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ABSTRACT: The importance of LMF in the outcome after acute ischemic stroke is increasingly recognized, but imaging presents a wide range of options for identification of collaterals and there is no single system for grading collateral flow. The aim of this study was to systematically review the literature on the available methods for measuring LMF adequacy.
We performed a systematic review of Ovid, MEDLINE, and Embase databases for studies in which flow in the leptomeningeal collateral vessels was evaluated. Imaging technique, grading scale, and reliability assessment for collateral flow measurement were recorded.
We found 81 publications describing 63 methods for grading collateral flow on the basis of conventional angiography (n = 41), CT (n = 7), MR imaging (n = 9), and transcranial Doppler (n = 6). Inter- and/or intraobserver agreement was assessed in only 8 publications.
There is inconsistency in how LMF is graded, with a variety of grading scales and imaging modalities being used. Consistency in evaluating collateral flow at baseline is required for the impact of collateral flow to be fully appreciated.
American Journal of Neuroradiology 12/2011; 33(3):576-82. · 2.93 Impact Factor
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ABSTRACT: In vitro and nonhuman in vivo studies demonstrating impaired fibrinolysis of thrombus by thrombolytic agents in the presence of iodinated contrast media (ICM) have prompted concern regarding the clinical use of ICM. A systematic review and meta-analysis were performed to investigate the proportion of patients with acute stroke experiencing recanalization after thrombolytic therapy in whom ICM were administered compared with those in whom they were not.
Embase and Medline searches identified studies reporting recanalization rates in acute ischemic anterior circulation stroke. Pooled proportions of patients who recanalized were calculated with a random-effects model, and studies involving contrast (CS) were compared with those without (NCS).
Six studies were found in which ICM were administered, and 12 studies, in which they were not. Studies were statistically heterogeneous. Combined pooled proportions and 95% confidence intervals (CI) for recanalization in unselected CS and NCS were 53% (36%-70%) and 61% (52%-71%), respectively. In a subgroup analysis in which only middle cerebral artery occlusions were considered, the pooled proportions in CS (n = 3 studies) and NCS (n = 9 studies) were 66% (95% CI, 49%-82%; I(2), 0%) and 63% (CI, 52%-74%; I(2), 82.5%).
Recanalization rates were not significantly different in patients who received iodinated contrast agents in clinical studies. A randomized trial to test whether ICM affect recanalization would require a prohibitively large number of subjects.
American Journal of Neuroradiology 09/2009; 31(1):170-4. · 2.93 Impact Factor
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K R Lees,
G A Ford, K W Muir,
N Ahmed,
A G Dyker,
S Atula,
L Kalra,
E A Warburton,
J-C Baron,
D F Jenkinson,
N G Wahlgren,
M R Walters
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ABSTRACT: To describe the United Kingdom (UK) experience with thrombolytic therapy with intravenous alteplase (rt-PA) for stroke, as captured by the Implementation of Thrombolysis in Stroke (SITS) project.
The multinational Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) was an observational study to assess the safety and efficacy of thrombolytic therapy, when administered within the first 3 h after onset of ischaemic stroke. SITS-MOST was embedded within the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR), an internet-based, international monitoring registry for auditing the safety and efficacy of routine therapeutic use of thrombolysis in acute ischaemic stroke. We performed an analysis of data contributed to SITS-MOST and SITS-ISTR from UK centres.
