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1.
Lancet Neurol ; 19(10): 860-871, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32949546

RESUMO

Multiple sclerosis is a chronic, demyelinating disease of the CNS. Cognitive impairment is a sometimes neglected, yet common, sign and symptom with a profound effect on instrumental activities of daily living. The prevalence of cognitive impairment in multiple sclerosis varies across the lifespan and might be difficult to distinguish from other causes in older age. MRI studies show that widespread changes to brain networks contribute to cognitive dysfunction, and grey matter atrophy is an early sign of potential future cognitive decline. Neuropsychological research suggests that cognitive processing speed and episodic memory are the most frequently affected cognitive domains. Narrowing evaluation to these core areas permits brief, routine assessment in the clinical setting. Owing to its brevity, reliability, and sensitivity, the Symbol Digit Modalities Test, or its computer-based analogues, can be used to monitor episodes of acute disease activity. The Symbol Digit Modalities Test can also be used in clinical trials, and data increasingly show that cognitive processing speed and memory are amenable to cognitive training interventions.


Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Gerenciamento Clínico , Imagem por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/psicologia , Adolescente , Idoso de 80 Anos ou mais , Disfunção Cognitiva/terapia , Feminino , Humanos , Esclerose Múltipla/terapia
2.
PLoS One ; 15(8): e0235615, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745132

RESUMO

No single neuroimaging technique or sequence is capable of reflecting the functional deficits manifest in MS. Given the interest in imaging biomarkers for short- to medium-term studies, we aimed to assess which imaging metrics might best represent functional impairment for monitoring in clinical trials. Given the complexity of functional impairment in MS, however, it is useful to isolate a particular functionally relevant pathway to understand the relationship between imaging and neurological function. We therefore analyzed existing data, combining multiparametric MRI and OCT to describe MS associated visual impairment. We assessed baseline data from fifty MS patients enrolled in ReBUILD, a prospective trial assessing the effect of a remyelinating drug (clemastine). Subjects underwent 3T MRI imaging, including Neurite Orientation Dispersion and Density Imaging (NODDI), myelin content quantification, and retinal imaging, using OCT. Visual function was assessed, using low-contrast letter acuity. MRI and OCT data were studied to model visual function in MS, using a partial, least-squares, regression analysis. Measures of neurodegeneration along the entire visual pathway, described most of the observed variance in visual disability, measured by low contrast letter acuity. In those patients with an identified history of ON, however, putative myelin measures also showed correlation with visual performance. In the absence of clinically identifiable inflammatory episodes, residual disability correlates with neurodegeneration, whereas after an identifiable exacerbation, putative measures of myelin content are additionally informative.


Assuntos
Esclerose Múltipla/diagnóstico por imagem , Visão Ocular , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Bainha de Mielina/patologia , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica
3.
Lancet Neurol ; 19(8): 678-688, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702337

RESUMO

The treatment of multiple sclerosis has been transformed by the successful development of immunotherapies that efficiently reduce disease activity and related clinical relapses during the relapsing-remitting phase of the disease. However, the prevention of disability progression, which is due to axonal and neuronal damage and loss, has yet to be achieved and is therapeutically challenging, particularly during the progressive phase of the disease. One strategy to counteract neurodegeneration is to promote neuroprotection by enhancing myelin regeneration, hence restoring nerve conduction and metabolic support to the axon. Animal studies have provided targets for interventions to improve brain and spinal cord remyelination, paving the way for the translation of this research to humans. From these initial and promising forays, further problems have emerged, including questions on how best to design these clinical trials and appropriately measure the outcomes. Solving these problems will need additional work before efficacious pro-remyelination therapies will be ready for people with multiple sclerosis, but there is a real sense of hope that researchers are getting closer to a successful therapy.


Assuntos
Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Remielinização/fisiologia , Progressão da Doença , Humanos , Esclerose Múltipla/diagnóstico por imagem , Bainha de Mielina/fisiologia
4.
PLoS One ; 15(7): e0236090, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702050

RESUMO

OBJECTIVES: To evaluate retinal axonal density and retinal capillary flow density (CFD) variations in patients affected by multiple sclerosis (MS) as documented by Optical Coherence Tomography Angiography (OCT-A). MATERIAL AND METHODS: A cross-sectional study was performed in a tertiary university eye hospital on 94 eyes from 48 MS patients compared to 37 eyes from 23 matched controls. MS patients were divided in two groups: those with previous episodes of optic neuritis (MS ON+, 71.4%) and those without any previous visual complaint (no optic neuritis group, MS ON, 28.6%). Patients underwent macular and optic nerve head OCT-A with Optovue XR Avanti (Optovue, Freemont, California) after that preliminary evaluation of the ganglion cell complex (GCC) and of the retinal nerve fiber layer (RNFL) was achieved for each single eye by SD-OCT. CFD was evaluated in three different retinal layers of MS patients and controls: superficial capillary plexus (SCP), deep capillary plexus (DCP) and the choriocapillaris layer (CL). Each layer was analyzed in 18 preset subregions automatically detected by the system. CFD values were then correlated to the RNFL thickness and GCC thickness in the groups: p values were computed by t-tests between each group of MS patients and controls. A p-value of <0.05 was considered significant. RESULTS: A significant difference in the overall CFD values was found between ON+ and ON- patients when compared to controls in 18 subregions of SCP. Furthermore, a significant difference was found between MS patients and controls in 16 subregions analyzed corresponding to the CL layer without difference between the two MS subgroups (ON+ and ON-). CONCLUSIONS: OCT-A when performed at the optic nerve head level and at the macular region is characterized by a reduction of retinal perfusion in a significant portion of MS patients independently if they had a previous history of optic nerve inflammation or not.


