Progression Of Brain Atrophy In Patients Research Articles

Longitudinal Mixed-Effect Model Analysis of the Association between Global and Tissue-Specific Brain Atrophy and Lesion Accumulation in Patients with Clinically Isolated Syndrome.

The relationship between lesion formation and brain atrophy development in the early phase of multiple sclerosis is unclear. We investigated the association between new lesion accumulation and brain atrophy progression in patients with clinically isolated syndrome over 48 months. Patients with clinically isolated syndrome (n = 210) were evaluated with 1.5T MR imaging at baseline and at 6, 12, 24, 36, and 48 months as part of a multicenter observational study of early administration of intramuscular interferon β-1a. Mixed-effect model analyses, adjusted for age, sex, and treatment status, investigated the association between accumulation of contrast-enhancing and T2 lesions and brain-volume percent changes in a 48-month period. In patients with clinically isolated syndrome, the average whole-brain volume decreased 2.5%, the mean lateral ventricle volume increased 16.9%, and a mean of 7.7 new/enlarging T2 lesions accumulated over the follow-up period. Patients with clinically isolated syndrome who showed greater percentages of change in whole-brain, white and gray matter, cortical, and lateral ventricle volumes over the follow-up period had more severe lesion outcomes at baseline (all P < .007). There were significant associations between decreased individual brain-volume measures at baseline and greater percentages of change during follow-up (P < .05). We found a significant association between the total cumulative number of new/enlarging T2 lesions and the evolution of whole-brain (P < .001), lateral ventricle (P = .007), gray matter and thalamic (P = .013), subcortical deep gray matter (P = .015), and cortical (P = .036) volumes over the follow-up period. Lesion accumulation and brain-volume changes occur simultaneously in the early phase of clinically isolated syndrome. More severe lesion and brain-volume outcomes at baseline were associated with greater development of brain atrophy over the follow-up period in patients with clinically isolated syndrome.

Writing Error May Be a Predictive Sign for Impending Brain Atrophy Progression in Amyotrophic Lateral Sclerosis: A Preliminary Study Using X-Ray Computed Tomography

Aim: To investigate whether writing errors are predictive of longitudinal brain atrophy progression in patients with amyotrophic lateral sclerosis (ALS). Methods: The frequency of writing errors in 6 ALS patients without dementia was compared with longitudinal changes in lateral ventricular areas of the bilateral anterior and inferior horns on X-ray computed tomography scans. The increase in area per month for the anterior and inferior horns was used as a measure of longitudinal brain atrophy progression, and was calculated as: (area on the initial scan – area on the follow-up scan)/scan interval (month). Results: The longitudinal rate of increase in the area of the anterior horns showed significant associations with the rates of total writing errors (r = 0.886, p = 0.0152), kana errors (r = 0.887, p = 0.0148) and kana omission (r = 0.856, p = 0.0268), whereas that for the inferior horns size showed no significant association with any writing errors. Conclusion: The increased area of the anterior horns indicates frontal-lobar atrophy, and writing errors may be a predictive sign for impending brain atrophy progression in the frontal lobes, which reflects the development of anterior-type dementia.

Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis

The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNβ-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI) measures are presented here. Patients received natalizumab 300 mg ( n = 589) or placebo ( n = 582) intravenously every 4 weeks plus IFNβ-1a 30 µg intramuscularly once weekly. Annual MRI scans allowed comparison of a range of MRI end points versus baseline. Over 2 years, 67% of patients receiving natalizumab plus IFNβ-1a remained free of new or enlarging T2-lesions compared with 30% of patients receiving IFNβ-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNβ-1a and increased in those receiving IFNβ-1a alone (–277.5 mm 3 versus 525.6 mm 3; p < 0.001). Compared with IFNβ-1a alone, add-on natalizumab therapy resulted in a smaller increase in mean T1-hypointense lesion volume after 2 years (1821.3 mm 3 versus 2210.5 mm 3; p < 0.001), a smaller mean number of new T1-hypointense lesions over 2 years (2.3 versus 4.1; p < 0.001), and a slower rate of brain atrophy during the second year of therapy (–0.31% versus –0.40%; p = 0.020). Natalizumab add-on therapy reduced gadolinium-enhancing, T1-hypointense, and T2 MRI lesion activity and slowed brain atrophy progression in patients with relapsing MS who experienced disease activity despite treatment with IFNβ-1a alone.

Steroids and brain atrophy in multiple sclerosis

In this review, we focus on different pathogenetic mechanisms of corticosteroids that induce short- and long-term brain volume fluctuations in a variety of systemic conditions and disorders, as well as on corticosteroid-induced immunomodulatory, immunosuppressive and anti-inflammatory mechanisms that contribute to the slowdown of brain atrophy progression in patients with multiple sclerosis (MS). It appears that chronic low-dose treatment with corticosteroids may contribute to irreversible loss of brain tissue in a variety of autoimmune diseases. This side effect of steroid therapy is probably mediated by steroid-induced protein catabolism mechanism. Evidence is mounting that high-dose corticosteroids may induce reversible short-term brain volume changes due to loss of intracellular water and reduction of abnormal vascular permeability, without there having been axonal loss. Other apoptotic and selective inhibiting mechanisms have been proposed to explain the nature of corticosteroid-induced brain volume fluctuations. It has been shown that chronic use of high dose intravenous methylprednisolone (IVMP) in patients with MS may limit brain atrophy progression over the long-term via different immunological mechanisms, including downregulation of adhesion molecule expression on endothelial cells, decreased cytokine and matrix metalloproteinase secretion, decreased autoreactive T-cell-mediated inflammation and T-cell apoptosis induction, blood–brain barrier closure, demyelination inhibition and, possibly, remyelination promotion. Studies in nonhuman primates have confirmed that short-term brain volume fluctuations may be induced by corticosteroid treatment, but that they are inconsistent, potentially reversible and probably dependent upon individual susceptibility to the effects of corticosteroids. Further longitudinal studies are needed to elucidate pathogenetic mechanisms contributing to brain volume fluctuations in autoimmune diseases and multiple sclerosis.