Necessity of technicians for computerized neuropsychological assessment devices in multiple sclerosis.

OBJECTIVE: Determine the influence of technician supervision on computer-administered cognitive tests in multiple sclerosis (MS). METHODS: Eighty MS patients underwent assessment using the CogState Brief Battery (CSBB) and the Cleveland Clinic Cognitive Battery (C3B). Each was administered twice, once with a technician guiding assessment, and once with technician-absent. Twenty-eight healthy controls were also evaluated. RESULTS: The influence of technician guidance was not statistically significant for group means on either test. For CSBB, administration problems were more common in the technician-absent condition. CONCLUSION: In this MS sample, reliable and valid test results were obtained from computer-assisted cognitive testing without technician guidance.

Trait neuroticism, extraversion, and conscientiousness in multiple sclerosis: Link to cognitive impairment?

BACKGROUND: Previous research suggests that patients with multiple sclerosis (MS) have higher neuroticism, lower extraversion, and lower conscientiousness relative to healthy controls (HCs). However, the prevalence of this maladaptive profile in MS and its relation to cognition is unknown. OBJECTIVE: Determine prevalence of maladaptive personality among MS patients, compared to HCs, and examine how it relates to cognitive dysfunction. METHODS: A sample of 275 MS patients and 55 HCs completed neuroperformance measures of information processing speed and memory. Self and informant ratings were obtained on the NEO Five-Factor Inventory. RESULTS: MS patients had higher neuroticism and lower extraversion than HCs. Cognitively impaired patients were also lower in conscientiousness. Cluster analysis revealed a configuration of these same three traits, representing a maladaptive profile. This profile was found in 50% of the overall MS sample, compared to 24% of HCs. However, only cognitively impaired MS patients had a higher prevalence of maladaptive personality compared to HCs. Among cognitively impaired patients, those with maladaptive traits were impaired in more cognitive domains than those with more adaptive traits. CONCLUSION: Cognitively impaired MS patients have a higher prevalence of seemingly maladaptive traits compared to HCs, demonstrating an association between cognition and personality in MS.

Differential effects of aging on motor and cognitive functioning in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) patients are impaired in motor and cognitive performance, but the extent to which these deficits are magnified by aging is unknown. In one prior study, differences in cognitive processing speed between MS patients and healthy individuals were of similar magnitude across the lifespan. Here, we have improved on this work by expanding assessment to multiple cognitive domains and motor functioning. OBJECTIVE: To determine whether the degree of cognitive and motor dysfunction in MS is magnified with increasing age. METHODS: In all, 698 MS patients (aged 29-71 years) and 226 healthy controls (HCs; aged 18-72 years) completed neuroperformance tests covering ambulation, upper extremity function, information processing speed, and memory. RESULTS: Linear regression models predicting cognitive and motor function revealed main effects of MS/HC diagnosis, age, and education across all measures. There was also an interaction between age and diagnosis on measures of motor function, but not on cognitive outcomes. CONCLUSION: The progression of motor decline is amplified by aging in MS. However, the degree of cognitive impairment does not vary across the lifespan. Thus, evidence of accelerated cognitive impairment in older adults with MS may signal the presence of other age-related cognitive pathologies.

Latent profile analysis of regression-based norms demonstrates relationship of compounding MS symptom burden and negative work events.

OBJECTIVE: We endeavored to clarify how distinct co-occurring symptoms relate to the presence of negative work events in employed multiple sclerosis (MS) patients. Latent profile analysis (LPA) was utilized to elucidate common disability patterns by isolating patient subpopulations. METHOD: Samples of 272 employed MS patients and 209 healthy controls (HC) were administered neuroperformance tests of ambulation, hand dexterity, processing speed, and memory. Regression-based norms were created from the HC sample. LPA identified latent profiles using the regression-based z-scores. Finally, multinomial logistic regression tested for negative work event differences among the latent profiles. RESULTS: Four profiles were identified via LPA: a common profile (55%) characterized by slightly below average performance in all domains, a broadly low-performing profile (18%), a poor motor abilities profile with average cognition (17%), and a generally high-functioning profile (9%). Multinomial regression analysis revealed that the uniformly low-performing profile demonstrated a higher likelihood of reported negative work events. CONCLUSIONS: Employed MS patients with co-occurring motor, memory and processing speed impairments were most likely to report a negative work event, classifying them as uniquely at risk for job loss.

Benchmarks of meaningful impairment on the MSFC and BICAMS.

BACKGROUND: Cognitive and motor abilities in multiple sclerosis (MS) are typically quantified using reliable, consensus standard tests validated in the MS population. While these performance measures are associated with vocational disability in parametric analyses, translation of raw scores into anchors reflecting clinically relevant, functional impairment requires further research. OBJECTIVE: To examine performance-based motor and cognitive outcomes among definitive anchors that designate varying degrees of functional impairment, thereby establishing benchmarks for score interpretation. METHODS: We evaluated MS patients and healthy controls, all undergoing a brief test battery. Outcomes were derived from the MS Functional Composite (MSFC) and the Brief International Cognitive Assessment for MS (BICAMS). Functional impairment anchors were (1) disability benefits, (2) employed with negative work events, and (3) employed without problems. RESULTS: All measures yielded statistically significant differences across all levels of work status, after accounting for the effects of age and education. Benchmark values distinguished the functional impairment groups. When evaluated in combination, the Timed 25-Foot Walk and the Symbol Digit Modalities Test were the most robust predictors of functional decline. CONCLUSION: We have established benchmark scores for popular motor and cognitive tests that are associated with specific degrees of impairment in work status.

