Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. ...The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of the CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition. However, the predictive value of the CVS for the development of clinical MS in patients with suspected demyelinating disease is still unknown. Moreover, the lack of standardization for the definition and imaging of the CVS currently limits its clinical implementation and validation. On the basis of a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative, this article provides statements and recommendations aimed at helping radiologists and neurologists to better understand, refine, standardize and evaluate the CVS in the diagnosis of MS.
Objective
A double‐blind, randomized, controlled study was undertaken to determine whether combined use of interferon β‐1a (IFN) 30μg intramuscularly weekly and glatiramer acetate (GA) 20mg daily is ...more efficacious than either agent alone in relapsing–remitting multiple sclerosis.
Methods
A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics.
Results
Combination IFN + GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity‐free status (DAFS) compared to either single arm, driven by the MRI results.
Interpretation
Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences. ANN NEUROL 2013;73:327–340
Previous studies reveal that a newly described white matter pathway, the frontal aslant tract (FAT), connecting inferior and superior frontal gyri has a role in speech and language functions. We ...explored the role of this tract in a phonemic and semantic fluency tasks in a cohort of multiple sclerosis patients diagnosed with cognitive impairment.
Thirty-five MS patients with varying degrees of cognitive impairment underwent diffusion tensor imaging and the Controlled Associated Word Test. Fractional anisotropy (FA) of FAT and arcuate fasciculus (AF) were obtained through a supervised, atlas-based tissue segmentation and parcellation method. Phonemic and semantic fluency scores were obtained from COWAT. We ran a multivariate regression model, and partial correlation analyses adjusted for age, education, and lesion load, and corrected for multiple comparisons. False discovery rate (FDR) was used for the correction of multiple comparisons.
Bilateral FAT FA showed significant association with phonemic verbal fluency task (Left; r = 0.46, p = 0.0058 and right; r = 0.46, p = 0.0059) but not semantic fluency task and this relation remained significant after FDR correction (p = 0.02 bilaterally). Although left AF showed some significant association with phonemic fluency task, this relation was insignificant after FDR correction.
We show that bilateral FAT are correlates of phonemic verbal fluency task but not semantic in an MS cohort with cognitive impairment. This finding suggests that FAT is more specialized in lexical retrieval function as semantic fluency test encompasses all the functions except the lexical retrieval.
The robustness of brain structural networks, estimated from diffusion MRI data, may be relevant to cognition. We investigate whether measures of network robustness, such as
, can explain cognitive ...impairment in multiple sclerosis (MS). We assessed whether local (i.e., cortical area) and/or global (i.e., whole brain) robustness, differs between cognitively impaired (MSCI) and non-impaired (MSNI) MS patients. Fifty patients, with Expanded Disability Status Scale mean (m): 3.2, disease duration m: 12 years, and age m: 40 years, were enrolled. Cognitive impairment scores were estimated from the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Images were obtained in a 3T MRI using a diffusion protocol with a 2 min acquisition time. Brain structural networks were created using 333 cortical areas. Local and global robustness was estimated for each individual, and comparisons were performed between MSCI and MSNI patients. 31 MSCI and 10 MSNI patients were included in the analyses. Brain structural network robustness and centrality showed significant correlations with cognitive impairment. Measures of network robustness and centrality identified specific cortical areas relevant to MS-related cognitive impairment. These measures can be obtained on clinical scanners and are succinct yet accurate potential biomarkers of cognitive impairment.
Eculizumab is approved for treatment of antibody positive neuromyelitis optica, myasthenia gravis, and hematologic disorders like paroxysmal nocturnal hemoglobinuria. Drug rash has not yet been ...reported as a side effect of eculizumab. We report a case of a cutaneous drug reaction soon after introduction of eculizumab therapy in a patient with refractory neuromyelitis optica. Clinicians should be aware of a drug reaction as a possible adverse reaction to eculizumab.
Purpose
Postacquisition combination of three‐dimensional T2‐weighted (T2w) and fluid‐attenuated inversion recovery (FLAIR) images can improve the visualization of brain lesions in multiple sclerosis ...(MS). However, an optimal way to combine these images has not been described so far. The main objective of this study is to investigate an optimal combination of T2w and FLAIR to improve the conspicuity of MS lesions.
Materials and Methods
We determined the parameters for a generalized multiplicative image combination which maximize the contrast‐to‐noise ratio (CNR) between lesions and normal‐appearing brain tissue through simulations and verified experimentally. MRI data from 11 MS patients acquired at 3 Tesla were retrospectively analyzed using the proposed approach and compared with conventional FLAIR, and to images obtained by direct multiplication of T2w and FLAIR (FLAIR2). Image quality was assessed by region‐of‐interest analysis. In addition, to evaluate the degree of cerebrospinal fluid (CSF) suppression, CSF‐to‐gray matter (CSF/GM) ratio was calculated. Reduction in global image contrast was assessed by computing the reduction in the contrast of mid‐level intensity values.
