168 results on '"Yiu, EM"'
Search Results
2. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination
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Ramanathan, Sudarshini, Mohammad, Shekeeb, Tantsis, Esther, Nguyen, Tina Kim, Merheb, Vera, Fung, Victor S C, White, Owen Bruce, Broadley, Simon, Lechner-Scott, Jeannette, Vucic, Steve, Henderson, Andrew P D, Barnett, Michael Harry, Reddel, Stephen W, Brilot, Fabienne, Dale, Russell C, Andrews, Pi, Barton, Jl, Burrow, Jnc, Butzkueven, H, Cairns, Ag, Calvert, S, Caruana, P, Chelakkadan, S, Clark, D, Fraser, Cl, Freeman, Jl, Gill, D, Grattan-smith, Pj, Gupta, S, Hardy, Ta, Kothur, K, Ling, Sr, Lopez, Ja, Malone, S, Marriott, Mp, Nosadini, M, O’grady, Gl, Orr, Cf, Ouvrier, R, Parratt, J, Patrick, E, Pilli, D, Riminton, Ds, Riney, K, Rodriguez-casero, V, Ryan, Mm, Scheffer, Ie, Shah, Uh, Shuey, N, Spooner, Cg, Subramanian, Gm, Tea, F, Thomas, T, Thompson, J, Troedson, C, Ware, Tl, Webster, Ri, Yiannikas, C, Yiu, Em, and Zou, A
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- 2018
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3. Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy
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D'Silva, AM, Holland, S, Kariyawasam, D, Herbert, K, Barclay, P, Cairns, A, MacLennan, SC, Ryan, MM, Sampaio, H, Smith, N, Woodcock, IR, Yiu, EM, Alexander, IE, Farrar, MA, D'Silva, AM, Holland, S, Kariyawasam, D, Herbert, K, Barclay, P, Cairns, A, MacLennan, SC, Ryan, MM, Sampaio, H, Smith, N, Woodcock, IR, Yiu, EM, Alexander, IE, and Farrar, MA
- Abstract
OBJECTIVE: To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real-world practice, in a broad population of infants with spinal muscular atrophy (SMA). METHODS: A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described. RESULTS: 21 children were treated (age range, 0.65-24 months; body weight range, 2.5-12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment-related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57-274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge. INTERPRETATION: This study provides real-world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks.
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- 2022
4. Delivering multidisciplinary neuromuscular care for children via telehealth
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Carroll, K, Adams, J, de Valle, K, Forbes, R, Kennedy, RA, Kornberg, AJ, Vandeleur, M, Villano, D, Woodcock, IR, Yiu, EM, Ryan, MM, Davidson, Z, Carroll, K, Adams, J, de Valle, K, Forbes, R, Kennedy, RA, Kornberg, AJ, Vandeleur, M, Villano, D, Woodcock, IR, Yiu, EM, Ryan, MM, and Davidson, Z
- Abstract
INTRODUCTION/AIMS: In response to coronavirus disease 2019 (COVID-19) pandemic restrictions int 2020, our face-to-face (F2F) multidisciplinary neuromuscular clinic (NMC) transitioned to widespread use of telehealth (TH). This study aimed to (1) understand parent/guardian, child, and clinician perceptions of TH; (2) examine TH-related changes in clinical activity; and (3) use these findings to inform a future model of care for the NMC. METHODS: A clinical audit was undertaken to examine clinical activity throughout 2018-2020. Online surveys were distributed to clinicians and parents of children attending the NMC via TH in 2020. A working group of clinicians created a checklist to guide a future hybrid model of TH and F2F care. RESULTS: Total clinical activity in 2020 was maintained from previous years; 62.8% of all appointments occurred via TH, and 82.3% of patients attended NMC by TH at least once. Ninety-nine parents (30.6% response rate), 52 children, and 17 clinicians (77% response rate) responded to the survey. All groups reported better interaction when F2F compared to TH. Eighty percent of parents identified advantages of TH and reported lower levels of stress. A lack of "hands-on" physical assessment was identified by parents and clinicians as a TH limitation. Most families (68.1% of parents; 58.8% of children) and all clinicians indicated a preference for a mix of TH and F2F NMC appointments in the future. DISCUSSION: This study has informed a checklist to guide future TH use in a new hybrid model of care. Further investigation is required to assess health impacts of TH use in pediatric neuromuscular care.
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- 2022
5. Determining the Validity of Conducting Rating Scales in Friedreich Ataxia through Video
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Tai, G, Corben, LA, Woodcock, IR, Yiu, EM, Delatycki, MB, Tai, G, Corben, LA, Woodcock, IR, Yiu, EM, and Delatycki, MB
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BACKGROUND: The Friedreich Ataxia Rating Scale (FARS) and the Scale for the Assessment and Rating of Ataxia (SARA) are commonly used neurological rating scales in Friedreich ataxia (FRDA). The modified Friedreich Ataxia Rating Scale (mFARS) has been accepted as an appropriate outcome measure for clinical trials in FRDA. OBJECTIVES: The COVID-19 pandemic has resulted in limited face-to-face interactions with individuals involved in natural history studies and clinical trials. The aim of this study was to determine the validity of conducting the mFARS and SARA through video. METHODS: Individuals who had the mFARS administered face-to-face in the previous 6 months were invited to participate. Participants were sent instructions and asked to have a carer present to assist. The mFARS and SARA were then administered by video. Differences between face-to-face and video scores and the reliability between scores obtained face-to-face and by video were examined. RESULTS: The mFARS and SARA were conducted by video with 19 individuals. Excellent test-retest reliability was seen in the mFARS lower limb coordination (ICC = 0.96, 95% CI 0.90-0.98) and upright stability sections (ICC = 0.97, 95% CI 0.93-0.99), total mFARS (ICC = 0.97, 95% CI 0.92-0.99) and SARA scores (ICC = 0.98, 95% CI 0.95-0.99). CONCLUSIONS: Excellent test-retest reliability was demonstrated in the majority of the mFARS sections, and in the total mFARS and SARA scores, suggesting that video is a valid method of conducting these scales. This method enables inclusion of participants who are unable to travel to study sites. A larger cohort will be required to further validate the use of video mFARS and SARA for future studies.
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- 2021
6. MRI Patterns Distinguish AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis
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Clarke, L, Arnett, S, Bukhari, W, Khalilidehkordi, E, Jimenez Sanchez, S, O'Gorman, C, Sun, J, Prain, KM, Woodhall, M, Silvestrini, R, Bundell, CS, Abernethy, DA, Bhuta, S, Blum, S, Boggild, M, Boundy, K, Brew, BJ, Brownlee, W, Butzkueven, H, Carroll, WM, Chen, C, Coulthard, A, Dale, RC, Das, C, Fabis-Pedrini, MJ, Gillis, D, Hawke, S, Heard, R, Henderson, APD, Heshmat, S, Hodgkinson, S, Kilpatrick, TJ, King, J, Kneebone, C, Kornberg, AJ, Lechner-Scott, J, Lin, MW, Lynch, C, Macdonell, RAL, Mason, DF, McCombe, PA, Pereira, J, Pollard, JD, Ramanathan, S, Reddel, SW, Shaw, Cameron, Spies, JM, Stankovich, J, Sutton, I, Vucic, S, Walsh, M, Wong, RC, Yiu, EM, Barnett, MH, Kermode, AGK, Marriott, MP, Parratt, JDE, Slee, M, Taylor, BV, Willoughby, E, Brilot, F, Vincent, A, Waters, P, Broadley, SA, Clarke, L, Arnett, S, Bukhari, W, Khalilidehkordi, E, Jimenez Sanchez, S, O'Gorman, C, Sun, J, Prain, KM, Woodhall, M, Silvestrini, R, Bundell, CS, Abernethy, DA, Bhuta, S, Blum, S, Boggild, M, Boundy, K, Brew, BJ, Brownlee, W, Butzkueven, H, Carroll, WM, Chen, C, Coulthard, A, Dale, RC, Das, C, Fabis-Pedrini, MJ, Gillis, D, Hawke, S, Heard, R, Henderson, APD, Heshmat, S, Hodgkinson, S, Kilpatrick, TJ, King, J, Kneebone, C, Kornberg, AJ, Lechner-Scott, J, Lin, MW, Lynch, C, Macdonell, RAL, Mason, DF, McCombe, PA, Pereira, J, Pollard, JD, Ramanathan, S, Reddel, SW, Shaw, Cameron, Spies, JM, Stankovich, J, Sutton, I, Vucic, S, Walsh, M, Wong, RC, Yiu, EM, Barnett, MH, Kermode, AGK, Marriott, MP, Parratt, JDE, Slee, M, Taylor, BV, Willoughby, E, Brilot, F, Vincent, A, Waters, P, and Broadley, SA
- Abstract
Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the CNS. Overlap in the clinical and MRI features of NMOSD and MS means that distinguishing these conditions can be difficult. With the aim of evaluating the diagnostic utility of MRI features in distinguishing NMOSD from MS, we have conducted a cross-sectional analysis of imaging data and developed predictive models to distinguish the two conditions. NMOSD and MS MRI lesions were identified and defined through a literature search. Aquaporin-4 (AQP4) antibody positive NMOSD cases and age- and sex-matched MS cases were collected. MRI of orbits, brain and spine were reported by at least two blinded reviewers. MRI brain or spine was available for 166/168 (99%) of cases. Longitudinally extensive (OR = 203), “bright spotty” (OR = 93.8), whole (axial; OR = 57.8) or gadolinium (Gd) enhancing (OR = 28.6) spinal cord lesions, bilateral (OR = 31.3) or Gd-enhancing (OR = 15.4) optic nerve lesions, and nucleus tractus solitarius (OR = 19.2), periaqueductal (OR = 16.8) or hypothalamic (OR = 7.2) brain lesions were associated with NMOSD. Ovoid (OR = 0.029), Dawson's fingers (OR = 0.031), pyramidal corpus callosum (OR = 0.058), periventricular (OR = 0.136), temporal lobe (OR = 0.137) and T1 black holes (OR = 0.154) brain lesions were associated with MS. A score-based algorithm and a decision tree determined by machine learning accurately predicted more than 85% of both diagnoses using first available imaging alone. We have confirmed NMOSD and MS specific MRI features and combined these in predictive models that can accurately identify more than 85% of cases as either AQP4 seropositive NMOSD or MS
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- 2021
7. Diretrizes Baseadas em Evidências Diagnóstico e manejo da Síndrome de Guillain–Barré em dez etapas
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Leonhard, SE, Mandarakas, MR, Gondim, FAA, Bateman, K, Ferreira, MLB, Cornblath, DR, Van Doorn, PA, Dourado, ME, Hughes, RAC, Islam, B, Kusunoki, S, Pardo, CA, Reisin, R, Sejvar, JJ, Shahrizaila, N, Soares, C, Umapathi, T, Wang, Y, Yiu, EM, Willison, HJ, Jacobs, BC, Leonhard, SE, Mandarakas, MR, Gondim, FAA, Bateman, K, Ferreira, MLB, Cornblath, DR, Van Doorn, PA, Dourado, ME, Hughes, RAC, Islam, B, Kusunoki, S, Pardo, CA, Reisin, R, Sejvar, JJ, Shahrizaila, N, Soares, C, Umapathi, T, Wang, Y, Yiu, EM, Willison, HJ, and Jacobs, BC
- Abstract
A síndrome de Guillain–Barré (SGB) é uma doença imunomediada rara, mas potencialmente fatal, dos nervos periféricos e das raízes nervosas, que é geralmente desencadeada por infecções. A incidência da SGB pode, portanto, aumentar durante surtos de doenças infecciosas, como foi observado durante a epidemia do vírus Zika em 2013 na Polinésia Francesa e em 2015 na América Latina. O diagnóstico e manejo da SGB podem ser complicados visto que sua apresentação clínica e o curso da doença são heterogêneos e não existem atualmente diretrizes clínicas internacionais disponíveis. Para auxiliar os médicos, especialmente em um cenário de surto, desenvolvemos uma diretriz globalmente aplicável para o diagnóstico e manejo da SGB. A diretriz se baseia no consenso de especialistas e na literatura atual e tem uma estrutura de dez etapas para facilitar seu uso na prática clínica. Primeiro fornecemos uma introdução aos critérios diagnósticos, às variantes clínicas e aos diagnósticos diferenciais da SGB. A seguir, as dez etapas abrangem o reconhecimento e o diagnóstico precoces da SGB, a internação na unidade de terapia intensiva, a indicação e seleção do tratamento, o monitoramento e tratamento da progressão da doença, o prognóstico do curso e resultado clínico e o manejo das complicações e sequelas.
