Raymond T.F. Cheung

Use of the Original, Modified, or New Intracerebral Hemorrhage Score to Predict Mortality and Morbidity After Intracerebral Hemorrhage

Background and Purpose— A simple clinical scale of intracerebral hemorrhage (ICH), comprising the Glasgow Coma Scale score, age, infratentorial origin, ICH volume, and intraventricular hemorrhage, was recently shown to predict 30-day mortality. We studied how well the original ICH Score would predict morbidity and mortality and determined whether modification would improve the predictions. Methods— Patients admitted to a regional hospital with acute ICH in 1999 were reviewed. Independent predictors of mortality or good outcome (modified Rankin score ≤2) at 30 days were identified by logistic regression to devise a new ICH Score for comparison with the original Score. A modified Score was created by substituting National Institutes of Health Stroke Scale (NIHSS) for the Glasgow Coma Scale. Results— The mortality rate was 22%, and 35% had good outcome. Independent factors for mortality were high NIHSS score, intraventricular hemorrhage, subarachnoid extension, and narrow pulse pressure. Independent factors for good outcome were low NIHSS score and low admission temperature. For all ICH Scores, no patient had a maximum score of 6. Cutoff values of ≥3 and <3 provided the best Youden’s index of diagnostic test in all ICH Scores for mortality and good outcome, respectively. The original and modified ICH Scores predict mortality equally well. The new and modified ICH Scores are slightly better for prediction of good outcome. Conclusions— All 3 ICH Scores are simple clinical grading scales. As reliable predictors of good outcome and/or mortality, they are useful in clinical research studies and standardization of clinical protocols.

Treatment of acute cerebral hemorrhage with intravenous glycerol. A double-blind, placebo-controlled, randomized trial.

Background and Purpose Hitherto, treatment of acute cerebral hemorrhage with intravenous glycerol has not been evaluated in rigorous clinical studies with sufficient patient numbers. Methods We undertook a double-blind, stratified and randomized, placebo-controlled clinical trial. Only patients with a first stroke admitted to the hospital within 24 hours after onset of symptoms were recruited, provided computed tomography confirmed hemorrhage and informed consent was obtained. After stratification into alert, semicoma, and coma subgroups using the Glasgow Coma Scale, 107 patients received active treatment (500 ml of 10% glycerol in saline by intravenous infusion over 4 hours on 6 consecutive days) and 109 were given corresponding saline treatment. Using a variety of objective scoring systems, patients were followed up for up to 6 months. Results At follow-up, all measures of outcome in the treated and control groups were very similar. At 6 months, respective mortality rates were 37 of 107 and 33 of 109. Corresponding mean±SD improvements in Scandinavian Stroke Study Group scores were 8.35±16.9 versus 11.55±15.6 (long-term) and 0.64±7.3 versus 2.40±6.9 (prognostic), and improvements in the Barthel Index ratings were 10.72±24.7 versus 13.95±23.3, respectively. Glasgow Coma Scale score improvements in the survivors were 0.81±1.5 and 1.16±1.7 in the treated and control groups, respectively. Hemolysis (generally subclinical) was the only adverse effect of glycerol noted. Conclusions In the absence of any clinically or statistically significant difference in outcome between the treated and control groups, this trial provides no justification for glycerol therapy following acute cerebral hemorrhage.s

The utility of melatonin in reducing cerebral damage resulting from ischemia and reperfusion

Abstract: The brain is highly susceptible to focal or global ischemia. Unless ischemia is promptly reversed, reperfusion produces further cerebral damage. Acute thrombolysis or defibrinogenation is effective only in selective patients with ischemic stroke and carries a significant risk of bleeding complications. Whereas numerous neuroprotectants were shown to be effective in experimental studies, none of them have been shown to work in clinical trials. The major pathogenetic mechanisms of ischemia/reperfusion injury include excitotoxicity, disturbed calcium ion homeostasis, overproduction of nitric oxide and other free radicals, inflammation, and apoptosis. Nitric oxide and other free radicals, the key mediators of excitotoxicity and disturbed calcium ion homeostasis, cause direct injury and also indirectly damage via inflammation and apoptosis. Melatonin is a potent free radical scavenger and an indirect antioxidant. This mini review summarizes the in vivo and in vitro evidence that melatonin protects against ischemia/reperfusion injury. There is convincing evidence from the literature that melatonin treatment is highly effective in different in vivo and in vitro models of excitotoxicity or ischemia/reperfusion in multiple animal species. Melatonin is safe and non‐toxic in humans, and its administration via the oral route or intravenous injection is convenient. While more experimental studies should be conducted to further explore the neuroprotective mechanisms and to document any synergistic or additive protection from combining melatonin with thrombolysis, defibrinogenation or other neuroprotectants, interested clinical scientists should consider planning phase II and III studies to confirm the benefit of melatonin as an acute stroke treatment or a preventive measure for stroke patients.

European Stroke Initiative Recommendations for Stroke Management

This article summarises recommendations for acute management of stroke by the European Stroke Initiative (EUSI), on behalf of the European Stroke Council (ESC), the European Neurological Society (ENS), and the European Federation of Neurological Societies (EFNS).

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.

