ABSTRACT
BACKGROUND: Individuals with MS undergoing immunoablative therapy and hematopoietic stem cell transplantation (HSCT) show substantial decrease in brain volume over 2.4 months, presumably from chemotoxic effects, although other mechanisms have also been postulated. OBJECTIVE: We examined whether volume loss was accompanied by a concomitant decrease in cognition. White and gray matter volumes, and the effect of stem cell dosage were considered. METHODS: Seven individuals with rapidly progressing MS and poor prognosis underwent high dose immunosuppression and autologous HSCT. Neuropsychological testing and MRI scans were performed at baseline, 2 and 24 months post-procedure. RESULTS: Cognitive impairment was noted at all times in most participants. Median decline of 1.39% in total brain volume was noted 2 months post-HSCT. By 24 months a further decline of 1.65% was noted. At 2 months significant decline was observed for areas of executive functioning. At 24 months almost no significant declines were noted. No significant correlations were found between cognitive decline and change in imaging variables or stem cell dosage. CONCLUSIONS: Cognition changed in the early period following treatment but with little apparent relationship to volume changes. With temporal distance from the HSCT procedure, cognition returned to baseline levels. With the caution of a very small sample, preliminary results suggest that immunoablation and HSCT may have no lasting deleterious effects on cognition.
ABSTRACT
BACKGROUND: Fatigue is a frequently reported and debilitating symptom in multiple sclerosis (MS). Cognitive fatigue (CF) can be defined as decreased performance with sustained cognitive effort. The effectiveness of the Paced Auditory Serial Addition Task (PASAT) and the Computerized Test of Information Processing (CTIP) at detecting CF was examined, as was the impact of methodology. Subjective fatigue was measured using the Fatigue Impact Scale (FIS). The relationship between objective and subjective fatigue was examined. METHODS: 70 MS and 72 healthy controls (HC) completed the PASAT (3â³ and 2â³), CTIP, and FIS as part of a larger battery. RESULTS: The MS and HCs performed worse on cognitively demanding tasks. Depending on methodology, PASAT performance varied between groups at the 3â³ inter-stimulus interval (ISI) and the MS group showed greater susceptibility to CF as their ability to meet task demands declined as the task progressed. CTIP performance for both groups varied differently over time depending on task. The relationship between subjective and objective measures of fatigue varied depending on methodology, with PASAT generally correlating well with the Cognitive Dimension of the FIS. CONCLUSIONS: The PASAT is a sensitive measure of CF in MS. Additional information is obtained with different scoring methods, with percent dyad scoring method being most sensitive to CF. The ability to detect a relationship between objective and subjective measures varied with methodology.
Subject(s)
Cognition Disorders/diagnosis , Fatigue/diagnosis , Fatigue/psychology , Multiple Sclerosis/psychology , Neuropsychological Tests , Psychomotor Performance/physiology , Acoustic Stimulation/methods , Adult , Cognition/physiology , Cognition Disorders/complications , Cognition Disorders/psychology , Fatigue/complications , Female , Humans , Male , Middle Aged , Multiple Sclerosis/complicationsABSTRACT
RATIONALE: Multiple sclerosis (MS) patients exhibit cognitive deficits that negatively impact quality of life. The Relative Consequence Model suggests that problems with information processing speed (IPS) may be the basis for many of these cognitive difficulties. OBJECTIVE: To investigate, with functional magnetic resonance imaging (fMRI), if an IPS task (the Computerized Test of Information Processing (CTIP)) would reveal neurophysiological differences between MS patients and matched controls. METHODS: Performance and neural activation were investigated in twelve cognitively impaired MS patients and 12 matched controls as each performed the CTIP. The CTIP measures reaction time (RT) and errors on three tasks (simple RT, choice RT and semantic search RT) with increasing cognitive demands. RESULTS: Participants demonstrated increased RT with increased task complexity. Patients showed longer RTs for the choice RT condition than controls but the pattern of performance across tasks did not vary between groups. Errors were not significantly different between groups. Imaging results for both the choice and the semantic search conditions revealed significant differences between groups involving a compensatory increase in activation in MS participants compared to controls in prefrontal cortex and right temporal gyri. However, there were also areas of decreased activity in MS participants when compared with controls in left temporal gyri. CONCLUSIONS: Significantly different neural activation patterns between MS patients and controls were associated with IPS, as measured by the CTIP.
Subject(s)
Cognition Disorders/diagnosis , Cognition Disorders/physiopathology , Diagnosis, Computer-Assisted/standards , Magnetic Resonance Imaging/standards , Multiple Sclerosis, Chronic Progressive/physiopathology , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Adult , Diagnosis, Computer-Assisted/methods , Disability Evaluation , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neuropsychological Tests/standardsABSTRACT
OBJECTIVE: To determine if different methods of evaluating cognitive change over time yield measurably different outcomes. METHODS: Twelve cognitively impaired patients with clinically definite Multiple sclerosis (10 relapsing-remitting, 2 secondary progressive) underwent neuropsychological testing (baseline, 6, 12 months). Data was analysed using: t-tests evaluating group differences on individual tests, group differences in composite scores, reliable change analyses at the level of the individual, and comparisons regarding number of tests failed at each time point. RESULTS: Group t-tests on individual tests yielded no change. When tests were grouped according to theoretical constructs, analyses revealed change in processing speed. Reliable change estimates revealed that 16% of the sample deteriorated. When change was measured with respect to the number of domains affected at each time point, 58% of the sample deteriorated on at least one subtest. CONCLUSIONS: Methodology has a significant impact on interpretation of longitudinal data. In the same group of subjects, traditional group analyses documented no change in individual test scores or change on a single composite score. Analyses of individual results documented change from 16 to 58% of the sample. Advantages and disadvantages of each method were discussed. Findings have implications for interpretation of longitudinal studies.
