OBJECTIVE: To develop an objective method for quantifying venous vasculature in brain parenchyma on susceptibility-weighted imaging (SWI). To apply this technique in multiple sclerosis (MS) patients and in healthy controls (HC). BACKGROUND: SWI is a MRI application that can directly image cerebral veins by exploiting venous blood oxygenation. DESIGN/METHODS: Sixty-two (62) MS patients (44 relapsing-remitting and 18 secondaryprogressive) and 33 age- and sex-matched HC were imaged on a 3T GE scanner using pre-contrast SWI. A subset of MS patients (50) and HC (7) obtained SWI-post gadolinium contrast sequence (0.1 mMol/Kg Gd-DTPA with 10 min delay). In-house developed segmentation algorithm, based on a 3D multi-scale line filter, was applied for vein segmentation. Absolute volumetric measurement for total vein vasculature was performed in milliliters (ml) and the relative venous intracranial fraction (VIF) was obtained to correct for head size and amount of brain atrophy. The size of individual veins was measured in mm and 4 groups were created according to their mean diameter: 0.9 mm. Voxel brain average distance-from-vein maps was also calculated with higher distance indicating fewer veins. RESULTS: A significantly lower absolute venous volume was detected in MS patients compared to HC, both in pre-contrast (67.5 vs. 82.7ml, -18.3%, p<0.001) and post-contrast (70.4 vs. 87.1ml, 19.1%, p<0.011) images. The VIF was significantly lower in MS patients (p<0.001). The highest mean diameter difference was found for the smallest veins (<0.3 mm), both on pre- (p<0.001) and post-contrast (p<0.018) images. The distance-from-veins was also significantly higher in MS patients (p<0.001). CONCLUSIONS/RELEVANCE: We developed and validated a quantitative vein segmentation method that showed altered visibility of venous vasculature on SWI pre- and post-contrast images in MS patients. These findings suggest severely compromised brain venous system in MS patients.

Background Cognitive impairment is common in multiple sclerosis (MS) affecting roughly 45–60% of patients. Because memory deficits have significant impact on employment, caregiver burden, and social functioning, neuropsychological (NP) assessment is often recommended. Two widely used and validated NP batteries for MS are the Rao Brief Repeatable Neuropsychological Battery (BRNB) and the Minimal Assessment of Cognitive Function in MS (MACFIMS). Although similar, these batteries differ in the specific auditory/verbal and visual/spatial memory tests employed. The relative sensitivity of these memory tests is unknown. Methods The BRNB and MACFIMS have considerable overlap but different memory tests: the former includes the Selective Reminding Test (SRT) and the 10/36 Spatial Recall Test (10/36) and the latter the California Verbal Learning Test, Second Edition (CVLT2) and Brief Visuospatial Memory Test, Revised (BVMTR). In 65 patients with MS and 46 demographically matched controls, we compared the sensitivity of these tests, and secondarily their respective batteries. Results The BRNB and MACFIMS were comparable in their overall sensitivity to disease status. Although the BVMTR showed greater discriminative validity than the 10/36, the CVLT2 and SRT were comparable in sensitivity. The SDMT was the most sensitive NP test across both batteries. Conclusions We conclude that the BRNB and MACFIMS have comparable sensitivity among patients with MS. The sensitivity of the auditory/verbal memory tests from these batteries is similar, but the BVMTR appears to be more sensitive than the 10/36. Clinical implications are discussed.

Objective To determine whether neuromyelitis optica (NMO) immunoglobulin (IgG) antibody status in NMO/Devic's disease patients followed prospectively is persistent or can change relative to the clinical status and/or response to therapy.Design A cross-sectional group of patients with NMO, relapsing extensive longitudinal transverse myelitis (RLETM) or optico-spinal multiple sclerosis (OSMS) were evaluated for the presence of NMO IgG antibodies. Repeated evaluation was made in all NMO/RLETM patients and in a subgroup of OSMS patients.Setting Baird Multiple Sclerosis Center, Buffalo, New York, an academic multiple sclerosis center.Results Out of a consecutive cohort of 38 patients evaluated for the presence of NMO IgG, 12 had NMO and 26 had OSMS. Five of the 12 NMO/RLETM patients were NMO IgG positive at the time of their initial evaluation. Four of these patients were repeatedly tested for NMO IgG: two of these became negative and two remained positive. One patient who was initially negative became positive during an acute event and again became negative during the stable disease phase following treatment. A positive test result was associated with active disease, whereas a negative NMO IgG result was consistently found in stable, long-term treated patients. None of the OSMS patients were positive for NMO IgG even during acute attacks.Conclusions NMO IgG antibodies are associated with active NMO/RLETM. A well-controlled stable disease usually under effective immunosuppressive therapy can transform the NMO IgG to a negative status. Repeated NMO IgG testing should be considered as a useful biological marker for monitoring NMO/RLETM disease and or response to therapy.

We evaluated the effects of the levo (l) enantiomer of amphetamine sulfate on cognitive function in multiple sclerosis (MS) patients. Using a counterbalanced within-subjects design, 19 MS patients received four single-dose administrations of placebo, 15 mg) 30 mg, or 45 mg of l-amphetamine. Neuropsychological tests measuring processing speed and memory served as the primary outcomes. Performance on tests of processing speed were improved following the 45 mg condition and the largest effects were observed on the Symbol Digit Modalities Test, which measures visual processing speed and working memory. While episodic memory test effects were in the expected direction, the findings were not statistically significant. These preliminary findings show promise for the use of l-amphetamine for the symptomatic treatment of slowed mental processing in MS. Further placebo-controlled trials are needed to confirm these findings.

