Cumulative Dose of Macrocyclic Gadolinium-Based Contrast Agent Improves Detection of Enhancing Lesions in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Gadolinium-enhanced MR imaging is currently the reference standard for detecting active inflammatory lesions in patients with multiple sclerosis. The sensitivity of MR imaging for this purpose may vary according to the physicochemical characteristics of the contrast agent used and the acquisition strategy. The purpose of this study was to compare detection of gadolinium-enhancing lesions or active disease following a single or cumulative dose of a macrocyclic gadolinium-based contrast agent with different image acquisition delays in patients with clinically isolated syndrome or relapsing multiple sclerosis. MATERIALS AND METHODS: All patients received a first dose (0.1 mmol/kg) of gadobutrol and, 20 minutes later, a second dose (0.1 mmol/kg), with a cumulative dose of 0.2 mmol/kg. Two contrast-enhanced T1-weighted sequences were performed at 5 and 15 minutes after the first contrast administration, and 2 additional T1-weighted sequences at 5 and 15 minutes after the second contrast administration with a 3T magnet. RESULTS: One hundred fifteen patients were considered evaluable. A significantly larger number of lesions were detected in scans obtained at 5 and 15 minutes after the second contrast injection compared with scans obtained at 5 and 15 minutes after the first injection (P < .001). The number of patients with active lesions on MR imaging was significantly higher after the second dose administration (52.0%, first dose versus 59.2%, second dose; P < .001). CONCLUSIONS: Cumulative dosing of a macrocyclic gadolinium-based contrast agent increases detection of enhancing lesions and patients with active lesions. These data could be considered in the design of MR imaging protocols aimed at detecting active multiple sclerosis lesions.

Comparison between gadolinium-enhanced 2D T1-weighted gradient-echo and spin-echo sequences in the detection of active multiple sclerosis lesions on 3.0T MRI.

OBJECTIVES: To compare the sensitivity of enhancing multiple sclerosis (MS) lesions in gadolinium-enhanced 2D T1-weighted gradient-echo (GRE) and spin-echo (SE) sequences, and to assess the influence of visual conspicuity and laterality on detection of these lesions. METHODS: One hundred MS patients underwent 3.0T brain MRI including gadolinium-enhanced 2D T1-weighted GRE and SE sequences. The two sets of contrast-enhanced scans were evaluated in random fashion by three experienced readers. Lesion conspicuity was assessed by the image contrast ratio (CR) and contrast-to-noise ratio (CNR). The intracranial region was divided into four quadrants and the impact of lesion location on detection was assessed in each slice. RESULTS: Six hundred and seven gadolinium-enhancing MS lesions were identified. GRE images were more sensitive for lesion detection (0.828) than SE images (0.767). Lesions showed a higher CR in SE than in GRE images, whereas the CNR was higher in GRE than SE. Most misclassifications occurred in the right posterior quadrant. CONCLUSIONS: The gadolinium-enhanced 2D T1-weighted GRE sequence at 3.0T MRI enables detection of enhancing MS lesions with higher sensitivity and better lesion conspicuity than 2D T1-weighted SE. Hence, we propose the use of gadolinium-enhanced GRE sequences rather than SE sequences for routine scanning of MS patients at 3.0T. KEY POINTS: • 2D SE and GRE sequences are useful for detecting active MS lesions. • Which of these sequences is more sensitive at high field remains uncertain. • GRE sequence showed better sensitivity for detecting active MS lesions than SE. • We propose GRE sequence for detecting active MS lesions at 3.0T.

Brain atrophy in natalizumab-treated patients: A 3-year follow-up.

BACKGROUND: A pseudoatrophy effect has been held responsible for the lack of net impact of natalizumab on brain volume outcomes in 2-year trials, but no data are available beyond 24 months. OBJECTIVE: We aimed to investigate brain volume dynamics in natalizumab-treated patients in up to 3 years after therapy initiation with clinical correlations. METHODS: Patients on natalizumab for at least 3 years were clinically assessed 3-monthly. Magnetic resonance imaging scans were performed at baseline and yearly. Brain volume changes were obtained with SIENA. Multivariate models were used to investigate the association between baseline inflammation and changes in brain volume and disability. RESULTS: Sixty-two patients with multiple sclerosis were analysed. Mean age and disease duration were 34.7 (SD: 8.3) and 10.4 (SD: 6.6) years. Presence of gadolinium enhancement at baseline was not associated with Expanded Disability Status Scale changes (p=0.468), but was associated with larger brain volume decreases (p=0.005) in the first (p=0.024) and second year (p=0.019) but not in the third year (p=0.863). Brain volume changes at 12 and 36 months were marginally associated with disability status at month 12 (p=0.094) and 36 (p=0.084), respectively. CONCLUSIONS: Baseline inflammation affects brain volume measures up to 24 months after natalizumab initiation. A marginal association of brain volume changes with disability is present.

