Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort.
Department of Neurology, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. Journal of Neurology
(Impact Factor: 3.38).
A study of cognitive, psychological and social aspects in benign multiple sclerosis (MS). Methods One hundred and sixty three patients with benign MS (defined as disease duration > or = 15 years and Expanded Disability Status Scale (EDSS) score < or = 3.0 ) underwent neuropsychological testing on the Rao's Brief Repeatable Battery (BRB) and the Stroop test, evaluation of depression on the Montgomery and Asberg Depression Rating Scale (MADRS), of fatigue on the Fatigue Severity Scale (FSS) and of handicap on the Environmental Status Scale (ESS). Patients' cognitive performance was compared with that of 111 demographically matched healthy controls. Cognitive impairment was defined as the failure in at least 3 tests, using the fifth percentile of controls' performance as the cut-off point. Clinical correlates of cognitive impairment were determined by multiple logistic regression analysis.
Cognitive assessment led to the identification of 74 subjects (45%) with cognitive impairment. Significant fatigue was found in 80 subjects (49%) and depression in 88 patients (54%). In comparison with cognitively preserved subjects, cognitively impaired patients exhibited higher handicap scores on the ESS (p = 0.005). In the regression analysis, only EDSS scores were significantly associated with cognitive impairment (OR 1.8, 95%CI 1.2-2.6).
Current definitions of benign MS may overestimate this entity, since they are mainly weighted for the patients' motor abilities and fail to capture relevant disease-related cognitive, psychological and social problems.
Available from: Mara Cercignani
- "In particular, failure of a test was defined when the score was at least two standard deviations (SDs) below the mean normative values. Consistently with previous works , , those patients who failed at least three tests were considered CI (cognitive impaired), and those who failed less than three tests were considered CP (cognitive preserved). A grading system was applied to each patient's score on each cognitive test, dependent on the number of SDs below the normative mean (0: patient scored at or above normative mean; 1: patient scored ≤1 SD below normative mean; 2: patient scored >1 SD, but ≤2 SD below normative mean, etc.). "
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ABSTRACT: Genetic ablation of type-1 cannabinoid receptors (CB1Rs) exacerbates the neurodegenerative damage of experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS). To address the role on CB1Rs in the pathophysiology of human MS, we first investigated the impact of AAT trinucleotide short tandem repeat polymorphism of CNR1 gene on CB1R cell expression, and secondly on the inflammatory neurodegeneration process responsible for irreversible disability in MS patients. We found that MS patients with long AAT repeats within the CNR1 gene (≥12 in both alleles) had more pronounced neuronal degeneration in response to inflammatory white matter damage both in the optic nerve and in the cortex. Optical Coherence Tomography (OCT), in fact, showed more severe alterations of the retinal nerve fiber layer (RNFL) thickness and of the macular volume (MV) after an episode of optic neuritis in MS patients carrying the long AAT genotype of CNR1. MS patients with long AAT repeats also had magnetic resonance imaging (MRI) evidence of increased gray matter damage in response to inflammatory lesions of the white matter, especially in areas with a major role in cognition. In parallel, visual abilities evaluated at the low contrast acuity test, and cognitive performances were negatively influenced by the long AAT CNR1 genotype in our sample of MS patients. Our results demonstrate the biological relevance of the (AAT)n CNR1 repeats in the inflammatory neurodegenerative damage of MS.
Available from: Maria Petracca
- "Recent studies have reported that about 45% of patients fulfilling classical criteria for BMS (disease duration ≥ 15 years, expanded disability status scale (EDSS) score ≤ 3.0)  are affected by significant cognitive impairment and have proposed that cognitive preservation should be an additional criteria to define BMS . Although often underestimated in patients with BMS, fatigue is a very common symptom occurring at a frequency comparable to that reported in other forms of MS . Neither commonly used clinical scales such as the EDSS  nor conventional magnetic resonance imaging (MRI) metrics such as T2-weighted lesion volume (T2LV) shows a strong correlation with cognitive impairment and fatigue . "
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ABSTRACT: BACKGROUND: Although benign multiple sclerosis (BMS) is traditionally defined by the presence of mild motor involvement decades after disease onset, symptoms of fatigue and cognitive impairment are very common. OBJECTIVE: To investigate the association between micro-structural damage in the anterior thalamic (AT) tracts and in the corpus callosum (CC), as measured by diffusion tensor imaging (DTI) tractography, and fatigue and cognitive deficits. METHODS: DTI data were acquired from 26 BMS patients and 24 sex- and age-matched healthy controls. RESULTS: General and mental fatigue scores were significantly impaired in patients compared with controls (p≤0.05 for both) and 38% of patients resulted cognitively impaired. Mean diffusivity (MD) of the AT and CC tracts was significantly higher and fractional anisotropy (FA) was lower in patients compared with controls (p<0.001 for all). Fatigue was associated with increased MD (p=0.01) of the AT tracts whereas deficit of executive functions and verbal learning were associated with decreased FA in the body (p=0.004) and genu (p=0.008) of the CC. Deficits in processing speed and attention were associated with the T2 lesion volume of the AT tracts (p<0.01 for all). DISCUSSION: These findings suggest that fatigue and cognitive impairment are quite frequent in BMS patients and are, at least in part, related to micro-structural damage and T2LV of WM tracts connecting the brain cortical and sub-cortical regions of the two hemispheres.
Available from: Elena Colicino
- "Recently, the diagnostic criteria for BMS have been redefined as an EDSS score ≤ 2.0 after a disease duration of at least 10 years
. However, the debate has been reopened by recent reports which state that cognitive impairment was detected in 45% of a large group of patients fulfilling traditional criteria for BMS
, but also by the suggestion that neuropsychological tests can contribute to a more accurate identification of “true” BMS
[23,27-29]. In this study we provide evidence that the EP score may be an interesting covariate for the definition of BMS. "
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The prognostic value of evoked potentials (EPs) in multiple sclerosis (MS) has not been fully established. The correlations between the Expanded Disability Status Scale (EDSS) at First Neurological Evaluation (FNE) and the duration of the disease, as well as between EDSS and EPs, have influenced the outcome of most previous studies. To overcome this confounding relations, we propose to test the prognostic value of EPs within an appropriate patient population which should be based on patients with low EDSS at FNE and short disease duration.
We retrospectively selected a sample of 143 early relapsing remitting MS (RRMS) patients with an EDSS < 3.5 from a larger database spanning 20 years. By means of bivariate logistic regressions, the best predictors of worsening were selected among several demographic and clinical variables. The best multivariate logistic model was statistically validated and prospectively applied to 50 patients examined during 2009–2011.
The Evoked Potentials score (EP score) and the Time to EDSS 2.0 (TT2) were the best predictors of worsening in our sample (Odds Ratio 1.10 and 0.82 respectively, p=0.001). Low EP score (below 15–20 points), short TT2 (lower than 3–5 years) and their interaction resulted to be the most useful for the identification of worsening patterns. Moreover, in patients with an EP score at FNE below 6 points and a TT2 greater than 3 years the probability of worsening was 10% after 4–5 years and rapidly decreased thereafter.
In an appropriate population of early RRMS patients, the EP score at FNE is a good predictor of disability at low values as well as in combination with a rapid buildup of disability. Interestingly, an EP score at FNE under the median together with a clinical stability lasting more than 3 years turned out to be a protective pattern. This finding may contribute to an early identification of benign patients, well before the term required to diagnose Benign MS (BMS).
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