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Biomedical subjects

L Jaap Kappelle

Publications and source records attributed to L Jaap Kappelle.

At least 19 recordsLinked to original sources

Spect measurements of regional cerebral perfusion and carbondioxide reactivity: correlation with cerebral collaterals in internal carotid artery occlusive disease.

BACKGROUND: The aim of the present study was to assess the regional variation in cerebral perfusion, vasomotor reactivity (VMR) and the role of cerebral collaterals in patients with symptomatic internal carotid artery (ICA). METHODS: Seventeen functionally independent patients (60+/-9 years, mean+/-SD) with a unilateral symptomatic internal carotid artery occlusion and a <30% contralateral ICA stenosis were investigated. (99 m) Tc-hexamethyl propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) was performed to study cerebral blood flow in rest and during a CO(2) challenge in the cerebellum, temporal lobe, occipital lobe, basal ganglia, frontal lobe and parietal lobe. Time of flight and phase contrast MRA were used to study collateral flow via circle of Willis. RESULTS: In rest, cerebral perfusion on the side ipsilateral to the ICA occlusion was decreased compared with the contralateral side in the basal ganglia (p<0.05), frontal lobe (p<0.01) and parietal lobe (p<0.01). During a CO(2) challenge only the ipsilateral frontal lobe demonstrated a perfusion decrease compared with the contralateral frontal lobe (p<0.05). Furthermore, in patients without collateral flow via the anterior circle of Willis the perfusion of the ipsilateral frontal lobe was significantly decreased (p<0.01) during the CO(2) challenge and crossed cerebellar diaschisis with a decreased perfusion on the contralateral cerebellar hemisphere was detected (p<0.05). No cerebral blood flow (CBF) differences were found for present/absent collateral flow via the posterior communicating artery. CONCLUSION: Regional assessment of cerebral perfusion and VMR with SPECT demonstrated the heterogeneity of cerebral hemodynamics and the importance of collateral flow via the anterior circle of Willis.

Aged↗

Hemicraniectomy after middle cerebral artery infarction with life-threatening Edema trial (HAMLET). Protocol for a randomised controlled trial of decompressive surgery in space-occupying hemispheric infarction.

BACKGROUND: Patients with a hemispheric infarct and massive space-occupying brain oedema have a poor prognosis. Despite maximal conservative treatment, the case fatality rate may be as high as 80%, and most survivors are left severely disabled. Non-randomised studies suggest that decompressive surgery reduces mortality substantially and improves functional outcome of survivors. This study is designed to compare the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction METHODS: The study design is that of a multi-centre, randomised clinical trial, which will include 112 patients aged between 18 and 60 years with a large hemispheric infarct with space-occupying oedema that leads to a decrease in consciousness. Patients will be randomised to receive either decompressive surgery in combination with medical treatment or best medical treatment alone. Randomisation will be stratified for the intended mode of conservative treatment (intensive care or stroke unit care). The primary outcome measure will be functional outcome, as determined by the score on the modified Rankin Scale, at one year.

Journal Article↗

Large subcortical infarcts: clinical features, risk factors, and long-term prognosis compared with cortical and small deep infarcts.

BACKGROUND AND PURPOSE: In this study we compared risk factors, clinical features, and stroke recurrence in a large series of patients with large subcortical, cortical, or small deep infarcts. METHODS: Patients with a transient or minor ischemic attack (modified Rankin Scale grade of < or =3) who had a single relevant supratentorial infarct of presumed noncardioembolic origin on CT were classified as suffering from a large subcortical (n=120), small deep (n=324), or cortical (n=211) infarct. Mean follow-up was 8 years. Rates of recurrent stroke were compared with Cox regression. RESULTS: The clinical deficits caused by large subcortical infarcts resembled either those of a cortical or those of a small deep infarct. Risk factor profiles were similar in the 3 groups. The rate of recurrent stroke in patients with a large subcortical infarct (25/120; 21%) did not differ from that of patients with a cortical infarct (46/211; 22%) or with a small deep infarct (60/324; 19%). After adjustment for age, sex, and vascular risk factors, hazard ratios for recurrent stroke of large subcortical and cortical infarcts were 1.05 (95% CI, 0.65 to 1.70) and 1.17 (95% CI, 0.79 to 1.73), respectively, compared with small deep infarcts. CONCLUSIONS: Clinical features, risk factor profiles, and stroke recurrence rate in patients with a large subcortical infarct only differ slightly from those in patients with small deep or cortical infarcts.

