Contributions
Abstract: 205
Type: Oral
Abstract Category: RIMS - Neurobiology & Rehabilitation
Background: The absence of a gold standard for improving physical disability in MS, especially in its progressive forms, mandates new, neuroscientifically grounded approaches to treatment. Physical training trials of MS to date have
(1) limited evidence for long-term post-treatment retention,
(2) only rarely shown real-world transfer of treatment-setting training effects, and
(3) had very restricted neuroplasticity changes.
Constraint-Induced Movement therapy (CI therapy) has over 25 years" controlled evidence of efficacy for overcoming behaviorally conditioned suppressed limb activity (“learned nonuse”) in various non-progressive paralytic disorders (stroke, cerebral palsy [CP], traumatic brain injury), with benefits retained for years, but its effects on a progressive disease such as MS have been little investigated. Moreover, CI therapy has been followed by profuse structural cortical grey matter increases on Voxel-Based Morphometry (VBM) in stroke and CP. This presentation will therefore summarize the clinical and MRI outcomes from our laboratory of CI therapy for progressive MS.
Method: 20 adults with chronic progressive hemiparetic MS and significant nonuse of the more paretic arm were randomised to 2 weeks (3.5 h/day) of either CI therapy or a dose-matched program of Complementary and Alternative Medicine (CAM) training (aquatic therapy, yoga, meditation, relaxation techniques). All participants underwent structural 3 Tesla MRI at pre- and post-treatment. Clinical changes were evaluated at post-treatment and 1-year follow-up.
Results: No adverse events. The groups had identical expectancy to benefit at pre-treatment. The CI group had greater improvement on the Motor Activity Log at post-treatment than did the CAM group
(p < 0.001, between-group effect size = 1.6). These treatment gains were retained at 1-year follow-up. Only the CI group showed significant grey matter structural increases on VBM, which appeared over the bilateral sensorimotor cortices, hippocampi, and diverse subcortical nuclei (thalamus, basal ganglia, amygdala), as well as significantly improved fractional anisotropy on Tract-Based Spatial Statistics, which involved the corpus callosum, corticospinal tract, and sub-occipital cortex (p < 0.05).
Conclusion: CI therapy shows promise for prolonged real-world motor training benefits as well as extensive neuroplastic grey and white matter structural increases. This presentation will also detail the treatment method.
Disclosure:
Victor Mark: Funding supported by the United States Department of Defense (DOD), the Patient Centered Outcomes Research Institute (PCORI), the National Institute on Disability, Independent Living, and Rehabilitation Research, and the National Institutes of Health (NIH)
Edward Taub: Funding supported by the DOD and PCORI
Michelle Haddad: Nothing to disclose
Ameen Barghi: Nothing to disclose
Gitendra Uswatte: Supported by the DOD and PCORI
Gary Cutter: serves on the Data and Safety Monitoring boards of Apotek, Biogen-Idec, Cleveland Clinic, Glaxo Smith Klein Pharmaceuticals, Gilead Pharmaceuticals, Modigenetech/Prolor, Merck/Ono Pharmaceuticals, Merck, Neuren, PCT Bio, Revalesio, Sanofi-Aventis, Teva, Vivus, NHLBI (Protocol Review Committee), NINDS, NMSS, NICHD (OPRU oversight committee), on the consultation and advisory boards of Alexion, Allozyne, Consortium of MS Centers, Diogenix, Klein-Buendel Incorporated, Genzyme, Medimmune, Novartis, Nuron Biotech, Receptos, Spiniflex Pharmaceuticals, Somahlution, Teva pharmaceuticals, Xenoport, and is the corporate president of Pythagoras, Inc.
Tyler Rickards: Nothing to disclose
Chelsey Sterling: Nothing to disclose
Brent Womble: Nothing to disclose
Jarrod Hicks: Nothing to disclose
Mary Bowman: Nothing to disclose
Staci McKay: Funding supported by the DOD and PCORI
David Morris: Nothing to disclose
Terrie Adams: Nothing to disclose
Jerzy Szaflarski: Funding supported by the NIH
Jane Allendorfer: Funding supported by the NIH
Abstract: 205
Type: Oral
Abstract Category: RIMS - Neurobiology & Rehabilitation
Background: The absence of a gold standard for improving physical disability in MS, especially in its progressive forms, mandates new, neuroscientifically grounded approaches to treatment. Physical training trials of MS to date have
(1) limited evidence for long-term post-treatment retention,
(2) only rarely shown real-world transfer of treatment-setting training effects, and
(3) had very restricted neuroplasticity changes.
