Multiple Sclerosis Cognition Abstracts

  1. Frontal Cortex atrophy predicts Cognitive Impairment in Multiple Sclerosis
    J NeuroPsychiatry Clin NeuroSci 2002 Winter;14(1):44-51

  2. Patterns of Cognitive Impairment in Secondary/Progressive stable phase of Multiple Sclerosis: correlations with MRI findings
    Eur Neurol 2001;45(1):11-8

  3. Wisconsin Card Sorting Test performance in patients with focal Frontal and Posterior Brain damage: effects of lesion location and test structure on separable Cognitive processes
    NeuroPsychologia 2000;38(4):388-402

  4. Cortical Cerebral metabolism correlates with MRI lesion load and Cognitive Dysfunction in MS
    Neurology 2000 Feb 8;54(3):558-64

  5. Cognitive dysfunction in Multiple Sclerosis: natural history, pathophysiology and management
    CNS Drugs 2002;16(7):445-55

  6. Ventricular enlargement in MS: one-year change at various stages of disease
    Neurology 2006 Mar 14;66(5):693-8

  7. Disconnection as a mechanism for Cognitive Dysfunction in Multiple Sclerosis
    Brain 2009 Jan;132(Pt 1):239-49


Frontal Cortex Atrophy Predicts Cognitive Impairment In Multiple Sclerosis

Benedict RH, Bakshi R, Simon JH, Priore R, Miller C, Munschauer F
J NeuroPsychiatry Clin NeuroSci 2002 Winter;14(1):44-51
State University of New York at Buffalo School of Medicine, Department of Neurology, Buffalo, USA
PMID# 11884654

The association between regional measures of Cortical Atrophy and NeuroPsychological (NP) dysfunction was studied in 35 Multiple Sclerosis (MS) patients.

Patients underwent Neurological Examination, MRI, and NP testing. Blind quantitative MRI analysis yielded total T2 lesion area (TLA) and Third Ventricle Width (3VW).

Cortical Atrophy, rated by blind visual inspection, was more extensive in Superior Frontal and Parietal Cortices than in other regions.

No MRI measures were correlated with Depression scores. TLA and 3VW were significantly correlated with each NP test.

Cortical Atrophy measures for BiLateral Superior Frontal Cortex were retained in regression models predicting Impairments in Verbal Learning, Spatial Learning, Attention, and Conceptual Reasoning.

The authors conclude that Cerebral Atrophy predicts NP impairment while accounting for the influence of TLA or 3VW.

Regions of Cortex most susceptible to Atrophic and Cognitive changes in MS are the Right and Left Superior Frontal Lobes.


Patterns Of Cognitive Impairment In Secondary/Progressive Stable Phase Of Multiple Sclerosis: Correlations With MRI Findings

Nocentini U, Rossini PM, Carlesimo GA, Graceffa A, Grasso MG, Lupoi D, Oliveri M, Orlacchio A, Pozzilli C, Rizzato B, Caltagirone C
Eur Neurol 2001;45(1):11-8
IRCCS S. Lucia, Rome, Italy
PMID# 11150835

Cognitive Impairment is commonly described in Multiple Sclerosis (MS), but conflicting results have been reported about its pattern by previous studies focused on heterogeneous patient groups.

The aim of this study was to investigate the Cognitive skills of a homogeneous group of Secondary/Progressive MS patients, and to examine the relationship of this Impairment to MRI parameters.

Forty-four MS patients underwent a series of NeuroPsychological tests devised to explore the main Cognitive domains, and T1- and T2-weighted Brain MRI.

Results showed the presence of deficits of Attention, Memory, Planning Abilities, Problem-Solving and Conceptual Reasoning (Frontal Functions) in a subgroup of MS patients.

Correlations between the performance in some 'Frontal' tests and the extent of Frontal Lobe MRI lesional area were present, but rather unspecific, the same performance being also correlated with the NonFrontal lesional area.

These findings suggest that in MS, overall macroscopic and microscopic Brain damage is more important than the corresponding focal Brain disease, even in determining deficits of selective Cognitive Domains.

