Correlating Brain Atrophy With Cognitive Dysfunction, Mood Disturbances, and Personality Disorder in Multiple Sclerosis

Abstract

Neuropsychological impairment is a common feature of multiple sclerosis. Affected patients often have deficits in information-processing speed and memory and exhibit psychopathological states such as depression. A minority of patients have rarer affect/mood disorders such as euphoria sclerotica and pathological laughter/crying. Neuropsychological impairment is a major predictor of low quality of life, unemployment, and caregiver distress. Studies evaluating correlations between neuropsychological impairment and findings on magnetic resonance imaging show that neuropsychological dysfunction is associated with lesion burden and diffuse disease in normal-appearing brain tissue. However, measures of tissue atrophy including whole-brain and central atrophy are especially well correlated with and predictive of cognitive impairment. Moreover, recent studies have shown that conventional measures of brain atrophy explain more variance in neuropsychological dysfunction than do measures of lesion burden. In particular, neuropsychological outcomes correspond highly with linear measures of subcortical atrophy such as ventricle enlargement. Within the domain of emotional dysfunction, both lesion burden and atrophy are related to major depressive disorder. Brain atrophy also predicts euphoria and disinhibition. The preliminary data suggest that although lesion burden primarily predicts depressive disorder, both lesion burden and atrophy predict the presence of euphoria. Euphoria and disinhibition likely represent personality change associated with worsening cognition as the disease progresses. Taken together, this growing body of data on magnetic resonance imaging to neuropsychological correlations supports the clinical relevance and validity of brain atrophy as a measure of disease progression in multiple sclerosis. Continuing research focuses on the possible relationship between measures of regional brain atrophy and cognitive and emotional impairment.

Cognitive impairment and “invisible symptoms” are not associated with CCSVI in MS

“…Several cross sectional studies demonstrated that the pathogenesis of CI in MS patients might not depend just on the extent and severity of the pathological process in the brain lesions, but also on the pathological changes affecting the normal appearing brain tissue [47-49]. Considering that, we could take into account the possible vascular hypothesis as a possible contribute to the presence of a spread or regional brain atrophy, which is one of the strongest factor correlated with the CI in MS [50-52]. Impaired cerebral perfusion seems to be related to CI [18] and a widespread cerebral hypo perfusion in MS, described as a potential cause of brain atrophy [50-52], could be the result of the venous outflow obstructions as seen in the CCSVI [19].…”

“…Considering that, we could take into account the possible vascular hypothesis as a possible contribute to the presence of a spread or regional brain atrophy, which is one of the strongest factor correlated with the CI in MS [50-52]. Impaired cerebral perfusion seems to be related to CI [18] and a widespread cerebral hypo perfusion in MS, described as a potential cause of brain atrophy [50-52], could be the result of the venous outflow obstructions as seen in the CCSVI [19]. Although there is no strong evidence suggesting that CCSVI is a cause of MS, there is some evidence that a slower cerebral venous flow in patients with MS might be secondary to the reduced cerebral blood flow [19].…”

Cannabis-induced alterations in brain activation during a test of information processing speed in patients with MS

“…29,30 In a study that explored the relationship between five brain MRI indices of pathology (T1 and T2 lesion volume, third ventricle width, bicaudate ratio and brain parenchymal fraction) and a host of cognitive variables, it was third ventricle width that emerged as the most robust predictor of cognitive impairment. 31 Moreover, the strongest correlation was found with the SDMT. More recently, subtle indices of thalamic pathology, such as resting state functional connectivity 32 and altered diffusion tensor imaging metrics such as mean diffusivity 33 have been linked to impaired cognition in MS patients.…”

Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis

“…16,17 WBA can be detected at all stages of MS disease and represents a summation of the destructive pathologic processes in MS. Many studies show significant correlations between WBA and overall clinical disability, cognitive impairment, 18–22 depression, 23 fatigue, 24,25 and quality of life. 26,27 However, WBA is a relatively crude measure of overall brain injury, lacking granularity to characterize localized injury.…”