Unexpected posthemorrhagic hydrocephalus in patients treated with rFVIIa.
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Aged↗
Biomedical subjects
M D Hill
Publications and source records attributed to M D Hill.
Outcome in hyperglycemic stroke with ultrasound-augmented thrombolytic therapy.
Hyperglycemia independently predicts poor outcome after acute ischemic stroke. CLOTBUST (Combined Lysis Of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic tPA) demonstrated that ultrasound-augmented thrombolysis improves recanalization and 24-hour outcome in patients with acute ischemic stroke. We hypothesized that ultrasound would preferentially benefit hyperglycemic patients, and reviewed CLOTBUST with respect to admission glucose and good outcome. We found that ultrasound's benefit on 90-day outcome was primarily apparent at higher glucose levels, suggesting that ultrasound therapy may improve outcome following hyperglycemic stroke.
Aged↗
Neuroprotection and neurogenesis: modulation of cornus ammonis 1 neuronal survival after transient forebrain ischemia by prior fimbria-fornix deafferentation.
Severe transient forebrain ischemia causes selective neuronal death in the hippocampal cornus ammonis 1 region. We tested the hypothesis that fimbria-fornix deafferentation can provide long-term protection to cornus ammonis 1 neurons and modulate neurogenesis following ischemia. Fimbria-fornix lesion or sham-fimbria-fornix lesion was performed on Wistar rats 13 days prior to 10 min forebrain ischemia or sham ischemia. Temperature was regulated and rats survived for 7, 14 or 28 days. Immunofluorescent bromodeoxyuridine and neuron specific nuclear protein staining and immunochemistry terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining were performed. At 7 days after ischemia, 73%+/-14% of cornus ammonis 1 neurons were damaged, while deafferentation reduced the injury to 36%+/-17% of cornus ammonis 1 neurons. This protection persisted for at least 28 days. Ischemia significantly increased the number of bromodeoxyuridine-positive cells (85-90 cells/section in stroke group vs. 6 to 11 cells/section in normal or sham stroke group), with very few terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-stained cells adjacent to the hippocampal cornus ammonis 1. Fimbria-fornix lesioning followed by ischemia increased the percentage of new neurons 13-fold over ischemia alone and 6.5-fold over sham lesion plus ischemia. The results indicate that fimbria-fornix deafferentation provides long-term neuroprotection in cornus ammonis 1 following forebrain ischemia and promotes neurogenesis after ischemic insults.
Analysis of Variance↗
Nucleotide and amino acid mutations in human immunodeficiency virus corresponding to CD4+ decline.
In a meta-analysis, gene sequences of the HIV-1 V3 and surrounding envelope region from studies examining longitudinally derived blood and plasma human immunodeficiency virus forms were analyzed for changes over disease course. CD4+ counts were used as a marker of disease progression; 58 subjects, followed an average of 56 months, were included. Genetic diversification was found early in disease progression. In mid-progression (CD4+ counts dropping from 488 to 329/mm3) diversification did not increase while loop charge dramatically increased. This is consistent with a charged form that dominates and induces disease progression at this critical time. Although the overall mean increase in loop charge was significant, this increase and the transition to amino acids known to change tropism occurred in only half of the subjects who progressed. Those with rapidly progressing disease (within 2 years post-infection) began with a loop charge similar to the end stage of normal progressors. DNA from blood-cell-derived sequences differed from concurrently obtained plasma counterparts by one nucleotide out of 238, but this difference was not reflected in differences in glycosylation patterns, loop charge, or tropism-conferring amino acids. Plasma-derived forms were poorer predictors of future viral forms than were cell-derived sequences.
CD4 Lymphocyte Count↗
The ALIAS (ALbumin In Acute Stroke) Phase III randomized multicentre clinical trial: design and progress report.
High-dose human ALB (albumin) therapy is highly neuroprotective in animal models of ischaemic stroke. A recently completed 82-subject pilot-phase dose-escalation trial has shown that ALB is safe, with strong preliminary suggestions of possible efficacy. We are now proceeding to a large randomized, double-blinded, placebo-controlled multicentre trial funded by the NIH (National Institutes of Health), the ALIAS (Albumin In Acute Stroke) Phase III Trial, which is designed to ascertain definitively whether high-dose ALB therapy confers neuroprotection in subjects with acute ischaemic stroke treated within 5 h of stroke onset. The primary efficacy outcome measure is a favourable outcome, defined as an NIHSS (NIH Stroke Scale) score of 0-1 or a modified Rankin Scale score of 0-1 at 3 months post-randomization. Separate randomization (1:1) to ALB or placebo therapy will be carried out in two cohorts of 900 subjects each, one that receives standard-of-care thrombolytic therapy and the other that does not. Approx. 60 North American clinical sites will participate. Subject enrollment is expected to commence in July 2006.
