Browsing by Author "van der Walt, Anneke"

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    Acoustic Speech Analytics Are Predictive of Cerebellar Dysfunction in Multiple Sclerosis
    (Springer, 2020-06) Noffs, Gustavo; Boonstra, Frederique; Perera, Thushara; Kolbe, Scott; Stankovich, Jim; Butzkueven, Helmut; Evans, Andrew; Vogel, Adam; van der Walt, Anneke
    Speech production relies on motor control and cognitive processing and is linked to cerebellar function. In diseases where the cerebellum is impaired, such as multiple sclerosis (MS), speech abnormalities are common and can be detected by instrumental assessments. However, the potential of speech assessments to be used to monitor cerebellar impairment in MS remains unexplored. The aim of this study is to build an objectively measured speech score that reflects cerebellar function, pathology and quality of life in MS. Eighty-five people with MS and 21 controls participated in the study. Speech was independently assessed through objective acoustic analysis and blind expert listener ratings. Cerebellar function and overall disease disability were measured through validated clinical scores; cerebellar pathology was assessed via magnetic resonance imaging, and validated questionnaires informed quality of life. Selected speech variables were entered in a regression model to predict cerebellar function. The resulting model was condensed into one composite speech score and tested for prediction of abnormal 9-hole peg test (9HPT), and for correlations with the remaining cerebellar scores, imaging measurements and self-assessed quality of life. Slow rate of syllable repetition and increased free speech pause percentage were the strongest predictors of cerebellar impairment, complemented by phonatory instability. Those variables formed the acoustic composite score that accounted for 54% of variation in cerebellar function, correlated with cerebellar white matter volume (r = 0.3, p = 0.017), quality of life (r = 0.5, p < 0.001) and predicted an abnormal 9HPT with 85% accuracy. An objective multi-feature speech metric was highly representative of motor cerebellar impairment in MS.
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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.
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    What speech can tell us: A systematic review of dysarthria characteristics in Multiple Sclerosis
    (Elsevier, Inc., 2018-12) Noffs, Gustavo; Perera, Thushara; Kolbe, Scott; Shanahan, Camille; Boonstra, Frederique; Evans, Andrew; Butzkueven, Helmut; van der Walt, Anneke; Vogel, Adam
    IMPORTANCE: Multiple sclerosis produces neurological impairments that are variable in duration, severity and quality. Speech is frequently impaired, resulting in decreased communication skills and quality of life. Advancements in technology now makes it possible to use quantitative acoustic assessment of speech as biomarkers of disease progression. OBSERVATIONS: Four domains of speech have been identified: articulation (slow articulation and imprecise consonants), voice (pitch and loudness instability), respiration (decreased phonatory time and expiratory pressure) and prosody (longer and frequent pauses, deficient loudness control). Studies also explored I) predictive models for diagnosis of MS and of ataxia using speech variables, II) the relationship of dysarthria with cognition and III) very few studies correlated neuroimaging with dysarthria. We could not identify longitudinal studies of speech or dysarthria in Multiple Sclerosis. CONCLUSION AND RELEVANCE: Refinement of objective measures of speech has enhanced our understanding of Multiple Sclerosis-related deficits in cross-sectional analysis while both integrative and longitudinal studies are identified as major gaps. This review highlights the potential for using quantitative acoustic assessments as clinical endpoints for diagnosing, monitoring progression and treatment in disease modifying trials.