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- 2021
8. The effects of calf massage in boys with Duchenne muscular dystrophy: a prospective interventional study
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Carroll, K, Yiu, EM, Ryan, MM, Kennedy, RA, de Valle, K, Carroll, K, Yiu, EM, Ryan, MM, Kennedy, RA, and de Valle, K
- Abstract
PURPOSE: We explored the effects of standardized calf massage in ambulant boys with Duchenne muscular dystrophy (DMD) using a prospective study design. MATERIALS AND METHODS: Twenty boys completed two study visits, 1 week apart. At both visits, each leg received a 10-min calf massage (intervention) and a 10-min control rest period (placebo) in randomized order. Muscle length of calf and hamstrings and gastrocnemius stiffness were measured by a blinded assessor before and after intervention and placebo. Measures of gait function (timed 10-m walk/run and spatio-temporal gait parameters); gastrocnemius muscle ultrasound findings; participant perception of leg pain, stiffness and effort of walking and general psychological well-being were also collected. RESULTS: Consistent significant small increases in muscle length of soleus, gastrocnemius and hamstrings were recorded post-massage, and gastrocnemius stiffness decreased. Small changes in gastrocnemius and soleus length only were also recorded following the control rest period. Gait function and general well-being remained stable throughout. Measurement across both study visits suggested that gains in muscle length may be cumulative with repeated massage. CONCLUSIONS: Calf massage is safe and associated with benefits to muscle length and stiffness for ambulant boys with DMD.Implications for RehabilitationIn a small sample of boys with Duchenne muscular dystrophy, calf massage was found to be safe, well-tolerated and associated with increased muscle length and decreased stiffness.The use of massage may assist in managing muscle length in boys with Duchenne muscular dystrophy.
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- 2021
9. The severe epilepsy syndromes of infancy: A population-based study
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Howell, KB, Freeman, JL, Mackay, MT, Fahey, MC, Archer, J, Berkovic, SF, Chan, E, Dabscheck, G, Eggers, S, Hayman, M, Holberton, J, Hunt, RW, Jacobs, SE, Kornberg, AJ, Leventer, RJ, Mandelstam, S, McMahon, JM, Mefford, HC, Panetta, J, Riseley, J, Rodriguez-Casero, V, Ryan, MM, Schneider, AL, Smith, LJ, Stark, Z, Wong, F, Yiu, EM, Scheffer, IE, Harvey, AS, Howell, KB, Freeman, JL, Mackay, MT, Fahey, MC, Archer, J, Berkovic, SF, Chan, E, Dabscheck, G, Eggers, S, Hayman, M, Holberton, J, Hunt, RW, Jacobs, SE, Kornberg, AJ, Leventer, RJ, Mandelstam, S, McMahon, JM, Mefford, HC, Panetta, J, Riseley, J, Rodriguez-Casero, V, Ryan, MM, Schneider, AL, Smith, LJ, Stark, Z, Wong, F, Yiu, EM, Scheffer, IE, and Harvey, AS
- Abstract
OBJECTIVE: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. METHODS: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. RESULTS: Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. SIGNIFICANCE: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initi
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- 2021
10. Relapse Patterns in NMOSD: Evidence for Earlier Occurrence of Optic Neuritis and Possible Seasonal Variation
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Khalilidehkordi, E, Clarke, L, Arnett, S, Bukhari, W, Jimenez Sanchez, S, O'Gorman, C, Sun, J, Prain, KM, Woodhall, M, Silvestrini, R, Bundell, CS, Abernethy, D, Bhuta, S, Blum, S, Boggild, M, Boundy, K, Brew, BJ, Brown, M, Brownlee, W, Butzkueven, H, Carroll, WM, Chen, C, Coulthard, A, Dale, RC, Das, C, Fabis-Pedrini, MJ, Fulcher, D, Gillis, D, Hawke, S, Heard, R, Henderson, APD, Heshmat, S, Hodgkinson, S, Kilpatrick, TJ, King, J, Kneebone, C, Kornberg, AJ, Lechner-Scott, J, Lin, MW, Lynch, C, Macdonell, RAL, Mason, DF, McCombe, PA, Pereira, J, Pollard, JD, Ramanathan, S, Reddel, SW, Shaw, C, Spies, J, Stankovich, J, Sutton, I, Vucic, S, Walsh, M, Wong, RC, Yiu, EM, Barnett, MH, Kermode, AG, Marriott, MP, Parratt, J, Slee, M, Taylor, BV, Willoughby, E, Brilot, F, Vincent, A, Waters, P, Broadley, SA, Khalilidehkordi, E, Clarke, L, Arnett, S, Bukhari, W, Jimenez Sanchez, S, O'Gorman, C, Sun, J, Prain, KM, Woodhall, M, Silvestrini, R, Bundell, CS, Abernethy, D, Bhuta, S, Blum, S, Boggild, M, Boundy, K, Brew, BJ, Brown, M, Brownlee, W, Butzkueven, H, Carroll, WM, Chen, C, Coulthard, A, Dale, RC, Das, C, Fabis-Pedrini, MJ, Fulcher, D, Gillis, D, Hawke, S, Heard, R, Henderson, APD, Heshmat, S, Hodgkinson, S, Kilpatrick, TJ, King, J, Kneebone, C, Kornberg, AJ, Lechner-Scott, J, Lin, MW, Lynch, C, Macdonell, RAL, Mason, DF, McCombe, PA, Pereira, J, Pollard, JD, Ramanathan, S, Reddel, SW, Shaw, C, Spies, J, Stankovich, J, Sutton, I, Vucic, S, Walsh, M, Wong, RC, Yiu, EM, Barnett, MH, Kermode, AG, Marriott, MP, Parratt, J, Slee, M, Taylor, BV, Willoughby, E, Brilot, F, Vincent, A, Waters, P, and Broadley, SA
- Abstract
Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) show overlap in their clinical features. We performed an analysis of relapses with the aim of determining differences between the two conditions. Cases of NMOSD and age- and sex-matched MS controls were collected from across Australia and New Zealand. Demographic and clinical information, including relapse histories, were recorded using a standard questionnaire. There were 75 cases of NMOSD and 101 MS controls. There were 328 relapses in the NMOSD cases and 375 in MS controls. Spinal cord and optic neuritis attacks were the most common relapses in both NMOSD and MS. Optic neuritis (p < 0.001) and area postrema relapses (P = 0.002) were more common in NMOSD and other brainstem attacks were more common in MS (p < 0.001). Prior to age 30 years, attacks of optic neuritis were more common in NMOSD than transverse myelitis. After 30 this pattern was reversed. Relapses in NMOSD were more likely to be treated with acute immunotherapies and were less likely to recover completely. Analysis by month of relapse in NMOSD showed a trend toward reduced risk of relapse in February to April compared to a peak in November to January (P = 0.065). Optic neuritis and transverse myelitis are the most common types of relapse in NMOSD and MS. Optic neuritis tends to occur more frequently in NMOSD prior to the age of 30, with transverse myelitis being more common thereafter. Relapses in NMOSD were more severe. A seasonal bias for relapses in spring-summer may exist in NMOSD.
