Multiple Sclerosis Lesion Load Research Articles

The effect of COVID-19 vaccination on multiple sclerosis activity as reflected by MRI.

Examining the safety oftheBNT162b2 mRNA vaccine in multiple sclerosis (MS) patientsremains inconclusive, particularly regarding the potential for disease exacerbations. Thisstudyaims to assess the effects ofBNT162b2 COVID-19vaccination on disease activityin MS patientsthroughsequential MRI imaging. A retrospective study of 84 MS patients from five Israeli hospitals was conducted. MS lesion load was determined from three brain MRI scans, one postvaccination and two prevaccination scans. Apost hocanalysis comparedsubgroupsfeaturingvaccinated and unvaccinated patientsrespectively,with early onset MS. The cohort included 70 women with early onset (mean age 16.4±0.8years) and adult onset (mean age 34.9±1.1years)MS. Among the early onset group, vaccinated patients showed an increased risk of new lesions (p=.00026), while there was no increased risk among adult-onset patients. Additionally, a comparison between early onset vaccinated and nonvaccinated groups revealed a higher risk of increased lesions in the vaccinated group (p=.024). Overall, the study suggests that the BNT162b2 vaccine is generally safe in MS patients, with no association found between vaccination and new lesions in most patients. However, close MRI follow-up is recommended for early-onset MS cases to monitor lesion development.

The Importance of Managing Modifiable Comorbidities in People with Multiple Sclerosis: A Narrative Review.

Multiple sclerosis (MS) is a chronic, inflammatory, degenerative demyelinating disease of the central nervous system (CNS) of unknown etiology that affects individuals in their early adulthood. In the last decade, life expectancy for people with MS (PwMS) has almost equaled that of the general population. This demographic shift necessitates a heightened awareness of comorbidities, especially the ones that can be prevented and modified, that can significantly impact disease progression and management. Vascular comorbidities are of particular interest as they are mostly modifiable health states, along with voluntary behaviors, such as smoking and alcohol consumption, commonly observed among individuals with MS. Vascular risk factors have also been implicated in the etiology of cerebral small vessel disease. Furthermore, differentiating between vascular and MS lesion load poses a significant challenge due to overlapping clinical and radiological features. This review describes the current evidence regarding the range of preventable and modifiable comorbidities and risk factors and their implications for PwMS.

Higher MRI lesion load in multiple sclerosis is related to the N-glycosylation changes of cerebrospinal fluid immunoglobulin G

BackgroundIntrathecal clonal expansion of antibody-producing plasma cells in multiple sclerosis (MS) perpetuates central nervous system injury and is associated with active demyelination. Immunoglobulin G (IgG) effector functions are modulated by linked N-glycan structures. The aim of the study was to detect potential differences in N-glycosylation of IgG in serum and cerebrospinal fluid (CSF) and total sera proteins between people with MS and those in whom the diagnosis of MS was excluded. Furthermore, we investigated the association with standard laboratory biomarkers of intrathecal inflammation as well as clinical and neuroradiological disease activity. MethodsThis cross-sectional study included patients with suspected demyelinating disease. MS diagnosis was based on the 2017 McDonald criteria and controls were patients with excluded MS diagnosis. N-glycans were compared with Expanded Disability Status Scale (EDSS), magnetic resonance imaging (MRI) markers of disease activity and biomarkers of intrathecal inflammation (cell count, CSF-IgG concentration, percentage of intrathecal IgG, oligoclonal bands (OCB), virus-specific antibody index (MRZH reaction)). ResultsDifferences between groups were observed only in the CSF-IgG N-glycome. In MS, the presence of bisecting N-acetylglucosamine (Padj=2.63E-05) and monogalactosylation (Padj=1.49E-06) were more abundant and associated with positive OCBs. N-glycans monogalactosylated at the α6 arm FA2[6]G1 (r = 0.56) and FA2[6]BG1 (r = 0.45) correlated with percentage of intrathecal IgG, but not total CSF-IgG. This trait was also more abundant in MRZH positive people with MS who had higher MRI lesion load (P = 0.018) but unrelated to active lesions or EDSS. ConclusionsMore abundant monogalactosylation of intrathecally synthesized IgG is the most prominent trait in MS and is associated with higher MRI lesion load.

