Medicine (RMH) - Research Publications

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Type: Abstract × Author: Perera, Thushara ×

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    Pathophysiology of MS tremor: an fMRI study
    Boonstra, FMC ; Noffs, G ; Perera, T ; Shanahan, CJ ; Vogel, AP ; Evans, A ; Butzkueven, H ; van der Walt, A ; Kolbe, SC (SAGE PUBLICATIONS LTD, 2017-10)
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    Subclinical speech signs correlate with MS disease severity and differentiates patients with and without clinical cerebellar dysfunction
    Noffs, G ; Boonstra, F ; Perera, T ; Kolbe, S ; Shanahan, C ; Evans, A ; Butzkueven, H ; Vogel, A ; van der Walt, A (SAGE PUBLICATIONS LTD, 2017-10-01)
    Background: Dysarthria is highly prevalent in Multiple Sclerosis (MS). The relationship between dysarthria, MS disease severity and other cerebellar manifestations (such as tremor) is poorly understood. Aim: To examine the relationship between objective markers of speech, disease severity and upper limb tremor in relapsing-remitting and secondary progressive MS. Method: An experienced neurologist determined A) the presence of upper limb tremor, B) the Expanded Disability Status Scale (EDSS) score and C) the degree of dysarthria (from 0, no disturbance to 4, unintelligible). We used acoustic analysis to investigate 4 speech domains: 1) stability of vocal pitch, in sustained utterance of the vowel /a/; 2) stability of loudness, in the same sustained vowel; 3) diadochokinetic speed, in fast repetition of the meaningless word /pa/ta/ka/ and 4) maximum speed of vocal tract movement (i.e. change in pharynx and mouth cavity shape), measured through change in the second formant frequency in the word “always”, from reading of the “Grandfather Passage”. After adjustment for multiple comparisons, a p< 0.0125 was considered for statistical significance. Results: We assessed 24 MS patients with upper limb tremor (47.2±12.3years, 75% female, EDSS=3.7±1.6) and 24 matched patients without tremor (51.2±10.7years, 75% female, EDSS=3.6±1.7). Clinical dysarthria (median=0, mean=0.375±0.76) moderately correlated with EDSS scores (Spearman's rho =.586, p< .001) and with syllable repetition rates (/pa/ta/ka/ rho=.561, p< .001), marginally correlated with speed of tract movement (rho=.363, p=.012), pitch stability (rho=.37, p=.011), loudness stability (rho=.37, p=.01) but not with upper limb tremor presence (p=.039). Only /pa/ta/ka/ rate correlated with EDSS (rho=.529, p< .001) and speed of tract movement differentiated tremor and non-tremor groups (2-tailed t-test p=0.002, rho=.418). Conclusion: Acoustic speech measurements correlate with MS disease severity and can differentiate overt cerebellar dysfunction. Further study is needed to understand the significance of this relationship longitudinally.
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    Objective analysis of speech correlates with disease severity in Multiple Sclerosis and differentiates groups with and without upper limb tremor
    Noffs, G ; Boonstra, F ; Perera, T ; Kolbe, SC ; Shanahan, CJ ; Evans, A ; Butzkueven, H ; Vogel, AP ; van der Walt, A (SAGE PUBLICATIONS LTD, 2017-11-01)
    Background: Dysarthria is highly prevalent in Multiple Sclerosis. The relationship between dysarthria, MS disease severity and other cerebellar manifestations (such as tremor) is poorly understood. Objective: To examine the relationship between objective markers of speech, disease severity and upper limb tremor in relapsing-remitting and secondary progressive Multiple Sclerosis. Design Methods: An experienced neurologist determined A) the presence of upper limb tremor, B) the Expanded Disability Status Scale (EDSS) score and C) the degree of dysarthria (from 0, no disturbance to 4, unintelligible). Through acoustic analysis of speech, we investigated: 1) stability of vocal pitch, in sustained utterance of the vowel /a/; 2) stability of loudness, in the same sustained vowel; 3) diadochokinetic speed, in fast repetition of the meaningless word /pa/ta/ka/ and 4) maximum speed of vocal tract movement (i.e. change in pharynx and mouth cavity shape), measured in the word “always” (from a standard reading passage). After adjustment for multiple comparisons, p<0.0125 was considered for statistical significance. Results: We assessed 24 participants with Multiple Sclerosis and upper limb tremor (47.2±12.3years, 75% female, EDSS=3.7±1.6) and 24 matched patients with Multiple Sclerosis without tremor (51.2±10.7years, 75% female, EDSS=3.6±1.7). Clinical dysarthria scores (median=0, mean=0.375±0.76) correlated with all acoustic variables measured: diadochokinetic speed Spearman’s rho=.561 (p<.001); pitch stability rho=.37 (p=.011); loudness stability rho=.37 (p=.01); and maximum speed of vocal tract movement rho=.363 (p=.012). Diadochokinetic speed strongly correlated with EDSS (rho=.529, p<.001). Speed of vocal tract movement correlated with tremor and differentiated tremor and non-tremor groups (2-tailed t-test p=0.002, rho=.418). Conclusions: In a typically non-to-mildly dysarthric cohort, acoustic speech measurements correlate with disease severity and can differentiate overt cerebellar dysfunction in Multiple Sclerosis. Further study is needed to understand the significance of this relationship longitudinally.
