Impairment In Multiple Sclerosis Patients Research Articles

Upper Cervical Cord Atrophy Predicts Disability Through Motor Clinical Impairment in Multiple Sclerosis Patients (P8-11.017)

Upper Cervical Cord Atrophy Predicts Disability Through Motor Clinical Impairment in Multiple Sclerosis Patients (P8-11.017)

Risk Factors for Cognitive Impairment in Multiple Sclerosis Patients

Cognitive impairment is one of the most significant burdens among the many neurological complaints in multiple sclerosis patients. Cognitive deficits negatively impact these patients’ quality of life, leading to partial or total loss of several mental functions, such as learning, memory, perception, or problem-solving. While the precise mechanisms involved in the onset and evolution of cognitive decline remain unknown, several risk factors have been associated with intellectual disability. With increasing data on this topic in recent years, the main aim of this review is to summarize the most relevant risk factors correlated with cognitive impairment in multiple sclerosis patients. Firstly, the authors demonstrate the importance of mental disability based on epidemiological data from multiple sclerosis patient cohorts. Subsequently, the intensely debated major risk factors for cognitive decline are discussed, with brief insights into the pathophysiology and possible underlying mechanisms. Finally, the authors describe the impact of medication on cognitive impairment in multiple sclerosis patients, highlighting the main research directions for future studies.

Unlocking the link: how hippocampal glutathione-glutamate coupling predicts cognitive impairment in multiple sclerosis patients.

Cognitive impairment is a common symptom of multiple sclerosis and profoundly impacts quality of life. Glutathione (GSH) and glutamate (Glu) are tightly linked in the brain, participating in cognitive function. However, GSH-Glu couplings in cognitive brain regions and their relationship with cognitive impairment in relapsing-remitting multiple sclerosis (RRMS) remains unclear. Forty-one RRMS patients and 43 healthy controls underwent magnetic resonance spectroscopy to measure GSH and Glu levels in the posterior cingulate cortex, medial prefrontal cortex and left hippocampus. Neuropsychological tests were used to evaluate the cognitive function. The Glu/GSH ratio was used to indicate the coupling between GSH and Glu and was tested as a predictor of cognitive performance. The results show that RRMS patients exhibited reduced hippocampal GSH and Glu levels, which were found to be significant predictors of worse verbal and visuospatial memory, respectively. Moreover, GSH levels were dissociated from Glu levels in the left hippocampus of RRMS patients. Hippocampal Glu/GSH ratio is significantly correlated with processing speed and has a greater predictive effect. Here we show the hippocampal Glu/GSH ratio could serve as a new potential marker for characterizing cognitive impairment in RRMS, providing a new direction for clinical detection of cognitive impairment.

Mini-Review: Gait and balance assessment in multiple sclerosis

BACKGROUND: Gait and balance deficiencies are significant concerns for people with multiple sclerosis, resulting in reduced walking capacity, falls and poor quality of life. Issues caused by sensory loss and the inability to properly reweight sensory information are often reported. Even at the early stages of the disease, subclinical gait and balance impairments can be found. AIM: In this article, we review objective measures used to assess gait and postural balance impairment in multiple sclerosis patients. INTERPRETATION: Although scales and clinical tests are important tools for assessing postural instability and walking performance, they can be insensitive to minor disabilities in multiple sclerosis. Instrumented measurements, such as kinematics, kinetics, spatiotemporal gait parameters and center of pressure, play an important role in detecting impairment and evaluating the effects of interventions in people with mild to moderate multiple sclerosis. Thus, objective measurements may be more suitable for tracking deficits in gait and postural balance in multiple sclerosis, contributing to the early detection of disease symptoms, and therefore allowing for the planning of effective interventions to control the speed of disease progression.