Adult↗

Classification of cause of death after stroke in clinical research.

BACKGROUND AND PURPOSE: Classification of outcome events is essential in clinical research. The Executive Committee of the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), a secondary prevention trial in patients with cerebral ischemia, repeatedly encountered problems in classifying the cause of death after a stroke if the interval between these events was relatively long. We aimed to develop guidelines for classifying such events. METHODS: Twenty-nine neurologists with a special interest in stroke filled out a questionnaire and audited 5 case vignettes. On the basis of this information, we developed a proposal for classifying causes of death after stroke. This proposal was evaluated in an interobserver analysis in which 10 neurologists or residents in neurology assessed 20 of 100 case vignettes. RESULTS: Initially, there was great variation in classifications of the case vignettes, mainly because the correspondents strongly disagreed about the relative importance of the interval between stroke and death, the degree of disability after stroke, the discharge destination (home or institutional care), and the coexistence of infection. In the new proposal, the main criteria were "interval after stroke" (cutoff point at 1 month) and "best Rankin grade after stroke" (cutoff at 3). In the interobserver analysis, good agreement was obtained among the 5 pairs of neurologists who assessed the 20 case vignettes (kappa 0.80 95% CI, 0.68 to 0.92). CONCLUSIONS: In the absence of guidelines, neurologists show striking variation in the classification of causes of death in patients who die after a stroke. With precise rules, agreement in the classification of death after stroke strongly improved.

Aged↗

Impaired glucose tolerance increases stroke risk in nondiabetic patients with transient ischemic attack or minor ischemic stroke.

BACKGROUND AND PURPOSE: Impaired glucose tolerance, an intermediate metabolic state between normal glucose and diabetes characterized by nonfasting glucose levels between 7.8 to 11.0 mmol/L, is associated with an increased stroke risk in patients with coronary heart disease. Whether impaired glucose tolerance increases the risk of stroke in patients with transient ischemic attack (TIA) or minor ischemic stroke is unknown. METHODS: In total, 3127 patients with a TIA or minor ischemic stroke participated in the Dutch TIA Trial, testing 2 different doses of aspirin and atenolol versus placebo. We estimated the risk of stroke and the risk of myocardial infarction or cardiac death in relation to baseline nonfasting glucose levels (mean 6.0, SD 2.2 mmol/L) with Cox proportional hazards regression analysis, adjusted for cardiovascular risk factors. RESULTS: During 2.6 years follow-up, 272 patients (9%) experienced a stroke and 200 (6%) a myocardial infarction or cardiac death. We found a J-shaped relationship between baseline nonfasting glucose levels and stroke risk. Stroke risk was nearly doubled in patients with impaired glucose tolerance (glucose 7.8 to 11.0 mmol/L) compared with those with normal glucose levels (hazard ratio [HR] 1.8, 95% CI, 1.1 to 3.0) and nearly tripled in diabetic patients (glucose > or =11.1 mmol/L; HR 2.8, 95% CI, 1.9 to 4.1). Patients with low glucose levels (<4.6 mmol/L) had a 50% increased stroke risk (HR 1.5, 95% CI, 1.0 to 2.2) compared with those with normal glucose levels. There was no association between glucose levels and risk of myocardial infarction or cardiac death. CONCLUSIONS: Impaired glucose tolerance is an independent risk factor for future stroke in nondiabetic patients with TIA or minor ischemic stroke.

Aged↗

Predicting long-term independency in activities of daily living after middle cerebral artery stroke: does information from MRI have added predictive value compared with clinical information?

