Asymptomatic spinal cord lesions do not predict the time to disability in patients with early multiple sclerosis

BACKGROUND: The presence of asymptomatic spinal cord (SC) lesions in patients with clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS) predicts conversion to clinically definite multiple sclerosis (CDMS). The relation between asymptomatic SC abnormalities and disability progression warrants further investigation. OBJECTIVE: To determine the prognostic value of asymptomatic SC lesions in CIS and early RRMS with respect to the time to disability development. METHODS: Clinical and demographic data, brain and SC magnetic resonance imaging (MRI) were collected of CIS or early RRMS patients. Two main analyses were performed. For the first analysis, patients were divided into two groups: (1) patients with asymptomatic SC lesions and (2) patients without SC lesions and patients with symptomatic SC lesions. The second analysis excluded patients with symptomatic SC lesions. Incidence curves were used to analyse differences between these groups in time to the development of disability and time to a second relapse. RESULTS: A total of 178 patients were included, and 42 patients (23.6%) had asymptomatic SC lesions. No significant differences were found on the time to disability development or the time to a second event. CONCLUSION: Asymptomatic SC lesions early in the disease course do not predict the time to disability development in patients diagnosed with CIS or early RRMS

Infratentorial and spinal cord lesions: Cumulative predictors of long-term disability?

OBJECTIVE: The objective of the study was to determine whether early infratentorial and/or spinal cord lesions are long-term cumulative predictors of disability progression in multiple sclerosis (MS). // METHODS: We selected 153 MS patients from the longitudinal Amsterdam MS cohort. Lesion analysis was performed at baseline and year 2. Disability progression after 6 and 11 years was measured using the Expanded Disability Status Scale (EDSS) and EDSS-plus (including 25-foot walk and 9-hole peg test). Patients with spinal cord or infratentorial lesions were compared for the risk of 6- and 11-year disability progression to patients without spinal cord or infratentorial lesions, respectively. Subsequently, patients with lesions on both locations were compared to patients with only spinal cord or only infratentorial lesions. // RESULTS: Baseline spinal cord lesions show a higher risk of 6-year EDSS progression (odds ratio (OR): 3.6, p = 0.007) and EDSS-plus progression (OR: 2.5, p = 0.028) and 11-year EDSS progression (OR: 2.8, p = 0.047). Patients with both infratentorial and spinal cord lesions did not have a higher risk of 6-year disability progression than patients with only infratentorial or only spinal cord lesions. // CONCLUSION: The presence of early spinal cord lesions seems to be a dominant risk factor of disability progression. Simultaneous presence of early infratentorial and spinal cord lesions did not undisputedly predict disability progression

Relationship between brain MRI lesion load and short-term disease evolution in non-disabling MS: a large-scale, multicentre study.

none17ROVARIS M; ROCCA MA; BARKHOF F; CALABRESE M; DE STEFANO N; KHALIL M; FAZEKAS F; FISNIKU L; GALLO P; MILLER DH; MONTALBAN X; POLMAN C; ROVIRA A; SOMBEKKE MH; M. SORMANI; STROMILLO ML; FILIPPI MRovaris, M; Rocca, Ma; Barkhof, F; Calabrese, M; DE STEFANO, N; Khalil, M; Fazekas, F; Fisniku, L; Gallo, P; Miller, Dh; Montalban, X; Polman, C; Rovira, A; Sombekke, Mh; Sormani, MARIA PIA; Stromillo, Ml; Filippi, M

Relationship between brain MRI lesion load and short-term disease evolution in non-disabling MS: A large-scale, multicentre study

BACKGROUND AND OBJECTIVES: We evaluated clinical and conventional MRI features of a large population of patients with non-disabling MS to identify potential markers of a benign disease course. METHODS: In seven MAGNIMS centres we retrospectively identified 182 patients with benign (B) MS (EDSS score ≤ 3.0, disease duration ≥ 15 years) and 187 patients with non-disabling relapsing-remitting MS (NDRRMS) (Expanded Disability Status Scale score ≤ 3.0, disease duration between 5 and 14 years), in whom clinical data were collected within two weeks from a brain T2-weighted scan. Brain T2 lesion volume (LV) was measured in all patients. In 146 BMS and 146 NDRRMS patients, clinical data were also available after a median follow up of 29 months (range: 7-104 months). RESULTS: Mean LV was higher in BMS than in NDRRMS patients (p<0.001), but the mean ratio between LV and disease duration was higher in NDRRMS than in BMS patients (1.1 vs. 0.6 ml/year, p<0.001). In BMS patients, brain LV was correlated with EDSS score increase at follow up (r=0.18, p=0.03). CONCLUSIONS: An overall low rate of brain LV increase during a long-lasting disease course might be a feature of BMS. In BMS patients, a high brain LV might be associated with worsening of locomotor disability at short-term follow u

Analysis of multiple candidate genes in association with phenotypes of multiple sclerosis

Multiple sclerosis is a heterogeneous neurological disease with varying degrees of severity. The common hypothesis is that susceptibility to multiple sclerosis and its phenotype are caused by a combination of environmental and genetic factors. The genetic part exerts its effect through several genes, each having modest effects. We evaluated whether disease severity could be predicted by a model based on clinical data and data from a DNA chip. The DNA chip was designed containing several single nucleotide polymorphisms in 44 genes, previously described to be associated with multiple sclerosis. A total of 605 patients with multiple sclerosis were included in this analysis, using gender, onset type and age at onset as clinical covariates. We correlated 80 single nucleotide polymorphisms to the degree of disease severity using the following three outcome measures: linear Multiple Sclerosis Severity Score, dichotomous Multiple Sclerosis Severity Score (using a cut-off point of 2.5) and time to reach Expanded Disability Status Scale score 6. Sixty-nine single nucleotide polymorphisms were included in the analysis. No individual single nucleotide polymorphism showed a significant association; however, a combination of single nucleotide polymorphisms significantly improved the prediction of disease severity in addition to the clinical variables. In all three models the Interleukin 2 gene was included, confirming a previously reported modest effect on disease severity. The highest power was obtained using the dichotomized Multiple Sclerosis Severity Score as outcome. Several single nucleotide polymorphisms showed their added predictive value over the clinical data in the predictive models. These results support our hypothesis that disease severity is determined by clinical variables and genetic influences (through several genes with small effects) in concert. © The Author(s) 2010