Browsing by Author "Jokubaitis, Vilija"

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    Functional neuroplasticity in response to cerebello-thalamic injury underpins the clinical presentation of tremor in multiple sclerosis
    (SAGE Publishing, 2019-03) Boonstra, Frederique; Noffs, Gustavo; Perera, Thushara; Jokubaitis, Vilija; Vogel, Adam; Moffat, Bradford; Butzkueven, Helmut; Evans, Andrew; van der Walt, Anneke; Kolbe, Scott
    BACKGROUND:: Tremor is present in almost half of multiple sclerosis (MS) patients. The lack of understanding of its pathophysiology is hampering progress in development of treatments. OBJECTIVES:: To clarify the structural and functional brain changes associated with the clinical phenotype of upper limb tremor in people with MS. METHODS:: Fifteen healthy controls (46.1 +/- 15.4 years), 27 MS participants without tremor (46.7 +/- 11.6 years) and 42 with tremor (46.6 +/- 11.5 years) were included. Tremor was quantified using the Bain score (0-10) for overall severity, handwriting and Archimedes spiral drawing. Functional magnetic resonance imaging activations were compared between participants groups during performance of a joystick task designed to isolate tremulous movement. Inflammation and atrophy of cerebello-thalamo-cortical brain structures were quantified. RESULTS:: Tremor participants were found to have atrophy of the cerebellum and thalamus, and higher ipsilateral cerebellar lesion load compared to participants without tremor ( p < 0.020). We found higher ipsilateral activation in the inferior parietal lobule, the premotor cortex and supplementary motor area in MS tremor participants compared to MS participants without tremor during the joystick task. Finally, stronger activation in those areas was associated with lower tremor severity. CONCLUSION:: Subcortical neurodegeneration and inflammation along the cerebello-thalamo-cortical and cortical functional neuroplasticity contribute to the severity of tremor in MS.
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    OnabotulinumtoxinA treatment for MS-tremor modifies fMRI tremor response in central sensory-motor integration areas
    (Elsevier B.V., 2020-02) Boonstra, Frederique; Evans, Andrew; Noffs, Gustavo; Perera, Thushara; Jokubaitis, Vilija; Stankovich, Jim; Vogel, Adam; Moffat, Bradford; Butzkueven, Helmut; Kolbe, Scott; van der Walt, Anneke
    Background: Treatment of tremor in MS is an unmet need. OnabotulinumtoxinA (BoNT-A) has shown promising results; however, little is known regarding its effects on the brain. The clinical presentation of tremor MS is shown to depend on subcortical neural damage and cortical neural plasticity. This study aimed to identify effects of onabotulinumtoxinA (BoNT-A) on brain activation in MS and upper-limb tremor using functional MRI. Methods: Forty-three MS participants with tremor were randomized to receive intramuscular injections of placebo (n = 22) or BoNT-A (n = 21). Tremor was quantified using the Bain score (0–10) for severity, handwriting and Archimedes drawing at baseline, 6 weeks and 12 weeks. Functional MRI activation within two previously identified clusters, ipsilateral inferior parietal cortex (IPL) and remotor/supplementary motor cortex (SMC) of compensatory activity, was measured at baseline and 6 weeks. Results: Treatment with BoNT-A resulted in improved handwriting tremor at 6 weeks (p = 0.049) and 12 weeks (p= 0.014), and tremor severity -0.79 (p=0.007) at 12 weeks. Furthermore, the patients that received BoNT-A showed a reduction in activation within the IPL (p = 0.034), but not in the SMC. The change in IPL activation correlated with the reduction in tremor severity from baseline to 12 weeks (β = 0.608; p = 0.015) in the BoNTA group. No tremor and fMRI changes were seen in the placebo treated group. Conclusion: We have shown that reduction in MS-tremor severity after intramuscular injection with BoNT-A is associated with changes in brain activity in sensorimotor integration regions.