Brain atrophy and lesion load as explaining parameters for cognitive impairment in multiple sclerosis

2005 ◽  
Vol 11 (5) ◽  
pp. 524-531 ◽  
Author(s):  
R HC Lazeron ◽  
J B Boringa ◽  
M Schouten ◽  
B MJ Uitdehaag ◽  
E Bergers ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Social Impact ◽  
Demyelinating Disease ◽  
Word List ◽  
Brain Regions ◽  
Cognitive Test ◽  
Lesion Load ◽  
Whole Brain ◽  
The Brain

Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system, with lesions widespread through the brain and spinal cord. An important manifestation is cognitive impairment, which, though difficult to measure, may have a major social impact. To better understand the relationship between structural tissue damage and cognitive impairment, we examined the extent and spatial distribution of brain lesions, as measured by magnetic resonance imaging (MRI), in relation to abnormal cognitive performance as measured by the Brief Repeatable Battery (BRB) in 82 MS patients. Possible confounders, like fatigue, pain and depression were also assessed. Brain MR image analysis included hyperintense T2 and hypointense T1 lesion load in the whole brain and the four lobes separately, as well as whole brain volume measurements. Cognitive impairment (defined as more than two abnormal tests) was found in 67% of the patients. Moderately strong correlations were found between the subtests of the BRB and the lesion loads in the brain regions hypothesized to be associated with that cognitive test, although these correlations were in general not much stronger than those between the subtests and the overall lesion load (due to strong interrelationships). The Spatial Recall Test correlated best with parietal lesion load; the Symbol Digit Modalities Test, the Paced Auditory Serial Addition Task (PASAT) and the Word List Generation best with frontal, parietal and temporal lesion load; while the Verbal List Generation Test Index correlated only with atrophy. Atrophy and lesion load were the main factors determining the test scores, explaining 10-25% of the variance in the test results, and were more important than fatigue, pain and depression; only depression had a minor, but significant, additional effect on the PASAT. In conclusion, cognitive impairment in MS is moderately dependent on amount (and distribution) of structural brain damage, especially in the more physically impaired patients group.

Olfactory dysfunction and extent of white matter abnormalities in multiple sclerosis: a clinical and MR study

2000 ◽  
Vol 6 (6) ◽  
pp. 386-390 ◽  
Author(s):  
Marino Zorzon ◽  
Maja Ukmar ◽  
Luisa Monti Bragadin ◽  
Francesca Zanier ◽  
Rodolfo M Antonello ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Standardized Test ◽  
Smoking Habit ◽  
Brain Regions ◽  
Olfactory Dysfunction ◽  
Lesion Load ◽  
White Matter Abnormalities ◽  
The Brain ◽  
Smell Loss

Background: The relative contribution to the olfactory dysfunction of the lesions in the specific brain regions involved in olfaction compared with the lesions scattered all over the rest of the brain has not been fully clarified yet in patients with multiple sclerosis (MS). The concurrent use of Magnetic Resonance Imaging (MRI) and a standardized test of odor identification ability now permits to study the relation between smell loss and the extent of white matter abnormalities. Methods: We tested the olfactory function of 40 patients with definite MS and of 40 age-sex- and smoking-habit-matched healthy controls by using the Cross Cultural Smell Identification Test. We measured also the lesion load on T2-weighted images in the inferior-frontal and temporal lobes and in the rest of the brain in MS patients. Therefore, we tried to correlate measures of lesion load and smell test scores. Results: A robust correlation was demonstrated between MR measures of lesion load in the white matter of the olfactory brain region and smell loss (r=70.739, P50.0001). A significant relationship has been found even after taking potential confounding factors, such as sex, age, disease duration, disability, anxiety and depression, into account (r=70.90, P50.0001). Conclusions: Our findings show, in MS patients with stable neurological impairment and no recent disease exacerbation, a correlation between smell loss and the lesion load in the regions of the brain involved in olfaction and support the theory that the extent and severity of MRI abnormalities in specific brain regions are related to the presence of selective neurologic and neuropsychologic impairment.

Torticollis as an Initial Manifestation of a Seronegative Demyelinating Disorder in a Child: A Case Report

2021 ◽  
Author(s):  
Sandesh Kini ◽  
Yellanthoor Ramesh Bhat ◽  
Lakshmikanth Halegubbi Karegowda
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Case Report ◽  
Demyelinating Disease ◽  
Oligoclonal Bands ◽  
Initial Manifestation ◽  
Demyelinating Disorder ◽  
The Brain

