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Background Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients. Methods Prospective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria. Results 307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2–11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01–1.46 and HR 1.26, 95% CI 1.10–1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease. Conclusion Low grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.

Background We developed and validated a risk score to predict delirium after stroke which was derived from our prospective cohort study where several risk factors were identified.Methods Using the β coefficients from the logistic regression model, we allocated a score to values of the risk factors. In the first model, stroke severity, stroke subtype, infection, stroke localisation, pre-existent cognitive decline and age were included. The second model included age, stroke severity, stroke subtype and infection. A third model only included age and stroke severity. The risk score was validated in an independent dataset.Results The area under the curve (AUC) of the first model was 0.85 (sensitivity 86%, specificity 74%). In the second model, the AUC was 0.84 (sensitivity 80%, specificity 75%). The third model had an AUC of 0.80 (sensitivity 79%, specificity 73%). In the validation set, model 1 had an AUC of 0.83 (sensitivity 78%, specificity 77%). The second had an AUC of 0.83 (sensitivity 76%, specificity 81%). The third model gave an AUC of 0.82 (sensitivity of 73%, specificity 75%). We conclude that model 2 is easy to use in clinical practice and slightly better than model 3 and, therefore, was used to create risk tables to use as a tool in clinical practice.Conclusions A model including age, stroke severity, stroke subtype and infection can be used to identify patients who have a high risk to develop delirium in the early phase of stroke.

Background: Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy (CEA) is a potential life-threatening complication. Therefore, early identification and treatment of patients at risk is essential. CHS can be predicted by a doubling of postoperative transcranial Doppler (TCD)-derived mean middle cerebral artery blood velocity (Vmean) compared to preoperative values. However, in approximately 15% of CEA patients, an adequate TCD signal cannot be obtained due to an insufficient temporal bone window. Moreover, the use of TCD requires specifically skilled personnel. An alternative and promising technique of noninvasive cerebral monitoring is relative frontal lobe oxygenation (rSO2) measured by near-infrared spectroscopy (NIRS), which offers on-line information about cerebral oxygenation without the need for specialized personnel. In this study, we assess whether NIRS and perioperative TCD are related to the onset CHS following CEA. Methods: Patients who underwent CEA under general anesthesia and had a sufficient TCD window were prospectively included. The Vmean and rSO2 measured before induction of anesthesia were compared to measurements performed in the first postoperative hour (ΔVmean, ΔrSO2, respectively). Logistic regression analysis was performed to determine the relationship between ΔV and ΔrSO2 and the occurrence of CHS. Subsequently, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values. Diagnostic values were shown as positive and negative predictive values (PPV and NPV). Results: In total, 151 patients were included, of which 7 patients developed CHS. The ΔVmean and ΔrSO2 differed between CHS and non-CHS patients (median, interquartile range), i.e. 74% (67–103) versus 16% (–2 to 41), p = 0.001, and 7% (4–15) versus 1% (–6 to 7), p = 0.009, respectively. The mean arterial blood pressure did not change. Postoperative ΔVmean and ΔrSO2 were significantly related to the occurrence of CHS [odds ratio (OR) 1.40 (95% CI 1.02–1.93) per 30% increase in Vmean and OR 1.82 (95% CI 1.11–2.99) per 5% increase in rSO2]. ROC curve analysis showed an area under the curve of 0.88 (p = 0.001) for ΔVmean and an optimal cutoff value of 67% increase (PPV 38% and NPV 99%), and an area under the curve of 0.79 (p = 0.009) for ΔrSO2 and an optimal cutoff value of 3% rSO2 increase (PPV 11% and NPV 100%). The combination of both monitoring techniques provided a PPV of 58% and an NPV of 99%. Conclusions: Both TCD and NIRS measurements can be used to safely identify patients not at risk of developing CHS. It appears that NIRS is a good alternative when a TCD signal cannot be obtained.

Background: Assessment of outcome after childhood stroke is important both for clinical practice and for research purposes. The objective of this study was to compare two frequently used outcome measures. Methods: In 40 children with arterial ischemic stroke (AIS), dichotomized outcome obtained from the Pediatric Stroke Outcome Measure (PSOM) was compared with a dichotomized modified Rankin Scale (mRS) combined with information on type of school attendance. In addition, we compared dichotomized outcome, obtained from the PSOM and the mRS combined with school attendance, with the results of pediatric quality of life (PedsQL) questionnaires and the impressions of the child’s general functioning on a visual analogue scale (VAS) that was filled out by parents and investigators. Results: In 35 children (88%), outcome classification was concordant between the two outcome measures. Five children had a poor outcome according to the PSOM and good outcome with the mRS including school performance. In these patients, mRS outcome classification agreed better with the impression of the investigators, as reflected by VAS scores ≧7.5. For both the PSOM and mRS in combination with school performance, patients with a good outcome had significantly higher PedsQL and VAS scores than those with a poor outcome (p values Conclusions: In children with AIS, both PSOM and mRS combined with school type correlated significantly with quality of life and VAS scores of general functioning. The mRS combined with school type is easier to obtain than the PSOM, reflects function rather than deficits, includes an important measure of cognitive outcome, and corresponds better with the doctor’s impression of outcome.

Near occlusion (NO) of the internal carotid artery (ICA) with full collapse (NOFC) is a rare condition, with a prevalence of around 1%. Guidelines on carotid stenosis recommend a conservative treatment in patients with a single-event ipsilateral to a NOFC, but the optimal treatment for patients with recurrent symptoms associated with NOFC remains uncertain. We describe a consecutive series of patients with recurrent symptoms associated with NOFC (RSNOFC) who underwent carotid endarterectomy (CEA).From 2008 to 2017, 17 consecutive patients with RSNOFC were treated according to our standardized multidisciplinary work-up and protocol and included for this single-center cohort study. NO was defined according to the angiographic North American Symptomatic Carotid Endarterectomy Trial criteria. Only patients with NOFC were included in this study.Standard longitudinal CEA was performed in 15 patients, whereas in 2 patients the ICA was ligated with concomitant endarterectomy of the ECA. Within 30 postoperative days, one patient died from a hemorrhagic infarction. During follow-up (median 23 months) one patient died of unknown cause 90 days after CEA. No TIA, stroke, myocardial infarction or re-stenosis occurred in the remaining patients.In patients with RSNOFC, CEA may be considered a potential treatment option. Although procedural risks in this small subgroup may be higher as compared to patients with low-to-moderate risk anatomy, this risk may outbalance the natural course.

Background: In patients with acute ischaemic stroke and hyperglycaemia, prolonged strict glycaemic control may improve clinical outcome. The question is how to achieve this prolonged strict glycaemic control. In this study, the efficacy and safety of two regimens with different basal to meal related insulin ratio are described. Methods: 33 patients with ischaemic stroke and hyperglycaemia at admission were randomised in an open design to receive: (1) conventional glucose lowering therapy, (2) strict glucose control with predominantly basal insulin using intravenous insulin or (3) strict glucose control with predominantly meal related insulin using subcutaneous insulin in the first 5 days after stroke. The target range of glucose control for the last two groups was 4.4-6.1 mmol/l. 16 consecutive patients without hyperglycaemia at admission were included to serve as normoglycaemic controls. Results: The median area under the curve (AUC) in the meal related insulin group was 386 mmol/l x 58 h (range 286-662) for days 2-5, and did not differ from the hyperglycaemic control group (median AUC 444 mmol/l x 58 h; range 388-620). There was also no difference in median AUC of the basal insulin group (453 mmol/l x 58 h, range 347-629) and the hyperglycaemic control group on days 2-5. In the first 12 hours, glucose profiles were lower in the groups treated with strict glucose control; median AUC was 90 mmol/l x 12 h (range 77-189) for the hyperglycaemic control group versus 81 mmol/l x 12 h (range 60-118) for the meal related insulin group (p = 0.03) and 74 mmol/l x 12 h (range 52-97) for the basal insulin group (p = 0.008). Conclusion: In intermittently fed ischaemic stroke patients, strict glycaemic control between day 2 and day 5 with two different basal bolus regimens did not result in lower glucose profiles due to postprandial hyperglycaemia. Continuous enteral feeding may therefore be needed to achieve prolonged strict glycaemic control in acute stroke patients