A total of 614 patients received thrombolysis for stroke between December 2002 and April 2006, 327 were registered to SITS-MOST and 287 to SITS-ISTR. Thirty-one centres treated patients in the UK, of which 23 registered patients in both SITS-MOST and SITS-ISTR and eight solely to SITS-ISTR. The median age from the UK SITS-MOST was identical to the non-UK SITS-MOST register: 68 years (IQR 59-75). The majority (96.1%) of patients from the UK were treated between 8.00 a.m. and 9.00 p.m., and only 18.4% were treated on weekend days, reflecting the difficulties of maintaining provision of a thrombolytic service out of hours. Median onset-to-treatment-time was 155 min (IQR 130-170 min) for the UK, compared to 140 min (IQR 114-165 min) for the non-UK SITS-MOST group (P < 0.001). UK SITS-MOST patients at baseline had more severe stroke in comparison with non-UK patients [median NIHSS 14.5 (IQR 9-19) vs. 12 (IQR 8-17) (P < 0.001)]. Forty-eight percent of UK patients achieved mRS of 0-2 (independence), compared to 55% of the non-UK SITS-MOST register. There was no significant difference in symptomatic intracerebral haemorrhage rate in the UK compared with the non-UK SITS-MOST patients [2.5% (95% CI 1.3-4.8) vs. 1.7% (95% CI 1.4-2.0) P = 0.28]. In the multivariate analysis, there was no statistically significant difference in any outcome between UK and non-UK SITS-MOST patients.
Thrombolytic therapy for stroke has been implemented successfully at a small number of UK stroke centres, with patchy provision throughout the country. The low frequency of treatment out with office hours suggests deficient infrastructure to support delivery. UK patients tended to be more severely affected at baseline and to be treated later. Outcomes are comparable to those seen at the non-UK SITS centres.
QJM: monthly journal of the Association of Physicians 08/2008; 101(11):863-9. · 2.33 Impact Factor
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ABSTRACT: To establish the validity of visual interpretation of immediately processed perfusion computed tomography (CT) maps in acute stroke for prediction of final infarction.
Perfusion CT studies acquired prospectively were reprocessed within six hours of stroke onset using standard CT console software. Four contiguous 5 mm thick images were obtained and maps of time to peak (TTP) and cerebral blood volume (CBV) generated. Volumes of lesions identified only by visual inspection were measured from manually drawn regions of interest. Volumes of tissue with prolonged TTP or reduced CBV were compared with independently calculated volume of infarction on non-contrast CT (NCCT) at 24-48 hours, and with clinical severity using the NIHSS score. Arterial patency at 24-48 h was included in analyses.
Studies were analysed from 17 patients 150 minutes (median) after stroke onset. Volume of tissue with prolonged TTP correlated with initial NIHSS (r = 0.62, p = 0.009), and with NCCT final infarct volume when arterial occlusion persisted (r = 0.953, p = 0.012). Volume of tissue with reduced CBV correlated with final infarct volume if recanalisation occurred (r = 0.835, p = 0.001). Recanalisation was associated with lower 24 h NIHSS score (6 (IQR, 5 to 9.5) v 19 (18 to 26), p = 0.027), and in 10 patients given rtPA for MCA M1 occlusion, with lower infarct volume (73 v 431 ml, p = 0.002).
Visual evaluation of TTP and CBV maps generated by standard perfusion CT software correlated with 24-48 hour CT infarct volumes. Comparison of TTP and CBV maps yields information on tissue viability. Perfusion CT represents a practical technique to aid acute clinical decision making. Recanalisation was a crucial determinant of clinical and radiological outcome.
Journal of Neurology Neurosurgery & Psychiatry 04/2006; 77(3):334-9. · 4.76 Impact Factor
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ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) has typical clinical features that include stroke, migraine, mood disturbances and cognitive decline. However, misdiagnosis is common. We hypothesized that family history is poorly elicited in individuals presenting with features of CADASIL and that enquiry into family history of all four cardinal manifestations of CADASIL is superior to elicitation of family history of premature stroke alone in raising the diagnostic possibility of CADASIL.
Retrospective review of family histories at presentation in 40 individuals with confirmed CADASIL was performed through structured interview in a Neurovascular Genetics clinic (182 first-degree and 242 second-degree relatives identified). Family history obtained from structured interview was compared to family history initially documented at presentation.
At initial presentation, 30% of individuals were inaccurately documented to have no family history of significant neurological illness. Thirty-five per cent of patients had an initial alternative diagnosis. Initial inaccurate documentation of negative family history was more frequent in individuals with an initial alternative diagnosis. After structured interviews, 34% of 182 first-degree and 35% of 242 second-degree relatives of CADASIL patients had history of stroke (16% of first-degree relatives had stroke before the age of 50 years). Forty-three per cent of first-degree and 28% of second-degree relatives had migraine, mood disturbance or cognitive decline.
