributes to a wide spectrum of clinical manifestations. RS FC reduction is related to T2 lesions. Such a paradigm is inverted for the thalamic network.

15.
Mult Scler ; 24(9): 1183-1195, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28657428

RESUMO

OBJECTIVE: To investigate sub-regional thalamic resting-state (RS) functional connectivity (FC) abnormalities in multiple sclerosis (MS) and their correlation with fatigue and its subcomponents (physical, cognitive, and psychosocial). METHODS: From 122 MS patients and 94 healthy controls, 5 thalamic sub-regions (frontal, motor, postcentral, occipital, temporal) were parcellated based on their cortico-thalamic structural connectivity and used for a seed-based RS FC analysis. Abnormalities of thalamic RS FC in MS patients and their correlation with Modified Fatigue Impact Scale (MFIS) were assessed. RESULTS: Compared to controls and non-fatigued MS ( n = 86), fatigued MS patients ( n = 36) showed thalamic RS FC abnormalities with middle frontal gyrus, sensorimotor network, precuneus, insula, and cerebellum, which correlated with global MFIS. Higher thalamic RS FC with precuneus and lower RS FC with posterior cerebellum correlated with cognitive MFIS. Higher thalamic RS FC with sensorimotor network in frontal-, motor-, and temporal thalamic sub-regions correlated with physical and psychosocial MFIS. Reduced thalamic RS FC with right insula in motor-, postcentral-, and occipital thalamic sub-regions correlated with psychosocial fatigue. CONCLUSION: Regional thalamic RS FC abnormalities with different cortical regions, including the frontal lobe, sensorimotor network, precuneus, insular cortices, and cerebellum contribute to fatigue in MS. Abnormal RS FC of selected thalamo-cortical connections explains different components of fatigue.

16.
Hum Brain Mapp ; 38(12): 6005-6018, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28881433

RESUMO

In spite of the well-known importance of thalami in multiple sclerosis (MS), only limited data on whole and subregional thalamic functional connectivity (FC) changes are available. Using diffusion tensor imaging, we performed a structural connectivity based thalamic parcellation and investigated subregional thalamic resting-state (RS) FC alterations and their relationship with clinical/cognitive measures in MS. MRI data from a reference set of healthy controls (HC) were used to parcellate the thalami into five subregions, according to their structural connectivity. For each thalamic subregion, a seed-based RS FC analysis was performed in 187 MS patients and 94 HC. Correlations between thalamic RS FC and clinical/cognitive variables were assessed. Compared to HC, MS patients showed increased intra- and inter-thalamic RS FC for almost all thalamic subregions, and increased RS FC between all thalamic subregions and the left insula. Frontal and motor thalamic subregions also showed reduced RS FC with the caudate nucleus. For the temporal thalamic subregion, we observed reduced RS FC with the ipsilateral thalamus, anterior and middle cingulate cortex, and cerebellum. Compared to cognitively preserved, cognitively impaired MS patients had higher thalamic RS FC with several temporal areas. In MS patients, lower RS FC between thalamic subregions and the caudate and cingulate cortex correlated with worse motor performance, whereas higher RS FC with the insula correlated with better motor performance. The main thalamic subregions have different RS-FC abnormalities in MS patients. Increased thalamic RS FC with the insula may have a compensatory role, whereas increased RS FC with temporal areas, observed in patients with cognitive impairment may reflect maladaptive mechanisms. Hum Brain Mapp 38:6005-6018, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/fisiopatologia , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia , Adulto , Mapeamento Encefálico , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Estudos Transversais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Esclerose Múltipla/patologia , Esclerose Múltipla/psicologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Descanso , Tálamo/patologia
17.
Mult Scler ; 23(14): 1864-1874, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28169581

RESUMO

BACKGROUND: Cognitive impairment and depression frequently affects patients with multiple sclerosis (MS). However, the relationship between the occurrence of depression and cognitive impairment and the development of cortical atrophy has not been fully elucidated yet. OBJECTIVES: To investigate the association of cortical and deep gray matter (GM) volume with depression and cognitive impairment in MS. METHODS: Three-dimensional (3D) T1-weighted scans were obtained from 126 MS patients and 59 matched healthy controls. Cognitive impairment was assessed using the Brief Repeatable Battery of Neuropsychological Tests and depression with the Montgomery-Asberg Depression Rating Scale (MADRS). Using FreeSurfer and FIRST software, we assessed cortical thickness (CTh) and deep GM volumetry. Magnetic resonance imaging (MRI) variables explaining depression and cognitive impairment were investigated using factorial and classification analysis. Multivariate regression models correlated GM abnormalities with symptoms severity. RESULTS: Compared with controls, MS patients exhibited widespread bilateral cortical thinning involving all brain lobes. Depressed MS showed selective CTh decrease in fronto-temporal regions, whereas cognitive impairment MS exhibited widespread fronto-parietal cortical and subcortical GM atrophy. Frontal cortical thinning was the best predictor of depression ( C-statistic = 0.7), whereas thinning of the right precuneus and high T2 lesion volume best predicted cognitive impairment ( C-statistic = 0.8). MADRS severity correlated with right entorhinal cortex thinning, whereas cognitive impairment severity correlated with left entorhinal and thalamus atrophy. CONCLUSION: MS-related depression is linked to circumscribed CTh changes in areas deputed to emotional behavior, whereas cognitive impairment is correlated with cortical and subcortical GM atrophy of circuits involved in cognition.