AbstractTorticollis refers to a condition in which the head is persistently tilted to one side, sometimes associated with pain. Torticollis in a child can be congenital or acquired. Torticollis as an initial manifestation of an underlying demyelinating syndrome is quite rare in children. Here, we report a 7-year-old girl who presented with persistent torticollis. Neuroimaging of the brain revealed features of a demyelinating disease. Further studies did not show any evidence of multiple sclerosis. Cerebrospinal fluid was negative for antiaquaporin-4 antibodies, antimyelin oligodendrocyte glycoprotein antibodies, and oligoclonal bands. A seronegative demyelinating disorder was considered. She was treated with pulsed methylprednisolone therapy. She responded well to steroids with no progression of illness during follow-up. Torticollis was partially improved.

scholarly journals Increased sensitivity to strong perturbations in a whole-brain model of LSD

2021 ◽  
Author(s):  
Beatrice M. Jobst ◽  
Selen Atasoy ◽  
Adrián Ponce-Alvarez ◽  
Ana Sanjuán ◽  
Leor Roseman ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
External Perturbation ◽  
Brain Regions ◽  
Lysergic Acid ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Whole Brain ◽  
Response Diversity ◽  
Brain States ◽  
The Brain

AbstractLysergic acid diethylamide (LSD) is a potent psychedelic drug, which has seen a revival in clinical and pharmacological research within recent years. Human neuroimaging studies have shown fundamental changes in brain-wide functional connectivity and an expansion of dynamical brain states, thus raising the question about a mechanistic explanation of the dynamics underlying these alterations. Here, we applied a novel perturbational approach based on a whole-brain computational model, which opens up the possibility to externally perturb different brain regions in silico and investigate differences in dynamical stability of different brain states, i.e. the dynamical response of a certain brain region to an external perturbation. After adjusting the whole-brain model parameters to reflect the dynamics of functional magnetic resonance imaging (fMRI) BOLD signals recorded under the influence of LSD or placebo, perturbations of different brain areas were simulated by either promoting or disrupting synchronization in the regarding brain region. After perturbation offset, we quantified the recovery characteristics of the brain area to its basal dynamical state with the Perturbational Integration Latency Index (PILI) and used this measure to distinguish between the two brain states. We found significant changes in dynamical complexity with consistently higher PILI values after LSD intake on a global level, which indicates a shift of the brain’s global working point further away from a stable equilibrium as compared to normal conditions. On a local level, we found that the largest differences were measured within the limbic network, the visual network and the default mode network. Additionally, we found a higher variability of PILI values across different brain regions after LSD intake, indicating higher response diversity under LSD after an external perturbation. Our results provide important new insights into the brain-wide dynamical changes underlying the psychedelic state - here provoked by LSD intake - and underline possible future clinical applications of psychedelic drugs in particular psychiatric disorders.HighlightsNovel offline perturbational method applied on functional magnetic resonance imaging (fMRI) data under the effect of lysergic acid diethylamide (LSD)Shift of brain’s global working point to more complex dynamics after LSD intakeConsistently longer recovery time after model perturbation under LSD influenceStrongest effects in resting state networks relevant for psychedelic experienceHigher response diversity across brain regions under LSD influence after an external in silico perturbation

Cerebrospinal fluid transferrin levels are reduced in patients with early multiple sclerosis

2014 ◽  
Vol 20 (12) ◽  
pp. 1569-1577 ◽  
Author(s):  
M Khalil ◽  
B Riedlbauer ◽  
C Langkammer ◽  
C Enzinger ◽  
S Ropele ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Biochemical Study ◽  
Iron Deposition ◽  
Lesion Load ◽  
Transporter Protein ◽  
In Cis ◽  
The Brain

Background: Previous magnetic resonance imaging (MRI) studies have demonstrated increased iron deposition in the basal ganglia of multiple sclerosis (MS) patients. However, it is not clear whether these alterations are associated with changes of iron metabolism in body fluids. Objectives: The purpose of this study was to investigate if iron metabolism markers in cerebrospinal fluid (CSF) and serum of clinically isolated syndrome (CIS) and MS patients differ from controls and how they relate to clinical and imaging parameters. Methods: We analysed serum ferritin, transferrin and soluble transferrin-receptor and CSF ferritin and transferrin by nephelometry in non-anaemic CIS ( n=60) or early MS ( n=14) patients and 68 controls. In CIS/MS we additionally assessed the T2 lesion load. Results: CSF transferrin was significantly decreased in CIS/MS compared to controls ( p<0.001), while no significant differences were seen in serum. Higher CSF transferrin levels correlated with lower physical disability scores ( r= −0.3, p<0.05). CSF transferrin levels did not correlate with other clinical data and the T2 lesion load. Conclusion: Our biochemical study provides evidence that altered iron homeostasis within the brain occurs in the very early phases of the disease, and suggests that the transporter protein transferrin may play a role in the increased iron deposition known to occur in the brain of MS patients.

