[show abstract][hide abstract] ABSTRACT: The majority of established telestroke services are based on "hub-and-spoke" models for providing acute clinical assessment and thrombolysis. We report results from the first year of the successful implementation of a locally based telemedicine network, without the need of 1 or more hub hospitals, across a largely rural landscape.
Following a successful pilot phase that demonstrated safety and feasibility, the East of England telestroke project was rolled out across 7 regional hospitals, covering an area of 7500 square miles and a population of 5.6 million to enable out-of-hours access to thrombolysis. Between November 2010 and November 2011, 142 telemedicine consultations were recorded out-of-hours. Seventy-four (52.11%) cases received thrombolysis. Median (IQR) onset-to-needle and door-to-needle times were 169 (141.5 to 201.5) minutes and 94 (72 to 113.5) minutes, respectively. Symptomatic hemorrhage rate was 7.3% and stroke mimic rate was 10.6%.
We demonstrate the safety and effectiveness of a horizontal networking approach for stroke telemedicine, which may be applicable to areas where traditional "hub-and-spoke" models may not be geographically feasible.
Journal of the American Heart Association. 01/2014; 3(1):e000408.
[show abstract][hide abstract] ABSTRACT: Mapping the ischaemic penumbra in acute stroke is of considerable clinical interest. For this purpose, mapping tissue hypoxia with (18)F-misonidazole (FMISO) PET is attractive, and is straightforward compared to (15)O PET. Given the current emphasis on penumbra imaging using diffusion/perfusion MR or CT perfusion, investigating the relationships between FMISO uptake and abnormalities with these modalities is important.
According to a prospective design, three patients (age 54-81 years; admission NIH stroke scale scores 16-22) with an anterior circulation stroke and extensive penumbra on CT- or MR-based perfusion imaging successfully completed FMISO PET, diffusion-weighted imaging and MR angiography 6-26 h after stroke onset, and follow-up FLAIR to map the final infarction. All had persistent proximal occlusion and a poor outcome despite thrombolysis. Significant FMISO trapping was defined voxel-wise relative to ten age-matched controls and mapped onto coregistered maps of the penumbra and irreversibly damaged ischaemic core.
FMISO trapping was present in all patients (volume range 18-119 ml) and overlapped mainly with the penumbra but also with the core in each patient. There was a significant (p ≤ 0.001) correlation in the expected direction between FMISO uptake and perfusion, with a sharp FMISO uptake bend around the expected penumbra threshold.
FMISO uptake had the expected overlap with the penumbra and relationship with local perfusion. However, consistent with recent animal data, our study suggests FMISO trapping may not be specific to the penumbra. If confirmed in larger samples, this preliminary finding would have potential implications for the clinical application of FMISO PET in acute ischaemic stroke.
European Journal of Nuclear Medicine 10/2013; · 4.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: After stroke, penumbral salvage determines clinical recovery. However, the rescued penumbra may be affected by selective neuronal loss, as documented both histopathologically in animals and using the validated in vivo positron emission tomography marker (11)C-flumazenil in humans. However, whether the non-infarcted penumbra is capable of neuronal activation, and how selective neuronal loss may interfere, is unknown. Here we prospectively mapped the topographical relationships between functional magnetic resonance imaging responses and non-infarcted penumbra, and tested the hypothesis that the former do take place in the latter, but only in its subsets spared selective neuronal loss. Seven patients (mean age 74 years; three thrombolysed) with first-ever acute anterior circulation stroke, presence of penumbra on computed tomography perfusion performed within 6 h of onset, and substantial deficit on admission but good outcome at 1-3 months (National Institute of Health Stroke Score range 6-13 and 0-1, respectively, P = 0.001), were studied. At follow-up, patients underwent structural magnetic resonance imaging to map the infarct, functional magnetic resonance imaging (three tasks selected to probe the right or left hemisphere), and (11)C-flumazenil positron emission tomography generating binding potential maps. Patients with significant carotid or middle-cerebral artery disease or impaired vasoreactivity were excluded. Following image coregistration, the non-infarcted penumbra comprised all acutely ischaemic voxels (identified on acute computed tomography perfusion using previously