A novel eye-movement impairment in multiple sclerosis indicating widespread cortical damage.

In multiple sclerosis, remyelination trials have yet to deliver success like that achieved for relapse rates with disease course modifying treatment trials. The challenge is to have a clinical, functional outcome measure. Currently, there are none that have been validated, other than visual evoked potentials in optic neuritis. Like vision, quick eye movements (saccades) are heavily dependent on myelination. We proposed that it is possible to extrapolate from demyelination of the medial longitudinal fasciculus in the brainstem to quantitative assessment of cortical networks governing saccadic eye movements in multiple sclerosis. We have developed and validated a double-step saccadic test, which consists of a pair of eye movements towards two stimuli presented in quick succession (the demonstrate eye movement networks with saccades protocol). In this single-centre, cross-sectional cohort study we interrogated the structural and functional relationships of double-step saccades in multiple sclerosis. Data were collected for double-step saccades, cognitive function (extended Rao's Brief Repeatable Battery), disability (Expanded Disability Status Scale) and visual functioning in daily life (National Eye Institute Visual Function Questionnaire). MRI was used to quantify grey matter atrophy and multiple sclerosis lesion load. Multivariable linear regression models were used for analysis of the relationships between double-step saccades and clinical and MRI metrics. We included 209 individuals with multiple sclerosis (mean age 54.3 ± 10.5 years, 58% female, 63% relapsing-remitting multiple sclerosis) and 60 healthy control subjects (mean age 52.1 ± 9.2 years, 53% female). The proportion of correct double-step saccades was significantly reduced in multiple sclerosis (mean 0.29 ± 0.22) compared to controls (0.45 ± 0.22, P < 0.001). Consistent with this, there was a significantly larger double-step dysmetric saccadic error in multiple sclerosis (mean vertical error -1.18 ± 1.20°) compared to controls (-0.54 ± 0.86°, P < 0.001). Impaired double-step saccadic metrics were consistently associated with more severe global and local grey matter atrophy (correct responses-cortical grey matter: β = 0.42, P < 0.001), lesion load (vertical error: β = -0.28, P < 0.001), progressive phenotypes, more severe physical and cognitive impairment (correct responses-information processing: β = 0.46, P < 0.001) and visual functioning. In conclusion, double-step saccades represent a robust metric that revealed a novel eye-movement impairment in individuals with multiple sclerosis. Double-step saccades outperformed other saccadic tasks in their statistical relationship with clinical, cognitive and visual functioning, as well as global and local grey matter atrophy. Double-step saccades should be evaluated longitudinally and tested as a potential novel outcome measure for remyelination trials in multiple sclerosis.

White matter lesion burden correlates with the free water distribution surrounding the lateral ventricle