Long non-coding RNAs BACE1-AS and BC200 in multiple sclerosis and their relation to cognitive function: A gene expression analysis

Cognitive impairment is a common and debilitating feature of multiple sclerosis (MS), and the dysregulation of synaptic plasticity is one of its direct causes. Long non-coding RNAs (lncRNAs) have been shown to play a role in synaptic plasticity, but their role in cognitive impairment in MS has not been fully explored. In this study, using quantitative real-time PCR, we examined the relative expression of two specific lncRNAs, BACE1-AS and BC200, in the serum of two cohorts of MS patients with and without cognitive impairment. Both lncRNAs were overexpressed in both cognitively impaired and non-cognitively impaired MS patients, with consistently higher levels in the cohort with cognitive impairment. We also found a strong positive correlation between the expression levels of these two lncRNAs. Notably, BACE1-AS was consistently higher in the remitting cases of both relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) groups than in the respective relapse cases of the same subtype, with the SPMS-Remitting group of cognitively impaired MS patients showing the highest expression of BACE1-AS among all MS groups. Additionally, we observed that the primary progressive MS (PPMS) group had the highest expression of BC200 in both cohorts of MS. Furthermore, we developed a model called Neuro_Lnc-2, which showed better diagnostic performance than either BACE1-AS or BC200 alone in predicting MS. Our findings suggest that these two lncRNAs may have a significant impact on the pathogenesis of the progressive types of MS and on the cognitive function of the patients. Future research is required to confirm these findings.

Diagnosis of Coexistent Neurodegenerative Dementias in Multiple Sclerosis (P12-3.018)

<h3>Objective:</h3> Use biomarkers such as PET and CSF proteins to distinguishing multiple sclerosis-related cognitive impairment from co-existent progressive neurodegenerative diseases such as Alzheimer disease. <h3>Background:</h3> Among people with multiple sclerosis, cognitive impairment occurs commonly and is a potent predictor of disability. Some multiple sclerosis patients present with severe cognitive impairment, and distinguishing multiple sclerosis-related cognitive impairment from co-existent progressive neurodegenerative diseases such as Alzheimer disease poses a diagnostic challenge. <h3>Design/Methods:</h3> The study was a retrospective, descriptive study on convenience samples of separate cohorts, one of cognitively impaired multiple sclerosis patients evaluated on autopsy to demonstrate coincidence of both multiple sclerosis and neurodegenerative cognitive diseases. The second cohort were cognitively impaired multiple sclerosis patients evaluated by biomarker to investigate possible additional neurodegenerative cognitive disorders contributing to the cognitive impairment. <h3>Results:</h3> We investigated selected biomarkers among 31 severely impaired patients (biomarker cohort) and 12 severely impaired patients assessed at autopsy and selected 24 (23 biomarker cohort, 1 autopsy cohort) had comprehensive neurocognitive testing. Biomarker cohort investigations included 18F-Fluorodeoxyglucose PET and/or CSF amyloid Aβ1–42, phospho-tau and total tau levels. The autopsy cohort was evaluated with comprehensive neuropathological assessment for aetiology of cognitive impairment. The cohorts shared similar sex, age at multiple sclerosis onset and multiple sclerosis clinical course. The autopsy-cohort patients were older at diagnosis (69.5 versus 57 years, P=0.006), had longer disease duration [median (range) 20 years (3–59) versus 9 (1–32), P=0.001] and had more impaired bedside mental status scores at last follow-up [Kokmen median (range) 23 (1–38) versus 31 (9–34) P=0.01]. Autopsy-cohort patients confirmed, or excluded, coexistent neurogenerative disease by neuropathology gold standard. Most bio marker-cohort patients had informative results evaluating coexistent neurogenerative disease. <h3>Conclusions:</h3> Biomarkers may be useful in indicating a coexistent neurodegenerative disease earlier, and in life, in patients with multiple sclerosis and significant cognitive impairment. <b>Disclosure:</b> Dr. Londono has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Arumaithurai has nothing to disclose. Eleni Constantopoulos has nothing to disclose. Dr. Basso has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Taylor and Francis. The institution of Ross Reichard has received research support from NIH. An immediate family member of Ross Reichard has received publishing royalties from a publication relating to health care. The institution of Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received research support from Viela Bio. Dr. Flanagan has received research support from UCB. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Keegan has received publishing royalties from a publication relating to health care.

