Contributions
Abstract: P1111
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neuropsychology
Background: Few studies have focused on cognitive changes occurring during multiple sclerosis (MS) relapses as measured by neurocognitive tests. In the few published studies, cognitive processing speed as measured by the Symbol Digit Modalities Test (SDMT) declined from baseline, and nearly normalized following conventional steroid therapy. In some studies, this effect was accompanied by changes in patient report outcomes (PROs), but not so in others. To date, there is no study on the effects of subcutaneous adrenocorticotropic hormone (ACTH) self-injection on cognitive outcomes.
Methods: The SDMT and the MS Neuropsychological Screening Questionnaire (MSNQ) were administered at baseline, during relapse but prior to therapy, and at 3-month follow-up. There were two groups of participants: [a] 14 patients with cognitive relapse as indicated by patient, caregiver, or clinician perceived decline and confirmed by a drop of 3 points on SDMT, and [b] 14 stable MS controls. Patients were treated for relapse with 5 days of 80 units/day ACTH self-injection. Follow-up SDMT and MSNQ scores were obtained 90 days later. Patients who recovered 3 or more points on the SDMT were categorized as ACTH responders (n = 7). Data were analyzed by mixed-factor ANOVA with a significance threshold of p < 0.05.
Results: Relapsing and stable patients differed on SDMT and MSNQ, with only relapsing patients declining at relapse, and showing statistically significant recovery. Within the relapsing group, the responder analysis revealed a significant interaction, or trend, on three MSNQ items: item 3 (slowed problem solving, p = 0.026), item 1 (easily distracted, p = 0.056) and item 7 (need instructions repeated, p = 0.096). Perceived worsening of impairment was observed at time of relapse in both groups, but only responders reported perceived improvement at 3 months.
Conclusions: These findings suggest a recovery from cognitive relapse in patients treated with subcutaneous ACTH self-injection. PRO changes are found concordant with changes noted on the SDMT. These results may have significant implications for future trial design examining cognitive relapse and recovery, and for ascribing clinical meaningfulness to changes in SDMT and self-reported measures of cognition. Future studies are warranted.
Disclosure: This research was supported by Mallinckrodt.
Katrina A. Kunker has nothing to disclose.
Allison S. Drake has nothing to disclose.
Lauren N. Irwin has nothing to disclose.
Anjum Khan has nothing to disclose.
Margaret Bucello has received personal compensation for speaking and serving on advisory boards for Mallinckrodt, Biogen, Teva, Genzyme and Sanofi.
Bianca Weinstock-Guttman has received personal compensation for consulting, speaking and serving on a scientific advisory board for Biogen Idec, Teva Neuroscience, EMD Serono, Novartis, Questcor and Genzyme & Sanofi. She has received financial support for research activities from NMSS, NIH, ITN, Teva Neuroscience, Biogen Idec, EMD Serono, Aspreva, Novartis, Genzyme.
Ralph HB Benedict receives research support from Biogen, Novartis, Genzyme, Acorda and Mallinckrodt, provides consultation for Biogen, Genentech, Teva, Novartis, and Sanofi, and conducts CME for EMD Serono.
Abstract: P1111
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neuropsychology
Background: Few studies have focused on cognitive changes occurring during multiple sclerosis (MS) relapses as measured by neurocognitive tests. In the few published studies, cognitive processing speed as measured by the Symbol Digit Modalities Test (SDMT) declined from baseline, and nearly normalized following conventional steroid therapy. In some studies, this effect was accompanied by changes in patient report outcomes (PROs), but not so in others. To date, there is no study on the effects of subcutaneous adrenocorticotropic hormone (ACTH) self-injection on cognitive outcomes.
Methods: The SDMT and the MS Neuropsychological Screening Questionnaire (MSNQ) were administered at baseline, during relapse but prior to therapy, and at 3-month follow-up. There were two groups of participants: [a] 14 patients with cognitive relapse as indicated by patient, caregiver, or clinician perceived decline and confirmed by a drop of 3 points on SDMT, and [b] 14 stable MS controls. Patients were treated for relapse with 5 days of 80 units/day ACTH self-injection. Follow-up SDMT and MSNQ scores were obtained 90 days later. Patients who recovered 3 or more points on the SDMT were categorized as ACTH responders (n = 7). Data were analyzed by mixed-factor ANOVA with a significance threshold of p < 0.05.
Results: Relapsing and stable patients differed on SDMT and MSNQ, with only relapsing patients declining at relapse, and showing statistically significant recovery. Within the relapsing group, the responder analysis revealed a significant interaction, or trend, on three MSNQ items: item 3 (slowed problem solving, p = 0.026), item 1 (easily distracted, p = 0.056) and item 7 (need instructions repeated, p = 0.096). Perceived worsening of impairment was observed at time of relapse in both groups, but only responders reported perceived improvement at 3 months.
Conclusions: These findings suggest a recovery from cognitive relapse in patients treated with subcutaneous ACTH self-injection. PRO changes are found concordant with changes noted on the SDMT. These results may have significant implications for future trial design examining cognitive relapse and recovery, and for ascribing clinical meaningfulness to changes in SDMT and self-reported measures of cognition. Future studies are warranted.
Disclosure: This research was supported by Mallinckrodt.
Katrina A. Kunker has nothing to disclose.
Allison S. Drake has nothing to disclose.
Lauren N. Irwin has nothing to disclose.
Anjum Khan has nothing to disclose.
Margaret Bucello has received personal compensation for speaking and serving on advisory boards for Mallinckrodt, Biogen, Teva, Genzyme and Sanofi.
Bianca Weinstock-Guttman has received personal compensation for consulting, speaking and serving on a scientific advisory board for Biogen Idec, Teva Neuroscience, EMD Serono, Novartis, Questcor and Genzyme & Sanofi. She has received financial support for research activities from NMSS, NIH, ITN, Teva Neuroscience, Biogen Idec, EMD Serono, Aspreva, Novartis, Genzyme.
Ralph HB Benedict receives research support from Biogen, Novartis, Genzyme, Acorda and Mallinckrodt, provides consultation for Biogen, Genentech, Teva, Novartis, and Sanofi, and conducts CME for EMD Serono.