Melatonin at repeated doses alleviates hyperglycemia-exacerbated cerebral ischemia-reperfusion injury at 72 h via anti-inflammation and anti-apoptosis.

Objective: We aimed to investigate how hyperglycemia would exacerbate cerebral ischemia-reperfusion injury (CIRI) in a rat model of type 1 diabetes mellitus (T1DM) and explore the beneficial effects of multiple doses of melatonin in T1DM induced CIRI. Method: The T1DM rat model was induced with streptozocin, and melatonin (10 mg/kg) was injected at 0.5 h before ischemia as well as at 24 and 48 h after reperfusion. Results: When compared to normoglycemic (NG) rats, T1DM rats had hyperglycemia with weight loss before CIRI. Despite comparable degrees of ischemia and initial reperfusion, T1DM rats tended to have greater weight loss and had worse neurological deficits and larger infarct volume than NG rats up to 72 h after CIRI. Persistent activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway but not of apoptosis or calpains was a crucial factor in T1DM-mediated exacerbation of CIRI at 72 h. Despite lacking effects on baseline hyperglycemia, ischemia and initial reperfusion, melatonin at multiple doses lessened post-CIRI weight loss, neurological deficits and infarct volume in T1DM rats at 72 h. when compared to vehicle-treated T1DM rats with CIRI. Beneficial effects of melatonin treatment included decreased activation of NF-κB pathway, apoptosis and calpains, leading to reduced expression of inducible nitric oxide synthase and enhanced neuronal density. Conclusion: Melatonin at multiple doses can alleviate T1DM-mediated exacerbation of CIRI at 72 h through anti-inflammation and anti-apoptosis.

Inhibitory dysfunction may cause prospective memory impairment in temporal lobe epilepsy (TLE) patients: an event-related potential study.

Introduction: Prospective memory (PM) is the ability to remember future intentions, and PM function is closely related to independence in daily life, particularly in patients with temporal lobe epilepsy (TLE). As PM involves various cognitive components of attention, working memory, inhibition and other executive functions, this study investigated how TLE may affect PM components and the underlying neural mechanisms. Methods: Sixty-four subjects were recruited, including 20 refractory TLE patients, 18 well-controlled TLE patients and 26 age-matched healthy controls. A set of neuropsychological tests was administered to assess specific brain functions. An event-related potential (ERP) task was used to further explore how PM and its components would be differentially affected in the two TLE types. Results: Our findings revealed that: (1) refractory TLE patients scored lower than the healthy controls in the digit span, Verbal Fluency Test and Symbol Digit Modalities Test; (2) refractory TLE patients exhibited impaired PM performance and reduced prospective positivity amplitudes over the frontal, central and parietal regions in ERP experiments when compared to the healthy controls; and (3) decreased P3 amplitudes in the nogo trials were observed over the frontal-central sites in refractory but not in well-controlled TLE patients. Discussion: To our knowledge, this is the first ERP study on PM that has specifically identified PM impairment in refractory but not in well-controlled TLE patients. Our finding of double dissociation in PM components suggests that inhibition dysfunction may be the main reason for PM deficit in refractory TLE patients. The present results have clinical implications for neuropsychological rehabilitation in TLE patients.

Melatonin mitigates type 1 diabetes-aggravated cerebral ischemia-reperfusion injury through anti-inflammatory and anti-apoptotic effects.