Clinical and Demographic Determinants of Cognitive Disorders in Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic, inflammatory, (auto) immune disease of the central nervous system (CNS). The aim of the study was to determine the distribution of cognitive disorders in MS in relation to demographic parameters, degree of clinical disability and depression. The prospective study included 135 subjects with MS in the Clinic of Neurology of the University Clinical Center in Tuzla. The first group consisted of women (101 respondents) and the second of men (34 respondents). Clinical assessment instruments were: Expanded Disability Status Scale Score, Mini Mental Status, Beck Depression Scale, Battery of Cognitive Function Assessment Tests: Wechsler Intelligence Scale, Revised Beta Test, Raven Coloured Progressive Matrix, Wechsler Memory Verification Scale, Audio Memory Test learning, Rey-Osterriecht complex character test, verbal fluency test. There were no significant differences between the mentioned groups in age, level of education, duration of the disease, severity of disease symptoms or in the prevalence of certain forms of MS. Cognitive disorders are present in 40-60 % of subjects with MS. Visuospatial, visuoconstructive, visuoperceptive functions, mnestic functions were most affected in both groups of respondents. There was no difference in the level of depression in relation to sex. Poor results of cognitive parameters in 32.7 % can be considered the cause of high scores of EDSS in female patients and in 29.2 % in patients, which is not statistically significant. The correlation between depression and EDSS is positive but not statistically significant in both sexes. Cognitive disorders are heterogeneous regardless of sex. Cognitive impairment in MS patients is related to impairment of working ability and memory, executive functions and attention. Subjects with a more severe degree of clinical disability had poorer cognitive functions.

Screening tests for the evaluation of cognitive impairment in multiple sclerosis patients

Multiple sclerosis (MS), the most common autoimmune neurological disease of young people, is a significant burden for the patient, significantly decreasing the quality of life. Besides motor deficits, sensory problems, and vision loss, in recent years, neurologists have focused also on the cognitive impairment related to this condition. The early detection of cognitive disturbances is currently an essential part of MS patients’ follow-ups, as any worsening suggests the inefficiency of the applied treatment and the need for a therapeutic switch. In this regard, this review aims to highlight the importance of cognitive screening tests in the periodical evaluation of MS patients. While in the first part, the most frequently used cognitive screening tests in Romania are presented in a detailed manner, in the second part of the article, the clinical impact of these tests is highlighted, based on the results of the most relevant randomized clinical trials published during the last 10 years. Finally, the authors suggest future research directions to improve cognitive screening testing in MS patients after exposing the limitations of currently used screening batteries.

Time perception impairment in multiple sclerosis patients: a survey on internal clock model.

Time perception is known as a mental ability to discern time. Although relative nature of time leaves its numerous aspects undefined, several models have been developed to describe temporal information processing in the brain as well as several areas of the brain have shown to be involved. Time perception alteration has been reported in several neurological conditions; however, the effect of multiple sclerosis (MS) on time perception has yet to be explained. In this study, we aimed to investigate the domains of temporal processing involved in patients with MS and the probable factors affecting it, such as the location of brain demyelinating plaques and gender. Two groups of participants (MS: n = 27 (8 men, 19 women), mean age = 33.85; control: n = 30 (10 men, 20 women), mean age = 28.46) were asked to perform quadruplet time perception tasks (prospective time estimation, duration discrimination, temporal reproduction, and paced motor timing) designed with a software program. Patients with MS had significantly higher scores in time estimation (p < 0.01) and duration discrimination (p < 0.001, in 100-ms interval; p < 0.05, in 1000-ms interval), indicating that MS patients overestimate the time. Since a slower internal clock for MS patients was expected as a result of axonal demyelination, these results suggest the time overestimation in patients with MS which is in contrast with the internal clock model. It means that a slow internal clock causes underestimating and perceiving the time slower.

NODDI, diffusion tensor microstructural abnormalities and atrophy of brain white matter and gray matter contribute to cognitive impairment in multiple sclerosis.