Background and aim: Published data suggest that patients with cerebral ischaemia and atrial fibrillation (CIAF) have higher inhospital mortality than patients with cerebral ischaemia of arterial origin (CIAO). Data on long term risks are scarce. We compared the long term risks of death and vascular events (VE) between these groups. Methods: We extended the follow-up of 2473 patients from the Dutch TIA Trial (recruitment March 1986 to March 1989, all treated with aspirin; CIAO) and 186 Dutch participants of the European Atrial Fibrillation Trial (recruitment June 1988 to May 1992, 26% on anticoagulants during the trial; CIAF). Hazard ratios (HRs) for death and VE of CIAF versus CIAO were analysed by means of Cox regression analysis and adjusted for age, sex and several cardiovascular risk factors. Results: After a mean follow-up of 10.1 years, 1484 patients with CIAO had died and 1336 had suffered at least one VE (377 cardiac, 455 stroke). Mean follow-up of the CIAF patients was 6.8 years; 150 patients had died and 136 had suffered at least one VE (41 cardiac, 63 stroke). Adjusted HRs (CIAF vs CIAO) were 1.46 (95% CI 1.22 to 1.74) for death, 1.49 (1.24 to 1.79) for first VE, 1.94 (1.47 to 2.55) for first stroke and 1.41 (1.01 to 1.96) for first cardiac event. These HRs were essentially the same as those for the duration of the trials. Conclusion: Our study shows that the long term risk of death or vascular events is 1.5 times higher in patients with CIAF than in those with CIAO, after adjustment for differences between the groups.

Background and Purpose: A reliable scoring method for ischemic cerebral white matter hyperintensities (WMH) will help to clarify the causes and consequences of these brain lesions. We compared an automated and two visual WMH scoring methods in their relations with age and cognitive function. Methods: MRI of the brain was performed on 154 participants of the Utrecht Diabetic Encephalopathy Study. WMH volumes were obtained with an automated segmentation method. Visual rating of deep and periventricular WMH (DWMH and PWMH) was performed with the Scheltens scale and the Rotterdam Scan Study (RSS) scale, respectively. Cognition was assessed with a battery of 11 tests. Results: Within the whole study group, the association with age was most evident for the automated measured WMH volume (β = 0.43, 95% CI = 0.29–0.57). With regard to cognition, automated measured WMH volume and Scheltens DWMH were significantly associated with information processing speed (β = –0.22, 95% CI = –0.40 to –0.06; β = –0.26, 95% CI = –0.42 to –0.10), whereas RSS PWMH were associated with attention and executive function (β = –0.19, 95% CI = –0.36 to –0.02). Conclusion: Measurements of WMH with an automated quantitative segmentation method are comparable with visual rating scales and highly suitable for use in future studies to assess the relationship between WMH and subtle impairments in cognitive function.

Background: Brain arteriovenous malformations (BAVMs) are thought to be sporadic developmental vascular lesions, but familial occurrence has been described. We compared characteristics of patients with familial BAVMs with those of patients with sporadic BAVMs. Methods: We systematically reviewed the literature on patients with familial BAVMs. Three families that were found in our centre were added. Age, sex distribution and clinical presentation of the identified patients were compared with those in population-based series of patients with sporadic BAVMs. Furthermore, we calculated the difference in mean age at diagnosis of parents and children to study possible anticipation. Results: We identified 53 patients in 25 families with BAVMs. Mean age at diagnosis of patients with familial BAVMs was 27 years (range 9 months-58 years), which was younger than in the reference population (difference between means 8 years, 95% confidence interval (CI) 3-13 years). Patients with familial BAVMs did not differ from the reference populations with respect to sex and mode of presentation. In families with BAVMs in successive generations, the age of the child at diagnosis was younger than the age of the parent (difference between means 22 years, 95% CI 13-30 years), which suggests clinical anticipation. Conclusions: Few patients with familial BAVMs have been described. These patients were diagnosed at younger age than sporadic BAVMs whereas their mode of presentation was similar. Although there are indications of anticipation, it remains as yet unclear whether the described families represent accidental aggregation or indicate true familial occurrence of BAVMs.

Item does not contain fulltext BACKGROUND: The presence of prodromal transient ischemic attacks (TIAs) has been associated with a favorable outcome in anterior circulation stroke. We aimed to determine the association between prodromal TIAs or minor stroke and outcomes at 1 month, in the Basilar Artery International Cooperation Study, a registry of patients presenting with an acute symptomatic and radiologically confirmed basilar artery occlusion. METHODS: A total of 619 patients were enrolled in the registry. Information on prodromal TIAs was available for 517 patients and on prodromal stroke for 487 patients. We calculated risk ratios and corresponding 95% confidence intervals (CIs) for poor clinical outcome (modified Rankin Scale score >/=4) according to the variables of interest. RESULTS: Prodromal minor stroke was associated with poor outcome (crude risk ratio [cRR], 1.26; 95% CI, 1.12-1.42), but TIAs were not (cRR, .93; 95% CI, .79-1.09). These associations remained essentially the same after adjustment for confounding variables. CONCLUSIONS: Prodromal minor stroke was associated with an unfavorable outcome in patients with basilar artery occlusion, whereas prodromal TIA was not.

Background: Stroke may have a major effect on survivors and on the healthcare system. Aims: To study the functional status and use of healthcare facilities in long-term survivors of a transient ischaemic attack (TIA) or minor ischaemic stroke (MIS) and evaluate associations with baseline and follow-up characteristics. Methods: Follow-up of patients who had participated in the Dutch TIA Trial or the European Atrial Fibrillation Trial was extended to a mean period of 15.6 years. Patients were interviewed through a postal questionnaire (n = 468) and a sample of this group was also interviewed at home (n = 198). Demographic data, information on comorbidity, functional status (Barthel Index, Frenchay Activities Index and modified Rankin Scale) and use of healthcare facilities were recorded. Results: About one third of the survivors interviewed at home experienced any residual disability and 26% were moderately to severely handicapped. Factors associated with poor functional status were advanced age and the presence of any infarct on a baseline computed tomography scan, the recurrence of a new major stroke or the presence of comorbidity of locomotion. One third of survivors used any kind of professional care, which was predominantly related to the functional status at follow-up. Conclusions: Recurrent stroke and the presence of comorbidity of locomotion are important determinants of long-term disability of survivors of a TIA or an MIS, which, in turn, is strongly associated with the long-term use of professional care. The need for measuring comorbidity with regard to functional status is recommended in research on stroke outcome.

To examine whether intravenous recombinant tissue plasminogen activator (rt-PA) treatment given in the acute phase of ischaemic stroke has a favourable effect on cognitive and functional outcome at six months post-stroke.The present study included 92 patients with a first-ever symptomatic infarct, of whom 25 (27%) were subjected to rt-PA treatment in the first three hours post-stroke. Multivariate logistic regression analyses adjusted for stroke severity, education, age, and sex were performed to examine whether rt-PA treatment influenced cognitive outcome (assessed with a neuropsychological examination covering 7 cognitive domains), basic ADL independence (modified Barthel Indexor = 19), and instrumental ADL independence (Frenchay Activities Indexor = 15) after six months.The adjusted odds ratio for intact cognition was 1.0 (95% CI 0.2 to 4.3), that for basic ADL outcome 13.5 (95 % CI 1.4 to 129.4) and for instrumental ADL 7.1 (95 % CI 1.2 to 42.2).Our findings suggest that rt-PA treatment is associated with a favourable basic and instrumental ADL outcome, but not with a beneficial cognitive outcome after 6 months.

