Brain atrophy rates in patients with multiple sclerosis on long term natalizumab resembles healthy controls.

BACKGROUND: Clinically stable multiple sclerosis (MS) patients often have negligible inflammatory MRI changes. Brain atrophy may provide insight into subclinical disease progression. The objective was to compare brain atrophy rates in stable patients on long term natalizumab treatment vs. age and gender matched healthy non-MS controls (HC) prospectively over two-years examining brain volume, cognition, and patient reported outcomes (PROs). METHODS: MS patients treated with natalizumab for a minimum of 2 years, age 18-60 were recruited and compared with age- and gender-matched healthy controls (HC). Both groups were followed prospectively to obtain two years of consecutive magnetic resonance imaging, clinical and PRO data. Baseline normalized brain volume (NBV), yearly T2 lesion volume (T2LV), and percent brain volume change (PBVC) were measured using SIENAX, JIM 6.0, and SIENA respectively. Neuropsychological tests from the MACFIMS battery were selected to optimize assessments for impairments in the domains of information processing speed and memory. Patient reported outcomes (PROs) for domains of physical, mental and social quality of life were evaluated using the NeuroQol short forms. RESULTS: Forty-eight natalizumab and 62 HC completed all study visits. At baseline, unadjusted mean NBV (natalizumab=1508.80cm (Popescu et al., 2013) vs. HC=1539.23cm (Popescu et al., 2013); p=0.033) and median baseline T2LV (natalizumab=1724.62mm (Popescu et al., 2013) vs. HC=44.20mm (Popescu et al., 2013); p=<0.0001) were different. The mean PBVC at year 2, adjusted for gender and baseline age was -0.57% (CI: 0.7620, -0.3716) for natalizumab and -0.50% (-0.7208, -0.2831) for HC, but the difference between groups was not statistically significant (0.073%; p=0.62). Over the 2-year period, HC demonstrated mild improvements in some cognitive tests vs. natalizumab subjects. However, PROs were similar between the two groups. CONCLUSION: Stable MS patients on natalizumab have similar brain volume loss as people who do not have MS, suggesting normalization of brain atrophy.

Brain Atrophy Rates for Stable Multiple Sclerosis Patients on Long-Term Fingolimod versus Glatiramer Acetate.

Background: Clinically stable multiple sclerosis (MS) patients on long-term therapy often have negligible acute inflammation on MRI. Brain atrophy may provide insight into subclinical disease progression in such populations. Objective: This study aims to compare brain atrophy for age- and gender-matched MS patients treated for >2 years with fingolimod (FTY) or glatiramer acetate (GA), examining brain volume, cognition, and patient-reported outcomes (PROs). Methods: Stable relapsing-MS patients, age 18-60, on FTY or GA for >2 years were followed up for 2 years. MRI brain and lesion volumes, cognitive measures, and PROs were collected at baseline and annually. Results: Forty-four FTY and forty-three GA patients completed baseline and year 2 visits. No differences in age, gender, or education were observed. Median EDSS was 2.0GA and 2.5FTY (p = 0.22). Treatment duration was longer for GA, 6.50GA vs. 3.73FTY years (p < 0.001). Baseline geometric mean T2LV were different, GA = 1,009.29 cm3 vs. FTY = 2,404.67 cm3 (p = 0.0071). Baseline brain volumes were similar, GA = 1,508 cm3 vs. FTY = 1,489 cm3 (p = 0.2381). Annualized atrophy rates, adjusted for baseline and at mean baseline value, were GA = -0.2775% vs. FTY = -0.2967% (p = 0.7979). No differences in cognitive measures or PROs were observed. Conclusions: Stable MS patients on long-term treatment with FTY and GA have similar brain volume loss rates. Differences in baseline disease severity may suggest patients with more aggressive disease treated with FTY may achieve similar brain volume loss rates as patients with milder baseline disease on GA.

Are Established Embedded Performance Validity Test Cut-Offs Generalizable to Patients With Multiple Sclerosis?

OBJECTIVE: Data for the use of embedded performance validity tests (ePVTs) with multiple sclerosis (MS) patients are limited. The purpose of the current study was to determine whether ePVTs previously validated in other neurological samples perform similarly in an MS sample. METHODS: In this retrospective study, the prevalence of below-criterion responding at different cut-off scores was calculated for each ePVT of interest among patients with MS who passed a stand-alone PVT. RESULTS: Previously established PVT cut-offs generally demonstrated acceptable specificity when applied to our sample. However, the overall cognitive burden of the sample was limited relative to that observed in prior large-scale MS studies. CONCLUSION: The current study provides initial data regarding the performance of select ePVTs among an MS sample. Results indicate most previously validated cut-offs avoid excessive false positive errors in a predominantly relapsing remitting MS sample. Further validation among MS patients with more advanced disease is warranted.

Sleep in patients with neurologic and psychiatric disorders.

Given the widely recognized association between many neurologic and psychiatric disorders and significant sleep disturbances, the International Classification of Sleep Disorders Diagnostic and Coding Manual recognizes "Sleep Disorders Associated with Mental, Neurologic, or Other Medical Disorders" as one of four major classification categories. Such sleep disturbances may exacerbate symptoms of the underlying neurologic or psychiatric disorder or produce further adverse medical, behavioral, or psychosocial consequences. Therefore, adequate assessment and recognition of sleep disturbances in these populations is essential. This article includes a summary of neurologic systems influencing sleep that may be affected by neurologic and psychiatric disorders, followed by a brief review of sleep disturbances associated with many common neurologic and psychiatric disorders.

Individual growth curve analysis of APOE epsilon 4-associated cognitive decline in Alzheimer disease.

BACKGROUND: The apolipoprotein E epsilon4 (APOE epsilon4) allele is associated with an increased risk of developing Alzheimer disease (AD). However, findings regarding an association between the APOE epsilon4 allele and the rate of decline in AD have been mixed. OBJECTIVE: To examine the relationship between the APOE epsilon4 allele and the rate of cognitive and functional decline in AD using individual growth curve analyses. DESIGN: Longitudinal cohort study. SETTING: Alzheimer Disease Research Center at Baylor College of Medicine. PATIENTS: A total of 189 patients meeting NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) criteria for probable AD at baseline who underwent annual follow-up evaluations for at least 2 years. MAIN OUTCOME MEASURES: Individual growth curve parameters derived from baseline and follow-up performance on global and specific measures of cognitive and functional abilities. RESULTS: Patients with 2 APOE epsilon4 alleles exhibited a slower rate of decline on measures of global cognitive functioning and functional abilities. No significant association was detected between the APOE epsilon4 allele and the rate of decline on measures of specific cognitive functions. CONCLUSIONS: Although the APOE epsilon4 allele is associated with an increased risk of developing AD, it seems that having 2 APOE epsilon4 alleles is associated with a slower clinical course. These findings are consistent with hypotheses that the biological processes contributing to the onset of AD are different from those involved in determining its clinical course.