Pathologically specific MRI measures may elucidate in-vivo the heterogeneous processes contributing to cognitive impairment in multiple sclerosis (MS). Using diffusion tensor and neurite orientation dispersion and density imaging (NODDI), we explored the contribution of focal lesions and normal-appearing (NA) tissue microstructural abnormalities to cognitive impairment in MS. One hundred and fifty-two MS patients underwent 3T brain MRI and a neuropsychological evaluation. Forty-eight healthy controls (HC) were also scanned. Fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (ICV_f) and orientation dispersion index (ODI) were assessed in cortical and white matter (WM) lesions, thalamus, NA cortex and NAWM. Predictors of cognitive impairment were identified using random forest. Fifty-two MS patients were cognitively impaired. Compared to cognitively preserved, impaired MS patients had higher WM lesion volume (LV), lower normalized brain volume (NBV), cortical volume (NCV), thalamic volume (NTV), and WM volume (p ≤ 0.021). They also showed lower NAWM FA, higher NAWM, NA cortex and thalamic MD, lower NAWM ICV_f, lower WM lesion ODI, and higher NAWM ODI (false discovery rate-p ≤ 0.026). Cortical lesion number and microstructural abnormalities were not significantly different. The best MRI predictors of cognitive impairment (relative importance) (out-of-bag area under the curve = 0.727) were NAWM FA (100%), NTV (96.0%), NBV (84.7%), thalamic MD (43.4%), NCV (40.6%), NA cortex MD (26.0%), WM LV (23.2%) and WM lesion ODI (17.9%). Our multiparametric MRI study including NODDI measures suggested that neuro-axonal damage and loss of microarchitecture integrity in focal WM lesions, NAWM, and GM contribute to cognitive impairment in MS.

Diagnosis of coexistent neurodegenerative dementias in multiple sclerosis.

Among people with multiple sclerosis, cognitive impairment occurs commonly and is a potent predictor of disability. Some multiple sclerosis patients present with severe cognitive impairment, and distinguishing multiple sclerosis-related cognitive impairment from co-existent progressive neurodegenerative diseases such as Alzheimer disease poses a diagnostic challenge. The use of biomarkers such as PET and CSF proteins may facilitate this distinction. The study was a retrospective, descriptive study on convenience samples of separate cohorts, one of cognitively impaired multiple sclerosis patients evaluated on autopsy to demonstrate coincidence of both multiple sclerosis and neurodegenerative cognitive diseases. The second cohort were cognitively impaired multiple sclerosis patients evaluated by biomarker to investigate possible additional neurodegenerative cognitive disorders contributing to the cognitive impairment. We investigated selected biomarkers among 31 severely impaired patients (biomarker cohort) and 12 severely impaired patients assessed at autopsy and selected 24 (23 biomarker cohort, 1 autopsy cohort) had comprehensive neurocognitive testing. Biomarker cohort investigations included 18F-Fluorodeoxyglucose PET and/or CSF amyloid Aβ1-42, phospho-tau and total tau levels. The autopsy cohort was evaluated with comprehensive neuropathological assessment for aetiology of cognitive impairment. The cohorts shared similar sex, age at multiple sclerosis onset and multiple sclerosis clinical course. The autopsy-cohort patients were older at diagnosis (69.5 versus 57 years, P = 0.006), had longer disease duration [median (range) 20 years (3–59) versus 9 (1–32), P = 0.001] and had more impaired bedside mental status scores at last follow-up [Kokmen median (range) 23 (1–38) versus 31 (9–34) P = 0.01]. Autopsy-cohort patients confirmed, or excluded, coexistent neurogenerative disease by neuropathology gold standard. Most biomarker-cohort patients had informative results evaluating coexistent neurogenerative disease. Biomarkers may be useful in indicating a coexistent neurodegenerative disease earlier, and in life, in patients with multiple sclerosis and significant cognitive impairment.

Working Memory Deficits in Multiple Sclerosis: An Overview of the Findings.

Although working memory (WM) and information processing speed (IPS) impairments in multiple sclerosis (MS) have been widely investigated, several questions, regarding the nature of these impairments and their relationship, remain unclear. The aim of this short communication article is to present an overview of our recent research findings regarding (a) the characteristics of WM impairment in MS patients and, more precisely, the degree of impairment observed in each WM’s component, i.e., phonological loop, visuospatial sketchpad, central executive, and episodic buffer and (b) the relationship between IPS and each of the four WM components, in an attempt to expand the existing rather narrow understanding of the interconnection between reduced IPS and WM impairment. Two studies of our research team are presented here and their findings are briefly discussed, highlighting the importance of further research on a specific component, namely the episodic buffer component among MS patients.

A more unstable resting-state functional network in cognitively declining multiple sclerosis.

