Publications by authors named "V Wee Yong"

429 Publications

Susceptibility weighted imaging detects prominent veins that precede or coincide with maximal motor disability in a model of multiple sclerosis: A pilot study.

Mult Scler Relat Disord 2021 Jun 30;54:103124. Epub 2021 Jun 30.

Department of Radiology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada; Experimental Imaging Centre, University of Calgary, Calgary, Alberta, Canada. Electronic address:

Background: Susceptibility weighted imaging (SWI) has detected veins in the center of white matter lesions and alterations in veins themselves in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, the relationship between SWI-detected venous alterations and disease progression is unclear. The objective of this study was to assess alterations in the lumbar spinal cord veins in EAE mice over the disease course using serial SWI.

Methods: EAE mice (n = 8) underwent imaging for SWI using a 9.4T Bruker Avance console at baseline, 7 days (pre-motor dysfunction), 12 days (typical motor dysfunction onset), and 16-18 days (typical peak disease) post-immunization. Naïve controls were imaged alongside EAE mice (n = 3). SWI hypointensities were counted by two subjects and compared between time points.

Results: SWI hypointensities appeared before motor dysfunction onset in most EAE mice. The ratio of SWI hypointensities to baseline was highly variable for EAE mice (0.45-6.75) while less so for controls (0.80-1.31). The time point for the maximum number of SWI hypointensities always preceded or coincided with maximum motor disability.

Conclusion: Venous alterations are detected before the onset of motor disability in some EAE mice using SWI which may relate to inflammation and/or tissue hypoxia.
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http://dx.doi.org/10.1016/j.msard.2021.103124DOI Listing
June 2021

An X-ray for myelin.

Trends Neurosci 2021 08 17;44(8):600-601. Epub 2021 Jun 17.

Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. Electronic address:

With substantial progress in experimental therapeutics to enhance the nervous system's capacity for remyelination, new methods to detect myelin are important advances. We discuss a small-angle X-ray scattering tensor tomography approach presented recently by Georgiadis et al. and the method's promise in providing a new window into the brain to evaluate myelin integrity in health and disease.
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http://dx.doi.org/10.1016/j.tins.2021.06.002DOI Listing
August 2021

Obesity in acute ischaemic stroke patients treated with intravenous thrombolysis therapy.

Neurol Res 2021 Jun 10:1-8. Epub 2021 Jun 10.

The Departments of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University.

: This article aimed to analyze the relationship between obesity and the efficacy of acute ischaemic stroke patients treated with IVT.: Stroke causes morbidity and mortality in large numbers of individuals annually. Intravenous thrombolysis (IVT)with recombinant tissue plasminogen activator (r-tPA) is currently the only approved by the FDA for treatment of acute ischaemic stroke. Researchers have focused on studying the mechanisms associated with ischaemic stroke. Obesity is an established vascular risk factor with increasing prevalence and a huge impact on public health worldwide. It is an independent predictor for ischaemic stroke with a 4% risk increase for each unit augmentation in body mass index (BMI). Therefore, obese patients will constitute an increasing subgroup of candidates for IVT. However, its impact on prognosis in acute ischaemic stroke patients with intravenous thrombolysis did not reach a consensus conclusion.: Systematic literature search of PUBMED databases published before August 2020, was performed to identify studies addressing the role of obesity in acute ischaemic stroke patients treated with IVT. Studies included randomized clinical trials, observational studies, guideline statements, and review articles.: Obesity may be related to long-term prognosis of large group of AIS patients treated with IVT. It depends on the scale of clinical study samples, follow-up time, and evaluation criteria.
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http://dx.doi.org/10.1080/01616412.2021.1939486DOI Listing
June 2021

The combination of deferoxamine and minocycline strengthens neuroprotective effect on acute intracerebral hemorrhage in rats.

Neurol Res 2021 Jun 10:1-11. Epub 2021 Jun 10.

Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, AL, Canada.

