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Ischemic stroke
ORIGINAL RESEARCH
Discrepancy between early neurological course and mid-term outcome in older stroke patients after mechanical thrombectomy Justus F Kleine,1 Tobias Boeckh-Behrens,1 Sascha Prothmann,1 Claus Zimmer,1 Thomas Liebig2 1
Department of Neuroradiology, Technische Universität München, Klinikum Rechts der Isar, München, Germany 2 Department of Neuroradiology, Universitätsklinik Köln, Köln, Germany Correspondence to Dr Justus F Kleine, Abteilung für Neuroradiologie, Klinikum Rechts der Isar, Ismaningerstr 22, 81675 München, Germany; [email protected] Received 17 February 2015 Revised 1 May 2015 Accepted 11 May 2015
ABSTRACT Background Stroke in aged patients has a relatively poor prognosis, even after recanalizing therapy. Potential reasons include mechanisms that relate directly to the extent of brain tissue damage, but also age-dependent factors which are not, or only indirectly, stroke-related, such as pre-existing functional deficits, comorbidities, and post-stroke complications (eg, infections). Objective To compare early neurological course with subsequent functional outcome in older (≥80 years) and younger stroke patients in order to estimate the relative impact of these factors. Specifically, to examine if the strong age-dependency of modified Rankin Scale (mRS) outcome scores in stroke patients after mechanical thrombectomy is paralleled by a similar age dependency of early postinterventional National Institute of Health Stroke Scale (NIHSS) scores—a more specific measure of stroke-induced brain damage. Methods We evaluated technical results, pre- and postinterventional NIHSS scores, mid-term mRS scores and early and overall mortality and their relation to age in 125 patients, 40 of them ≥80 years, with acute middle cerebral artery occlusion, treated by mechanical thrombectomy. Results Technical success, pre- and postinterventional NIHSS scores and early mortality were age-independent. Early neurological improvement depended on successful recanalization, but not on age. Nevertheless, good mRS outcome (mRS 0–2) was much rarer, and overall mortality almost threefold higher in aged patients. Conclusions Older patients exhibit a similar early neurological course and responsiveness to mechanical thrombectomy as younger patients, but this is not reflected in mid-term functional outcome scores. This indicates that post-stroke complications and other factors that are not, or only indirectly, related to the brain tissue damage induced by the incident stroke have a dominant role in their poor prognosis.
INTRODUCTION
To cite: Kleine JF, BoeckhBehrens T, Prothmann S, et al. J NeuroIntervent Surg Published Online First: [please include Day Month Year] doi:10.1136/ neurintsurg-2015-011702
Stroke in patients ≥80 years presently accounts for about one-third of all strokes in developed societies, and this proportion will continue to increase in the upcoming decades.1 Advanced age is associated with relatively poor post-stroke functional outcome, with ‘outcome’ commonly assessed by the modified Rankin Scale (mRS),2 at 3 months after the incident stroke. This negative association holds for all relevant acute treatment modalities, including intravenous thrombolysis,3–5 intra-arterial thrombolysis,6 7 and mechanical thrombectomy
(MTE).8–12 It has important implications for clinical decision-making in individual patients, health economics, and for the design and interpretation of stroke trials. From the comparably poor mRS outcome of older patients, researchers had inferred a high likelihood of ‘futile’ recanalization,8 a relatively unfavorable risk–benefit-ratio,7 11 and relatively poor cost-effectiveness13 of endovascular stroke therapy in this age group. Recent subgroup analyses of the MR CLEAN and ESCAPE trials indicate that MTE with stent retrievers is an effective treatment also for older patients14 15 but their average outcome is still modest, and mortality remains much higher than in younger patients,15 so that further improvement is desirable. However, the poorer mRS outcome of older patients with acute stroke is not necessarily due to the direct negative impact of the stroke-induced brain damage alone. mRS scores are known also to be sensitive to, for example, comorbidities, prestroke physical and cognitive impairment, and medical complications such as infections—that is, factors that are unrelated, or only indirectly related, to the incident stroke.16 17 This may have negligible influence in young patients, in whom any observable post-stroke functional deficit is likely to be caused directly by the incident stroke, but become important in older patients, in whom such conditions are more prevalent and/or graver. The National Institute of Health Stroke Scale (NIHSS) has been designed to assess stroke-induced neurological deficits and reflects functionally relevant brain tissue damage more directly and specifically. Treatment-related effects of acute therapies that are intended to salvage brain tissue at risk— and, correspondingly, also the lack, or age-related limitations, of such effects—may therefore be recognized more clearly in early NIHSS scores than in mid-term mRS scores. Hence, if the relatively poor mRS outcome of older stroke patients after thrombectomy is mainly attributable to more extensive or more severe neurologically relevant brain damage, this should be reflected in age-related differences in neurological scores that parallel the age dependency of mRS outcome data. In this study, we examined this subject by analyzing and comparing technical results, pre- and posttreatment NIHSS scores, subsequent mRS outcome, and early and overall mortality in older and younger stroke patients with acute occlusion of the middle cerebral artery (MCA), treated by MTE.
