Background: Pathology in the cervical spinal cord is considered an important cause of disability in multiple sclerosis. However, the majority of serial studies have failed to find a correlation between spinal cord atrophy and disability. Objectives: To use a highly reproducible and accurate method to quantify spinal cord area change on three dimensional magnetic resonance imaging and relate this to disability change in patients with multiple sclerosis. Methods: 38 patients with multiple sclerosis (20 with the relapsing-remitting (RRMS) form and 18 with the secondary progressive (SPMS) form) were imaged at baseline and at months 6, 12, 18, and 48 during two treatment trials of the high dose subcutaneous thrice weekly interferon β-1a (IFNβ, Rebif). Thirty one healthy subjects were also imaged at baseline. Upper cervical cord area (UCCA) was measured using Sobel edge detection. Results: The intraobserver coefficient of variation of the method was 0.42%. A significant reduction in UCCA was detected at month 6 in the placebo group (p = 0.04) and at month 12 for INFβ (p = 0.03). The mean reduction of UCCA at month 48 was 5.7% for patients initially on placebo who received treatment at 24 months (RRMS) or at 36 months (SPMS), and 4.5% for those on IFNβ throughout the study (p = 0.35). The change in UCCA was significantly correlated with change in the expanded disability status scale at month 12 (r = 0.4, p = 0.016), month 18 (r = 0.32, p = 0.05), and month 48 (r = 0.4, p = 0.016) in the total cohort. Conclusions: Despite the small number of patients studied and the possible confounding effects of interferon treatment, this study showed that edge detection is reproducible and sensitive to changes in spinal cord area, and that this change is related to changes in clinical disability. This suggests a role for measurement of spinal cord atrophy in monitoring disease progression and possible treatment effects in clinical trails.

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ADC(av), MTR and atrophy measures in the CC may offer a sensitive method detecting subtle macroscopic and microscopic changes associated with cognitive impairment in MS.

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.

We focus on an analytical overview of current natural product databases, and further discuss the good, bad or imperfection of current ones, in the hope of better integrating existing relevant outcomes, thus providing new routes for future drug discovery.

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Pathology and magnetic resonance imaging (MRI) studies have provided evidence of widespread axonal loss and reductions of cerebral and spinal cord volume in multiple sclerosis (MS). Atrophy measures on MRI may be a useful surrogate marker of worsening disability in MS, but the published studies are of relatively short duration. Change in brain volume (atrophy) was measured over a four-year period in 20 patients with relapsing-remitting (RR) and 18 with secondary progressive (SP) MS using three-dimensional (3D) MRI acquired during treatment trials of interferon-beta-1a (Rebif). Brain parenchymal and lateral ventricle volume changes were determined and correlated with clinical measures. Over four years, brain parenchymal volume (BPV) decreased in RRMS and SPMS patients by 0.9% (P = 0.006) and 0.3% (P = 0.118), respectively, and the lateral ventricle volumes increased by 15% (P < 0.0001) and 13% (P < 0.0001), respectively. In RRMS patients both lateral ventricle volume (r = 0.63, P = 0.004) and BPV change (r = -0.47, P = 0.037) were related to disability change, as measured by the Expanded Disability Status Scale. Even though a small study and despite the possible confounding effects of interferon treatment, this study demonstrated an association between measures of cerebral atrophy and worsening disability. The data also provides evidence that brain atrophy can be detected early in the disease course and central white matter atrophy as reflected by ventricle enlargement appears to be a continuous process.

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