Objective: To study the association between the epsilon 4 allele of apolipoprotein E (APOE epsilon 4) and delirium in a stroke population. Methods: 527 consecutive stroke patients were screened for delirium during the first week of admission with the confusion assessment method. In three hundred fifty-three patients genomic DNA isolation was available. Results: The incidence of delirium after stroke in the 353 patients was 11.3%. There was no association between APOE epsilon 4 and delirium. Even after adjustment for IQCODE, stroke localization, stroke subtype, stroke severity, infection, and brain atrophy no association was found (odds ratio: 0.9; 95% confidence interval: 0.4-2.1). Delirium did not last longer in patients with an APOE epsilon 4 allele compared to patients without an APOE epsilon 4 allele (median: 5.6 days [range: 1-21] versus median: 4.6 days [range: 1-15], p = 0.5). Conclusion: There was no association between the presence of an APOE epsilon 4 allele and the occurrence of delirium in the acute phase after stroke.

Background and Purpose— There is no conclusive experimental support that decompressive surgery in late stages of space-occupying cerebral infarction will improve outcome. We studied the effects of delayed decompressive surgery on the development of tissue damage, edema formation, and cerebral perfusion with different MRI techniques in a rat model of space-occupying cerebral infarction. Methods— Permanent middle cerebral artery (MCA) occlusion was performed in 6 Fisher 344 rats. Decompressive surgery was performed 17 hours after the occlusion. Each animal was assessed before surgery and 2 and 4 hours after surgery by means, of diffusion-weighted T2-weighted, and flow-sensitive alternating inversion recovery perfusion-weighted MRI. Ischemic damage was also evaluated in hematoxylin-eosin-stained brain sections. Results— Lesion volume as derived from apparent diffusion coefficient (ADC) maps decreased from 522±98 mm 3 before to 405±100 mm 3 ( P =0.016) 4 hours after decompressive surgery, whereas lesion volume from T2 maps increased from 420±66 mm 3 before to 510±92 mm 3 ( P =0.048) 4 hours after decompressive surgery. Midline shift decreased from 1.4±0.1 mm to 0.5±0.2 mm ( P =0.001). Blood flow in the noninfarcted area of the ipsilateral hemisphere improved from 25±9 mL/min/100 g of tissue to 38±9 mL/min/100 g of tissue ( P =0.035). Despite the pseudonormalization of ADC, irreversible damage was found in the entire MCA territory on histological evaluation. Conclusions— In rats with space-occupying cerebral infarction, delayed decompressive surgery leads to a decrease in lesion volume derived from ADC maps, which is probably because of an increase of extracellular water formation. There are no signs that this reflects rescue of ischemic tissue.

Background and Purpose —Body temperature is a strong predictor of outcome in acute stroke. However, it is unknown whether antipyretic treatment leads to early and clinically worthwhile reduction of body temperature in patients with acute stroke, especially when they have no fever. The main purpose of this trial was to study whether early treatment of acute ischemic stroke patients with acetaminophen (paracetamol) reduces body temperature. Methods —Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 500 mg (low dose) or 1000 mg (high dose) acetaminophen or with placebo, administered as suppositories 6 times daily during 5 days. Body temperatures were measured with a rectal electronic thermometer at the start of treatment and after 24 hours and with an infrared tympanic thermometer at 2-hour intervals during the first 24 hours and at 6-hour intervals thereafter. The primary outcome measure was rectal temperature at 24 hours after the start of treatment. Results —Treatment with high-dose acetaminophen resulted in 0.4°C lower body temperatures than placebo treatment at 24 hours (95% CI 0.1°C to 0.7°C). The mean reduction from baseline temperature with high-dose acetaminophen was 0.3°C (95% CI 0°C to 0.6°C) higher than that in placebo-treated patients. Treatment with low-dose acetaminophen did not result in lower body temperatures. After 5 days of treatment, no differences in temperature were found between the placebo and the high- or low-dose acetaminophen groups. Conclusions —Treatment with a daily dose of 6000 mg acetaminophen may result in a small, but potentially beneficial, decrease in body temperature shortly after ischemic stroke, even in normothermic and subfebrile patients. Further studies should determine whether this effect is reproducible and whether early reduction of body temperature leads to improved outcome.

OBJECTIVES—The aetiology of clinical symptoms in patients with severe internal carotid artery (ICA) lesions may be thromboembolic or haemodynamic. The purpose was to assess whether changes in cerebropetal blood flow caused by an ICA occlusion have an effect on clinical symptoms and cerebral metabolism. METHODS—Forty three patients with an ICA occlusion who had hemispheric ischaemia (transient ischaemic attack or stroke), retinal ischaemia, or without symptoms, and 34 patients without significant ICA lesions with either hemispheric ischaemia or no symptoms were studied. Magnetic resonance angiography (MRA) was used to investigate total cerebropetal flow (flow in the ICAs plus basilar artery) and the flow in the middle cerebral arteries. Cerebral metabolic changes in the flow territory of the middle cerebral artery were determined with proton MR spectroscopy. RESULTS—Low total cerebropetal flow (r=−0.15, p

Cardiovascular disease and cancer share important risk factors and pathophysiology, including smoking, obesity, physical inactivity, insulin resistance, and inflammation. As the survival of acute ischemic events has increased notably, the number of patients in the chronic phase of vascular disease

Objective: To assess whether patients with carotid artery occlusion (CAO) who have clinical features suggesting a haemodynamic origin have a poor haemodynamic or metabolic state of the brain. Methods: In 117 patients with ischaemic symptoms of the eye or brain that were transient or at most moderately disabling and associated with a CAO, we compared CO2 reactivity, quantitative flow measurement by magnetic resonance (MR) angiography, metabolic ratios measured by 1H-MR spectroscopy, collateral blood flow patterns and the presence of infarcts of the borderzone type between patients grouped by the following clinical features: (1) presence or absence of at least one of the ‘classical’ haemodynamic symptoms: limb shaking, retinal claudication, precipitation of symptoms by exercise, by rising from a sitting or lying position, by transition from a cold to a warm environment, or by documented hypotension, and (2) symptoms having occurred after demonstration of the CAO or only before the occlusion was documented. Results: Patients with (n = 16) and without (n = 101) one of the ‘classical’ haemodynamic symptoms did not differ in any of the measured indices. Patients with recurrent symptoms after documentation of the CAO (n = 56) had lower CO2 reactivity (difference 8.3%, 95% confidence interval 0.1–16.5) than those with symptoms only before documentation of the occlusion (n = 61), whereas no significant differences were found in any of the other measured indices. The difference in CO2 reactivity was no longer significant after adjustment for the interval between the patients’ last symptoms and the CO2 reactivity measurement. Conclusion: In patients with CAO we could not find an association between symptoms that have been associated with hypoperfusion and a poor haemodynamic or metabolic state of the brain.

This article describes a standardized administration and scoring procedure for the widely used Corsi Block-Tapping Task, designed to assess the visual memory span. This method was applied in a group of healthy participants (n = 70) and a group of patients with cerebral lesions (n = 70), that were categorized on the basis of lesion location (left or right hemisphere, bilateral or subcortical). The percentile distribution as well as cutoff points on the basis of the control data are provided. It was found that 20% of the patients perform in the borderline range on this task, and over 8% have an impaired performance ("retarded"). In addition, right hemisphere patients performed worse than left hemisphere patients. These data show that the Corsi Block-Tapping Task can be effectively used to assess visuospatial short-term memory in patients with brain damage, and is selective for the side of the lesion.