BACKGROUND AND PURPOSE: To investigate whether neuroimaging information has added predictive value compared with clinical information for independency in activities of daily living (ADL) 1 year after stroke. METHODS: Seventy-five first-ever middle cerebral artery stroke survivors were evaluated in logistic regression analyses. Model 1 was derived on the basis of clinical variables; for model 2, neuroimaging variables were added to model 1. Independent variables were stroke severity (National Institutes of Health Stroke Scale), consciousness (Glasgow Coma Scale), urinary continence, demographic variables (age, gender, relationship, educational level), hospital of admission, and clinical instruments: sitting balance (trunk control test), motor functioning (Motricity Index), and ADL (Barthel Index). Neuroimaging variables, determined on conventional MRI scans, included: number of days to scanning, lesion volume, lesion localization (cortex/subcortex), hemisphere, and the presence of white matter lesions. ADL independency was defined as 19 and 20 points on Barthel Index. Differences in accuracy of prediction of ADL independence between models 1 and 2 were analyzed by comparing areas under the curve (AUC) in a receiver operating characteristic analysis. RESULTS: Model 1 contained as significant predictors: age and ADL (AUC 0.84), correctly predicting 77%. In model 2, number of days to scanning, hemisphere, and lesion volume were added to model 1, increasing the AUC from 0.84 to 0.87, accurately predicting 83% of the surviving patients. CONCLUSIONS: Clinical variables in the second week after stroke are good predictors for independency in ADL 1 year after stroke. Neuroimaging variables on conventional MRI scans do not have added value in long-term prediction of ADL.

Activities of Daily Living↗

National Stroke Association guidelines for the management of transient ischemic attacks.

OBJECTIVE: 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. METHODS: Fifteen expert panelists were selected based on objective criteria, using publication metrics that predicted nomination by practitioners in the field. Prior published guidelines were identified through systematic review, and recommendations derived from them were rated independently for quality by the experts. Highest quality recommendations were selected and subsequently edited by the panelists using a modified Delphi approach with multiple iterations of questionnaires to reach consensus on new changes. Experts were provided systematic reviews of recent clinical studies and were asked to justify wording changes based on new evidence and to rate the final recommendations based on level of evidence and quality. No expert was allowed to contribute to recommendations on a topic for which there could be any perception of a conflict of interest. RESULTS: Of 257 guidelines documents identified by systematic review, 13 documents containing 137 recommendations met all entry criteria. Six iterations of questionnaires were required to reach consensus on wording of 53 final recommendations. Final recommendations covered initial management, evaluation, medical treatment, surgical treatment, and risk factor management. INTERPRETATION: The final recommendations on the care of patients with transient ischemic attacks emphasize the importance of urgent evaluation and treatment. The novel approach used to develop these guidelines is feasible, allows for rapid updating, and may reduce bias.

Health Planning Guidelines↗

Diagnostic pitfalls in paediatric ischaemic stroke.

Diagnosing ischaemic stroke and determining its cause is difficult in children. Both are important for selection of treatment and prediction of outcome. This study explored the diagnostic changes that lead to a delay in the correct diagnosis of paediatric stroke. Case histories of 45 children with ischaemic stroke (31 males, 14 females; median age 6y; age range 2mo-16y) were retrospectively reviewed. The initial clinical diagnosis, based on the interpretation of presenting symptoms, was compared with the final aetiological stroke diagnosis after completion and review of diagnostic work-up. The type of diagnostic change, consequent time delay until correct diagnosis, reasons for change of diagnosis, and alterations to management were evaluated. Twenty-four diagnostic changes were identified; 19 in 'primary stroke diagnosis' (symptoms initially not attributed to stroke), and five in 'aetiological diagnosis' (incorrect initial determination of type or cause of stroke). The median interval between initial and final diagnosis was 7 days (3h-2y). The change in diagnosis led to therapeutic alterations in 17 patients. Risk factors for childhood stroke differ from those in adults. Stroke is frequently not recognized as the cause of the child's symptoms, and the correct determination of stroke aetiology takes time. We recommend that children with stroke be evaluated in a centre with expertize, using standardized diagnostic protocols and careful follow-up.