INTRODUCTION: Cerebral ischemia and diabetes mellitus (DM) are common diseases that often coexist and interact with each other. DM doubles the risk of ischemic stroke, and cerebral ischemia causes stress-induced hyperglycemia. Most experimental stroke studies used healthy animals. Melatonin is neuroprotective against cerebral ischemia-reperfusion injury (CIRI) in non-DM, normoglycemic animals through anti-oxidant effect, anti-inflammation, and anti-apoptosis. Previous studies have also reported a negative correlation between hyperglycemia and urinary melatonin metabolite. OBJECTIVES: The present study investigated the effects of type 1 DM (T1DM) on CIRI in rats and the role of melatonin against CIRI in T1DM animals. RESULTS: Our results revealed that T1DM aggravated CIRI, leading to greater weight loss, increased infarct volume, and worse neurological deficit. T1DM aggravated the post-CIRI activation of nuclear factor kappa B (NF-κB) pathway and increase in pro-apoptotic markers. A single intraperitoneal injection of melatonin at 10 mg/kg given 30 min before ischemia onset attenuated CIRI in T1DM rats, resulting in less weight loss, decreased infarct volume, and milder neurological deficit when compared with the vehicle group. Melatonin treatment achieved anti-inflammatory and anti-apoptotic effects with reduced NF-κB pathway activation, reduced mitochondrial cytochrome C release, decreased calpain-mediated spectrin breakdown product (SBDP), and decreased caspase-3-mediated SBDP. The treatment also led to fewer iNOS+ cells, milder CD-68+ macrophage/microglia infiltration, decreased TUNEL+ apoptotic cells, and better neuronal survival. CONCLUSIONS: T1DM aggravates CIRI. Melatonin treatment is neuroprotective against CIRI in T1DM rats via anti-inflammatory and anti-apoptotic effects.

Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions.

Evidence accumulated from the last decade has proven that silent cerebrovascular lesions (SCLs) and their underlying pathogenic processes contribute to cognitive decline in the elderly. However, the distinct effects of each type of the lesions on cognitive performance remain unclear. Moreover, research data from Chinese elderly with SCLs is scarce. In this study, 398 otherwise healthy hypertensive elderly subjects (median age 72 years) were included and assessed. All participates were required to complete a battery of structured neuropsychological assessment, including forward and backward digit span tests, symbol digit modalities test, Stroop test, verbal fluency test and Montreal Cognitive Assessment. These tests were used to assess attention, executive function, information processing speed, language, memory and visuospatial function. A multi-sequence 3T MRI scanning was arranged within one month of the neuropsychological assessment to evaluate the burden of SCLs. SCLs were rated visually. Cerebral microbleeds (CMBs) and silent lacunes (SLs) were identified as strictly lobar CMBs and SLs or deep CMBs and SLs according to their locations, respectively. Similarly, white matter hyperintensities (WMHs) were separated into periventricular WMHs (PVHs) and deep WMHs (DWMHs). A series of linear regression models were used to assess the correlation between each type of SCLs and individual cognitive function domain. The results showed that CMBs tend to impair language-related cognition. Deep SLs affect executive function, but this association disappeared after controlling for other types of SCLs. PVHs, rather than DWMHs, are associated with cognitive decline, especially in executive function and processing speed. It is concluded that different aspects of SCLs have differential impact on cognitive performance in hypertensive elderly Chinese.

Distinct profiles of cognitive impairment associated with different silent cerebrovascular lesions in hypertensive elderly Chinese.

BACKGROUND/OBJECTIVES: Silent cerebrovascular lesions (SCLs) and their underlying pathology are now recognized as important causes of cognitive impairment in the elderly. However, the distinct profile of cognitive deficits associated with each type of SCLs remains unclear. METHODS: Of 497 otherwise healthy hypertensive elderly Chinese, 398 participants (mean age 72.0, ranging from 65 to 99, SD = 5.1) successfully completed a battery of structured neuropsychological tests and a multi-sequence 3 T MRI scanning. SCLs were rated independently. Correlations between each MRI marker and cognitive function were assessed using a series of linear regression models. RESULTS: Strictly lobar cerebral microbleeds were linked to impaired language function (B = -0.231, p < 0.05). Silent lacunes were associated with poor executive function, but the association disappeared after additional adjustment for white matter hyperintensities. White matter hyperintensities (especially periventricular hyperintensities) were associated with poor executive function (B = -0.126, p < 0.05) and slower information processing speed (B = -0.149, p < 0.05). CONCLUSION: Different SCLs were associated with different patterns of cognitive deficits, indicating that different SCLs may have distinct impacts on cognitive performance.

Total small vessel disease score and risk of recurrent stroke: Validation in 2 large cohorts.