Assuntos
Esclerose Múltipla/diagnóstico por imagem , Tomografia de Coerência Óptica , Axônios/metabolismo , Capilares/diagnóstico por imagem , Capilares/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Reações Falso-Positivas , Humanos , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Fibras Nervosas/metabolismo , Retina/diagnóstico por imagem , Retina/fisiopatologia
5.
Neurology ; 95(6): e745-e754, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32690785

RESUMO

OBJECTIVE: To determine whether natalizumab efficacy is maintained when switching to personalized extended interval dosing based on individual natalizumab trough concentrations in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: This was a prospective multicenter single-arm trial with 1 year follow-up and a 1-year extension phase. Participants were adult persons with RRMS treated with natalizumab without disease activity in the year prior to enrollment. The natalizumab treatment interval was based on longitudinal natalizumab trough concentrations. Patients received 3 monthly MRI scans, relapse assessments, and disability scoring during follow-up. The primary endpoint was the occurrence of gadolinium-enhancing lesions on MRI. Secondary endpoints were new/enlarging T2 lesions on MRI and relapses and progression on the Expanded Disability Status Scale (EDSS) during follow-up and extension phase. RESULTS: Sixty-one patients were included. Eighty-four percent extended the interval from a 4-week interval to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI] 0%-7.4%) during follow-up. No new/enlarging T2 lesions (95% CI 0%-7.4%) or relapses (95% CI 0%-7.4%) were reported during follow-up and in the extension phase. Median EDSS was comparable at baseline (3.0, interquartile range [IQR] 2.0-5.0) and after follow-up (3.0, IQR 2.0-5.0). CONCLUSION: Personalized extended interval dosing did not induce recurrence of MS disease activity. Natalizumab efficacy was maintained in stable patients with RRMS receiving personalized extended interval dosing based on individual natalizumab concentrations. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that personalized extended interval dosing of natalizumab does not result in recurrence of disease activity in stable patients with RRMS.


Assuntos
Esclerose Múltipla/tratamento farmacológico , Natalizumab/administração & dosagem , Adulto , Avaliação da Deficiência , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Seguimentos , Humanos , Integrina alfa4beta1/antagonistas & inibidores , Integrina alfa4beta1/imunologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/diagnóstico por imagem , Natalizumab/sangue , Natalizumab/uso terapêutico , Países Baixos , Neuroimagem , Medicina de Precisão , Estudos Prospectivos , Índice de Gravidade de Doença
6.
Neurology ; 95(6): e733-e744, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32723802

RESUMO

OBJECTIVE: To evaluate the ability of intereye retinal thickness difference (IETD) measured by optical coherence tomography (OCT) to detect asymptomatic optic nerve involvement in clinically isolated syndrome (CIS). METHODS: We conducted a cross-sectional study of patients who recently presented a CIS (≤4.5 months). All patients underwent OCT and brain/optic nerve MRI. Optic nerve involvement was defined clinically (episode of optic neuritis [ON] or not) and radiologically (optic nerve hypersignal on 3D double inversion recovery [3D-DIR]). We evaluated the sensitivity and specificity of previously published IETD thresholds and report the observed optimal thresholds for identifying symptomatic optic nerve involvement but also for identifying asymptomatic optic nerve involvement (optic nerve hypersignal without ON history). Primary outcomes were ganglion cell-inner plexiform layer (GC-IPL) and peripapillary retinal nerve fiber layer IETD. RESULTS: The study group consisted of 130 patients. In the CIS with ON group, 3D-DIR showed a hypersignal in all 41 symptomatic optic nerves and in 11 asymptomatic optic nerves. In the CIS without ON group, 3D-DIR showed a unilateral optic nerve hypersignal in 22 patients and a bilateral optic nerve hypersignal in 7 patients. For the detection of symptomatic and asymptomatic optic nerve lesion, GC-IPL IETD had better performance. We found an optimal GC-IPL IETD threshold ≥2.83 µm (sensitivity 88.2, specificity 83.3%) for the detection of symptomatic lesions and an optimal GC-IPL IETD ≥1.42 µm (sensitivity 89.3%, specificity 72.6%) for the detection of asymptomatic lesions. CONCLUSIONS: Detection of asymptomatic optic nerve lesions in CIS requires lower IETD thresholds than previously reported. GC-IPL IETD represents an alternative biomarker to MRI for the detection of asymptomatic optic nerve lesions. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that OCT accurately identifies asymptomatic optic nerve involvement in patients with CIS.