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- 2020
11. Energy metabolism and mitochondrial defects in X-linked Charcot-Marie-Tooth (CMTX6) iPSC-derived motor neurons with the p.R158H PDK3 mutation
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Perez-Siles, G, Cutrupi, A, Ellis, M, Screnci, R, Mao, D, Uesugi, M, Yiu, EM, Ryan, MM, Choi, BO, Nicholson, G, Kennerson, ML, Perez-Siles, G, Cutrupi, A, Ellis, M, Screnci, R, Mao, D, Uesugi, M, Yiu, EM, Ryan, MM, Choi, BO, Nicholson, G, and Kennerson, ML
- Abstract
Charcot-Marie-Tooth (CMT) is a group of inherited diseases clinically and genetically heterogenous, characterised by length dependent degeneration of axons of the peripheral nervous system. A missense mutation (p.R158H) in the pyruvate dehydrogenase kinase 3 gene (PDK3) has been identified as the genetic cause for an X-linked form of CMT (CMTX6) in two unrelated families. PDK3 is one of four PDK isoenzymes that regulate the activity of the pyruvate dehydrogenase complex (PDC). The balance between kinases (PDKs) and phosphatases (PDPs) determines the extend of oxidative decarboxylation of pyruvate to generate acetyl CoA, critically linking glycolysis and the energy producing Krebs cycle. We had shown the p.R158H mutation causes hyperactivity of PDK3 and CMTX6 fibroblasts show hyperphosphorylation of PDC, leading to reduced PDC activity and ATP production. In this manuscript we have generated induced pluripotent stem cells (iPSCs) by re-programming CMTX6 fibroblasts (iPSCCMTX6). We also have engineered an isogenic control (iPSCisogenic) and demonstrated that genetic correction of the p.R158H mutation reverses the CMTX6 phenotype. Patient-derived motor neurons (MNCMTX6) show increased phosphorylation of the PDC, energy metabolism defects and mitochondrial abnormalities, including reduced velocity of trafficking mitochondria in the affected axons. Treatment of the MNCMTX6 with a PDK inhibitor reverses PDC hyperphosphorylation and the associated functional deficits founds in the patient motor neurons, demonstrating that the MNCMTX6 and MNisogenic motor neurons provide an excellent neuronal system for compound screening approaches to identify drugs for the treatment of CMTX6.
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- 2020
12. Hyperinsulinaemic hypoglycaemia: A rare association of vanishing white matter disease.
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Bursle, C, Yiu, EM, Yeung, A, Freeman, JL, Stutterd, C, Leventer, RJ, Vanderver, A, Yaplito-Lee, J, Bursle, C, Yiu, EM, Yeung, A, Freeman, JL, Stutterd, C, Leventer, RJ, Vanderver, A, and Yaplito-Lee, J
- Abstract
We report two unrelated patients with infantile onset leukoencephalopathy with vanishing white matter (VWM) and hyperinsulinaemic hypoglycaemia. To our knowledge, this association has not been described previously. Both patients had compound heterozygous pathogenic variants in EIF2B4 detected on exome sequencing and absence of other variants which might explain the hyperinsulinism. Hypoglycaemia became apparent at 6 and 8 months, respectively, although in one patient, transient neonatal hypoglycaemia was also documented. One patient responded to diazoxide and the other was managed with continuous nasogastric feeding. We hypothesise that the pathophysiology of hyperinsulinism in VWM may involve dysregulation of transcription of genes related to insulin secretion.
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- 2020
13. Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination
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Tea, F, Lopez, JA, Ramanathan, S, Merheb, V, Lee, FXZ, Zou, A, Pilli, D, Patrick, E, van der Walt, A, Monif, M, Tantsis, EM, Yiu, EM, Vucic, S, Henderson, APD, Fok, A, Fraser, CL, Lechner-Scott, J, Reddel, SW, Broadley, S, Barnett, MH, Brown, DA, Lunemann, JD, Dale, RC, Brilot, F, Sinclair, A, Kermode, AG, Kornberg, A, Bye, A, McGettigan, B, Trewin, B, Brew, B, Taylor, B, Bundell, C, Miteff, C, Troedson, C, Pridmore, C, Spooner, C, Yiannikas, C, O'Gorman, C, Clark, D, Suan, D, Jones, D, Kilfoyle, D, Gill, D, Wakefield, D, Hofmann, D, Mathey, E, O'Grady, G, Jones, HF, Beadnall, H, Butzkueven, H, Joshi, H, Andrews, I, Sutton, I, MacIntyre, J, Sandbach, JM, Freeman, J, King, J, O'Neill, JH, Parratt, J, Barton, J, Garber, J, Ahmad, K, Riney, K, Buzzard, K, Kothur, K, Cantrill, LC, Menezes, MP, Paine, MA, Marriot, M, Ghadiri, M, Boggild, M, Lawlor, M, Badve, M, Ryan, M, Aaqib, M, Shuey, N, Jordan, N, Urriola, N, Lawn, N, White, O, McCombe, P, Patel, R, Leventer, R, Webster, R, Smith, R, Gupta, S, Mohammad, SS, Pillai, S, Hawke, S, Simon, S, Calvert, S, Blum, S, Malone, S, Hodgkinson, S, Nguyen, TK, Hardy, TA, Kalincik, T, Ware, T, Fung, VSC, Huynh, W, Tea, F, Lopez, JA, Ramanathan, S, Merheb, V, Lee, FXZ, Zou, A, Pilli, D, Patrick, E, van der Walt, A, Monif, M, Tantsis, EM, Yiu, EM, Vucic, S, Henderson, APD, Fok, A, Fraser, CL, Lechner-Scott, J, Reddel, SW, Broadley, S, Barnett, MH, Brown, DA, Lunemann, JD, Dale, RC, Brilot, F, Sinclair, A, Kermode, AG, Kornberg, A, Bye, A, McGettigan, B, Trewin, B, Brew, B, Taylor, B, Bundell, C, Miteff, C, Troedson, C, Pridmore, C, Spooner, C, Yiannikas, C, O'Gorman, C, Clark, D, Suan, D, Jones, D, Kilfoyle, D, Gill, D, Wakefield, D, Hofmann, D, Mathey, E, O'Grady, G, Jones, HF, Beadnall, H, Butzkueven, H, Joshi, H, Andrews, I, Sutton, I, MacIntyre, J, Sandbach, JM, Freeman, J, King, J, O'Neill, JH, Parratt, J, Barton, J, Garber, J, Ahmad, K, Riney, K, Buzzard, K, Kothur, K, Cantrill, LC, Menezes, MP, Paine, MA, Marriot, M, Ghadiri, M, Boggild, M, Lawlor, M, Badve, M, Ryan, M, Aaqib, M, Shuey, N, Jordan, N, Urriola, N, Lawn, N, White, O, McCombe, P, Patel, R, Leventer, R, Webster, R, Smith, R, Gupta, S, Mohammad, SS, Pillai, S, Hawke, S, Simon, S, Calvert, S, Blum, S, Malone, S, Hodgkinson, S, Nguyen, TK, Hardy, TA, Kalincik, T, Ware, T, Fung, VSC, and Huynh, W
- Abstract
Over recent years, human autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG Ab) have been associated with monophasic and relapsing central nervous system demyelination involving the optic nerves, spinal cord, and brain. While the clinical relevance of MOG Ab detection is becoming increasingly clear as therapeutic and prognostic differences from multiple sclerosis are acknowledged, an in-depth characterization of human MOG Ab is required to answer key challenges in patient diagnosis, treatment, and prognosis. Herein, we investigated the epitope, binding sensitivity, and affinity of MOG Ab in a cohort of 139 and 148 MOG antibody-seropositive children and adults (n = 287 patients at baseline, 130 longitudinal samples, and 22 cerebrospinal fluid samples). MOG extracellular domain was also immobilized to determine the affinity of MOG Ab. MOG Ab response was of immunoglobulin G1 isotype, and was of peripheral rather than intrathecal origin. High affinity MOG Ab were detected in 15% paediatric and 18% adult sera. More than 75% of paediatric and adult MOG Ab targeted a dominant extracellular antigenic region around Proline42. MOG Ab titers fluctuated over the progression of disease, but affinity and reactivity to Proline42 remained stable. Adults with a relapsing course intrinsically presented with a reduced immunoreactivity to Proline42 and had a more diverse MOG Ab response, a feature that may be harnessed for predicting relapse. Higher titers of MOG Ab were observed in more severe phenotypes and during active disease, supporting the pathogenic role of MOG Ab. Loss of MOG Ab seropositivity was observed upon conformational changes to MOG, and this greatly impacted the sensitivity of the detection of relapsing disorders, largely considered as more severe. Careful consideration of the binding characteristics of autoantigens should be taken into account when detecting disease-relevant autoantibodies.
- Published
- 2019
14. Diagnosis and management of Guillain-Barre syndrome in ten steps
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Leonhard, SE, Mandarakas, MR, Gondim, FAA, Bateman, K, Ferreira, MLB, Cornblath, DR, van Doorn, PA, Dourado, ME, Hughes, RAC, Islam, B, Kusunoki, S, Pardo, CA, Reisin, R, Sejvar, JJ, Shahrizaila, N, Soares, C, Umapathi, T, Wang, Y, Yiu, EM, Willison, HJ, Jacobs, BC, Leonhard, SE, Mandarakas, MR, Gondim, FAA, Bateman, K, Ferreira, MLB, Cornblath, DR, van Doorn, PA, Dourado, ME, Hughes, RAC, Islam, B, Kusunoki, S, Pardo, CA, Reisin, R, Sejvar, JJ, Shahrizaila, N, Soares, C, Umapathi, T, Wang, Y, Yiu, EM, Willison, HJ, and Jacobs, BC
- Abstract
Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.
- Published
- 2019
15. Diagnosis and management of Guillain-Barre syndrome in ten steps
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Leonhard, Sonja, Mandarakas, Melissa, Gondim, FAA, Bateman, K, Ferreira, MLB, Cornblath, DR, van Doorn, Pieter, Dourado, ME, Hughes, RAC, Islam, Badrul, Kusunoki, S, Pardo, CA, Reisin, R, Sejvar, JJ, Shahrizaila, N, Soares, C, Umapathi, T, Wang, YZ, Yiu, EM, Willison, HJ, Jacobs, B.C., Leonhard, Sonja, Mandarakas, Melissa, Gondim, FAA, Bateman, K, Ferreira, MLB, Cornblath, DR, van Doorn, Pieter, Dourado, ME, Hughes, RAC, Islam, Badrul, Kusunoki, S, Pardo, CA, Reisin, R, Sejvar, JJ, Shahrizaila, N, Soares, C, Umapathi, T, Wang, YZ, Yiu, EM, Willison, HJ, and Jacobs, B.C.
