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Martin M Brown

Publications and source records attributed to Martin M Brown.

At least 19 recordsLinked to original sources
PubMed2006

The evidence for medicine versus surgery for carotid stenosis.

Atherosclerotic stenosis of the internal carotid artery is an important cause of stroke. Several large randomised trials have compared best medical management with carotid endarterectomy and provide a strong evidence base for advising and selecting patients for carotid surgery. Best medical management of carotid stenosis includes lowering of blood pressure, treatment with statins and antiplatelet therapy in symptomatic patients. Combined analysis of the symptomatic carotid surgery trials, together with observational data, has shown that patients with recently symptomatic severe carotid stenosis have a very high risk of recurrent stroke in the first few days and weeks after symptoms. Carotid endarterectomy has a risk of causing stroke or death at the time of surgery in symptomatic patients of around 5-7%, but in patients with recently symptomatic stenosis of more than 70%, the benefits of endarterectomy outweigh the risks. In patients with moderate stenosis of between 50 and 69%, the benefits may justify surgery in patients with very recent symptoms, and in patients older than 75 years within a few months of symptoms. Patients with less than 50% stenosis do not benefit from surgery. In asymptomatic patients, or those whose symptoms occurred more than 6 months ago, the benefits of surgery are considerably less. Patients with asymptomatic stenosis treated medically only have a small risk of future stroke when treated medically of about 2% per annum. If carotid endarterectomy can be performed safely with a perioperative stroke and death rate of no more than 3%, then the randomised trials showed a significant benefit of surgery over 5 years follow-up, with an overall reduction in the risk of stroke from about 11% over 5 years down to 6%. However, of 100 patients operated, only 5 will benefit from avoiding a stroke over 5 years. The majority of neurologists have concluded that this does not justify a policy of routine screening and endarterectomy for asymptomatic stenosis. Patients known to have asymptomatic stenosis should be advised of the risks and benefits. The trials provide justification for surgery at centres with a proven low complication rate, in asymptomatic patients prepared to take a small immediate risk in exchange for a small longer term benefit. Those that opt for medical management alone should be advised to seek urgent medical attention should they become symptomatic in the future.

Antihypertensive Agents↗
PubMed2006

Longitudinal changes in cerebral response to proprioceptive input in individual patients after stroke: an FMRI study.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) provides an opportunity to study the relationship between cerebral reorganization and functional recovery after stroke. The authors set out to demonstrate the feasibility of using fMRI to investigate mechanisms of recovery in individual patients presenting with severe motor impairment. METHODS: fMRI was performed during passive movement at both affected and unaffected wrists separately in 2 patients with pure motor stroke. Six scanning sessions were performed in each patient over the first 4 months after stroke. Seven control subjects were also studied, 1 of them over 6 sessions. The authors examined for longitudinal changes in cerebral responses to proprioceptive afferent input that correlated with motor recovery. RESULTS: In control subjects, passive movement of either wrist led to relative increases in brain activation in the contralateral sensorimotor cortex and supplementary motor area, the bilateral inferior parietal cortex and secondary somatosensory areas, and the ipsilateral cerebellum. Increases in brain activation correlating with motor recovery were observed in both the ipsilesional primary sensory and primary motor cortex in 1 patient with good motor recovery but not in another patient with poor recovery. No longitudinal changes were seen in the control subject. CONCLUSIONS: These 2 case reports demonstrate that functionally relevant changes in cerebral organization can be identified in individual patients.

Adult↗
PubMed2005

Safety and efficacy of endovascular treatment of carotid artery stenosis compared with carotid endarterectomy: a Cochrane systematic review of the randomized evidence.