Assuntos
Esclerose Múltipla/diagnóstico por imagem , Nervo Óptico/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto , Doenças Assintomáticas , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Esclerose Múltipla/líquido cefalorraquidiano , Bandas Oligoclonais/líquido cefalorraquidiano , Estudos Prospectivos , Retina/diagnóstico por imagem , Retina/ultraestrutura , Síndrome , Acuidade Visual , Adulto Jovem
7.
Br J Radiol ; 93(1113): 20200552, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32614611

RESUMO

OBJECTIVE: T2 blackout (TBO) effect, which is a common finding in the brains of multiple sclerosis (MS) patients and older population that are imaged for other reasons on diffusion weighted imagings (DWI) and apparent diffusion coefficient (ADC) map show the existence of paramagnetic materials in the tissue. Because iron is known to accumulate in especially deep gray matter (DGM) structures in MS brains, we aimed to investigate the relationship between TBO and clinico-radiological parameters that may be iron-related in MS. METHODS: We retrospectively reviewed the latest MR images of MS patients on 3 Tesla MR scanner between 2018 and 2019. TBO existence and severity on DWI-ADC was assessed by two radiologists and its correlation with several outcomes of MS was investigated. RESULTS: No significant relationship was found between TBO and gender, subtype of MS whereas TBO was positively correlated with parameters such as black-hole lesions, cortical atrophy, duration of disease, age and extended disability status scale (EDSS) score. CONCLUSIONS: TBO shows correlation with the conditions which were revealed to be associated with iron accumulation in the brain of MS patients in the literature. Therefore, we concluded that TBO and its severity in DGM may represent iron accumulation in MS brains. ADVANCES IN KNOWLEDGE: TBO effect as a frequent imaging finding in daily practice may be used as predictor of the disease course of MS due to possible effects of iron accumulation in brain and thereby may be useful in modifying treatment strategies.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Imagem de Difusão por Ressonância Magnética/métodos , Ferro/metabolismo , Esclerose Múltipla/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/metabolismo , Variações Dependentes do Observador , Estudos Retrospectivos , Estatísticas não Paramétricas , Adulto Jovem
8.
Cogn Behav Neurol ; 33(2): 90-102, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32496294

RESUMO

Multiple sclerosis (MS) is the most common inflammatory neurologic disease in young adults. Its pathological mechanisms include demyelination, neurodegeneration, and synaptopathy. Cognitive deficits occur in up to 65% of individuals with MS and affect both nonsocial (eg, information processing speed, memory, and executive functions) and social (ie, emotion recognition, theory of mind, and empathy) cognitive domains. In the last 3 decades, there has been a growing interest in social cognition and its relationship with neuropsychological, sociodemographic, and disease characteristics in individuals with MS. Uncovering the neuropathological correlates of social cognitive deficits is now a crucial aim that would also help us better understand the underlying mechanisms of social cognition. We reviewed 11 neuroimaging studies to investigate social cognition in MS. These studies focused mainly on facial emotion recognition and theory of mind, with the findings suggesting that a disrupted cortico-subcortical network forms the basis of social deficits involving both domains. We then interpreted these results in the context of multiple disconnection syndrome, which occurs as a result of axonal demyelination and degeneration within the connexome of several neural hubs devoted to social cognition. Heterogeneity in social cognitive performance, observed among our study participants, is discussed with reference to the cognitive reserve and brain reserve hypotheses. These reserves may explain why individuals with comparable clinical characteristics of MS may exhibit different cognitive profiles. Further research is required to generalize these findings to the MS population and to inform the development of effective interventions to improve psychosocial functioning in individuals with MS.


Assuntos
Encéfalo/patologia , Esclerose Múltipla/psicologia , Neuroimagem/métodos , Feminino , Humanos , Masculino , Esclerose Múltipla/diagnóstico por imagem
9.
Brain Nerve ; 72(5): 493-508, 2020 May.
Artigo em Japonês | MEDLINE | ID: mdl-32381747

RESUMO

Magnetic resonance imaging (MRI) is the imaging modality of choice for patients with multiple sclerosis (MS). The roles of MRI in MS include diagnosis, imaging biomarkers, and safety monitoring for patients receiving disease-modifying drugs (DMDs). In terms of diagnosis, MRI plays a pivotal role in the international diagnosis criteria (McDonald criteria). MRI is also useful for differential diagnosis. The rate of MS misdiagnosis might be as high as 10%, and careful interpretation of MRI may reduce rates of misdiagnosis. Quantified MRI data have been widely used as primary and secondary outcomes in clinical trials of DMDs. MRI is also a powerful tool for monitoring the efficacy of DMDs in individual patients (i.e., determination of responder status for each drug). MRI assists with early detection of the side effects of DMDs. MRI can detect lesions of natalizumab-induced progressive multifocal leukoencephalopathy (PML) before symptoms occur. This review summarizes our current understanding of the utility of MRI in the diagnosis and treatment of patients with MS.


