Publications by authors named "Tak-Hong Tsoi"

15 Publications

  • Page 1 of 1

Clinical and pathological characterization of FLNC-related myofibrillar myopathy caused by founder variant c.8129G>A in Hong Kong Chinese.

Clin Genet 2020 05 23;97(5):747-757. Epub 2020 Feb 23.

Department of Pathology, Queen Elizabeth Hospital, Hong Kong.

FLNC-related myofibrillar myopathy could manifest as autosomal dominant late-onset slowly progressive proximal muscle weakness; involvements of cardiac and/or respiratory functions are common. We describe 34 patients in nine families of FLNC-related myofibrillar myopathy in Hong Kong ethnic Chinese diagnosed over the last 12 years, in whom the same pathogenic variant c.8129G>A (p.Trp2710*) was detected. Twenty-six patients were symptomatic when diagnosed; four patients died of pneumonia and/or respiratory failure. Abnormal amorphous material or granulofilamentous masses were detected in half of the cases, with mitochondrial abnormalities noted in two-thirds. We also show by haplotype analysis the founder effect associated with this Hong Kong variant, which might have occurred 42 to 71 generations ago or around Tang and Song dynasties, and underlain a higher incidence of myofibrillar myopathy among Hong Kong Chinese. The late-onset nature and slowly progressive course of the highly penetrant condition could have significant impact on the family members, and an early diagnosis could benefit the whole family. Considering another neighboring founder variant in FLNC in German patients, we advocate development of specific therapies such as chaperone-based or antisense oligonucleotide strategies for this particular type of myopathy.
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http://dx.doi.org/10.1111/cge.13715DOI Listing
May 2020

Evolution of intracranial atherosclerotic disease under modern medical therapy.

Ann Neurol 2015 Mar 29;77(3):478-86. Epub 2015 Jan 29.

Division of Neurology, Department of Medicine and Therapeutics.

Objective: Understanding how symptomatic intracranial atherosclerotic disease (ICAD) evolves with current medical therapy may inform secondary stroke prevention.

Methods: In a prospective academic-initiated study, we recruited 50 patients (mean age = 63.4 ± 9.0 years) with acute strokes attributed to high-grade (≥70%) intracranial atherosclerotic stenosis for 3-dimensional rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low-density lipoprotein ≤ 70mg/dl, glycosylated hemoglobin (HbA1c) ≤ 6.5%, and systolic blood pressure ≤ 140 mmHg. We analyzed infarct topography and monitored microembolic signal in recurrent strokes. The reference group was a published cohort of 143 ICAD patients.

Results: Overall, the stenoses regressed from 79% at baseline (interquartile range [IQR] = 71-87%) to 63% (IQR = 54-74%) in 1 year (p < 0.001). Specifically, the qualifying lesions (n = 49) regressed (stenosis reduced >10%) in 24 patients (49%), remained quiescent (stenosis same or ±10%) in 21 patients (43%), and progressed (stenosis increased >10%) in 4 patients (8%). There was no difference in intensity of risk factor control between groups of diverging clinical or angiographic outcomes. Higher HbA1c at baseline predicted plaque regression at 1 year (odds ratio = 4.4, 95% confidence interval = 1.4-14.5, p = 0.006). Among the 6 patients with recurrent strokes pertaining to the qualifying stenosis, 5 patients had solitary or rosarylike acute infarcts along the internal or anterior border zones, and 2 patients showed microembolic signals in transcranial Doppler ultrasound.

Interpretation: A majority of symptomatic high-grade intracranial plaques had regressed or remained quiescent by 12 months under intensive medical therapy. Artery-to-artery thromboembolism with impaired washout at border zones was a common mechanism in stroke recurrence.
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http://dx.doi.org/10.1002/ana.24340DOI Listing
March 2015

Single-nucleotide polymorphism of transient axonal glycoprotein-1 and its correlation with clinical features and prognosis in chronic inflammatory demyelinating polyneuropathy.

J Peripher Nerv Syst 2012 Mar;17(1):72-5

Department of Medicine, The University of Hong Kong, Queen Mary Hospital Department of Medicine, Hong Kong SAR, China.

