Tak Hong Tsoi

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

Summary 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 ≥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.

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

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.

Impulse control disorders in Chinese Parkinson's disease patients: The effect of ergot derived dopamine agonist

OBJECTIVE We studied the prevalence and related risk factors of impulse control disorders in Chinese Parkinsons disease patients. METHOD We screened all non-demented Parkinsons disease patients attending our Parkinsons disease clinic from August 2009 to March 2010. The clinical characteristics of patients with impulse control disorders and those without were compared. RESULTS Of the 213 PD subjects screened, 15 (7.0%) with impulse control disorders were identified. Fourteen of these subjects were on both a dopamine agonist and Levodopa, and one was on Levodopa alone. Of the fourteen subjects on both a dopamine agonist and Levodopa, eleven were on bromocriptine and Levodopa; 10.5% of the subjects exposed to bromocriptine had impulse control disorder. Upon multivariate analysis, dose of dopamine agonist used, young age at onset of Parkinsons disease and a history of anxiety or depression were independent predictors for developing impulse control disorders. CONCLUSIONS 7% of our Chinese PD subjects had impulse control disorders. When young Parkinsons disease patients with a history of anxiety or depression are treated with high dose of DA, they are at risk of developing impulse control disorders.

Evolution of intracranial atherosclerotic disease under modern medical therapy.

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

Association of diffusion weighted imaging abnormalities and recurrence in transient global amnesia

Since the first description of transient global amnesia (TGA) in 1964, its etiology has remained obscure. Reversible diffusion weighted imaging (DWI) hyperintensities in the hippocampus have been found on MRI of some patients with TGA during acute events. The implication of this is not well understood. We identified 47 patients with TGA between November 2004 and November 2009, and enrolled 27 patients with brain MRI within 72 hours of symptom onset for analysis and recorded subsequent relapse or stroke occurrence during follow-up. Nine of the 27 patients had reversible hippocampal punctuate hyperintensities, with complete resolution noted on a second MRI on average 4 months after the initial TGA. Patients with a first relapse (their second TGA attack) had a significantly higher association of DWI hippocampal abnormalities (p=0.03) compared to patients with their first TGA event. None of the 27 patients had a stroke or further relapse during the mean follow-up period of 32.6 months. Thus, patients with recurrent TGA have a significantly higher association of reversible DWI abnormality.

Predictors of poststroke quality of life in older Chinese adults

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.

Topiramate for migraine prophylaxis among Chinese population.

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.

Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial

BACKGROUND The optimal treatment for patients with ischaemic stroke with a high risk of cerebral haemorrhage is unclear. We assessed the efficacy and safety of cilostazol versus aspirin, with and without probucol, in these patients. METHODS In this randomised, controlled, 2 × 2 factorial trial, we enrolled patients with ischaemic stroke with a history of or imaging findings of intracerebral haemorrhage or two or more microbleeds from 67 centres in three Asian countries. Patients were randomly assigned (1:1:1:1) to receive oral cilostazol (100 mg twice a day), aspirin (100 mg once a day), cilostazol plus probucol (250 mg twice a day), or aspirin plus probucol with centralised blocks stratified by centre. Cilostazol versus aspirin was investigated double-blinded; probucol treatment was open-label, but the outcome assessor was masked to assignment. The co-primary outcomes were incidence of the composite of stroke, myocardial infarction, or vascular death (efficacy) and incidence of haemorrhagic stroke (safety), which were assessed in intention-to-treat and modified intention-to-treat populations. Efficacy was analysed with a non-inferiority test and a superiority test if non-inferiority was satisfied. Safety was assessed with a superiority test only. This trial is registered with ClinicalTrials.gov, NCT01013532. FINDINGS Between Aug 1, 2009, and Aug 31, 2015, we randomly assigned 1534 patients to one of the four study groups, of whom 1512 were assessed for the co-primary endpoints. During a median follow-up of 1·9 years (IQR 1·0-3·0), the incidence of composite vascular events was 4·27 per 100 person-years in patients who received cilostazol and 5·33 per 100 person-years in patients who received aspirin (HR 0·80, 95% CI 0·57-1·11; non-inferiority p=0·0077; superiority p=0·18). Incidence of cerebral haemorrhage was 0·61 per 100 person-years in patients who received cilostazol and 1·20 per 100 person-years in those who received aspirin (HR 0·51, 97·5% CI 0·20-1·27; superiority p=0·18). The incidence of vascular events was 3·91 per 100 person-years in the probucol group compared with 5·75 per 100 person-years in the non-probucol group (HR 0·69, 95% CI 0·50-0·97; superiority p=0·0316). The incidence of cerebral haemorrhage was 0·72 per 100 person-years in the probucol group and 1·11 per 100 person-years in the non-probucol group (HR 0·65, 97·5% CI 0·27-1·57; p=0·55). Adverse events were similar across the four study groups; the most common events were dizziness, headache, diarrhoea, and constipation. INTERPRETATION In patients with ischaemic stroke at high risk of cerebral haemorrhage, cilostazol was non-inferior to aspirin for the prevention of cardiovascular events, but did not reduce the risk of haemorrhagic stroke. Addition of probucol to aspirin or cilostazol could be beneficial for reducing the incidence of cardiovascular events. FUNDING Korea Otsuka Pharmaceutical.

Herbs and Rehabilitation after Stroke Study: A Multi-center, Double-blinded, Randomized Trial in Hong Kong

Raymond Cheung, Li Xiong, Shek Kwan Chang, Choi Ting Tse, Yin Yu Pang, Vincent Mok, Thomas Leung, Tak Hong Tsoi, Richard Li, May Mok, Chee My Chang, Kwok Kwong Lau, Bun Sheng, Terrence Li, Jonas Yeung, Ping Chung Leung, Ping Chook, Ka Sing Wong Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong, Hong Kong Department of Medicine, Ruttonjee Hospital, Hong Kong, Hong Kong Department of Medicine, Princess Margaret Hospital, Hong Kong, Hong Kong Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, Hong Kong Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong Letter to the Editor