OBJECTIVE: In patients with TIA and ischemic stroke, we validated the total small vessel disease (SVD) score by determining its prognostic value for recurrent stroke. METHODS: Two independent prospective studies were conducted, one comprising predominantly Caucasian patients with TIA/ischemic stroke (Oxford Vascular Study [OXVASC]) and one predominantly Chinese patients with ischemic stroke (University of Hong Kong [HKU]). Cerebral MRI was performed and assessed for lacunes, microbleeds, white matter hyperintensities (WMH), and perivascular spaces (PVS). Predictive value of total SVD score for risk of recurrent stroke was determined and potential refinements considered. RESULTS: In 2,002 patients with TIA/ischemic stroke (OXVASC n = 1,028, HKU n = 974, 6,924 patient-years follow-up), a higher score was associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio [HR] per unit increase: 1.32, 1.16-1.51, p < 0.0001; c statistic 0.61, 0.56-0.65, p < 0.0001) and intracerebral hemorrhage (ICH) (HR 1.54, 1.11-2.13, p = 0.009; c statistic 0.65, 0.54-0.76, p = 0.006). A higher score predicted recurrent stroke in SVD and non-SVD TIA/ischemic stroke subtypes (c statistic 0.67, 0.59-0.74, p < 0.0001 and 0.60, 0.55-0.65, p < 0.0001). Including burden of microbleeds and WMH and adjusting the cutoff of basal ganglia PVS potentially improved predictive power for ICH (c statistic 0.71, 0.60-0.81, phet = 0.45), but not for recurrent ischemic stroke (c statistic 0.60, 0.56-0.65, phet = 0.76) on internal validation. CONCLUSIONS: The total SVD score has predictive value for recurrent stroke after TIA/ischemic stroke. Prediction of recurrence in patients with nonlacunar events highlights the potential role of SVD in wider stroke etiology.

Electrophysiological Study on Cognitive Function in Systemic Lupus Erythematosus Patients With Previous Neuropsychiatric Involvement.

This study aimed to evaluate P300 as an electrophysiological marker of cognitive function in patients with systemic lupus erythematosus (SLE) who had previous neuropsychiatric (NPSLE) involvement and were diagnosed to have cognitive impairment by standard neuropsychological tests. Event-related potentials (ERPs) were assessed by the auditory and visual oddball paradigms. Amplitude and latency of P300 at the frontal (Fz), central (Cz), and parietal (Pz) regions were determined and compared with controls. P300 detection was performed in NPSLE patients with pre-diagnosed cognitive impairment (n = 9), matched SLE patients without previous NPSLE (non-NPSLE) (n = 9), and healthy controls (n = 15). Auditory oddball task did not show any P300 abnormality between groups. Visual oddball task revealed reduced amplitude of P300 over Fz ( P = .002) and Cz ( P = .009) electrodes in NPSLE patients compared with healthy controls and among those who had predominant memory deficit ( P = .01 at Fz). Abnormal P300 was also observed in non-NPSLE patients at Fz and Cz. Using visual oddball paradigm, abnormal P300 was found in NPSLE patients over frontal and parietal regions compared with normal controls but was not discriminative from possible subclinical disease in non-NPSLE patients. In conclusion, visual oddball paradigm was a more sensitive electrophysiological marker than auditory oddball paradigm for cognitive impairment in NPSLE patients.

Mediterranean-style diet is associated with reduced blood pressure variability and subsequent stroke risk in patients with coronary artery disease.

