Assessing current genetic status of the Hainan gibbon using historical and demographic baselines: implications for conservation management of species of extreme rarity.

Evidence-based conservation planning is crucial for informing management decisions for species of extreme rarity, but collection of robust data on genetic status or other parameters can be extremely challenging for such species. The Hainan gibbon, possibly the world's rarest mammal, consists of a single population of ~25 individuals restricted to one protected area on Hainan Island, China, and has persisted for over 30 years at exceptionally low population size. Analysis of genotypes at 11 microsatellite loci from faecal samples for 36% of the current global population and tissue samples from 62% of existing historical museum specimens demonstrates limited current genetic diversity (Na = 2.27, Ar = 2.24, He  = 0.43); diversity has declined since the 19th century and even further within the last 30 years, representing declines of ~30% from historical levels (Na = 3.36, Ar = 3.29, He  = 0.63). Significant differentiation is seen between current and historical samples (FST  = 0.156, P = 0.0315), and the current population exhibits extremely small Ne (current Ne  = 2.16). There is evidence for both a recent population bottleneck and an earlier bottleneck, with population size already reasonably low by the late 19th century (historical Ne  = 1162.96). Individuals in the current population are related at the level of half- to full-siblings between social groups, and full-siblings or parent-offspring within a social group, suggesting that inbreeding is likely to increase in the future. The species' current reduced genetic diversity must be considered during conservation planning, particularly for expectations of likely population recovery, indicating that intensive, carefully planned management is essential.

Brain attack: needing resuscitation.

The brain is extremely susceptible to focal ischaemia. Following vascular occlusion, a core of severely damaged brain tissue develops, surrounded by an ischaemic penumbra. This potentially-salvageable penumbra may be estimated by advanced neuroimaging techniques, particularly by diffusion-perfusion mismatch. Clinical trials have demonstrated the efficacy of intravenous thrombolysis within three hours of onset of ischaemic stroke in reducing short-term disability. Recanalisation is enhanced by intra-arterial thrombolysis, sonothrombolysis and clot-retrieval devices. Occasionally, reperfusion injury may lead to clinical deterioration. The search continues for effective neuroprotectants. Brain perfusion needs to be maintained through blood and intracranial pressure management. Hemicraniectomy for 'malignant' cerebral oedema reduces death and disability. Elevated glucose should be controlled and hypoxia alleviated. Public education of symptoms and the need for immediate presentation to a medical facility is needed. Stroke unit care reduces death and disability with little increase in cost. Current evidence supports urgent efforts to resuscitate the brain after stroke.

Multicenter external validation of the ABCD2 score in triaging TIA patients.

OBJECTIVES: A simple clinical score (ABCD(2) score) has been introduced to triage TIA patients with a high early risk of stroke. External validation studies have yielded inconsistent results regarding the predictive ability of the ABCD(2) score. We aimed to prospectively validate the former score in a multicenter case series study. METHODS: We prospectively calculated the ABCD(2) score (age [> or = 60 years: 1 point]; blood pressure [systolic >140 mm Hg or diastolic >90 mm Hg: 1[; clinical features [unilateral weakness: 2, speech disturbance without weakness: 1, other symptom: 0]; duration of symptoms [ <10 minutes: 0, 10-59 minutes: 1, > or = 60 minutes: 2]; diabetes mellitus [yes: 1]) in consecutive TIA patients hospitalized in 3 tertiary care neurology departments across 2 different racial populations (white and Asian). RESULTS: The 7-day and 90-day risks of stroke in the present case series (n = 148) were 8% (95% CI 4%-12%) and 16% (95% CI 10%-22%). The ABCD(2) score accurately discriminated between TIA patients with high 7-day (c statistic 0.72, 95% CI 0.57-0.88) and 90-day (c statistic 0.75, 95% CI 0.65-0.86) risks of stroke. The 90-day risk of stroke was 7-fold higher in patients with an ABCD(2) score >3 points (28%, 95% CI 18%-38%) than in patients with an ABCD(2) score < or = 3 points (4%, 95% CI 0%-9%). After adjustment for stroke risk factors, race, history of previous TIA, medication use before the index TIA and secondary prevention treatment strategies, an ABCD(2) score of >2 was associated with a nearly 5-fold greater 90-day risk of stroke (hazard ratio 4.65, 95% CI 1.04-20.84, p = 0.045). CONCLUSION: Our findings externally validate the usefulness of the ABCD(2) score in triaging TIA patients with a high risk of early stroke in a multiethnic sample of hospitalized patients. The present data support current guidelines endorsing the immediate hospitalization of patients with an ABCD(2) score >2.

