Brain MRI correlates of cognitive impairment in primary and secondary progressive multiple sclerosis

doi:10.1016/0022-510X(95)00168-2

Journal of the Neurological Sciences

Volume 132, Issue 2, October 1995, Pages 222-227

https://doi.org/10.1016/0022-510X(95)00168-2 Get rights and content

Abstract

Brain magnetic resonance imaging (MRI) and an extensive battery of neuropsychological tests exploring frontal functions, short and long-term memory, visuo-spatial skills, attention and language were applied to 14 patients with primary progressive multiple sclerosis (PPMS) and 17 patients with secondary progressive MS (SPMS). Patients with PPMS and SPMS did not differ in degree of physical disability, but cognitive deficits were found in $917$ (53%) patients with SPMS and in only $114$ (7%) of those with PPMS (p = 0.01). Patients with SPMS had higher total (p = 0.004), periventricular (p = 0.008) and non-periventricular (p = 0.04) MRI lesion loads than patients with PPMS. In detail, patients with SPMS had greater involvement of frontal (p = 0.05) and occipital (p = 0.02) horns, trigones (p = 0.04), third ventricle (p = 0.03), basal ganglia (p = 0.02), parietal (p = 0.02), temporal (p = 0.004) and occipital (p = 0.03) lobes. Patients with SPMS and neuropsychological deficits had higher non-periventricular lesion loads than patients with SPMS who did not have such deficits (p = 0.005). Our results indicate that both neuropsychological and brain MRI abnormalities are more extensive in patients with SPMS. Since physical disability was similar for both groups, disability in PPMS may be predominantly due to spinal cord involvement.

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Citation Excerpt :
The potential treatment effect on frontal lobe function warrants further discussion. Several studies have described impaired frontal lobe function in multiple sclerosis,22–26 and a recent, large cross-sectional study,25 including 74 patients with SPMS, revealed a heavy burden of executive dysfunction in all progressive multiple sclerosis subtypes. Although Ruano and colleagues25 showed patients with PPMS more frequently had executive dysfunction compared with patients with other subtypes of multiple sclerosis, others have shown frontal lobe capabilities to be affected to a greater extent in SPMS than in PPMS.22–24
In the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures.
We did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov, number NCT00647348.
Baseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6–7·8; p<0·0001) and non-verbal memory (decline of 6·8 points, 4·8–8·7; p<0·0001). At 24 months, the FAB score was 1·2 points higher in the simvastatin-treated group than in the placebo group (95% CI 0·2–2·3). The simvastatin group also had a 2·5 points better mean physical component score of the SF-36 (95% CI 0·3–4·8; p=0·028). A treatment effect was not noted for any other outcomes.
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For the greater part of the past century clinicians have grossly underestimated the relevance of cognitive impairment (CI) in multiple sclerosis (MS) patients, and only over the past decades have they become aware of its prevalence and profound impact on function. The last decade, in particular, has seen a great deal of research addressing some of the key issues in this area: documenting CI in different disease stages and subtypes and its functional impact, also independent of the degree of physical impairment; developing and validating appropriate assessment tools; understanding the mechanisms underlying CI through neuroimaging studies; and addressing the potential for therapeutic interventions. In this chapter, we summarize current understanding of MS-related CI and review available evidence on treatment strategies, based on both pharmacological approaches and cognitive rehabilitation, focusing on the most salient studies in the field.
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It has also been concluded that cognitive impairments may be infrequent in PPMS (Comi et al., 1995; Thompson et al., 1997). Similarly, patients with SPMS have been found to have more frequent and more severe cognitive impairment (Comi et al., 1995; Denney et al., 2005; Huijbregts et al., 2004; Potagas et al., 2008) than patients with PPMS. In contrast to these, also similar cognitive performance in the two types of progressive disease courses has been reported (Foong et al., 2000).
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Research articleBrain MRI correlates of cognitive impairment in primary and secondary progressive multiple sclerosis

Abstract

Abnormalities in the macroscopically normal white matter in cases of mild or spinal multiple sclerosis

Acta. Neuropathol. (Berl.)

Relationship between frontal lobe lesions and Wisconsin Card Sorting Test performance in patients with multiple sclerosis

Neurology

Quantitative multiple sclerosis plaque assessment with magnetic resonance imaging. Its correlation with clinical parameters, evoked potentials and intrablood-brain-barrier IgG synthesis

Arch. Neural.

Cognitive disturbances in patients with relapsing-remitting multiple sclerosis

Arch. Neurol.

A comparison of multimodal evoked potentials, nuclear magnetic resonance imaging and CSF profile for the diagnosis of multiple sclerosis

Correlation between multimodal evoked potentials and magnetic resonance imaging in multiple sclerosis

J. Neurol.

Cognitive function impairment in multiple sclerosis: a 18F-FDG and PET study

Brain magnetic resonance imaging of cognitive impairment in multiple sclerosis

J. Neurol. Sci.

Course and prognosis of multiple sclerosis assessed by computerised data processing of 349 patients

Brain

Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetic transfer imaging

Radiology

Clinically isolated lesions of the type seen in multiple sclerosis: a cognitive, psychiatric and MRI study

J. Neurol. Neurosurg. Psychiat.

A quantitative brain MRI study in benign and secondary progressive multiple sclerosis

J. Neurol.

Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis

Neurology

Correlations between changes in disability and T2-weighted MRI activity in multiple sclerosis: a follow up study

Neurology

Correlation of magnetization transfer ratio with clinical disability in multiple sclerosis

Ann. Neurol.

Neuropsychological findings in relapsing-remitting and chronic-progressive multiple sclerosis

J. Consult. Clin. Psychol.

Spinal cord MRI using multi-array coils and fast spin echo. II. Findings in multiple sclerosis

Neurology

Benign versus chronic progressive multiple sclerosis: magnetic resonance imaging features

Ann. Neurol.

Rating neurological impairment in multiple sclerosis: an expanded disability status scale (EDSS)

Neurology

Research article
Brain MRI correlates of cognitive impairment in primary and secondary progressive multiple sclerosis

Correlations between changes in disability and T₂-weighted MRI activity in multiple sclerosis: a follow up study