Acta Neurol Scand DOI: 10.1111/ane.12399
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Predictors of progression in patients presenting with minor subcortical stroke Nannoni S, Del Bene A, Palumbo V, Petrone L, Sottile F, Pracucci G, Inzitari D. Predictors of progression in patients presenting with minor subcortical stroke. Acta Neurol Scand: DOI: 10.1111/ane.12399. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives – Early neurological worsening is common in minor subcortical strokes (SS) and may lead to a poor outcome. We aimed to describe clinical and imaging features associated with progression. Material and methods – Consecutive patients with SS were divided into progressive and non-progressive. Progression was defined as an increase of NIHSS motor score ≥1 point within 72 h from onset. Vascular risk factors and imaging features (vascular territory, size and number of slices in which the lesion was visible, the presence of leukoaraiosis) were compared in the two groups. We investigated potential independent determinants of progression using stepwise logistic regression. Results – Thirty of 94 patients (31.9%) underwent progression. The distribution of vascular risk factors did not differ significantly between the two groups. Increasing number of risk factors was associated with a higher risk of progression (OR 2.2; 95% CI 1.1–4.5). Patients who progressed were more likely to have a lesion ≥15 mm in diameter (P = 0.004) or a lesion visible ≥3 slices (P = 0.007). After logistic regression stepwise adjustment for all the considered potential determinants, diameter ≥15 mm and severe leukoaraiosis proved to be independently associated with neurological worsening (OR = 6.3, 95% CI 2.0–19.6 and OR = 5.9, 95% CI 1.3–25.7, respectively). Conclusion – In a series of consecutive SS, early neurological worsening was associated with a high vascular risk profile, a larger infarct size and the presence of severe leukoaraiosis. Based on the knowledge that extensive microvascular changes are a feature of severe leukoaraiosis, we hypothesize that stroke progression could be promoted through an impaired compensatory flow in the penumbral area.
S. Nannoni1, A. Del Bene1, V. Palumbo2, L. Petrone1, F. Sottile3, G. Pracucci1, D. Inzitari1 1
NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy; 2Stroke Unit and Neurology, Careggi University Hospital, Florence, Italy; 3 Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Key words: ischemic stroke; leukoaraiosis; subcortical stroke; stroke progression; vascular risk factors S. Nannoni, MD, NEUROFARBA Department, Neuroscience Section, University of Florence, Largo Brambilla 3, 50134 Florence, Italy Tel.: +39 0557947665 Fax: +39 0557947665 e-mail: [email protected] Accepted for publication 3 March 2015
Introduction
Material and methods
Between 20% and 30% of patients with subcortical strokes (SS) experience worsening of neurological deficit in hours or even days from stroke onset (1–3). Deterioration involves especially motor function and is often associated with an outcome worse than expected (4). No reliable clinical predictors of progression have been identified so far (5). Early recognition of patients at risk of progression might be of importance to prevent clinical worsening. The aim of this study was to investigate clinical or imaging features independently associated with progression in SS.
Patients were selected from a registry of patients consecutively admitted to the Stroke Unit of the Careggi University Hospital (Florence, Italy) between January 2007 and December 2012. Recruitment was based on the following criteria: (i) exclusion of cortical symptoms/signs and a clinical presentation characterized by one of the classical lacunar syndromes: pure motor, pure sensory, sensorimotor, dysarthria–clumsy hand or ataxic hemiparesis syndromes; (ii) evidence of a subcortical infarct on neuroimaging consistent with the clinical deficit. According to the recently published STandards for ReportIng Vascular 1
Nannoni et al. changes on nEuroimaging (STRIVE) criteria (6), we included patients with evidence of acute small subcortical infarcts, infarcts in the anterior choroidal artery (AChA) territory and striatocapsular infarcts. In case of the absence of lesion on neuroimaging, we included patients according to their clinical presentation. Progression was defined as a deterioration of NIHSS motor score of ≥1 points during the first 72 h after stroke onset or fluctuation of symptoms (neurological worsening alternating with improvement with at least some residual deficit). We studied clinical characteristics and laboratory data of 94 patients assessed on admission and throughout hospitalization. Stroke severity was rated using National Institutes of Health Stroke Scale (NIHSS) on admission, every 6–8 h during hospitalization, and at discharge. Extracranial and intracranial arteries were examined in all patients with ultrasound methods. All patients had 12-lead ECG, 24-h Holter monitoring and echocardiography to rule out cardiac sources of emboli. Patients were divided into two groups: those with progression and those