Background:
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS). Although cognitive impairment (CI) affects a large proportion of MS patients, only few ...data are available about its prognostic value associated with advanced magnetic resonance imaging (MRI) metrics.
Objectives:
We aimed at investigating the relationship between the early CI and the disease progression over 8-year follow-up in MS patients.
Methods:
We conducted a retrospective 8-year longitudinal study involving 78 patients with relapsing-remitting MS, who completed neuropsychological examination and structural MRI at the time of diagnosis. Each patient was clinically evaluated every 6 months, and cortical thickness was quantified at baseline and at the end of the follow-up. Patients were classified as having normal cognition and mild or severe CI.
Results:
The results show that CI at the time of diagnosis is a good predictor of conversion to definite MS (p < 0.001), disability progression (p < 0.001), as well as of transition to secondary progressive phase (p < 0.001) and of cortical thinning (p < 0.001).
Conclusion:
We confirmed and extended the evidence that early CI might be helpful in the identification of MS patients at high risk of disability progression and poor clinical outcome and should be considered as a marker of most aggressive pathology.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background:
Identifying magnetic resonance imaging (MRI) markers in myelin-oligodendrocytes-glycoprotein antibody-associated disease (MOGAD), neuromyelitis optica spectrum disorder-aquaporin-4 ...positive (NMOSD-AQP4) and multiple sclerosis (MS) is essential for establishing objective outcome measures.
Objectives:
To quantify imaging patterns of central nervous system (CNS) damage in MOGAD during the remission stage, and to compare it with NMOSD-AQP4 and MS.
Methods:
20 MOGAD, 19 NMOSD-AQP4, 18 MS in remission with brain or spinal cord involvement and 18 healthy controls (HC) were recruited. Volumetrics, lesions and cortical lesions, diffusion-imaging measures, were analysed.
Results:
Deep grey matter volumes were lower in MOGAD (p = 0.02) and MS (p = 0.0001), compared to HC and were strongly correlated with current lesion volume (MOGAD R = −0.93, p < 0.001, MS R = −0.65, p = 0.0034). Cortical/juxtacortical lesions were seen in a minority of MOGAD, in a majority of MS and in none of NMOSD-AQP4. Non-lesional tissue fractional anisotropy (FA) was only reduced in MS (p = 0.01), although focal reductions were noted in NMOSD-AQP4, reflecting mainly optic nerve and corticospinal tract pathways.
Conclusion:
MOGAD patients are left with grey matter damage, and this may be related to persistent white matter lesions. NMOSD-AQP4 patients showed a relative sparing of deep grey matter volumes, but reduced non-lesional tissue FA. Observations from our study can be used to identify new markers of damage for future multicentre studies.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Purpose
Patients affected with multiple sclerosis suffer from depression more frequently than the general population. Beyond psychosocial, genetic and immune-inflammatory factors, also the brain ...damage which is peculiar of multiple sclerosis has been claimed to have a role in the aetiology of depression in those patients. The study of this interesting relation has been implemented with both conventional and advanced magnetic resonance imaging techniques. The aim of this review is to provide a historical perspective on the link between multiple sclerosis-related depression and structural and functional brain damage.
Methods
In this review, the results of the MRI studies regarding multiple sclerosis-related brain damage and the presence of depression are presented.
Results
The findings of the reports reveal a link between brain pathology and depressive symptoms or the diagnosis of depression in multiple sclerosis.