Assuntos
Imagem por Ressonância Magnética , Esclerose Múltipla/diagnóstico por imagem , Erros de Diagnóstico , Diagnóstico Precoce , Humanos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Esclerose Múltipla/tratamento farmacológico , Natalizumab/efeitos adversos
10.
Adv Clin Exp Med ; 29(4): 441-448, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32369275

RESUMO

BACKGROUND: Several studies have identified changes in the spinal cord DTI measurements in patients with multiple sclerosis (MS). However, correlations between changes in DTI parameters in normal appearing cervical spine and neurological findings have not been clearly established. OBJECTIVES: To determine whether diffusion tensor imaging (DTI) measurements such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) are sufficiently sensitive in detecting microstructure alterations in normal-appearing spinal cords in patients with MS and whether they reflect these patients' clinical disability. MATERIAL AND METHODS: Fifteen patients diagnosed with relapsing-remitting MS (RRMS) with normal-appearing cervical spinal cords on plain MRI and 11 asymptomatic volunteers were enrolled in the study. Overall, 75 cervical spinal segments were analyzed. The regions of interest were drawn from the entire spinal cord cross-section and in the normal-appearing white matter tracts: the superior and inferior cerebellar peduncles and the posterior limbs of the internal capsules. Neurological deficit and the level of disability were evaluated using the Expanded Disability Status Scale (EDSS), the timed 25-foot walk test (T25FW) and the 9-hole peg test (9HPT) for manual dexterity. RESULTS: A significant difference (p < 0.05) in FA values between patients with MS and the control group was found at levels C2 (p = 0.047) and C3 (p = 0.023). No significant changes in ADC values were found. There was correlation between FA and ADC values in selected white matter tracts and at particular spinal cord levels. We also observed significant correlations between diffusion tensor imaging parameters and manual dexterity. CONCLUSIONS: Our preliminary results may suggest that the spinal cord's structural loss is the dominant factor in the inflammatory/demyelinating component in patients with MS. Diffusion tensor imaging changes in the spinal cord correlate with brain DTI changes. Manual functioning seems to be more affected than walking.


Assuntos
Encéfalo/diagnóstico por imagem , Medula Cervical/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Medula Espinal/anatomia & histologia , Medula Espinal/patologia , Anisotropia , Humanos , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Fibras Nervosas Mielinizadas/patologia
11.
Neurology ; 94(23): e2468-e2478, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32434868

RESUMO

OBJECTIVE: To evaluate the frequency of asymptomatic optic nerve lesions and their role in the asymptomatic retinal neuroaxonal loss observed in multiple sclerosis (MS). METHODS: We included patients with remitting-relapsing MS in the VWIMS study (Analysis of Neurodegenerative Process Within Visual Ways In Multiple Sclerosis) (ClinicalTrials.gov Identifier: 03656055). Included patients underwent optical coherence tomography (OCT), optic nerve and brain MRI, and low-contrast visual acuity measurement. In eyes of patients with MS without optic neuritis (MS-NON), an optic nerve lesion on MRI (3D double inversion recovery [DIR] sequence) was considered as an asymptomatic lesion. We considered the following OCT/MRI measures: peripapillary retinal nerve fiber layer thickness, macular ganglion cell + inner plexiform layer (mGCIPL) volumes, optic nerve lesion length, T2 lesion burden, and fractional anisotropy within optic radiations. RESULTS: An optic nerve lesion was detected in half of MS-NON eyes. Compared to optic nerves without any lesion and independently of the optic radiation lesions, the asymptomatic lesions were associated with thinner inner retinal layers (p < 0.0001) and a lower contrast visual acuity (p ≤ 0.003). Within eyes with asymptomatic optic nerve lesions, optic nerve lesion length was the only MRI measure significantly associated with retinal neuroaxonal loss (p < 0.03). Intereye mGCIPL thickness difference (IETD) was lower in patients with bilateral optic nerve DIR hypersignal compared to patients with unilateral hypersignal (p = 0.0317). For the diagnosis of history of optic neuritis, sensitivity of 3D DIR and of mGCIPL IETD were 84.9% and 63.5%, respectively. CONCLUSIONS: Asymptomatic optic nerve lesions are an underestimated and preponderant cause of retinal neuroaxonal loss in MS. 3D DIR sequence may be more sensitive than IETD measured by OCT for the detection of optic nerve lesions.


