Segmented corpus callosum diffusivity correlates with the Expanded Disability Status Scale score in the early stages of relapsing-remitting multiple sclerosis

OBJECTIVE: The aim of this study was to characterize the microscopic damage to the corpus callosum in relapsing-remitting multiple sclerosis (RRMS) with diffusion tensor imaging and to investigate the correlation of this damage with disability. The diffusion tensor imaging parameters of fractional anisotropy and mean diffusivity provide information about the integrity of cell membranes, offering two more specific indices, namely the axial and radial diffusivities, which are useful for discriminating axon loss from demyelination. METHOD: Brain magnetic resonance imaging exams of 30 relapsing-remitting multiple sclerosis patients and 30 age- and sex-matched healthy controls were acquired in a 3T scanner. The axial diffusivities, radial diffusivities, fractional anisotropy, and mean diffusivity of five segments of the corpus callosum, correlated to the Expanded Disability Status Scale score, were obtained. RESULTS: All corpus callosum segments showed increased radial diffusivities and mean diffusivity, as well as decreased fractional anisotropy, in the relapsing-remitting multiple sclerosis group. The axial diffusivity was increased in the posterior midbody and splenium. The Expanded Disability Status Scale scores correlated more strongly with axial diffusivities and mean diffusivity, with an isolated correlation with radial diffusivities in the posterior midbody of the corpus callosum. There was no significant correlation with lesion loads. CONCLUSION: Neurological dysfunction in relapsing-remitting multiple sclerosis can be influenced by commissural disconnection, and the diffusion indices of diffusion tensor imaging are potential biomarkers of disability that can be assessed during follow-up

Corpus Callosum Microstructural Changes Correlate with Cognitive Dysfunction in Early Stages of Relapsing-Remitting Multiple Sclerosis: Axial and Radial Diffusivities Approach

The corpus callosum is the largest fiber bundle in the central nervous system and it takes part in several cognitive pathways. It can be affected by multiple sclerosis (MS) early in the disease. DTI is capable of infering the microstructural organization of the white matter. The vectorial analysis of the DTI offers the more specific indices of axial diffusivity (AD) and radial diffusivity (RD), which have shown to be useful to discriminate myelin damage from axon loss, respectively. This study presents DTI results (mean diffusivity (MD), fractional anisotropy (FA), RD, and AD) of 23 relapsing-remitting MS patients and its correlation with cognitive performance. There were 47.8% of cognitive impaired patients (MS CI). We found signs of demyelination, reflected by increased RD, and incipient axon loss, reflected by AD increase, which was slightly higher in the MS CI. The cognitive changes correlated with the DTI parameters, suggesting that loss of complexity in CC connections can impair neural conduction. Thus, cognitive impairment can be related to callosal disconnection, and DTI can be a promising tool to evaluate those changes

The microstructural changes in the neural tissue and the degree of cortical atrophy in the initial stages of relapsing remitting multiple sclerosis

