MRI evolution of new MS lesions enhancing after different doses of gadolinium

Objective - To investigate the evolution of multiple sclerosis (MS) lesions enhancing after single dose (SD) or triple dose (TD) of gadolinium-DTPA (Gd). Material and methods - For 3 months, 30 relapsing-remitting MS patients underwent 2 monthly MRI sessions, consisting of Gd-enhanced T₁weighted scans, after SD (i.e., 0.1 mmol/kg) in one session and TD (i.e., 0.3 mmol/kg) in the other. New enhancing lesions on month 1 and month 2 follow-up scans were studied and for them any persistence of enhancement was evaluated on the scans obtained the next month. Results - In all, 151 lesions enhancing after both SD and TD and 91 lesions enhancing only after TD entered the analysis. After 1 month, for the 151 lesions enhancing after both SD and TD, 73 (48%) were not enhancing, 50 (33%) were still enhancing after both SD and TD and 28 (19%) were enhancing only after TD. For the 91 lesions enhancing only after TD, 61 (67%; P <0.005) were not enhancing, 16 (18%; P <0.01) were still enhancing only after TD and 14 (15%; P =NS) showed enhancement after both SD and TD. Conclusion -Enhancing lesions in patients with MS are heterogeneous. Those enhancing only after TD of Gd are characterized by a milder and shorter opening of the blood-brain barrier.     

Long-term follow-up of MS: disease activity detected clinically and by MRI

Prospective clinical and magnetic resonance imaging (MRI) studies were performed over a period of 2-3 years on 51 MS patients. Comparing cerebral MRI and neurological evaluation for sensitivity in detecting disease activity, follow-up MRI turned out to be superior to standardized clinical assessment. In particular, an interval during which the clinical findings remain stable may not necessarily indicate that there is no florid inflammatory activity during this time. The morphological progression demonstrated a preference towards periventricular localization around the posterior horns of the lateral ventricles, and non-periventricularly in the frontal white matter. Longitudinal MRI studies of the disease activity can be an aid in obtaining a more definite diagnosis. Patients having had the disease for a longer period showed a more rapid clinical and morphological progression. Clinical progression and an increase in periventricular involvement were observed more often in the primary unremitting-progressive form of MS than in the relapsing-remitting form.     

Structural and functional MRI correlates of Stroop control in benign MS

The objective of this study was to assess the functional and structural substrates of cognitive network changes in patients with benign multiple sclerosis (BMS), using an analysis of effective connectivity and MR tractography. Using a 3-Tesla scanner, we acquired dual-echo, diffusion tensor (DT) and functional MRI during the performance of the Stroop task from 15 BMS patients and 19 healthy controls. DT MRI tractography was used to calculate DT derived metrics from several white matter (WM) fiber bundles, thought to be involved in cognitive performance. DT MRI metrics from WM fiber bundles not directly related with cognitive performance were also derived. Effective connectivity analysis was performed using statistical parametric mapping. MS patients had significantly abnormal DT MRI metrics in all the structures analyzed. Compared with controls, MS patients had more significant activations of several areas of the cognitive network involved in Stroop performance, bilaterally. Compared with controls, BMS patients also had increased connectivity strengths between several cortical areas of the sensorimotor network and the right (R) inferior frontal gyrus and the R cerebellum, as well as decreased connectivity strengths with the anterior cingulate cortex. Coefficients of altered connectivity were moderately correlated with structural MRI metrics of tissue damage within intra- and inter-hemispheric cognitive-related WM fiber bundles, while no correlations were found with the remaining fiber bundles studied, suggesting that functional cortical changes in patients with BMS might represent an adaptive response driven by damage of specific WM structures.     

Impact of magnetic resonance imaging (MRI) on the epidemiology of MS

The availability of MRI has turned out to have less impact on the epidemiology of MS than originally expected. Only 3/69 patients diagnosed between 1986 and 1990 in the epidemiologic area of South Lower Saxony (Germany) would have been missed without MRI. However in 18/50 patients the diagnostic classification changed, mostly from possible to probable MS. As we included possible cases from the beginning of our studies, the overall figures remain essentially unchanged. Epidemiologists who excluded possible cases from their surveys may experience more problems with the introduction of MRI.     

Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis

OBJECTIVES: The present study was planned to investigate the relationship between the plasma lipid profile and disease activity in patients with a first clinical episode suggestive of multiple sclerosis (MS). MATERIAL AND METHODS: Eighteen consecutive out-patients underwent a monthly brain magnetic resonance imaging (MRI), blood sample and neurological assessment over 6 months. Blood samples were used to evaluate total cholesterol and triglyceride levels as well as their lipoprotein fractions. Plasma total apolipoprotein E concentration was also determined. RESULTS: We found a significant correlation between the mean number of enhancing lesions and the mean plasma level of both total and low density lipoprotein cholesterol. The total plasma cholesterol level increased on average by 4.4 mg/dl for each enhancing lesion. CONCLUSION: Our preliminary data suggest a potential role of plasma cholesterol level as a biological marker of disease activity after a first demyelinating event. Further studies need, however, to be designed to determine whether the plasma cholesterol level is of practical use in monitoring the disease course.     

Depressive symptoms and MRI changes in multiple sclerosis

To determine whether changes in specific regions of the brain can contribute to the development of depression in patients with multiple sclerosis (MS). We prospectively studied 90 patients with clinically definite MS. Disability, independence, cognitive performances, and depressive and anxiety symptoms have been assessed at baseline and 2 years later. At these two time-points, patients underwent a 1.5-T magnetic resonance examination of the brain including T1- and T2-weighted images. Calculation of regional and total lesion loads (LL) have been performed by a semiautomatic technique; total and regional brain volumes have been calculated by a fully automatic highly reproducible computerized interactive program. Measurements of LL did not show any significant difference between depressed and non-depressed patients. Brain atrophy was significantly more conspicuous in the left frontal lobe (P=0.039), in both frontal lobes (P=0.046) and showed a trend towards a difference in the right frontal lobe (P=0.056), in the right temporal lobe (P=0.057) and in both temporal lobes (P=0.072) of depressed patients. Disability, independence and cognitive performances were similar in depressed and non-depressed patients (P=NS). Spearman correlation analysis and multiple-regression analysis demonstrated that the severity of the depressive symptoms score was associated both with the disability score and the right temporal brain volume. Destructive lesions in the right temporal lobe can contribute to the severity of depression in patients with MS but the influence of the severity of neurological impairment should be taken into account.     

Correlation between magnetic resonance imaging and clinical parameters in multiple sclerosis

In this study, the course of 60 consecutive multiple sclerosis patients (relapsing-remitting (RR), relapsing-progressive (RP), primary-progressive (PP)) was compared with the number and mean size of the lesions as well as the total load of the lesions as shown on magnetic resonance imaging (MRI). Significant differences were found between RR and RP patients in total load and number of lesions. Between RR and PP patients statistical significant differences were found in total load, number and size of the lesions when correlated with EDSS. Between RP and PP patients statistical differences were found in total load and size of the lesions on MRI. Patients with a relapsing course of the MS (RR or RP) had a higher total load and size of the lesions than PP patients. The total load, number and size of the lesions corrected for EDSS were also lower compared to relapsing patients. Factor analysis showed a correlation between clinical progression rate and progression rate of MRI abnormalities. No correlation between EDSS and total load of MRI lesions could be found. In conclusion, this study confirms the results of previous studies of differences between MRI scans of patients with a different course of MS.     

Staging of multiple sclerosis (MS) lesions: pathology of the time frame of MS

Several processes take place during an attack of demyelination in multiple sclerosis (MS). The timing of these various processes, and thus of the attack in its entirety, is important if therapeutic stratagies are to be planned. Attempts have been made to introduce and investigate variables relevant to timing the disease processes, leading to staging systems for MS. Here, the terminology and the various parameters used are reviewed, including inflammatory cells, glial cells, axonal loss and myelin staining; then the different systems are compared, including the system put forward by Bö and Trapp, our own modification of that, the Brück and Lassmann system and the recent consensus reached at a Vienna meeting. It is concluded that an ideal staging system does not yet exist, and that, more than anything else, the material dictates the choice for a staging system. The terminology of the Vienna consensus could be used as a reference to facilitate international comparison.     

Myelopathy of unknown etiology A clinical follow-up and MRI study of 57 cases

After a careful differential diagnosis of 264 consecutive cases of spinal cord syndrome seen over a period of 10 years, no diagnosis was reached in 72 patients. Of these cases, known as myelopathy of unknown etiology (MUE), 57 were followed-up for a mean of 2.33 years, 50 being chronic cases and 7 acute cases. Diagnosis was reached in 29 (58%) of the 50 chronic cases, the remaining 21 (42%) still being of unknown etiology. The most frequent diagnosis was either definite or probable multiple sclerosis (MS). Magnetic resonance imaging (MRI) was of great value in detecting asymptomatic brain lesions. We conclude that after a long clinical follow-up and the use of MRI we were able to diagnose more than half the previously MUE patients.     

