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.
Highlights
Dystonia is thought to sometimes result from brain plasticity “gone wrong,” with too much of a good thing resulting in pathophysiology of the sensorimotor system [1,2,3]
These findings provide evidence that Botulinum toxin (BTX) treatment in dystonia affects function of the basal ganglia circuitry, and support a role for this circuitry in the expression of cervical dystonia symptoms
The laterality of the asymmetry is consistent with a conceptual model that proposes dystonia reflects amplification of a left-lateralized functional brain system, namely the system controlling posture and body stabilization
Summary
Dystonia is thought to sometimes result from brain plasticity “gone wrong,” with too much of a good thing resulting in pathophysiology of the sensorimotor system [1,2,3]. It is believed that changes in brain structure and function following BTX [e.g., [6,7,8,9,10,11]] are exerted through changes in motor afferent function reflecting the changes in muscle function Such indirect central effects are thought to facilitate or complement the direct, peripheral effects of BTX in some cases in either an acute or more longitudinal (e.g., plastic) manner, and may temporarily help to break a cycle of excessive function in the sensorimotor circuitry. These effects are likely not able to remove the primary driver of excessive central function in dystonia, so once the effects of BTX wear off and muscle function increases again, the central abnormalities are expected in most cases to be reinstated, along with dystonia symptoms
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