without progression. All patients had baseline CT scan on admission. Patients who progressed underwent CT or 1.5 T MRI within 24 h from the onset of worsening; in all the other patients, a follow-up neuroimaging (CT or MRI) was repeated before discharge. Several MRI scanners were used over the study period; T2, T1, DWI and FLAIR were acquired for every patients. Brain imaging (MRI or CT scans) were re-examined using an ad hoc designed protocol aiming at identifying imaging features potentially associated with progression. Two trained neurologists (A.D.B. and S.N.), blinded to clinical data, independently assessed and rated all scans: final definitions and rating were reached by consensus. In case of disagreement, scans were independently assessed by a senior neurologist (V.P.). The following features were assessed: 1. Size of subcortical infarct, measuring the maximum diameter on axial sections and longitudinal extent of the lesion estimated by counting the number of slices in which the lesion was visible. Considering a 5 mm slice thickness, a lesion extending over three slices was estimated to have a 15 mm longitudinal diameter. 2. Lesion location including internal capsule, corona radiata and centrum semiovale, basal ganglia, thalamus, pons and midbrain. 3. Vascular territory including that pertaining to the AChA, the lenticulostriate arteries, the superficial perforators and the vertebrobasilar territory (7). 2
4. Presence and severity of leukoaraiosis (LA): we used the Van Swieten Scale (8) for patients studied by CT scan only and the Fazekas scale (9) for those examined by MRI. LA was rated as severe if the Van Swieten Scale score was >2 or the Fazekas scale score was = 3, as previously reported (10). 5. Presence and number of old infarcts, divided into territorial and lacunar. Patients with progression were compared with patients without progression for age, gender and a number of vascular risk factors including hypertension (defined as receiving medication for hypertension or blood pressure >140/90 mm Hg on repeated measurements), diabetes mellitus (defined as receiving medication for diabetes mellitus or a fasting blood glucose level ≥ 126 mg/dl or symptoms of diabetes plus plasma glucose concentration ≥ 200 mg/dl), hypercholesterolaemia (defined as receiving cholesterol-reducing agents or a fasting total cholesterol level > 200 mg/dl), current smoking and clinical characteristics on admission. The two groups were also compared for imaging features. Statistical analysis was performed using the chi-square test for categorical variables and ANOVA for continuous variables. A probability value of P < 0.05 was considered statistically significant. Using a stepwise logistic regression model, the following factors were investigated as potential independent determinants of progression: age, gender, all the considered vascular risk factors, previous stroke, vascular territory, extension of symptomatic lesion (more or less than three slices), lesion diameter (more or
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Predictors of progression in patients presenting with minor subcortical stroke Nannoni S, Del Bene A, Palumbo V, Petrone L, Sottile F, Pracucci G, Inzitari D. Predictors of progression in patients presenting with minor subcortical stroke. Acta Neurol Scand: DOI: 10.1111/ane.12399. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives – Early neurological worsening is common in minor subcortical strokes (SS) and may lead to a poor outcome. We aimed to describe clinical and imaging features associated with progression. Material and methods – Consecutive patients with SS were divided into progressive and non-progressive. Progression was defined as an increase of NIHSS motor score ≥1 point within 72 h from onset. Vascular risk factors and imaging features (vascular territory, size and number of slices in which the lesion was visible, the presence of leukoaraiosis) were compared in the two groups. We investigated potential independent determinants of progression using stepwise logistic regression. Results – Thirty of 94 patients (31.9%) underwent progression. The distribution of vascular risk factors did not differ significantly between the two groups. Increasing number of risk factors was associated with a higher risk of progression (OR 2.2; 95% CI 1.1–4.5). Patients who progressed were more likely to have a lesion ≥15 mm in diameter (P = 0.004) or a lesion visible ≥3 slices (P = 0.007). After logistic regression stepwise adjustment for all the considered potential determinants, diameter ≥15 mm and severe leukoaraiosis proved to be independently associated with neurological worsening (OR = 6.3, 95% CI 2.0–19.6 and OR = 5.9, 95% CI 1.3–25.7, respectively). Conclusion – In a series of consecutive SS, early neurological worsening was associated with a high vascular risk profile, a larger infarct size and the presence of severe leukoaraiosis. Based on the knowledge that extensive microvascular changes are a feature of severe leukoaraiosis, we hypothesize that stroke progression could be promoted through an impaired compensatory flow in the penumbral area.
