L. Jaap Kappelle

Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial

BACKGROUND Patients with space-occupying hemispheric infarctions have a poor prognosis, with case fatality rates of up to 80%. In a pooled analysis of randomised trials, surgical decompression within 48 h of stroke onset reduced case fatality and improved functional outcome; however, the effect of surgery after longer intervals is unknown. The aim of HAMLET was to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction. METHODS Patients with space-occupying hemispheric infarction were randomly assigned within 4 days of stroke onset to surgical decompression or best medical treatment. The primary outcome measure was the modified Rankin scale (mRS) score at 1 year, which was dichotomised between good (0-3) and poor (4-6) outcome. Other outcome measures were the dichotomy of mRS score between 4 and 5, case fatality, quality of life, and symptoms of depression. Analysis was by intention to treat. This trial is registered, ISRCTN94237756. FINDINGS Between November, 2002, and October, 2007, 64 patients were included; 32 were randomly assigned to surgical decompression and 32 to best medical treatment. Surgical decompression had no effect on the primary outcome measure (absolute risk reduction [ARR] 0%, 95% CI -21 to 21) but did reduce case fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction), DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke onset, surgical decompression reduced poor outcome (ARR 16%, -0.1 to 33) and case fatality (ARR 50%, 34 to 66). INTERPRETATION Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset. The decision to perform the operation should depend on the emphasis patients and relatives attribute to survival and dependency.

Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study.

BACKGROUND Treatment strategies for acute basilar artery occlusion (BAO) are based on case series and data that have been extrapolated from stroke intervention trials in other cerebrovascular territories, and information on the efficacy of different treatments in unselected patients with BAO is scarce. We therefore assessed outcomes and differences in treatment response after BAO. METHODS The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO between November 1, 2002, and October 1, 2007. Stroke severity at time of treatment was dichotomised as severe (coma, locked-in state, or tetraplegia) or mild to moderate (any deficit that was less than severe). Outcome was assessed at 1 month. Poor outcome was defined as a modified Rankin scale score of 4 or 5, or death. Patients were divided into three groups according to the treatment they received: antithrombotic treatment only (AT), which comprised antiplatelet drugs or systemic anticoagulation; primary intravenous thrombolysis (IVT), including subsequent intra-arterial thrombolysis; or intra-arterial therapy (IAT), which comprised thrombolysis, mechanical thrombectomy, stenting, or a combination of these approaches. Risk ratios (RR) for treatment effects were adjusted for age, the severity of neurological deficits at the time of treatment, time to treatment, prodromal minor stroke, location of the occlusion, and diabetes. FINDINGS 619 patients were entered in the registry. 27 patients were excluded from the analyses because they did not receive AT, IVT, or IAT, and all had a poor outcome. Of the 592 patients who were analysed, 183 were treated with only AT, 121 with IVT, and 288 with IAT. Overall, 402 (68%) of the analysed patients had a poor outcome. No statistically significant superiority was found for any treatment strategy. Compared with outcome after AT, patients with a mild-to-moderate deficit (n=245) had about the same risk of poor outcome after IVT (adjusted RR 0.94, 95% CI 0.60-1.45) or after IAT (adjusted RR 1.29, 0.97-1.72) but had a worse outcome after IAT compared with IVT (adjusted RR 1.49, 1.00-2.23). Compared with AT, patients with a severe deficit (n=347) had a lower risk of poor outcome after IVT (adjusted RR 0.88, 0.76-1.01) or IAT (adjusted RR 0.94, 0.86-1.02), whereas outcomes were similar after treatment with IAT or IVT (adjusted RR 1.06, 0.91-1.22). INTERPRETATION Most patients in the BASICS registry received IAT. Our results do not support unequivocal superiority of IAT over IVT, and the efficacy of IAT versus IVT in patients with an acute BAO needs to be assessed in a randomised controlled trial. FUNDING Department of Neurology, University Medical Center Utrecht.

Symptomatic carotid artery occlusion. A reappraisal of hemodynamic factors.

BACKGROUND Over the last several years evidence has accumulated that in addition to embolism, a compromised cerebral blood flow may play an important role in causing transient ischemic attacks and ischemic stroke in patients with occlusion of the internal carotid artery. This evidence is found in both clinical features and ancillary investigations, particularly measurements of cerebral blood flow. SUMMARY OF REVIEW On the basis of 20 follow-up studies in patients with transient ischemic attacks or minor ischemic stroke associated with an occluded carotid artery, the annual risk of stroke was 5.5% (95% confidence interval [CI], 5.0% to 6.0%), and that of ipsilateral stroke (distinguished in 11 of the 20 studies) was 2.1% (95% CI, 1.6% to 2.8%). Patients with a compromised cerebral blood flow as measured by positron emission tomography, single-photon emission CT, transcranial Doppler, or stable xenon CT (six studies) have an even higher annual risk of stroke (all strokes: 12.5%; 95% CI, 8.9% to 17.6%; ipsilateral stroke: 9.5%; 95% CI, 6.4% to 14.0%). CONCLUSIONS Because a compromised cerebral blood flow may be an important causal factor in patients with symptomatic carotid artery occlusion, medical and surgical options for treatment are reviewed in this light.