validated thresholds) not part of the final infarct. To test our hypotheses, the overlap between functional magnetic resonance imaging activation clusters and non-infarcted penumbra was mapped, and binding potential values then computed both within and outside this overlap. In addition, the overlap between functional magnetic resonance imaging activation clusters and areas of significantly reduced binding potential (determined using Statistical Parametric Mapping against 16 age-matched control subjects) was assessed in each patient. An overlap between non-infarcted penumbra and functional magnetic resonance imaging clusters was present in seven of seven patients, substantial in four. Binding potential was significantly reduced in the whole non-infarcted penumbra (P < 0.01) but not within the functional magnetic resonance imaging overlap. Clusters with significantly reduced binding potential showed virtually no overlap with functional magnetic resonance imaging activation compared with 12 age-matched controls (P = 0.04).The results from this proof of principle study suggest that 1-3 months after stroke the non-infarcted penumbra is capable of neuronal activation, consistent with its established role in recovery of neurological functions. However, although the non-infarcted penumbra as a whole was affected by selective neuronal loss, activations tended to occur within portions spared selective neuronal loss, suggesting the latter impedes neuronal activation. Although its clinical correlates are still elusive, selective neuronal loss may represent a novel therapeutic target in the aftermath of ischaemic stroke.
[show abstract][hide abstract] ABSTRACT: OBJECTIVES: The usefulness of the implantable loop recorder (ILR) with improved atrial fibrillation (AF) detection capability (Reveal XT) and the factors associated with AF in the setting of unexplained stroke were investigated. METHODS: A cohort study is reported of 51 patients in whom ILRs were implanted for the investigation of ischemic stroke for which no cause had been found (cryptogenic) following appropriate vascular and cardiac imaging and at least 24 hours of cardiac rhythm monitoring. RESULTS: The patients were aged from 17 to 73 (median 52) years. Of the 30 patients with a shunt investigation, 22 had a patent foramen ovale (73.3%; 95% confidence interval [CI] 56.5%-90.1%). AF was identified in 13 (25.5%; 95% CI 13.1%-37.9%) cases. AF was associated with increasing age (p = 0.018), interatrial conduction block (p = 0.02), left atrial volume (p = 0.025), and the occurrence of atrial premature contractions on preceding external monitoring (p = 0.004). The median (range) of monitoring prior to AF detection was 48 (0-154) days. CONCLUSION: In patients with unexplained stroke, AF was detected by ILR in 25.5%. Predictors of AF were identified, which may help to target investigations. ILRs may have a central role in the future in the investigation of patients with unexplained stroke.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Increasing age is the single largest non-modifiable risk factor for ischaemic stroke. Animal models have substantiated the view that age related neuron vulnerability to ischaemia plays a role in stroke and other age related neurological diseases. Given the key role of the ischaemic penumbra in stroke pathophysiology, we hypothesised that age has an impact on penumbral tissue and its acute determinants. METHODS: We studied a prospective cohort of patients (n=39) at a mean time of 154.7 min from stroke onset, using state of the art whole brain perfusion CT and CT angiography. Penumbral and core were defined using quantitative voxel based thresholds for mean transit time and cerebral blood volume (CBV). Collateral vessel scores were assessed and haemodynamic variables (ie, cerebral blood flow and CBV) were measured in affected and unaffected tissues. RESULTS: While age correlated negatively with normalised penumbral volume (Kendall's τ b=-0.234, p=0.048) and lesion volume (Kendall's τ b=0.238, p=0.045), core volume remained unchanged, accompanied by an incremental collateral response with age (Kendall's τ b=0.496, p<0.0001). Haemodynamic variables remained unaffected by age in our cohort. CONCLUSIONS: These findings, described for the first time in a clinical cohort using whole brain CT perfusion and concomitant vascular imaging, suggest that age has a differential effect on acute tissue compartments in the wake of a preserved collateral vascular response and haemodynamic parameters. In agreement with the preclinical literature, the results point to a distinct tissue response to acute ischaemia in the ageing brain and merit validation studies in larger cohorts, particularly in relation to clinical outcomes.