- Published
- 2019
16. Nusinersen for SMA: expanded access programme
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Farrar, MA, Teoh, HL, Carey, KA, Cairns, A, Forbes, R, Herbert, K, Holland, S, Jones, KJ, Menezes, MP, Morrison, M, Munro, K, Villano, D, Webster, R, Woodcock, IR, Yiu, EM, Sampaio, H, Ryan, MM, Farrar, MA, Teoh, HL, Carey, KA, Cairns, A, Forbes, R, Herbert, K, Holland, S, Jones, KJ, Menezes, MP, Morrison, M, Munro, K, Villano, D, Webster, R, Woodcock, IR, Yiu, EM, Sampaio, H, and Ryan, MM
- Published
- 2018
17. Dejerine-Sottas disease in childhood-Genetic and sonographic heterogeneity
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Hobbelink, SMR, Brockley, CR, Kennedy, RA, Carroll, K, de Valle, K, Rao, P, Davis, MR, Laing, NG, Voermans, NC, Ryan, MM, Yiu, EM, Hobbelink, SMR, Brockley, CR, Kennedy, RA, Carroll, K, de Valle, K, Rao, P, Davis, MR, Laing, NG, Voermans, NC, Ryan, MM, and Yiu, EM
- Abstract
INTRODUCTION: The nerve sonographic features of Dejerine-Sottas disease (DSD) have not previously been described. METHODS: This exploratory cross-sectional, matched, case-control study investigated differences in nerve cross-sectional area (CSA) in children with DSD compared to healthy controls and children with Charcot-Marie-Tooth disease type 1A (CMT1A). CSA of the median, ulnar, tibial, and sural nerves was measured by peripheral nerve ultrasound. The mean difference in CSA between children with DSD, controls, and CMT1A was determined individually and within each group. RESULTS: Five children with DSD and five age- and sex-matched controls were enrolled. Data from five age-matched children with CMT1A was also included. Group comparison showed no mean difference in nerve CSA between children with DSD and controls. Individual analysis of each DSD patient with their matched control indicated an increase in nerve CSA in three of the five children. The largest increase was observed in a child with a heterozygous PMP22 point mutation (nerve CSA fivefold larger than a control and twofold larger than a child with CMT1A). Nerve CSA was moderately increased in two children-one with a heterozygous mutation in MPZ and the other of unknown genetic etiology. CONCLUSIONS: Changes in nerve CSA on ultrasonography in children with DSD differ according to the underlying genetic etiology, confirming the variation in underlying pathobiologic processes and downstream morphological abnormalities of DSD subtypes. Nerve ultrasound may assist in the clinical phenotyping of DSD and act as an adjunct to known distinctive clinical and neurophysiologic findings of DSD subtypes. Larger studies in DSD cohorts are required to confirm these findings.
- Published
- 2018
18. Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy
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Walsh, M, Bell, KM, Chong, B, Creed, E, Brett, GR, Pope, K, Thorne, NP, Sadedin, S, Georgeson, P, Phelan, DG, Day, T, Taylor, JA, Sexton, A, Lockhart, PJ, Kiers, L, Fahey, M, Macciocca, I, Gaff, CL, Oshlack, A, Yiu, EM, James, PA, Stark, Z, Ryan, MM, and Melbourne Genomics Health Alliance
- Subjects
1103 Clinical Sciences, 1109 Neurosciences - Abstract
OBJECTIVE: To explore the diagnostic utility and cost effectiveness of whole exome sequencing (WES) in a cohort of individuals with peripheral neuropathy. METHODS: Singleton WES was performed in individuals recruited though one pediatric and one adult tertiary center between February 2014 and December 2015. Initial analysis was restricted to a virtual panel of 55 genes associated with peripheral neuropathies. Patients with uninformative results underwent expanded analysis of the WES data. Data on the cost of prior investigations and assessments performed for diagnostic purposes in each patient was collected. RESULTS: Fifty patients with a peripheral neuropathy were recruited (median age 18 years; range 2-68 years). The median time from initial presentation to study enrollment was 6 years 9 months (range 2 months-62 years), and the average cost of prior investigations and assessments for diagnostic purposes AU$4013 per patient. Eleven individuals received a diagnosis from the virtual panel. Eight individuals received a diagnosis following expanded analysis of the WES data, increasing the overall diagnostic yield to 38%. Two additional individuals were diagnosed with pathogenic copy number variants through SNP microarray. CONCLUSIONS: This study provides evidence that WES has a high diagnostic utility and is cost effective in patients with a peripheral neuropathy. Expanded analysis of WES data significantly improves the diagnostic yield in patients in whom a diagnosis is not found on the initial targeted analysis. This is primarily due to diagnosis of conditions caused by newly discovered genes and the resolution of complex and atypical phenotypes.
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- 2017
19. A longitudinal study of the SF-36 version 2 in Friedreich ataxia
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Tai, G, Corben, LA, Yiu, EM, Delatycki, MB, Tai, G, Corben, LA, Yiu, EM, and Delatycki, MB
- Abstract
OBJECTIVES: The Medical Outcomes Study 36 item Short-Form Health Survey (SF-36) is one of the most commonly used patient reported outcome measure. This study aimed to examine the relationship between SF-36 version 2 (SF-36V2) summary scores and Friedreich ataxia (FRDA) clinical characteristics, and to investigate the responsiveness of the scale, in comparison with the Friedreich Ataxia Rating Scale (FARS), over 1, 2 and 3 years. MATERIALS AND METHODS: Descriptive statistics were used to examine the characteristics of the cohort at baseline and years 1, 2 and 3. Correlations between FRDA clinical characteristics and SF-36V2 summary scores were reported. Responsiveness was measured using paired t tests. RESULTS: We found significant correlations between the physical component summary (PCS) of the SF-36V2 and various FRDA clinical parameters but none for the mental component summary. No significant changes in the SF-36V2 were seen over 1 or 2 years; however, PCS scores at Year 3 were significantly lower than at baseline (-3.3, SD [7.6], P=.01). FARS scores were found to be significantly greater at Years 1, 2 and 3 when compared to baseline. CONCLUSIONS: Our findings suggest that despite physical decline, individuals with FRDA have relatively stable mental well-being. This study demonstrates that the SF-36V2 is unlikely to be a useful tool for identifying clinical change in FRDA therapeutic trials.
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- 2017
20. Progression of Friedreich ataxia: quantitative characterization over 5 years
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Patel, M, Isaacs, CJ, Seyer, L, Brigatti, K, Gelbard, S, Strawser, C, Foerster, D, Shinnick, J, Schadt, K, Yiu, EM, Delatycki, MB, Perlman, S, Wilmot, GR, Zesiewicz, T, Mathews, K, Gomez, CM, Yoon, G, Subramony, SH, Brocht, A, Farmer, J, Lynch, DR, Patel, M, Isaacs, CJ, Seyer, L, Brigatti, K, Gelbard, S, Strawser, C, Foerster, D, Shinnick, J, Schadt, K, Yiu, EM, Delatycki, MB, Perlman, S, Wilmot, GR, Zesiewicz, T, Mathews, K, Gomez, CM, Yoon, G, Subramony, SH, Brocht, A, Farmer, J, and Lynch, DR
- Abstract
OBJECTIVE: Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder of adults and children. This study analyzed neurological outcomes and changes to identify predictors of progression and generate power calculations for clinical trials. METHODS: Eight hundred and twelve subjects in a natural history study were evaluated annually across 12 sites using the Friedreich Ataxia Rating Scale (FARS), 9-Hole Peg Test, Timed 25-Foot Walk, visual acuity tests, self-reported surveys and disability scales. Cross-sectional outcomes were assessed from recent visits, and longitudinal changes were gaged over 5 years from baseline. RESULTS: Cross-sectional outcomes correlated with measures of disease severity. Age, genetic severity (guanine-adenine-adenine [GAA] repeat length), and testing site predicted performance. Serial progression was relatively linear using FARS and composite measures of performance, while individual performance outcomes were nonlinear over time. Age strongly predicted change from baseline until removing the effects of baseline FARS scores, when GAA becomes a more important factor. Progression is fastest in younger subjects and subjects with longer GAA repeats. Improved coefficients of variation show that progression results are more reproducible over longer assessment durations. INTERPRETATION: While age predicted progression speed in simple analyses and may provide an effective way to stratify cohorts, separating the effects of age and genetic severity is difficult. Controlling for baseline severity, GAA is the major determinant of progression rate in FRDA. Clinical trials will benefit from enrollment of younger subjects, and sample size requirements will shrink with longer assessment periods. These findings should prove useful in devising gene therapy trials in the near future.
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- 2016
21. Complete callosal agenesis, pontocerebellar hypoplasia, and axonal neuropathy due to AMPD2 loss
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Marsh, APL, Lukic, V, Pope, K, Bromhead, C, Tankard, R, Ryan, MM, Yiu, EM, Sim, JCH, Delarycki, MB, Amor, DJ, McGillivray, G, Sherr, EH, Bahlo, M, Leventer, RJ, Lockhart, PJ, Marsh, APL, Lukic, V, Pope, K, Bromhead, C, Tankard, R, Ryan, MM, Yiu, EM, Sim, JCH, Delarycki, MB, Amor, DJ, McGillivray, G, Sherr, EH, Bahlo, M, Leventer, RJ, and Lockhart, PJ
- Abstract
OBJECTIVE: To determine the molecular basis of a severe neurologic disorder in a large consanguineous family with complete agenesis of the corpus callosum (ACC), pontocerebellar hypoplasia (PCH), and peripheral axonal neuropathy. METHODS: Assessment included clinical evaluation, neuroimaging, and nerve conduction studies (NCSs). Linkage analysis used genotypes from 7 family members, and the exome of 3 affected siblings was sequenced. Molecular analyses used Sanger sequencing to perform segregation studies and cohort analysis and Western blot of patient-derived cells. RESULTS: Affected family members presented with postnatal microcephaly and profound developmental delay, with early death in 3. Neuroimaging, including a fetal MRI at 30 weeks, showed complete ACC and PCH. Clinical evaluation showed areflexia, and NCSs revealed a severe axonal neuropathy in the 2 individuals available for electrophysiologic study. A novel homozygous stopgain mutation in adenosine monophosphate deaminase 2 (AMPD2) was identified within the linkage region on chromosome 1. Molecular analyses confirmed that the mutation segregated with disease and resulted in the loss of AMPD2. Subsequent screening of a cohort of 42 unrelated individuals with related imaging phenotypes did not reveal additional AMPD2 mutations. CONCLUSIONS: We describe a family with a novel stopgain mutation in AMPD2. We expand the phenotype recently described as PCH type 9 to include progressive postnatal microcephaly, complete ACC, and peripheral axonal neuropathy. Screening of additional individuals with related imaging phenotypes failed to identify mutations in AMPD2, suggesting that AMPD2 mutations are not a common cause of combined callosal and pontocerebellar defects.