Cognitive impairment is common in people with multiple sclerosis and strongly affects their daily functioning. Reports have linked disturbed cognitive functioning in multiple sclerosis to changes in the organization of the functional network. In a healthy brain, communication between brain regions and which network a region belongs to is continuously and dynamically adapted to enable adequate cognitive function. However, this dynamic network adaptation has not been investigated in multiple sclerosis, and longitudinal network data remain particularly rare. Therefore, the aim of this study was to longitudinally identify patterns of dynamic network reconfigurations that are related to the worsening of cognitive decline in multiple sclerosis. Resting-state functional MRI and cognitive scores (expanded Brief Repeatable Battery of Neuropsychological tests) were acquired in 230 patients with multiple sclerosis and 59 matched healthy controls, at baseline (mean disease duration: 15 years) and at 5-year follow-up. A sliding-window approach was used for functional MRI analyses, where brain regions were dynamically assigned to one of seven literature-based subnetworks. Dynamic reconfigurations of subnetworks were characterized using measures of promiscuity (number of subnetworks switched to), flexibility (number of switches), cohesion (mutual switches) and disjointedness (independent switches). Cross-sectional differences between cognitive groups and longitudinal changes were assessed, as well as relations with structural damage and performance on specific cognitive domains. At baseline, 23% of patients were cognitively impaired (≥2/7 domains Z < −2) and 18% were mildly impaired (≥2/7 domains Z < −1.5). Longitudinally, 28% of patients declined over time (0.25 yearly change on ≥2/7 domains based on reliable change index). Cognitively impaired patients displayed more dynamic network reconfigurations across the whole brain compared with cognitively preserved patients and controls, i.e. showing higher promiscuity (P = 0.047), flexibility (P = 0.008) and cohesion (P = 0.008). Over time, cognitively declining patients showed a further increase in cohesion (P = 0.004), which was not seen in stable patients (P = 0.544). More cohesion was related to more severe structural damage (average r = 0.166, P = 0.015) and worse verbal memory (r = −0.156, P = 0.022), information processing speed (r = −0.202, P = 0.003) and working memory (r = −0.163, P = 0.017). Cognitively impaired multiple sclerosis patients exhibited a more unstable network reconfiguration compared to preserved patients, i.e. brain regions switched between subnetworks more often, which was related to structural damage. This shift to more unstable network reconfigurations was also demonstrated longitudinally in patients that showed cognitive decline only. These results indicate the potential relevance of a progressive destabilization of network topology for understanding cognitive decline in multiple sclerosis.

Characteristics of cognitive impairment in multiple sclerosis patients depending on different risk factors

Cognitive impairment (CI), along with motor deficit, is a crucial component of a disability aggravation in multiple sclerosis (MS) patients. The aim of this study was to asses characteristics of CI in separate cognitive domains depending on socio-demographic (age, sex, level of education), disease parameters (severity, course type and disease duration) and external factors (smoking). The current study enrolled 137 MS patients (102 women and 35 men) aged from 22 to 69 years. All participants were divided into two groups depending on the disease course: group А – patients with relapsing-remitting (RR-MS) type (n=106) and group B – participants with progressive forms of the disease (n=31). The following study discovered that disruption of separate cognitive domains was present even without the apparent CI according to MоCA (Montreal Cognitive Assessment): executive functions impairment (p=0,0013) was found most frequently in case of RR-MS, and memory (p=0,0233) decline in case of progressive forms. In the group A moderate CI were associated with decrease of memory (p&lt;0,0001), attention (p=0,0061), executive functions (p=0,0005), language (p=0,0080) and abstract thinking (p=0,0018); severe CI – with disorders of attention (p=0,0055), language (p&lt;0,0001) and abstract thinking (p=0,0144). As for the group B, moderate CI were associated with decline of abstract thinking (p&lt;0,0001), and severe CI – with impairment of memory and executive functions (p=0,0337). Level of physical disability and smoking impact CI independently of MS course, meanwhile, presence of higher education proves to be beneficial for preserving cognitive functions. In addition, disease duration, number of exacerbations and male gender (concerning attention decline) can affect cognition in relapsing-remitting course of MS.

An interpretable machine learning model to explain the interplay between brain lesions and cortical atrophy in multiple sclerosis.

