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Biomedical subjects

R T F Cheung

Publications and source records attributed to R T F Cheung.

18 recordsLinked to original sources

Myopia as a latent phenotype of a pleiotropic gene positively selected for facilitating neurocognitive development, and the effects of environmental factors in its expression.

Myopia has become an almost pandemic problem in many populations. There are compelling evidence to suggest that myopia is a hereditary condition. However, myopia would constitute a definite selection disadvantage during most stages of human evolution, which is incompatible with its moderate to high prevalence in most modern populations. The rapid upsurge of myopia over just a few decades also implies that its inheritance does not follow any of the usual patterns, and environmental factors may have an important role in precipitating its occurrence in those who are genetically predisposed. Previous studies showed that myopes were, on average, more intelligent than non-myopes, and this association had been attributed to a biological link between eye growth and brain development. We propose a pleiotropic genetic model to explain the atypical epidemiologic and inheritance pattern of myopia and its relationship with neurocognitive development. This pleiotropic gene was positively selected for its facilitation of human intelligence. The myopic component is a latent phenotype; myopia will not be expressed unless some novel external factors are encountered (i.e. a "quirk" phenomenon). Therefore, the myopic component was selectively neutral in our ancestral environment. The net gain in Darwinian fitness enables the pleiotropic gene to attain a high frequency in the human population, as reflected by our current prevalence of myopia.

Animals↗

Idiopathic inflammatory demyelinating disorders after acute transverse myelitis.

Acute transverse myelitis (ATM) is commonly para-infectious. Recurrent ATM occurs in connective tissue diseases (CTD), infective myelitis and idiopathic inflammatory demyelinating disorders (IIDD) including multiple sclerosis (MS) and neuromyelitis optica (NMO). Previous studies might include NMO and idiopathic recurrent transverse myelitis (IRTM) as MS. The aim was to study the outcome of patients after a first attack of idiopathic ATM. Idiopathic ATM patients over a 6-year period were retrospectively studied. Known causes of myelopathy were excluded. Among 32 patients studied, 20 (63%) had single ATM attack upon follow up for 39-93 months, three developed recurrent ATM related to CTD (two systemic lupus erythematosus and one anti-Ro antibody positive) and nine (28.1%) developed recurrent neuroinflammation compatible with IIDD. Among IIDD patients, three had NMO, two restricted variant of NMO, three IRTM and one classical MS. NMO, its variant and IRTM had mean spinal MRI abnormality of 3.7, 2.1 and 3.9 vertebral segments respectively while non-recurrent ATM had 1.6 vertebral segments. Four (80%) of the five patients with NMO or its variant had poor neurological prognosis versus only one (5%) of non-recurrent ATM patients. IRTM patients had advanced mean onset age, 62 years vs. 43 years for non-recurrent ATM patients. In IIDD patients presenting with ATM as first attack of neuroinflammation, NMO and its variant (56%) were most frequent, then IRTM (33%), with classical MS (11%) the rarest. As long-term treatments for NMO are different from MS, early recognition of NMO and its variant is important for prevention of serious neurological deficits.

Adult↗

Cerebral infarcts complicating tuberculous meningitis.

Cerebral infarction (CI) is a serious complication of tuberculous meningitis (TBM). It can be asymptomatic or symptomatic, causing stroke. We studied 40 TBM patients. All had initial CT brain scan, CT/MRI brain scan 3 months later and urgent CT brain scan for deterioration. CI was classified into lacunar infarction (LI) or large artery infarction (LAI). Twelve (30%) had CI, in 9 (23%) it was symptomatic and in 3 (8%) silent. Seven (58%) had LAI +/- LI. Eight (67%) had multiple CI. Two died from brainstem CI and 6 were dependent at 1 year. Patients with LAI might develop posterior circulation CI more frequently than those with LI only. CI is a common complication of TBM locally, with LAI and multiple CI being common. Two thirds of TBM patients complicated by CI had poor prognosis despite adjunctive dexamethasone treatment.

Adolescent↗

Cerebral venous thrombosis in a gentleman presenting with fever, convulsion and frontotemporal haemorrhages.

Cerebral venous thrombosis (CVT) is an uncommon but serious type of stroke. Thrombosis may involve the cortical or deep veins or the venous sinuses. The presenting clinical features are non-specific. We report a 48-year-old man with CVT who presented with fever, bitemporal throbbing headache, and generalised convulsion. Computed tomography (CT) of the brain revealed acute haemorrhages over right anterior frontal and posterior temporal regions with surrounding oedema and right anterior temporal subcortical oedema. The initial diagnosis was herpes simplex encephalitis. Absence of venous flow over the right transverse and sigmoid sinuses during the venous phase of digital subtraction angiography (DSA) revealed CVT. He was anti-coagulated for 6 months. An underlying cause of CVT was not detected. A high index of suspicion is required when risk factors of CVT are present. CT brain may be normal or showing non-specific findings. Magnetic resonance imaging plus venography, CT venography, or DSA is diagnostic.