A false-negative family history was commonly documented in individuals presenting with features of CADASIL and was associated with initial misdiagnosis. Restriction of family history to premature stroke alone is probably inadequate to identify affected CADASIL pedigrees.
Acta Neurologica Scandinavica 12/2005; 112(5):323-6. · 2.47 Impact Factor
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Journal of Neurology 10/2005; 252(9):1011-20. · 3.47 Impact Factor
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Journal of Neurology Neurosurgery & Psychiatry 10/2005; 76 Suppl 3:iii19-iii28. · 4.76 Impact Factor
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ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is caused by mutations of the Notch3 gene on 19p13. Varying phenotypic expression leads to under recognition and misdiagnosis. Prevalence therefore remains uncertain. We sought to estimate the prevalence of CADASIL in the west of Scotland.
A register for CADASIL was established at a regional neurosciences centre in 2002. All patients with genetically (exons 3, 4, 5, and 6) or histologically confirmed CADASIL residing in two defined administrative health areas were identified. Pedigree members at varying risk of carrying the mutation were also identified and the number of probable Notch3 mutation carriers in the defined population was predicted. Prevalence was calculated for definite CADASIL cases, with and without probable carrier numbers, based upon adult population figures from the 2002 national census.
Twenty two individuals from seven pedigrees with confirmed CADASIL and resident in the defined geographical area were identified, yielding a prevalence of 1.98 (95% confidence interval 1.24-3.00) per 100 000 adults. An additional 37 individuals were predicted to be carriers of the Notch3 mutation, yielding a probable mutation prevalence of 4.14 (3.04-5.53) per 100,000 adults.
The prevalence of genetically proven CADASIL was 1.98 per 100,000 adults in the defined population. This figure underestimates disease burden.
Journal of Neurology Neurosurgery & Psychiatry 06/2005; 76(5):739-41. · 4.76 Impact Factor
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ABSTRACT: To present the preliminary experience of implementing intravenous thrombolytic therapy for acute ischaemic stroke in three UK stroke centres.
Recombinant tissue plasminogen activator for ischaemic stroke received approval from UK regulatory authorities in April 2003. Since 1997, a small number of UK centres had used thrombolytic therapy in highly selected stroke patients. We present the early experience of that treatment in Glasgow and Newcastle.
Patients were selected and treated in accordance with the American Heart Association guidelines. Additionally, radiologic criteria employed in the European-Australasian Acute Stroke Studies were applied. National Institutes of Health Stroke Scale (NIHSS) scores were measured on admission, and Modified Rankin Scale (MRS) scores were assessed at 3 months for all patients with stroke treated prior to initiation of the Safe Implementation of Thrombolysis in Stroke monitoring program for implementation of thrombolysis in stroke in April 2001. Intracranial and systemic haemorrhagic complications were recorded.
120 patients received thrombolytic treatment (approximately 1% of all admissions with presumed stroke). Mean age was 69 years (range 22-93) and initial median NIHSS score was 17 (range 3-31). In the two centres for which temporal data were available, the mean delay between symptom onset and treatment was 139 min (range 20-185). Sixteen episodes of cerebral haemorrhage or haemorrhagic transformation of any degree occurred, of which 5 (4%) were symptomatic. One patient deteriorated and died before repeat CT imaging could be performed. One non-fatal episode of systemic bleeding occurred. One patient was lost to follow-up. At 3 months, 31% of recipients had achieved good (MRS 0-1) outcome, 22% moderate (MRS 2-3) outcome and 21% (MRS 4-5) poor outcome. Twenty-one per cent died within 3 months of stroke. Observed frequency of bleeding complications and protocol violations (6%) was similar to those reported elsewhere.