Humans↗
Insular cortical ischaemia does not independently predict acute hypertension or hyperglycaemia within 3 h of onset.
OBJECTIVES: To test the hypothesis that insular cortical ischaemia is associated with acute hypertension and hyperglycaemia. METHODS: From the Canadian Activase for Stroke Effectiveness Study, which included only patients treated with thrombolysis hyperacutely (ie, within 3 h of onset of stroke), 966 patients were identified with ischaemia affecting (n = 685), or sparing (n = 281), the insular cortex. Demographic and clinical data, pretreatment indices of blood pressure, blood glucose, atrial fibrillation, and clinical imaging and outcome measures were compared between the two groups. Multivariable linear regression was used to assess predictors of systolic blood pressure and glucose levels before thrombolysis. RESULTS: Pretreatment hypertension (p = 0.009), but not hyperglycaemia (p = 0.32), was predicted by insular ischaemia in univariable linear regression analyses. After adjusting for other factors, however, insular cortical ischaemia was not found to be an independent predictor for acute hypertension or hyperglycaemia. CONCLUSIONS: Raised blood pressure or serum glucose levels in hyperacute (<3 h) cerebral ischaemia is not independently predicted by insular involvement. Several hours are required for sympathetic manifestations of insular ischaemia to evolve.
Acute Disease↗
Multicenter evaluation of a self-expanding carotid stent system with distal protection in the treatment of carotid stenosis.
PURPOSE: Carotid artery stent placement may be limited by the embolization of atheromatous material. We evaluated the safety and feasibility of the Medtronic Self-Expanding Carotid Stent (Exponent) in combination with the Medtronic Interceptor Carotid Filter System for the treatment of carotid stenosis among patients at high risk for carotid endarterectomy. METHODS: Patients at high risk for carotid endarterectomy but amenable to percutaneous treatment with stent placement were enrolled. Clinical follow-up was performed at 30 days and 6 and 12 months postprocedure. The National Institutes of Health Stroke Scale was assessed before and within 3 days postprocedure and at 30 days and 6 months postprocedure. Angiography was performed pre- and postprocedure, and carotid duplex scans were performed at baseline and at 30 days and 6 months. RESULTS: Fifty-two carotid procedures were performed in 51 patients (mean age, 69 years; 84% of patients were men). The major adverse event (MAE) rate (death, stroke, and myocardial infarction [MI]) at 30 days was 5.9%: 2 strokes and a single death from periprocedural MI. MAE rates after 6 and 12 months were 5.9% and 11.8%, respectively. The delivery success rate was 94.2% (49/52) for the Interceptor Filter System and 95.9% (47/49) for the Exponent Stent. The mean diameter stenosis of the target lesion was reduced from 62.4% preprocedure to 21.2% postprocedure. CONCLUSION: High delivery success rates were achieved with a low rate of MAE (death, stroke, or MI) in a high-risk population. Treatment of carotid artery disease with the Exponent Carotid Stent combined with distal protection from the Interceptor Filter System is effective and safe.
Aged↗
Using the baseline CT scan to select acute stroke patients for IV-IA therapy.
BACKGROUND: Intra-arterial therapies for acute ischemic stroke are increasingly available. Intravenous therapy (IV) followed immediately by intra-arterial therapy (IA) has been shown to be safe, but such therapy is resource intensive. Selecting the best patients for this therapy may be accomplished with the use of baseline neuroimaging. METHODS: We used data from the IMS-1 and National Institute for Neurological Disorders and Stroke tissue plasminogen activator (tPA) stroke studies to compare outcomes among IV-IA tPA, IV-tPA, and placebo treatment stratified by the baseline CT scan appearance. The CT scans were scored using the Alberta Stroke Program Early CT (ASPECT) score and dichotomized into ASPECT score > 7 (favorable scan) and ASPECT score < or = 7 (unfavorable scan). Logistic regression was used to assess for an ASPECT score by treatment interaction. RESULTS: A total of 460 patients was included. Age and sex were similar among the 3 groups. The IV-IA tPA cohort had a higher median National Institutes of Health stroke scale (NIHSS) score (18 versus 17) compared with the IV tPA cohort. The proportion of patients with favorable CT scans (ASPECT score > 7) was lowest in the IV-IA tPA group. A multiplicative interaction effect was shown indicating that patients with an ASPECT score > 7 in the IV-IA cohort were more likely to have a good outcome compared with IV tPA and with placebo. Harm may accrue to patients treated with IV-IA therapy who have an unfavorable baseline CT scan appearance. CONCLUSIONS: Patients with a favorable baseline CT scan appearance are the most likely to benefit from IV-IA therapy. This hypothesis will be tested in the IMS-3 study.