AbstractBackgroundThe clearance function is considered playing significant role in the neurodegeneration and neuroinflammation diseases, such as Alzheimer's disease (AD), Parkinson disease (PD) and multiple sclerosis (MS), etc. The enlarged perivascular space (EPVS) is believed to be a main pathway for the clearance of metabolic wastes. The free water in the PVS helps to clear the waste. The dysfunction of clearance function may accelerate the progression of diseases. We propose to use a T2 relaxometry based free water mapping to investigate the free water distribution in MS subjects. We call the free water mapping as cerebrospinal fluid water fraction (CSFF).MethodMulti‐echo T2 image was acquired with 7 echoes (TE = 0, 7.5, 17.5, 67.5, 147.5, 307.5, 1000 ms). Then the T2 data was fitted to three‐compartment water model (myelin water, intro‐extracellular water, and free water) by the T2 relaxometry of different tissue type. The CSFF in the white matter region is extracted from the FreeSurfer processed white matter mask. For each subject, the extracted WM CSFF was organized into a column vector and then fed in the k‐means algorithm. The number of categories is set to k = 8, which is sufficient to categorize the WM CSFF pattern into detailed tissue structure. We are interested in the distribution pattern of smallest CSFF values in WM, i.e., the category that has smallest mean CSFF.We then check the correspondence between the smallest CSFF pattern with the anatomic structure. If the distribution of the smallest CSFF is continuous region near the posterior of ventricle CSF, then we call the subject CSFF‐negative (Fig. 1a), otherwise it’s CSF‐positive (Fig. 1b).ResultThe distribution of the smallest WM CSFF in the MS cohort is significantly related to the severity of the disease. CSFF‐positive subjects have light MS lesion load, while the CSFF‐negative subjects have heavy MS lesion load (Fig.2).ConclusionThe results show that the T2 relaxometry based free water mapping could be treated as a biomarker of MS load. This finding might be helpful for the understanding of development of MS disease.

IL-22 Binding Protein Promotes the Disease Process in Multiple Sclerosis

Genome-wide association studies have mapped the specific sequence variants that predispose for multiple sclerosis (MS). The pathogenic mechanisms that underlie these associations could be leveraged to develop safer and more effective MS treatments but are still poorly understood. In this article, we study the genetic risk variant rs17066096 and the candidate gene that encodes IL-22 binding protein (IL-22BP), an antagonist molecule of the cytokine IL-22. We show that monocytes from carriers of the risk genotype of rs17066096 express more IL-22BP in vitro and cerebrospinal fluid levels of IL-22BP correlate with MS lesion load on magnetic resonance imaging. We confirm the pathogenicity of IL-22BP in both rat and mouse models of MS and go on to suggest a pathogenic mechanism involving lack of IL-22-mediated inhibition of T cell-derived IFN-γ expression. Our results demonstrate a pathogenic role of IL-22BP in three species with a potential mechanism of action involving T cell polarization, suggesting a therapeutic potential of IL-22 in the context of MS.

Partial volume-aware assessment of multiple sclerosis lesions.

White-matter lesion count and volume estimation are key to the diagnosis and monitoring of multiple sclerosis (MS). Automated MS lesion segmentation methods that have been proposed in the past 20 years reach their limits when applied to patients in early disease stages characterized by low lesion load and small lesions. We propose an algorithm to automatically assess MS lesion load (number and volume) while taking into account the mixing of healthy and lesional tissue in the image voxels due to partial volume effects. The proposed method works on 3D MPRAGE and 3D FLAIR images as obtained from current routine MS clinical protocols. The method was evaluated and compared with manual segmentation on a cohort of 39 early-stage MS patients with low disability, and showed higher Dice similarity coefficients (median DSC = 0.55) and higher detection rate (median DR = 61%) than two widely used methods (median DSC = 0.50, median DR < 45%) for automated MS lesion segmentation. We argue that this is due to the higher performance in segmentation of small lesions, which are inherently prone to partial volume effects.

Cerebral autoregulation is preserved in multiple sclerosis patients

Multiple sclerosis (MS) is an inflammatory disease that may also be associated with vascular dysfunction. One master component of vascular regulation is cerebral autoregulation (CA). We aimed to investigate the integrity of CA in MS patients and study its relationship with autonomic dysfunction (AD), magnetic-resonance-imaging (MRI) lesion load and hemodynamic parameters. We enrolled 20 relapsing-remitting MS and 20 healthy subjects. CA was assessed by transfer function analysis parameters (coherence, gain and phase), as obtained in the very low, low and high-frequency domains (VLF, LF, HF, respectively). We evaluated the autonomic parameters heart rate variability and spontaneous baroreflex sensitivity (BRS). There were no significant differences in CA parameters between MS and controls (p>0.05). Lesion load was not correlated with any CA parameter. LF gain was positively correlated with BRS in both groups (MS: p=0.017; controls: p=0.025). Brainstem lesion load in MS was associated with higher systolic blood pressure (SBP; p=0.009). Our findings suggest that CA is preserved in our MS cohort. On the other hand, AD in MS patients with brainstem lesions could contribute to the increase of supine SBP. Whether this systemic deregulation could contribute to disease burden remains to be investigated.