Journal of neurology, neurosurgery, and psychiatry 11/2012; · 4.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Age has a differential effect on cognition, with word retrieval being one of the cognitive domains most affected by aging. This study examined the functional and structural neural correlates of phonological word retrieval in younger and older adults using word and picture rhyme judgment tasks. Although the behavioral performance in the fMRI task was similar for the two age groups, the older adults had increased activation in the right pars triangularis across tasks and in the right pars orbitalis for the word task only. Increased activation together with preserved performance in the older participants would suggest that increased activation was related to compensatory processing. We validated this hypothesis by showing that right pars triangularis activation during correct rhyme judgments was highest in participants who made overall more errors, therefore being most error-prone. Our findings demonstrate that the effect of aging differ in adjacent but distinct right inferior frontal regions. The differential effect of age on word and picture tasks also provides new clues to the level of processing that is most affected by age in speech production tasks. Specifically, we suggest that right inferior frontal activation in older participants is needed to inhibit errors.
Journal of Cognitive Neuroscience 07/2012; 24(11):2135-46. · 4.49 Impact Factor
[show abstract][hide abstract] ABSTRACT: Studies attempting to map post-stroke cognitive or motor symptoms to lesion location have been available in the literature for over 150 years. In the last two decades, two computational techniques have been developed to identify the lesion sites associated with behavioural impairments. Voxel Based Morphometry (VBM) has now been used extensively for this purpose in many different patient populations. More recently, Voxel-based Lesion Symptom Mapping (VLSM) was developed specifically for the purpose of identifying lesion-symptom relationships in stroke patients, and has been used extensively to study, among others functions, language, motor abilities and attention. However, no studies have compared the results of these two techniques so far. In this study we compared VLSM and VBM in a cohort of 20 patients with chronic post-stroke aphasia. Comparison of the two techniques showed overlap in regions previously found to be relevant for the tasks used, suggesting that using both techniques and looking for overlaps between them can increase the reliability of the results obtained. However, overall VBM and VLSM provided only partially concordant results and the differences between the two techniques are discussed.
[show abstract][hide abstract] ABSTRACT: The neural correlates of inner speech have been investigated previously using functional imaging. However, methodological and other limitations have so far precluded a clear description of the neural anatomy of inner speech and its relation to overt speech. Specifically, studies that examine only inner speech often fail to control for subjects' behaviour in the scanner and therefore cannot determine the relation between inner and overt speech. Functional imaging studies comparing inner and overt speech have not produced replicable results and some have similar methodological caveats as studies looking only at inner speech. Lesion analysis can avoid the methodological pitfalls associated with using inner and overt speech in functional imaging studies, while at the same time providing important data about the neural correlates essential for the specific function. Despite its advantages, a study of the neural correlates of inner speech using lesion analysis has not been carried out before. In this study, 17 patients with chronic post-stroke aphasia performed inner speech tasks (rhyme and homophone judgements), and overt speech tasks (reading aloud). The relationship between brain structure and language ability was studied using voxel-based lesion-symptom mapping. This showed that inner speech abilities were affected by lesions to the left pars opercularis in the inferior frontal gyrus and to the white matter adjacent to the left supramarginal gyrus, over and above overt speech production and working memory. These results suggest that inner speech cannot be assumed to be simply overt speech without a motor component. It also suggests that the use of overt speech to understand inner speech and vice versa might result in misleading conclusions, both in imaging studies and clinical practice.
[show abstract][hide abstract] ABSTRACT: Despite use in clinical practice and major positive trials of thrombolysis, non-contrast computed tomography (NCCT) is not sensitive for identifying penumbral tissue in acute stroke. This study evaluated how physiological imaging using CT perfusion (CTP) could add to the diagnostic utility of an NCCT and inform clinical decisions regarding thrombolysis.