BACKGROUND AND PURPOSE: The Mediterranean-style diet is widely advocated for the prevention of cardiovascular diseases (CVD). Meanwhile, blood pressure variability (BPV) is a novel risk factor for CVD. It is unknown whether dietary pattern plays a role in modulating BPV. METHODS: We prospectively followed-up 274 consecutive patients with stable coronary artery disease (CAD). The Mediterranean diet score (MDS) was derived for all individuals upon recruitment, blood pressure (BP) was measured during each subsequent clinic visit and the visit-to-visit BPV was calculated. The occurrence of major adverse cardiovascular events (MACEs) and all-cause mortality was monitored. RESULTS: After a mean follow-up of 77±12 months, 16.1% of the study population developed MACEs. About 11.3% died from all causes. Patients who developed MACEs or all-cause mortality had a greater systolic BPV compared to those who did not develop an adverse event. Patients who developed a MACE had a lower MDS and further analysis revealed those who developed a stroke had a lower MDS compared with those who did not develop a stroke, but there were no significant differences in MDS between CAD patients with or without subsequent acute coronary syndrome, cardiovascular, or all-cause mortality. After adjusting for confounding variables, a high MDS was an independent predictor for low systolic BPV (B -0.74, 95% confidence interval -1.27 to -0.21, P < 0.01) and was noted to be protective against subsequent development of stroke (hazards ratio 0.48, 95% confidence interval 0.24 to 0.94, P = 0.03). CONCLUSIONS: Among patients with CAD, a higher MDS is associated with a lower visit-to-visit BPV and with lower stroke risk.

A self-assembling nanomaterial reduces acute brain injury and enhances functional recovery in a rat model of intracerebral hemorrhage.

There is no effective treatment for intracerebral hemorrhage (ICH). Intracerebral delivery of nanomaterials into the hemorrhagic lesion may be a new therapeutic strategy. In a rat model of ICH plus ultra-early hematoma aspiration, we found that locally delivered self-assembling peptide nanofiber scaffold (SAPNS) replaced the hematoma, reduced acute brain injury and brain cavity formation, and improved sensorimotor functional recovery. SAPNS serves as biocompatible material in the hemorrhagic brain cavity. Local delivery of this nanomaterial may facilitate the repair of ICH related brain injury and functional recovery. From the clinical editor: In a rat model of intracranial hemorrhage, these authors demonstrate that following ultra-early hematoma aspiration, local delivery of a self-assembling peptide nanofiber scaffold replaces the hematoma, reduces brain cavity formation, and improves sensorimotor functional recovery. Similar approaches would be welcome additions to the clinical treatment of this often devastating condition.

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases--relationships and comparisons with vascular markers of atherosclerosis.

BACKGROUND: Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. METHODS: We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits. RESULTS: After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P<0.01). BPV significantly correlated with all of the vascular assessments (P<0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69 ± 0.03, P<0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65 ± 0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). CONCLUSIONS: Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases.

Stroke patients with a past history of cancer are at increased risk of recurrent stroke and cardiovascular mortality.

BACKGROUND AND PURPOSE: Cancer patients are at increased risk of cardiovascular and cerebrovascular events. It is unclear whether cancer confers any additional risk for recurrent stroke or cardiovascular mortality after stroke. METHODS: This was a single center, observational study of 1,105 consecutive Chinese ischemic stroke patients recruited from a large stroke rehabilitation unit based in Hong Kong. We sought to determine whether patients with cancer are at higher risk of recurrent stroke and cardiovascular mortality. RESULTS: Amongst 1,105 patients, 58 patients (5.2%) had cancer, of whom 74% were in remission. After a mean follow-up of 76 ± 18 months, 241 patients developed a recurrent stroke: 22 in patients with cancer (38%, annual incidence 13.94%/year), substantially more than those without cancer (21%, 4.65%/year) (p<0.01). In a Cox regression model, cancer, age and atrial fibrillation were the 3 independent predictors of recurrent stroke with a hazard ratio (HR) of 2.42 (95% confidence interval (CI): 1.54-3.80), 1.01 (1.00-1.03) and 1.35 (1.01-1.82) respectively. Likewise, patients with cancer had a higher cardiovascular mortality compared with those without cancer (4.30%/year vs. 2.35%/year, p = 0.08). In Cox regression analysis, cancer (HR: 2.08, 95% CI: 1.08-4.02), age (HR: 1.04, 95% CI 1.02-1.06), heart failure (HR: 3.06, 95% CI 1.72-5.47) and significant carotid atherosclerosis (HR: 1.55, 95% CI 1.02-2.36) were independent predictors for cardiovascular mortality. CONCLUSIONS: Stroke patients with a past history of cancer are at increased risk of recurrent stroke and cardiovascular mortality.