Treatment of Brain Arteriovenous Malformations: A Systematic Review and Meta-analysis

CONTEXT Outcomes following treatment of brain arteriovenous malformations (AVMs) with microsurgery, embolization, stereotactic radiosurgery (SRS), or combinations vary greatly between studies. OBJECTIVES To assess rates of case fatality, long-term risk of hemorrhage, complications, and successful obliteration of brain AVMs after interventional treatment and to assess determinants of these outcomes. DATA SOURCES We searched PubMed and EMBASE to March 1, 2011, and hand-searched 6 journals from January 2000 until March 2011. STUDY SELECTION AND DATA EXTRACTION We identified studies fulfilling predefined inclusion criteria. We used Poisson regression analyses to explore associations of patient and study characteristics with case fatality, complications, long-term risk of hemorrhage, and successful brain AVM obliteration. DATA SYNTHESIS We identified 137 observational studies including 142 cohorts, totaling 13,698 patients and 46,314 patient-years of follow-up. Case fatality was 0.68 (95% CI, 0.61-0.76) per 100 person-years overall, 1.1 (95% CI, 0.87-1.3; n = 2549) after microsurgery, 0.50 (95% CI, 0.43-0.58; n = 9436) after SRS, and 0.96 (95% CI, 0.67-1.4; n = 1019) after embolization. Intracranial hemorrhage rates were 1.4 (95% CI, 1.3-1.5) per 100 person-years overall, 0.18 (95% CI, 0.10-0.30) after microsurgery, 1.7 (95% CI, 1.5-1.8) after SRS, and 1.7 (95% CI, 1.3-2.3) after embolization. More recent studies were associated with lower case-fatality rates (rate ratio [RR], 0.972; 95% CI, 0.955-0.989) but increased rates of hemorrhage (RR, 1.02; 95% CI, 1.00-1.03). Male sex (RR, 0.964; 95% CI, 0.945-0.984), small brain AVMs (RR, 0.988; 95% CI, 0.981-0.995), and those with strictly deep venous drainage (RR, 0.975; 95% CI, 0.960-0.990) were associated with lower case fatality. Lower hemorrhage rates were associated with male sex (RR, 0.976, 95% CI, 0.964-0.988), small brain AVMs (RR, 0.988, 95% CI, 0.980-0.996), and brain AVMs with deep venous drainage (0.982, 95% CI, 0.969-0.996). Complications leading to permanent neurological deficits or death occurred in a median 7.4% (range, 0%-40%) of patients after microsurgery, 5.1% (range, 0%-21%) after SRS, and 6.6% (range, 0%-28%) after embolization. Successful brain AVM obliteration was achieved in 96% (range, 0%-100%) of patients after microsurgery, 38% (range, 0%-75%) after SRS, and 13% (range, 0%-94%) after embolization. CONCLUSIONS Although case fatality after treatment has decreased over time, treatment of brain AVM remains associated with considerable risks and incomplete efficacy. Randomized controlled trials comparing different treatment modalities appear justified.

Type 2 diabetes mellitus, hypertension, dyslipidemia and obesity: A systematic comparison of their impact on cognition

Vascular risk factors, such as type 2 diabetes mellitus, hypertension, dyslipidemia and obesity, have been associated with an increased risk of cognitive dysfunction, particularly in the elderly. The aim of this systematic review was to compare these risk factors with regard to the nature and magnitude of the associated cognitive decrements. Cross-sectional and longitudinal studies that assessed cognitive functioning in non-demented persons in relation to diabetes/impaired glucose metabolism (k = 36), hypertension (k = 24), dyslipidemia (k = 7) and obesity (k = 6) and that adjusted or matched for age, gender and education were included. When possible, effect sizes (Cohens d) were computed per cognitive domain. Diabetes and hypertension were clearly associated with cognitive decrements; the results for obesity and dyslipidemia were less consistent. Effect sizes were moderate (median approximately -0.3) for all risk factors. Decline was found in all cognitive domains, although the effects on cognitive speed, mental flexibility and memory were most consistent. Methodological aspects of included studies and implications of these findings are discussed.

Diabetes, hyperglycaemia, and acute ischaemic stroke

Diabetes and ischaemic stroke often arise together. People with diabetes have more than double the risk of ischaemic stroke after correction for other risk factors, relative to individuals without diabetes. Multifactorial treatment of risk factors for stroke-in particular, lifestyle factors, hypertension, and dyslipidaemia-will prevent a substantial number of these disabling strokes. Hyperglycaemia occurs in 30-40% of patients with acute ischaemic stroke, also in individuals without a known history of diabetes. Admission hyperglycaemia is associated with poor functional outcome, possibly through aggravation of ischaemic damage by disturbing recanalisation and increasing reperfusion injury. Uncertainty surrounds the question of whether glucose-lowering treatment for early stroke can improve clinical outcome. Achievement of normoglycaemia in the early stage of stroke can be difficult, and the possibility of hypoglycaemia remains a concern. Phase 3 studies of glucose-lowering therapy in acute ischaemic stroke are underway.