Results
An optimal combination was found to be the third order expression: FLAIR3 = FLAIR1.55 × T2w1.45. Compared with FLAIR, the lesion CNR was significantly increased by 1.9× (P < 0.005) and 2.5× (P < 0.001) using FLAIR2 and FLAIR3, respectively. CSF/GM ratio was increased by 1.7× in FLAIR2 (P < 0.001) compared with FLAIR, while it was reduced to 0.7× on FLAIR3 (P < 0.05). The mid‐intensity contrast was preserved on FLAIR2 (P = 0.2), and decreased by 29% on FLAIR3 (P < 0.001).
Conclusion
These results show that the optimized combination of FLAIR and T2w can improve MS lesion conspicuity. J. Magn. Reson. Imaging 2016;44:1293–1300.
ABSTRACT
BACKGROUND AND PURPOSE
In 1948, Paul Yakovlev described an additional limbic circuit located basolateral to James Papez's circuit (1937) and included orbitofrontal cortex, amygdala, and ...dorsomedial nucleus of thalamus. This circuit is shown to be an important component of subcortical cognitive abilities. We aimed to demonstrate this circuit in a multiple sclerosis (MS) cohort using diffusion tensor imaging (DTI) and evaluate its role in MS‐related cognitive impairment (CI).
METHODS
We enrolled cognitively intact (n = 10) and impaired (n = 36) MS patients who underwent a comprehensive cognitive assessment; the minimal assessment of cognitive function in MS (MACFIMS) and structural magnetic resonance imaging. Correlation analyses between volumetric and DTI‐derived values of the orbitofrontothalamic (OFT), amygdalothalamic tracts (ATTs), and dorsomedial nucleus of thalamus and CI index derived from MACFIMS were computed after adjustment for age, education, and lesion load.
RESULTS
We observed a consistent trend between CI index and bilateral dorsomedial nucleus’ mean diffusivity (MD) (r = .316; P = .02), left OFT Fractional anisotropy (FA) (r = −.302; P = .02), MD (r = .380; .006), and radial diffusivities (RDs) (r = .432; P = .002), also with right ATT FA (r = −.475; P = .0006) and left ATT FA ( = −.487; P = .0005). After Bonferroni correction, correlations of left OFT RD and right and left ATT FA with CI were found to be significant.
CONCLUSIONS
Our study provides in vivo DTI delineation of Yakovlev's historical basolateral limbic circuit and establishes a role in MS‐related CI. These findings may potentially pave the way for future clinical studies using targeted invasive and noninvasive neurostimulation modalities for CI in MS.
Although the thalamus is not considered primarily as a limbic structure, abundant evidence indicates the essential role of the thalamus as a modulator of limbic functions indirectly through the ...amygdala. The amygdala is a central component of the limbic system and serves an essential role in modulating the core processes including the memory, decision‐making, and emotional reactions. The amygdalothalamic pathway is the largest direct amygdalo‐diencephalic connection in the primates including the human brain. Given the crucial role of the amygdalothalamic tract (ATT) in memory function and diencephalic amnesia in stroke patients, diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of this pathway noninvasively. To date, few diffusion‐weighted studies have focused on the amygdala, yet the fine neuronal connection of the amygdala and thalamus known as the ATT has yet to be elucidated. This study aimed to investigate the utility of high spatial resolution diffusion tensor tractography for mapping the trajectory of the ATT in the human brain. We studied 15 healthy right‐handed human subjects (12 men and 3 women with age range of 24–37 years old). Using a high‐resolution diffusion tensor tractography technique, for the first time, we were able to reconstruct and measure the trajectory of the ATT. We further revealed the close relationship of the ATT with the temporopontine tract and the fornix bilaterally in 15 healthy adult human brains.
The amygdalothalamic tract (ATT) is the most important direct thalamo‐limbic connection in the primates including the human brain connecting the amygdala (AG) with the thalamus (TH).
Cognitive impairment (CI) is common in multiple sclerosis (MS), but underlying mechanisms and their imaging correlates are not completely understood. The gray and white matter structures of the ...limbic system (LS) play crucial roles in different aspects of cognition. To investigate their role in MS related CI, and since a detailed evaluations are lacking in the literature, we used a comprehensive neuroimaging approach to evaluate CI's correlations with the main components of the LS.
Ten non-cognitively impaired MS patients and 30 MS patients with diagnosed CI, who underwent a comprehensive neuropsychological evaluation were included in the analysis. Microstructural integrity, volumetry of main limbic gray and white matter structures and cortical thickness were assessed for associations with CI.
Fornix and cingulum/cingulate cortices were found to be the strongest correlates of CI in MS. As expected, LS' gray and white matter structures were involved in various cognitive functions. Uncinate fasciculi showed significant correlation with verbal and visuospatial learning and memory, phonemic and semantic fluency; hippocampi with visuospatial skills, phonemic and semantic fluency, executive functions, and processing speed; thalami with verbal learning, visuospatial skills, semantic fluency; and amygdala with verbal recognition discrimination.
This comprehensive neuroimaging approach elucidated the role of the main limbic structures in cognitive functions associated with MS-related CI.
PDF