Rat model of intracerebral hemorrhage permitting hematoma aspiration plus intralesional injection.

A combination of hematoma aspiration and local delivery of chemicals may be more effective than either therapy in intracerebral hemorrhage (ICH). The aim of the present study was to develop a rat model of hematoma aspiration plus intralesional injection after ICH. ICH was induced in adult Sprague-Dawley rats by an intrastriatal injection of bacterial collagenase IV. Hematoma aspiration was performed 3.5 h after ICH onset. Following aspiration, normal saline was injected into the lesion cavity. Hematoma aspiration with or without subsequent saline injection significantly reduced the hematoma volume, lesion volume, and perihematomal neutrophil infiltration. Hematoma aspiration plus subsequent intralesional injection is simple, feasible, and safe. This ICH model can be used to assess the effectiveness of hematoma removal plus local delivery of chemicals.

Elevated blood pressure aggravates intracerebral hemorrhage-induced brain injury.

Elevated blood pressure (BP) is commonly seen in patients with intracerebral hemorrhage (ICH), and is independently associated with poor functional outcomes. Little is known about how elevated BP influences ICH-related brain injury. In the present study, we investigated the physiological and brain histological changes, as well as functional recovery following ICH in renovascular hypertensive rats. Renovascular hypertension (RVHT) was achieved by applying a silver clip onto the left renal artery of adult Sprague-Dawley rats. ICH was induced by an intrastriatal injection of bacterial collagenase IV about 5-6 weeks after left renal artery clipping or the sham operation. Following induction of ICH, both the normotensive and RVHT rats demonstrated an ultra-acute elevation in BP. Elevated BP increased hematoma volume, brain swelling, and apoptosis in the perihematomal areas. Brain degeneration, including local atrophy and lateral ventricle enlargement, was greater in the RVHT rats. In addition, many proliferating cells were seen over the ipsilateral striatum in the RVHT rats after ICH. The modified limb placing tests were done weekly for 3 weeks. In line with the histological damage, elevated BP worsened neurological deficits. These results suggest that ICH in the hypertensive rats mimics the clinical scenario of hypertensive ICH and may provide a platform to study the mechanisms of ICH-induced brain injury and potential therapies for ICH.

Possible retrogenesis observed with fiber tracking: an anteroposterior pattern of white matter disintegrity in normal aging and Alzheimer's disease.

Retrogenesis refers to the phenomenon by which degenerative processes in aging reverse the sequence of acquisition in development. Although there has been some evidence for brain retrogenesis in abnormal aging, e.g., Alzheimer's disease (AD), it has not been explicitly addressed in the normal aging. Using diffusion tensor imaging and tractography, we explored the effects of normal and abnormal aging on the integrity of white matter (WM) in fifty participants, including 18 AD patients, 17 normal elderly, and 15 normal young adults. Compared with young adults, the traditional voxel-based analysis, and the quantitative fiber tracking methods revealed lower fractional anisotrophy (FA) for both normal elderly and AD patients, indicating WM disintegrity in the anterior part of the brain with developmentally late-myelinating fiber bundles. Furthermore, AD patients showed lower FA in the posterior part of the brain with relatively early-myelinating fiber bundles. Additional analysis on axial diffusion and radial diffusion measures suggest that demyelination may be the main mechanism underlying the observed microstructural impairments. Consistent with a proposal of retrogenesis, our results demonstrate an anteroposterior pattern of white matter disintegrity in both normal aging and AD, with the pattern being more salient in the latter than in the former.

Ischemic stroke related to intracranial branch atheromatous disease and comparison with large and small artery diseases.