The single-nucleotide polymorphism (SNP) rs2275697 in the transient axonal glycoprotein-1 (TAG-1) gene was reported to be associated with responsiveness to intravenous immunoglobulin (IVIG) treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, it is not known if this SNP is associated with long-term prognosis. We examined the case records of 32 Chinese CIDP patients. The overall response rate to IVIG, prednisolone, or plasmapheresis was 83%. After 5.4 years, 57% of patients were on maintenance immunotherapy. Patients with higher modified Rankin score and more prolonged distal motor latencies in the upper limbs on presentation had a higher risk (odds ratio [OR] 3.86, 95% confidence interval [CI] 1.23-12.11 and OR 1.04, 95% CI 1.01-1.07, respectively) of being on maintenance immunotherapy. Blood samples from 24 patients and 147 controls were examined for their genotypes of four non-synonymous SNPs (rs41264871, rs36074532, rs5611135, and rs2275697) in the coding region of TAG-1. The G allelic frequency of rs2275697 was similar between CIDP patients and controls (56% and 50%, respectively) and was not associated with treatment responsiveness, treatment dependence, disability, or mortality.
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http://dx.doi.org/10.1111/j.1529-8027.2012.00380.xDOI Listing
March 2012

Two-stage genome-wide association study identifies variants in CAMSAP1L1 as susceptibility loci for epilepsy in Chinese.

Hum Mol Genet 2012 Mar 24;21(5):1184-9. Epub 2011 Nov 24.

Department of Psychiatry and The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.

In the majority of patients, epilepsy is a complex disorder with multiple susceptibility genes interacting with environmental factors. However, we understand little about its genetic risks. Here, we report the first genome-wide association study (GWAS) to identify common susceptibility variants of epilepsy in Chinese. This two-stage GWAS included a total of 1087 patients and 3444 matched controls. In the combined analysis of the two stages, the strongest signals were observed with two highly correlated variants, rs2292096 [G] [P= 1.0 × 10(-8), odds ratio (OR) = 0.63] and rs6660197 [T] (P= 9.9 × 10(-7), OR = 0.69), with the former reaching genome-wide significance, on 1q32.1 in the CAMSAP1L1 gene, which encodes a cytoskeletal protein. We also refined a previously reported association with rs9390754 (P= 1.7 × 10(-5)) on 6q21 in the GRIK2 gene, which encodes a glutamate receptor, and identified several other loci in genes involved in neurotransmission or neuronal networking that warrant further investigation. Our results suggest that common genetic variants may increase the susceptibility to epilepsy in Chinese.
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http://dx.doi.org/10.1093/hmg/ddr550DOI Listing
March 2012

A fast modified protocol for random-access ultra-high density whole-genome scan: a tool for personalized genomic medicine, positional mapping, and cytogenetic analysis.

Clin Chim Acta 2009 Aug 13;406(1-2):31-5. Epub 2009 May 13.

Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.

Background: High density single nucleotide polymorphism (SNP) genotyping array is widely applied on genome-wide association study of common diseases. In these studies, a fixed batch-size of 48 or 96 samples allows high-throughput analysis. To enhance the clinical application of microarray analysis on personalized medicine, we describe a modified PCR purification protocol without batch-size limitation for whole-genome scan using ultra-high density SNP microarray.

Methods: Enzyme-digested PCR products were purified with the use of magnetic beads. Separation of the magnetic particles applies magnetic stand devices instead of vacuum pumps. With no batch-size limitation, we genotyped 17 genomic samples and 3 whole genome amplified samples in order to examine the performance of the modified protocol.

Results: Our method is simple and fast, provides sufficient amount and high quality PCR products for subsequent fragmentation and labeling procedures prior to GeneChip hybridization. We show that the purified DNA can be genotyped with good QC call rate of >93% in average similar to standard protocol. With the use of the short protocol, we successfully identified the breakpoint localization of a ring chromosome in a female and located the disease gene in a consanguineous family affected by limb-girdle muscular dystrophy.

Conclusion: By modifying a single step in the original protocol, we are able to speed up the overall genotyping analysis and change the batch-wise analysis to random-access analysis for ultra-high density whole-genome scan for personalized medicine, positional mapping, and cytogenetic analysis.
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http://dx.doi.org/10.1016/j.cca.2009.05.005DOI Listing
August 2009

Predictors of poststroke quality of life in older Chinese adults.

J Adv Nurs 2009 Mar;65(3):554-64

Department of Nursing Studies, The University of Hong Kong, China.

Aim: This paper is a report of a study to identify the changes in poststroke quality of life and other clinical issues among older Chinese adults from 1 month to 6 months after stroke and the predictors of poststroke quality of life at 6 months.

Background: Stroke survivors are known to suffer from prolonged and multiple impairments leading to a compromised quality of life, but few studies report early predictors for quality of life among older Chinese adults after active rehabilitation has been undertaken during the first 6 months after stroke.