: Intracerebral hemorrhage (ICH) is a devastating type of strokes that carries high mortality rates, but effective therapeutic options are still lacking. Here, the adult rat model of ICH was used to investigate the efficacy of a combinational therapy of deferoxamine (DFX) and minocycline.: The ICH was induced by stereotaxic infusion of collagenase into striatum of adult rats. After the induction of ICH, rats were treated with intraperitoneal injection of deferoxamine (50 mg/kg), minocycline (45 mg/kg), or both agents, at 2 hours after ICH and then every 12 hours for up to 3 days. The vehicle group were treated with phosphate-buffered saline (PBS) only. Rats were killed at 1, 2, and 3 day(s) for examination of iron deposition, neuronal death, neurological deficits, the area of brain damage, activation of microglia/macrophages.: Our data revealed that the systemic administration of DFX and/or minocycline decreased iron accumulation. And immunofluorescence staining results indicated that drug-treated group significantly decreased the neuronal degeneration, the number of activated microglia/macrophages and the amount of cell death after ICH. In addition, neurological deficits caused by ICH were improved in the presence of DFX and/or minocycline compare with vehicle group. Furthermore, the combination treatment showed better effects in neuroprotection and anti-inflammation when compared to the monotherapy groups.: The combination therapy significantly reduces the number of neuronal deaths, suppresses of the activation of microglia/macrophages, decreases iron accumulation in the area around the hematoma, lessening the brain damage area, and improving neurological deficits in ICH.
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http://dx.doi.org/10.1080/01616412.2021.1939487DOI Listing
June 2021

Repurposing Domperidone in Secondary Progressive Multiple Sclerosis: A Simon 2-Stage Phase 2 Futility Trial.

Neurology 2021 05 23;96(18):e2313-e2322. Epub 2021 Mar 23.

From the Departments of Clinical Neurosciences (M.W.K., K.S., S.K., J.K., G.C., V.W.Y., L.M.M.) and Community Health Sciences (M.W.K.), University of Calgary, Alberta, Canada; and Department of Biostatistics (G.R.C.), University of Alabama at Birmingham.

Objective: To assess whether treatment with the generic drug domperidone can reduce the progression of disability in secondary progressive multiple sclerosis (SPMS), we conducted a phase 2 futility trial following the Simon 2-stage design.

Methods: We enrolled patients in an open-label, Simon 2-stage, single-center, phase 2, single-arm futility trial at the Calgary Multiple Sclerosis Clinic if they met the following criteria: age of 18 to 60 years, SPMS, screening Expanded Disability Status Scale score of 4.0 to 6.5, and screening timed 25-ft walk (T25FW) of ≥9 seconds. Patients received domperidone 10 mg 4 times daily for 1 year. The primary outcome was worsening of disability, defined as worsening of the T25FW performance by ≥20% at 12 months compared to baseline. This trial is registered with ClinicalTrials.gov (NCT02308137).

Results: Between February 13, 2015, and January 3, 2020, 110 patients were screened, 81 received treatment, and 64 completed follow-up, of whom 62 were analyzed. The study did not meet its primary endpoint: 22 of 62 (35%) patients experienced significant worsening of disability, which is close to the expected proportion of 40% and above the predefined futility threshold. Patients with higher prolactin levels during the study had a significantly lower risk of disability progression, which may warrant further investigation. Domperidone treatment was reasonably well tolerated, but adverse events occurred in 84% and serious adverse events in 15% of patients.

Conclusions: Domperidone treatment could not reject futility in reducing disability progression in SPMS. The Simon 2-stage trial model may be a useful model for phase 2 studies in progressive MS.

Trial Registration Information: ClinicalTrials.gov Identifier: NCT02308137.

Classification Of Evidence: This study provides Class III evidence that in individuals with SPMS participating in a futility trial, domperidone treatment could not reject futility in reducing disability progression at 12 months.
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http://dx.doi.org/10.1212/WNL.0000000000011863DOI Listing
May 2021
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