TY - JOUR
T1 - White matter changes in cervical dystonia relate to clinical effectiveness of botulinum toxin treatment
AU - Blood, Anne J.
AU - Kuster, John K.
AU - Waugh, Jeff L.
AU - Levenstein, Jacob M.
AU - Multhaupt-Buell, Trisha J.
AU - Sudarsky, Lewis R.
AU - Breiter, Hans C.
AU - Sharma, Nutan
N1 - Funding Information:
The general infrastructure of the Martinos Center for Biomedical Imaging in which research on these grants was conducted, was supported by National Center for Research Resources (grant number P41 RR14075 to Bruce R. Rosen), and the Mental Illness and Neuroscience Discovery (MIND) Institute (Bruce R. Rosen). Prescreening and exams were conducted in
Funding Information:
This work was supported by grants from the National Institute of Neurological Disorders and Stroke [grant numbers R01NS052368 and R21NS046348 to AB (primary funding for this work), and grant number P50NS037409 NS and Xandra O. Breakefield], and a grant from the Dystonia Medical Research Foundation to AB (primary funding for this work). This work was also supported by the Bachmann-Strauss Dystonia and Parkinson Foundation (Silverman Family Fellowship [JW]), and the American Brain Foundation (Clinical Research Training Fellowship [JW]). This work was also supported by grants to HB (P20DA026002, R33DA026104, R01DA027804) from NIDA, Bethesda, MD. Further support was provided to HB by the Warren Wright Adolescent Center at Northwestern Memorial Hospital & Northwestern University, Chicago, IL.
Publisher Copyright:
© 2019 Blood, Kuster, Waugh, Levenstein, Multhaupt-Buell, Sudarsky, Breiter and Sharma.
PY - 2019
Y1 - 2019
N2 - In a previous report showing white matter microstructural hemispheric asymmetries medial to the pallidum in focal dystonias, we showed preliminary evidence that this abnormality was reduced 4 weeks after botulinum toxin (BTX) injections. In the current study we report the completed treatment study in a full-size cohort of CD patients (n = 14). In addition to showing a shift toward normalization of the hemispheric asymmetry, we evaluated clinical relevance of these findings by relating white matter changes to degree of symptom improvement. We also evaluated whether the magnitude of the white matter asymmetry before treatment was related to severity, laterality, duration of dystonia, and/or number of previous BTX injections. Our results confirm the findings of our preliminary report: we observed significant fractional anisotropy (FA) changes medial to the pallidum 4 weeks after BTX in CD participants that were not observed in controls scanned at the same interval. There was a significant relationship between magnitude of hemispheric asymmetry and dystonia symptom improvement, as measured by percent reduction in dystonia scale scores. There was also a trend toward a relationship between magnitude of pre-injection white matter asymmetry and symptom severity, but not symptom laterality, disorder duration, or number of previous BTX injections. Post-hoc analyses suggested the FA changes at least partially reflected changes in pathophysiology, but a dissociation between patient perception of benefit from injections and FA changes suggested the changes did not reflect changes to the primary “driver” of the dystonia. In contrast, there were no changes or group differences in DTI diffusivity measures, suggesting the hemispheric asymmetry in CD does not reflect irreversible white matter tissue loss. These findings support the hypothesis that central nervous system white matter changes are involved in the mechanism by which BTX exerts clinical benefit.
AB - In a previous report showing white matter microstructural hemispheric asymmetries medial to the pallidum in focal dystonias, we showed preliminary evidence that this abnormality was reduced 4 weeks after botulinum toxin (BTX) injections. In the current study we report the completed treatment study in a full-size cohort of CD patients (n = 14). In addition to showing a shift toward normalization of the hemispheric asymmetry, we evaluated clinical relevance of these findings by relating white matter changes to degree of symptom improvement. We also evaluated whether the magnitude of the white matter asymmetry before treatment was related to severity, laterality, duration of dystonia, and/or number of previous BTX injections. Our results confirm the findings of our preliminary report: we observed significant fractional anisotropy (FA) changes medial to the pallidum 4 weeks after BTX in CD participants that were not observed in controls scanned at the same interval. There was a significant relationship between magnitude of hemispheric asymmetry and dystonia symptom improvement, as measured by percent reduction in dystonia scale scores. There was also a trend toward a relationship between magnitude of pre-injection white matter asymmetry and symptom severity, but not symptom laterality, disorder duration, or number of previous BTX injections. Post-hoc analyses suggested the FA changes at least partially reflected changes in pathophysiology, but a dissociation between patient perception of benefit from injections and FA changes suggested the changes did not reflect changes to the primary “driver” of the dystonia. In contrast, there were no changes or group differences in DTI diffusivity measures, suggesting the hemispheric asymmetry in CD does not reflect irreversible white matter tissue loss. These findings support the hypothesis that central nervous system white matter changes are involved in the mechanism by which BTX exerts clinical benefit.
KW - Ansa lenticularis
KW - Basal ganglia
KW - Botulinum toxin
KW - Diffusion tensor imaging
KW - Dystonia
KW - Laterality
KW - Repeated measures analyses
KW - White matter plasticity
UR - http://www.scopus.com/inward/record.url?scp=85067861259&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067861259&partnerID=8YFLogxK
U2 - 10.3389/fneur.2019.00265
DO - 10.3389/fneur.2019.00265
M3 - Article
C2 - 31019484
AN - SCOPUS:85067861259
SN - 1664-2295
VL - 10
JO - Frontiers in Neurology
JF - Frontiers in Neurology
IS - APR
M1 - 265
ER -