A small proportion of stroke patients received thrombolytic treatment. Patients treated were more severely affected than in other published European and North American series. Outcomes and complications were consistent with experience elsewhere.
Cerebrovascular Diseases 02/2005; 20(6):438-42. · 2.72 Impact Factor
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Journal of Neurology 01/2005; 252(9):1011-1020. · 3.47 Impact Factor
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ABSTRACT: Magnesium is neuroprotective in animal models of stroke, and findings of small clinical pilot trials suggest potential benefit in people. We aimed to test whether intravenous magnesium sulphate, given within 12 h of stroke onset, reduces death or disability at 90 days.
2589 patients were randomised within 12h of acute stroke to receive 16 mmol MgSO4 intravenously over 15 min and then 65 mmol over 24 h, or matching placebo. Primary outcome was a global endpoint statistic expressed as the common odds ratio for death or disability at day 90. Secondary outcomes were mortality and death or disability, variously defined as Barthel score less than 95, Barthel score less than 60, and modified Rankin scale more than 1. Predefined subgroup analyses were for the primary endpoint in patients in whom treatment commenced within 6 h versus after 6 h, ischaemic versus non-ischaemic strokes, and cortical stroke syndromes versus non-cortical strokes. Intention-to-treat and efficacy analyses were done.
The efficacy dataset included 2386 patients. Primary outcome was not improved by magnesium (odds ratio 0.95, 95% CI 0.80-1.13, p=0.59). Mortality was slightly higher in the magnesium-treated group than in the placebo group (hazard ratio 1.18, 95% CI 0.97-1.42, p=0.098). Secondary outcomes did not show any treatment effect. Planned subgroup analyses showed benefit of magnesium in non-cortical strokes (p=0.011) whereas greater benefit had been expected in the cortical group.
Magnesium given within 12 h of acute stroke does not reduce the chances of death or disability significantly, although it may be of benefit in lacunar strokes.
The Lancet 03/2004; 363(9407):439-45. · 38.28 Impact Factor
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Neurology 07/2003; 60(12):2019-20; author reply 2020. · 8.31 Impact Factor
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ABSTRACT: To determine the relationship between the apolipoprotein E (APOE) epsilon4 allele and in-hospital mortality from intracerebral haemorrhage (ICH).
Patients admitted to two acute stroke units with ICH were prospectively evaluated and APOE genotyped. In-hospital survival was recorded in 176 patients.
There were 85 men and 91 women, mean age 68 years. Fifty-two (30%) of the 176 patients died in hospital. After adjusting for sex, age, hospital, and race, increased age (P = 0.009) and the presence of the APOEepsilon4 allele (P = 0.026) significantly reduced in-hospital survival.
The APOEepsilon4 allele in this population may be associated with poor survival following ICH.
Acta Neurologica Scandinavica 03/2003; 107(2):106-9. · 2.47 Impact Factor
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ABSTRACT: Identifying the appropriate long-term anti-thrombotic therapy following acute ischaemic stroke is a challenging area in which computer-based decision support may provide assistance. Aim: To evaluate the influence on prescribing practice of a computer-based decision support system (CDSS) that provided patient-specific estimates of the expected ischaemic and haemorrhagic vascular event rates under each potential anti-thrombotic therapy.
Cluster-randomized controlled trial.
We recruited patients who presented for a first investigation of ischaemic stroke or TIA symptoms, excluding those with a poor prognosis or major contraindication to anticoagulation. After observation of routine prescribing practice (6 months) in each hospital, centres were randomized for 6 months to either control (routine practice observed) or intervention (practice observed while the CDSS provided patient-specific information). We compared, between control and intervention centres, the risk reduction (estimated by the CDSS) in ischaemic and haemorrhagic vascular events achieved by long-term anti-thrombotic therapy, and the proportions of subjects prescribed the optimal therapy identified by the CDSS.
Sixteen hospitals recruited 1952 subjects. When the CDSS provided information, the mean relative risk reduction attained by prescribing increased by 2.7 percentage units (95%CI -0.3 to 5.7) and the odds ratio for the optimal therapy being prescribed was 1.32 (0.83 to 1.80). Some 55% (5/9) of clinicians believed the CDSS had influenced their prescribing.