Kleine JF, et al. J NeuroIntervent Surg 2015;0:1–6. doi:10.1136/neurintsurg-2015-011702
1
Downloaded from http://jnis.bmj.com/ on November 17, 2015 - Published by group.bmj.com
Ischemic stroke PATIENTS AND METHODS Single-center analysis was carried out of all consecutive patients (n=125; age range 18–96 years) with acute, isolated occlusion of the MCA, subjected to MTE between March 2007 and February 2012, including 40 ‘older’ patients (≥80 years). The threshold of 80 years was chosen, because most previous related studies, including recent large trials on MTE (MR CLEAN, ESCAPE), used the same cutoff value.1 3–7 10 14 15 18 19 Formalized data on living conditions and nursing requirements of the patients before the stroke were retrieved from the medical documentation system of our institution, allowing us to identify patients who had been ‘functionally independent at home’, corresponding to pre-stroke mRS scores of 0–2 (table 1). ‘Bridging’ thrombolysis with intravenous recombinant tissue plasminogen activator (rtPA) was applied in 83 patients (66%), approximately equally frequently in older and younger patients (73% and 64%, respectively, p=0.3). MTE, in most cases with stent-retrievers, was performed according to standard techniques described previuosly.20 Data for the technical results, and clinical outcome had been collected prospectively and were retrieved from the large-scale stroke database run by the departments of neurology and neuroradiology of our institution. Alberta Stroke Program Early CT scores (ASPECTS) in pretreatment CT-scans, and post-MTE recanalization status were reassessed by two experienced neuroradiologists blinded to the clinical data. Recanalization was graded according to the Thrombolysis in cerebral Infarction (TICI) scale, with grades 2b/ 3 defined as ‘successful’. NIHSS scores were assessed in all patients at presentation (NIHSS-pre) and after treatment before discharge (NIHSS-post) by trained neurologists. Improvements in post-treatment versus pretreatment NIHSS scores ≥4 and ≥8 were defined as ‘moderate’ and ‘substantial’, respectively. Mid-term mRS scores at ∼90 days were assessed by telephone interview or derived from the formalized documentation of the patient’s rehabilitation centers, by two trained judges blinded to Table 1 Summary of baseline and technical and clinical outcome data Outcome data
Ischemic stroke
ORIGINAL RESEARCH
Discrepancy between early neurological course and mid-term outcome in older stroke patients after mechanical thrombectomy Justus F Kleine,1 Tobias Boeckh-Behrens,1 Sascha Prothmann,1 Claus Zimmer,1 Thomas Liebig2 1
Department of Neuroradiology, Technische Universität München, Klinikum Rechts der Isar, München, Germany 2 Department of Neuroradiology, Universitätsklinik Köln, Köln, Germany Correspondence to Dr Justus F Kleine, Abteilung für Neuroradiologie, Klinikum Rechts der Isar, Ismaningerstr 22, 81675 München, Germany; [email protected] Received 17 February 2015 Revised 1 May 2015 Accepted 11 May 2015
ABSTRACT Background Stroke in aged patients has a relatively poor prognosis, even after recanalizing therapy. Potential reasons include mechanisms that relate directly to the extent of brain tissue damage, but also age-dependent factors which are not, or only indirectly, stroke-related, such as pre-existing functional deficits, comorbidities, and post-stroke complications (eg, infections). Objective To compare early neurological course with subsequent functional outcome in older (≥80 years) and younger stroke patients in order to estimate the relative impact of these factors. Specifically, to examine if the strong age-dependency of modified Rankin Scale (mRS) outcome scores in stroke patients after mechanical thrombectomy is paralleled by a similar age dependency of early postinterventional National Institute of Health Stroke Scale (NIHSS) scores—a more specific measure of stroke-induced brain damage. Methods We evaluated technical results, pre- and postinterventional NIHSS scores, mid-term mRS scores and early and overall mortality and their relation to age in 125 patients, 40 of them ≥80 years, with acute middle cerebral artery occlusion, treated by mechanical thrombectomy. Results Technical success, pre- and postinterventional NIHSS scores and early mortality were age-independent. Early neurological improvement depended on successful recanalization, but not on age. Nevertheless, good mRS outcome (mRS 0–2) was much rarer, and overall mortality almost threefold higher in aged patients. Conclusions Older patients exhibit a similar early neurological course and responsiveness to mechanical thrombectomy as younger patients, but this is not reflected in mid-term functional outcome scores. This indicates that post-stroke complications and other factors that are not, or only indirectly, related to the brain tissue damage induced by the incident stroke have a dominant role in their poor prognosis.