Adolescent↗

Cognitive performance, psychological well-being, and brain magnetic resonance imaging in older patients with type 1 diabetes.

Modest cognitive impairment has been reported in young-adult patients with type 1 diabetes. In older patients with type 2 diabetes, cognitive impairments are more pronounced, which might be due to age but also to differential effects of type 1 diabetes and type 2 diabetes on the brain. This study therefore assessed cognitive performance and magnetic resonance imaging (MRI) of the brain in older type 1 diabetic patients. Forty type 1 diabetic patients (age >50 years) and 40 age-matched control subjects were included. Neuropsychological assessment included all major cognitive domains, and psychological well-being was assessed with questionnaires. Atrophy, white-matter abnormalities, and infarcts were rated on MRI scans. Type 1 diabetic patients performed slightly (effect sizes <0.4) worse on cognitive tasks, but only "speed of information processing" reached statistical significance. No significant between-group differences were found on any of the MRI parameters. Type 1 diabetic patients tended to report more cognitive and depressive problems than control subjects, but this did not correlate with the performance on cognitive tests. We conclude that cognition in older type 1 diabetic patients is only mildly disturbed. Chronic exposure to hyperglycemia is in itself, even at older age, apparently not sufficient to have considerable impact on the brain.

Aged↗

Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes.

The structural correlates of impaired cognition in type 2 diabetes are unclear. The present study compared cognition and brain magnetic resonance imaging (MRI) between type 2 diabetic patients and nondiabetic control subjects and assessed the relationship between cognition and MRI findings and blood pressure and metabolic control. The study included 113 patients and 51 control subjects. Brain MRI scans were rated for white matter lesions (WMLs), cortical and subcortical atrophy, and infarcts. Neuropsychological test scores were divided into five cognitive domains and expressed as standardized Z values. Type 2 diabetes was associated with deep WMLs (P = 0.02), cortical (P < 0.001) and subcortical (P < 0.05) atrophy, (silent) infarcts (P = 0.06), and impaired cognitive performance (attention and executive function, information-processing speed, and memory, all P < 0.05). Adjustment for hypertension did not affect the results. Within the type 2 diabetic group, cognitive function was inversely related with WMLs, atrophy, and the presence of infarcts (adjusted for age, sex, and estimated IQ), and there was a modest association with HbA1c and diabetes duration. This association was strongest for age, even more so than in control subjects. We conclude that cognitive impairments in patients with type 2 diabetes are not only associated with subcortical ischemic changes in the brain, but also with increased brain atrophy.

Aged↗

Neural correlates of human wayfinding in stroke patients.

Wayfinding is a complex cognitive function involving different types of information, such as knowledge about landmarks and direction information. This variety of processes suggest that multiple neural mechanisms are involved, e.g., the hippocampal system, the posterior parietal and temporal cortical areas. Although patient studies and imaging studies have given important insights in the exact neural circuitry underlying wayfinding, many controversies remain. Therefore, the current study sets out to further examine the neuroanatomical correlates of wayfinding in a sample of 31 stroke patients with unilateral lesions, tested with a series of different wayfinding tasks, including landmark recognition, landmark ordering, route reversal and route drawing. For all patients, the exact location of their lesion was determined using CT or MRI scans. Based on existing literature, a number of relevant brain areas were demarcated, after which the extent of damage to these areas was determined for each patient separately. Performance on the landmark recognition task was impaired by damage to the right hippocampal formation, whereas a weak correlation was found between damage to the dorsolateral prefrontal cortex and processing the order of the landmarks. Several brain areas were found to be involved in retracing a route from the end to the beginning, including the right hippocampal formation, the right posterior parietal cortex, the right dorsolateral prefrontal cortex and the right temporal lobe. Finally, damage to the right temporal lobe impaired the ability to draw the route.