Aged↗
Silent ischemia in minor stroke and TIA patients identified on MR imaging.
BACKGROUND: In a general population of patients with stroke, the rate of new MRI lesions at 1 week was much higher than expected. With patients with minor stroke and TIA having a higher risk of recurrent clinical events, the authors examined whether patients with minor stroke and TIA also had a high rate of asymptomatic lesions on repeat MRI scanning. METHODS: Patients with minor stroke and TIA presenting within 12 hours of symptom onset with a NIH Stroke Scale score less than six, who had a baseline MRI and a 1-month follow-up, were enrolled in this study. The follow-up study was examined for new diffusion-weighted imaging lesions as compared to the baseline study. Clinical or MRI factors predicting recurrent lesions were examined. RESULTS: A total of 143 patients were enrolled and 14 patients (9.8%; 95% CI 5.4, 15.9) had MR evidence of new lesions at 30 days. Six of these new lesions were clinically asymptomatic (42.9%; 95% CI 17.7, 71.1). A trend to increased likelihood of new lesions at 30 days was seen with progressing baseline scan lesion number (none [2.2%], solitary [12.9%], multiple [19.8%]: p = 0.046). Patients whose mechanism of stroke was large artery or cardioembolic were the most likely to have new lesions on follow-up MRI. CONCLUSION: Minor stroke and TIA are associated with a 10% risk of new lesions on MRI and half of these new lesions are asymptomatic. This risk is lower than seen in more severely affected patients with stroke. Patients with multiple lesions at baseline are at an increased risk for new ischemic lesions.
Aged↗
Simultaneous carotid endarterectomy and coronary artery bypass surgery in Canada.
Stroke neurologists are commonly asked to review patients who require coronary artery bypass grafting (CABG) but who also have comorbid severe carotid stenosis; such patients may be offered simultaneous carotid endarterectomy (CEA). In Canada, 0.51% of CABG procedures were combined CEA-CABG. The adjusted stroke and death rate was 2.67-fold greater in the combined CEA-CABG group compared to CABG alone. Randomized trials of the combined procedure are needed.
Brain Ischemia↗
Imaging of the brain in acute ischaemic stroke: comparison of computed tomography and magnetic resonance diffusion-weighted imaging.
BACKGROUND AND OBJECTIVES: Controversy exists about the optimal imaging technique in acute stroke. It was hypothesised that CT is comparable with DWI, when both are read systematically using quantitative scoring. METHODS: Ischaemic stroke patients who had CT within six hours and DWI within seven hours of onset were included. Five readers used a quantitative scoring system (ASPECTS) to read the baseline (b) and follow up CT and DWI. Use of MRI in acute stroke was also assessed in patients treated with tissue plasminogen activator (tPA) by prospectively recording reasons for exclusion. Patients were followed clinically at three months. RESULTS: bDWI and bCT were available for 100 consecutive patients (admission median NIHSS = 9). The mean bDWI and bCT ASPECTS were positively related (p<0.001). The level of interrater agreement ranged from good to excellent across all modalities and time periods. Bland-Altman plots showed more variability between bCT and bDWI than at 24 hours. The difference between bCT and bDWI was < or =2 ASPECTS points. Of bCT scans with ASPECTS 8-10, 81% had DWI ASPECTS 8-10. Patients with bCT ASPECTS of 8-10 were 1.9 times more likely to have a favourable outcome at 90 days than those with a score of 0-7 (95% CI 1.1 to 3.1, p = 0.002). The relative likelihood of favourable outcome with a bDWI ASPECTS 8-10 was 1.4 (95% CI 1.0 to 1.9, p = 0.10). Of patients receiving tPA 45% had contraindications to urgent MRI. CONCLUSION: The differences between CT and DWI in visualising early infarction are small when using ASPECTS. CT is faster and more accessible than MRI, and therefore is the better neuroimaging modality for the treatment of acute stroke.