Copyright 2001 S. Karger AG, Basel


Wisconsin Card Sorting Test Performance In Patients With Focal Frontal And Posterior Brain Damage: Effects Of Lesion Location And Test Structure On Separable Cognitive Processes

Stuss DT, Levine B, Alexander MP, Hong J, Palumbo C, Hamer L, Murphy KJ, Izukawa D
NeuroPsychologia 2000;38(4):388-402
University of Toronto, Rotman Research Institute, Baycrest Centre for Geriatric Care, 3560 Bathurst Street, Toronto, Canada
PMID# 10683390

Forty-six patients with single focal lesions (35 Frontal, 11 NonFrontal) were administered the Wisconsin Card Sorting Test (WCST) under three conditions of test administration.

The three conditions varied in the amount of external support provided via specificity of instructions.

The WCST, while a multifactorial test, is specifically sensitive to the effects of Frontal Lobe damage if deficits in Language Comprehension and Visual-Spatial search are controlled.

There is also specificity of functioning within the Frontal Lobes: patients with Inferior Medial Frontal lesions, unilateral or bilateral, were not impaired on the standard measures.

Although they had increased Loss Of Set when informed of the sorting categories.

Verbal instructions may provide a probe to improve diagnosis and prognosis, assessment of the potential efficacy of treatment, and the time frame of plasticity of specific Cognitive Operations.


Cortical Cerebral Metabolism Correlates With MRI Lesion Load And Cognitive Dysfunction In MS

Blinkenberg M, Rune K, Jensen CV, Ravnborg M, Kyllingsbaek S, Holm S, Paulson OB, Sorensen PS
Neurology 2000 Feb 8;54(3):558-64
Copenhagen University Hospital, MS Research Unit, Denmark
PMID# 10680783

To study the association between the Cortical Cerebral metabolic rate of Glucose (CMRglc), MRI T2-weighted total lesion area (TLA), Cognitive Dysfunction, and Neurologic disability in MS.

MRI lesion load is widely used in the clinical evaluation of the MS patient but little is known about the associated changes in Cortical activation.

Twenty-three patients with Clinically Definite MS underwent measurements of CMRglc, TLA, Motor Evoked Potentials (MEPs), and Cognitive and Neurologic disability.

CMRglc was calculated using PET and 18-F-DeoxyGlucose and compared with nine normal control subjects.

Reductions in CMRglc (p < 0.01) were found in the Cortical global and regional Lobar measurements.

Furthermore, regional CMRglc (rCMRglc) was reduced in the DorsoLateral PreFrontal Cortex, OrbitoFrontal Cortex, Caudate, Putamen, Thalamus, and Hippocampus.

Global Cortical CMRglc correlated with TLA (Spearman rank correlation coefficient [SRCC] = -0.66, p = 0.001), and rCMRglc correlated with Regional Lesion Load in all Cerebral Lobes (p < or = 0.05).

Global Cortical CMRglc and Cognitive disability also correlated (SRCC = 0.58, p = 0.015), and stepwise regression analysis showed a significant association between rCMRglc of the Right Thalamus and Cognitive performance as well as TLA.

There was no correlation between CMRglc and Neurologic disability (Expanded Disability Status Scale) or MEP.

Global and regional Cortical CMRglc is reduced significantly in MS patients compared with normal control subjects.

Furthermore, the CMRglc reductions correlate with TLA as well as with Cognitive Dysfunction, which indicates that MRI White Matter lesion burden has a deteriorating effect on Cortical Cerebral Neural function.


Cognitive Dysfunction In Multiple Sclerosis: Natural History, PathoPhysiology And Management

Bagert B, Camplair P, Bourdette D
CNS Drugs 2002;16(7):445-55
Research and Neurology Services, Department of Veterans Affairs Medical Center, Portland, Oregon, USA
PMID# 12056920

Cognitive Dysfunction is a major cause of disability in patients with Multiple Sclerosis (MS). The prevalence of Cognitive Dysfunction is estimated at 45 to 65%.

Natural history studies suggest that once Cognitive Dysfunction develops in a patient with MS, it is not likely to remit.

Unlike physical disability in MS, Cognitive disability correlates weakly with T2 lesion burden on Brain Magnetic Resonance Imaging (MRI).

More robust correlations exist with Magnetization Transfer imaging and MRI measures of Brain Atrophy.

Patients with MS who have Cognitive Impairment most commonly display deficits in the Cognitive domains of Memory, Learning, Attention and Information Processing.

In diagnosing Cognitive Dysfunction in a patient with MS, it is important first to recognize and treat the common comorbidities of Fatigue and Depression.

The first step in the treatment of Cognitive Dysfunction is to delay disease progression.