National Stroke Association guidelines for the management of transient ischemic attacks

Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence‐based guidelines for the management of patients with transient ischemic attacks.

Preoperative Diagnosis of Carotid Artery Stenosis Accuracy of Noninvasive Testing

Background and Purpose— Carotid endarterectomy has been shown to be beneficial in symptomatic patients with a severe stenosis (70% to 99%) of the internal carotid artery (ICA). Digital subtraction angiography (DSA) is the standard of reference in the diagnosis of carotid artery stenosis but has a relatively high complication rate. In a diagnostic study we investigated the accuracy of noninvasive testing compared with DSA. Methods— In a prospective diagnostic study we performed duplex ultrasound (DUS), magnetic resonance angiography (MRA), and DSA on 350 consecutive symptomatic patients. Stenoses were measured with the observers blinded for clinical information and other test results. Separate and combined test results of DUS and MRA were compared with the reference standard DSA. Only the stenosis measurements of the arteries on the symptomatic side were included in the analyses. Results— DUS analyzed with previously defined criteria resulted in a sensitivity of 87.5% (95% CI, 82.1% to 92.9%) and a specificity of 75.7% (95% CI, 69.3% to 82.2%) in identifying severe ICA stenosis (70% to 99%). Stenosis measurements on MRA yielded a sensitivity of 92.2% (95% CI, 86.2% to 96.2%) and a specificity of 75.7% (95% CI, 68.6% to 82.5%). When we combined MRA and DUS results, agreement between these 2 modalities (84% of patients) gave a sensitivity of 96.3% (95% CI, 90.8% to 99.0%) and a specificity of 80.2% (95% CI, 73.1% to 87.3%) for identifying severe stenosis. Conclusions— MRA showed a slightly better accuracy than DUS in the diagnosis of carotid artery stenosis. To achieve the best accuracy, however, both tests should be performed subsequently.

Asymptomatic carotid artery stenosis and the risk of new vascular events in patients with manifest arterial disease: the SMART study.

Background and Purpose— The frequency of asymptomatic carotid artery stenosis (CAS) increases with age from 0.5% in individuals below 50 years of age to 5% to 10% in individuals over 65 years of age in the general population. Its prognostic value has been examined in the general population but less often in patients with clinical manifestations of arterial disease other than retinal or cerebral ischemia. We examined the relationship between asymptomatic CAS and the risk of subsequent events in this specific group of patients. Methods— This study involved 2684 consecutive patients with clinical manifestations of arterial disease or type 2 diabetes mellitus, but without a history of cerebral ischemia, enrolled in the SMART study (Second Manifestations of ARTerial disease). The degree of asymptomatic CAS was assessed with Duplex scanning and defined on the basis of the blood flow velocity patterns at baseline in both carotid arteries. None of the patients underwent carotid endarterectomy or endovascular intervention. During the follow-up period, vascular events (vascular death, ischemic stroke, and myocardial infarction) were documented in detail. Data were analyzed with Cox proportional hazards regression and adjusted for age, gender, and classic vascular risk factors. Results— Asymptomatic CAS of 50% or greater was present in 221 (8%) patients. During a mean follow up of 3.6 years (SD=2.3), a first vascular event occurred in 253 patients (9%). The cumulative incidence rate for the composite of subsequent vascular events after 5 years was 12.3% (95% CI=10.7 to 13.9), for cerebral infarction 2.2% (95% CI=1.4 to 2.8), and for myocardial infarction 8.0% (95% CI=6.6 to 9.4). Adjusted for age and gender, asymptomatic CAS of 50% or greater was related to a higher risk of subsequent vascular events (hazard ratio=1.5, 95% CI=1.1 to 2.1), in particular of vascular death (hazard ratio=1.8, 95% CI=1.2 to 2.6). After additional adjustment for vascular risk factors, the hazard ratios remained essentially the same. Conclusion— Asymptomatic carotid artery stenosis is an independent predictor of vascular events, especially vascular death, in patients with clinical manifestations of arterial disease or type 2 diabetes but without a history of cerebral ischemia.

Varieties of human spatial memory : a meta-analysis on the effects of hippocampal lesions

The current meta-analysis included 27 studies on spatial-memory dysfunction in patients with hippocampal damage. Each study was classified on the basis of the task that was used, i.e., maze learning, working memory, object-location memory, or positional memory. The overall results demonstrated impairments on all spatial-memory tasks. Clear differences in effect size were found between positional memory on the one hand and maze learning, object-location memory, and working memory on the other hand. Lateralization was found only on maze learning and object-location memory. These findings clearly indicate that specific aspects of spatial memory can be affected in various degrees in patients with hippocampal lesions. Moreover, these results strongly support the notion that the hippocampus is important in the processing of metric positional information, probably in the form of an allocentric cognitive map.