Introdução: Os processos degenerativos vêm sendo considerados determinantes da progressão do déficit neurológico na esclerose múltipla (EM) e são associados sobretudo à perda neuronal e axonal. A patologia na substância branca (SB) manifesta-se pela quebra de membranas e perda da complexidade microestrutural dos tratos cerebrais, o que pode ser estudado indiretamente pelas alterações nos índices de fração de anisotropia (FA) e difusividade média (DM), obtidos por meio das análises das imagens por tensores de difusão (diffusion tensor imaging - DTI). Essa técnica oferece outros dois índices mais específicos, a difusividade axial () e difusividade radial (), que são associados aos processos de perda axonal e desmielinização, respectivamente. A perda neuronal na substância cinzenta (SC) pode ser avaliada pelo grau de atrofia do córtex cerebral. Este estudo tem como objetivos mensurar os índices de DTI na maior comissura cerebral, o corpo caloso (CC), e o grau e distribuição da atrofia cortical em indivíduos com EM remitente-recorrente (EMRR) e baixos escores de incapacidade funcional, correlacionando essas alterações com o volume de lesões macroscópicas e os principais parâmetros clínicos. Método: 31 indivíduos (22 mulheres, idade média 30,5 anos ± 8,7) com EMRR e um grupo controle (GC) composto por 34 indivíduos saudáveis (27 mulheres, idade média 32,3 anos ± 7,8) realizaram exames de crânio em aparelho de ressonância magnética de 3 Tesla (3T), sendo adquiridas imagens de DTI com 32 direções de gradiente, obtendo-se os índices de FA, DM, e de cinco segmentos na secção sagital do corpo caloso (CC). Através da segmentação de imagens volumétricas ponderadas em T1 foram obtidas as espessuras corticais regionais nos grupos. Esses resultados foram correlacionados com os volumes lesionais de imagens ponderadas em T1 e T2/FLAIR e os escores da escala expandida do estado de incapacidade (Expanded Disability Status Scale - EDSS), considerando-se significativos resultados com p< 0,05. Resultados: Os índices de FA, DM e do CC estavam difusamente alterados no grupo EMRR e a , alterada significativamente no esplênio, tronco médio anterior e tronco médio posterior do CC. Observou-se atrofia cortical significativa no terço anterior dos lobos temporais, bilateralmente, e nas regiões parietal inferior, insular e fronto-orbitária direitas, com uma tendência à atrofia no giro frontal superior esquerdo. As FA, DM e correlacionaram-se com os volumes lesionais T1 e, mais significativamente, com os volumes lesionais T2/FLAIR, porém não houve correlação entre os volumes lesionais e a . A espessura cortical no grupo EMRR apresentou correlações com ambos os volumes lesionais, mais significativamente com as lesões em T1. O escore médio da EDSS era 1,1 ± 0,9 (variando de 0-3), apresentando correlações com a DM e a no esplênio, tronco médio anterior e posterior do CC, com uma correlação com a no tronco médio posterior. O EDSS correlacionou-se com a espessura cortical na topografia do giro frontal superior esquerdo. Discussão e conclusão: Houve alteração difusa nos índices de FA, DM e nos segmentos do CC, com acometimento mais localizado, predominantemente médio posterior, da , o que pode sugerir desmielinização difusa do CC, porém axonopatia ou degeneração mais acentuada em algumas regiões da SB. A atrofia cortical também apresentou uma distribuição regional característica, afetando sobretudo as regiões temporais, bilateralmente, parietal inferior, insular e fronto-orbitária direitas. As correlações encontradas entre os índices de DTI e a espessura cortical e os volumes lesionais demonstraram que, ao menos em parte, as degenerações das SB e SC podem ser relacionadas à degeneração Walleriana, secundária ao acúmulo de placas lesionais. As correlações entre a DM, de alguns segmentos do CC e a espessura cortical do giro frontal superior com os escores da EDSS favoreceram à hipótese de que a degeneração tecidual na EM foi um fator preponderante na progressão do déficit neurológico na EMRRIntroduction: The degenerative processes are gaining attention as predictors of the neurological deficit in multiple sclerosis (MS), being reflected by the degree of axon loss and central nervous system atrophy. The white matter pathology (WM) is characterized by cellular membranes disruption and loss of the microstructural complexity, which can be accessed by the diffusion tensor imaging (DTI) indices of fractional anisotropy (FA) and mean diffusivity (MD). This imaging technique also offers two more specific indices: the axial diffusivity () and radial diffusivity (), which are useful to differentiate between axon loss and demyelination, respectively. The gray matter (GM) neuronal loss can be accessed by the degree of cortical atrophy. The aim of this study is to measure the DTI indices in the greatest WM commisure, the corpus callosum (CC), and the degree and distribution of cortical atrophy in patients with relapsing remitting MS (RRMS) and low disability scores, correlating them to the macroscopic lesion load and the main clinical scores. Method: 31 RRMS patients (22 women, mean age 30.5 years ± 8.7) and 34 healthy control (HC) subjects (27 women, mean age 32.3 years ± 7.8) were submitted to brain examinations in a 3T magnetic resonance image scanner. From DTI with 32 gradient encoding directions were extracted the indices of FA, MD, and , which were measured in 5 segments of the mid-sagital section of the corpus callosum (CC). The cortical thickness was obtained from the segmentation of volumetric T1 images. These results were correlated with the macroscopic lesion loads in the T1 and T2/FLAIR images and the scores in the Expanded Disability Status Scale EDSS, considering significant the results with p< 0.05. Results: The FA, MD and were diffusively abnormal in all 5 segments of the CC in the RRMS group and the was abnormal only in the splenium, anterior midbody and posterior mid-body. The anterior area of the both temporal lobes and right inferior parietal, some orbital-frontal and insular regions showed significant atrophy, with a tendency of atrophy in the superior frontal gyrus. The FA, MD and correlated with the T1 lesion load and, more significantly, with the T2/FLAIR lesion load. The cortical thickness correlated with T1 and T2/FLAIR lesion loads, more significantly with the T1 lesion load. The mean EDSS in the RRMS group was 1.1 ± 0.9 (range 0-3), correlating with the MD and of the splenium, anterior and posterior mid-body of the CC. The EDSS correlated to cortical thickness in the topography of the superior frontal gyrus. Discussion and conclusion: The FA, MD and are diffusively abnormal in the CC, with abnormalities in the , restricted to the medial and posterior segments. These results can be interpreted as signs of diffuse demyelination in the CC and a predominance of axonopathy or more advanced degeneration in some segments. The cortical atrophy also followed a characteristic regional distribution, affecting predominantly the bilateral temporal lobes, and inferior parietal, orbital-frontal and insular regions, in the right hemisphere. The correlations found between the DTI indices and the cortical thickness and the macroscopic lesion loads show that, at least partially, the WM and GM degeneration can be related to Wallerian degeneration secondary to macroscopic lesion accumulation. The correlations between the DM, , in some of the CC segments, and cortical thickness, in the superior frontal gyrus, and the EDSS scores reinforces the hypothesis that the degenerative processes in MS can play a role in the disability status of the patient