Assuntos
Esclerose Múltipla/patologia , Nervo Óptico/patologia , Retina/patologia , Adolescente , Adulto , Idoso , Anisotropia , Doenças Assintomáticas , Atrofia , Sensibilidades de Contraste , Estudos Transversais , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Natalizumab/uso terapêutico , Fibras Nervosas/patologia , Neuroimagem , Nervo Óptico/diagnóstico por imagem , Tamanho do Órgão , Projetos Piloto , Retina/diagnóstico por imagem , Degeneração Retiniana/etiologia , Degeneração Retiniana/patologia , Sensibilidade e Especificidade , Tomografia de Coerência Óptica , Córtex Visual/diagnóstico por imagem , Córtex Visual/patologia , Adulto Jovem
12.
PLoS One ; 15(4): e0224419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32251416

RESUMO

OBJECTIVE: To investigate the difference of fatigue and pain in patients with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). METHODS: Data from the Modified Fatigue Impact Scale (MFIS) and Pain Effects Scale (PES) were compared between 51 NMOSD and 85 MS patients. Each score was compared in each disease group with or without clinical abnormalities. Since almost no MS patients are without brain magnetic resonance imaging abnormalities, volumetry analysis by the Lesion Segmentation Tool and statistical parametric mapping 12 were added to obtain total lesion volume and intracranial volume in MS patients, and the correlations between total lesion volume/intracranial volume and each score were investigated. RESULTS: Compared to the MS group, the NMOSD group showed a higher PES score (median, 15.0 vs. 7.0, P = 0.045), no difference in MFIS, and an increased percentage of patients with extended spinal cord lesions (58.8% vs. 8.2%, P < 0.001). Moreover, NMOSD and MS patients with extended spinal cord lesions tended to demonstrate higher PES scores than those without. A positive correlation between MFIS and PES were found in patients with NMOSD and MS. On the other hand, MS patients showed a higher percentage of brain abnormalities (80.4% vs. 97.6%, P = 0.001) and a positive correlation between total lesion volume/intracranial volume and MFIS (Spearman's ρ = 0.50, P = 0.033). CONCLUSIONS: The origin of fatigue may be associated with spinal cord lesions causing pain in NMOSD patients, but with brain lesions in MS patients.


Assuntos
Fadiga/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Neuromielite Óptica/diagnóstico por imagem , Dor/diagnóstico por imagem , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Fadiga/etiologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/patologia , Neuromielite Óptica/complicações , Neuromielite Óptica/patologia , Dor/etiologia , Medula Espinal/diagnóstico por imagem
13.
PLoS One ; 15(4): e0231225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32243459

RESUMO

INTRODUCTION: Progressive brain atrophy, development of T1-hypointense areas, and T2-fluid-attenuated inversion recovery (FLAIR)-hyperintense lesion formation in multiple sclerosis (MS) are popular volumetric data that are often utilized as clinical outcomes. However, the exact clinical interpretation of these volumetric data has not yet been fully established. METHODS: We enrolled 42 consecutive patients with MS who fulfilled the revised McDonald criteria of 2010. They were followed-up for more than 3 years from onset, and cross-sectional brain volumetry was performed. Patients with no brain lesions were excluded in advance from this study. For the brain volumetric data, we evaluated several parameters including age-adjusted gray-matter volume atrophy, age-adjusted white-matter volume atrophy, and T2-FLAIR lesion volume. The numbers of T1-hypointense and T2-FLAIR-hyperintense areas were also measured along the same timeline. The clinical data pertaining to disease duration, expanded disability status scale (EDSS), and MS severity score (MSSS) at the timing of volumetry were collected. RESULTS: Among the 42 patients with MS and brain lesions, the number of T1-hypointensity (rho = 0.51, p<0.001), gray-matter atrophy (rho = 0.40, p<0.01) and white-matter atrophy (rho = 0.49, p<0.001) correlated with the EDSS. T1-hypointensity count divided by FLAIR lesion volume correlated with the MSSS (rho = 0.60, p<0.001). Meanwhile, counts or volumes of FLAIR-hyperintense lesions were associated only with the times of past relapses, and did not correlate with present neurological disability level or ongoing disease activity. These findings were consistent regardless of the presence of spinal cord lesions. CONCLUSION: Numbers of T1-hypointensities and brain atrophy equally indicated the current neurological disability in MS. The number of T1-hypointensities divided by FLAIR lesion volume represented the clinical severity. The size or number of FLAIR lesions reflected earlier relapses but was not a good indicator of neurological disability or clinical severity.