Brain↗

Antiplatelet drugs in the secondary prevention after stroke: differential efficacy in large versus small vessel disease? A subgroup analysis from ESPS-2.

BACKGROUND AND PURPOSE: Arterial disease resulting in cerebral ischemia can be classified into large vessel disease (LVD) and small vessel disease (SVD). We assessed whether antiplatelet drugs were more efficacious in large than in small vessel cerebrovascular disease. METHODS: Individual patient data of the second European Stroke Prevention Study (n=6602), in which patients with a previous transient ischemic attack or ischemic stroke were randomized to aspirin, dipyridamole, their combination, or placebo, were reanalyzed. Type of vessel disease was classified according to clinical symptoms or physical examination. Presence of a lacunar syndrome was considered typical for SVD and evidence of cortical dysfunction for LVD. Vascular events (nonfatal stroke, nonfatal myocardial infarction, nonfatal other vascular event, or vascular death) were taken as outcome. Cox regression analyses were performed. RESULTS: A total of 419 first vascular events occurred in 2600 patients with SVD and 367 in 1816 patients with LVD (mean follow-up 1.7 years). For aspirin versus placebo, the hazard ratio (HR) was 0.86 (95% CI, 0.66 to 1.11) in patients with SVD and 0.80 (95% CI, 0.61 to 1.06) in those with LVD (Pinteraction=0.74). For dipyridamole versus placebo, the HR was 0.86 (95% CI, 0.67 to 1.12) in patients with SVD and 0.90 (95% CI, 0.68 to 1.19) in patients with LVD (Pinteraction=0.84). Similar observations were made for the outcome stroke only. CONCLUSIONS: Our findings do not concur with the hypothesis that aspirin, dipyridamole, or the combination may be especially effective in preventing vascular events in patients with previous cerebral ischemia that was caused by LVD compared with SVD.

Aged↗

Brain areas involved in spatial working memory.

Spatial working memory entails the ability to keep spatial information active in working memory over a short period of time. To study the areas of the brain that are involved in spatial working memory, a group of stroke patients was tested with a spatial search task. Patients and healthy controls were asked to search through a number of boxes shown at different locations on a touch-sensitive computer screen in order to find a target object. In subsequent trials, new target objects were hidden in boxes that were previously empty. Within-search errors were made if a participant returned to an already searched box; between-search errors occurred if a participant returned to a box that was already known to contain a target item. The use of a strategy to remember the locations of the target objects was calculated as well. Damage to the right posterior parietal and right dorsolateral prefrontal cortex impaired the ability to keep spatial information 'on-line', as was indicated by performance on the Corsi Block-Tapping task and the within-search errors. Moreover, patients with damage to the right posterior parietal cortex, the right dorsolateral prefrontal cortex and the hippocampal formation bilaterally made more between-search errors, indicating the importance of these areas in maintaining spatial information in working memory over an extended time period.

Brain↗

PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial [ISCRTN 74418480].

BACKGROUND: In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1 degrees C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3 degrees C (95% CI: 0.1-0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic. METHODS/DESIGN: Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level. DISCUSSION: This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one.

Acetaminophen↗

Outcome in patients with stroke associated with internal carotid artery occlusion.