Craniocervical junction anomalies : morfological analysis by magnetic resonance imaging with considerations about joint function and brain stem physiology

Orientador: Alberto Cliquet JuniorDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: A Junção craniocervical (JCC) é uma região anatômica de transição formada pelo osso occipital e pelas primeiras vértebras cervicais, o atlas e o axis. Esse arcabouço esquelético envolve importantes estruturas do sistema nervoso central (SNC), como o tronco cerebral, o cerebelo e a porção proximal da medula cervical. O complexo e delicado desenvolvimento embrionário dessa região sujeita essa topografia a diversas variações anatômicas e malformações congênitas. Embora algumas deformidades ósseas estejam presentes ao nascimento, alguns pacientes desenvolvem sintomas após a terceira ou quarta décadas de vida. Foi realizada a análise retrospectiva de imagens de Ressonância Magnética (RM) de 61 pacientes selecionados por apresentarem pelo menos uma das principais malformações esqueléticas ou antropométricas da JCC, discriminando a presença de compressão, alteração de sinal nas seqüências de TR longo e siringomielia. Observou-se correlação significativa entre a gravidade das malformações ósseas e o grau de comprometimento neural, com a maior redução ângulos clivuscanal (ACC) e o maior grau de invaginação basilar (IB) relacionando-se, principalmente, à compressão anterior e a alteração do sinal magnético no neuro-eixo. A siringomielia correlacionou-se à maior freqüência de invaginação tonsilar (IT). Alguns aspectos das malformações da JCC são francamente congênitos. Porém, a instabilidade crônica e a sobrecarga articular decorrentes de distúrbios biomecânicos impostos pelas deformidades esqueléticas podem se correlacionar a desordens osteoarticulares adquiridas. 19,7% desses pacientes apresentaram subluxação atlanto-axial, correlacionada com alterações morfológicas da vértebra occipital. Foram observados sinais de degeneração articular atlanto-axial em 42,6%, apresentando correlação significativa com assimilação atlanto-occipital (AAO). Foram realizadas análises de potenciais evocados auditivos do tronco cerebral (PEATC) em 8 pacientes. Dois pacientes não apresentavam compressão neural; 2 apresentavam compressão e elevação de sinal em T2, e 4 indivíduos tinham siringomielia. Um paciente sem compressão apresentou atraso em todas as ondas auditivas. Um dos pacientes com compressão e hipersinal em T2 apresentou as maiores latências nos intervalos I-III e I-V, demonstrando atraso global da via auditiva do tronco cerebral. Todos os pacientes com siringomielia apresentaram alargamento do intervalo I-V, mesmo após a abordagem cirúrgica da JCC. Todos os pacientes com sinais de lesão tecidual significativo, nos exames de RM, apresentaram assincronia dos picos após a aquisição binaural, com defasagem das ondas V do lado contralateral. A RM é uma ferramenta importante na avaliação morfológica da JCC. A avaliação global e detalhada das estruturas ósseas, ligamentares e neurais da JCC é indispensável para classificar o espectro das malformações congênitas e para predizer o risco de desenvolvimento de desordens osteoarticulares e neurológicas adquiridas. A idade do surgimento dos sintomas, algumas vezes, é discrepante ao tempo de duração da injúria tecidual. Por isso, questiona-se se o quadro fisiológico é secundário puramente às injúrias compressivas, ou se existem malformações ocultas do tecido neural. As análises dos PEATC não são realizadas de maneira rotineira, nesses pacientes. Os dados preliminares deste estudo demonstram que a correlação eletrofisiológica à análise por RM pode revelar aspectos da fisiologia do tronco cerebral e da etiologia das lesões neurológicas nas malformações da JCC.Abstract: The craniocervical junction (CCJ) is formed by the combination of the occipital bone and the first cervical vertebrae, the atlas and the axis. It comprehends the brainstem, proximal cervical spinal cord and cerebelar structures and is subjected to several congenital anomalies and