Method: A total of 214 patients with first-ever ischaemic stroke were interviewed by a research nurse at 1 month and 188 patients were interviewed again 6 months after hospital admission for stroke. Assessment of quality of life was done using the Modified Rankin Scale for Quality of Life. Changes in and relationships between quality of life and variables in five domains were explored: bio-anatomical, physical, emotional, cognitive, communicative and social support. The data were collected in 2004-2005.

Results: Quality of life among two-thirds of participants was unchanged or lower when scores at 1 month and 6 months after stroke were compared. Length of hospital stay after admission for stroke and other 1-month factors - level of worry over current health, cognitive and self-care deficits - were identified as having independent effects on quality of life at 6 months.

Conclusion: Clinicians need to observe for early signs of mild cognitive impairments and emotional needs of stroke survivors, as well as to consider longer-term interventions to enhance poststroke quality of life.
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http://dx.doi.org/10.1111/j.1365-2648.2008.04918.xDOI Listing
March 2009

Familial Parkinsonism with digenic parkin and PINK1 mutations.

Mov Disord 2008 Jul;23(10):1461-5

Research Institute for Diseases of Old Age, Juntendo University School of Medicine, Bunkyo-Ku, Tokyo, Japan.

To clarify the genetic correlation between parkin and PINK1, we screened for PINK1 mutations in 175 parkinsonism patients with parkin mutations. We detected two sibling pairs and one sporadic patient carrying both parkin and PINK1 mutations. The age at onset of Parkinsonism of patients with the digenic mutations was lower than that of patients with the same parkin mutation alone. In addition, two of three patients carrying both parkin and PINK1 mutations had schizophrenia. These findings indicate that PINK1 mutation might modify parkin mutation-positive Parkinsonism, and PINK1 mutations might be associated with psychiatric disorders.
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http://dx.doi.org/10.1002/mds.22143DOI Listing
July 2008

Topiramate for migraine prophylaxis among Chinese population.

Headache 2007 Apr;47(4):616-9

Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, China.

We evaluated the efficacy and safety of topiramate for migraine prophylaxis among Chinese patients in a multicenter prospective observational study. We found that topiramate at low doses was effective in preventing migraine headache in Chinese patients and was generally well tolerated. There was no difference in baseline headache frequency or intensity between responders and nonresponders.
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http://dx.doi.org/10.1111/j.1526-4610.2007.00763_3.xDOI Listing
April 2007

Low-molecular-weight heparin compared with aspirin for the treatment of acute ischaemic stroke in Asian patients with large artery occlusive disease: a randomised study.

Lancet Neurol 2007 May;6(5):407-13

Department of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China.

Background: Acute stroke patients with large artery occlusive disease (LAOD) have a distinct pathophysiology and may respond differently to anticoagulation treatments. We compared the efficacy of a low-molecular-weight heparin (LMWH), nadroparin calcium, with aspirin in Asian acute stroke patients with LAOD.

Methods: Acute ischaemic stroke patients with onset of symptoms less than 48 h and LAOD (diagnosed by transcranial doppler imaging, carotid duplex scan, or magnetic resonance angiography) were recruited. Patients were randomly assigned to receive either subcutaneous nadroparin calcium 3800 anti-factor Xa IU/0.4 mL twice daily or oral aspirin 160 mg daily for 10 days, and then all received aspirin 80-300 mg once daily for 6 months. This study is registered at www.strokecenter.org/trials (number 493).

Findings: Among 603 patients recruited, 353 (180 LMWH, 173 aspirin) had LAOD (300 had intracranial LAOD only, 42 had both intracranial and extracranial disease, and 11 had extracranial disease only). The proportion of patients with good outcomes at 6 months (Barthel index >or=85) was 73% in the LMWH group and 69% in the aspirin group (absolute risk reduction 4%; 95% CI -5 to 13). Analysis of prespecified secondary outcome measures showed a benefit in outcome for LMWH versus aspirin on the modified Rankin scale dichotomised at 0-1 (odds ratio 1.55, 95% CI 1.02-2.35). Haemorrhagic transformation of infarct and severe adverse events were similar in both groups. Post-hoc analyses of patients without LAOD, and all treated patients, showed similar proportions with a good outcome in aspirin and LMWH groups (78%vs 79% and 73%vs 75%, respectively).

Interpretation: Overall, the results do not support a significant benefit of LMWH over aspirin in patients with LAOD. The benefits indicated in most outcome measures warrant further investigation into the use of anticoagulation for acute stroke in patients with large artery atherosclerosis, particularly in intracranial atherosclerosis.
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http://dx.doi.org/10.1016/S1474-4422(07)70079-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185651PMC
May 2007

Pulsatile ocular blood flow in patients with asymmetric internal carotid artery stenosis.