Assuntos
Córtex Cerebral/patologia , Disfunção Cognitiva/fisiopatologia , Depressão/fisiopatologia , Substância Cinzenta/patologia , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Adulto , Atrofia/patologia , Córtex Cerebral/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Depressão/etiologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem
18.
Hum Brain Mapp ; 38(5): 2580-2588, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28205364

RESUMO

Primary progressive multiple sclerosis (PPMS) leads to physical and cognitive disability. Specifically, cognitive deficits in PPMS have been explained by both grey matter atrophy and white matter lesions. However, existing research still lacks in the understanding of how the brain of a patient with PPMS functions under cognitive control demands. Thus, the aim of the current study was to examine information integration in patients with PPMS using a search-based effective connectivity method. Fourteen patients with PPMS and 22 age- and gender-matched healthy controls (HC) performed the Stroop task, a cognitively demanding interference task that taxes neural resources required for cognitive control and response inhibition. Results showed that compared to HC, PPMS patients exhibited poor behavioral performance and alterations in information flow, manifested in the form of the loss of top-down connections, reversal of connections, and hyperconnectivity. Significant correlations were observed between connection strengths and behavioral measures. The connection between the posterior parietal cortex (PCC) and left posterior parietal lobule, which was present in both groups, showed a negative correlation with performance accuracy on incongruent trials. The connection between the left dorsolateral prefrontal cortex and PCC showed a positive correlation with performance accuracy on incongruent trials. However, the adaptive nature of this connection was not significant on a behavioral level as the PPMS group performed significantly worse compared to the HC group during the Stroop task. Thus, the current study provides important evidence about effective connectivity patterns that can be characterized as maladaptive cerebral re-organization in the PPMS brain. Hum Brain Mapp 38:2580-2588, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Mapeamento Encefálico , Transtornos Cognitivos/etiologia , Inibição (Psicologia) , Esclerose Múltipla Crônica Progressiva/complicações , Esclerose Múltipla Crônica Progressiva/patologia , Lobo Parietal/diagnóstico por imagem , Estudos de Casos e Controles , Transtornos Cognitivos/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/psicologia , Vias Neurais/diagnóstico por imagem , Tempo de Reação/fisiologia , Estatística como Assunto , Fatores de Tempo
19.
Parkinsonism Relat Disord ; 31: 65-71, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27453032

RESUMO

INTRODUCTION: Beside motor symptoms, patients with progressive supranuclear palsy syndrome (PSPs) commonly present cognitive and behavioral disorders. In this study we aimed to assess the structural brain correlates of cognitive impairment in PSPs. METHODS: We enrolled 23 patients with probable PSP Richardson's syndrome and 15 matched healthy controls. Patients underwent an extensive clinical and neuropsychological evaluation. Cortical thickness measures and diffusion tensor metrics of white matter tracts were obtained. Random forest analysis was used to identify the strongest MRI predictors of cognitive impairment in PSPs at an individual patient level. RESULTS: PSPs patients were in a moderate stage of the disease showing mild cognitive deficits with prominent executive dysfunction. Relative to controls, PSPs patients had a focal, bilateral cortical thinning mainly located in the prefrontal/precentral cortex and temporal pole. PSPs patients also showed a distributed white matter damage involving the main tracts including the superior cerebellar peduncle, corpus callosum, corticospinal tract, and extramotor tracts, such as the inferior fronto-occipital, superior longitudinal and uncinate fasciculi, and cingulum, bilaterally. Regional cortical thinning measures did not relate with cognitive features, while white matter damage showed a significant impact on cognitive impairment (r values ranging from -0.80 to 0.74). CONCLUSIONS: PSPs patients show both focal cortical thinning in dorsolateral anterior regions and a distributed white matter damage involving the main motor and extramotor tracts. White matter measures are highly associated with cognitive deficits. Diffusion tensor MRI metrics are likely to be the most sensitive markers of extramotor deficits in PSPs.


Assuntos
Disfunção Cognitiva/etiologia , Paralisia Supranuclear Progressiva/complicações , Substância Branca/patologia , Idoso , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Retrospectivos , Substância Branca/diagnóstico por imagem
20.
Radiology ; 280(3): 869-79, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27002420

RESUMO

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 (ß = 0.606, P = .001), together with thalamic activation (ß = -0.410, 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.


Assuntos
Função Executiva , Imagem por Ressonância Magnética/métodos , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/psicologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Tempo de Reação , Tálamo/diagnóstico por imagem
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