Correlations between depression, cognitive status, functional scores, disability and lesion load in multiple sclerosis treated with interferon beta 1a

Abstract Introduction: Depression and cognitive impairment are the most frequent mental disorders in multiple sclerosis (MS) and represent an important cause of morbidity and mortality. The aim of the study was to analyse the main determinants of depression in multiple sclerosis. Materials and methods: Thirty-two patients with relapsing remitting multiple sclerosis (RRMS), treated with Interferon Beta 1a, without relapses and corticosteroid treatment in the last 30 days, were included in the study. The mean age of the patients was 35.4±9.2 years, M/F ratio 0.33. Depression level was evaluated by the Romanian version of Beck Depression Inventory (BDI) and the cognitive function with Paced Auditory Serial Addition Test 3 (PASAT 3), Symbol Digit Modalities Test (SDMT). The functional status and disability level of the patients were evaluated with Multiple Sclerosis Functional Composite and Expanded Disability Status Scale. In all patients a cerebral MRI with intravenous contrast administration was performed using a 1.5T MRI device. Results: Twenty-three patients were free of depression (score 1-10), 4 patients presented mild mood disturbance (score 11-16), 3 borderline clinical depression (score 17-20) and 2 moderate depression (score 21-30). The mean BDI score was 8.71±7.16. BDI score correlated significantly with EDSS (R=0.38, p=0.03), PASAT 3 (R=-0.42, p=0.01), SDMT (R=-0.58, p=0.0007), Timed 25-Foot Walk (R=0.43, p=0.01) and 9-Hole Peg Test (R=0.45, p=0.008). From the EDSS functional scores, significant correlations were found with the urinary score (R=0.4, p=0.01) and sensitive score (R=0.49, p=0.004). BDI score correlated significantly with the total number of T2 lesions (R=0.31, p=0.05) while there was no correlation with the number of active lesions. Conclusions: The main determinants of depression in RRMS patients are the cognitive impairment, the affection of fine hand movements (9-HP), gait impairment (T25FT) and bladder and sensitive dysfunction.

Added value of double inversion recovery magnetic resonance sequence in detection of cortical and white matter brain lesions in multiple sclerosis

ObjectiveThe aim of this study was to evaluate the value of double inversion recovery (DIR) magnetic resonance (MR) sequence in the detection of brain cortical and white matter lesions in multiple sclerosis (MS). Patients and methodsFifteen patients with remitting relapsing MS were included in this study. Imaging was performed on a 1.T MR system using DIR, fluid-attenuated inversion-recovery (FLAIR), and T2-weighted image (T2WI) sequences. The sensitivity of DIR was compared with the corresponding sensitivity of FLAIR and T2WI sequences. The contrast between lesions and normal-appearing gray matter (NAGM), normal-appearing white matter (NAWM), and cerebrospinal fluid (CSF) was determined for all sequences. ResultsDIR showed significantly more MS lesion load overall when compared to T2WI or FLAIR. Significantly higher number of lesions was seen in the supra- and infratentorial locations. DIR detected higher periventricular white matter lesions when compared to FLAIR, but did not detect significantly higher lesions when compared to T2WI. Significantly higher deep white matter, juxtacortical, and intracortical lesions were seen on DIR when compared to both T2WI and FLAIR. The image contrast measurements between the MS lesions and the NAWM in all anatomical locations were significantly higher in DIR sequence compared to both T2WI and FLAIR sequences. However, there was no significant statistical difference between the DIR and both T2WI and FLAIR sequences regarding the contrast of intracortical lesions compared to NAGM. ConclusionDIR sequence is valuable in the imaging workup of MS as it can detect more MS lesions compared to the T2W and FLAIR sequences in all anatomical locations. DIR showed better delineation between the white matter, gray matter, and the MS lesions due to its high image contrast. DIR sequence should be included in the routine MR protocol of MS patients especially to answer the question about intra-cortical and juxta-cortical MS lesions.