The aim of this study was to evaluate the differences in cerebral perfusion seen on mean transit time (MTT) and cerebral blood volume (CBV) maps and to assess the subsequent prognostic value of the MTT–DWI (diffusion-weighted MRI) and CBV–DWI mismatch in the first three days of stroke on lesion enlargement and clinical outcome. In 38 patients, imaged 1–46 h after onset of symptoms, lesion volumes on proton-density (PD)-weighted MRI, DWI and PWI (both MTT and CBV maps) were compared with lesion volumes on follow-up PD-weighted scans, and to clinical outcome (National Institutes of Health Stroke Scale, Barthel index, and Rankin scale). The MTT-CBV, MTT–DWI and CBV–DWI mismatches were compared with change in lesion volume between initial and follow-up PD-weighted scans. Lesion volume on both DWI and PWI correlated significantly with clinical outcome parameters (p < 0.001) with strongest correlation for lesion volume on CBV. Perfusion–diffusion mismatches were found for both CBV and MTT and correlated significantly with lesion enlargement on PD-weighted imaging with strongest correlation for the CBV–DWI mismatch. The CBV–DWI mismatch has the highest accuracy in predicting lesion size on follow-up imaging and in predicting clinical outcome. Lesion volume measurements on CBV maps have a higher specificity than on PD-weighted, MTT or DWI images in predicting clinical follow-up imaging and in predicting clinical outcome.

A considerable proportion of patients discontinue dipyridamole therapy because of headache. Risk indicators for the development of dipyridamole induced headache were identified by means of an exploratory analysis of data from the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) and the Second European Stroke Prevention Study (ESPS 2). In ESPRIT, dipyridamole induced headache was significantly associated with female sex, absence of hypertension and non-smoking (area under the receiver operator characteristic (ROC) curve 0.63 (95% CI 0.58 to 0.68)) and in ESPS 2 with female sex and absence of ischaemic lesions on imaging (area under the ROC curve 0.64 (95% CI 0.59 to 0.69)).

The objective of this study was to evaluate the role of collateral blood flow via the anterior and posterior communicating arteries (ACoA and PCoA) and via the ophthalmic artery (OphA) on cerebral hemodynamics, metabolism, and border zone infarcts in 57 patients with unilateral symptomatic occlusions of the internal carotid artery. Collateral flow via the ACoA and PCoA was determined with magnetic resonance angiography (MRA) and collateral flow via the OphA with transcranial Doppler (TCD). Volume flow was studied with MRA, metabolism with 1H MR spectroscopy, CO2 reactivity with TCD, and the incidence of border zone infarcts with MRI. Compared with controls, patients had deteriorated volume flow, metabolism, and CO2 reactivity. No differences were found between patients with and patients without collateral flow through the ACoA and/or PCoA, or between patients with or without collateral flow via the OphA. Patients without collateral flow via any of these collaterals had decreased volume flow in the middle cerebral artery, decreased N-acetylaspartate/choline, and increased lactate/N-acetylaspartate, compared with the other patients. Patients with symptomatic internal carotid artery occlusion have deteriorated cerebral hemodynamics and metabolism. Different collateral flow patterns via the ACoA, PCoA, or OphA have no effect on the hemodynamic and metabolic parameters, as long as one of these pathways is present.

The accuracy of duplex sonography in predicting the degree of an internal carotid artery (ICA) stenosis is decreased when a contralateral high-grade stenosis or occlusion is present. The purpose of this study was to determine whether this overestimation of the stenosis by duplex sonography is associated with an increase in volume flow through the ipsilateral ICA.Forty-seven patients (89 vessels) with a symptomatic ICA stenosis or occlusion who underwent duplex sonography, intraarterial digital subtraction angiography, and magnetic resonance angiography flow quantification of the ICAs were evaluated.With the use of peak systolic velocity criteria, duplex overestimated stenoses more frequently (chi2: p = 0.03) in vessels with high volume flow (= mean volume flow in control group + 2 SD (274 ml/min), 46% overestimation) than in vessels with normal or low volume flow (274 ml/min, 20% overestimation). A correlation coefficient of 0.75 (p0.001) was found between volume flow and peak systolic velocity in the distal ICA, indicating that increased volume flow causes the peak systolic velocity to increase. Compared with volume flow in the control group (mean +/- SD = 198 +/- 38 ml/min), volume flow was increased in vessels with a 0% to 49% stenosis (mean +/- SD = 272 +/- 100 ml/min, p0.05) and in vessels with a 50% to 69% stenosis (mean +/- SD = 291 +/- 79 ml/min, p0.01) when the contralateral ICA had a 70% to 99% stenosis or occlusion.Increase in volume flow through the ICA frequently causes overestimation of stenoses in the ICA. Increased volume flow is frequently found in ICAs with a70% stenosis that are contralateral to ICAs with a70% stenosis or an occlusion.

Background: In stroke erythrocyte-rich thrombi are more sensitive to intravenous thrombolysis with recombinant tissue plasminogen activator (IV-rtPA) and have higher density on non-contrast CT (NCCT). We investigated the relationship between thrombus density and recanalization and whether persistent occlusions can be predicted by Hounsfield unit (HU) measurements. Methods: In 88 IV-rtPA-treated patients with intracranial ICA or MCA occluding thrombus and follow-up imaging, thrombus and contralateral vessel attenuation measurements were performed on thin-slice NCCT. Mean absolute and relative HU were compared between patients with persistent occlusion (modified Thrombolysis in Cerebral Infarction system, grade 0/1/2a) and recanalization (grade 2b/3). Univariate and multivariate (adjusted for stroke subtype, clot burden score, occlusion site and time to thrombolysis) odds ratios for persistent occlusion were calculated. Additional prognostic value for persistent occlusion was estimated by adding HU measurements to the area under the curve (AUC) of known determinants and calculating optimal cut-off values. Results: Patients with persistent occlusion (n = 19) had significant lower mean HU (absolute 52.2 ± 9.5, relative 1.29 ± 0.20) compared to recanalization (absolute 63.1 ± 10.7, relative 1.54 ± 0.23, both p < 0.0001). Odds ratios for persistent occlusion were 3.1 (95% confidence interval, CI 1.6-6.0) univariate and 3.1 (95% CI 1.7-5.7) multivariate per 10 absolute HU decrease and 3.2 (95% CI 1.6-6.5) univariate and 4.1 (95% CI 1.8-9.1) multivariate per 0.20 relative HU decrease. Attenuation measurements significantly increased the AUC (0.67) of the known determinants to 0.84 (absolute HU) and 0.86 (relative HU). Cut-off values of Conclusions: Thrombus density is related to recanalization rate. Lower absolute and relative HU are independently related to persistent occlusion and HU measurements significantly increase discriminative performances of known recanalization determinants.

Background: Little is known about cerebral blood flow (CBF) in young patients with ischemic stroke caused by an intracranial arteriopathy. Arterial spin labeling (ASL) perfusion is a noninvasive technique for measuring CBF. We aimed to investigate whether, in young patients with unilateral intracranial arteriopathy and previous ischemic stroke, CBF is compromised in noninfarcted brain areas of the symptomatic hemisphere and whether this is related to the severity of the arteriopathy. Methods: Patients aged 5-50 years, with previous middle cerebral artery (MCA) territory infarction and a unilateral intracranial arteriopathy, underwent magnetic resonance imaging (MRI), MR angiography and pseudocontinuous ASL perfusion MRI. We assessed the severity of stenosis of arteries that fed the symptomatic MCA territory, quantified CBF in the noninfarcted cortex of both MCA territories and generated CBF maps for visual CBF interpretation. Results: A total of 17 patients were included (median age 29 years, range 5-49, 29% male). We found a similar median quantified CBF in the symptomatic and asymptomatic MCA territories (86 ml·100 g-1·min-1). CBF maps showed hypoperfusion in the symptomatic MCA territory in 59% of patients compared to 18% based on quantified CBF. Patients with a severe arteriopathy more often showed hypoperfusion on CBF maps than patients with a mild arteriopathy. In 53% of patients, small foci of increased signal intensity were visible on CBF maps around an area of hypoperfusion, indicating vascular artifacts. In these patients, we found large intraindividual variation in the quantified CBF in the symptomatic hemisphere. In 47% of patients, the visual interpretation of perfusion did not correspond with the quantified CBF. Conclusions: This study shows that more than half of young patients with previous ischemic stroke in the MCA territory and a unilateral intracranial arteriopathy have hypoperfusion in the noninfarcted cortex of the symptomatic hemisphere when CBF is visually assessed using a CBF map, in particular in patients with a severe arteriopathy. In the same patients, quantification of CBF shows hypoperfusion in the symptomatic hemisphere in only 18%. This discrepancy is caused by labeled blood within the arteries that has not yet reached the tissue at the time of imaging. Visual assessment can show hypoperfusion, while the quantified CBF in a similar region appears higher when the intravascular labeled blood is included in the region of interest. Further research should focus on elucidating whether cerebral perfusion deficits in young stroke patients with intracranial arteriopathy might help to identify patients who are at risk of poor outcome or stroke recurrence.