And, there are currently five such disease-modifying agents approved for the treatment of MS (two preparations of Interferon-beta-1a, Interferon-beta-1b, Glatiramer Acetate and Mitoxantrone).

NonPharmacological measures, such as Cognitive Rehabilitation, Occupational Therapy and PsychoTherapy, are the mainstays of symptomatic treatment.

Pharmacological symptomatic therapy centres on the treatment of comorbid Fatigue and Depression. There are currently no effective pharmacological agents approved as symptomatic therapy of Cognitive Dysfunction in MS.


Ventricular Enlargement In MS: One-Year Change At Various Stages Of Disease

Dalton CM, Miszkiel KA, O'Connor PW, Plant GT, Rice GP, Miller DH
Neurology 2006 Mar 14;66(5):693-8
Institute of Neurology, London, UK
PMID# 16534105

To investigate Ventricular Enlargement (VE) over 1 year at three different stages of Multiple Sclerosis (MS).

A semi-automated technique for measuring VE was applied to MRI scans in 26 patients with Clinically Isolated Syndromes (CIS) suggestive of MS, 30 with early relapse-onset MS of 1 year duration, 41 with established Relapsing/Remitting (RR) MS, and 23 with Secondary/Progressive (SP) MS.

VE at 1 year was seen in early MS (median increase 0.3 mL [p = 0.003]), RRMS (median increase 0.5 mL [p = 0.001]), and SPMS (median increase 1.1 mL [p = 0.001]).

Allowing for age there was more VE in the SPMS group (p = 0.005). No VE was observed in the CIS only group (median decrease -0.001 mL [p = 0.829]).

Significant increases in T2 and T1 HypoIntense lesion load volume were seen in all MS subgroups: there were no differences between the groups in T2 volume increase but there was a larger increase in T1 HypoIntense lesion volume in the SPMS group compared with early RRMS.

Ventricular Enlargement is a sensitive measure of progressive Cerebral Atrophy that is seen at all stages of Multiple Sclerosis (MS) and is more marked in Secondary/Progressive than Relapsing/Remitting MS.


Disconnection As A Mechanism For Cognitive Dysfunction In Multiple Sclerosis

Dineen RA, Vilisaar J, Hlinka J, Bradshaw CM, Morgan PS, Constantinescu CS, Auer DP
Brain 2009 Jan;132(Pt 1):239-49
University of Nottingham, Queen's Medical Centre, Department of Academic Radiology, Nottingham, UK
PMID# 18953055

Disconnection of Cognitively important processing regions by injury to the interconnecting White Matter provides a potential mechanism for Cognitive Dysfunction in Multiple Sclerosis.

The contribution of tract-specific White Matter injury to dysfunction in different Cognitive Domains in patients with Multiple Sclerosis has not previously been studied.

We apply Tract-Based Spatial Statistics (TBSS) to Diffusion Tensor Imaging (DTI) in a cohort of Multiple Sclerosis patients to identify loci where reduced White Matter Tract Fractional Anisotropy (FA) predicts impaired performance in Cognitive testing.

Thirty-seven Multiple Sclerosis patients in remission (median age 43.5 years; Expanded Disability Status Scale range 1.5-6.5; 35 Relapsing/Remitting, two Secondary/Progressive) underwent 3T MRI including high-resolution DTI.

Multiple Sclerosis patients underwent formal testing of performance in multiple Cognitive Domains.

Normalized Cognitive scores were used for voxel-wise statistical analysis using TBSS, while treating age as a covariate of no interest.

Permutation-based inference on cluster size (t > 2, P < 0.05 corrected) was used to correct for multiple comparisons.

Statistical mapping revealed differential patterns of FA reduction for tests of Sustained Attention, Working Memory and Processing Speed, Visual Working Memory and Verbal Learning and Recall.

FA was not associated with Frontal Lobe function or VisuoSpatial perception.

Cognitively relevant tract localizations only partially overlapped with areas of high FLAIR lesion probability, confirming the contribution of Normal-Appearing White Matter abnormality to Cognitive Dysfunction.

Of note, tract localizations showing significant associations with Cognitive Impairment were found to interconnect Cortical regions thought to be involved in processing in these Cognitive Domains, or involve possible compensatory processing pathways.

This suggests that TBSS reveals functionally relevant tract injury underlying Cognitive Dysfunction in patients with Multiple Sclerosis.

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