- Published
- 2015
22. AN OPEN LABEL CLINICAL PILOT STUDY OF RESVERATROL AS A TREATMENT FOR FRIEDREICH ATAXIA
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Yiu, EM, Tai, G, Peverill, R, Lee, K, Croft, K, Mori, T, Scheiber-Mojdehkar, B, Sturm, B, Praschberger, M, Vogel, A, Rance, G, Stephenson, S, Lockhart, P, Sarsero, J, Stockley, C, Churchyard, A, Evans-Galea, M, Ryan, MM, Corben, L, Delatycki, M, Yiu, EM, Tai, G, Peverill, R, Lee, K, Croft, K, Mori, T, Scheiber-Mojdehkar, B, Sturm, B, Praschberger, M, Vogel, A, Rance, G, Stephenson, S, Lockhart, P, Sarsero, J, Stockley, C, Churchyard, A, Evans-Galea, M, Ryan, MM, Corben, L, and Delatycki, M
- Published
- 2013
23. A retrospective review of X-linked Charcot-Marie-Tooth disease in childhood.
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Yiu EM, Geevasinga N, Nicholson GA, Fagan ER, Ryan MM, and Ouvrier RA
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- 2011
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24. Duchenne muscular dystrophy.
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Yiu EM, Kornberg AJ, Yiu, Eppie M, and Kornberg, Andrew J
- Abstract
Duchenne muscular dystrophy (DMD), an X-linked disorder, is the most common muscular dystrophy in children, presenting in early childhood and characterized by proximal muscle weakness and calf hypertrophy in affected boys. Patients usually become wheelchair-bound by the age of 12 years, and die of cardiorespiratory complications in their late teens to early twenties. Advances in the management of DMD, including treatment with corticosteroids and the use of intermittent positive pressure ventilation have provided improvements in function, ambulation, quality of life and life expectancy, although novel therapies still aim to provide a cure for this devastating disorder. The clinical features, investigations, and management of DMD are reviewed, as well as the latest in some of the novel therapies. [ABSTRACT FROM AUTHOR]
- Published
- 2008
25. Application of the ICF in voice disorders.
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Ma EP, Yiu EM, and Abbott KV
- Abstract
The aim of this article is to describe how the World Health Organization's International Classification of Functioning, Disability and Health (ICF) can be adapted to describe the consequences of voice disorders. It first describes voice disorders under the four key components of the ICF: Body Functions, Body Structures, Activities and Participation, and Contextual (Environmental and Personal) Factors. It then describes the assessment and treatment tools for voice disorders using the ICF framework. Finally, a case example illustrating how the ICF frames the rehabilitation of an individual with voice disorders is presented. [ABSTRACT FROM AUTHOR]
- Published
- 2007
26. Scaling voice activity limitation and participation restriction in dysphonic individuals.
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Ma EP and Yiu EM
- Abstract
The purpose of this study was to determine the most appropriate scaling procedure for evaluating voice activity limitation (AL) and voice participation restriction (PR). In a randomly counterbalanced design, 32 dysphonic individuals rated their self-perceived extents of voice AL and PR using two scaling procedures [equal-appearing interval (EAI) scaling and visual analogue (VA) scaling]. Results revealed that test-retest reliabilities were similar for the two scaling procedures. The overall extents of voice AL and PR obtained from the two scaling procedures were similar. Moreover, the significant linear relationships obtained between the EAI and VA data of voice AL and PR suggest both dimensions as metathetic in nature. Therefore, either EAI or VA scaling procedure would be considered as appropriate for rating voice AL and PR. However, the relative ease to use by consumers favours the choice of EAI over VA scaling procedure for evaluating voice AL and PR. [ABSTRACT FROM AUTHOR]
- Published
- 2007
27. Multiparametric evaluation of dysphonic severity.
- Author
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Ma EP and Yiu EM
- Abstract
In recent years, the multiparametric approach for evaluating perceptual rating of voice quality has been advocated. This study evaluates the accuracy of predicting perceived overall severity of voice quality with a minimal set of aerodynamic, voice range profile (phonetogram), and acoustic perturbation measures. One hundred and twelve dysphonic persons (93 women and 19 men) with laryngeal pathologies and 41 normal controls (35 women and six men) with normal voices participated in this study. Perceptual severity judgement was carried out by four listeners rating the G (overall grade) parameter of the GRBAS scale. The minimal set of instrumental measures was selected based on the ability of the measure to discriminate between dysphonic and normal voices, and to attain at least a moderate correlation with perceived overall severity. Results indicated that perceived overall severity was best described by maximum phonation time of sustained /a/, peak intraoral pressure of the consonant-vowel /pi/ strings production, voice range profile area, and acoustic jitter. Direct-entry discriminant function analysis revealed that these four voice measures in combination correctly predicted 67.3% of perceived overall severity levels. [ABSTRACT FROM AUTHOR]
- Published
- 2006
28. Acoustic and perceptual analysis of modal and falsetto registers in females with dysphonia.
- Author
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Li NYK and Yiu EM
- Abstract
Modal and falsetto registers are the basic vocal qualities used in female speaking voices. The purpose of this study was to identify the frequency at which modal register changed to falsetto register and the frequency range of each modal and falsetto register produced under three loudness levels: soft, comfortable and loud phonations in normal and dysphonic speakers. These data provide information on the relationship between vocal registers. It is hypothesized that vocal pathologies affect the frequency at which register change from one mode to another mode. Fifteen dysphonic and 15 non-dysphonic females were assessed on their ability to produce tone series from the lowest to the highest frequency at soft, comfortable and loud phonations. Fourteen listeners served as judges to identify the first production of falsetto voice in each tone series. The first falsetto tone perceived was considered to represent the frequency at which the modal-falsetto register change occurred perceptually. The change from modal to falsetto register in the tone series occurred between G4 (360.74 Hz) and B4 (485.23 Hz) in the dysphonic group and between A4 (421.00 Hz) and B4 (476.13 Hz) in the non-dysphonic group among the three loudness levels. The results showed that the presence of dysphonia affected the production of vocal registers The dysphonic group demonstrated the modal-falsetto register change at a significantly lower frequency and reduced frequency range in the modal register than those of the non-dysphonic group in the soft and comfortable phonations. In producing falsetto register, the dysphonic group demonstrated reduced ability in producing falsetto register in soft and loud phonations when compared to the non-dysphonic group. Physiological explanations are used to account for the observations. [ABSTRACT FROM AUTHOR]
- Published
- 2006
29. Cross-cultural adaptation and validation of the Chinese Voice Handicap Index-10.
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Lam PKY, Chan KM, Ho WK, Kwong E, Yiu EM, and Wei WI
- Published
- 2006
30. Suitability of acoustic perturbation measures in analysing periodic and nearly periodic voice signals.
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Ma EP and Yiu EM
- Published
- 2005
31. Voice Activity and Participation Profile: assessing the impact of voice disorders on daily activities.
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Ma EP and Yiu EM
- Abstract
Traditional clinical voice evaluation focuses primarily on the severity of voice impairment, with little emphasis on the impact of voice disorders on the individual's quality of life. This study reports the development of a 28-item assessment tool that evaluates the perception of voice problem, activity limitation, and participation restriction using the International Classification of Impairments, Disabilities and Handicaps-2 Beta-1 concept (World Health Organization, 1997). The questionnaire was administered to 40 subjects with dysphonia and 40 control subjects with normal voices. Results showed that the dysphonic group reported significantly more severe voice problems, limitation in daily voice activities, and restricted participation in these activities than the control group. The study also showed that the perception of a voice problem by the dysphonic subjects correlated positively with the perception of limitation in voice activities and restricted participation. However, the self-perceived voice problem had little correlation with the degree of voice-quality impairment measured acoustically and perceptually by speech pathologists. The data also showed that the aggregate scores of activity limitation and participation restriction were positively correlated, and the extent of activity limitation and participation restriction was similar in all except the job area. These findings highlight the importance of identifying and quantifying the impact of dysphonia on the individual's quality of life in the clinical management of voice disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2001
32. Phonological disruption and subsequent self-correcting behaviour in Cantonese aphasic speakers.
- Author
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Lee RK, Yiu EM, and Stonham J
- Abstract
This study investigated the phonological disruption and subsequent self-correcting behaviour in Cantonese aphasic speakers. The self-correcting behaviour was investigated by examining the sequence of successive spontaneous attempts in producing a target sound. Five anomic, five non-fluent aphasic and five normal control subjects were assessed by using a confrontation naming task which included monosyllabic, disyllabic and trisyllabic targets. All the aphasic subjects demonstrated successive phonological self-corrections towards the target. Initial consonants were more vulnerable to phonological disruption and more resistant to self-correction than vowels, lexical tones and final consonants. [ABSTRACT FROM AUTHOR]
- Published
- 2000
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33. Intuitive phonatory function model: a theory in need of more evidence.