Impact of Pharmacotherapy on Cognitive Dysfunction in Patients with Multiple Sclerosis.

Cognitive impairment is a common symptom of multiple sclerosis (MS), adversely impacting many spheres of daily functioning. Yet the effectiveness of pharmacological interventions for cognitive impairment in MS is unclear. Clinicians and patients alike would benefit from formal guidelines regarding effective management of cognitive symptoms. We reviewed the background on the measurement, pathophysiology and risk factors for cognitive dysfunction in MS, and then examined the published clinical trials of pharmacotherapy, including both disease-modifying treatments (DMTs) and symptom-management therapies (SMTs). Our review of DMTs revealed only a single well-designed, randomized, controlled trial where intramuscular interferon (IFN)-ß1a, administered once weekly, was compared with placebo. The results showed significant benefits in terms of cognitive processing speed and memory. Less convincing but promising data have shown the potential benefits of IFN-ß1b and natalizumab. The literature on SMTs is replete with placebo-controlled, single-centre studies, with a failure to replicate initially promising results. The results for SMTs such as acetylcholinesterase inhibitors and psychostimulants are mixed. Some encouraging data show promise but not to a threshold of indication for standard clinical use. Numerous methodological factors hamper research in this area. Acknowledging the lack of firm conclusions, we argue that all DMTs are likely to benefit cognition and that, if otherwise safe, SMTs with some empirical support may be attempted at the discretion of the treating clinician. We offer some guidance on the assessment and monitoring of cognitive function to inform off-license treatment of cognitive impairment in MS patients.

Stable neuropsychiatric status in multiple sclerosis: a 3-year study.

Personality changes and neuropsychiatric symptoms are found in multiple sclerosis (MS), but no study has evaluated decline compared to healthy controls. This study assessed personality traits and neuropsychiatric symptoms over 3 years using the NEO Five Factor Inventory and the Neuropsychiatric Inventory. Additional metrics evaluated ambulation, manual dexterity and cognitive function. Contrary to hypothesis, patients showed no significant change in personality or neuropsychiatric status relative to controls. Patients were impaired in motor and cognitive function at baseline and follow-up, but showed only slowing in ambulation over time. The findings indicate that neuropsychiatric status is stable in MS over 3 years.

Negative work events reported online precede job loss in multiple sclerosis.

PURPOSE: Determine if a recently validated online survey of negative work events can predict future job loss among multiple sclerosis (MS) patients. METHOD: Evaluated were 284 employed individuals (63 healthy controls, 221 MS patients), every three months, using an online vocational monitoring tool. Job loss rates in MS patients were compared with the healthy controls. Survey responses from MS patients suffering job loss (n=23) were then compared to those maintaining employment. Analyses focused on the frequency of negative work events. RESULTS: While 23 (10%) of MS patients lost their job after baseline, there was no job loss among the healthy controls. Compared to stably employed patients, those suffering job loss had been diagnosed with MS later in life, were more likely to report a progressive disease course, and had greater physical disability as measured by the Patient Derived Disease Steps (PDDS). Declining patients were also more likely to report negative work events within three months of job loss (e.g., verbal criticism for errors or removal of responsibilities). Stepwise logistic regression predicting MS job loss retained the PDDS, age at diagnosis, years working for employer and reporting a negative work event. CONCLUSIONS: The results show that physical disability and patient reported risk factors for job loss can be monitored using an online survey tool. The tool can trigger clinical assessments to help prevent unemployment and assist patients in procuring disability benefits.

Targeting 11q23 positive acute leukemia cells with high molecular weight-melanoma associated antigen-specific monoclonal antibodies.

BACKGROUND: Acute leukemia with 11q23 aberrations is associated with a poor outcome with therapy. The lack of efficacy of conventional therapy has stimulated interest in developing novel strategies. Recent studies have shown that 11q23-positive acute leukemia cells express the high molecular weight-melanoma associated antigen (HMW-MAA). This tumor antigen represents a useful target to control growth of human melanoma tumors in patients and in severe combined immunodeficient (SCID) mice, utilizing antibody-based immunotherapy. This effect appears to be mediated by inhibition of the HMW-MAA function such as triggering of the focal adhesion kinase/proline-rich tyrosine kinase 2 (Pyk2) pathways. Therefore, in this study we tested whether HMW-MAA-specific monoclonal antibodies (mAb) could inhibit growth of 11q23-positive leukemia cells in SCID mice. METHODS: HMW-MAA-specific mAb were tested for their ability to inhibit the in vitro proliferation of an 11q23-positive acute myeloid leukemia (AML) cell line and blasts from four patients with 11q23 aberrations and their in vivo growth in subcutaneous and disseminated xenograft models. RESULTS: The HMW-MAA-specific mAb did not affect in vitro proliferation although they down-regulated phosphorylated (P) Pyk2 expression. Furthermore, the mAb enhanced the in vitro anti-proliferative effect of cytarabine. In vivo the mAb inhibited the growth of leukemic cells in a dose-dependent fashion. However, the difference did not reach statistical significance. No effect was detected on P-Pyk2 expression. Furthermore, HMW-MAA-specific mAb in combination with cytarabine did not improve tumor inhibition. Lastly, the combination of two mAb which recognize distinct HMW-MAA determinants had no detectable effect on survival in a disseminated xenograft model. CONCLUSIONS: HMW-MAA-specific mAb down-regulated P-Pyk2 expression and enhanced the anti-proliferative effect of cytarabine in vitro, but had no detectable effect on survival or growth of leukemia cells in vivo. Whether the HMW-MAA-specific mAb can be used as carriers of toxins or chemotherapeutic agents against 11q23-acute leukemia remains to be determined.