To examine neurological and magnetic resonance imaging (MRI) changes following discontinuation of interferon (IFN)-beta-1a treatment in secondary progressive multiple sclerosis (SPMS).The study involved 21 SPMS patients who received subcutaneous (s.c.) IFN-beta-1a 44 microg three times weekly (t.i.w.) for 12 months and were thereafter followed up without treatment for a further 12 months. The number of relapses, disability on the Expanded Disability Status Scale (EDSS) and MRI were recorded at baseline, at 12 months of IFN-beta-1a 44 microg t.i.w. and 1 year after discontinuation of treatment.During the 12-month treatment EDSS score and volumes of brain T2- and T1-weighted lesions remained without significant progression, but at 12 months after treatment discontinuation both EDSS score and the volumes of cerebral lesions increased significantly. Cerebrospinal fluid fraction increased significantly both during the treatment and during follow-up.Discontinuation of IFN-beta-1a 44 microg t.i.w. in SPMS may be associated with an increase in neurological disability and brain lesions on MRI.
To study the effect of weekly injected subcutaneous interferon (IFN)-beta-1a 22 microg on the extent of brain lesions on magnetic resonance imaging (MRI) and the level of serum matrix metalloproteinase (MMP)-9 in patients with secondary progressive multiple sclerosis (SPMS).All the 28 Finnish patients participating in the Nordic multicentre trial on the clinical efficacy of weekly IFN-beta-1a (Rebif) 22 microg in SPMS were studied neurologically and by volumetric MRI during a 3-year follow-up. The levels of MMP-9 in serum were measured over the 3-year study.There was no obvious effect on the number of contrast medium-enhancing lesions, the volume of T1 or T2 lesions or level of serum MMP-9, nor was any effect detected on the relapse rate and the Expanded Disability Status Scale (EDSS). Brain atrophy progression was not affected by the treatment.The lack of effect on MRI, clinical outcomes or the levels of MMP-9 indicates that subcutaneous administration of low-dose low-frequency IFN-beta-1a is insufficient in controlling either the inflammatory constitutes or the neurodegenerative changes of advanced SPMS.
In primary progressive multiple sclerosis (PPMS) abnormalities in brain magnetic resonance imaging (MRI) differ from abnormalities in other subtypes of multiple sclerosis (MS). It was investigated whether the extent of brain and spinal cord MRI abnormalities is reflected in the neurological disability in PPMS. Focal and diffuse changes and atrophy in central nervous system (CNS) in patients with PPMS ( n = 28) and healthy controls ( n = 20) were assessed by semi‐automatic MRI segmentation and volumetric analysis. The measurements were related to neurological disability as expressed by the expanded disability status scale (EDSS), the regional functional scoring system (RFSS), the arm index and the ambulation index. Plaques in T1‐ and/or T2‐weighted images were seen in all brains, while spinal plaques were detected in 23 of 28 patients (82%). The total volumes of brain and spinal cord were significantly smaller in patients than in controls ( P = 0.001 and 0.000, respectively). The volumes of T1 or T2 lesions in the brain correlated to the ambulation index ( r = 0.51, P = 0.005 and r = 0.53, P = 0.004, respectively). No correlations were detected between MRI measurements and total EDSS score, but relative brain atrophy correlated inversely with the total RFSS scores, poor arm index and higher cerebral disturbances ( r = −0.53, P = 0.004; r = −0.53, P = 0.004; and r = −0.52, P = 0.005, respectively). Although the number of spinal T2 lesions correlated with sensory disturbances ( r = 0.60, P = 0.001), no correlations were found between EDSS subscores and spinal cord atrophy. These findings show that marked atrophy of brain and spinal cord detected by volumetric quantitation correlates with neurological disability. This observation indicates the importance of neurodegenerative events in PPMS.
Functional polymorphisms of the genes for interleukin-10 (IL-10; promoter position −1082), chemokine receptor-5 (CCR5 32 bp deletion), tumor necrous factor-α (TNFα promoter position −308) and cytotoxic T-lymphocyte antigen-4 (CTLA-4 exon 1 position 49) were investigated for possible influence on susceptibility and outcome of multiple sclerosis (MS). The polymorphisms were typed by polymerase chain reaction based methods or by direct sequencing in MS patients (n = 93–116) and controls (n = 109–400). The studied genes were not associated with MS susceptibility. Patients were classified as suffering from a mild/moderate [Expanded Disability Status Scale (EDSS) 0–5.5] or severe (EDSS 6–8.0) form of MS. The AG genotype of IL-10 proved to be protective against severe MS in all patients (OR = 0.32, P = 0.010), the effect being increased over the years (10 years; OR = 0.33, P = 0.043, 15 years; OR = 0.21, P = 0.025 or 20 years; OR = 0.14, P = 0.026). Our results suggest that differential production of IL-10 might be a factor in the severity of MS.
Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice.To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients.In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files.Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented.SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.
The DRB1/3/4/5 loci from 97 patients with MS and 100 normal control subjects were analyzed. DRB1*15 increased the risk of MS (OR = 4.2, p < 0.0001), whereas DR1 decreased the risk (OR = 0.30, pc = 0.005). In analyses of the DR1 risk in relation to DR51, DR52, and DR53 alleles, DR1 in combination with DR53 was found to have the strongest protective effect against MS in all subjects (OR = 0.05, p < 0.0001) and in DRB1*15-negative subjects (OR = 0.09, pc = 0.026). DR53 may be an important allele or haplotype, acting together with DR1 to protect against MS.