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Yiu EM
- Published
- 2000
34. Language and communication disorders in Chinese.
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Stokes SF and Yiu EM
- Published
- 2000
35. Nutrition outcomes of disease modifying therapies in spinal muscular atrophy: A systematic review.
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O'Brien K, Nguo K, Yiu EM, Woodcock IR, Billich N, and Davidson ZE
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- Child, Humans, Infant, Biological Products, Nutritional Status, Recombinant Fusion Proteins, Spinal Muscular Atrophies of Childhood diet therapy, Spinal Muscular Atrophies of Childhood drug therapy, Treatment Outcome, Muscular Atrophy, Spinal therapy, Muscular Atrophy, Spinal drug therapy, Oligonucleotides therapeutic use, Oligonucleotides administration & dosage
- Abstract
The nutritional implications of spinal muscular atrophy (SMA) are profound. Disease modifying therapies (DMT) have improved clinical outcomes. This review describes the impact of DMT on nutrition outcomes. A systematic search strategy was applied across seven databases until May 2023. Eligible studies measured nutrition outcomes in individuals with SMA on DMT (nusinersen, risdiplam or onasemnogene abeparvovec [OA]) compared to untreated comparators. Nutrition outcomes included anthropometry, feeding route, swallowing dysfunction, dietary intake, dietetic intervention, nutritional biochemistry, metabolism, gastrointestinal issues and energy expenditure. Articles retrieved were screened in duplicate, data were extracted and appraised systematically. Sixty three articles from 54 studies were included; 41% (n = 22) investigated nusinersen in pediatric participants with SMA type 1. Anthropometry (n = 18), feeding route (n = 39), and swallowing dysfunction (n = 18) were the most commonly reported outcomes. In combined pediatric and adult cohorts, BMI z-score remained stable post nusinersen therapy. The proportion of children with SMA requiring enteral nutrition was stable post nusinersen therapy. Ability to thrive at age 1.5 years was higher in children treated in early infancy with OA compared to historical controls. Significant heterogeneity existed across study population characteristics and outcome measures. Nusinersen may prevent deterioration in some nutrition outcomes; and OA in early infancy may be associated with improved nutrition outcomes. Timing of DMT initiation is an important consideration for future nutrition research. Studies investigating nutrition as a primary outcome of DMT, using consistent outcome measures are required for nutritional management strategies for this cohort to be appropriately tailored., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)
- Published
- 2024
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36. Translating a Clinical Practice Guideline to a Portuguese, Spanish and English Practice Brief to promote exercise therapy for paediatric Charcot-Marie-Tooth disease.
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de Paula CS, Donlevy G, Cardoso J, Cornett KMD, Kennedy R, Yiu EM, Mattiello-Sverzut AC, and Burns J
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- Humans, Child, Australia, Brazil, Translations, Adolescent, Charcot-Marie-Tooth Disease rehabilitation, Exercise Therapy methods, Practice Guidelines as Topic
- Abstract
Background: Implementing scientific knowledge in clinical practice is a challenge. In this context, the effective dissemination of scientific findings is of utmost importance., Objective: The aim of this study was to develop a Practice Brief in Portuguese, Spanish and English based on a previously published Clinical Practice Guideline to promote safe and effective exercise for children and young people with Charcot-Marie-Tooth disease and related neuropathies (CMT)., Methods: The Practice Brief was developed by eight health professionals from Brazil and Australia with English, Portuguese, and Spanish translations. The target audience chosen were the medical and allied health professionals involved in the rehabilitation of paediatric CMT. The content was based on the world first "Clinical Practice Guideline for the management of paediatric Charcot-Marie-Tooth disease" [1]. The layout of the Practice Brief was designed according to the criteria for the development of educational materials. The disclosure plan for the Practice Brief involves its publication on University and Hospital websites, www.ClinicalOutcomeMeasures.org and through social media platforms such as ResearchGate, Instagram, Facebook and Twitter, as well as in print format for CMT patient care centres., Results: The English, Portuguese and Spanish versions of the Practice Brief is organised into six sections about assessment, exercise and physical rehabilitation, of which one is focused on progressive resistance exercises for the foot dorsiflexor muscles., Conclusion: We developed a Practice Brief in three languages (English, Portuguese and Spanish), synthesising the main recommendations for exercise and related rehabilitative therapies for paediatric CMT from a published clinical guideline., Competing Interests: Conflict of interest statement The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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37. Is Surface Electromyography (sEMG) a Useful Tool in Identifying Muscle Tension Dysphonia? An Integrative Review of the Current Evidence.
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Wang F and Yiu EM
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Young Adult, Phonation, Reproducibility of Results, Voice Quality, Dysphonia diagnosis, Dysphonia physiopathology, Electromyography, Laryngeal Muscles physiopathology, Muscle Tonus, Predictive Value of Tests
- Abstract
Objective: This integrative review aims to determine the quality level of evidence on using surface electromyography (sEMG) as a diagnostic tool in identifying muscle tension dysphonia., Method: Two independent reviewers used one search engine and five databases to identify sEMG studies published between January 1980 and December 2020, using a set of specified search terms related to muscle tension dysphonia. The selected articles were systematically evaluated by two independent raters using a modified critical appraisal of diagnostic evidence (m-CADE) form., Results: Nine articles that satisfied the inclusion criteria were selected from among 576 studies for evaluation. These nine studies showed varied methodological approaches in sEMG measurements, including electrode configuration and position, tasks used in sEMG data collection, outcome measure, and normalization procedures. Five studies showed relatively high m-CADE scores, which were indicative of "suggestive validity and compelling importance". Two studies were rated as "suggestive validity and importance", while two remaining studies were rated as "less suggestive or equivocal validity and importance"., Conclusions: The review found a moderate level of evidence that sEMG can be a potentially useful tool with diagnostic value in identifying muscle tension dysphonia. However, evidence is not yet available to determine the diagnostic accuracy of sEMG for muscle tension dysphonia. More studies are needed, and it is recommended that future studies involving sEMG and reference measurements should be undertaken using a blinding procedure in order to control any subjective biases. Details of the population that the sEMG has been tested on should be outlined clearly so that spectrum bias could be eliminated or minimized in the application process. Furthermore, it is suggested that a reliable and valid protocol in collecting sEMG data during speech should be developed to minimize the variability of sEMG measures in assessing muscle activities during speech., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2024
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38. Frequency Transmission of Oscillation from External Whole-Body Vibration Platform to the Larynx.
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Yiu EM, Cheng LKH, and Wang F
- Abstract
Purpose: This study investigates (1) the presence of frequency transmission of oscillation from an external whole-body vibration (WBV) platform to the larynx; and (2) the factors that influence this frequency transmission., Methods: Thirty participants (mean age=22.3years) with normal voice were exposed to four frequency-intensity levels of WBV (10 Hz-10%, 10 Hz-20%, 20 Hz-10%, 20 Hz-20%) and were instructed to produce the natural vowel /a/ three times during each WBV setting. The frequency was extracted from the middle 1-second of each electroglottographic (EGG) signal after passing through a Hann band filter with a range of 6-24 Hz. Linear mixed-effects models were applied to determine the factors that influenced the absolute deviation of the frequency transmission., Results: All participants exhibit an extracted EGG frequency that aligns with the external WBV frequency, deviating by - 0.6 to 1.2 Hz. The absolute deviation of WBV frequency transmission is consistent for both sexes across various WBV settings, except the 10 Hz-10% setting where men tend to exhibit significantly higher deviations (P = 0.018)., Conclusion: Oscillations at a specific frequency are transmitted from an external WBV platform to the larynx. This study proposes the use of a "spring" system to investigate the effect of WBV on the larynx, and recommends further research to explore the potential of WBV in managing voice disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2024
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39. Remediation of Perceptual Deficits in Progressive Auditory Neuropathy: A Case Study.
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Rance G, Tomlin D, Yiu EM, and Zanin J
- Abstract
Background: Auditory neuropathy (AN) is a hearing disorder that affects neural activity in the VIIIth cranial nerve and central auditory pathways. Progressive forms have been reported in a number of neurodegenerative diseases and may occur as a result of both the deafferentiation and desynchronisation of neuronal processes. The purpose of this study was to describe changes in auditory function over time in a patient with axonal neuropathy and to explore the effect of auditory intervention., Methods: We tracked auditory function in a child with progressive AN associated with Charcot-Marie-Tooth (Type 2C) disease, evaluating hearing levels, auditory-evoked potentials, and perceptual abilities over a 3-year period. Furthermore, we explored the effect of auditory intervention on everyday listening and neuroplastic development., Results: While sound detection thresholds remained constant throughout, both electrophysiologic and behavioural evidence suggested auditory neural degeneration over the course of the study. Auditory brainstem response amplitudes were reduced, and perception of auditory timing cues worsened over time. Functional hearing ability (speech perception in noise) also deteriorated through the first 1.5 years of study until the child was fitted with a "remote-microphone" listening device, which subsequently improved binaural processing and restored speech perception ability to normal levels., Conclusions: Despite the deterioration of auditory neural function consistent with peripheral axonopathy, sustained experience with the remote-microphone listening system appeared to produce neuroplastic changes, which improved the patient's everyday listening ability-even when not wearing the device.
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- 2024
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40. Rare homozygous disease-associated sequence variants in children with spinal muscular atrophy: a phenotypic description and review of the literature.
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Li L, Menezes MP, Smith M, Forbes R, Züchner S, Burgess A, Woodcock IR, Delatycki MB, and Yiu EM
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- Child, Humans, Exons, Motor Neurons, Nerve Tissue Proteins genetics, Phenotype, Survival of Motor Neuron 1 Protein genetics, Muscular Atrophy, Spinal genetics, Muscular Atrophy, Spinal diagnosis
- Abstract
5q-associated spinal muscular atrophy (SMA) is the most common autosomal recessive neurological disease. Depletion in functional SMN protein leads to dysfunction and irreversible degeneration of the motor neurons. Over 95 % of individuals with SMA have homozygous exon 7 deletions in the SMN1 gene. Most of the remaining 4-5 % are compound heterozygous for deletion and a disease-associated sequence variant in the non-deleted allele. Individuals with SMA due to bi-allelic SMN1 sequence variants have rarely been reported. Data regarding their clinical phenotype, disease progression, outcome and treatment response are sparse. This study describes six individuals from three families, all with homozygous sequence variants in SMN1, and four of whom received treatment with disease-modifying therapies. We also describe the challenges faced during the diagnostic process and intrafamilial phenotypic variability observed between siblings., Competing Interests: Declaration of competing interest EMY has received advisory board honoraria from Biogen and Roche and has received research support from Biogen, Roche, Pfizer and PTC therapeutics unrelated to the content of this manuscript. MPM has received advisory board honoraria from Biogen unrelated to the content of this manuscript. IRW has received honoraria for work performed including educational activities and attendance at advisory board meetings from Biogen, Novartis, Roche and Avidity and an educational travel bursary to attend an international conference in 2016 from Biogen. IRW has received grants for research work from FSHD Global Research Foundation, FSHD Society and Fulcrum Therapeutics. None of these disclosures were related to the content of this manuscript., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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41. Pilot study of a virtual weight management program for Duchenne muscular dystrophy.