The authors assessed the time of onset of the hypothermic effect of acetaminophen in 102 patients with acute ischemic stroke. These patients were randomized to treatment with either 1000 mg of acetaminophen (n = 52) or placebo (n = 50), given six times daily. Treatment with high-dose acetaminophen resulted in a 0.26 °C (95% CI 0.07 to 0.46 °C) lower mean body temperature than placebo treatment within 4 hours. This effect remained present throughout the next 20 hours. A large phase III trial seems warranted.

We studied the value of clinical and electroencephalographic assessment in patients with acute first-ever supratentorial ischemia in predicting functional outcome after 1 year. In 55 consecutive patients admitted after a median interval of less than 24 hours, the degree of handicap was dichotomized as moderate (Rankin grade 1, 2, or 3) or severe (Rankin grade 4 or 5). Clinical deficits were categorized according to signs of a lacunar or a cortical syndrome. Without knowledge of clinical data, electroencephalograms (EEGs) were classified according to findings predicting good or poor prognosis. The outcome after 1 year was assessed as good (Rankin grade 3 or less) or poor (Rankin grade 4 or 5 or death from stroke) and was correlated to clinical data and to EEG findings in the acute stage. Thirty patients with a moderate handicap on admission all had a good outcome (predictive value [PV] of the initial handicap, 1.00; 95% confidence interval [CI], 0.88 to 1.00). Of the 25 patients with severe handicap on admission a poor outcome occurred in 13 (PV, 0.52; 95% CI, 0.31 to 0.72). If these patients with severe handicap at baseline were subdivided according to clinical features, a lacunar syndrome predicted good outcome in 4 of 5 patients (PV, 0.80; 95% CI, 0.28 to 1.00), but a cortical syndrome predicted poor outcome in only 12 of 20 patients (PV, 0.60; 95% CI, 0.36 to 0.81). Of the 20 patients with severe handicap and a cortical syndrome at baseline, an EEG with features predicting a good prognosis correctly predicted good outcome in 6 of 7 patients (PV, 0.86; 95% CI, 0.42 to 1.00). An EEG with features predicting poor prognosis correctly predicted poor outcome in 11 of 13 patients (PV, 0.85; 95% CI, 0.55 to 0.98). Electroencephalography improves the prediction of functional outcome in patients with a severe neurological deficit in the acute stage of cerebral ischemia. This may have implications for the design of future intervention trials in acute stroke.

Objectives: This prospective cohort study assesses incidence of delirium after stroke. In addition, risk factors during the first week were assessed. Finally, outcome in relation to development of delirium was studied. Methods: A total of 527 consecutive patients with stroke (median age, 72 years; range, 29–96 years) were screened for delirium during the first week after admission. We diagnosed delirium with the Confusion Assessment Method. Cognitive functioning prior to the stroke was assessed with the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Neurologic deficits were assessed with the NIH Stroke Scale. Results: A total of 62 patients with stroke (11.8%) developed delirium during the first week of admission. Independent risk factors were preexisting cognitive decline (odds ratio [OR] for IQCODE above 50: 2.6, 95% confidence interval [CI] 1.2–5.7) and infection (OR 3.4, 95% CI 1.7–6.8). Furthermore, right-sided hemispheric stroke (OR 2.0, 95% CI 1.0–3.0), anterior circulation large-vessel stroke (OR 3.4, 95% CI 1.1–10.2), the highest tertile of the NIH Stroke Scale (OR for highest vs lowest tertile 15.1, 95% CI 3.3–69.0), and brain atrophy (OR for highest versus lowest tertile 2.7, 95% CI 1.1–6.8) increased the risk for delirium. Delirium was associated with a worse outcome in terms of duration of hospitalization, mortality, and functional outcome. Conclusions: Delirium occurs in almost 1 out of every 8 patients with stroke on a stroke unit and is associated with cognitive decline, infection, right-sided hemispheric stroke, anterior circulation large-vessel stroke, stroke severity, and brain atrophy. Delirium after stroke is associated with a worse outcome.

Electroencephalograms of 12 patients with a recent lacunar infarct, 12 patients with a recent cortical infarct and 12 control patients were studied without previous information about the clinical features and the corresponding CT scan findings. EEG assessment included both visual and computerised analysis, in both the eyes closed and the eyes open condition. The specificity and the sensitivity of the EEG in the diagnosis of lacunar infarction in this study were both 0.8 (95% confidence limits 0.5-1). The positive predictive value of diagnosing a lacunar infarct on the basis of the EEG was 0.7 (95% confidence limits 0.4-0.9). The chance-corrected coefficient of agreement (kappa) between CT scanning and EEG was 0.75. Thus, in contrast to the results of previous studies, most EEGs of patients with recent lacunar infarction show rather specific abnormalities.

BACKGROUND: Post-stroke hyperglycemia (HG) is associated with poor physical recovery, in particular in patients with cortical stroke. We tested whether HG is also associated with cognitive impairment after ischemic stroke. METHODS: We recruited patients from a prospective consecutive cohort with a first-ever supratentorial infarct. Neuropsychological examination included abstract reasoning, verbal memory, visual memory, visual perception and construction, language, and executive functioning. We related HG (glucose >7.0 mmol/L) to cognition and functional outcome (modified Barthel Index) at baseline and after 6-10 months, and to neurological deficit (National Institutes of Health Stroke Scale) and infarct size at baseline. In additional analyses cortical and subcortical infarcts were considered separately. RESULTS: Of 113 patients, 43 had HG (38%) and 55 had cortical infarcts (49%). Follow-up was obtained from 76 patients (68%). In the acute phase, in patients with cortical infarcts HG was associated with impaired executive function (B=-0.65; 95% confidence limits (CL): -1.3-0.00; p

Oral anticoagulant treatment for secondary prevention after cerebral ischaemia of presumed arterial origin is associated with a higher bleeding rate than cardioembolic stroke. This discrepancy is only partly explained by known bleeding risk factors. Haemostatic genetic variants and AB0 blood group may be involved. We performed a nested casecontrol study in patients with cerebral ischaemia of presumed arterial origin on anticoagulant treatment (International Normalized Ratio between 3.0–4.5). All 34 cases with non-fatal haemorrhage (10 intracranial and 24 extracranial) and 68 control patients on anticoagulant treatment without such a bleeding were selected from the SPIRIT study. AB0 blood group and 11 haemostatic genetic variants were investigated. The Thr312Ala variant of the alpha fibrinogen gene was associated with a decreased bleeding risk (odds ratio (OR) 0.3 for Ala/Ala and Thr/Ala versus Thr/Thr genotype; 95% CI 0.1–0.8). Factor V Leiden was associated with an increased bleeding risk (OR 11.6; 95% CI 1.3–103). The APOE2 allele (OR 0.5; 95% CI 0.2–1.7) and the Tyr204Phe variant in the factor XIII subunit A (OR 2.1; 0.9–5) had nonsignificant relationships with bleeding risk. AB0 blood group and 7 other genetic variants in coagulation factors II and XIII, vitamin K epoxide reductase complex, beta fibrinogen and apolipoprotein E were not related with the risk of haemorrhage. The Ala312Thr variant in the alpha fibrinogen gene is associated with a decreased and factor V Leiden with an increased bleeding risk in patients on anticoagulant treatment after cerebral ischaemia of presumed arterial origin.