Forty imaging datasets containing NCCT and CTP were retrospectively identified from a cohort of consecutive acute stroke patients. Two sets of observers (n = 6) and a neuroradiologist evaluated the images without knowledge of clinical symptoms. Inter-observer agreement was calculated using the κ statistic for identifying acute ischaemic change on NCCT: perfusion abnormalities (namely cerebral blood volume, cerebral blood flow and time to peak), and penumbral tissue on perfusion maps obtained by two image processing algorithms.
Inter-rater agreement was moderate (κ = 0.54) for early ischaemic change on NCCT. Perfusion maps improved this to substantial for cerebral blood volume (κ = 0.67) and to almost perfect for time to peak (κ = 0.87) and cerebral blood flow (κ = 0.87). The agreement for qualitative assessment of penumbral tissue was substantial to perfect for images obtained using the two different perfusion algorithms. Overall, there was a high rate of decision to thrombolyse based on NCCT (81.25%). CTP strengthened the decision to thrombolyse based on NCCT in 38.3% of cases. It negatively influenced the decision in 14.6% of cases, this being significantly more common in experienced observers (p = 0.02).
We demonstrate that the qualitative evaluation of CTP produces near perfect inter-observer agreement, regardless of the post-processing method used. CTP is a reliable, accessible and practical imaging modality that improves confidence in reaching the appropriate diagnosis. It is particularly useful for less experienced clinicians, to arrive at a physiologically informed treatment decision.
[show abstract][hide abstract] ABSTRACT: Deep watershed infarcts are frequent in high-grade carotid disease and are thought to result from hemodynamic impairment, particularly when adopting a rosary-like pattern. However, a role for microembolism has also been suggested, though never directly tested. Here, we studied the relationships among microembolic signals (MES) on transcranial Doppler, rosary-like deep watershed infarcts on brain imaging, and cerebral hemodynamic compromise on positron emission tomography (PET), all in severe symptomatic carotid disease. We hypothesized that rosary-like infarcts would be significantly associated with worse hemodynamic status, independent of the presence of MES.
Sixteen patients with ≥70% carotid disease ipsilateral to recent transient ischemic attack/minor stroke underwent magnetic resonance imaging including diffusion-weighted imaging, (15)O-PET, and transcranial Doppler. Mean transit time, a specific marker for hemodynamic impairment, was obtained in the symptomatic and unaffected hemispheres.
Eleven of 16 patients had rosary-like infarcts (Rosary+) and 8 patients had MES. Mean transit time was significantly higher (P=0.008) in Rosary+ patients than in healthy controls (n=10), and prevalence of MES was not different between Rosary+ and Rosary- patients. Contrary to our hypothesis, however, the presence of MES within the Rosary+ subset was associated (P=0.03) with a better hemodynamic status than in their absence, with a significant (P=0.02) negative correlation between mean transit time and rate of MES/h.
Contrary to mainstream understanding, rosary-like infarcts were not independent of presence and rate of MES, suggesting that microembolism plays a role in their pathogenesis, probably in association with hemodynamic impairment. Pending confirmation in a larger sample, these findings have management implications for patients with carotid disease and rosary-like infarcts.
[show abstract][hide abstract] ABSTRACT: There is ample evidence that in anterior circulation stroke, the diffusion-weighted imaging (DWI) lesion may escape infarction and thus is not a reliable infarct predictor. In this study, we assessed the predictive value of the mean transit time (MTT) for final infarction within the DWI lesion, first in patients scanned back-to-back with 15O-positron emission tomography and MR (DWI and perfusion-weighted imaging; "Cambridge sample") within 7 to 21 hours of clinical onset, then in a large sample of patients with anterior circulation stroke receiving DWI and perfusion-weighted imaging within 12 hours (85% within 6 hours; "I-KNOW sample").