Angiography, Digital Subtraction↗

Wilson's disease with depression and parkinsonism.

Wilson's disease (WD) is an autosomal recessive disorder with reduced biliary excretion of copper plus impaired formation of ceruloplasmin, leading to copper accumulation in the liver, brain, kidney, and cornea. Clinical manifestations include liver damage, psychiatric symptoms, and neurological features. We report a 35-year-old woman with a history of deranged liver functions who had severe depression several years later and eventually presented with parkinsonian features. The underlying diagnosis is WD and family screening revealed WD in 2 other siblings. She could not tolerate penicillamine because of fever and leucopenia. While taking trientine hydrochloride and zinc sulphate, her parkinsonism improved and her depression remained in remission. WD should be considered in patients with unexplained liver function derangement or psychiatric symptoms. Early diagnosis and initiation of specific treatment are crucial in minimising any further cerebral and hepatic damage as well as securing possible improvement in organ functions.

Adult↗

A possible explanation for the racial difference in distribution of large-arterial cerebrovascular disease: ancestral European settlers evolved genetic resistance to atherosclerosis, but confined to the intracranial arteries.

The pattern of cerebral atherosclerosis is not the same among different races. White patients rarely have intracranial large arterial steno-occlusive disease even if their systemic arteries are extensively involved, while non-white patients frequently have their intracranial arteries affected. We postulate that during human population diversification, those who settled in Europe had acquired a stroke-suppressor genotype that increases their resistance against atherogenesis, but with protection confined to the intracranial large arteries. The contemporary affluent lifestyle accelerates the development of atherosclerosis. In the whites, it involves the whole arterial bed except the intracranial vessels. People living in non-Western countries used to have a healthier way of living. They did not develop significant atherosclerotic diseases until recently when a westernised lifestyle was adopted. Unlike the whites, their intracranial arteries will not be spared. Atherosclerosis has become a major cause of premature mortality in the modern world, and an anti-atherogenic mechanism would confer a selection advantage. With further adaptive intensification, this protection may extend to the rest of the arterial bed. As a result, future Homo sapiens will be able to tolerate an affluent lifestyle without much adverse sequel such as premature vascular death. Alternatively, if the mediator of this anti-atherogenic mechanism can be identified and applied therapeutically, we will have an ultimate mean to prevent atherosclerosis.

Antioxidants↗

An epidemiological study of motor neuron disease in Hong Kong.

Worldwide, the incidence of motor neuron disease (MND) has been increasing steadily over recent decades. We reported a follow-up epidemiology study of MND in this locality. We identified the subjects from the computer database of the government hospital system between 1 January 1997 and 31 January 2002 by searching the ICD code starting from 335.xx. Every retrieved case or their records were reviewed and validated by neurologist(s) of the responsible regional hospitals which the patients attended. One hundred and twenty cases from seven regional hospitals (serving 48.05% of the HKSAR population) were identified, validated and confirmed to be MND or related diseases. Ninety-eight new cases were diagnosed during the study period. Average age of onset was 58.76 years; SD 14.12 (28-89) years. Male to female ratio was 1.72:1. Peak age of onset was 60-64 years without sex difference. The adjusted incidence rate was 0.60/100,000/year. The adjusted point prevalence at the prevalence date (31 January 2001) was 3.04/100,000. Despite the incidence and prevalence of MND among Hong Kong Chinese, it remained low compared to worldwide figures, and our data suggested a significant rise of MND or related disease in the last decade. A territory-wide prospective epidemiological study is indicated.

Adult↗

Cerebrospinal fluid to serum glucose ratio in non-hypoglycorrhachic neurological conditions.

OBJECTIVE: To explore the relevance of cerebrospinal fluid to serum glucose ratio in non-hypoglycorrhachic conditions. DESIGN: Retrospective observational study. SETTING: Neurology ward, university teaching hospital, Hong Kong. PATIENTS: Adult patients with conditions unrelated to hypoglycorrhachia who underwent lumbar puncture. MAIN OUTCOME MEASURES: Cerebrospinal fluid and simultaneous serum glucose concentrations, and their ratio to each other. RESULTS: Between September 1998 and August 2003, 170 cerebrospinal fluid and serum glucose samples were collected from 138 patients. Mean cerebrospinal fluid to serum glucose ratio was 0.61 (standard deviation, 0.142; range, 0.21-1.00). With the exception of cerebrospinal fluid protein level, laboratory parameters were similar among different diseases. The glucose ratio was lower than 0.6 in 43% and lower than 0.5 in 19% of samples. Cases with a low glucose ratio appeared to have higher serum glucose concentrations (significant among groups with different glucose ratios, P<0.001). The mean glucose ratio (0.65) was also significantly higher in patients with serum glucose concentration of lower than 7.8 mmol/L compared with those with serum glucose concentration between 7.8 and 11.1 mmol/L (mean, 0.46), or higher than 11.1 mmol/L (mean, 0.46) [P<0.001]. There was a strong negative correlation between the glucose ratio and serum glucose concentration (r= -0.704, P<0.001). CONCLUSION: A lowered cerebrospinal fluid to serum glucose ratio is often seen in the absence of an appropriate disorder, especially when simultaneous serum glucose concentration is elevated. This may be explained by the saturation kinetics of glucose transportation in hyperglycaemia, and the time lag for cerebrospinal fluid and glucose to equilibrate when the blood level fluctuates.