Transitional progressive multiple sclerosis: MRI and MTI findings

Transitional progressive multiple sclerosis (MS) is quite an unusual form of presentation and course of the disease. A case with this progressive form is presented and brain MRI and MTI findings are discussed in relation to the possible insight they may provide for understanding the mechanisms that determine progressive disability in MS.     

Mitoxantrone treatment in multiple sclerosis: a 5-year clinical and MRI follow-up

Mitoxantrone (MTX) is an antineoplastic agent approved for treatment of secondary progressive and rapidly worsening relapsing-remitting multiple sclerosis (MS). We designed a longitudinal open-label prospective study to evaluate the efficacy and toxicity of MTX over a 2-year treatment period with a further 3-year follow-up. Fifty consecutive MS patients were included and received MTX intravenously (8 mg/m² every 2 months for a total of 12 infusions). Efficacy was assessed clinically and by brain MRI performed before MTX therapy, at the end of treatment and at the end of each year of follow-up. Forty-nine patients completed the 5-year study, 44 (89.8%) completed the MTX course, five (10.2%) interrupted the treatment because of side effects. Fifteen (30.6%) patients showed Expanded Disability Status Scale (EDSS) progression on treatment and nine (18.4%) during follow-up. Seventeen (34.7%) patients had enhancing lesions at baseline, nine (18.4%) at the end of treatment, but none at the end of follow-up. In conclusion, we observed EDSS progression in about 1/3 of the patients during the treatment period and in 1/5 during the further 3-year follow-up period. This evidence suggests a delayed beneficial effect after MTX treatment is completed with only a minority of patients showing disability progression once the drug was suspended.     

Increased disability and MRI lesions after discontinuation of IFN-beta-1a in secondary progressive MS

OBJECTIVE: To examine neurological and magnetic resonance imaging (MRI) changes following discontinuation of interferon (IFN)-beta-1a treatment in secondary progressive multiple sclerosis (SPMS). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

The influence of clinical relapses and steroid therapy on the development of Gd-enhancing lesions: a longitudinal MRI study in relapsing—remitting multiple sclerosis patients

Fifty-three patients with relapsing-remitting multiple sclerosis who had monthly Gd (gadolinium) enhanced MRI (Magnetic Resonance Imaging) and clinical evaluation, were divided into two subgroups: 1) patients with a clinical relapse, treated with IVMP (intravenous methylprednisolone) and at least one enhancing lesion on MRI. 2) patients who did not have a clinical relapse but with at least one enhancing lesion on MRI. In group 1, we evaluated the number and volume of enhancing lesions on the scan before and three scans after IVMP therapy; in group 2, we considered the first scan with enhancing lesions and the subsequent three scans. The mean number and volume of enhancing lesions on the first scan was significantly higher in patients with clinical relapse compared to patients without clinical relapse. In group 1, we found a consistent reduction in the first scan following steroid treatment which returned to initial levels at the following scan. Both volumetric and numerical evaluation are appropiate MRI outcome measures in monitoring therapeutic trials.     

One-year MRI scan predicts clinical response to interferon beta in multiple sclerosis

Background and purpose:  To define the predictive value of clinical and magnetic resonance imaging (MRI) characteristics in identifying relapsing-remitting multiple sclerosis (RR-MS) patients with sustained disability progression during interferon beta (IFNB) treatment.
Methods:  All patients receiving treatment with one of the available IFNB formulations for at least 1 year were included in this single-centre, prospective and post-marketing study. Demographic, clinical and MRI data were collected at IFNB start and at 1 year of therapy; patients were followed-up at least yearly. Poor clinical response was defined as the occurrence of a sustained disability progression of ≥1 point in the Expanded Disability Status Scale (EDSS) during the follow-up period.
Results:  Out of 454 RR-MS patients starting IFNB therapy, data coming from 394 patients with a mean follow-up of 4.8 (2.4) years were analysed. Sixty patients were excluded because of too short follow-up. Less than 1/3 (30.4%) of the patients satisfied the criterion of 'poor responders'. Patients presenting new lesions on T2-weighted MRI scan after 1 year of therapy (compared with baseline) had a higher risk of being poor responder to treatment with IFNB during the follow-up period (HR 16.8, 95% CI 7.6–37.1, P  < 0.001). An augmented risk increasing the number of lesions was observed, with a 10-fold increase for each new lesion.
Conclusions:  Developing new T2-hyperintense lesions during IFNB treatment was the best predictor of long-term poor response to therapy. MRI scans performed after 1 year of IFNB treatment may be useful in contributing to early identification of poor responders.     