Both samples underwent structural MRI at approximately 1 month to map final infarcts. For both imaging modalities, MTT was calculated as cerebral blood volume/cerebral blood flow. After image coregistration and matrix resampling, the MTT values between voxels of interest that later infarcted or not were compared separately within and outside DWI lesions (DWI+ and DWI-, respectively) both within and across patients. In the I-KNOW sample, receiver operating characteristic curves were calculated for these voxel of interest populations and areas under the curve and optimal thresholds calculated.
In the Cambridge data set (n=4), there was good concordance between predictive values of MTT (positron emission tomography) and MTT (perfusion-weighted imaging) for both DWI+ and DWI- voxels of interest indicating adequate reliability of MTT (perfusion-weighted imaging) for this purpose. In the I-KNOW data set (N=42), the MTT significantly added to the DWI lesion to predict infarction in both DWI- and DWI+ voxels of interest with areas under the curve approximately 0.78 and 0.64 (both P<0.001) and optimal thresholds approximately 8 seconds and 11 seconds, respectively.
Despite the relatively small samples, this study suggests that adding MTT (perfusion-weighted imaging) may improve infarct prediction not only as already known outside, but also within, DWI lesions.
[show abstract][hide abstract] ABSTRACT: There is considerable intersubject variability in early neurological course after anterior circulation stroke, yet the pathophysiology underlying this variability is not fully understood. Here, we hypothesize that, although not predicted by current pathophysiological models, infarction of 'non-core-non-penumbral' (i.e. clinically silent) brain tissue may nevertheless occur, and negatively influence clinical course over and above the established positive impact of penumbral salvage. In order to test this hypothesis, non-core-non-penumbral tissue was identified in two independent prospectively recruited cohorts, using computed tomography perfusion, and magnetic resonance perfusion- and diffusion-weighted imaging, respectively. Follow-up structural magnetic resonance imaging was obtained about 1 month later in all patients to map the final infarct. The volumes of both the acutely silent but eventually infarcted tissue, and the eventually non-infarcted penumbra, were determined by performing voxel-wise analysis of the acute and follow-up image sets, using previously validated perfusion thresholds. Early neurological course was expressed as change in National Institutes of Health Stroke Scale scores between the acute and 1-month assessments, relative to the acute score. The relationship between the acutely silent but eventually infarcted tissue volume and early neurological course was tested using a multivariate regression model that included the volume of non-infarcted penumbra. Thirty-four and 58 patients were recruited in the computed tomography perfusion and magnetic resonance perfusion cohorts, respectively (mean onset-to-imaging time: 136 and 156 min; 27 and 42 patients received intravenous thrombolysis, respectively). Infarction of acutely silent tissue was identified in most patients in both cohorts. Although its volume (median 0.2 and 2 ml, respectively) was much smaller than that of salvaged penumbra (59.3 and 93 ml, respectively), it was substantial in ∼10% of patients. As expected, salvaged penumbra strongly positively influenced early neurological course. Even after correcting for the latter effect in the multivariate model, infarction of acutely silent tissue independently negatively influenced early neurological course in both cohorts (P=0.018 and 0.031, respectively). This is the first systematic study to document infarction of acutely silent tissue after anterior circulation stroke, and to show that it affects a sizeable fraction of patients and has the predicted negative impact on clinical course. These findings were replicated in two independent cohorts, regardless of the perfusion imaging modality used. Preventing infarction of the tissue not initially at risk should have direct clinical benefit.