Assuntos
Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Adolescente , Adulto , Atrofia/patologia , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Análise de Regressão , Adulto Jovem
14.
PLoS One ; 15(4): e0231868, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32320404

RESUMO

BACKGROUND & OBJECTIVE: Deficits in cognitive functions dependent upon the integrity of the prefrontal cortex have been described in Multiple Sclerosis (MS). In a series of studies we have shown that fluid intelligence (g) is a substantial contributor to frontal deficits and that, for some classical "executive" tasks, frontal deficits were entirely explained by g. However, for another group of frontal tasks deficits remained once g was introduced as a covariate. This second set of tests included multitasking and theory of mind tasks. In the present study, we aimed at determining the role of fluid intelligence in frontal deficits seen in patients with MS. METHODS: A group of patients with Relapsing Remitting MS (n = 36) and a group of control subjects (n = 42) were assessed with a battery of classical executive tests (which included the Wisconsin Card Sorting Test, Verbal Fluency, and Trail Making Test B), a multitasking test, a theory of mind test and a fluid intelligence test. RESULTS: MS patients showed significant deficits in the fluid intelligence task. We found differences between patients and control subjects in all tests except for the multitasking test. The differences in the classical executive tests became non-significant once fluid intelligence was introduced as a covariate, but differences in theory of mind remained. CONCLUSIONS: The present results suggest that fluid intelligence can be affected in MS and that this impairment can play a role in the executive deficits described in MS.


Assuntos
Função Executiva , Inteligência , Esclerose Múltipla/psicologia , Adulto , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Adulto Jovem
15.
Ann Neurol ; 88(1): 93-105, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32285956

RESUMO

OBJECTIVE: During the natural course of multiple sclerosis (MS), the brain is exposed to aging as well as disease effects. Brain aging can be modeled statistically; the so-called "brain-age" paradigm. Here, we evaluated whether brain-predicted age difference (brain-PAD) was sensitive to the presence of MS, clinical progression, and future outcomes. METHODS: In a longitudinal, multicenter sample of 3,565 magnetic resonance imaging (MRI) scans, in 1,204 patients with MS and clinically isolated syndrome (CIS) and 150 healthy controls (mean follow-up time: patients 3.41 years, healthy controls 1.97 years), we measured "brain-predicted age" using T1-weighted MRI. We compared brain-PAD among patients with MS and patients with CIS and healthy controls, and between disease subtypes. Relationships between brain-PAD and Expanded Disability Status Scale (EDSS) were explored. RESULTS: Patients with MS had markedly higher brain-PAD than healthy controls (mean brain-PAD +10.3 years; 95% confidence interval [CI] = 8.5-12.1] versus 4.3 years; 95% CI = 2.1 to 6.4; p < 0.001). The highest brain-PADs were in secondary-progressive MS (+13.3 years; 95% CI = 11.3-15.3). Brain-PAD at study entry predicted time-to-disability progression (hazard ratio 1.02; 95% CI = 1.01-1.03; p < 0.001); although normalized brain volume was a stronger predictor. Greater annualized brain-PAD increases were associated with greater annualized EDSS score (r = 0.26; p < 0.001). INTERPRETATION: The brain-age paradigm is sensitive to MS-related atrophy and clinical progression. A higher brain-PAD at baseline was associated with more rapid disability progression and the rate of change in brain-PAD related to worsening disability. Potentially, "brain-age" could be used as a prognostic biomarker in early-stage MS, to track disease progression or stratify patients for clinical trial enrollment. ANN NEUROL 2020 ANN NEUROL 2020;88:93-105.


Assuntos
Envelhecimento/patologia , Encéfalo/patologia , Doenças Desmielinizantes/patologia , Esclerose Múltipla/patologia , Adolescente , Adulto , Idoso , Atrofia/diagnóstico por imagem , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Doenças Desmielinizantes/diagnóstico por imagem , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Adulto Jovem
16.
Ann Neurol ; 88(1): 81-92, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32286701

RESUMO

OBJECTIVE: Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thalamic demyelinated lesions, thalamic neuronal loss, and cerebral white matter (WM) lesions to thalamic volume. METHODS: We used postmortem in situ magnetic resonance imaging (MRI) scans of 95 subjects with MS to correlate thalamic lesion volumes with global MRI metrics. We histologically characterized thalamic demyelination patterns and compared neuronal loss and neuritic pathology in the thalami with the extremes of volume. RESULTS: Grossly apparent thalamic discolorations in cm-thick brain slices were T2/fluid-attenuated inversion recovery (FLAIR) hyperintense, T1-hypointense, and appeared as perivascular demyelinated lesions with dystrophic neurons/axons. Subependymal demyelinated lesions with axonal loss and microglial/macrophage activation were also observed. The 12 subjects with the least thalamic volume had a 17.6% reduction of median neuronal density in the dorsomedial/ventrolateral and pulvinar nuclei compared with the 14 subjects with the greatest thalamic volume (p = 0.03). After correcting for age, disease duration, sex, and T2 lesion volume, the total (p = 0.20), ovoid (p = 0.31), or subependymal (p = 0.44) MRI thalamic lesion volumes correlated with thalamic volume. Thalamic volume correlated with cerebral T2 lesion volume (Spearman's rho = -0.65, p < 0.001; p < 0.0001 after correcting for age, disease duration, and sex). INTERPRETATION: Our findings suggest the degeneration of efferent/afferent thalamic projections and/or a neurodegenerative process as greater contributors to thalamic atrophy than thalamic demyelinating lesions. ANN NEUROL 2020 ANN NEUROL 2020;88:81-92.