Cognitive impairment is common in multiple sclerosis (MS), yet difficult to detect duringroutine neurologic examination. Therefore, briefscreening tests that identify patients who may benefit from a more thorough assessment or treatment are needed. We investigated the utility of the Symbol Digit Modalities Test (SDMT) as a screen for cognitive dysfunction because it can be administered and scored in about 5 minutes. One hundred MS patients and 50 healthy controls, matched on demographic variables, participated in the study. Examination procedures included the neuropsychological (NP) tests included in the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery. Patients were considered impaired if they performed one and a half standard deviations below controls on two or more MACFIMS variables, excluding theSDMT. Bayesian statistics showed that a total score of 55 or lower onthe SDMT accurately categorized 72% of patients, yielding sensitivityof 0.82, specificity of 0.60, positive predictive value (PPV) of 0.71, and negative predictive value (NPV) of 0.73. These results suggest that the effectiveness of the SDMT as a screen for cognitive impairment in MS is roughly equal to that of other psychometric and questionnaire methods.

Grey matter hypointensity on T2-weighted magnetic resonance imaging (MRI) scans, suggesting iron deposition, has been described in multiple sclerosis (MS) and is related to physical disability, disease course and brain atrophy. We tested the hypothesis that subcortical grey matter T2 hypointensity is related to cognitive impairment after adjusting for the effect of MRI lesion and atrophy measures. We studied 33 patients with MS and 14 healthy controls. Normalized T2 signal intensity in the caudate, putamen, globus pallidus and thalamus, total brain T1-hypointense lesion volume (T1LV), fluid-attenuated inversion-recovery-hyperintense lesion volume (FLLV) and brain parenchymal fraction (BPF) were obtained quantitatively. A neuropsychological composite score (NCS) encompassed new learning, attention, working memory, spatial processing and executive function. In each of the regions of interest, the normalized T2 intensity was lower in the MS versus control group (all P<0.001). Regression modelling tested the relative association between all MRI variables and NCS. Globus pallidus T2 hypointensity was the only variable selected in the final model (R2 = 0.301, P = 0.007). Pearson correlations between MRI and NCS were T1LV: r = -0.319; FLLV: r = -0.347; BPF: r = 0.374; T2 hypointensity of the caudate: r = 0.305; globus pallidus: r = 0.395; putamen: r = 0.321; and thalamus: r = 0.265. Basal ganglia T2 hypointensity and BPF demonstrated the strongest associations with cognitive impairment on individual cognitive subtests. Subcortical grey matter T2 hypointensity is related to cognitive impairment in MS, supporting the clinical relevance of T2 hypointensity as a biological marker of MS tissue damage. These data implicate a role for basal ganglia iron deposition in neuropsychological dysfunction.

Objectives: To determine whether a low fat diet supplemented with omega-3 positively affects quality of life (QOL) in relapsing-remitting MS (RRMS) patients. In this 1-year long double-blind, randomized trial, patients were randomized to two dietary interventions: the "Fish Oil" (FO) group received a low fat diet (15% fat) with omega-3 FOs and the "Olive Oil" (OO) group received the AHA Step I diet (fat <= 30%) with OO supplements. The primary outcome measure was the Physical Components Summary Scale (PCs) of the Short Health Status Questionnaire (SF-36). Additional measures using MS specific QOL questionnaires, neurological status and relapse rate were obtained.Results: 31 RRMS patients were enrolled, with mean follow up over 11 +/- SD 2.9 months. Clinical benefits favoring the FO group were observed on PCS/SF-36 (P = 0.050) and MHI (P = 0.050) at 6 months. Reduced fatigue was seen on the OO diet at 6 months (P = 0.035). The relapse rate decreased in both groups relative to the rates during the I year preceding the study: mean change in relapse rate in the FO group: -0.79 +/- SD 1.12 relapses/year (P = 0.021) vs. -0.69 +/- SD 1.11 (P = 0.044) in the OO group. This study suggests that a low fat diet supplemented with omega-3 PUFA can have moderate benefits in RRMS patients on concurrent disease modifying therapies. (c) 2005 Elsevier Ltd. All rights reserved.

On August 30, 2002, an international panel of neurologists who specialize in the treatment of multiple sclerosis (MS) was convened in Paris (France) to discuss the issue of neutralizing antibodies (NAb) to interferon beta (IFN‐ β ) therapy in patients with MS. The goals of this meeting were to: (i) review the most recent clinical information on NAb, (ii) come to a consensus on the clinical relevance of NAb in the management of patients with MS receiving IFN‐ β therapy, and (iii) establish a framework for the development of patient management guidelines based on scientific consensus. The meeting was chaired by Hans‐Peter Hartung (Heinrich‐Heine University, Düsseldorf, Germany) and Huub Schellekens (Utrecht University, Utrecht, the Netherlands). This article summarizes the opinions of the expert panel on a number of key issues raised at the meeting.