Serial MRI in multiple sclerosis: a prospective pilot study of lesion load, whole brain volume and thalamic atrophy

2004 ◽  
Vol 11 (2) ◽  
pp. 153-158 ◽  
Author(s):  
I Taylor ◽  
H Butzkueven ◽  
L Litewka ◽  
L.R MacGregor ◽  
C Szoeke ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Pilot Study ◽  
Brain Volume ◽  
Lesion Load ◽  
Whole Brain ◽  
Prospective Pilot Study ◽  
Serial Mri

Microstructural fronto-striatal and temporo-insular alterations are associated with fatigue in patients with multiple sclerosis independent of white matter lesion load and depression

2019 ◽  
Vol 26 (13) ◽  
pp. 1708-1718 ◽  
Author(s):  
Miklos Palotai ◽  
Michele Cavallari ◽  
Ismail Koubiyr ◽  
Alfredo Morales Pinzon ◽  
Aria Nazeri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Physical Disability ◽  
Disease Duration ◽  
White Matter Lesion ◽  
Brain Magnetic Resonance Imaging ◽  
Brain Regions ◽  
Specific Substrate ◽  
Patient Stratification ◽  
Lesion Load

Background: Fatigue in multiple sclerosis (MS) has been inconsistently associated with disruption of specific brain circuitries. Temporal fluctuations of fatigue have not been considered. Objective: The aim of this study was to investigate the association of fatigue with brain diffusion abnormalities, using robust criteria for patient stratification based on longitudinal patterns of fatigue. Methods: Patient stratification: (1) sustained fatigue (SF, n = 26): latest two Modified Fatigue Impact Scale (MFIS) ⩾ 38; (2) reversible fatigue (RF, n = 25): latest MFIS < 38 and minimum one previous MFIS ⩾ 38; and (3) never fatigued (NF, n = 42): MFIS always < 38 (five assessments minimum). 3T brain magnetic resonance imaging (MRI) was used to perform voxel-wise comparison of fractional anisotropy (FA) between the groups controlling for age, sex, disease duration, physical disability, white matter lesion load (T2LV), and depression. Results: SF and, to a lesser extent, RF patients showed lower FA in multiple brain regions compared to NF patients, independent of age, sex, disease duration, and physical disability. In cingulo-postcommissural-striato-thalamic regions, the differences in FA between SF and NF (but not between RF and NF or SF) patients were independent of T2LV, and in ventromedial prefronto-precommissuro-striatal and temporo-insular areas, independent of T2LV and depression. Conclusion: Damage to ventromedial prefronto-precommissuro-striatal and temporo-insular pathways appears to be a specific substrate of SF in MS.

Brain atrophy evolution and lesion load accrual in multiple sclerosis: a 2-year follow-up study

2008 ◽  
Vol 15 (2) ◽  
pp. 204-211 ◽  
Author(s):  
G Tedeschi ◽  
D Dinacci ◽  
M Comerci ◽  
L Lavorgna ◽  
G Savettieri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Disease Progression ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Disease Duration ◽  
Lesion Load ◽  
Whole Brain ◽  
Gray Matter Atrophy

Background To investigate in a large cohort of patients with multiple sclerosis (MS), lesion load and atrophy evolution, and the relationship between clinical and magnetic resonance imaging (MRI) correlates of disease progression. Methods Two hundred and sixty-seven patients with MS were studied at baseline and two years later using the same MRI protocol. Abnormal white matter fraction, normal appearing white matter fraction, global white matter fraction, gray matter fraction and whole brain fraction, T2-hyperintense, and T1-hypointense lesions were measured at both time points. Results The majority of patients were clinically stable, whereas MRI-derived brain tissue fractions were significantly different after 2 years. The correlation between MRI data at baseline and their variation during the follow-up showed that lower basal gray matter atrophy was significantly related with higher progression of gray matter atrophy during follow-up. The correlation between MRI parameters and disease duration showed that gray matter atrophy rate decreased with increasing disease duration, whereas the rate of white matter atrophy had a constant pattern. Lower basal gray matter atrophy was associated with increased probability of developing gray matter atrophy at follow-up, whereas gray matter atrophy progression over 2 years and new T2 lesion load were risk factors for whole brain atrophy progression. Conclusions In MS, brain atrophy occurs even after a relatively short period of time and in patients with limited progression of disability. Short-term brain atrophy progression rates differ across tissue compartments, as gray matter atrophy results more pronounced than white matter atrophy and appears to be a early phenomenon in the MS-related disease progression.