Assuntos
Esclerose Múltipla/patologia , Tálamo/patologia , Substância Branca/patologia , Idoso , Atrofia/diagnóstico por imagem , Atrofia/patologia , Progressão da Doença , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Neurônios/patologia , Pulvinar/diagnóstico por imagem , Pulvinar/patologia , Tálamo/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
17.
PLoS One ; 15(3): e0230202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32155225

RESUMO

People with multiple sclerosis (PwMS) who exhibit minimal to no disability are still over twice as likely to fall as the general population and many of these falls occur during walking. There is a need for more effective ways to detect preclinical walking balance deficits in PwMS. Therefore, the purpose of this study was to investigate the effects of optical flow perturbations applied using virtual reality on walking balance in PwMS compared to age-matched controls. We hypothesized that susceptibility to perturbations-especially those in the mediolateral direction-would be larger in PwMS compared to controls. Fourteen PwMS and fourteen age-matched controls walked on a treadmill while viewing a virtual hallway with and without optical flow perturbations in the mediolateral or anterior-posterior directions. We quantified foot placement kinematics, gait variability, lateral margin of stability and, in a separate session, performance on the standing sensory organization test (SOT). We found only modest differences between groups during normal, unperturbed walking. These differences were larger and more pervasive in the presence of mediolateral perturbations, evidenced by higher variability in step width, sacrum position, and margin of stability at heel-strike in PwMS than controls. PwMS also performed worse than controls on the SOT, and there was a modest correlation between step width variability during perturbed gait and SOT visual score. In conclusion, mediolateral optical flow perturbations revealed differences in walking balance in PwMS that went undetected during normal, unperturbed walking. Targeting this difference may be a promising approach to more effectively detect preclinical walking balance deficits in PwMS.


Assuntos
Teste de Esforço/métodos , Esclerose Múltipla/fisiopatologia , Fluxo Óptico/fisiologia , Equilíbrio Postural/fisiologia , Acidentes por Quedas/prevenção & controle , Adulto , Fenômenos Biomecânicos/fisiologia , Feminino , Pé/fisiologia , Marcha/fisiologia , Humanos , Extremidade Inferior/fisiologia , Masculino , Esclerose Múltipla/diagnóstico por imagem , Realidade Virtual , Caminhada/fisiologia
18.
Nat Rev Neurol ; 16(3): 171-182, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32094485

RESUMO

Early evaluation of treatment response and prediction of disease evolution are key issues in the management of people with multiple sclerosis (MS). In the past 20 years, MRI has become the most useful paraclinical tool in both situations and is used clinically to assess the inflammatory component of the disease, particularly the presence and evolution of focal lesions - the pathological hallmark of MS. However, diffuse neurodegenerative processes that are at least partly independent of inflammatory mechanisms can develop early in people with MS and are closely related to disability. The effects of these neurodegenerative processes at a macroscopic level can be quantified by estimation of brain and spinal cord atrophy with MRI. MRI measurements of atrophy in MS have also been proposed as a complementary approach to lesion assessment to facilitate the prediction of clinical outcomes and to assess treatment responses. In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group critically review the application of brain and spinal cord atrophy in clinical practice in the management of MS, considering the role of atrophy measures in prognosis and treatment monitoring and the barriers to clinical use of these measures. On the basis of this review, the group makes consensus statements and recommendations for future research.


Assuntos
Encéfalo/patologia , Consenso , Imagem por Ressonância Magnética/normas , Esclerose Múltipla/diagnóstico por imagem , Guias de Prática Clínica como Assunto/normas , Índice de Gravidade de Doença , Medula Espinal/diagnóstico por imagem , Atrofia/diagnóstico por imagem , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética/métodos , Esclerose Múltipla/patologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Medula Espinal/patologia
19.
J Neurol Neurosurg Psychiatry ; 91(4): 388-391, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32034114

RESUMO

OBJECTIVE: To determine if vascular risk factor (VRF), that is, smoking, arterial hypertension (HT), dyslipidaemia and diabetes, have an effect on multiple sclerosis (MS) pathology as measured by MS typical brain lesions, we have compared brain MRIs from patients with MS with and without VRF age-matched and sex-matched. METHODS: Brain MRIs from five centres were scored for the presence of Dawson's fingers (DF) and juxtacortical lesions (JCL). A regression model was built to predict the effect of each individual VRF on DF and JCL, considering age and disease duration. RESULTS: 92 MS cases without VRF and 106 MS with one or more VRF (80 ever-smokers, 43 hypertensives, 25 dyslipidaemics and 10 diabetics) were included. Ever-smoking associated with a higher burden of DF (Exp(B)=1.29, 95% CI 1.10 to 1.51, p<0.01) and JCL (Exp(B)=1.38, 95% CI 1.21 to 1.57, p<0.01). No other VRF had an impact on DF. Dyslipidaemia associated with increased JCL (Exp(B)=1.30, 95% CI 1.10 to 1.56, p<0.01) but HT did not associate with any of the outcomes. CONCLUSIONS: Individual VRF appear to affect MS-specific lesions differently. An increase in MS lesions was mainly seen in smokers; however, this VRF is most likely to be present from onset of MS, and other VRF effects may be partly mitigated by treatment. Our findings support that treating VRF and cessation of smoking may be important in the management of MS.