BACKGROUND AND PURPOSE: Endovascular treatment of atherosclerotic carotid artery stenosis may be an alternative to surgical endarterectomy. To evaluate the safety and efficacy of endovascular techniques, we conducted a systematic review of randomized studies that compared endovascular treatment with surgery for carotid stenosis. METHODS: We searched the Cochrane Stroke Group trials register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Science Citation Index for randomized trials of carotid angioplasty and/or stenting compared with surgery. We also contacted researchers in the field and balloon catheter and stent manufacturers. RESULTS: Five trials involving 1269 patients were included. Analysis of 30-day safety data found no significant difference in the odds of treatment-related death or any stroke (odds ratio [OR], endovascular surgery, 1.33; 95% confidence interval [CI], 0.86 to 2.04), death or disabling stroke (OR, 1.22; CI, 0.61 to 2.41), or death, any stroke, or myocardial infarction (OR, 1.04; CI, 0.69 to 1.57). At 1 year after randomization, there was no significant difference between the 2 treatments in the rate of any stroke or death (OR, 1.01; CI, 0.71 to 1.44). Endovascular treatment significantly reduced the risk of cranial nerve injury (OR, 0.13; CI, 0.06 to 0.25). There was substantial heterogeneity between the trials for 4 of the 5 outcomes. CONCLUSIONS: No significant difference in the major risks of treatment was found but the wide confidence intervals indicate that it is not possible to exclude a difference in favor of one treatment. Minor complication rates favor endovascular treatment. There is currently insufficient evidence to support a widespread change in clinical practice away from recommending carotid endarterectomy as the treatment of choice for suitable carotid artery stenosis. Patients suitable for carotid endarterectomy should only be offered stenting within the ongoing randomized trials of stenting versus surgery.

Angioplasty↗
PubMed2005

Restenosis after carotid angioplasty, stenting, or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS).

BACKGROUND AND PURPOSE: Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) patients with carotid stenosis were randomized between endovascular treatment and endarterectomy. The rates of residual severe stenosis and restenosis and their contribution to recurrent symptoms was unclear. METHODS: Endovascular patients were treated by balloon angioplasty alone (88%) or stenting (22%). Patches were used in 63% of endarterectomy patients. Carotid stenosis was categorized as mild (0% to 49%), moderate (50% to 69%), severe (70% to 99%), or occluded, using standardized Doppler ultrasound criteria at the examination closest to 1 month (n=283) and 1 year (n=347) after treatment. Recurrent cerebrovascular symptoms during follow-up were analyzed. RESULTS: More patients had > or =70% stenosis of the ipsilateral carotid artery 1 year after endovascular treatment than after endarterectomy (18.5% versus 5.2%, P=0.0001). Residual severe stenosis was present in 6.5% of patients at 1 month after endovascular treatment. Between 1 month and 1 year, restenosis to > or =70% stenosis occurred in 10.5% of the endovascular group. After endarterectomy, 1.7% had residual severe stenosis at 1 month, and 2.5% developed severe restenosis. The results were significantly better after stenting compared with angioplasty alone at 1 month (P<0.001) but not at 1 year. Recurrent ipsilateral symptoms were more common in endovascular patients with severe stenosis (5/32 [15.6%]) compared with lesser degrees of stenosis at 1 year (11/141 [7.8%], P=0.02), but most were transient ischemic attacks and none were disabling or fatal strokes. There were no recurrent symptoms in the 9 endarterectomy patients with > or =70% stenosis at 1 year. CONCLUSIONS: Carotid stenosis 1 year after endovascular treatment is partly explained by poor initial anatomical results and partly by restenosis. The majority of patients were treated by angioplasty without stenting. Further randomized studies are required to determine whether newer carotid stenting techniques are associated with a lower risk of restenosis. The low rate of recurrent stroke in both endovascular and endarterectomy patients suggests that treatment of restenosis should be limited to patients with recurrent symptoms, but long term follow up data are required.

Angioplasty, Balloon↗
PubMed2005

Spatial working memory capacity in unilateral neglect.