Neutralising and binding anti-interferon-β-1 b (IFN-b-1 b) antibodies during IFN-β-1 b treatment of multiple sclerosis

1997 ◽  
Vol 3 (3) ◽  
pp. 184-190 ◽  
Author(s):  
P. Kivisäkk ◽  
GV Alm ◽  
WZ Tian ◽  
D. Matusevicius ◽  
S. Fredrikson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Solid Phase ◽  
Inflammatory Diseases ◽  
Neurological Diseases ◽  
Resonance Imaging ◽  
Interferon Β ◽  
Lesion Load ◽  
Neutralising Antibodies ◽  
The Brain ◽  
Antibody Secreting Cells

Interferon-β-1b (IFN-β-1b) is an immunomodulatory therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-β-1b could be hampered by the development of neutralising antibodies against the compound. Our results confirmed earlier studies, showing that 42% of MS patients treated with IFN-β-1b for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-β-1b antibodies, presently not believed to impede the clinical efficacy of IFN-β-1b, were demonstrated by an immunoassay in some patients already after I month of treatment and in 78% after 3 months. The development of binding antibodies seemed to be an early phenomenon, preceding the appearance of neutralising antibodies. Antibodies crossreacting with IFN-β-1a and natural IFN-β were also found in a majority of IFN-β-1b treated patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay, 68% of MS patients treated with IFN-β-1b for 1 -23 months had elevated numbers of anti-IFN-β-1b-antibody secreting cells in blood, compared to 18% of untreated MS patients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-β-1 b is immunogenic in MS patients. High levels of anti-IFN-β-1b antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-β-1b antibodies might also occur spontaneously.

scholarly journals Dementing brain processes in patients with Wilson’s disease and multiple sclerosis (pathogenesis and treatment approaches)

2019 ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Wilson’S Disease ◽  
Early Stage ◽  
Critical Mass ◽  
Wilson's Disease ◽  
Biological Aging ◽  
Cognitive Mechanisms ◽  
The Impact ◽  
The Brain

This article discusses various aspects of dementing processes in patients with Wilson’s disease (WD) and multiple sclerosis (MS), followed by a discussion of current pathogenetic treatment methods for these patients. A comprehensive clinical and laboratory study showed that the pathogenesis and staged development of the dementing process in patients with WD and MS largely coincides with those in patients with Alzheimer's disease and depends on three groups of factors: genetic predisposition, natural (biological) aging, and endo and exogenous pathogenic factors effects on the brain. Therefore, on the basis of the data presented by us, as well as literature data, it allows us to state that dementia is an organic pathophysiological syndrome of destruction of the critical mass of structural-functional blocks and systems of cognitive mechanisms of the brain. Each individual has his own, genetically determined, critical mass of cognitive mechanisms. Like any false system, this one is ultimately subject to both natural (slow) decay and pathological (accelerated) decay due to the death of neurons both in the type of apoptosis and in the type of necrosis. Thus, in patients with WD and MS, the pathogenetic process always involves structures sooner or later that ensure the functioning of the cognitive functions of the brain and lead to the development of their defects, therefore, therapy should be prescribed for the treatment of these patients. Dementia should be treated at its early stage, at the stage of cognitive impairment (CI). The general principles of managing patients with CI are the determination of the etiopathogenetic cause underlying the development of cognitive impairment, the reduction in the degree and prevention of the progression of cognitive deficit and the impact, if possible, on risk factors. Also, at all stages of cognitive deficiency, treatment of concomitant somatic diseases and correction of the emotional state are relevant. Therefore, timely prescribed comprehensive, pathogenetically substantiated personified therapy helps prevent irreversible consequences and improves the quality of life of patients.

scholarly journals Screening of Cognitive Impairment in Patients with Multiple Sclerosis: A Cross-Sectional Study in Georgia

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Nazibrola Botchorishvili ◽  
Nino Shiukashvili ◽  
Nina Mikeladze ◽  
Ann Dzagnidze ◽  
Nino Mikava ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Cognitive Assessment ◽  
Negative Impact ◽  
Cognitive Status ◽  
Screening Tools ◽  
Cognitive Test ◽  
Favorable Effect ◽  
Common Symptom ◽  
Disability Status

Cognitive impairment (CI) is a common symptom of multiple sclerosis (MS), with a significant negative impact on the occupational and social functioning of patients. This study aimed to estimate the prevalence and characteristics of CI among MS patients in Georgia. Sixty-eight patients with MS attending a neurology outpatient clinic in Tbilisi, Georgia, were enrolled in the study. Cognitive status was evaluated using two screening tools: the Brief International Cognitive Assessment for MS and the Montreal Cognitive Assessment. The overall prevalence of CI in our MS patients was 47%. We found negative associations between cognitive test results and patients’ age, disability status, and depression. Lower education, higher scores on the Expanded Disability Status Scale, and the progressive course of MS were the main predictors of CI in the logistic regression analysis. This is the first study in Georgia to evaluate CI in patients with MS. The prevalence of CI in our study was comparable with those reported in other countries; however, we found greater impairment of the executive system compared to other cognitive domains. In our study, patients who were on continuous DMT showed significantly better performance on the cognitive tests used, indicating possible favorable effect of immunomodulatory drugs on cognition.

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