anatomic variations. Although the morphological abnormalities are present at birth, many patients develop symptoms after their third and fourth decades. Magnetic Ressonance Imaging (MRI) analyses were performed for 61 patients with these malformations towards discriminating the degree of compression, elevated signal in fluid sensitive sequences and presence of syringomyelia. The severity of skeletal disturbances correlated with the degree of neural tissue damage, with shorter skull base (represented by basilar hypoplasia) and higher basilar invagination (elevation of odontoid tip) correlating with compression and signals of tissue injury. The small posterior fossa correlated to a higher frequence of tonsilar invagination, and with higher incidence of syringomyelia. Some aspects of the CCJ malformations are trully congenital. But the chronical instability and the articular overload imposed by the skeletal deformities add biomecanical disturbances that can be correlated to acquired disorders. 19.7% of the patients presented atlanto-axial subluxation, correlated to morfological abnormalities classified as manifestations of the occipital vertebrae. Signals of degeneration of the atlanto-axial joints were shown in 42.6%, correlated to atlanto-occipital assimilation (AAO). Brainstem auditory evoked potentials (BAEP) tests were performed for 8 patients. 2 patients did not present compression of neuro-axis; 2 showed compression and magnetic signal alteration, and 4 presented syringomyelia. One of the patients without compression presented prolonged latencies of all evoked brainstem potential waves. One patient with compression and hyperintense signal in fluid sensitive sequences presented the longest delays in intervals I-III and I-V of auditory pathway. All patients with syringomyelia presented longer I-V interval, even after decompressive surgery. All patients with significant compromise to neural tissue presented assyncrhonic waves on binaural acquisition, with phase shift of wave V. MRI is an important tool to assess the morphological abnormalities of craniocervical junction. The comprehensive approach of the bone, ligamentar and neurological structures of the CCJ is important to classify the range of congenital abnormalities and to predict the risk of acquired articular and neurological compromise. The discrepance between the duration of compressive injury and appearence of symptoms does not allow the understanding wether functional impairment is secondary to compressive state or to unknown neural tissue incipient malformations. BAEP analyses of these patients are not routinelly done, and these previous data demonstrated that the image and functional correlation can lead to unrevealing features of morphophysiology of the craniocervical juntion malformations.MestradoPesquisa ExperimentalMestre em Cirurgi

Causes, effects and connectivity changes in MS-related cognitive decline

Cognitive decline is a frequent but undervalued aspect of multiple sclerosis (MS). Currently, it remains unclear what the strongest determinants of cognitive dysfunction are, with grey matter damage most directly related to cognitive impairment. Multi-parametric studies seem to indicate that individual factors of MS-pathology are highly interdependent causes of grey matter atrophy and permanent brain damage. They are associated with intermediate functional effects (e.g. in functional MRI) representing a balance between disconnection and (mal) adaptive connectivity changes. Therefore, a more comprehensive MRI approach is warranted, aiming to link structural changes with functional brain organization. To better understand the disconnection syndromes and cognitive decline in MS, this paper reviews the associations between MRI metrics and cognitive performance, by discussing the interactions between multiple facets of MS pathology as determinants of brain damage and how they affect network efficiency

Assessing cognitive control and the reward system in overweight young adults using sensitivity to incentives and white matter integrity.