It has been proposed recently that a deficit in keeping track of spatial locations may contribute to the severity of unilateral neglect in some right hemisphere stroke patients. However, performance on traditional spatial working memory (SWM) tasks (e.g. Corsi blocks) might be confounded by failure to encode leftward locations, rather than a true deficit of maintaining locations in SWM. Here we introduced new procedures for circumventing this to measure SWM capacity in neglect. In a first experiment, 20 right hemisphere stroke patients (10 with and 10 without neglect) were tested on a computerized vertical variant of the Corsi task. Sequences of spatial locations in a vertical column were displayed and participants had to tap out the remembered sequence on a touchscreen. Patients with left neglect were impaired on this vertical SWM task compared with all control groups. However, poor performance on this task (as for Corsi blocks) might involve impaired memory for stimulus sequence, or poor visuomotor control of manual responding, rather than reduced SWM capacity per se. A second experiment therefore employed a purer measure of vertical SWM. After the displayed sequence, a single location was now probed visually, with observers judging verbally (yes/no) if it had been in the preceding sequence. Hence order no longer mattered, and no spatial motor response was required. Again, the neglect group was impaired relative to all others, now with very little overlap between the performances of individual neglect patients versus individuals in control groups. Poor performance on the second task, which provides a purer measure of SWM capacity, correlated with severity of left neglect on cancellation tasks (but not on line bisection), consistent with recent proposals that SWM deficits can exacerbate left neglect on visual search tasks when present conjointly. Lesion anatomy indicated that neglect patients with a SWM deficit were most likely to have damage to parietal white matter, plus, in the second experiment, to the insula also. These findings demonstrate that an impairment in SWM capacity can contribute to the neglect syndrome in patients with stroke involving regions within the right parietal lobe and insula.

Adult↗
PubMed2005

Assessment of the antiplatelet effects of low to medium dose aspirin in the early and late phases after ischaemic stroke and TIA.

Vascular events commonly recur in stroke patients on aspirin, and may reflect incomplete inhibition of platelet function with aspirin therapy. The platelet function analyser (PFA-100) activates platelets by aspirating a blood sample at a moderately high shear rate through a capillary to a biologically active membrane with a central aperture. The membrane is coated with collagen, and either ADP (C-ADP) or epinephrine (C-EPI). The time taken for activated platelets to adhere, aggregate, and occlude the aperture is called the closure time. Previous studies have shown that aspirin prolongs the C-EPI closure time, without prolongation of the C-ADP closure time, in the majority of control subjects. We hypothesised that the PFA-100 would provide a sensitive assay for the detection of early and convalescent phase cerebrovascular disease (CVD) patients who had incomplete inhibition of platelet function with aspirin. We investigated potential cyclooxygenase-dependent and -independent mechanisms that might influence the responsiveness to aspirin using the PFA-100. Patients were studied during the early (< or = 4 weeks, n=57) and convalescent phases ((< or = 3 months, n=46) after ischaemic stroke or TIA. To investigate potential mechanisms that could contribute to aspirin responsiveness on the PFA-100, we measured von Willebrand factor antigen levels, and carried out platelet aggregometry experiments in platelet-rich plasma in response to sodium arachidonate (1 mM) and ADP (5 microM). Sixty percent of patients in the early phase and 43% of patients in the convalescent phase did not have prolonged C-EPI closure times on 75-300 mg of aspirin daily, and were defined as aspirin non-responders. Median C-ADP closure times were significantly shorter in aspirin non-responders than aspirin-responders in both the early and convalescent phases after symptom onset (P=0.008), suggesting platelet hyper-reactivity to collagen or ADP in the aspirin non-responder subgroup. There was a significant inverse relationship between plasma von Willebrand factor antigen levels and C-EPI closure times in both early and convalescent phase CVD patients (P=0.008). Mean von Willebrand factor antigen levels were significantly higher in aspirin non-responders than aspirin responsive patients in the early (P=0.001), but not convalescent phase (P=0.2) after stroke and TIA. None of the patients studied were defined as being aspirin-resistant using sodium arachidonate- or ADP-induced platelet aggregometry. A large proportion of ischaemic CVD patients have incomplete inhibition of platelet function with low to medium dose aspirin using the PFA-100. The results suggest that cyclooxygenase-independent mechanisms, including elevated von Willebrand factor antigen levels, play an important role in mediating aspirin non-responsiveness on the PFA-100.

Adenosine Diphosphate↗
PubMed2004

Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI.