Conclusions
Although a multifactorial aetiology has been theorized for depression and depressive symptoms in patients with multiple sclerosis, this review supports the hypothesis that the structural and functional brain impairment might substantially be amongst those factors. Thus, depression itself might be a symptom with a neuro-biological basis and not only the consequence of the disability derived from the neurological impairment.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary During the past 10 years, the intense involvement of the grey matter of the CNS in the pathology of multiple sclerosis has become evident. On gross inspection, demyelination in the grey ...matter is rather inconspicuous, and lesions in the grey matter are mostly undetectable with traditional MRI sequences. However, the results of immunohistochemical studies have shown extensive involvement of grey matter, and researchers have developed and applied new MRI acquisition methods as a result. Imaging techniques specifically developed to visualise grey matter lesions indicate early involvement, and image analysis techniques designed to measure the volume of grey matter show progressive loss. Together, these techniques have shown that grey matter pathology is associated with neurological and neuropsychological disability, and the strength of this association exceeds that related to white matter lesions or whole brain atrophy. By focusing on the latest insights into the in-vivo measurement of grey matter lesions and atrophy, we can assess their clinical effects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background:
The cerebrospinal fluid (CSF) molecular milieu is a marker of diffuse intrathecal inflammation in the meninges that, in turn, targets the grey matter (GM) in multiple sclerosis (MS). ...Cognitive impairment (CI) is associated with brain damage in MS and is often present early in people with MS (pwMS).
Objective:
To investigate whether a specific CSF inflammatory profile is associated with different degrees of CI in newly diagnosed pwMS.
Methods:
Sixty-nine pwMS and 43 healthy controls (HCs) underwent neuropsychological testing. The presence and levels of 57 inflammatory mediators in the CSF were assessed.
Results:
Apparently cognitively normal (ACN) pwMS had impaired executive functioning compared to HCs but performed better than pwMS with mild and severe CI (mCI and sCI) in all tests. CSF mediators involving innate immunity and immune activation and recruitment, differentiate ACN from pwMS with mCI, while CSF mediators related to B- and T-cell immunity and chemotaxis differentiate both ACN and mCI from those with sCI. CXCL13 was the only molecule that differentiated sCI from mCI pwMS.
Conclusion:
Specific CSF molecular patterns, reflecting the involvement of both innate and adaptive immune responses, are associated with the severity of CI in newly diagnosed pwMS.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Quantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, ...quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion MRI, complement conventional MRI techniques by providing insight into disease mechanisms. These include: (i) presence and extent of diffuse damage in CNS tissue outside lesions (normal-appearing tissue); (ii) heterogeneity of damage and repair in focal lesions; and (iii) specific damage to CNS tissue components. This review summarizes recent technical advances in quantitative MRI, existing pathological validation of quantitative MRI techniques, and emerging applications of quantitative MRI to patients with multiple sclerosis in both research and clinical settings. The current level of clinical maturity of each quantitative MRI technique, especially regarding its integration into clinical routine, is discussed. We aim to provide a better understanding of how quantitative MRI may help clinical practice by improving stratification of patients with multiple sclerosis, and assessment of disease progression, and evaluation of treatment response.
Background:
Cognitive phenotyping may be useful for predicting rehabilitation response in multiple sclerosis.
Objective:
To evaluate the association between cognitive phenotype(s) and response to ...restorative cognitive rehabilitation (RRCR).
Methods:
In a post hoc retrospective analysis of the RRCR study including 51 multiple sclerosis patients, we evaluated both impairment within specific cognitive domains as well as overall global impairment severity to investigate their relationship to improvement following rehabilitation.
Results:
Greater improvement in executive function was predicted by impairment within this domain as well as by having fewer impaired cognitive domains overall. Similar results were observed for visuospatial memory.