Adult↗

Consensus statement on ischaemic stroke care in Hong Kong.

OBJECTIVE: To issue guidelines for the care of acute stroke in Hong Kong, with the target audience of all health care professionals who are involved in acute stroke care. PARTICIPANTS: The Hong Kong Neurological Society and the Hong Kong Stroke Society. EVIDENCE: The panel applied the 'rule of evidence' used by the United States Agency for Health Care Policy and Research. When there is insufficient evidence, the recommendation was based on customary practice and was circulated among the members and fellows of the two societies before coming to a consensus. CONSENSUS PROCESS: Group meetings were held in 2002 to review the literature about acute care for patients with ischaemic stroke and to issue a consensus statement with reference to the local health care system. Participants of the meetings were appointed by the councils of The Hong Kong Neurological Society and the Hong Kong Stroke Society. The draft statement was circulated among the members and fellows of the two societies for comments before it was finalized. CONCLUSIONS: Ischaemic stroke is a heavy health care burden to Hong Kong. The current consensus statement provides a framework to establish a multidisciplinary approach towards its acute management.

Aged↗

Intracerebroventricular injection of a neuropeptide Y-Y1 receptor agonist increases while BIBP3226, a Y1 antagonist, reduces the infarct volume following transient middle cerebral artery occlusion in rats.

Recent studies using middle cerebral artery occlusion in the rat have suggested a role of neuropeptide Y in ischemic pathophysiology. In this study, we investigated the effects of an i.c.v. injection of a neuropeptide Y-Y2 receptor agonist, neuropeptide Y 3-36, a Y1 receptor agonist, [Leu(31),Pro(34)]-neuropeptide Y, or a Y1 receptor antagonist, BIBP3226, on infarct volume and hemodynamic parameters following middle cerebral artery occlusion. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 2 h. A single i.c.v. injection of neuropeptide Y 3-36 (15 microg/kg), [Leu(31),Pro(34)]-neuropeptide Y (30 microg/kg), or BIBP3226 (5, 15, or 45 microg/kg) was given at 30 min of ischemia. Blood pressure, heart rate, and regional cerebral perfusion were monitored during ischemia and reperfusion. The rats were decapitated after 70 h of reperfusion, and their brains were cut into 2-mm-thick coronal slices before reaction with a 2% solution of 2,3,5-triphenyltetrazolium chloride to reveal the infarct. When compared with an infarct volume of 17.4+/-4.4% of the ipsilateral hemisphere following injection of neuropeptide Y 3-36, administration of the Y1 receptor analogs significantly modified the infarct volume (ordinary one-way analysis of variance (ANOVA), P<0.0001). [Leu(31),Pro(34)]-neuropeptide Y increased the infarct volume to 32.0+/-4.1% (Student-Newman-Keuls post-test, P<0.01), whereas BIBP3226 at 15 microg/kg decreased the infarct volume to 6.5+/-1.0% (post-test P<0.05). Although there was no major difference in the hemodynamic parameters among the groups, injection of [Leu(31),Pro(34)]-neuropeptide Y tended to further reduce cerebral perfusion during ischemia, while injection of BIBP3226 at 15 microg/kg appeared to have the opposite effect. In addition to glutamate, calcium ion and nitric oxide, activation of the neuropeptide Y-Y1 receptors may mediate cerebral damage during focal ischemia. Conversely, inhibiting the Y1 receptors may protect the brain against ischemic injury. Further studies are warranted to confirm the neuroprotective potential of neuropeptide Y-Y1 receptor inhibition.

Animals↗

Melatonin reduces nitric oxide level during ischemia but not blood-brain barrier breakdown during reperfusion in a rat middle cerebral artery occlusion stroke model.