[show abstract][hide abstract] ABSTRACT: Background: Diffusion tensor imaging (DTI) is an emerging research technique that is used to map and characterise white matter tracts in the healthy and damaged brain.Aims: The aim of this paper is to familiarise the readers with DTI while giving the tools to understand and evaluate recent developments in aphasia research that use DTI methodology.Main Contribution: Principles of DTI technology as well as its main caveats are described. An overview of studies that used DTI to explore the language system and aphasia is given. Future directions and the potential contribution of DTI to the understanding of aphasia diagnosis and recovery are highlighted.Conclusions: DTI is an emerging technology, increasingly being applied to further our understanding of aphasia and its recovery. So far it has contributed to our knowledge in four areas of research. In the area of brain anatomy it is used to redefine the borders between various parts of the cortex based on their structural connectivity, to acquire a more accurate map of the tracts connecting the various parts of the language system, and to measure hemispheric asymmetry. Future studies might be able to further our understanding of language anatomy and relate hemispheric asymmetry to recovery potential. Second, DTI can help in relating structure to function. So far many studies focused on repetition deficits and conduction aphasia. Future studies can explore the anatomy of other language deficits. Third, DTI has been used in the study of brain damage and recovery. Studies have documented the damage that occurs to white matter following stroke and other insults, and the spontaneous reorganisation that follows. In the future DTI might contribute to the debate about the role of the right hemisphere in recovery from aphasia. Lastly, in the area of aphasia rehabilitation there is great lack of data. The studies reviewed here have shown that rehabilitation potential is dependent on white matter integrity and that white matter changes can occur as a result of therapy. Future studies should further our understanding of the role of white matter integrity in recovery, therefore contributing to the question of why some patients show good recovery while others do not. Future studies should also try and map white matter changes that are associated with successful versus unsuccessful rehabilitation, and with different stages of recovery.
[show abstract][hide abstract] ABSTRACT: Background: Patients with aphasia often complain that there is a poor correlation between the words they think (inner speech) and the words they say (overt speech).Aims: This study tried to characterise the relation between inner speech and overt speech in post-stroke aphasia.Methods & Procedures: We tested language abilities, speech apraxia, and performance on inner speech tasks, including homophone and rhyme judgements, of 27 patients with chronic post-stroke aphasia.Outcomes & Results: The patients with aphasia were distributed across the entire spectrum of abilities related to both inner and overt speech. For most patients, performance levels of inner and overt speech were similar. However, some patients had relatively better-preserved inner speech with a marked deficit in overt speech, while in others the opposite pattern was observed.Conclusions: The results are discussed within the framework of current models of language, and their implications for language therapy and aphasia diagnosis are outlined.
[show abstract][hide abstract] ABSTRACT: Telemedicine refers to the transfer of medical information from one site to another using distance communications technology. This approach has benefitted many medical specialties, with telestroke being a prelude to its applications in neurology. Our review will focus on the use of telemedicine in neurological practice (teleneurology) following a brief discussion of telestroke. Given the emerging nature of trial evidence in teleneurology, our aim is to provide a narrative review and highlight areas that merit further investigation.
Journal of Neurology 02/2011; 258(6):971-81. · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: Stroke is the third leading cause of death in developed countries and the leading cause of long-term disability worldwide. A series of national stroke audits in the UK highlighted the differences in stroke care between hospitals. The study aims to describe variation in outcomes following stroke and to identify the characteristics of services that are associated with better outcomes, after accounting for case mix differences and individual prognostic factors.
We will conduct a cohort study in eight acute NHS trusts within East of England, with at least one year of follow-up after stroke. The study population will be a systematically selected representative sample of patients admitted with stroke during the study period, recruited within each hospital. We will collect individual patient data on prognostic characteristics, health care received, outcomes and costs of care and we will also record relevant characteristics of each provider organisation. The determinants of one year outcome including patient reported outcome will be assessed statistically with proportional hazards regression models. Self (or proxy) completed EuroQol (EQ-5D) questionnaires will measure quality of life at baseline and follow-up for cost utility analyses.
This study will provide observational data about health service factors associated with variations in patient outcomes and health care costs following hospital admission for acute stroke. This will form the basis for future RCTs by identifying promising health service interventions, assessing the feasibility of recruiting and following up trial patients, and provide evidence about frequency and variances in outcomes, and intra-cluster correlation of outcomes, for sample size calculations. The results will inform clinicians, public, service providers, commissioners and policy makers to drive further improvement in health services which will bring direct benefit to the patients.
BMC Health Services Research 02/2011; 11:50. · 1.77 Impact Factor