S. Nannoni1, A. Del Bene1, V. Palumbo2, L. Petrone1, F. Sottile3, G. Pracucci1, D. Inzitari1 1
NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy; 2Stroke Unit and Neurology, Careggi University Hospital, Florence, Italy; 3 Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Key words: ischemic stroke; leukoaraiosis; subcortical stroke; stroke progression; vascular risk factors S. Nannoni, MD, NEUROFARBA Department, Neuroscience Section, University of Florence, Largo Brambilla 3, 50134 Florence, Italy Tel.: +39 0557947665 Fax: +39 0557947665 e-mail: [email protected] Accepted for publication 3 March 2015
Introduction
Material and methods
Between 20% and 30% of patients with subcortical strokes (SS) experience worsening of neurological deficit in hours or even days from stroke onset (1–3). Deterioration involves especially motor function and is often associated with an outcome worse than expected (4). No reliable clinical predictors of progression have been identified so far (5). Early recognition of patients at risk of progression might be of importance to prevent clinical worsening. The aim of this study was to investigate clinical or imaging features independently associated with progression in SS.
Patients were selected from a registry of patients consecutively admitted to the Stroke Unit of the Careggi University Hospital (Florence, Italy) between January 2007 and December 2012. Recruitment was based on the following criteria: (i) exclusion of cortical symptoms/signs and a clinical presentation characterized by one of the classical lacunar syndromes: pure motor, pure sensory, sensorimotor, dysarthria–clumsy hand or ataxic hemiparesis syndromes; (ii) evidence of a subcortical infarct on neuroimaging consistent with the clinical deficit. According to the recently published STandards for ReportIng Vascular 1
Nannoni et al. changes on nEuroimaging (STRIVE) criteria (6), we included patients with evidence of acute small subcortical infarcts, infarcts in the anterior choroidal artery (AChA) territory and striatocapsular infarcts. In case of the absence of lesion on neuroimaging, we included patients according to their clinical presentation. Progression was defined as a deterioration of NIHSS motor score of ≥1 points during the first 72 h after stroke onset or fluctuation of symptoms (neurological worsening alternating with improvement with at least some residual deficit). We studied clinical characteristics and laboratory data of 94 patients assessed on admission and throughout hospitalization. Stroke severity was rated using National Institutes of Health Stroke Scale (NIHSS) on admission, every 6–8 h during hospitalization, and at discharge. Extracranial and intracranial arteries were examined in all patients with ultrasound methods. All patients had 12-lead ECG, 24-h Holter monitoring and echocardiography to rule out cardiac sources of emboli. Patients were divided into two groups: those with progression and those without progression. All patients had baseline CT scan on admission. Patients who progressed underwent CT or 1.5 T MRI within 24 h from the onset of worsening; in all the other patients, a follow-up neuroimaging (CT or MRI) was repeated before discharge. Several MRI scanners were used over the study period; T2, T1, DWI and FLAIR were acquired for every patients. Brain imaging (MRI or CT scans) were re-examined using an ad hoc designed protocol aiming at identifying imaging features potentially associated with progression. Two trained neurologists (A.D.B. and S.N.), blinded to clinical data, independently assessed and rated all scans: final definitions and rating were reached by consensus. In case of disagreement, scans were independently assessed by a senior neurologist (V.P.). The following features were assessed: 1. Size of subcortical infarct, measuring the maximum diameter on axial sections and longitudinal extent of the lesion estimated by counting the number of slices in which the lesion was visible. Considering a 5 mm slice thickness, a lesion extending over three slices was estimated to have a 15 mm longitudinal diameter. 2. Lesion location including internal capsule, corona radiata and centrum semiovale, basal ganglia, thalamus, pons and midbrain. 3. Vascular territory including that pertaining to the AChA, the lenticulostriate arteries, the superficial perforators and the vertebrobasilar territory (7). 2
4. Presence and severity of leukoaraiosis (LA): we used the Van Swieten Scale (8) for patients studied by CT scan only and the Fazekas scale (9) for those examined by MRI. LA was rated as severe if the Van Swieten Scale score was >2 or the Fazekas scale score was = 3, as previously reported (10). 5. Presence and number of old infarcts, divided into territorial and lacunar. Patients with progression were compared with patients without progression for age, gender and a number of vascular risk factors including hypertension (defined as receiving medication for hypertension or blood pressure >140/90 mm Hg on repeated measurements), diabetes mellitus (defined as receiving medication for diabetes mellitus or a fasting blood glucose level ≥ 126 mg/dl or symptoms of diabetes plus plasma glucose concentration ≥ 200 mg/dl), hypercholesterolaemia (defined as receiving cholesterol-reducing agents or a fasting total cholesterol level > 200 mg/dl), current smoking and clinical characteristics on admission. The two groups were also compared for imaging features. Statistical analysis was performed using the chi-square test for categorical variables and ANOVA for continuous variables. A probability value of P < 0.05 was considered statistically significant. Using a stepwise logistic regression model, the following factors were investigated as potential independent determinants of progression: age, gender, all the considered vascular risk factors, previous stroke, vascular territory, extension of symptomatic lesion (more or less than three slices), lesion diameter (more or