Gradient echo T2*-weighted MRI has high sensitivity in detecting cerebral microbleeds, which appear as small dot-like hypointense lesions. Microbleeds are strongly associated with intracerebral haemorrhage, hypertension, lacunar stroke and ischaemic small vessel disease, and have generated interest as a marker of bleeding-prone microangiopathy. Microbleeds have generally been considered to be clinically silent; however, since they are located in widespread cortical and basal ganglia regions and are histologically characterized by tissue damage, we hypothesized that they would cause cognitive dysfunction. We therefore studied patients with microbleeds (n = 25) and a non-microbleed control group (n = 30) matched for age, gender and intelligence quotient. To avoid the confounding effects of coexisting cerebrovascular disease, the groups were also matched for the extent of MRI-visible white matter changes of presumed ischaemic origin, location of cortical strokes, and for the proportion of patients with different stroke subtypes (including lacunar stroke). A battery of neuropsychological tests was used to assess current intellectual function, verbal and visual memory, naming and perceptual skills, speed and attention and executive function. Microbleeds were most common in the basal ganglia but were also found in frontal, parieto-occipital, temporal and infratentorial regions. There was a striking difference between the groups in the prevalence of executive dysfunction, which was present in 60% of microbleed patients compared with 30% of non-microbleed patients (P = 0.03). Logistic regression confirmed that microbleeds (but not white matter changes) were an independent predictor of executive impairment (adjusted odds ratio = 1.32, 95% confidence interval 1.01-1.70, P = 0.04). Patients with executive dysfunction had more microbleeds in the frontal region (mean count 1.54 versus 0.03; P = 0.002) and in the basal ganglia (mean 1.17 versus 0.32; P = 0.048). There was a modest correlation between the number of microbleeds and the number of cognitive domains impaired (r = 0.44, P = 0.03). This study provides novel evidence that microbleeds are associated with cognitive dysfunction, independent of the extent of white matter changes of presumed ischaemic origin, or the presence of ischaemic stroke. The striking effect of microbleeds on executive dysfunction is likely to result from associated tissue damage in the frontal lobes and basal ganglia. These findings have implications for the diagnosis of stroke patients with cognitive impairment, and for the appropriate use of antihypertensive and antiplatelet treatments in these patients.

Aged↗
PubMed2004

Carotid artery stenting:the need for randomised trials.

Endovascular treatment for carotid artery stenosis avoids some of the complications of carotid endarterectomy, but has not been widely accepted. Concerns about the risks and benefits of endovascular treatment led to the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS). There was no difference in major outcome events between endovascular treatment and carotid endarterectomy, but the rate of procedural stroke or death was higher than desirable. There was no difference either in the rate of stroke during follow-up, but the confidence intervals were very wide and severe ipsilateral carotid stenosis was more frequent 1 year after endovascular treatment than after carotid surgery. Two other randomised trials of carotid stenting were stopped early after poor outcomes in stented patients. These early trials used techniques which have now been superseded, but the results emphasise the need to improve the safety of endovascular treatment. Recent advances designed to improve safety include new designs of stents and delivery systems, and devices designed to protect the brain from embolisation during stenting. However, there is little convincing evidence that these new devices reduce the rate of stroke. Moreover, a systematic review of the existing randomised trial data concluded that there the current evidence does not support a shift away from recommending carotid endarterectomy as the standard treatment for carotid stenosis. There is therefore a clear need for further randomised trials of carotid stenting. Three of the ongoing trials, EVA-3S, SPACE and ICSS (CAVATAS-2), have prospectively agreed to combine individual patient data after completion of follow-up. This meta-analysis will provide results similar to a mega-trial and should also allow informative subgroup analyses. The co-operation between the trials in agreeing to perform this meta-analysis is a major advance in trial design. The result should determine whether carotid stenting truly rivals carotid endarterectomy as the treatment of choice for carotid stenosis.

Carotid Stenosis↗
PubMed2004

International carotid stenting study: protocol for a randomised clinical trial comparing carotid stenting with endarterectomy in symptomatic carotid artery stenosis.