Multiple Sclerosis: Identification of Temporal Changes in Brain Lesions with Computer-Assisted Detection Software

Multiple sclerosis (MS) is a chronic disease with a progressing and evolving course. Serial imaging with MRI is the mainstay in monitoring and managing MS patients. In this work we demonstrate the performance of a locally developed computer-assisted detection (CAD) software used to track temporal changes in brain MS lesions. CAD tracks changes in T2-bright MS lesions between two time points on a 3D high-resolution isotropic FLAIR MR sequence of the brain acquired at 3 Tesla. The program consists of an image-processing pipeline, and displays scrollable difference maps used as an aid to the neuroradiologist for assessing lesional change. To assess the value of the software we have compared diagnostic accuracy and duration of interpretation of the CAD-assisted and routine clinical interpretations in 98 randomly chosen, paired MR examinations from 88 patients (68 women, 20 men, mean age 43.5, age range 21-75) with a diagnosis of definite MS. The ground truth was determined by a three-expert panel. In case-wise analysis, CAD interpretation showed higher sensitivity than a clinical report (87% vs 77%, respectively). Lesion-wise analysis demonstrated improved sensitivity of CAD over a routine clinical interpretation of 40%-48%. Mean software-assisted interpretation time was 2.7 min. Our study demonstrates the potential of including CAD software in the workflow of neuroradiology practice for the detection of MS lesional change. Automated quantification of temporal change in MS lesion load may also be used in clinical research, e.g., in drug trials.

A Cellular Neural Network methodology for the automated segmentation of multiple sclerosis lesions

We present a new application based on genetic algorithms (GAs) that evolves a Cellular Neural Network (CNN) capable of automatically determining the lesion load in multiple sclerosis (MS) patients from magnetic resonance imaging (MRI). In particular, it seeks to identify brain areas affected by lesions, whose presence is revealed by areas of higher intensity if compared to healthy tissue. The performance of the CNN algorithm has been quantitatively evaluated by comparing the CNN output with the expert's manual delineation of MS lesions. The CNN algorithm was run on a data set of 11 MS patients; for each one a single dataset of MRI images (matrix resolution of 256×256 pixels) was acquired. Our automated approach gives satisfactory results showing that after the learning process the CNN is capable of detecting MS lesions with different shapes and intensities (mean DICE coefficient=0.64). The system could provide a useful support tool for the evaluation of lesions in MS patients, although it needs to be evolved and developed in the future.

Semi-automated thresholding technique for measuring lesion volumes in multiple sclerosis: effects of the change of the threshold on the computed lesion loads.

Quantitative evaluation of lesion load in multiple sclerosis (MS) from magnetic resonance imaging (MRI) scans is becoming important in understanding and monitoring the progression of the disease. Methods of MS lesion segmentation based on intensity thresholding offer one of the most robust and easily-implemented means of computing the total lesion volume. This study evaluated the effects of slight changes in the choice of intensity threshold on computed lesion volumes in 20 patients with MS using such a technique. After judging the optimum choice of threshold value, the threshold value was increased and decreased by 3% in 1% steps around this value; we observed a mean change of 15% in computed lesion volumes for 1% changes of threshold value. Larger changes in lesion volume were found when the threshold was changed by larger amounts. On the other hand, the amount of time required for manual review decreased, and the confidence with which manual review could be performed increased when using lower thresholds. This study shows that the choice of threshold is a crucial factor in measuring lesion volumes in MS when using intensity-based techniques. It also suggests that in multicenter and/or longitudinal studies, criteria for choosing the threshold should be developed whereby the threshold level should be set such that all MR visible lesions are above it, in order to minimise the human interaction and, consequently, the reproducibility of the results.