Melatonin is a potent antioxidant and free radical scavenger. Previously, we showed that a single injection of melatonin before ischemia significantly reduced the infarct volume in both permanent and 3-hr middle cerebral artery occlusion (MCAO) rat stroke models. Nitric oxide (NO) and other free radicals play an important role in the pathogenesis of cerebral ischemia, and they have been postulated to mediate the breakdown of the blood-brain barrier (BBB) during ischemia. In this study, we evaluated the influence of melatonin, given at 30 min before MCAO, on brain NO concentration and BBB breakdown. Brain NO concentration was measured at 15 min of MCAO using electron paramagnetic resonance spectroscopy. BBB breakdown at 3 hr of reperfusion following 3 hr of MCAO was assessed using Evans blue extravasation. The relative brain NO concentration was increased to 141.69 +/- 9.71% (mean +/- S.E.M.; n = 9) at 15 min of MCAO. Treatment with melatonin at 1.5, 5, or 50 mg/kg significantly reduced the brain NO concentration to 104.20 +/- 11.20% (n = 8), 55.67 +/- 5.58% (n = 11), and 104.86 +/- 12.56% (n = 9), respectively. Melatonin at 5 mg/kg did not affect Evans blue extravasation. Our results suggest that a single injection of melatonin protects against focal cerebral ischemia partly via inhibition of ischemia-induced NO production and that this regimen does not prevent BBB breakdown following ischemia-reperfusion.

Animals↗

Clinical relevance of hydrocephalus as a presenting feature of tuberculous meningitis.

BACKGROUND: Hydrocephalus is a common complication of tuberculous meningitis (TBM). AIM: To study the incidence, associated clinical features, and impact on outcome of hydrocephalus at presentation in TBM. DESIGN: Observational study. SETTING: Regional hospital serving 500,000 people. METHODS: Adult patients with TBM were studied over 57 months. Those with hydrocephalus on initial CT scan were assessed by neurosurgeons. Clinical, neuroradiological, and biochemical features of patients with hydrocephalus upon presentation were compared to those without initial hydrocephalus. RESULTS: Of 31 TBM patients during the study period, nine (29.0%) had hydrocephalus at presentation, and eight of them (25.8% of all) underwent urgent neurosurgical intervention. Of the 22 patients without initial hydrocephalus, hydrocephalus developed after commencement of chemotherapy in one patient only. Hydrocephalus at presentation was associated with a longer duration of presenting symptoms (p = 0.01), ataxia (p = 0.001), later stages of TBM (p = 0.045), a longer delay before commencement of anti-tuberculous chemotherapy (p = 0.001), stroke (p = 0.012), and a poor outcome at 1 year (p = 0.001). DISCUSSION: Hydrocephalus upon presentation is common in our TBM patients. This may be a poor prognostic marker associated with severe TBM and a higher risk of stroke.

Adult↗

Visualization of ischaemic penumbra using a computed tomography perfusion method.

A computed tomography (CT) perfusion imaging and a diffusion/perfusion magnetic resonance imaging (MRI) were performed in a 51-year-old man at 15 and 15.5 h of onset of left middle cerebral artery infarction, respectively. The established infarct, as revealed by the diffusion-weighted MRI, had low values of cerebral blood flow (CBF) and cerebral blood volume (CBV) on the CT perfusion study. The ischaemic penumbra, as reflected by the perfusion-diffusion mismatch on MRI, had reduced CBF, prolonged mean transit time (MTT) and compensated CBV. Spontaneous bleeding occurred in the medial part of the left lentiform nucleus, immediately following decompressive craniectomy. CT measurements of CBF, CBV and MTT may visualize the ischaemic penumbra and explain the site of bleeding after surgical decompression.

Brain Ischemia↗

Pretreatment with melatonin reduces volume of cerebral infarction in a rat middle cerebral artery occlusion stroke model.

Melatonin is a potent scavenger of free radicals and an indirect antioxidant. Recent studies have shown that melatonin possesses beneficial effects in experimental models of brain trauma and global cerebral ischemia. The effects of pretreatment with melatonin on volume of cerebral infarction were investigated in the present study. Adult male Sprague-Dawley rats were anesthetized with sodium pentobarbital to undergo right-sided endovascular middle cerebral artery occlusion (MCAO) for 3 hr. A single dose of melatonin (1.5, 5, 15, or 50 mg/kg in 1 mL normal saline) or its vehicle was given via an intraperitoneal injection at 0.5 hr before MCAO. Relative infarction volumes on day 3 after MCAO were significantly reduced in the groups treated with melatonin at 5 (mean +/- S.E.M., 15.7 +/- 2.5%) or 15 (21.4 +/- 3.1 %) mg/kg but not at 1.5 (30.6 +/- 3.5%) or 50 (26.7 +/- 2.8%) mg/ kg when compared with the vehicle group (33.9 +/- 3.5%). There was no significant difference in the arterial blood pressure (BP), heart rate (HR) and relative cerebral blood flow among the experimental groups. These results indicate that pretreatment with melatonin at a dose between 5 and 15 mg/kg protects against focal cerebral ischemia.

Animals↗