The relationship of brain and cervical cord volume to disability in clinical subtypes of multiple sclerosis: a three-dimensional MRI study

OBJECTIVES: Brain and cervical cord volume is a potentially valuable index marker of irreversible pathological processes in multiple sclerosis (MS). Volume in both brain and cervical cord regions in the same patients has only been investigated in a small number of subjects. We aimed at measuring volume in different parts of the central nervous system, and its relationship with clinical measures, in relapsing-remitting (RR) and secondary progressive (SP) MS patients. MATERIAL AND METHODS: Conventional dual echo and three-dimensional (3-D) magnetization prepared rapid acquisition gradient echo imaging was performed on 97 (49 RR and 48 SP) MS patients, and on 31 age- and gender-matched healthy controls. The volumes of the supratentorial brain, lateral ventricles, brainstem, cerebellum and upper cervical cord (UCC) were determined on 3-D magnetic resonance imaging. RESULTS: RR MS patients had significantly smaller supratentorial brain (P=0.002) and larger lateral ventricles (P=0.047) compared with controls, but no differences were found for cerebellum, brainstem and UCC volumes. Significantly smaller supratentorial brain (P<0.0001), cerebellum (P=0.007), brainstem (P=0.0004) and UCC (P<0.0001) volumes, and larger lateral ventricles (P<0.0001) were observed in SP MS patients than in controls. In RR MS, T2-lesion volume correlated with supratentorial (r=-0.46, P=0.0009), lateral ventricular (r=0.65, P<0.0001), cerebellar (r=-0.42, P=0.003) and brainstem (r=-0.35, P=0.01) volumes, but not with UCC volume (r=-0.18, P=0.22). In SP MS, apart from lateral ventricular volume (r=0.52, P=0.0002), none of the estimated structural volumes correlated with T2-lesion volume. The UCC volume correlated with brainstem volume in both RR MS (r=0.35, P=0.016) and SP MS (r=0.38, P=0.007). Multiple regression analysis showed that supratentorial brain volume in RR group, and UCC volume in SP group, were single significant contributors (P=0.01 and 0.04, respectively) to the Expanded Disability Status Scale of all factors entered into the regression model. CONCLUSION: Atrophy is confined to the supratentorial compartment early in the disease course corresponding to the RR stage, but becomes more pronounced in the brain and cervical spinal cord in the SP phase. The estimate of cervical cord volume for SP MS is relevant to functional disability and may be helpful in monitoring MS evolution in the progressive form of disease.     

Translating pathology in multiple sclerosis: the combination of postmortem imaging,histopathology and clinical findings

Background – Studies combining postmortem magnetic resonance imaging (MRI) and histopathology have provided important insights into the abnormalities reflected by MRI. Materials and methods – A short overview of these studies applied to multiple sclerosis (MS) is provided in this review, and the Amsterdam postmortem imaging protocol is specifically highlighted. Conclusion – Postmortem MRI and histopathology correlation studies have enabled a direct translation of basic pathology in MS to the clinical setting, and have simultaneously served as a biological validation of new MRI techniques.     

Brain MRI in late-onset multiple sclerosis

Multiple sclerosis (MS) with clinical onset after 50 years of age is unusual (between 1 and 6%) and is frequently misdiagnosed. Furthermore, brain magnetic resonance imaging (MRI) abnormalities are frequently observed in subjects over 50 years of age. The aim of this study was to describe brain MRI in late-onset MS to evaluate the sensitivity and specificity of radiological MS criteria in patients aged over 50 years. We evaluated the brain MRI of 20 patients with onset of MS after 50 years of age. We compared these MRI with 26 controls matched for age, sex and vascular risk factors. MRI were blindly analysed by two neuroradiologists according to Paty et al.'s [Neurology38 (1988) 180] criteria, Fazekas et al.'s [Neurology38 (1988) 1822] criteria and Barkhof et al.'s [Brain120 (1997) 2059] criteria. The mean age at MRI scanning was 58 years. Sensitivity was 90% for Paty et al.'s criteria, 80% for Fazekas et al.'s criteria and 85% for Barkhof et al.'s criteria. Specificity was 54% for Paty et al.'s criteria, 69% for Fazekas et al.'s criteria and 65% for Barkhof et al.'s criteria. Barkhof et al.'s criteria are less specific in older patients than in young patients. We suggest that spinal cord MRI and cerebrospinal fluid analysis should be systematically performed in suspected late-onset MS in order to increase the specificity of the diagnosis.