Movement preparation is affected by tissue damage in multiple sclerosis: Evidence from EEG event-related desynchronization

Objective To investigate the impact of brain tissue damage in Multiple Sclerosis (MS) on the efficiency of programming of voluntary movement, assessed using event-related desynchronization of the EEG. Methods The onset latency of mu ERD (percent desyncronization of the mu rhythm preceding movement onset) to hand movement was studied in 34 MS patients. ERD onset was compared with normative data and correlated with T1 and T2 total lesion volume (TLV) at magnetic resonance imaging (MRI). Results ERD onset latency was significantly correlated with T1-TLV ( r=0.53, P=0.001) and T2 lesion load ( r=0.5, P=0.003), even after correcting for disability. Patients with higher T1-TLV had significantly delayed ERD onset compared with normal subjects and with patients with lower T1-TLV; patients with higher T2-TLV had significantly delayed ERD compared with normal subjects only. ERD onset latency was not correlated to clinical disability. Conclusions Our finding of delayed ERD onset in patients with more severe measures of brain damage, independently from clinical disability, suggests that functional cortico-cortical and cortico-subcortical connections underlying the expression of ERD during programming of voluntary movement are disrupted by the MS related pathological process. Further, studies are needed to evaluate the role of specific anatomical cortico-subcortical circuits in determining this abnormality. Significance The extent of brain lesion load in multiple sclerosis affects cortical changes related to motor preparation, detected by analysis of onset latency of event-related desynchronization (ERD) of the mu rhythm to self-paced movement.

Quantification of multiple sclerosis lesion load and brain tissue volumetry using multiparameter MRI: methodology and reproducibility

Quantitative characterization of multiple sclerosis (MS) lesion load is of considerable interest to clinical follow-up studies. Based on fuzzy clustering of multiparameter magnetic resonance images, we have developed a computer-assisted system for volumetric quantification of brain tissue. Tests on patient data show that the system is very efficient, and volumetric measurements characterized are highly reproducible. The high reproducibility and efficiency offer the potential of routine laboratory and clinical use for quantification of MS lesion load.

Cardiovascular autonomic dysfunction correlates with brain MRI lesion load in MS

Objective The aim of the present study was to investigate the cardiovascular autonomic control in clinically definite multiple sclerosis (MS) patients with a standardised battery of cardiovascular tests and to correlate these findings with the brain magnetic resonance imaging (MRI) lesion load. Methods Fifty-one patients with MS and 50 healthy controls were studied. Brain MRI was performed in all patients showing typical MS lesions. The cardiovascular tests were carried out using a standardised battery. Results Heart rate (HR) responses to deep breathing ( P<0.05) and tilt table testing ( P<0.001) were significantly decreased in MS patients when compared to those of the controls. Blood pressure (BP) responses in the tilt table test were also impaired in MS patients (diastolic P<0.001, systolic P<0.05). Of the different brain areas investigated the total volume of the midbrain MRI lesions ( P<0.05) was the one most clearly associated with the impaired BP responses. Conclusions MS results in both reduced HR variation and decreased BP reactions indicating disturbed cardiovascular regulation. In particular, the midbrain lesions found in MS are associated with cardiovascular dysfunction.