Background: Although cognitive impairment early after stroke is a powerful predictor of long-term functional dependence and dementia, little is known about the characteristics and determinants of cognitive dysfunction in acute stroke. Methods: We administered a neuropsychological examination covering 7 cognitive domains to 190 patients within 3 weeks after a first stroke. We also assembled lesion characteristics, clinical factors at admission, demographic characteristics and vascular risk factors. Multivariate logistic regression adjusted for age, gender and education was performed to examine determinants of acute cognitive impairment. Results:Overall, 74% of patients with a cortical stroke, 46% with a subcortical stroke and 43% with an infratentorial stroke demonstrated acute cognitive impairment.Disorders in executive functioning (39%) and visual perception/construction (38%) were the most common. The prevalence and severity of deficits in executive functioning, language, verbal memory and abstract reasoning was more pronounced following left compared to right cortical stroke (all p < 0.05). Intracerebral haemorrhage (OR = 5.6; 95% CI = 1.2–25.4) and cortical involvement of the stroke (OR = 3.6; 95%, CI = 1.3–9.9) were independent determinants of acute cognitive impairment, whereas premorbid moderate alcohol consumption exerted a protective effect (OR = 0.4; 95% CI = 0.1–1.1). Conclusions:Cognitive impairment is common in the first weeks after stroke, with executive and perceptual disorders being the most frequent. Intracerebral haemorrhage, cortical involvement of the lesion and premorbid moderate alcohol consumption are independently associated with acute cognitive impairment.

Patients with left-sided neglect frequently show repetitive behaviour on the ipsilesional side, such as re-markings on cancellation tasks or extensive elaboration on drawings. It is unclear whether these perseverative responses occur as a symptom of hemi-neglect or inattention in general, and/or whether they are related to anatomical brain correlates such as lesion location, lesion side or volume. In a first study, we examined the prevalence and neuropsychological correlates of perseverative responses in 206 subacute stroke patients and 63 healthy controls. Perseverative responses were considered present when there was at least one re-marking on the Star Cancellation, and both the degree and spatial distribution of re-markings were examined. A distinction was made between hemi-neglect and non-lateralized inattention. Spatial and verbal working memory were assessed with the Corsi Block Span and the Digit Span. Verbal and non-verbal executive function was assessed with the Visual Elevator and Letter Fluency. Stroke patients without inattention demonstrated re-markings that were related to executive performance, and the degree of perseveration was equally distributed across the sheet. Hemi-neglect patients but not patients with generalized inattention demonstrated more re-markings than controls, suggesting that a lateralized spatial attention bias triggers the perseverative responses. Patients with left and right hemi-neglect showed the same prevalence of perseveration, but the distribution of re-markings was more lateralized towards the ipsilesional side in patients with right-hemispheric stroke. The degree of perseveration in patients with hemi-neglect was related to the severity of the neglect. The goal of the second study on a subset of patients (n = 127) was to determine the neuroanatomical correlates of perseverative responses in the early phase of stroke. Lesion anatomy was administered by indicating involvement of frontal, parietal, temporal, occipital lobe, caudate nucleus, lenticular nucleus and/or thalamus. Lesion volume was calculated using a manual tracing technique. Lesion analyses indicated that perseverative behaviour is strongly associated with lesions involving the caudate nucleus or the lenticular nucleus, independent of lesion volume. The caudate nucleus was an important correlate of perseveration independent of the presence of hemi-neglect. No association was found between lesion side and perseverative responses, in contrast to previous studies. In conclusion, a stroke involving the basal ganglia and the presence of (left- or right-sided) hemi-neglect are two important associates of perseverative responses in the subacute phase of stroke.

The objective of this study is to examine the prognosis of acute cognitive disorders post-stroke, and to evaluate which clinical factors predict domain-specific cognitive recovery. We followed the course of cognitive functioning in 111 stroke patients and 77 healthy controls by administering two neuropsychological examinations with a 6 to 10 month interval (mean interval, 7.5 +/- 1.3 months). The baseline examination was administered within three weeks post-stroke (mean interval, 7.9 +/- 4.2 days). To examine determinants of domain-specific cognitive recovery, we recorded vascular risk factors, clinical variables, and lesion characteristics. Recovery in visual perception/construction (83%) and visual memory (78%) was the most common. An acute cognitive disorder predicted a long-term disorder in the same domain (all p < .05), except for visual perception/construction. Factors associated with poor cognitive recovery were age (all p < .01), preexistent verbal ability (all p < .005), lesion locations involving the temporal (all p < .05), frontal (p < .05) and occipital lobe (allp < .05), lesion volume (p < or = .001), and diabetes mellitus (p < .01). An early neuropsychological examination provides valuable information on long-term cognitive performance. The prognosis of higher-level visual disorders is the most favorable. Cognitive recovery is associated with age, preexistent ability, lesion volume, lesion location, and diabetes mellitus.

Background and Purpose: Type 2 diabetes mellitus (DM2) is associated with an increased risk of stroke. DM2 is also associated with cognitive impairments. Vascular dysfunction, such as impaired cerebrovascular reserve capacity (CVR), may be a determinant of these changes, but previous studies on CVR in DM2 have provided variable results in selected populations of patients. We aimed to examine CVR in a population-based sample of DM2 patients. Methods: The CO2 reactivity of the middle cerebral artery was examined using transcranial Doppler ultrasonography in 81 DM2 patients and 38 controls. In DM2 patients CVR was correlated with diabetic parameters, vascular risk factors and cognitive functioning.Results: CVR was similar in patients and controls (51 vs. 49%). Within the DM2 group, there was no statistically significant relationship between CVR and DM duration, HbA1c, albuminuria, blood pressure, intima-media thickness and cognition. CVR tended to be lower in diabetic patients with retinopathy [46 vs. 55%, mean difference: –7.9 (confidence interval –18.0, 2.2)]. Conclusion: We conclude that CVR is not impaired in unselected patients with DM2 and probably does not, therefore, play a major role in the aetiology of cognitive impairment.

Objective The aim of the present study was to examine the predictive value of cognitive impairment in the acute phase after stroke as a risk factor for long-term (six to ten months after stroke) depressive symptoms (DS) and a reduced quality of life (QOL), independent of demographic and neurological predictors. Methods We evaluated 143 patients within the first 3 weeks post-stroke. Predictor variables included domain-specific cognitive function, demographic data, vascular risk factors, lesion characteristics, and clinical factors. Predictor variables associated with long-term DS (Montgomery ?sberg Depression Rating Scale ≥ 7) and QOL (Stroke-Specific Quality of Life Scale) were identified with multiple logistic and linear regression. Results Long-term DS were independently predicted by cognitive impairment at baseline, DS at baseline, female sex, diabetes mellitus, and previous TIA(s). Cognitive impairment, increasing age, and functional dependence predicted a reduced QOL, whereas hypercholesterolaemia predicted a better QOL. Among all cognitive disorders, unilateral neglect was the greatest risk factor for DS after 6 months, whereas a disorder in visual perception and construction affected QOL the most. Conclusions Cognitive impairment and vascular risk factors are important predictors of long-term DS and QOL after stroke. The prognostic value of cognition suggests a reactive component in the development or continuation of long-term DS.

