Longitudinal change in Paced Auditory Serial Addition Test (PASAT) performance following immunoablative therapy and haematopoietic stem cell transplant in multiple sclerosis

Background: Immediately following immunoablation and hematopoietic stem cell transplantation (IA-HSCT) for MS a median decrease in brain volume of 3.2 % over 2.4 months occurs. After 2 years, rates of atrophy are comparable to normal volunteers. Potential impact of atrophy on cognition was evaluated by examining performance on the Paced Auditory Serial Addition Test (PASAT) preand post-IA-HSCT. Methods: Twenty-three individuals with rapidly progressing/poor prognosis MS underwent high dose IA-HSCT. Individuals completed the 3” PASAT at baseline and 6/12/18/24/30/36 months post-procedure. Results: Mean decline in performance between baseline and 6-months occurred, though it was not statistically significant. Minor declines were offset by an overall trend for improvement over time. The largest (non-significant) cognitive gains were between months 30 and 36. Neither level of impairment at baseline, nor demographic variables, influenced likelihood of improvement. No relationship between changes in cognition and changes in volumes was detected, likely secondary to small sample size. Conclusions: While an initial decline in cognition was noted 6 months post-IA-HSCT, there were no lasting negative effects of treatment given the overall trend for improvement. Initial cognitive decline and marked volume loss are likely secondary to acute toxic effects of chemotherapy. Gains in cognition noted over 36 months suggest long-term follow-up is essential.