BACKGROUND: Carotid stenting avoids general anaesthesia, cranial nerve injury and the discomforts of surgical treatment of carotid stenosis. A systematic review of the randomised trials showed no overall difference in the major risks of endovascular treatment for carotid stenosis compared with surgery, but the confidence intervals were wide and both methods carried a significant risk of stroke. The use of protection devices appears to improve the safety of endovascular treatment, but there are little randomised data available about long-term outcomes. We have therefore set up an international, multicentre, randomised, controlled, open, prospective clinical trial, namely the International Carotid Stenting Study (ICSS), also known as CAVATAS-2. The objectives of the ICSS are to compare the risks, benefits and cost-effectiveness of a treatment policy of referral for carotid stenting compared with referral for carotid endarterectomy. METHODS: Centres are required to have a team with audited expertise in carotid endarterectomy and stenting procedures, including at least one neurologist or stroke physician, a surgeon and an interventionalist. Attendance at a carotid stenting training course is required. Centres with more limited experience can join the trial as probationary centres, but stenting must then be proctored by an experienced interventionalist. Symptomatic patients are included over the age of 40 years with atherosclerotic carotid stenosis, suitable for both stenting and surgery, and are randomised in equal proportions between carotid endarterectomy and stenting. Stents and other devices are chosen for use at the discretion of the interventionalists but must be approved by the devices committee. The protocol recommends that a cerebral protection system should be used whenever the operator thinks one can be safely deployed. The combination of aspirin and clopidogrel is recommended to cover stenting procedures. Standard or eversion endarterectomy is allowed using local or general anaesthesia, shunts or patches. All patients will receive best medical care. Patients will be followed up by neurologists at 30 days after treatment, 6 months after randomisation and then annually up to 5 years after randomisation. The primary outcome measure is the difference in the long-term rate of fatal or disabling stroke in any territory between patients randomised to stenting or surgery. Secondary outcome measures include any stroke, myocardial infarction or death within 30 days of treatment, treatment- related cranial nerve palsy or haematoma. Restenosis (>70%) on ultrasound follow-up, economic measures and quality of life will also be analysed. The sample size is estimated at 1,500 patients, which will provide 95% confidence intervals of +/- 3.0 percentage points for the outcome measure of 30-day disabling stroke and death rate and +/- 3.3 percentage points for the outcome measure of death or stroke during follow-up. The trial office monitors outcome events at individual centres and a rate of events above a given threshold triggers a blinded assessment of the events, submitted to the chairman of the data-monitoring committee. CONCLUSIONS: The ICSS protocol incorporates a number of novel features to ensure patient safety, including the concept of probationary centres, proctoring of inexperienced investigators and monitoring of individual centre results on an ongoing basis. The protocol is also designed to mirror routine clinical practice as far as possible, so that the results will be widely applicable and relevant to determining the place of carotid stenting in clinical practice in the future.

Carotid Stenosis↗
PubMed2004

Triptans in migraine: the risks of stroke, cardiovascular disease, and death in practice.

BACKGROUND: Triptans are widely used to treat migraine but have been associated with stroke, myocardial infarction (MI), and ischemic heart disease (IHD) in case reports. OBJECTIVE: To estimate the incidence of stroke, cardiovascular events, and death in a migraine cohort, stratified by triptan prescription, and investigate whether the risk of these events was increased in those treated with triptans. METHODS: Migraine patients and matched nonmigraine control subjects were identified from the General Practice Research Database. Computerized records were searched for triptan prescriptions, stroke, TIA, MI, IHD, death, arrhythmia, and confounding variables. Incidence rates were calculated and migraine groups compared with controls using a Cox model, adjusting for confounders. RESULTS: Of 63,575 migraine patients, 13,664 were prescribed a triptan. There was no association between triptan prescription and stroke (hazard ratio [HR] 1.13; 95% CI 0.78, 1.65), MI (HR 0.93; 95% CI 0.60, 1.43), or other outcomes studied. The larger group of migraine patients not prescribed a triptan had an increased risk of stroke (HR 1.51; 95% CI 1.26, 1.82) and IHD (HR 1.35; 95% CI 1.18, 1.54) and a decreased risk of all-cause mortality (HR 0.72; 95% CI 0.65, 0.80). CONCLUSIONS: In general practice, triptan treatment in migraine does not increase the risk of stroke, MI, cardiovascular death, IHD, or mortality. Triptans are prescribed to those less at risk of these events.