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Billich N, Bray P, Truby H, Evans M, Carroll K, de Valle K, Adams J, Kennedy RA, Villano D, Kornberg AJ, Yiu EM, Ryan MM, and Davidson ZE
- Subjects
- Male, Humans, Adolescent, Child, Preschool, Child, Pilot Projects, Quality of Life, Obesity, Muscular Dystrophy, Duchenne therapy, Muscular Dystrophy, Duchenne complications, Weight Reduction Programs
- Abstract
Introduction/aims: Young people with Duchenne muscular dystrophy (DMD) are at increased risk of obesity. Weight management is important to families; however, several barriers exist. This pilot study aimed to investigate the feasibility and acceptability of a co-designed weight management program for DMD., Methods: The Supporting Nutrition and Optimizing Wellbeing Program (SNOW-P) was a single-arm diet and behavior weight management intervention delivered via weekly telehealth/phone visits over 6 weeks to young people with DMD and obesity (body mass index (BMI) ≥95th percentile) and their caregivers. Using an online survey, caregivers of boys with DMD were consulted on the structure and topics delivered in SNOW-P. Primary outcomes were feasibility and acceptability; secondary outcomes were weight, physical function, and quality of life at 6- and 12-weeks follow-up., Results: Of nineteen eligible participants, eight were enrolled (median age 11.4 years, range 4.9-15.8), and seven completed the program. Visit attendance was high (88%-100%); most participants reported high satisfaction and that participation was easy. Suggested changes included online and visual DMD-specific resources. At 6-weeks, median change in weight z-scores was -0.01 (IQR: -0.23, 0.17) indicating that on average, weight gain tracked as expected for age. Waist circumference measured by caregivers lacked accuracy and the completion rate of caregiver-reported secondary outcome measures (e.g., food diaries) was low., Discussion: A co-designed, telehealth/phone weight management program appeared to be feasible and acceptable in a small group of boys with DMD. An adapted, hybrid telehealth and face-to-face program is recommended for efficacy testing., (© 2024 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)
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- 2024
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42. Predicting Dysphonia by Measuring Surface Electromyographic Activity of the Supralaryngeal Muscles.
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Wang F and Yiu EM
- Subjects
- Adult, Male, Humans, Female, Neck Muscles, Phonation, Voice Quality, Electromyography, Dysphonia diagnosis
- Abstract
Purpose: This study set out to investigate whether individuals with dysphonia, as determined by either self-assessment or clinician-based auditory-perceptual judgment, exhibited differences in perilaryngeal muscle activities using surface electromyography (sEMG) during various phonatory tasks. Additionally, the study aimed to assess the effectiveness of sEMG in identifying dysphonic cases., Method: A total of 77 adults (44 women, 33 men, M
age = 30.4 years) participated in this study, with dysphonic cases identified separately using either a 10-item Voice Handicap Index (VHI-10) or clinician-based auditory-perceptual voice quality (APVQ) evaluation. sEMG activities were measured from the areas of suprahyoid and sternocleidomastoid muscles during prolonged vowel /i/ phonations at different pitch and loudness levels. Normalized root-mean-square value against the maximal voluntary contraction (RMS %MVC) of the sEMG signals was obtained for each phonation and compared between subject groups and across phonatory tasks. Additionally, binary logistic regression analysis was performed to determine how the sEMG measures could predict the VHI-10-based or APVQ-based dysphonic cases., Results: Participants who scored above the criteria on either the VHI-10 ( n = 29) or APVQ judgment ( n = 17) exhibited significantly higher RMS %MVC in the right suprahyoid muscles compared to the corresponding control groups. Although the RMS %MVC value from the right suprahyoid muscles alone was not a significant predictor of self-evaluated dysphonic cases, a combination of the RMS %MVC values from both the right and left suprahyoid muscles significantly predicted APVQ-based dysphonic cases with a 69.66% fair level., Conclusions: This study found that individuals with dysphonia, as determined by either self-assessment or APVQ judgment, displayed more imbalanced suprahyoid muscle activities in voice production compared to nondysphonic groups. The combination of the sEMG measures from both left and right suprahyoid muscles showed potential as a predictor of dysphonia with a fair level of confidence., Supplemental Material: https://doi.org/10.23641/asha.25112804.- Published
- 2024
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43. Practical approach to the child presenting with acute generalised weakness.
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Leung R and Yiu EM
- Subjects
- Child, Humans, Neurologic Examination, Diagnosis, Differential, Muscle Weakness diagnosis, Muscle Weakness etiology, Guillain-Barre Syndrome complications
- Abstract
Acute generalised muscle weakness in children is a paediatric emergency with a broad differential diagnosis. A careful history and neurologic examination guides timely investigation and management. We review some of the more common causes of acute generalised muscle weakness in children, highlighting key history and examination findings, along with an approach to lesion localisation to guide differential diagnosis and further investigation., (© 2024 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)
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- 2024
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44. A phase 2 open-label study of the safety and efficacy of weekly dosing of ATL1102 in patients with non-ambulatory Duchenne muscular dystrophy and pharmacology in mdx mice.
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Woodcock IR, Tachas G, Desem N, Houweling PJ, Kean M, Emmanuel J, Kennedy R, Carroll K, de Valle K, Adams J, Lamandé SR, Coles C, Tiong C, Burton M, Villano D, Button P, Hogrel JY, Catling-Seyffer S, Ryan MM, Delatycki MB, and Yiu EM
- Subjects
- Male, Child, Animals, Mice, Humans, Mice, Inbred mdx, Australia, Muscle, Skeletal metabolism, Adrenal Cortex Hormones adverse effects, Adrenal Cortex Hormones metabolism, Inflammation metabolism, Muscular Dystrophy, Duchenne drug therapy, Muscular Dystrophy, Duchenne genetics, Muscular Dystrophy, Duchenne complications
- Abstract
Background: ATL1102 is a 2'MOE gapmer antisense oligonucleotide to the CD49d alpha subunit of VLA-4, inhibiting expression of CD49d on lymphocytes, reducing survival, activation and migration to sites of inflammation. Children with DMD have dystrophin deficient muscles susceptible to contraction induced injury, which triggers the immune system, exacerbating muscle damage. CD49d is a biomarker of disease severity in DMD, with increased numbers of high CD49d expressing T cells correlating with more severe and progressive weakess, despite corticosteroid treatment., Methods: This Phase 2 open label study assessed the safety, efficacy and pharmacokinetic profile of ATL1102 administered as 25 mg weekly by subcutaneous injection for 24 weeks in 9 non-ambulatory boys with DMD aged 10-18 years. The main objective was to assess safety and tolerability of ATL1102. Secondary objectives included the effect of ATL1102 on lymphocyte numbers in the blood, functional changes in upper limb function as assessed by Performance of Upper Limb test (PUL 2.0) and upper limb strength using MyoGrip and MyoPinch compared to baseline., Results: Eight out of nine participants were on a stable dose of corticosteroids. ATL1102 was generally safe and well tolerated. No serious adverse events were reported. There were no participant withdrawals from the study. The most commonly reported adverse events were injection site erythema and skin discoloration. There was no statistically significant change in lymphocyte count from baseline to week 8, 12 or 24 of dosing however, the CD3+CD49d+ T lymphocytes were statistically significantly higher at week 28 compared to week 24, four weeks past the last dose (mean change 0.40x109/L 95%CI 0.05, 0.74; p = 0.030). Functional muscle strength, as measured by the PUL2.0, EK2 and Myoset grip and pinch measures, and MRI fat fraction of the forearm muscles were stable throughout the trial period., Conclusion: ATL1102, a novel antisense drug being developed for the treatment of inflammation that exacerbates muscle fibre damage in DMD, appears to be safe and well tolerated in non-ambulant boys with DMD. The apparent stabilisation observed on multiple muscle disease progression parameters assessed over the study duration support the continued development of ATL1102 for the treatment of DMD., Trial Registration: Clinical Trial Registration. Australian New Zealand Clinical Trials Registry Number: ACTRN12618000970246., Competing Interests: The ATL1102 in DMD clinical trial was funded in its entirety by the commercial sponsor Antisense Therapeutics Ltd. Antisense Therapeutics Ltd is a publicly traded company, listed on the Australian ASX. At the time of the trial, authors Ms Desem and Dr Tachas were employees of the sponsor and so received payment for services from the sponsor as employees. Ms. Desem and Dr Tachas hold an equity interest in the sponsor. Dr Tachas and Ms Desem along with other sponsor employees and sub-contracted specialists were involved in the study design and data analysis. Ms Desem has since left the company and no longer is employed by the sponsor. Authors Dr Woodcock and Dr Ryan were at the time of the trial employees of the Royal Children’s Hospital and Murdoch Children’s Research Institute and are not affiliated with the sponsor in any way and have not received any direct personal payment or honoraria from the sponsors, nor do they or their family members hold a financial interest or stock in the sponsor company. Dr Woodcock is still an employee of the above institutions, but Dr Ryan has since left the employment to take up public office as a Member of the Australian Parliament. Dr Woodcock and Dr Ryan were involved in the trial design as unpaid consultants. Dr Woodcock has received honoraria for work performed including educational activities and attendance at advisory board meetings from pharmaceutical companies Biogen, Novartis, Roche and Avidity and an educational travel bursary to attend an international conference in 2016 from Biogen. Dr Woodcock has received grants for research work from FSHD Global Research Foundation, FSHD Society and Fulcrum Therapeutics. Dr Woodcock has been principal investigator on a number of industry-sponsored clinical trials. None of these disclosures affected the work Dr Woodcock performed on this clinical trial. Dr Ryan has received honoraria for work performed including educational activities and attendance at advisory board meetings from pharmaceutical companies Biogen, Novartis, Roche. Dr Ryan has been principal investigator on a number of industry-sponsored clinical trials. None of these disclosures affected the work Dr Ryan performed on this clinical trial. Dr Yiu has received advisory board honoraria from Biogen and Roche, and has received research support from Biogen, Roche, Pfizer and PTC therapeutics unrelated to the content of this manuscript. Dr Yiu has been principal investigator on a number of industry-sponsored clinical trials. None of these disclosures affected the work Dr Yiu performed on this clinical trial. Prof. Delatycki has received grant awards from NHMRC and is principal investigator in industry sponsored clinical trials including trials sponsored by Rearta and PTC. As this was a clinical trial, publication was always planned from trial inception. No employees of the sponsor were involved in the data collection, although Ms Desem did liaise closely with the MCRI/RCH site staff and Clinical Trial Organisation throughout the trial. As the study statistician, author Dr Button was paid a consultancy fee for his services from the trial sponsor commercial company Antisense Therapeutics Ltd. Authors Dr Houweling, Dr Coles and Dr Tiong were recipients of a grant to perform the MDX studies. This grant was paid by the sponsor Antisense Therapeutics Ltd. None of the other authors received any payment from the sponsor to conduct this study. All other authors had input into writing or revising this manuscript. The authors confirm that the involvement of employees of the sponsor Antisense Therapeutics Ltd in the trial design, data analysis and decision to publish this data does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Woodcock et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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45. Multiple cranial neuropathies in an adolescent with myelin-oligodendrocyte glycoprotein antibody-associated disease.