BACKGROUND: The clinical outcome in patients with stroke associated with internal carotid artery (ICA) occlusion is poor, although a minority may recover without dependency. The purposes of this study were (1) to assess the predictive factors of adverse outcome in patients with stroke associated with an occlusion of the ICA and (2) to evaluate the rate of spontaneous recanalization of an occluded ICA. METHODS: A total of 177 consecutive patients with first-ever ischemic stroke associated with ICA occlusion were prospectively examined from the Perugia Stroke Registry. Mean age was 71.4 +/- 14.3 years; 53% were males. Multiple regression models were used to analyze predictors of mortality, dependency and ipsilateral stroke recurrence. RESULTS: The most probable cause of occlusion was atherosclerosis in 65%, cardioembolism in 22%, dissection in 9% and other causes in 4%. Thirty percent of the patients died within 30 days. After a mean follow-up of 420 days (range 1-1,970 days), 45% of the patients had died and 75% had died or were disabled. Another 6% of the patients had a recurrent stroke ipsilateral to the occluded carotid artery. Age was the only predictor of 30-day mortality (77.7 +/- 9.7 vs. 68.7 +/- 15.2 years; p = 0.03) and of long-term mortality or disability (p < 0.003). Hypertension (OR 0.42; 95% CI 0.17-1.00; p = 0.05) was associated with a better outcome within 30 days from stroke onset. Previous ipsilateral transient ischemic attack (OR 0.24; 95% CI 0.06-0.89; p = 0.03) and hyperlipidemia (OR 0.38; 95% CI 0.15-0.99; p = 0.049) were predictors of a better outcome with respect to long-term mortality or disability. No predictors of ipsilateral stroke recurrence were found. One hundred and five out of 177 patients had adequate follow-up ultrasound data. After a mean follow-up of 1.8 years, 10 patients had recanalization of the occluded ICA (2/71 atherosclerosis, 3/19 cardioembolism and 5/15 dissection). CONCLUSIONS: After a mean follow-up of 1.2 years, 45% of the patients with stroke associated with ICA occlusion had died, while 75% had died or were functionally dependent. The presence of either previous ipsilateral transient ischemic attack, hypertension or hyperlipidemia was associated with a favorable outcome. Recanalization of an occluded ICA occurred in a minority of patients and it was associated with cardioembolism and with arterial dissection.

Aged↗

The effects of type 1 diabetes on cognitive performance: a meta-analysis.

OBJECTIVE: To investigate the exact nature and magnitude of cognitive impairments in patients with type 1 diabetes and the possible association with other disease variables, such as recurrent episodes of hypoglycemia and metabolic control. RESEARCH DESIGN AND METHODS: MedLine and PsycLit search engines were used to identify studies on cognitive performance in patients with type 1 diabetes. Effect sizes (Cohen's d), which are the standardized differences between the experimental and the control group, were calculated. In the meta-analysis, a combined d value was calculated, expressing the magnitude of associations across studies. RESULTS: A total of 33 studies were identified that met the inclusion criteria. Compared with nondiabetic control subjects, the type 1 diabetic group demonstrated a significantly lowered performance on the following cognitive domains: intelligence (d = -0.7), speed of information processing (d = -0.3), psychomotor efficiency (d = -0.6), visual (d = -0.4) and sustained attention (d = -0.3), cognitive flexibility (d = -0.5), and visual perception (d = -0.4). Lowered cognitive performance in diabetic patients appeared to be associated with the presence of microvascular complications but not with the occurrence of severe hypoglycemic episodes or with poor metabolic control. CONCLUSIONS: In patients with type 1 diabetes, cognitive dysfunction is characterized by a slowing of mental speed and a diminished mental flexibility, whereas learning and memory are spared.The magnitude of the cognitive deficits is mild to moderate, but even mild forms of cognitive dysfunction might hamper everyday activities since they can be expected to present problems in more demanding situations.

Attention↗

Internal carotid artery occlusion assessed at pulsed arterial spin-labeling perfusion MR imaging at multiple delay times.

Magnetic resonance (MR) imaging with pulsed arterial spin labeling (ASL) was performed at six different inversion times in nine patients with internal carotid artery (ICA) occlusion and in 11 control subjects. The hospital's commission on scientific research on human subjects approved the study protocol, and all study subjects gave informed consent. Cerebral blood flow (CBF) in the middle cerebral artery territories was calculated from the combined signal intensities measured with ASL at the multiple inversion times. In the patients with ICA occlusion, mean CBF values were decreased in the gray matter of the hemisphere ipsilateral to the occlusion, as compared with values in the gray matter of the contralateral hemisphere (P < .05) and with values in the gray matter of the control subjects (P < .05). Quantification of CBF with ASL at multiple inversion times can compensate for the blood transit delays in patients with ICA occlusion.

Adult↗