Cognitive control and incentive sensitivity are related to overeating and obesity. Optimal white matter integrity is relevant for an efficient interaction among reward-related brain regions. However, its relationship with sensitivity to incentives remains controversial. The aim of this study was to assess the incentive sensitivity and its relationship to white matter integrity in normal-weight and overweight groups. Seventy-six young adults participated in this study: 31 were normal-weight (body mass index [BMI] 18.5 to < 25.0 kg/m2, 14 females) and 45 were overweight (BMI ≥ 25.0 kg/m2, 22 females). Incentive sensitivity was assessed using an antisaccade task that evaluates the effect of incentives (neutral, reward, and loss avoidance) on cognitive control performance. Diffusion tensor imaging studies were performed to assess white matter integrity. The relationship between white matter microstructure and incentive sensitivity was investigated through tract-based spatial statistics. Behavioral antisaccade results showed that normal-weight participants presented higher accuracy (78.0 vs. 66.7%, p = 0.01) for loss avoidance incentive compared to overweight participants. Diffusion tensor imaging analysis revealed a positive relationship between fractional anisotropy and loss avoidance accuracy in the normal-weight group (p < 0.05). No relationship reached significance in the overweight group. These results support the hypothesis that white matter integrity is relevant for performance in an incentivized antisaccade task

Toxic Leukoencephalopathies, Including Drug, Medication, Environmental, and Radiation-Induced Encephalopathic Syndromes

Toxic leukoencephalopathies can be secondary to the exposure to a wide variety of exogenous agents, including cranial irradiation, chemotherapy, antiepileptic agents, drugs of abuse, and environmental toxins. There is no typical clinical picture, and patients can present with a wide array of signs and symptoms. Involvement of white matter is a key finding in this scenario, although in some circumstances other high metabolic areas of the central nervous system can also be affected. Magnetic resonance (MR) imaging usually discloses bilateral and symmetric white matter areas of hyperintense signal on T2-weighted and fluid-attenuated inversion recovery images, and signs of restricted diffusion are associated in the acute stage. In most cases, the changes are reversible, especially with prompt recognition of the disease and discontinuation of the noxious agent. Either the MR or clinical features may be similar to several nontoxic entities, such as demyelinating diseases, leukodystrophies, hepatic encephalopathy, vascular disease, hypoxic-ischemic states, and others. A high index of suspicion should be maintained whenever a patient presents recent onset of neurologic deficit, searching the risk of exposure to a neurotoxic agent. Getting to know the most frequent MR appearances and mechanisms of action of causative agents may help to make an early diagnosis and begin therapy, improving outcome. In this review, some of the most important causes of leukoencephalopathies are presented; as well as other 2 related conditions: strokelike migraine attacks after radiation therapy syndrome and reversible splenial lesions. (C) 2014 Elsevier Inc. All rights reserved

AQP4-IgG NMOSD, MOGAD, and double-seronegative NMOSD: is it possible to depict the antibody subtype using magnetic resonance imaging?

Background There is clinical and radiological overlap among demyelinating diseases. However, their pathophysiological mechanisms are different and carry distinct prognoses and treatment demands. Objective To investigate magnetic resonance imaging (MRI) features of patients with myelin-oligodendrocyte glycoprotein associated disease (MOGAD), antibody against aquaporin-4(AQP-4)-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), and double-seronegative patients. Methods A cross-sectional retrospective study was performed to analyze the topography and morphology of central nervous system (CNS) lesions. Two neuroradiologists consensually analyzed the brain, orbit, and spinal cord images. Results In total, 68 patients were enrolled in the study (25 with AQP4-IgG-positive NMOSD, 28 with MOGAD, and 15 double-seronegative patients). There were differences in clinical presentation among the groups. The MOGAD group had less brain involvement (39.2%) than the NMOSD group (p = 0.002), mostly in the subcortical/juxtacortical, the midbrain, the middle cerebellar peduncle, and the cerebellum. Double-seronegative patients had more brain involvement (80%) with larger and tumefactive lesion morphology. In addition, double-seronegative patients showed the longest optic neuritis (p = 0.006), which was more prevalent in the intracranial optic nerve compartment. AQP4-IgG-positive NMOSD optic neuritis had a predominant optic-chiasm location, and brain lesions mainly affected hypothalamic regions and the postrema area (MOGAD versus AQP4-IgG-positive NMOSD, p= 0 .013). Furthermore, this group had more spinal cord lesions (78.3%), and bright spotty lesions were a paramount finding to differentiate it from MOGAD (p = 0.003). Conclusion The pooled analysis of lesion topography, morphology, and signal intensity provides critical information to help clinicians form a timely differential diagnosis