Cluster-randomized trials provide excellent frameworks for evaluating novel clinical management methods. Our CDSS was feasible to implement and acceptable to clinicians, but did not substantially influence prescribing practice for anti-thrombotic drugs after acute ischaemic stroke.
QJM: monthly journal of the Association of Physicians 03/2003; 96(2):143-53. · 2.33 Impact Factor
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ABSTRACT: Focal cerebral ischaemia causes release of excitatory amino acid (EAA) neurotransmitters, principally glutamate, with resultant over-stimulation of EAA receptors and downstream pathways. Excess glutamate release is a pivotal event in the evolution of irreversible ischaemic damage in animal models of ischaemia, and drugs that modulate glutamate action either by inhibiting its release, or blocking post-synaptic receptors, are potent neuroprotective agents. Many clinical trials with EAA modulating drugs have been conducted, none individually demonstrating efficacy.
To synthesise all the available data on all different classes of EAA modulators and to evaluate evidence of effects on outcome systematically.
Relevant trials were identified in the Specialised Register of Controlled Trials (last searched May 2001). In addition, MEDLINE and EMBASE online searches for the terms "neuroprotection" (and its variants), "neuroprotective agent", for all individual drugs and drug classes included in the review, hand searches of conference proceedings from European, International, American Heart Association and Princeton conferences on Stroke, American Neurological Association and American Academy of Neurology meetings from 1992-2001, and direct contact with individual investigators and pharmaceutical companies.
Trials were included if they were randomised, controlled studies giving agents with pharmacological properties that included modification of release of EAAs, or blockade of EAA receptors, in stroke within 24h of onset. Efficacy analysis was restricted to trials with a parallel group design: dose escalation studies were excluded. Intention-to-treat analyses were performed on all data. Outcome had to be reported in terms of death or dependence 1-12 months after the acute event.
Data were available for 36 of 41 relevant trials identified, involving 11,209 subjects. Data were unavailable for 632 participants (517 in trials fulfilling criteria for efficacy analysis). Seven trials did not report disability data, which were available for 29 trials involving 10,802 subjects. Twenty one of these trials, involving 10,342 subjects, were parallel group studies included in the primary efficacy analysis. Efficacy analysis included data derived from 9 trials not primarily designed to assess efficacy (1022 subjects). The primary (efficacy) end-point was the proportion of patients dead or disabled at final follow-up (defined by Barthel Index<60 at 3 months by preference). Mortality was a secondary end-point. Drugs were considered as individual agents, and also grouped principally into categories of ion channel modulators (glutamate release inhibition) and NMDA antagonists.
There was no significant heterogeneity of outcome amongst individual drugs, or of drug classes either for the primary efficacy analysis (death or dependence) or for mortality at final follow-up. For the primary efficacy analysis, odds of death or dependence were 1.03 [95% confidence interval 0.96-1.12], and for mortality 1.02 [0.92-1.12]. Neither ion channel modulators (death or dependence 1.02 [0.90-1.16]) nor NMDA antagonists (death or dependence 1.05 [0.95-1.16]) differed from the principal analysis including all compounds. Trends for increased mortality with three NMDA antagonists were seen - selfotel (OR 1.19 [0.81-1.74]), aptiganel (OR 1.32 [0.91-1.93]) and gavestinel (OR 1.12 [0.95-1.32]) - but this did not achieve significance for the NMDA antagonists considered as a class (1.09 [0.96-1.23]). Aptiganel was also associated with a trend towards worse functional outcome (OR 1.20 [0.88-1.65]) although this was not the case for either of the other two compounds. No statistically significant detriment of psychotomimetic NMDA antagonists was found, although a trend towards higher mortality in this sub-group was seen (OR 1.25 [0.96-1.64]).
There was no evidence of significant benefit or harm from drugs modulating excitatory amino acid action. Reductio]).
