Smriti Agarwal

Does perfusion computed tomography facilitate clinical decision making for thrombolysis in unselected acute patients with suspected ischaemic stroke

Background: 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. Methods: 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 ĸ 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. Results: Inter-rater agreement was moderate (ĸ = 0.54) for early ischaemic change on NCCT. Perfusion maps improved this to substantial for cerebral blood volume (ĸ = 0.67) and to almost perfect for time to peak (ĸ = 0.87) and cerebral blood flow (ĸ = 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). Conclusions: 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.

Thrombolysis Delivery by a Regional Telestroke Network—Experience From the UK National Health Service

Background 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. Methods and Results 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%. Conclusions 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.

Interaction of age with the ischaemic penumbra, leptomeningeal collateral circulation and haemodynamic variables in acute stroke: a pilot study

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 (Kendalls τ b=−0.234, p=0.048) and lesion volume (Kendalls τ b=0.238, p=0.045), core volume remained unchanged, accompanied by an incremental collateral response with age (Kendalls 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.

Collateral response modulates the time–penumbra relationship in proximal arterial occlusions

Objective While clinical benefit from thrombolysis decreases with increase in time from stroke onset, the relationship of acute physiologic tissue compartments and collateral response to stroke onset time remains unclear. Methods We studied consecutive patients with proximal arterial occlusions (n = 355) with whole-brain perfusion CT with CT angiography within 6 hours of stroke onset. Penumbra and core were defined using voxel-based thresholds. Tissue mismatch was defined as the ratio of penumbra to core. Collateral scores were assessed using a previously validated visual score. Results Mean (SD) age was 72.1 (12.4) years, median (interquartile range) NIH Stroke Scale score 16 (4), mean (SD) time to imaging 152.5 (69.7) minutes. Penumbra volume (Spearman ρ = 0.119, p = 0.026) and mismatch increased (Spearman ρ = 0.115, p = 0.030) with time from onset. Core volume decreased (Spearman ρ = −0.112, p = 0.035) while collateral scores increased with time (Spearman ρ = 0.117, p = 0.028). On multivariable regression, good collateral scores predicted longer time since onset (β = 0.101, p = 0.039) while mismatch was not a predictor (β = 0.001, p = 0.351). Good collateral score was the strongest independent predictor of final infarct volume and improvement in clinical deficit. Conclusions In our large patient cohort study of proximal arterial occlusions, we found an incremental collateral response and preserved penumbral volume with time. Thus, tissue viability can be maintained in this time window (0–6 hours) after stroke if leptomeningeal collaterals are able to sustain the penumbra. Our findings suggest that a longer therapeutic window may exist for intra-arterial intervention and that multimodal imaging may have a role in strokes of unknown onset time.

Is CT-Based Perfusion and Collateral Imaging Sensitive to Time Since Stroke Onset?

Purpose CT-based perfusion and collateral imaging is increasingly used in the assessment of patients with acute stroke. Time of stroke onset is a critical factor in determining eligibility for and benefit from thrombolysis. Animal studies predict that the volume of ischemic penumbra decreases with time. Here, we evaluate if CT is able to detect a relationship between perfusion or collateral status, as assessed by CT, and time since stroke onset. Materials and methods We studied 53 consecutive patients with proximal vessel occlusions, mean (SD) age of 71.3 (14.9) years, at a mean (SD) of 125.2 (55.3) minutes from onset, using whole-brain CT perfusion (CTp) imaging. Penumbra was defined using voxel-based thresholds for cerebral blood flow (CBF) and mean transit time (MTT); core was defined by cerebral blood volume (CBV). Normalized penumbra fraction was calculated as Penumbra volume/(Penumbra volume + Core volume) for both CBF and MTT (PenCBF and PenMTT, respectively). Collaterals were assessed on CT angiography (CTA). CTp ASPECTS score was applied visually, lower scores indicating larger lesions. ASPECTS ratios were calculated corresponding to penumbra fractions. Results Both PenCBF and PenMTT showed decremental trends with increasing time since onset (Kendall’s tau-b = −0.196, p = 0.055, and −0.187, p = 0.068, respectively). The CBF/CBV ASPECTS ratio, which showed a relationship to PenCBF (Kendall’s tau-b = 0.190, p = 0.070), decreased with increasing time since onset (Kendall’s tau-b = −0.265, p = 0.006). Collateral response did not relate to time (Kendall’s tau-b = −0.039, p = 0.724). Conclusion Even within 4.5 h since stroke onset, a decremental relationship between penumbra and time, but not between collateral status and time, may be detected using perfusion CT imaging. The trends that we demonstrate merit evaluation in larger datasets to confirm our results, which may have potential wider applications, e.g., in the setting of strokes of unknown onset time.

Dominant hemisphere functional networks compensate for structural connectivity loss to preserve phonological retrieval with aging.

Loss of hemispheric asymmetry during cognitive tasks has been previously demonstrated in the literature. In the context of language, increased right hemisphere activation is observed with aging. Whether this relates to compensation to preserve cognitive function or dedifferentiation implying loss of hemispheric specificity without functional consequence, remains unclear.

Etiologic investigation of ischemic stroke in young adults

# {#article-title-2} To the Editor: We read with interest the article by Larrue et al.1 We recently assessed the impact of newer stroke classification systems on stroke subtypes.2 We also agree with the conclusion regarding the contribution of atrial septal abnormalities to stroke in younger people. Despite the thorough cardiac investigation, Larrue et al. report a relatively low proportion of patients with unexplained stroke with patent foramen ovale (PFO). Of 160 cases investigated, 67 (41.2%) had a PFO (24 isolated, 43 with an atrial septal aneurysm [ASA]). In our institution, of those with …

PO.12 Perfusion CT based thrombolysis in acute ischaemic stroke

Background Despite use in clinical practice and trials of thrombolysis, a non-contrast CT is not sensitive for identifying penumbral tissue in acute stroke. This study evaluated how it compares with physiological imaging using CT perfusion. Methods 40 imaging datasets with non-contrast CT (NCCT) and perfusion CT (CTP) were retrospectively identified. 2 sets of observers (n=6) and a neuroradiologist made a blind evaluation of the images. Inter-observer agreement was calculated for identifying ischaemic change on NCCT, and abnormalities on cerebral blood flow, time to peak and cerebral blood volume maps. A prospective cohort of 73 patients with anterior circulation cortical strokes were thrombolysed based on qualitative assessment of penumbral tissue on CTP within 3 h of stroke onset. Functional outcome was assessed at 3 months. Results Inter-rater agreement was moderate (k=0.54) for early ischaemic change on NCCT. Perfusion maps improved this to substantial for deficit in cerebral blood volume (k=0.67) and almost perfect for time to peak and cerebral blood flow (both k=0.87). In the prospective arm, 58.9% of patients with cortical strokes were thrombolysed. There was no significant difference in attainment of complete recovery (p=0.184) between the thrombolysed and non-thrombolysed group. Conclusions We demonstrate how perfusion CT aids clinical decision-making in acute stroke. Good functional outcomes from thrombolysis can be safely achieved using this physiologically informed approach.