A double-blind, placebo-controlled, randomized, multicenter study to investigate CHInese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES Study).

UNLABELLED: Rationale Traditional Chinese Medications(TCM) have been reported to have beneficial effects in stroke patients, but were not rigorously evaluated by GCP standards. Aim This study tests the hypothesis that Neuroaid, a TCM widely used in China post-stroke, is superior to placebo in reducing neurological deficit and improving functional outcome in patients with acute cerebral infarction of an intermediate severity. Design This is a multicenter, randomised, double-blind, placebo-controlled study of Neuroaid in ischemic stroke patients with National Institute of Health Stroke Scale(NIHSS) 6-14 treated within 48 h of stroke onset. Neuroaid or placebo is taken (4 capsules) 3 times daily for 3 months. Treatments are assigned using block randomization, stratified for centers, via a central web-randomization system. With a power of 90% and two-sided test of 5% type I error, a sample size is 874. Allowing for a drop-out rate of up to 20%, 1100 individuals should be enrolled in this study. Study Outcomes The primary efficacy endpoint is the modified Rankin Scale(mRS) grades at 3 months. Secondary efficacy endpoints are the NIHSS score at 3 months; difference of NIHSS scores between baseline and 10 days, and between baseline and 3 months; difference of NIHSS sub-scores between baseline and 10 days, and between baseline and 3 months; mRS at 10 days, 1 month, and 3 months; Barthel index at 3 months; Mini Mental State Examination at 10 days and 3 months. Safety outcomes include complete blood count, renal and liver panels, and electrocardiogram. STUDY REGISTRATION: ClinicalTrials.gov identifier: NCT00554723.

Neuropsychiatric lupus and reversible posterior leucoencephalopathy syndrome: a challenging clinical dilemma.

Reversible posterior leucoencephalopathy syndrome (RPLS) has been increasingly recognized and reported in the literature. While the condition has been well described in patients with acute hypertension, pre-eclampsia, eclampsia, post-transplantation and chemotherapy, RPLS has been increasingly identified in patients with autoimmune diseases such as systemic lupus erythematosus (SLE). Though experience in the diagnosis and management of RPLS in patients with SLE is likely accumulating, few have systematically worked out the strategy to distinguish RPLS from neuropsychiatric SLE (NPSLE) and lupus-related complications of the central nervous system (CNS). Prompt recognition of, and differentiation between, these conditions is essential since their clinical presentations substantially overlap and yet their management strategy and subsequent outcomes can be entirely different. Indeed, inappropriate treatment such as augmentation of immunosuppression may be detrimental to patients with RPLS. A high index of suspicion of RPLS, prompt magnetic resonance imaging of the brain, including diffusion imaging, exclusion of CNS infection and metabolic derangement, a comprehensive medication review accompanied by timely and aggressive control of blood pressure and seizure are keys to successful management of RPLS. Such treatment strategy ensures a very high chance of total neurological recovery in lupus patients with RPLS.

Vasospasm followed by diastolic flow reversal in the intracranial arteries after subarachnoid haemorrhage.

Vasospasm and raised intracranial pressure (ICP) are common complications in subarachnoid haemorrhage (SAH) due to ruptured intracranial aneurysm. Vasospasm can be reliably monitored by repeated transcranial Doppler (TCD) examinations. The changes in flow velocities due to vasospasm are useful for early diagnosis, monitoring effectiveness of treatment and determining prognosis. Intracranial pressure can also increase to dangerous levels and affect blood flow in the intracranial circulation. These changes in ICP may be evaluated by the spectral waveform patterns obtained during TCD examination. We describe the dynamic TCD spectral changes in a patient with SAH that progressed from vasospasm to diastolic flow reversal. These temporal changes observed during serial TCD examinations were well correlated with the ICP. Transcranial Doppler is a reliable, beat-to-beat, non-invasive and reproducible bedside test that can be used to monitor vasospasm and ICP in SAH. The use of TCD can be extended to other intracranial diseases that can potentially lead to an abnormally high ICP.