There was no evidence of significant benefit or harm from drugs modulating excitatory amino acid action. Reduction of death or dependence by 8% or more has been excluded for gavestinel and lubeluzole, which contribute most of the data for this review. However, mechanistic understanding of neuroprotection is too poor to extrapolate from these two failed development plans to all glutamate modulators. Further clinical trials of neuroprotective agents remain justified, since confidence limits around estimates of effect remain wide for most agents, and cannot reliably exclude benefit. Although numbers of patients are too small to confirm or refute a trend towards increased mortality with some NMDA antagonists, further commercial development of these agents is exceedingly unlikely.
Cochrane database of systematic reviews (Online) 01/2003; · 5.72 Impact Factor
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K W Muir
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ABSTRACT: Magnesium is involved in multiple physiological processes that may be relevant to cerebral ischaemia, including antagonism of glutamate release, NMDA receptor blockade, calcium channel antagonism, and maintenance of cerebral blood flow. Systemically administered magnesium at doses that double physiological serum concentration significantly reduces infarct volume in animal models of stroke, with a window of up to six hours after onset and favourable dose-response characteristics when compared with previously tested neuroprotective agents. Small clinical trials have reported benefit, but results are not statistically significant in systematic review. A large ongoing trial (IMAGES) will report in 2003-4 and further trials are planned.
Postgraduate Medical Journal 12/2002; 78(925):641-5. · 1.94 Impact Factor
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ABSTRACT: The authors hypothesized that divergent influences of the APOE epsilon4 allele on ischemic and hemorrhagic stroke survival might result from differences in coagulation profiles. In 49 hemorrhagic stroke patients, epsilon4 carriers had higher partial thromboplastin time ratios (p < 0.01) than non-epsilon4 carriers. Among 529 ischemic stroke patients, increasing epsilon4 allele dose was associated with improved survival (p = 0.03) after adjusting for baseline NIH stroke scale (p = 0.00001) and partial thromboplastin time ratio (p = 0.01). Relative anticoagulation does not fully explain the survival advantage in epsilon4-carrying ischemic stroke patients.
Neurology 09/2001; 57(6):1097-100. · 8.31 Impact Factor
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K W Muir
Journal of Neurology Neurosurgery & Psychiatry 05/2001; 70 Suppl 1:I12-6. · 4.76 Impact Factor
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K W Muir
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ABSTRACT: Magnesium exhibits a range of neuronal and vascular actions that may ameliorate ischaemic CNS insults, including stroke. Significant neuroprotection with magnesium has been observed in different models of focal cerebral ischaemia in many laboratories, with infarct volume reductions between 25 and 61%. Maximal neuroprotection is evident at readily attainable serum concentrations, and neuroprotection is still seen when administration is delayed up to 6 hours after onset of ischaemia. Clinical use of magnesium in pre-eclampsia and acute myocardial infarction confirms its safety and tolerability. Five small trials in acute stroke have reported reduced odds of death or dependence with administration of magnesium, but confidence intervals are wide, and definitive data from ongoing large trials are awaited.
CNS Drugs 02/2001; 15(12):921-30. · 4.80 Impact Factor
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ABSTRACT: We report facial palsy as the sole cranial neuropathy complicating an ipsilateral internal carotid artery dissection. A previously healthy 44-year-old man developed retro-orbital and temporal headache with associated nausea while engaged in modest physical exercise. On the following morning he noticed a left ptosis and miotic pupil. One week later he woke with a left facial weakness. On the same day he had a 90-minute episode of expressive dysphasia. Magnetic resonance imaging and angiography demonstrated left internal carotid artery dissection. The temporal association between our patient's facial nerve palsy and typical features of spontaneous internal carotid artery dissection suggests a common aetiology. We suggest that involvement of the VII cranial nerve in isolation followed disruption of an anomalous nutrient artery. The delay in clinical manifestation may imply extension of the dissection.
European Journal of Neurology 12/2000; 7(6):723-5. · 3.69 Impact Factor