Type 2 diabetes mellitus (DM2) is associated with moderate cognitive impairment in verbal memory, mental flexibility, and information processing speed, while other cognitive functions remain relatively unaffected.1 Moreover, epidemiological studies have shown that DM2 patients have a twofold increased risk of developing either vascular dementia or Alzheimer’s disease.1,2 In the present study we examined whether mild cognitive impairment (MCI) and “cognitive impairment, no dementia” (CIND)—two concepts that are used to describe cognitive impairment in the transitional state between normal aging and early dementia—can be applied to the cognitive impairments encountered in a population based sample of DM2 patients. Recently, these concepts have attracted considerable attention, as individuals who meet the criteria for either MCI or CIND are known to have a substantially increased risk of developing dementia.3,4 MCI is defined as a memory deficit without impairments in other cognitive domains.3 Patients with MCI develop Alzheimer’s disease at an annual incidence of between 6% and 25%, compared with 0.2–3.9% in the general population of the same age. The broader concept of CIND is used to describe more general cognitive impairments, often encountered in relation to vascular risk factors. The diagnosis requires impairment in one or more cognitive domains and no dementia.5 A fivefold increased risk of developing Alzheimer’s disease, vascular dementia, or mixed Alzheimer/vascular dementia has been reported in patients with CIND.4 If either of the concepts MCI or CIND is …

Background: Most data on the outcome of basilar artery occlusion are from recent case series of patients treated with intra-arterial thrombolysis. The limited knowledge on the outcome after a conventional treatment approach comes from a few small case series of highly selected patients. Objective: To provide more data on the outcome of conventional treatment. Methods: Data were analysed on patients from three centres with symptomatic basilar artery occlusion treated conventionally. Conventional therapy was defined as treatment with antiplatelets, anticoagulation, or both. Results: Data were available on 82 patients. The case fatality was 40%. Among survivors, 65% remained dependent (Rankin score 4–5). Patients younger than 60 years (odds ratio = 3.1 (95% confidence interval, 1.0 to 9.5)) and those with a minor stroke (OR = 3.1 (1.0 to 9.6)) were more likely to have a good outcome (Rankin score 0–3). Patients with a progressive stroke were less likely to have a good outcome (OR = 0.3 (0.08 to 1.2)) than patients with a maximum deficit at onset or fluctuating symptoms at presentation. Conclusions: Conventional treatment of symptomatic basilar artery occlusion is associated with a poor outcome in almost 80% of patients, which emphasises the importance of the search for a more effective treatment approach.

When reaching towards a visual stimulus, spatial information about the target must be transformed into an appropriate motor command. Visual information is coded initially in retinotopic coordinates, while the reaching movement ultimately requires the specification of the target position in limb-centred coordinates. It is well established that the posterior parietal cortex (PPC) plays an important role in transforming visual target information into motor commands. Lesions in the PPC can result in optic ataxia, a condition in which the visual guidance of goal-directed movements is impaired. Here, we present evidence from two patients with unilateral optic ataxia following right PPC lesions, that the pattern of reaching errors is linked to an eye-centred frame of reference. Both patients made large errors when reaching to visual targets on the left side of space, while facing and fixating straight ahead. By varying the location of fixation and the orientation of the head and body, we were able to establish that these large errors were made specifically to targets to the left of eye-fixation, rather than to the left of head-, body-, or limb-relative space. These data support the idea that visual targets for reaching movements are coded in eye-centred coordinates within the posterior parietal cortex.

The purpose of this investigation was to study the familial aggregation of ischemic stroke and the association between the PDE4D gene and ischemic stroke.The study was performed in an isolated population in The Netherlands, where the authors identified 91 patients with ischemic stroke. Ischemic stroke was subclassified in large- and small-vessel infarction. The authors calculated kinship and inbreeding coefficients and genotyped all patients for three single-nucleotide polymorphisms (SNPs) in the PDE4D gene.The proportion of related pairs was higher in patients with ischemic stroke (68.8%) compared with controls (30.7%; p0.001). For large-vessel infarction, the proportion of related pairs was higher (71%) compared with small-vessel infarction (62.8%; p0.001). Familial aggregation was strongest for patients with early onset (age at onset45 years). All stroke groups were significantly more inbred compared with controls. In inbred individuals, the C allele of SNP45 increased the risk of small-vessel infarction 4.8 times (95% CI 1.1 to 22.3) compared with controls (p = 0.04). The T allele of SNP39 increased the risk of small-vessel infarction 6.3 times (95% CI 1.4 to 28.7) compared with controls (p = 0.02). No associations were found for large-vessel stroke.There was familial aggregation of ischemic stroke and a difference in degree of familial clustering between stroke subtypes. The authors also found that the PDE4D gene is significantly associated with small-vessel infarction in inbred individuals.

While the Mini-Mental State Examination (MMSE) was originally developed to screen for dementia and delirium, many neurologists use this measure as a screening instrument for 'cognitive impairment' in hospitalized stroke patients. However, the validity of the MMSE as such has never been evaluated in acute stroke. We administered the MMSE in addition to a neuropsychological examination covering six cognitive domains to 34 stroke patients (mean interval between stroke and examination, 6.5+/-2.9 days) and 34 healthy controls. The area under the receiver operating characteristic curve (AUC) was calculated in addition to the sensitivity and specificity for various cut-off points on the MMSE. Seventy percent of the patients were impaired in at least one cognitive domain. The accuracy of the MMSE in detecting cognitive impairment was no better than chance (AUC = 0.67; p = 0.13). No optimum MMSE cut-off value could be identified. The MMSE is particularly insensitive to impairments in abstract reasoning, executive functioning, and visual perception/construction.

Objective: To evaluate the prognostic value of domain-specific cognitive abilities in acute stroke with respect to long-term cognitive and functional outcome in addition to neurologic and demographic predictors. Methods: The authors evaluated 168 patients within the first 3 weeks after first-ever stroke. The prevalence of neuropsychological impairment was calculated vs 75 matched healthy controls. The authors also recorded demographic data, vascular risk factors, lesion characteristics, and clinical factors at admission. Independent predictor variables associated with long-term cognitive impairment (assessed with a follow-up neuropsychological examination) and functional impairment (assessed with the modified Barthel Index and the Frenchay Activities Index) were identified with stepwise multiple logistic regression. Areas under receiver operator characteristic curves were used to compare the predictive value of three models, i.e., a standard medical model, a purely cognitive model, and a model consisting of both medical and cognitive predictors. Results: Thirty-one percent of patients showed long-term cognitive impairment. Basic and instrumental ADL disturbances remained present in 19% and 24% of patients. Domain-specific cognitive functioning predicted cognitive and functional outcome better than any other variable. Moreover, the prediction of instrumental ADL functioning improved when cognitive predictors were added to the standard medical model (p 0.05). Impairments in abstract reasoning and executive functioning were independent predictors of long-term cognitive impairment. Inattention and perceptual disor- ders were more important in predicting long-term functional impairment. Conclusion: Domain-specific cognitive abilities in the early phase of stroke are excellent independent predictors of long-term cognitive and functional outcome. NEUROLOGY 2005;64:821-827

Objective: To examine the relation between depressive symptoms and specific cognitive functions in patients with a recent stroke and to examine associations with lesion characteristics. Methods: We studied 126 of 183 consecutive patients within 3 weeks after a first-ever symptomatic stroke (mean interval, 8.3F4.3 days). Presence and severity of depressive symptoms was assessed with the Montgomery 2sberg Depression Rating Scale. Neuropsychological functioning was examined by means of a detailed neuropsychological examination covering six cognitive domains. We included a healthy control group (N=75) to obtain normative data for the neuropsychological examination. Functional impairment was measured with the modified Barthel Index and the modified Rankin Scale. Symptomatic and preexistent lesion characteristics were determined on CT or MRI. Results: Of the included patients, 40% demonstrated mild and 12% moderate to severe depressive symptoms. Severity of depressive symptoms was related to lesion volume (p=0.008), functional impairment (all pb0.004), and degree of overall cognitive impairment (p=0.005). After adjustment for lesion size, a specific neuropsychological profile emerged in patients with moderate to severe depressive symptoms, affecting primarily memory, visual perception, and language (all pb0.05). No association was found between severity of depressive symptoms and lesion location, presence of preexistent lesions (white matter lesions and silent infarcts), and demographic factors (age, education, and gender). Conclusions: Moderate or severe symptoms of depression in the early stage poststroke are associated with a specific pattern of cognitive impairment, lesion size, and functional status. We suggest that depressive symptoms early after stroke are, at least in part, a reactive phenomenon secondary to severe cognitive and functional deficits. D 2004 Elsevier B.V. All rights reserved.

