Abstract-The Perceived Deficits Questionnaire (PDQ) is a part of the Multiple Sclerosis (MS) Quality of Life Inventory that assesses self-perceived cognitive difficulties. We used baseline data from 49 MS subjects participating in a clinical trial to evaluate the correlation of the PDQ with two measures of cognitive impairment, the Paced Auditory Serial Addition Test (PASAT) and the California Verbal Learning Test, 2nd edition (CVLT-II), total score, and one measure of depression, the Beck Depression Inventory-Amended (BDI-IA). The PDQ correlated significantly (r = 0.42; 95% confidence interval [CI], 0.15 to 0.62; p = 0.003) with the BDI-IA scores but not with either the PASAT (r = -0.22; 95% CI, -0.48 to 0.06; p = 0.2) or the CVLT-II total (r = -0.17; 95% CI, -0.43 to 0.12; p = 0.25). A subset of 38 of these subjects who scored worse than 0.5 standard deviation below the mean on the PASAT or CVLT-II received a more extensive neuropsychological battery of tests. No significant correlations were found between any of these tests and the PDQ. These results suggest that self-perceived cognitive dysfunction relates more to depression than to objective cognitive dysfunction.

References 30 (max is 30) * > 0•5% patients per system organ class and > 1% patients per preferred term (MedDRA Version 19•1 System Organ Class Preferred Term; MedDRA = Medical Dictionary for Regulatory Activities) TEAE = Treatment Emergent Adverse Event * Based on Safety population; MD1003 n=331 and placebo n=311. ^ T2 imaging analysis at M6 is M0-M6 and at M15 is M6-M15. DMT = disease modifying treatment; Gd+ = gadolinium enhanced; MRI = Magnetic Resonance Imaging

Overall, GB did not show a statistically significant improvement in cognitive function. A treatment effect trend, limited to the Stroop test, suggests that GB may have an effect on cognitive domains assessed by this test, such as susceptibility to interference and mental flexibility.

No abstract

Abstract-To evaluate the potential effects of medications with central nervous system (CNS) activity on cognitive function and fatigue in multiple sclerosis (MS), we performed a retrospective analysis of medication use among 70 subjects with MS who were participating in a clinical trial for evaluation of the effects of yoga and exercise programs on cognition and fatigue. Among these MS subjects, 74% were taking at least one potentially CNS-active medication. These 70 subjects were divided into two groups: those taking at least one CNS-active medication (n = 52) and those not on any medications with potential CNS activity (n = 18). We compared assessments of cognitive function and fatigue using an analysis of covariance. MS subjects on CNS-active medication had greater impairment on measures of processing speed, sustained attention, and fatigue than those not on these medications. While these findings do not establish a causal relationship between medication use and cognitive impairment and fatigue, the data indicate that researchers need to control for use of CNS-active medications when conducting studies of cognitive impairment and fatigue in MS subjects.

Cognitive dysfunction is a major cause of disability in patients with multiple sclerosis (MS). The prevalence of cognitive dysfunction is estimated at 45 to 65%. Natural history studies suggest that once cognitive dysfunction develops in a patient with MS, it is not likely to remit. Unlike physical disability in MS, cognitive disability correlates weakly with T2 lesion burden on brain magnetic resonance imaging (MRI). More robust correlations exist with magnetisation transfer imaging and MRI measures of brain atrophy. Patients with MS who have cognitive impairment most commonly display deficits in the cognitive domains of memory, learning, attention and information processing. In diagnosing cognitive dysfunction in a patient with MS, it is important first to recognise and treat the common comorbidities of fatigue and depression. The first step in the treatment of cognitive dysfunction is to delay disease progression, and there are currently five such disease-modifying agents approved for the treatment of MS (two preparations of interferon-beta-1a, interferon-beta-1b, glatiramer acetate and mitoxantrone). Nonpharmacological measures, such as cognitive rehabilitation, occupational therapy and psychotherapy, are the mainstays of symptomatic treatment. Pharmacological symptomatic therapy centres on the treatment of comorbid fatigue and depression. There are currently no effective pharmacological agents approved as symptomatic therapy of cognitive dysfunction in MS.

Background: Magnetic resonance imaging (MRI) enhanced with gadolinium-based contrast agents (GBCAs) is an essential tool in the diagnosis and management of many neurologic diseases, including multiple sclerosis, brain tumors, and infections. The clinical utility of GBCAs is evidenced by their widespread use. GBCAs are produced in macrocyclic and linear forms. Since 2014, evidence has suggested that repeated administration of GBCAs can lead to gadolinium deposition in the brain. Methods: We review the literature on gadolinium deposition, including both animal and human studies, as well as the literature on GBCA-associated health outcomes. Additionally, we summarize and discuss the updated medical society recommendations and perspectives on GBCA use in clinical practice. Results: The first publication reporting gadolinium deposition in the human brain was published in 2014. Since that seminal report, multiple studies have demonstrated that exposure to linear GBCAs is associated with gadolinium deposition in the dentate nucleus and globus pallidus as seen on brain MRI. Macrocyclic GBCA exposure has not convincingly been associated with gadolinium deposition evident on brain MRI. Conclusion: Clear evidence demonstrates that GBCAs lead to gadolinium deposition in the brain in a dose-dependent manner; however, only linear GBCAs have been associated with gadolinium deposition visualized on MRI. To date, no evidence links gadolinium deposition with any adverse health outcome. Updated medical society guidelines emphasize the importance of an individualized risk-benefit analysis with each administration of GBCAs.

Recent seroepidemiologic and pathologic evidence suggests that prior infection with Epstein-Barr virus (EBV) may be necessary for the development of multiple sclerosis (MS). EBV infects more than 90% of all humans, most of whom remain healthy. In contrast, 99% of MS patients have evidence of prior infection with EBV. EBV infects resting B lymphocytes, immortalizing them into long-lived memory B cells that survive largely undetected by the immune system in the peripheral circulation. MS patients show elevated titers to EBV years before developing any neurologic symptoms. Postmortem pathologic analysis of brains of patients with MS has revealed diffuse EBV-associated B-cell dysregulation in all forms of MS. Theories of pathogenesis of EBV in MS include antigenic mimicry, immortalization of B-cell clones, and cytotoxic T-cell dysfunction against virally infected B cells. This article reviews the existing evidence of the relationship between EBV and MS and considers the therapeutic implication of this evidence.