BACKGROUND: The mechanism of ischemic stroke in intracranial branch atheromatous disease (BAD) is different from large artery atherothrombotic disease (LAD) or lacunar infarction (LACI). The concept of BAD is underused in clinical practice and research. METHODS: Patients admitted over 24-months with ischemic stroke caused by atherosclerotic disease were reviewed retrospectively and classified according to radiological±clinical criteria into LAD, BAD and LACI. The BAD cases were further divided into 5 BAD syndromes. Clinical characteristics, vascular risk factors, results of vascular workup and outcome among these subgroups were compared. RESULTS: 123 cases of LAD (17% of all stroke patients or 33% of all studied patients), 147 BAD (20% or 40%) and 102 LACI (14% or 27%) presented during the study period. Compared to LAD, BAD patients had milder neurological deficits, were less often diabetic and carotid stenosis was less common, while stenosis of the intracranial arteries was more frequent in BAD as compared with LACI patients. Outcome in BAD patients was intermediate between LAD and LACI. Comparisons among the BAD syndromes indicated they were homogenous conditions. CONCLUSIONS: BAD is the most prevalent ischemic stroke subtype in our cohort. The homogeneity among the BAD syndromes suggests they might represent a distinctive stroke entity.

New-onset constipation at acute stage after first stroke: incidence, risk factors, and impact on the stroke outcome.

BACKGROUND AND PURPOSE: The prevalence of constipation after stroke varies from 30% to 60%. The incidence of new-onset constipation during the early stage of stroke remains uncertain. The present study was designed to investigate the prevalence of new-onset constipation, its risk factors, and its impact on stroke outcome in patients with their first stroke at acute stage. METHODS: This is a prospective cohort study of 154 patients admitted with their first stroke. New-onset constipation during the first 4 weeks of stroke was recorded, using the Rome II criteria for constipation. Demographics, characteristics of the stroke, laboratory parameters, and use of medications were evaluated as risk factors for constipation. Death, recurrent stroke, and handicap at 12 weeks were regarded as poor outcome. The impact of constipation on poor outcome was also studied. RESULTS: The cumulative incidence of new-onset constipation was 55.2% at 4 weeks poststroke. The occurrence of constipation was associated with dependence (P<0.01) and use of bedpan for defecation (P<0.05). Among patients with moderate stroke severity (NIHSS 4 to 11) at baseline, constipation at 4 weeks was associated with a poor outcome at 12 weeks. CONCLUSIONS: New-onset constipation is a common complication of acute stroke. Its occurrence is associated with dependence and use of bedpan for defecation. Its development may predict a poor outcome at 12 weeks in patients with moderately severe stroke.

Migraine disability awareness campaign in Asia: migraine assessment for prophylaxis.

OBJECTIVES: This study aimed to survey the headache diagnoses and consequences among outpatients attending neurological services in 8 Asian countries. METHODS: This survey recruited patients who consulted neurologists for the first time with the chief complaint of headache. Patients suffering from headaches for 15 or more days per month were excluded. Patients answered a self-administered questionnaire, and their physicians independently completed a separate questionnaire. In this study, the migraine diagnosis given by the neurologists was used for analysis. The headache symptoms collected in the physician questionnaire were based on the diagnostic criteria of migraine proposed by the International Classification of Headache Disorders, second edition (ICHD-2). RESULTS: A total of 2782 patients (72% females; mean age 38.1 15.1 years) finished the study.Of them, 66.6% of patients were diagnosed by the neurologists to have migraine, ranging from 50.9% to 85.8% across different countries.Taken as a group, 41.4% of those patients diagnosed with migraine had not been previously diagnosed to have migraine prior to this consultation. On average, patients with migraine had 4.9 severe headaches per month with 65% of patients missing school,work, or household chores. Most (87.5%) patients with migraine took medications for acute treatment. Thirty-six percent of the patients had at least one emergency room consultation within one year. Only 29.2% were on prophylactic medications. Neurologists recommended pharmacological prophylaxis in 68.2% of patients not on preventive treatment. In comparison, migraine prevalence was the highest with ICHD-2 "any migraine" (ie, migraine with or without migraine and probable migraine) (73.3%) followed by neurologist-diagnosed migraine (66.6%) and ICHD-2 "strict migraine" (ie, migraine with or without aura only) (51.3%). About 88.6% patients with neurologist-diagnosed migraine fulfilled ICHD-2 any migraine but only 67.1% fulfilled the criteria of ICHD-2 strict migraine. CONCLUSIONS: Migraine is the most common headache diagnosis in neurological services in Asia. The prevalence of migraine was higher in countries with higher referral rates of patients to neurological services. Migraine remains underdiagnosed and under-treated in this region even though a high disability was found in patients with migraine. Probable migraine was adopted into the migraine diagnostic spectrum by neurologists in this study.