Clin Exp Optom 2005 Nov;88(6):382-6

School of Optometry, The Hong Kong Polytechnic University, Hong Kong SAR, China.

Background: The pulsatile ocular blood flow (POBF) of patients with asymmetric internal carotid artery (ICA) stenosis was measured bilaterally. The purpose of this study was to investigate the sensitivity of POBF assessments in screening for ICA stenosis.

Methods: Seventeen subjects with asymmetric ICA stenosis confirmed with carotid duplex ultrasound were recruited. The diagnoses of ICA stenosis were categorised into less than 50 per cent, 50 to 69 per cent and 70 per cent or greater. Their POBF and ocular dimensions were measured after local anaesthesia. Twenty-three normal healthy subjects were recruited as the control. All of the subjects had an inter-ocular axial length difference of less than one millimetre.

Results: There were 14 males and three females in the patient group with a median age of 74 years. Fourteen patients had reduced POBF to the eye ipsilateral on the side with greater ICA stenosis. The reduction in POBF ranged from 3.1 to 49.2 per cent. Two patients had reduced POBF contralateral to the side with greater ICA stenosis. One patient had similar POBF between the eyes. The control group included six males and 17 females with a median age of 65 years. The difference in their POBF between the eyes ranged from 0.3 to 13.0 per cent.

Conclusions: Stenosis of the internal carotid artery was found to reduce the POBF ipsilateral to the side with greater stenosis. The overlap in the difference in inter-ocular POBF between the patient and control groups led to a low sensitivity (calculated as 41.2 per cent) for screening ICA stenosis from an assessment of POBF. Therefore, POBF assessment is not a good diagnostic tool for screening for ICA stenosis.
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http://dx.doi.org/10.1111/j.1444-0938.2005.tb05104.xDOI Listing
November 2005

The lowest effective intensity of prophylactic anticoagulation for patients with atrial fibrillation.

Cerebrovasc Dis 2005 5;20(2):114-9. Epub 2005 Jul 5.

Department of Medicine, Pamela Youde Nethersole Eastern Hospital, University of Hong Kong, Queen Mary Hospital, Chai Wan, Hong Kong, SAR, China.

Background: Stroke prevention trials in patients with atrial fibrillation (AF) mainly studied the use of warfarin in Caucasians, and the international normalized ratio (INR) was targeted in the range of 2-4. The result may not necessarily be applicable to other ethnic groups. This study aimed to determine the optimal intensity of anticoagulation for stroke prevention in Chinese patients.

Methods: We performed a retrospective study on all Chinese patients with AF taking warfarin for stroke prevention in our hospital from January 1, 2000, to June 30, 2002. Patients with a mechanical heart valve were excluded. We systematically studied their indication of using warfarin, duration of therapy and all INR results. Only those patients whose indications of using warfarin were consistent with the ACC/AHA/ESC Executive Summary were included. Thrombo-embolic episodes, sudden death, major bleeding, intracranial haemorrhage and the INR at the time of the event were recorded. The INR range was divided into six categories: <1.5, 1.5-1.9, 2.0-2.5, 2.6-3.0, 3.1-3.5, >3.5. The number of events was recorded for each category, and this formed the numerator. The denominator was the summation of time each patient stayed in each category of INR. The event rate was then calculated for each INR category.

Results: 555 patients were included in the analysis, they constituted 893 patient-years. The INR was kept below 2.6 in 84.9% of the time and between 1.5 and 1.9 in 35% of the time. The overall event rate in our patients was 6.0%, of which 3.9% were due to thrombo-embolic events and 2.1% were due to serious bleeding. The overall event rate was lowest in the INR range from 1.5 to 1.9. which is not significantly different from that of INR 2.0-2.5 and 2.6-3.0. The overall event rate was 3.6% in INR 1.5-3.0 which was significantly lower than 15.1% in INR <1.5 and 20.5% in INR >3.0 (p < 0.01).

Conclusions: Our retrospective cohort showed that a lower INR range of 1.5-3.0 was safe and effective for stroke prevention in Chinese patients treated in a single hospital.
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http://dx.doi.org/10.1159/000086801DOI Listing
September 2005

Behçet's aortitis and aortic regurgitation: a report of two cases.

J Am Soc Echocardiogr 2004 Jan;17(1):83-6

Department of Medicine, Pamela Youde Nethersole Eastern Hospital, 3 Lok Man Rd, Chai Wan, Hong Kong SAR, China.