Administration of Melatonin After Onset of Ischemia Reduces the Volume of Cerebral Infarction in a Rat Middle Cerebral Artery Occlusion Stroke Model

Background and Purpose— In both permanent and transient 3-hour middle cerebral artery occlusion rat stroke models, a single intraperitoneal injection of melatonin at 5 or 15 mg/kg given before ischemia was shown to reduce infarct volume at 72 hours. The present study was conducted to examine the treatment time window when melatonin was commenced after onset of ischemia. Methods— Adult male Sprague-Dawley rats were anesthetized to undergo right-sided middle cerebral artery occlusion for 3 hours. A single intraperitoneal injection of vehicle or melatonin at 5 mg/kg was given at 0, 1, or 3 hours after onset of ischemia. Other groups received multiple injections of vehicle or melatonin at 5 mg/kg with the first injection given at 1, 2, or 3 hours after onset of ischemia and the second and third injections at 24 and 48 hours, respectively. Multiple injections of melatonin at 15 mg/kg with the first injection given at 3 hours were also made. The infarct volume was determined at 72 hours. Results— A single dose of melatonin at 5 mg/kg given at 0 or 1 but not 3 hours after onset of ischemia reduced the infarct volume. Multiple doses of melatonin at 5 mg/kg also reduced the infarct volume when the first dose was given at 1 or 2 but not 3 hours after onset. Significant hemodynamic effects were not observed. Conclusions— Our results indicate that melatonin at 5 mg/kg given as a single injection or multiple injections protects against focal cerebral ischemia when commenced within 2 hours of onset.

Prevalence of Migraine, Tension-type Headache, and Other Headaches in Hong Kong

Objective.—To assess the prevalence of migraine and other headaches in Hong Kong in 1998.

Visual cortical activations on fMRI upon stimulation of the vision-implicated acupoints.

We used fMRI to reveal the visual cortical activations during conventional or electro-acupuncture over four vision-implicated acupoints in 18 healthy volunteers and compared the results with those obtained during direct visual stimulation. Positive activations were seen over the visual cortex during visual stimulation in all subjects, and similar activations were observed in 10 subjects during conventional acupuncture as well as in eight and seven subjects during electro-acupuncture at 2 and 20 Hz, respectively. Negative activations were also seen over the occipital lobes, temporal gyri and frontal gyri bilaterally in 13 subjects during conventional acupuncture. Thus, acupuncture may modulate the activity of relevant brain sites. Our results also suggest that electro-acupuncture is useful in future studies.

Pretreatment with melatonin exerts anti-inflammatory effects against ischemia/reperfusion injury in a rat middle cerebral artery occlusion stroke model

Abstract:  Inflammatory response following cerebral ischemia/reperfusion plays a key pathogenic role in ischemic cerebral damage. Nitric oxide (NO), cyclooxygenase‐2 (COX‐2) and myeloperoxidase (MPO) are important inflammatory mediators. Neuronal NO synthase (nNOS) is a major initial source of excessive NO during ischemia/reperfusion. Induction of COX‐2 and infiltration of polymorphonuclear cells expressing MPO are critical factors in delayed inflammatory damage. Previously, we demonstrated that administration of melatonin before ischemia significantly reduced the infarct volume in a rat middle cerebral artery occlusion (MCAO) stroke model. In this study, we examined the effect of pretreatment with melatonin at 5 mg/kg on the immunoreactivity (ir) for nNOS, COX‐2, MPO, and glial fibrillary acidic protein (GFAP) at 24, 48, and 72 hr after right‐sided endovascular MCAO for 1 hr in adult male Sprague–Dawley rats. Melatonin did not affect the hemodynamic parameters. When compared with rats with sham MCAO, ischemia/reperfusion led to an ipsilateral increase in cells with positive ir for nNOS (similar at all times) and in ir‐GFAP (similar at all times). Ischemia/reperfusion led to appearance of cells with positive ir for COX‐2 (greatest at 24 hr with a tendency to increase again at 72 hr) or MPO (greatest at 24 hr). A single dose of melatonin significantly lessened the ipsilateral increase in cells with positive ir for nNOS, COX‐2 or MPO, but did not influence the ipsilateral change in ir‐GFAP. Our results suggest that melatonin treatment mediates neuroprotection against ischemia/reperfusion injury partly via inhibition of the consequential inflammatory response.

An fMRI study comparing brain activation between word generation and electrical stimulation of language-implicated acupoints

We compared the brain activation on functional magnetic resonance imaging (MRI) during word generation with the activation during electrical stimulation of two language‐implicated acupoints in 17 healthy, Mandarin‐speaking, Chinese male volunteers (age 19–26 years). All subjects were strongly right handed according to a handedness inventory. Using a standard functional MRI procedure and a word‐generation paradigm, significant activation was seen in the left and right inferior frontal gyri (BA 44, 45) as well as the left superior temporal gyrus (BA 22, 42). Stronger activation with a larger volume was seen in the left hemisphere. Electrical stimulation of either one of the two language‐implicated acupoints, SJ 8 (11 subjects) and Du 15 (6 subjects), without the word‐generation paradigm in the same cohort, produced significant activation in the right inferior frontal gyrus (BA 44, 46) and in the left and right superior temporal gyri (BA 22, 42), respectively. Nevertheless, no activation was seen in the left inferior frontal gyrus. In addition, electrical stimulation of the adjacent non‐acupoints did not produce any significant brain activation. Although our results support the notion of acupoint–brain activation, applying acupuncture at SJ 8 or Du 15 does not activate the typical language areas in the left inferior frontal cortex. Hum. Brain Mapping 18:233–238, 2003.