Multiple Sclerosis (MS) is the most common cause, (after trauma) of neurological disability in young adults in Western countries. While several Magnetic Resonance Imaging (MRI) studies have demonstrated a strong association between the presence of cortical grey matter atrophy and the progression of neurological impairment in MS patients, the neurobiological substrates of cortical atrophy in MS, and in particular its relationship with white matter (WM) and cortical lesions, remain unknown. The aim of this study was to investigate the interplay between cortical atrophy and different types of lesions at Ultra-High Field (UHF) 7 T MRI, including cortical lesions and lesions with a susceptibility rim (a feature which histopathological studies have associated with impaired remyelination and progressive tissue destruction). We combined lesion characterization with a recent machine learning (ML) framework which includes explainability, and we were able to predict cortical atrophy in MS from a handful of lesion-related features extracted from 7 T MR imaging. This highlights not only the importance of UHF MRI for accurately evaluating intracortical and rim lesion load, but also the differential contributions that these types of lesions may bring to determine disease evolution and severity. Also, we found that a small subset of features [WM lesion volume (not considering rim lesions), patient age and WM lesion count (not considering rim lesions), intracortical lesion volume] carried most of the prediction power. Interestingly, an almost opposite pattern emerged when contrasting cortical with WM lesion load: WM lesion load is most important when it is small, whereas cortical lesion load behaves in the opposite way.Clinical Relevance- Our results suggest that disconnection and axonal degeneration due to WM lesions and local cortical demyelination are the main factors determining cortical thinning. These findings further elucidate the complexity of MS pathology across the whole brain and the need for both statistical and mechanistic approaches to understanding the etiopathogenesis of lesions.

Myelin imaging measures as predictors of cognitive impairment in MS patients: A hybrid PET-MRI study

BackgroundCognitive impairment is one of the concerns of Multiple Sclerosis (MS) and has been related to myelin loss. Different neuroimaging methods have been used to quantify myelin and relate it to cognitive dysfunctions, among them Magnetization Transfer Ratio (MTR), Diffusion Tensor Imaging (DTI), and, more recently, Positron Emission Tomography (PET) with 11C-PIB. ObjectiveTo investigate different myelin imaging modalities as predictors of cognitive dysfunction. MethodsFifty-one MS patients and 24 healthy controls underwent clinical and neuropsychological assessment and MTR, DTI (Axial Diffusion-AD and Fractional Anisotropy-FA maps), and 11C-PIB PET images in a PET/MR hybrid system. ResultsMTR and DTI(FA) differed in patients with or without cognitive impairment. There was an association of DTI(FA) and DTI(AD) with cognition and psychomotor speed for progressive MS, and of 11C-PIB uptake and MTR for relapsing-remitting MS. MTR in the Thalamus (β= -0.51, p = 0.021) and Corpus Callosum (β= -0.24, p = 0.033) were predictive of cognitive impairment. DTI-FA in the Caudate (β= -26.93, p = 0.006) presented abnormal predictive result. ConclusionLower myelin content by 11C-PIB uptake was associated with worse cognitive status. MTR was predictive of cognitive impairment in MS.

CSF Tau protein correlates with cognitive impairment in multiple sclerosis patients at diagnosis

Cognitive impairment (CI) is a frequent and disabling symptom in Multiple Sclerosis (MS). Axonal damage may contribute to CI development from early stages. Nevertheless, no biomarkers are at the moment available to track CI in MS patients. We aimed to explore the correlation of cerebrospinal fluid (CSF) axonal biomarkers, in particular: light-chain neurofilaments (NFL), Tau, and Beta-amyloid protein (Abeta) in MS patients with CI at the diagnosis.

Unraveling the substrates of cognitive impairment in multiple sclerosis: A multiparametric structural and functional magnetic resonance imaging study.