Conclusions:
Patients most likely to benefit from restorative cognitive rehabilitation may exhibit impairment within the domain of interest yet lower cognitive burden overall.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) recently emerged as a potential biomarker in patients with inflammatory demyelinating diseases of the central nervous system. We here ...compare the clinical and laboratory findings observed in a cohort of MOG-Ab seropositive and seronegative cases and describe IgG subclass analysis results. Consecutive serum samples referred to Verona University Neuropathology Laboratory for aquaporin-4 (AQP4)-Ab and/or MOG-Ab testing were analysed between March 2014 and May 2017. The presence of AQP4-Ab was determined using a cell-based assay. A live cell immunofluorescence assay was used for the detection of MOG-IgG and IgG subclass analysis. Among 454 analysed samples, 29 were excluded due to AQP4-Ab positivity or to the final demonstration of a disorder not compatible with MOG-Ab. We obtained clinical data in 154 out of 425 cases. Of these, 22 subjects resulted MOG-Ab positive. MOG-Ab positive patients were mainly characterised by the involvement of the optic nerve and/or spinal cord. Half of the cases presented relapses and the recovery was usually partial. Brain MRI was heterogeneous while short lesions were the prevalent observation on spinal cord MRI. MOG-Ab titre usually decreased in non-relapsing cases. In all MOG-IgG positive cases, we observed IgG1 antibodies, which were predominant in most subjects. IgG2 (5/22), IgG3 (9/22) and IgG4 (3/22) antibodies were also detectable. We confirm that MOG-Ab-related syndromes have distinct features in the spectrum of demyelinating conditions, and we describe the possible role of the different IgG subclasses in this condition.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Since its identification in 1989, hepatitis C virus(HCV) has emerged as a worldwide health problem with roughly 185 million chronic infections, representing individuals at high risk of developing ...cirrhosis and liver cancer. In addition to being a frequent cause of morbidity and mortality due to liver disease, HCV has emerged as an important trigger of lymphoproliferative disorders, owing to its lymphotropism, and of a wide spectrum of extrahepatic manifestations(HCV-EHMs) affecting different organ systems. The most frequently observed HCV-EHMs include mixed cryoglobulinemia and cryoglobulinemic vasculitis, B-cell non-Hodgkin’s lymphoma, nephropathies, thyreopathies, type 2 diabetes mellitus, cardiovascular diseases, and several neurological conditions. In addition, neuropsychiatric disorders and neurocognitive dysfunction are reported in nearly 50% of patients with chronic HCV infection, which are independent of the severity of liver disease or HCV replication rates. Fatigue, sleep disturbance, depression and reduced quality of life are commonly associated with neurocognitive alterations in patients with non-cirrhotic chronic HCV infection, regardless of the stage of liver fibrosis and the infecting genotype. These manifestations, which are the topic of this review, typically occur in the absence of structural brain damage or signal abnormalities on conventional brain magnetic resonance imaging(MRI), although metabolic and microstructural changes can be detected by in vivo proton magnetic resonance spectroscopy, perfusion-weighted and diffusion tensorMRI, and neurophysiological tests of cognitive processing. Several lines of evidence, including comparative and longitudinal neuropsychological assessments in patients achieving spontaneous or treatment-induced viral clearance, support a major pathogenic role for HCV in neuropsychiatric and neurocognitive disorders.
OBJECTIVE:We tested whether brain gray matter (GM) imaging measures can differentiate between multiple sclerosis (MS) and neuromyelitis optica (NMO) using random-forest classification.
METHODS:Ninety ...participants (25 patients with MS, 30 patients with NMO, and 35 healthy controls HCs) were studied in Tehran, Iran, and 54 (24 patients with MS, 20 patients with NMO, and 10 HCs) in Padua, Italy. Participants underwent brain T1 and T2/fluid-attenuated inversion recovery MRI. Volume, thickness, and surface of 50 cortical GM regions and volumes of the deep GM nuclei were calculated and used to construct 3 random-forest models to classify patients as either NMO or MS, and separate each patient group from HCs. Clinical diagnosis was the gold standard against which the accuracy was calculated.
RESULTS:The classifier distinguished patients with MS, who showed greater atrophy especially in deep GM, from those with NMO with an average accuracy of 74% (sensitivity/specificity77/72; p < 0.01). When we used thalamic volume (the most discriminating GM measure) together with the white matter lesion volume, the accuracy of the classification of MS vs NMO was 80%. The classifications of MS vs HCs and NMO vs HCs achieved higher accuracies (92% and 88%).
CONCLUSIONS:GM imaging biomarkers, automatically obtained from clinical scans, can be used to distinguish NMO from MS, even in a 2-center setting, and may facilitate the differential diagnosis in clinical practice.
CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that GM imaging biomarkers can distinguish patients with NMO from those with MS.
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