INTRODUCTION
To cite: Kleine JF, BoeckhBehrens T, Prothmann S, et al. J NeuroIntervent Surg Published Online First: [please include Day Month Year] doi:10.1136/ neurintsurg-2015-011702
Stroke in patients ≥80 years presently accounts for about one-third of all strokes in developed societies, and this proportion will continue to increase in the upcoming decades.1 Advanced age is associated with relatively poor post-stroke functional outcome, with ‘outcome’ commonly assessed by the modified Rankin Scale (mRS),2 at 3 months after the incident stroke. This negative association holds for all relevant acute treatment modalities, including intravenous thrombolysis,3–5 intra-arterial thrombolysis,6 7 and mechanical thrombectomy
(MTE).8–12 It has important implications for clinical decision-making in individual patients, health economics, and for the design and interpretation of stroke trials. From the comparably poor mRS outcome of older patients, researchers had inferred a high likelihood of ‘futile’ recanalization,8 a relatively unfavorable risk–benefit-ratio,7 11 and relatively poor cost-effectiveness13 of endovascular stroke therapy in this age group. Recent subgroup analyses of the MR CLEAN and ESCAPE trials indicate that MTE with stent retrievers is an effective treatment also for older patients14 15 but their average outcome is still modest, and mortality remains much higher than in younger patients,15 so that further improvement is desirable. However, the poorer mRS outcome of older patients with acute stroke is not necessarily due to the direct negative impact of the stroke-induced brain damage alone. mRS scores are known also to be sensitive to, for example, comorbidities, prestroke physical and cognitive impairment, and medical complications such as infections—that is, factors that are unrelated, or only indirectly related, to the incident stroke.16 17 This may have negligible influence in young patients, in whom any observable post-stroke functional deficit is likely to be caused directly by the incident stroke, but become important in older patients, in whom such conditions are more prevalent and/or graver. The National Institute of Health Stroke Scale (NIHSS) has been designed to assess stroke-induced neurological deficits and reflects functionally relevant brain tissue damage more directly and specifically. Treatment-related effects of acute therapies that are intended to salvage brain tissue at risk— and, correspondingly, also the lack, or age-related limitations, of such effects—may therefore be recognized more clearly in early NIHSS scores than in mid-term mRS scores. Hence, if the relatively poor mRS outcome of older stroke patients after thrombectomy is mainly attributable to more extensive or more severe neurologically relevant brain damage, this should be reflected in age-related differences in neurological scores that parallel the age dependency of mRS outcome data. In this study, we examined this subject by analyzing and comparing technical results, pre- and posttreatment NIHSS scores, subsequent mRS outcome, and early and overall mortality in older and younger stroke patients with acute occlusion of the middle cerebral artery (MCA), treated by MTE.
Kleine JF, et al. J NeuroIntervent Surg 2015;0:1–6. doi:10.1136/neurintsurg-2015-011702
1
Downloaded from http://jnis.bmj.com/ on November 17, 2015 - Published by group.bmj.com
Ischemic stroke PATIENTS AND METHODS Single-center analysis was carried out of all consecutive patients (n=125; age range 18–96 years) with acute, isolated occlusion of the MCA, subjected to MTE between March 2007 and February 2012, including 40 ‘older’ patients (≥80 years). The threshold of 80 years was chosen, because most previous related studies, including recent large trials on MTE (MR CLEAN, ESCAPE), used the same cutoff value.1 3–7 10 14 15 18 19 Formalized data on living conditions and nursing requirements of the patients before the stroke were retrieved from the medical documentation system of our institution, allowing us to identify patients who had been ‘functionally independent at home’, corresponding to pre-stroke mRS scores of 0–2 (table 1). ‘Bridging’ thrombolysis with intravenous recombinant tissue plasminogen activator (rtPA) was applied in 83 patients (66%), approximately equally frequently in older and younger patients (73% and 64%, respectively, p=0.3). MTE, in most cases with stent-retrievers, was performed according to standard techniques described previuosly.20 Data for the technical results, and clinical outcome had been collected prospectively and were retrieved from the large-scale stroke database run by the departments of neurology and neuroradiology of our institution. Alberta Stroke Program Early CT scores (ASPECTS) in pretreatment CT-scans, and post-MTE recanalization status were reassessed by two experienced neuroradiologists blinded to the clinical data. Recanalization was graded according to the Thrombolysis in cerebral Infarction (TICI) scale, with grades 2b/ 3 defined as ‘successful’. NIHSS scores were assessed in all patients at presentation (NIHSS-pre) and after treatment before discharge (NIHSS-post) by trained neurologists. Improvements in post-treatment versus pretreatment NIHSS scores ≥4 and ≥8 were defined as ‘moderate’ and ‘substantial’, respectively. Mid-term mRS scores at ∼90 days were assessed by telephone interview or derived from the formalized documentation of the patient’s rehabilitation centers, by two trained judges blinded to Table 1 Summary of baseline and technical and clinical outcome data Outcome data