Cognitive impairment frequently affects multiple sclerosis (MS) patients. However, its neuroanatomical correlates still need to be fully explored. We investigated the contribution of structural and functional magnetic resonance imaging (MRI) abnormalities in explaining cognitive impairment in MS. Brain dual-echo, diffusion tensor, 3D T1-weighted and resting-state (RS) MRI sequences were acquired from 276MS patients and 102healthy controls. Using random forest analysis, the contribution of regional white matter (WM) lesions, WM fractional anisotropy (FA) abnormalities, gray matter (GM) atrophy and RS functional connectivity (FC) alterations to cognitive impairment in MS patients was investigated. Eighty-four MS patients (30.4%) were cognitively impaired. The best MRI predictors of cognitive impairment (relative importance [%]) (out-of-bag area under the curve [AUC]=0.795) were (a) WM lesions in the right superior longitudinal fasciculus (100%), left anterior thalamic radiation (93.4%), left posterior corona radiata (78.5%), left medial lemniscus (74.2%), left inferior longitudinal fasciculus (70.4%), left optic radiation (68.7%), right middle cerebellar peduncle (60.6%) and right optic radiation (53.5%); (b) decreased FA in the splenium of the corpus callosum (64.3%), left optic radiation (61.0%), body of the corpus callosum (51.9%) and fornix (50.9%); and (c) atrophy of the left precuneus (91.4%), right cerebellum crus I (84.4%), right caudate nucleus (78.6%), left thalamus (76.2%) and left supplementary motor area (59.8%). The relevance of these MRI measures in explaining cognitive impairment was confirmed in a cross-validation analysis (AUC=0.765). Structural damage in strategic WM and GM regions explains cognitive impairment in MS patients more than RS FC abnormalities.

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in the Russian Population.

Cognitive dysfunction is common in multiple sclerosis (MS). The Brief International Cognitive Assessment for MS (BICAMS) battery of tests has been suggested as a measure for the evaluation of the cognitive status of MS patients. This study aims to validate the BICAMS battery in the Russian population of MS patients. Age- and sex-matched MS patients (n = 98) and healthy individuals (n = 86) were included in the study. Symbol Digit Modalities Test (SDMT), California Verbal Learning Test, 2nd edition (CVLT-II) and the Brief Visuospatial Memory Test - Revised (BVMT-R) were administered to all participants. The battery was readministered 1 month later to 44 MS patients to investigate the test-retest reliability. MS patients exhibited a significantly lower performance in testing with BICAMS than the control group in all three neuropsychological tests. Test-retest reliability was good for SDMT and CVLT-II (r=.82 and r=.85, respectively) and adequate for BVMT-R (r=.70). Based on the proposed criterion for impairment as z score below 1.5 SD the mean of the control group, we found that 34/98 (35%) of MS patients were found impaired at least in one cognitive domain. Patients with Expanded Disability Status Scale score ≥3.5 performed significantly worse than controls (SDMT, p<.0001; CVLT-II, p=.03; BVMT-R, p=.0004), while those with ≤3.0 scores did not. This study demonstrates that the BICAMS battery is a valid instrument to identify cognitive impairment in MS patients and it can be recommended for routine use in the Russian Federation.

Thalamic nuclei degeneration in multiple sclerosis

ObjectivesTo define both the severity and extent of structural alteration in certain thalamic nuclei by means of MR morphometry and to compare these findings with clinical performance in different phenotypes of multiple sclerosis (MS). MethodsWe comparatively measured the thalamus nuclei volumes of patients with remitting-relapsing (RRMS) and secondary-progressive (SPMS) phenotypes of multiple sclerosis and healthy control subjects (HC). The evaluation of neurological performance was based on the results of Expanded Disability Status Scale and Multiple Sclerosis Severity Scale. Cognitive and mental state was rated according to the results of Mini-Mental State Examination, Frontal Assessment Battery, Montreal Cognitive Assessment and Symbol Digit Modalities Test. Freesurfer 6.0 was used for thalamic nuclei volumes calculation. ResultsThe median volume decline in thalamic pulvinar nuclei in RRMS group on the left side (anterior nucleus − 186,6 mm3, posterior nucleus – 149,4 mm3, medial nucleus 852,4 mm3) compared to HC (anterior nucleus – 229,2 mm3, posterior nucleus – 187,5 mm3, medical nucleus – 1081,3 mm3). Same group, right side – anterior nucleus – 219,5 mm3, posterior nucleus 187,1 mm3, medial nucleus – 989,6 mm3; HC group – anterior nucleus 261,1 mm3, posterior nucleus 240,5 mm3, medial nucleus – 1196,7 mm3 (p < 0,05). The highest correlation of the written section of SDMT was observed with the left ventral anterior nucleus (r = 0,71). ConclusionThese findings indicate the credible correlation between clinical progression of neurological and cognitive impairment in MS patients with asymmetry left-sided thalamic nuclei atrophy and may be considered a potential predicting tool of MS progression.