Behçet's disease is a rare systemic vasculitis that may lead to neurologic complications and rare manifestations of aortitis and aortic regurgitation. We report 2 cases of Behçet's aortitis and aortic regurgitation. The first patient presented with acute stroke. Recognition of acute aortitis on echocardiography led to the diagnosis of vasculitis as the cause of the cerebral event. This case highlights the echocardiographic features of aortic root pathology from acute aortitis to subsequent aortic valve perforation. In both cases, severe aortic regurgitation necessitated aortic valve replacement. Both were complicated by valve dehiscence requiring reoperation, illustrating the postoperative morbidity in this inflammatory condition.
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http://dx.doi.org/10.1016/j.echo.2003.09.009DOI Listing
January 2004

Efficacy, safety, and tolerability of pramipexole in untreated and levodopa-treated patients with Parkinson's disease.

J Neurol Sci 2003 Dec;216(1):81-7

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.

Objective: To evaluate the efficacy and safety of the non-ergot dopamine agonist pramipexole in untreated and levodopa-treated Chinese patients with early or advanced Parkinson's disease.

Methods: This randomized, double-blind, placebo-controlled, parallel-group study, which was conducted in Hong Kong and Taiwan, comprised a screening period of at least 1 week, a dose-escalation period of 7 weeks, and a maintenance period of 8 weeks (total duration of treatment: 15 weeks). During the dose-escalation period, the dose of pramipexole (or number of placebo tablets) was escalated in a blinded fashion according to a predetermined schedule to the optimum tolerated dose of pramipexole, administered three times a day (minimum dose=0.375 mg/day; maximum dose=4.5 mg/day). This dose was then maintained for the duration of the maintenance period. Efficacy was primarily assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). Safety and tolerability were evaluated by treatment-emergent adverse event reports, clinical laboratory test results (blood chemistry, hematology, and urinalysis), vital signs, and electrocardiograms.

Results: Pramipexole was significantly more effective than placebo in reducing the total scores of the UPDRS Part II, Part III, and Parts II and III combined. Approximately 70% of both the placebo- and pramipexole-treated patients evaluated in this analysis were on levodopa. Regardless of levodopa use, the mean UPDRS total scores showed a consistently greater improvement in pramipexole patients than in placebo patients. Mean scores for pramipexole patients not on levodopa showed a greater improvement than did pramipexole patients on levodopa. The mean improvement for the pramipexole/no levodopa group relative to the placebo/no levodopa group at week 15 was 10.93 points (i.e., -14.43 points minus -3.50 points). The mean improvement for the pramipexole/levodopa group relative to the placebo/levodopa group at week 15 was 9.04 points (i.e., -10.26 points minus -1.22 points). Pramipexole was also superior to placebo as measured by improvement in the modified Hoehn and Yahr Scale and a reduction in the number of "off" hours for patients on concomitant levodopa therapy.

Conclusions: Pramipexole is an effective and well-tolerated therapy, with or without concomitant levodopa, for Chinese patients with Parkinson's disease.
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http://dx.doi.org/10.1016/s0022-510x(03)00217-xDOI Listing
December 2003

Epileptic seizure after stroke in Chinese patients.

J Neurol 2003 Jul;250(7):839-43

Department of Medicine, Pamela Youde Nethersole Eastern Hospital, 3 Lok Man Road, Chai Wan, Hong Kong.

This was a hospital-based cohort study aiming at determining the occurrence rate of post-stroke seizures and the associated risk factors. From 27 July 1996 to 16 June 1998, the first 1000 consecutive patients in the acute stroke registry were retrospectively reviewed for one year after acute stroke to identify seizure occurrence. The demographic data, seizure onset time, seizure type, drug treatment, response to medication, electroencephalogram findings and cranial computed tomogram findings were collected. Thirty-four patients (3.4%) developed seizure within one year after acute stroke. Univariate analysis revealed that male, age greater than 65 years, total anterior circulation infarction, partial anterior circulation infarction, cortical location and large lesion were significantly associated with post-stroke seizure while multivariate analysis showed that only male (adjusted OR 3.21, p<0.01) and cortical location (adjusted OR 3.83, p<0.05) were significant independent risk factors. Fifty-six percent of early seizures were partial type whereas 72% of late seizures were generalized tonic-clonic type of undetermined onset. Seizures occurred in 3.4% of patients within one year after the onset of stroke. This percentage of seizure occurrence and associated risk factors were similar to other studies. However, intracerebral and subarachnoid haemorrhage were not shown to be risk factors in our study.
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http://dx.doi.org/10.1007/s00415-003-1091-3DOI Listing
July 2003
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