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    Pathophysiology of MS tremor: an fMRI study
    Boonstra, F ; Noffs, G ; Perera, T ; Shanahan, C ; Vogel, A ; Evans, A ; Butzkueven, H ; van der Walt, A ; Kolbe, S (SAGE PUBLICATIONS LTD, 2017-11)
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    A comparison of human and digital speech analysis to describe and monitor cerebellar dysfunction and disease severity in multiple sclerosis.
    Noffs, G ; Boonstra, F ; Maldonado, F ; Perera, T ; Kolbe, S ; Evans, A ; Butzkeuven, H ; Vogel, A ; van der Walt, A (SAGE PUBLICATIONS LTD, 2018-10)
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    Functional neuroplasticity in response to cerebello-thalamic injury underpins the clinical presentation of tremor in multiple sclerosis
    Boonstra, FMC ; Noffs, G ; Perera, T ; Jokubaitis, VG ; Vogel, AP ; Moffat, BA ; Butzkueven, H ; Evans, A ; van der Walt, A ; Kolbe, SC (SAGE PUBLICATIONS LTD, 2020-05)
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    Validation of the tremor biomechanics analysis laboratory (TREMBAL) software in MS tremor
    Van der Walt, A ; Boonstra, FMC ; Yohanandan, SAC ; Vogel, AP ; Kolbe, SC ; Ly, J ; Noffs, G ; Butzkueven, H ; Evans, AH ; Perera, T (SAGE PUBLICATIONS LTD, 2016-09-01)
    Type: Poster Abstract Category: Clinical aspects of MS - Clinical assessment tools Background: Tremor in MS (MST) is difficult to treat and the development of new interventions is limited by the absence of universal measuring systems. At present, therapeutic outcomes are measured by a variety of clinical rating scales that are subjective and lack sufficient sensitivity. With increasing use of interventional treatments such as Botulinum toxin injections or Deep Brain Stimulation for MST, it has become critical to develop precise measurement instruments. Objective: To clinically validate the TREMBAL software in MST. Methods: TREMBAL (Bionics Institute, Melbourne, Australia) utilises an electromagnetic motion tracker (Ascension, Vermont, US) to acquire absolute displacements and rotations of a tremulous body part. Tremor was recorded bilaterally from four locations (second phalanx of the middle finger, wrist dorsum, forearm and upper arm) in five positions (hands resting on lap, arms outstretched in front, finger-nose, batwing static and batwing action). Tremor exercises were video recorded (GoPro Hero3, GoPro Inc., San Mateo, California) and rated by two experts using the 5-point Unified Tremor Rating Assessment (UTRA) scale where 0=no tremor and 4=severe. TREMBAL tremor displacements (measured in units of millimetres) were averaged and log transformed to match the distribution of clinical ratings. Data were pooled across exercises. Congruence between TREMBAL measures and mean clinical ratings was explored using regression analysis and Pearson´s correlation. Results: We assessed ten MST patients over 6 months and rated 200 videos. The median pooled UTRA score was 0.5 (interquartile range 0, 1.5). The average TREMBAL recorded tremor displacement was 1.65 mm (standard deviation 2.1). A strong correlation between UTRA scores and log transformed TREMBAL displacement was found, r = 0.749, p< 0.001. Conclusions: TREMBAL measurements are highly accurate when compared to clinical measurements. While other objective tremor measures exist, only a few have been benchmarked specifically against MST clinical ratings. The validation of an objective, 3 dimensional tremor measurement system provides real-time tremor severity measurements for clinicians and can be applied in clinical trials of putative therapies for MST.