Constraint-Induced Movement therapy (CI therapy) has over 25 years" controlled evidence of efficacy for overcoming behaviorally conditioned suppressed limb activity (“learned nonuse”) in various non-progressive paralytic disorders (stroke, cerebral palsy [CP], traumatic brain injury), with benefits retained for years, but its effects on a progressive disease such as MS have been little investigated. Moreover, CI therapy has been followed by profuse structural cortical grey matter increases on Voxel-Based Morphometry (VBM) in stroke and CP. This presentation will therefore summarize the clinical and MRI outcomes from our laboratory of CI therapy for progressive MS.
Method: 20 adults with chronic progressive hemiparetic MS and significant nonuse of the more paretic arm were randomised to 2 weeks (3.5 h/day) of either CI therapy or a dose-matched program of Complementary and Alternative Medicine (CAM) training (aquatic therapy, yoga, meditation, relaxation techniques). All participants underwent structural 3 Tesla MRI at pre- and post-treatment. Clinical changes were evaluated at post-treatment and 1-year follow-up.
Results: No adverse events. The groups had identical expectancy to benefit at pre-treatment. The CI group had greater improvement on the Motor Activity Log at post-treatment than did the CAM group
(p < 0.001, between-group effect size = 1.6). These treatment gains were retained at 1-year follow-up. Only the CI group showed significant grey matter structural increases on VBM, which appeared over the bilateral sensorimotor cortices, hippocampi, and diverse subcortical nuclei (thalamus, basal ganglia, amygdala), as well as significantly improved fractional anisotropy on Tract-Based Spatial Statistics, which involved the corpus callosum, corticospinal tract, and sub-occipital cortex (p < 0.05).
Conclusion: CI therapy shows promise for prolonged real-world motor training benefits as well as extensive neuroplastic grey and white matter structural increases. This presentation will also detail the treatment method.
Disclosure:
Victor Mark: Funding supported by the United States Department of Defense (DOD), the Patient Centered Outcomes Research Institute (PCORI), the National Institute on Disability, Independent Living, and Rehabilitation Research, and the National Institutes of Health (NIH)
Edward Taub: Funding supported by the DOD and PCORI
Michelle Haddad: Nothing to disclose
Ameen Barghi: Nothing to disclose
Gitendra Uswatte: Supported by the DOD and PCORI
Gary Cutter: serves on the Data and Safety Monitoring boards of Apotek, Biogen-Idec, Cleveland Clinic, Glaxo Smith Klein Pharmaceuticals, Gilead Pharmaceuticals, Modigenetech/Prolor, Merck/Ono Pharmaceuticals, Merck, Neuren, PCT Bio, Revalesio, Sanofi-Aventis, Teva, Vivus, NHLBI (Protocol Review Committee), NINDS, NMSS, NICHD (OPRU oversight committee), on the consultation and advisory boards of Alexion, Allozyne, Consortium of MS Centers, Diogenix, Klein-Buendel Incorporated, Genzyme, Medimmune, Novartis, Nuron Biotech, Receptos, Spiniflex Pharmaceuticals, Somahlution, Teva pharmaceuticals, Xenoport, and is the corporate president of Pythagoras, Inc.
Tyler Rickards: Nothing to disclose
Chelsey Sterling: Nothing to disclose
Brent Womble: Nothing to disclose
Jarrod Hicks: Nothing to disclose
Mary Bowman: Nothing to disclose
Staci McKay: Funding supported by the DOD and PCORI
David Morris: Nothing to disclose
Terrie Adams: Nothing to disclose
Jerzy Szaflarski: Funding supported by the NIH
Jane Allendorfer: Funding supported by the NIH