Adolescent↗
PubMed2004

The influence of time after stroke on brain activations during a motor task.

After stroke, the pattern of brain activation during performance of a motor task is related to outcome. Here, we compare this relationship in the early (10-14 days) and late (at least 3 months) phases after first-ever stroke. A negative linear relationship between task-related brain activation, as measured by functional magnetic resonance imaging, and outcome is seen in several identical primary and nonprimary motor regions that is independent of time after stroke. In other words, patients with poorer outcome scores recruit more widely within motor-related regions in both the early or late poststroke phase. However, in contralesional middle intraparietal sulcus, contralesional cerebellum, and ipsilesional rostral premotor cortex, this relationship is seen only in the early poststroke phase. Thus, patients with poorer outcome scores recruit these areas in only the early and not the late poststroke phase. These results suggest that there are differences in the cerebral implementation of action in patients with poor outcome that are dependent on the time since stroke. Thus, in those patients with the most to gain from rehabilitation, different therapeutic approaches may be required at different stages after stroke.

Adult↗
PubMed2004

Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack.

Flow cytometric studies suggest that platelets are activated in ischaemic stroke or transient ischaemic attack (TIA). However, few studies have measured circulating leucocyte-platelet complexes in this patient population. Whole blood flow cytometry was used to quantify the expression of CD62P-, CD63-, and PAC1-binding, and the percentages of leucocyte-platelet complexes in acute (1-27 d, n = 79) and convalescent (79-725 d, n = 70) ischaemic cerebrovascular disease (CVD) patients compared with controls without CVD (n = 27). We performed a full blood count, and measured plasma levels of soluble P-selectin, soluble E-selectin, and von Willebrand factor antigen (VWF:Ag) as additional markers of platelet and/or endothelial cell activation. The median percentage CD62P expression and the median percentage monocyte-platelet complexes were higher in both acute and convalescent CVD patients than controls (P </= 0.02). The mean white cell count and mean VWF:Ag levels were significantly elevated in the acute and convalescent phases after ischaemic stroke or TIA (P </= 0.02). Otherwise, there was no significant increase in any other marker of platelet or endothelial activation in CVD patients. There was a positive correlation between the percentage expression of CD62P and the percentages of both neutrophil-platelet and monocyte-platelet complexes in the acute phase, and the percentages of all leucocyte-platelet complexes in the convalescent phase after ischaemic CVD. This study provides evidence for ongoing excessive platelet and/or endothelial activation in ischaemic CVD patients despite treatment with antithrombotic therapy.

Acute Disease↗
PubMed2004

Circulating reticulated platelets in the early and late phases after ischaemic stroke and transient ischaemic attack.

The percentage of reticulated platelets (% RP) could be a useful marker of increased platelet production and/or turnover in patients with increased platelet activation, but few flow cytometric studies have measured the % RP in patients with ischaemic cerebrovascular disease (CVD). Whole blood flow cytometry using thiazole orange was performed to compare the % RP in patients in the early (1-27 d, n = 79) and late phases (79-725 d, n = 70) after ischaemic stroke or transient ischaemic attack (TIA) with controls without CVD (n = 27). The impact of aspirin dose escalation (75-300 mg/d) on the % RP was investigated in 10 patients in the late phase after stroke/TIA. The platelet count and mean platelet volume (MPV) were similar in CVD patients and controls. Compared with controls, the unadjusted % RP was not significantly higher in early or late phase CVD patients (P < or = 0.3). However, having adjusted for age, the % RP was higher in early (P = 0.047) and late phase CVD patients (P = 0.01). There was a positive correlation between % RP and MPV in EDTA- and citrate-anticoagulated blood in both early and late phase CVD patients (P< or = 0.01). The % RP was not significantly influenced by aspirin dose. These data do not convincingly support an excessive stimulus to platelet production in the early or late phases after ischaemic stroke/TIA, but are consistent with the hypothesis that reticulated platelets are larger than more mature 'non-reticulated' platelets in ischaemic CVD.

Aged↗