Assuntos
Encéfalo/patologia , Esclerose Múltipla/patologia , Substância Branca/patologia , Adulto , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Fumar , Substância Branca/diagnóstico por imagem
20.
Radiología (Madr., Ed. impr.) ; 62(1): 59-66, ene.-feb. 2020. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-194147

RESUMO

INTRODUCCIÓN: La leucoencefalopatía multifocal progresiva (LMP) es una enfermedad desmielinizante del sistema nervioso central causada por la reactivación del virus JC. Esta encefalopatía oportunista se asocia mayormente a pacientes inmunodeprimidos con VIH en estadio III, y en los últimos años se ha asociado a tratamientos inmunosupresores como el natalizumab. La resonancia magnética (RM) tiene un papel importante tanto en el diagnóstico precoz como en el seguimiento de esta enfermedad. Recientemente, se han descrito en las secuencias eco de gradiente T2 (EGT2) y secuencias de susceptibilidad magnética (SWI) hipointensidades en las fibras-U y en la corteza adyacente a las lesiones de sustancia blanca características de la enfermedad. OBJETIVO: Nuestro objetivo es analizar la presencia y utilidad del signo de la hipointensidad cortical en secuencias EGT2 en relación con el diagnóstico de LMP, así como realizar una revisión bibliográfica sobre el tema. MATERIAL Y MÉTODOS: En este trabajo se analizan tres casos de LMP vistos en nuestro centro en 3 pacientes diferentes con inmunosupresión de distinto origen: uno con enfermedad por VIH en estadio III, otro con esclerosis múltiple en tratamiento con natalizumab y otro con artritis reumatoide en tratamiento con rituximab. RESULTADOS: En los tres casos se observa en la RM el hallazgo de hipointensidad cortical adyacente a la lesión de la sustancia blanca en la secuencia EGT2. En la paciente con esclerosis múltiple, este signo fue más precoz que la alteración de señal en la sustancia blanca. El paciente en tratamiento con rituximab fue diagnosticado post mortem y se presenta una correlación radiopatológica. CONCLUSIÓN: La hipointensidad cortical descrita en el EGT2 en los estudios de RM parece ser un hallazgo que apoyaría el diagnóstico de la LMP, independientemente del tipo de inmunosupresión, lo que nos hace plantear su inclusión de forma rutinaria entre los hallazgos a evaluar en RM en los pacientes con sospecha de LMP


INTRODUCTION: Progressive multifocal leukoencephalopathy is a demyelinating disease of the central nervous system caused by the reactivation of the JC virus. This opportunistic encephalopathy mainly affects immunodepressed patients with stage III HIV infection, although in recent years it has also been found in association with treatment with immunosuppressors such as natalizumab. MRI plays an important role in both the early diagnosis and follow-up of this disease. Recently, it has been reported that hypointensities in U-fibers and cortex adjacent to white-matter lesions characteristic of the disease can be identified on T2-weighted gradient-echo and susceptibility-weighted sequences in patients with progressive multifocal leukoencephalopathy. OBJECTIVE: We aimed to analyze the presence and usefulness of cortical hypointensity on T2-weighted gradient-echo sequences in relation to the diagnosis of progressive multifocal leukoencephalopathy and to review the literature on the topic. MATERIAL AND METHODS: We analyze three cases of progressive multifocal leukoencephalopathy seen at our center in three patients with immunosuppression of different origins: one with stage III HIV infection, one with multiple sclerosis being treated with natalizumab, and one with rheumatoid arthritis being treated with rituximab. RESULTS: In all three cases MRI showed the cortical hypointensity adjacent to the white-matter lesion in the T2-weighted gradient-echo sequence. In the patient with multiple sclerosis, this sign appeared earlier than the abnormal signal in the white matter. The patient being treated with rituximab was diagnosed postmortem and the pathology findings correlated with the MRI findings. CONCLUSION: The finding of cortical hypointensity on T2-weighted gradient-echo MRI sequences seems to support the diagnosis of progressive multifocal leukoencephalopathy, regardless of the type of immunosuppression, so this finding should routinely assessed in patients suspected of having this disease


Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Idoso de 80 Anos ou mais , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Imunossupressão , Natalizumab/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Rituximab/uso terapêutico , Cérebro/diagnóstico por imagem , Espectroscopia de Ressonância Magnética , Mefloquina/uso terapêutico , Mirtazapina/uso terapêutico
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