Cognitive dysfunction in patients with mildly disabling relapsing–remitting multiple sclerosis: an exploratory study with diffusion tensor MR imaging

Previous studies assessing the magnetic resonance imaging (MRI) correlates of cognitive dysfunction in multiple sclerosis (MS) achieved conflicting results. Diffusion tensor (DT)-MRI provides metrics that are sensitive to the macro- and microscopic MS lesion load with increased specificity to the more destructive aspects of MS pathology than conventional imaging. We performed an exploratory study to assess the magnitude of the correlation between quantities derived from DT-MRI and measures of cognitive impairment in patients with relapsing–remitting (RR) MS. T2, T1, DT-MRI scans of the brain and an extensive battery of neuropsychological tests (exploring language, complex reasoning, attention and memory) were obtained from 34 RRMS patients. We measured T2 and T1 lesion volumes (LV) and brain volume. Average lesion mean diffusivity ( D̄) and fractional anisotropy (FA) were calculated. D̄ and FA histograms from the brain tissue (BT), the normal-appearing brain tissue (NABT), the normal-appearing white matter (NAWM) and the normal-appearing gray matter (NAGM) were also obtained. Nine patients (26.5%) were found to be cognitively impaired. Moderate correlations were found between symbol digit modalities test, verbal fluency test and 10/36 spatial recall test scores and T2 LV, T1 LV and average lesion, WBT, NABT, NAWM and NAGM values ( r values ranging from −0.30 to −0.53). No correlations were found between any of the neuropsychological test scores and brain volume, average lesion FA and WBT FA. DT-MRI provides quantitative metrics that seem to reflect the severity of language, attention and memory deficits in patients with RRMS. This study also suggests that the extent and the intrinsic nature of the macroscopic lesions as well as the damage of the NAWM and NAGM all contribute to the neuropsychological deficits of RRMS patients.

A multiparametric MRI study of frontal lobe dementia in multiple sclerosis

Previous studies achieved conflicting results when correlating magnetic resonance imaging (MRI) abnormalities and cognitive impairment in multiple sclerosis (MS) patients. Recently, the estimation of MS lesion load on T1-weighted images and the analysis of magnetization transfer ratio (MTR) histograms, increased the degree of the correlation between physical disability and MRI findings in MS. We assessed the relationship of conventional and non-conventional MRI-derived measures with frontal lobe dementia in MS. Dual echo, T1-weighted and MT MRI scans of the brain were obtained in 11 MS patients with and in 11 without frontal lobe dementia, matched for age, sex, education and disability. Total (TLL) and frontal (FLL) lesion loads were assessed from T2- and T1-weighted scans. MTR histogram analysis was performed for the whole brain, the frontal lobe and the cerebellum. Median TLL and FLL were significantly higher in cognitively impaired patients on both T2- and T1-weighted scans. The MRI measure that better discriminated the two groups of patients was T1-weighted TLL (median values were 19.1 ml for demented and 1.9 ml for non-demented patients, P=0.006). Average MTR, peak height and location of overall brain and frontal lobe histograms were significantly lower for cognitively impaired than for cognitively intact patients (P values ranged from 0.0001 to 0.001). Cerebellar MTR histogram metrics did not significantly differ in patients with and without cognitive decline. The presence of cognitive decline in MS is associated with the extent and pathological severity of brain MRI abnormalities.

Correlating Mr Lesions and Functional Deficits in Multiple Sclerosis Patients: Anatomical Atlas Registration

Although brain magnetic resonance (MR) imaging is increasingly being used as an objective outcome measure in treatment trials for multiple sclerosis (MS), findings correlating conventional MR imaging and disabilities in established MS have been inconsistent. In some studies, measures of MR lesion status, such as numbers of lesions or MS lesion load (volume), have shown limited correlations with clinical scores such as the Kurtzke Expanded disability scale (EDSS). Other studies have shown clear correlations between MR findings and measures of disability in MS. Further development of image processing techniques should help elucidate the relationships between MR findings and disease processes in MS.

Precision and reliability for measurement of change in MRI lesion volume in multiple sclerosis: a comparison of two computer assisted techniques

OBJECTIVEThe serial quantification of MRI lesion load in multiple sclerosis provides an effective tool for monitoring disease progression and this has led to its increasing use as an outcome measure...