Clinical impact of early brain atrophy in clinically isolated syndromes.

BACKGROUND: The impact of global and tissue-specific brain atrophy on conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS) is not fully gauged. OBJECTIVES: We aimed to determine the magnitude and clinical relevance of brain volume dynamics in the first year after a CIS. METHODS: We assessed 176 patients with CIS within 3 months of onset, clinically and by conventional magnetic resonance imaging (MRI) scans, at baseline and 1 year after clinical onset. We determined the percentage of brain volume change (PBVC) and the brain parenchymal (BPF), grey matter (GMF) and white matter (WMF) fractions. RESULTS: The mean follow-up time was 53 months (SD = 16.8): 76 patients (43%) experienced a second attack, 32 (18%) fulfilled MRI-only 2005 McDonald criteria and 68 (39%) remained as CIS. Statistically significant decreases in the volume measures tested were observed in patients with a second attack, for BPF and PBVC; in both MS groups for GMF; whereas in all groups, the WMF was unchanged. Patients with a second attack had larger PBVC decreases (- 0.65% versus + 0.059%; p < 0.001). PBVC decreases below - 0.817% independently predicted shorter times to a second attack. CONCLUSIONS: Global brain and grey matter volume loss occurred within the first year after a CIS; brain volume loss predicted conversion to MS.

Biexponential analysis of diffusion-tensor imaging of the brain in patients with cirrhosis before and after liver transplantation.

BACKGROUND AND PURPOSE: DTI has shown increased MD of water molecules in the brain of patients with cirrhosis, consistent with low-grade edema. This study further characterizes this edema by using biexponential analysis of DTI data, a technique that may differentiate cytotoxic and vasogenic edema. MATERIALS AND METHODS: A total of 41 patients with cirrhosis awaiting liver transplantation and 16 healthy controls were studied by DTI by using a single-shot echo-planar technique with 11 b-values (range, 0-7500 s/mm(2)) and 6 noncollinear directions. Measurements were fitted to biexponential function to determine MD and FA for the fast and slow diffusion components. Regions of interest were selected in the parietal white matter and corticospinal tract. The assessment was repeated 1 year after liver transplantation in 24 of these patients. RESULTS: In parietal white matter, patients with cirrhosis showed an increase in fast MD and a decrease in fast FA that normalized after liver transplantation. In the corticospinal tract, there was an increase in fast and slow MD that normalized after transplantation, and a decrease in FA that persisted posttransplantation. There was no association of DTI parameters with minimal HE (n =12). CONCLUSIONS: Biexponential analysis of DTI supports the presence of edema in the brain of patients with cirrhosis that reverts after transplantation. In parietal white matter, the increase in brain water was mainly located in the interstitial compartment, while the corticospinal tract showed a mixed pattern (intra- and extracellular). In addition, the findings on posttransplantation were consistent with microstructural damage along the corticospinal tract.

An observational study of the effectiveness and safety of natalizumab in the treatment of multiple sclerosis.

AIM: To analyse the safety and effectiveness of natalizumab in the treatment of multiple sclerosis in a real clinical practice setting and according to the approved indications. PATIENTS AND METHODS: All patients with multiple sclerosis treated with natalizumab in our centre were evaluated. The clinical and radiological disease activity during the first year of treatment was analyzed in patients who received at least 12 doses of the drug. The data regarding moderate and severe adverse events in the entire study sample was also evaluated. RESULTS: A total of 112 patients were included in the study, of which 110 had been previously treated with other drugs and 76 had received at least 12 doses of natalizumab. In this group, the annualized relapse rate was reduced by 89% compared to the preceding year and 80% of patients were free from relapses after one year of treatment. Nine percent of patients exhibited 3-month confirmed disability progression. At month 12, the mean number of gadolinium-enhancing lesions on brain MRI was decreased by 99% compared to the pre-treatment MRI. During the first year of treatment, 76% of patients remained free from clinical activity and 33% remained free from both clinical and radiological disease activity. Twenty-nine percent of patients had at least one moderate or severe adverse event, which led to treatment discontinuation in 6%. Four percent of patients experienced immediate hypersensitivity reactions. CONCLUSION: This study suggests that natalizumab is effective in reducing disease activity in patients with relapsing multiple sclerosis and inadequate response to other therapies, with a favorable risk-benefit ratio.

Consensus recommendations for MS cortical lesion scoring using double inversion recovery MRI.