Aged↗
Acute stroke: evaluation and treatment.
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Antihypertensive Agents↗
Intra-arterial thrombolysis for retinal artery occlusion: the Calgary experience.
INTRODUCTION: Retinal artery occlusion represents a medical emergency with poor prognosis for visual recovery. Spontaneous improvement is estimated to occur in less than 15% of central retinal artery occlusion (CRAO) cases and conventional treatments have provided only limited benefit. Intra-arterial thrombolysis has been reported as a potentially efficacious and safe treatment. METHODS: We performed a retrospective chart review of all retinal artery occlusion cases treated with intra-arterial recombinant tissue-type plasminogen activator (rtPA) from January 1998 to May 2004. Patients received Goldmann perimetry visual field testing at a variable interval following the procedure (2 days-2.5 years). Visual acuity (VA) was re-assessed in May 2004. RESULTS: Eight cases (59-77 years) were treated for CRAO, 6-18 hours post-onset with intra-arterial rtPA (10-20 mg over 15-60 minutes); one case of branch occlusion (BRAO) was treated with 30 mg rtPA over 75 minutes, 12 hours post-onset. Among the six patients with CRAO assessed in clinic, three experienced improvement in VA by two or more gradations (Snellen lines); three improved by one gradation. However, none achieved a final VA better than 20/300. The case of branch occlusion improved to a VA of 20/20. All patients had residual monocular field defects. CONCLUSIONS: Our findings reveal a limited benefit for intra-arterial tPA compared to the rate of spontaneous improvement and conventional forms of therapy for retinal artery occlusion.
Adult↗
The high risk of stroke immediately after transient ischemic attack: a population-based study.
BACKGROUND: The risk of stroke is elevated in the first 48 hours after TIA. Previous prognostic models suggest that diabetes mellitus, age, and clinical symptomatology predict stroke. The authors evaluated the magnitude of risk of stroke and predictors of stroke after TIA in an entire population over time. METHODS: Administrative data from four different databases were used to define TIA and stroke for the entire province of Alberta for the fiscal year (April 1999-March 2000). The age-adjusted incidence of TIA was estimated using direct standardization to the 1996 Canadian population. The risk of stroke after a diagnosis of TIA in an Alberta emergency room was defined using a Kaplan-Meier survival function. Cox proportional hazards modeling was used to develop adjusted risk estimates. Risk assessment began 24 hours after presentation and therefore the risk of stroke in the first few hours after TIA is not captured by our approach. RESULTS: TIA was reported among 2,285 patients for an emergency room diagnosed, age-adjusted incidence of 68.2 per 100,000 population (95% CI 65.3 to 70.9). The risk of stroke after TIA was 9.5% (95% CI 8.3 to 10.7) at 90 days and 14.5% (95% CI 12.8 to 16.2) at 1 year. The risk of combined stroke, myocardial infarction, or death was 21.8% (95% CI 20.0 to 23.6) at 1 year. Hypertension, diabetes mellitus, and older age predicted stroke at 1 year but not earlier. CONCLUSIONS: Although stroke is common after TIA, the early risk is not predicted by clinical and demographic factors. Validated models to identify which patients require urgent intervention are needed.
Aged↗
Trends in hospital admission for stroke in Calgary.
BACKGROUND: Stroke incidence has fallen since 1950. Recent trends suggest that stroke incidence may be stabilizing or increasing. We investigated time trends in stroke occurrence and in-hospital morbidity and mortality in the Calgary Health Region. METHODS: All patients admitted to hospitals in the Calgary Health Region between 1994 and 2002 with a primary discharge diagnosis code (ICD-9 or ICD-10) of stroke were included. In-hospital strokes were also included. Stroke type, date of admission, age, gender, discharge disposition (died, discharged) and in-hospital complications (pneumonia, pulmonary embolism, deep venous thrombosis) were recorded. Poisson and simple linear regression was used to model time trends of occurrence by stroke type and age-group and to extrapolate future time trends. RESULTS: From 1994 to 2002, 11642 stroke events were observed. Of these, 9879 patients (84.8%) were discharged from hospital, 1763 (15.1%) died in hospital, and 591 (5.1%) developed in-hospital complications from pneumonia, pulmonary embolism or deep venous thrombosis. Both in-hospital mortality and complication rates were highest for hemorrhages. Over the period of study, the rate of stroke admission has remained stable. However, total numbers of stroke admission to hospital have faced a significant increase (p=0.012) due to the combination of increases in intracerebral hemorrhage (p=0.021) and ischemic stroke admissions (p=0.011). Sub-arachnoid hemorrhage rates have declined. In-hospital stroke mortality has experienced an overall decline due to a decrease in deaths from ischemic stroke, intracerebral hemorrhage and sub-arachnoid hemorrhage. CONCLUSIONS: Although age-adjusted stroke occurrence rates were stable from 1994 to 2002, this is associated with both a sharp increase in the absolute number of stroke admissions and decline in proportional in-hospital mortality. Further research is needed into changes in stroke severity over time to understand the causes of declining in-hospital stroke mortality rates.