Update on medical and surgical management of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) accounts for 15% of all strokes in the US and Europe and 20% to 30% in Asian populations. ICH is associated with a higher morbidity, disability and mortality than ischemic strokes. Primary ICH originates from spontaneous rupture of small arteries and arterioles previously damaged by chronic hypertension or amyloid angiopathy. Secondary ICH is associated with underlying vascular abnormalities or other pathologies. Manifestation is acute with focal neurological signs and features of raised intracranial pressure. Despite our improved understanding of the pathophysiology of hematoma expansion and edema formation, management is primarily supportive, and outcomes remain poor. A recently published report has confirmed that there is no overall benefit from early surgery when compared with initial conservative treatment. In contrast, treatment with recombinant activated factor VII within 4 hours of onset limits hematoma growth at 24 hours, and reduces mortality and improves functional outcomes at 90 days. Several ICH scoring methods have recently been proposed for better prediction of outcome. These scoring methods may be useful in selecting suitable patients for clinical trials. Microbleeds are commonly seen on magnetic resonance imaging. Further studies are awaited to clarify the association between microbleeds and the future risk of ICH.

Incidence and predictors of depression after stroke (DAS).

Objective. Depression after stroke (DAS) poses a treble burden to patients, families and health care system. The purpose of this paper is to estimate the incidence of depression among first-ever ischemic stroke patients and identify the predictors of DAS. Methods. A longitudinal study design was undertaken. Of 836 patients admitted to the stroke unit of two regional hospitals in Hong Kong during the period 1 June 2004 to 31 May 2005, 295 patients fulfilled the inclusion and exclusion criteria. A total of 260 patients had given their consents and were interviewed at 1 month after stroke onset. Results. Nearly one-quarter of the first ischemic stroke patients, who were known to be free of personal and family history of psychiatric illnesses, were found to satisfy the criteria of depression using Diagnostic and Statistical Manual IV (24%, 48 out of 200 participants; 95% CI: 18.6%, 30.4%). This result was close to that assessed by the Geriatric Depression Scale (GDS) - 15 items. The psycho-emotional factor and level of dependency were found to be most significant predictors for DAS onset. Conclusion. The high incidence of DAS and low rate of accessibility to treatment indicate timely action to be undertaken.

Preclinical evaluation of pharmacokinetics and safety of melatonin in propylene glycol for intravenous administration.

Melatonin is a highly effective treatment in different animal models of excitotoxicity or ischemia/reperfusion injury. Due to a lack of patentability, commercial sponsors are not interested in funding clinical evaluations of melatonin. Investigators may initiate small-scale clinical evaluation, and intravenous (i.v.) administration is appropriate in acute stroke patients. Institutional Review Boards may require proper preclinical evaluation of the preparation. In this pharmacokinetic and safety study, melatonin in propylene glycol was evaluated in adult male Sprague-Dawley rats. Following a single i.v. injection at 5 or 15 mg/kg, plasma concentrations of melatonin increased to 39 and 199 million pg/mL at 2 min and 128,000 and 772,000 pg/mL at 120 min. Within 60 min of injection, the blood pressure, heart rate and body temperature remained unaffected. Melatonin at 5 mg/kg did not influence the complete blood counts at 60 min, but melatonin at 15 mg/kg had some effects on the differential white cell and platelet counts. Melatonin at 5 or 15 mg/kg slightly elevated some liver enzymes at 60 min of injection, and melatonin at higher dose also elevated plasma creatinine and lactate dehydrogenase levels. At 24 hr after completion of six daily injections of melatonin, there was a 5.5% reduction in body weight. Gross postmortem examination and histological examination of the brain, kidney, liver and spleen did not reveal any evidence of toxicity. In conclusion, melatonin in propylene glycol markedly elevates plasma levels of melatonin with no serious toxicity. This preparation should be further evaluated in human patients.