BACKGROUND: Different double inversion recovery (DIR) sequences are currently used in multiple sclerosis (MS) research centers to visualize cortical lesions, making it difficult to compare published data. This study aimed to formulate consensus recommendations for scoring cortical lesions in patients with MS, using DIR images acquired in 6 European centers according to local protocols. METHODS: Consensus recommendations were formulated and tested in a multinational meeting. RESULTS: Cortical lesions were defined as focal abnormalities on DIR, hyperintense compared to adjacent normal-appearing gray matter, and were not scored unless ≥ 3 pixels in size, based on at least 1.0 mm(2) in-plane resolution. Besides these 2 obligatory criteria, additional, supportive recommendations concerned a priori artifact definition on DIR, use of additional MRI contrasts to verify suspected lesions, and a constant level of displayed image contrast. Robustness of the recommendations was tested in a small dataset of available, heterogeneous DIR images, provided by the different participating centers. An overall moderate agreement was reached when using the proposed recommendations: more than half of the readers agreed on slightly more than half (54%) of the cortical lesions scored, whereas complete agreement was reached in 19.4% of the lesions (usually larger, mixed white matter/gray matter lesions). CONCLUSIONS: Although not designed as a formal interobserver study, the current study suggests that comparing available literature data on cortical lesions may be problematic, and increased consistency in acquisition protocols may improve scoring agreement. Sensitivity and specificity of the proposed recommendations should now be studied in a more formal, prospective, multicenter setting using similar DIR protocols.

Brainstem lesions in clinically isolated syndromes.

BACKGROUND: Number of baseline lesions has been shown to predict future attacks and disability in clinically isolated syndromes (CIS). OBJECTIVE: To investigate the role of baseline infratentorial lesions in long-term prognosis. METHODS: Subjects were included in a prospective cohort of patients with CIS. Patients underwent brain MRI within 3 months after CIS onset. Number and location of lesions at baseline were prospectively studied. Retrospective scan analysis was conducted to specifically look at number and location of infratentorial lesions. We analyzed the time to a second attack and to reach EDSS 3.0. RESULTS: We included 246 patients with CIS followed for a median of 7.7 years. Patients with infratentorial lesions had both a higher risk of conversion (71.4% vs 29.6%; hazard ratio [HR] 3.3; 95% confidence interval [CI] 2.2-4.8; p < 0.001) and of developing disability (32.5% vs 12.4%; HR 2.4; 95% CI 1.3-4.3; p = 0.003). Presence of at least one cerebellar lesion was associated with an increased risk of conversion (HR 2.4; 95% CI 1.3-4.5; p = 0.007). Presence of at least one brainstem lesion increased both the risk of conversion (HR 2.9; 95% CI 1.7-5.0; p < 0.001) and disability (HR 2.5; 95% CI 1.1-5.4; p = 0.026). Broken down into number of lesions, the presence of infratentorial lesions increased both the risk of conversion (83% vs 61%) (HR 22.3; 95% CI 9.7-51.1; p < 0.001) and of reaching EDSS 3.0 (40% vs 19%) (HR 3.2; 95% CI 1.3-7.4; p = 0.008) only in patients with 9 or more lesions. CONCLUSIONS: Presence of infratentorial lesions increases the risk for disability. Brainstem rather than cerebellar lesions may be responsible for poor prognosis.

Relationship between MRI lesion activity and response to IFN-beta in relapsing-remitting multiple sclerosis patients.

OBJECTIVE: Our objective in this study is to evaluate whether brain magnetic resonance imaging (MRI) performed at interferon-beta (IFN-beta) onset and after 12 months allow us to identify relapsing-remitting multiple sclerosis (RRMS) patients with a disability increase in the first 2 years of therapy. METHODS: This is a prospective and longitudinal study of patients with RRMS treated with IFN-beta. All patients included underwent brain MRI before the onset of therapy with IFN-beta and 12 months after. MRI measures (T2, unenhanced T1-weighted and gadolinium-enhancing T1-weighted brain lesion load, brain parenchymal fraction) were undertaken at baseline and after 12 months. The number of active lesions (new or enlarging T2 plus gadolinium-enhancing brain lesions) was also assessed on the 12 months MRI scan. Expanded Disability Status Scale (EDSS) was scored every 3 months. We defined an increase in disability as an increase of at least 1 EDSS point confirmed and sustained during the first 2 years of therapy with IFN-beta. Regression analysis was performed in order to identify MRI variables of response. RESULTS: We included 152 patients who were followed-up for at least 2 years. After 2 years of therapy, 24 patients (16%) had an increase in disability. The logistic regression model showed that active lesions in the scan performed at 12 months were the most important factor related with the increase of disability after 2 years of therapy (odds ratio 8.3, 95% confidence interval 3.1-21.9; p < 0.0001). CONCLUSIONS: In RRMS patients treated with IFN-beta the MRI changes occurring during the first year may have a prognostic value for identifying patients with a confirmed increase of disability after 2 years of therapy.