Alberta↗
Predicting final disposition after stroke using the Orpington Prognostic Score.
BACKGROUND: Prediction of outcome after stroke is important for triage decisions, prognostic estimates for family and for appropriate resource utilization. Prognostication must be timely and simply applied. Several scales have shown good prognostic value. In Calgary, the Orpington Prognostic Score (OPS) has been used to predict outcome as an aid to rehabilitation triage. However, the OPS has not been assessed at one week for predictive capability. METHODS: Among patients admitted to a sub-acute stroke unit, OPS from the first week were examined to determine if any correlation existed between final disposition after rehabilitation and first week score. The predictive validity of the OPS at one week was compared to National Institute of Health Stroke Scale (NIHSS) score at 24 hours using logistic regression and receiver operator characteristics analysis. The primary outcome was final disposition after discharge from the stroke unit if the patient went directly home, or died, or from the inpatient rehabilitation unit. RESULTS: The first week OPS was highly predictive of final disposition. However, no major advantage in using the first week OPS was observed when compared to 24h NIHSS score. Both scales were equally predictive of final disposition of stroke patients, post rehabilitation. CONCLUSIONS: The first week OPS can be used to predict final outcome. The NIHSS at 24h provides the same prognostic information.
Activities of Daily Living↗
The probability of middle cerebral artery MRA flow signal abnormality with quantified CT ischaemic change: targets for future therapeutic studies.
OBJECTIVES: In this study we define the probability of vascular abnormality in the middle cerebral artery (MCA) territory according to the extent of ischaemic change seen using computed tomography (CT). We assessed the sensitivity and specificity of the hyperdense middle cerebral artery (HMCA) and the "dot" sign using magnetic resonance angiography (MRA). METHODS: Patients presenting with ischaemic stroke had a CT scan (<6 h) prior to MRI (<7 h). A quantitative CT scoring system (ASPECTS) was applied to CT and diffusion weighted images (DWI) at baseline and follow up (24 h) by five independent observers. The presence of HMCA and the MCA "dot" sign was also evaluated. An expert reader assessed the 3D time of flight (TOF) MRA in the anterior circulation for areas of decreased vascular signal in the MCA territory, with an absent signal taken to represent severely reduced or absent flow. RESULTS: A total of 100 consecutive patients had baseline CT and MR scans. The median NIHSS was 9. The median CT ASPECTS was 8 and equalled the median DWI ASPECTS. There were a total of 10 HMCA and 19 MCA "dot" signs, with four patients having both HMCA and "dot" signs. A total of 47 MRA flow signal abnormalities were observed in the anterior circulation. CONCLUSIONS: In the absence of accessible neurovascular imaging, the extent of CT ischaemia (ASPECTS) is a strong predictor of vascular occlusion. The CT hyperdense artery signs have a high positive predictive value but low negative predictive value.
Aged↗
The rise and fall of NMDA antagonists for ischemic stroke.
It has long been accepted that high concentrations of glutamate can destroy neurons, and this is the basis of the theory of excitotoxicity during brain injury such as stroke. Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists such as Selfotel, Aptiganel, Gavestinel and others failed to show neuroprotective efficacy in human clinical trials or produced intolerable central nervous system adverse effects. The failure of these agents has been attributed to poor studies in animal models and to poorly designed clinical trials. We also speculate that NMDA receptor antagonism may have hindered endogenous mechanisms for neuronal survival and neuroregeneration. It remains to be proven in human stroke whether NMDA receptor antagonism can be neuroprotective.
Animals↗