The NORSE (new-onset refractory status epilepticus) syndrome: defining a disease entity.

INTRODUCTION: To characterise a homogeneous group of patients with new-onset refractory status epilepticus (NORSE syndrome). MATERIALS AND METHODS: This is a descriptive, semiprospective review of all cases of NORSE syndrome seen between 2000 and 2004 at a tertiary care public hospital in Singapore. A review of the literature was performed to identify possible additional similar cases for comparison. RESULTS: Seven patients with NORSE syndrome were identified. Characterising features were female gender, young age, previous good health, cerebrospinal fluid pleocytosis (in 4), antecedent febrile illness (in 5), extraordinarily prolonged status epilepticus (average 32 days), failure of extensive investigations to reveal an underlying cause, catastrophic outcome as well as temporal lobe and leptomeningeal abnormality on brain magnetic resonance imaging. A review of the literature identified 12 similar patients, comprising both adults and children. CONCLUSIONS: Based on our patients and those described in the literature, we characterise the NORSE syndrome. Increased recognition of this clinical entity is needed to help delineate the underlying aetiology of this unique severe illness.

Stroke disease management--a framework for comprehensive stroke care.

Disease management is an approach to patient care that coordinates medical resources for the patient across the entire healthcare delivery system throughout the lifetime of the patient with the disease. Stroke is suitable for disease management as it is a well-known disease with a high prevalence, high cost, variable practice pattern, poor clinical outcome, and managed by a non-integrated healthcare system. It has measurable and actionable outcomes, with available local expertise and support of the Ministry of Health. Developing the programme requires a multidisciplinary team, baseline data on target populations and healthcare services, identification of core components, collaboration with key stakeholders, development of evidence-based clinical practice guidelines and carepaths, institution of care coordinators, use of information technology and continuous quality improvement to produce an effective plan. Core components include public education, risk factor screening and management, primary care and specialist clinics, acute stroke units, inpatient and outpatient rehabilitation facilities, and supportive community services including medical, nursing, therapy, home help and support groups for patients and carers. The family physician plays a key role. Coordination of services is best done by a network of hospital and community-based care managers, and is enhanced by a coordinating call centre. Continuous quality improvement is required, with audit of processes and outcomes, facilitated by a disease registry. Pitfalls include inappropriate exclusion of deserving patients, misuse, loss of physician and patient independence, over-estimation of benefits, and care fragmentation. Collaboration and cooperative among all parties will help ensure a successful and sustainable programme.

Update in the management of stroke.

Recent advances have improved the outlook for patients with stroke, Singapore's fourth leading cause of death. Stroke unit care reduces death, dependency and institutionalisation, independent of age, gender and stroke severity. Neuroimaging is essential prior to initiation of specific therapies. While computed tomography (CT) Head remains the most widely used modality, magnetic resonance imaging (MRI), particularly diffusion weighted imaging (DWI) has enhanced the positive diagnosis of ischaemic stroke. General medical measures include close monitoring, adequate oxygenation, avoidance of excessive blood pressure lowering, reduction of hyperthermia, control of hyperglycaemia, adequate nutrition, prevention of complications and early rehabilitation. Despite the risk of fatal intracranial haemorrhage, thrombolysis may improve outcomes in appropriately selected patients with ischaemic stroke. No safe and effective neuroprotectant has been found. While suboccipital craniectomy is established for large cerebellar infarcts and haemorrhage, surgical evacuation of supratentorial haemorrhage has not been shown to be beneficial. Hemicraniectomy reduces mortality after massive hemispheric ischemic stroke. Early and sustained antiplatelet use after atherothrombotic stroke reduces stroke recurrence. Stroke recurrence is also reduced by sustained warfarin use for cardioembolic stroke, carotid endarterectomy for severe symptomatic internal carotid artery stenosis, blood pressure lowering starting after the acute phase of stroke and lipid lowering. On-going clinical trails are likely to provide better treatments in the near future.