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Leung R, Mignone C, Kornberg AJ, Freeman JL, and Yiu EM
- Subjects
- Humans, Myelin-Oligodendrocyte Glycoprotein, Autoantibodies, Cranial Nerve Diseases diagnosis
- Published
- 2023
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46. Fracture risk and impact in boys with Duchenne muscular dystrophy: A retrospective cohort study.
- Author
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Liaw J, Billich N, Carroll K, Adams J, Ryan MM, Yiu EM, Zacharin M, Simm P, and Davidson ZE
- Abstract
Introduction/aims: Boys with Duchenne muscular dystrophy (DMD) are at increased risk of fracture. This study investigated the incidence of fractures, factors contributing to risk of first fracture with emphasis on body mass index (BMI), and the impact of fractures on functional capacity in an Australian cohort of boys with DMD., Methods: A retrospective cohort study included boys with DMD who attended a pediatric neuromuscular clinic from 2011 to 2018. Information regarding fractures, anthropometry measurements, body composition and functional assessment was collected. Factors associated with first fracture risk were analyzed with Cox-proportional hazards. Longitudinal analysis of function post-fracture was also conducted., Results: This study included 155 boys with DMD. At least one fracture occurred in 71 (45%) boys; overall incidence of fractures was 399-per-10,000 persons-years. The first fracture was vertebral in 55%; 41% had non-vertebral fractures and 4% had both. Vertebral fractures occurred in significantly older (12.28 vs 9.28 y) boys with longer exposure to glucocorticoids (5.45 vs 2.50 y) compared to non-vertebral fractures. Boys with a history of fracture(s) had a steeper rate of functional decline (measured by Northstar Ambulatory Assessment score) than those with no recorded fractures., Discussion: A high fracture burden was observed in a large Australian cohort of boys with DMD. Further investigation is required to understand preventative strategies and modifiable risk factors to reduce the incidence of fractures in DMD. The impact on fractures on ambulatory capacity should be closely monitored., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)
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- 2023
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47. Surface electromyographic (sEMG) activity of the suprahyoid and sternocleidomastoid muscles in pitch and loudness control.
- Author
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Wang F and Yiu EM
- Abstract
Purpose: This study set out to determine the contributions of the suprahyoid and sternocleidomastoid (SCM) muscles in changing pitch and loudness during phonation among vocally healthy populations. Method: Thirty-nine participants were first recruited, and twenty-nine of them who passed the screening test (Voice Handicap Index [VHI]-10 score ≤11, auditory-perceptual voice rating score ≤2) were finally selected (mean age = 28.2 years). All participants were measured for their surface electromyographic (sEMG) activity collected from the bilateral suprahyoid and SCM muscles when producing the vowel /a/, /i/, and /u/ in natural (baseline) and at different pitch (+3, +6, -3, -6 semitones) and loudness (+5, +10, -5 dB) levels. Linear mixed-effects models were performed to determine the influencing factors on the root-mean-square percentage of maximal voluntary contraction (RMS %MVC) value of the sEMG signals. Results: Compared with the baseline, a significant decrease of RMS %MVC was found in the suprahyoid muscles during overall phonations of lower pitches (-3 and -6 semitones) and loudness (-5 dB). However, no significant change was detected when producing speech at higher pitch (+3 and +6 semitones) and loudness (+5 and +10 dB) levels. Among the three vowels, /i/ demonstrated significantly higher RMS %MVC than those of /a/ and /u/. The SCM muscles, however, did not show any significant change in the RMS %MVC values among different vowels in relation to the pitch and loudness changes. When the muscles were compared across the two sides, significantly higher RMS %MVC was found in the right side of the suprahyoid (in pitch and loudness control) and SCM (in pitch control) when compared to the left side. Conclusions: The suprahyoid muscle activities were significantly decreased when producing lower pitches and intensities compared to the natural baselines. The production of sustained /i/ required significantly more suprahyoid muscle activities than those of /a/ and /u/. The SCM muscles did not show much sEMG activity in any of the pitch and loudness levels, which could be used potentially as the calibration or normalization of peri-laryngeal sEMG measurement. The findings also showed a tendency for bilateral asymmetry in the use of suprahyoid and SCM muscles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang and Yiu.)
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- 2023
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48. Geographic Expansion of Japanese Encephalitis Virus to Australia: Neuroinflammatory Sequelae and Consideration of Immunomodulation.
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Cole E, Boast A, Yiu EM, Kornberg AJ, Jadhav T, Mignone C, Abo YN, Britton PN, Osowicki J, and Macdonald-Laurs E
- Subjects
- Child, Humans, Australia epidemiology, Immunomodulation, Steroids, Encephalitis Virus, Japanese, Encephalitis, Japanese therapy, Encephalitis, Japanese diagnosis
- Abstract
We report a child from Southern Australia (New South Wales) who presented during a La Niña event with encephalopathy and acute flaccid paralysis. Magnetic resonance imaging suggested Japanese encephalitis (JE). Steroids and intravenous immunoglobulin did not improve symptoms. Therapeutic plasma exchange (TPE) resulted in rapid improvement and tracheostomy decannulation. Our case illustrates the complex pathophysiology of JE, its' geographic expansion into Southern Australia and potential use of TPE for neuroinflammatory sequelae., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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49. Comparing the Effects of Self-Generated and Platform-Generated Whole Body Vibration on Vocal Fatigue.
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Yiu EM and Lee SCH
- Subjects
- Adult, Humans, Female, Young Adult, Vibration therapeutic use, Voice Disorders, Voice, Singing
- Abstract
Objectives: A whole body vibration platform using vertical oscillation has been shown to be efficacious in reducing vocal fatigue in adults. This study aimed to investigate whether this platform-generated whole body vibration was unique in reducing vocal fatigue by comparing it with self-generated whole body vibration., Methods: Twenty-four female adults (mean age = 23.96 years) were randomly assigned to one of the following three groups: a machine-generated whole body vibration group (N = 8), a self-generated whole body vibration group (N = 8), and a placebo vocal resting group (N = 8). All participants performed a karaoke singing task for at least 95 minutes. Each participant received 10 minutes of platform-generated vibration, self-vibration, or sham localised vibration (placebo group with basically voice rest only), according to their group allocation. Vocal function ability, measured by the highest fundamental frequency produced, and a self-reported vocal fatigue score were evaluated at three time points: baseline (prefatigue), after the singing task (post-fatigue) and post-vibration., Results: The study revealed that machine-generated whole body vibration was significantly better at improving vocal fatigue than self-generated whole body vibration or voice rest., Conclusion: The findings support previous research that machine-generated whole body vibration is effective in reducing vocal fatigue. The non-significant results of self-generated whole body vibration in terms of relieving vocal fatigue suggest that inadequate vibration frequency or amplitude together with leg muscle fatigue may have been the main factor of ineffectiveness., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2023
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50. Fatigue-Related Change in Surface Electromyographic Activities of the Perilaryngeal Muscles.
- Author
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Yiu EM, Lau GWH, and Wang F
- Subjects
- Humans, Young Adult, Adult, Neck Muscles physiology, Voice, Voice Disorders, Singing
- Abstract
Purpose: This study set out to quantify the fatigue-related changes in surface electromyographic (sEMG) activities of the perilaryngeal muscles following a vocal loading task., Method: Thirty-six young healthy participants ( M
age = 22.4 years) with normal voice performed karaoke singing for at least 100 min. Before the singing task, all participants underwent the sEMG measure and completed a Perceived Vocal Fatigue Score (P-VFS) questionnaire. After the singing task, all participants were immediately measured with the P-VFS again. Half of the participants were then measured for their sEMG immediately after their karaoke singing task, and the other half were given 20 min of rest before undertaking the sEMG measure. The P-VFS and the median frequency (MDF) of the sEMG signals collected from the suprahyoid, infrahyoid, and sternocleidomastoid muscles before and after the singing task were compared using a linear mixed-effects model., Results: All participants reported a perceived vocal fatigue after singing, with a significantly increased P-VFS. Compared with the presinging baseline, the MDF of the sEMG signals in perilaryngeal muscles was significantly lower immediately after the singing task. Such a significant difference was also found after 20 min following the singing task., Conclusions: The MDF analysis of the sEMG signals could identify and quantify the performance vocal fatigue contributed by perilaryngeal muscles following a vocal loading task. The findings also showed that such fatigue in perilaryngeal muscles, as far as sEMG activities are concerned, can last for at least 20 min.- Published
- 2023
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