White matter changes in cervical dystonia relate to clinical effectiveness of botulinum toxin treatment

Anne J. Blood, John K. Kuster, Jeff L Waugh, Jacob M. Levenstein, Trisha J. Multhaupt-Buell, Lewis R. Sudarsky, Hans C. Breiter, Nutan Sharma

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article number265
JournalFrontiers in Neurology
Volume10
Issue numberAPR
DOIs
StatePublished - Jan 1 2019

Fingerprint

Torticollis
Botulinum Toxins
Dystonia
Anisotropy
Injections
Dystonic Disorders
Globus Pallidus
Therapeutics
White Matter
Central Nervous System

Keywords

  • Ansa lenticularis
  • Basal ganglia
  • Botulinum toxin
  • Diffusion tensor imaging
  • Dystonia
  • Laterality
  • Repeated measures analyses
  • White matter plasticity

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Blood, A. J., Kuster, J. K., Waugh, J. L., Levenstein, J. M., Multhaupt-Buell, T. J., Sudarsky, L. R., ... Sharma, N. (2019). White matter changes in cervical dystonia relate to clinical effectiveness of botulinum toxin treatment. Frontiers in Neurology, 10(APR), [265]. https://doi.org/10.3389/fneur.2019.00265

White matter changes in cervical dystonia relate to clinical effectiveness of botulinum toxin treatment. / Blood, Anne J.; Kuster, John K.; Waugh, Jeff L; Levenstein, Jacob M.; Multhaupt-Buell, Trisha J.; Sudarsky, Lewis R.; Breiter, Hans C.; Sharma, Nutan.

In: Frontiers in Neurology, Vol. 10, No. APR, 265, 01.01.2019.

Research output: Contribution to journalArticle

Blood, AJ, Kuster, JK, Waugh, JL, Levenstein, JM, Multhaupt-Buell, TJ, Sudarsky, LR, Breiter, HC & Sharma, N 2019, 'White matter changes in cervical dystonia relate to clinical effectiveness of botulinum toxin treatment', Frontiers in Neurology, vol. 10, no. APR, 265. https://doi.org/10.3389/fneur.2019.00265
Blood, Anne J. ; Kuster, John K. ; Waugh, Jeff L ; Levenstein, Jacob M. ; Multhaupt-Buell, Trisha J. ; Sudarsky, Lewis R. ; Breiter, Hans C. ; Sharma, Nutan. / White matter changes in cervical dystonia relate to clinical effectiveness of botulinum toxin treatment. In: Frontiers in Neurology. 2019 ; Vol. 10, No. APR.
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