The frequency of silent infarction is an important issue because it is a marker of vascular disease. We studied the occurrence of silent infarction in a sample of patients from the Dutch TIA trial, in which patients were randomized between 30 and 283 mg of aspirin. A total of 91 patients with TIA or non-disabling ischemic stroke and who did not suffer a stroke during a period of one to four years (mean 32 months) underwent CT scanning both on entry and at the end of the study. A cardiac source of embolism was an exclusion criterion for the trial. We found only one patient with a possibly silent infarction; in four patients a previously detected symptomatic infarct on CT was no longer visible. The rarity of silent infarction in this study may have several explanations: 1. (1) the relatively short period of follow-up, 2. (2) the selection of patients (no cardiac source of embolism), 3. (3) the clinical monitoring at four monthly intervals aimed at detection of focal ischemia, 4. (4) the use of aspirin. Given these circumstances, silent infarction is an infrequent problem.

Background and Purpose — We investigated whether patients with transient ischemic attack (TIA) have systemic low flow to the brain or an abnormal intracranial flow distribution caused by an abnormal anatomy of the circle of Willis. Furthermore, we investigated whether metabolic changes were present in the brain. Methods — Forty-four patients with clinically diagnosed TIA were prospectively included in our study. Clinical and neurological data were compiled. MR imaging; quantitative flow measurements of the internal carotid, middle cerebral, and basilar arteries; MR angiography of the circle of Willis; and 1 H-MR spectroscopy were performed in all patients within 3 days of onset of symptoms. Results — Compared with control subjects, TIA patients did not have altered flow volume in any of the arteries and had normal flow distribution through the circle of Willis. In TIA patients, the N -acetylaspartate (NAA)/choline ratio in noninfarcted regions was significantly decreased in the symptomatic hemisphere (1.73±0.16) compared with the asymptomatic hemisphere (1.84±0.19, P P P P P Conclusions — TIA patients have neurological deficits that are transient; however, metabolic damage to the brain is present up to 3 days after the onset of the symptoms. These metabolic changes are not restricted to the symptomatic hemisphere or to areas close to ischemic lesions.

Objectives: We performed a systematic review of the literature to assess the impact of potential risk factors of recurrent stroke other than a compromised cerebral blood flow in patients with carotid occlusion or intracranial arterial lesions. In addition, we investigated the effect of treatment with aspirin or oral anticoagulation on recurrent stroke rate and assessed whether the incidence of recurrent stroke has decreased over the years. Methods: We searched Medline (1966 and onwards) and reference lists of identified articles for papers reporting on the recurrent stroke risk in patients with carotid occlusion or intracranial arterial lesions. Two authors independently extracted information from all papers. The influence of study characteristics on the risk of the endpoints ‘recurrent stroke’, ‘ipsilateral stroke’ and ‘vascular death’ was determined by Poisson regression analysis. Rate ratios were calculated per 10 percentage points increase of a characteristic. Results and Conclusions: Patients with intracranial carotid stenosis or occlusion had a higher rate of recurrent stroke (rate ratio 1.09; 95% CI 1.05–1.14) than patients with extracranial carotid occlusion or middle cerebral artery stenosis or occlusion. In patients with bilateral carotid occlusion the rate was lower (rate ratio 0.82; 95% CI 0.68–0.98). No other vascular risk factors than hypertension (rate ratio 1.23; 95% CI 1.07–1.41) could be shown to increase the rate of recurrent stroke. Oral anticoagulation but not aspirin had a protective effect on the incidence of recurrent stroke (rate ratio 0.86; 95% CI 0.79–0.93). The reported rates of recurrent stroke in patients with symptomatic occlusion of the internal carotid artery or intracranial arterial lesions have not decreased over the years.

Human spatial memory can be divided into multiple, partly separate cognitive processes. In this study, object location memory was studied using a set of tasks that assessed three different spatial memory aspects: positional memory, object location binding, and a combined process. Also, maze learning and spatial span memory were measured. Ten patients who had undergone intracranial tumour resection participated, and their individual results were compared with control data from 24 healthy subjects. Four patients showed selective spatial memory impairments; two patients were impaired at positional memory, and two other patients were impaired on object location binding and the combined process. This double dissociation provides further evidence for the notion that object location memory is not a unitary system, but consists of at least two separate mechanisms. In addition, spatial memory problems were predominantly present in the patients with lesions in either the right hemisphere or in the parietal lobe. These results are in agreement with previous findings on the involvement of the right hemisphere and the posterior parietal cortices in spatial processing.

Purpose: To assess whether patients with transient monocular blindness (TMB) and patients with hemispheric transient ischemic attacks (hTIA) differ from each other with respect to cerebral hemodynamic parameters. Methods: Seventeen TMB patients and 23 hTIA patients with a moderate to severe stenosis or an occlusion of the internal carotid artery (ICA) underwent magnetic resonance (MR) angiography, 1H MR spectroscopy and transcranial Doppler sonography. Thirty-one control subjects were investigated to obtain reference values for the MR investigations. Quantitative flow was measured in the ICAs, the basilar artery and the middle cerebral arteries (MCA). Metabolic changes in the MCA territory were studied by assessing N-acetyl-aspartate (NAA)/choline ratios and prevalences of lactate. The prevalence of collateral flow was assessed in the circle of Willis and the ophthalmic arteries. The vasomotor reactivity was studied by measuring the CO2 reactivity of the MCA territories. Results: Quantitative flow in the cerebropetal arteries and the MCAs did not differ between TMB patients and hTIA patients. Also patterns of collateral flow, prevalence of lactate and CO2 reactivity were similar. The mean ipsilateral NAA/choline ratio was lower in hTIA patients compared with TMB patients (p < 0.01), and was predominantly correlated with symptomatology (p < 0.01), i.e. whether patients had TMB or hTIA, and not with ipsilateral MCA flow (p = 0.2) or ipsilateral CO2 reactivity (p = 0.7). Conclusion: The results of this study indicate that there are no cerebral hemodynamic differences between TMB patients and hTIA patients. It is therefore unlikely that hemodynamic factors account for differences in clinical characteristics between the two patient groups.

OBJECTIVES The long term outcome after a single symptomatic lacunar infarct may be less favourable than is generally assumed. Patients often present with complaints such as fatigue or “being different from before the stroke”, for which there are no obvious physical explanations. Although cognitive functioning is considered normal in most patients with lacunar infarction in the internal capsule or corona radiata, a study was carried out to determine if subclinical changes in mental or emotional function can explain these vague complaints characteristic for their disablement. METHODS Sixteen patients, each with a single symptomatic supratentorial lacunar infarct, and 16 matched healthy controls were examined with an extensive neuropsychological screening battery and a standardised questionnaire aimed at emotional problems. The mean number of correct responses was calculated for each subject and averaged within each group. RESULTS Although, on the whole, there were no differences in performance, patients’ results on the following tasks in different modalities showed evidence for decreased performance under relatively more demanding conditions: line orientation task (mean difference (MD) 261 ms; 95% confidence interval (95%CI) 94 to 428), Rey-Osterrieth delayed recall (MD−3.8, 95% CI −7.5 to 0.0), visual elevator subtest of the everyday attention task (EAT) (MD −0.7, 95% CI −1.5 to 0.1), lottery subtest of the EAT (MD −0.6, 95% CI −1.3 to 0.1) and WAIS similarities (MD −3.2 95% CI −6.3 to 0.1). Patients also more often had emotional disturbances than controls. CONCLUSION Both subtle cognitive impairments and emotional disturbances may play a part in the decreased competence in everyday life of patients with a supratentorial lacunar infarct.