Vessel occlusion and functional outcome after acute stroke : prediction and evaluation

In the acute setting of ischaemic stroke, two proven treatments are available: intravenous thrombolysis (iv-tPA) with alteplase and endovascular thrombectomy. The main aim of this thesis was to investigate the associations between symptom severity in the acute setting of ischaemic stroke and 1) the presence of arterial occlusions and 2) long-term functional outcome assessed at 3 months. The first 3 studies were based on patients registered in the large Safe Implementation of Treatments in Stroke - International Stroke Thrombolysis Register (SITS-ISTR). In the final project, conceptually separated from the first 3 studies, we aimed to investigate a novel method for assessing 3-month functional outcome after acute stroke. Study 1. We aimed at finding thresholds for baseline stroke severity as measured by National Institutes of Health Stroke Scale (NIHSS) scores that predicted long-term functional outcome and baseline arterial occlusion. We analysed 44 331 iv-tPA treated ischaemic stroke patients with available functional outcome assessed by the modified Rankin Scale (mRS) at three-months and 11 632 patients with available computed tomography/magnetic resonance angiography data at baseline. For functional independency (mRS 0-2), NIHSS scores of 12 [area under the curve (AUC) 0.775] and for baseline arterial occlusion, NIHSS scores of 11 (AUC 0.678) were optimal threshold values. NIHSS thresholds decreased with time from stroke onset to imaging, with 2–3 points, respectively, if time to imaging exceeded three-hours. We concluded that an NIHSS threshold of 9 or 10 points could be considered in the pre-hospital selection of patients for immediate transfer to centres with arterial imaging and availability of endovascular thrombectomy. Study 2. ASTRAL and DRAGON are two recently developed scores for predicting long-term functional outcome after acute stroke in unselected acute ischaemic stroke patients and in patients treated with iv-tPA, respectively. We aimed to perform external validation of these scores. We calculated the ASTRAL and DRAGON scores in 36131 and 33716 iv-tPA treated patients, respectively, registered in the SITS-ISTR between 2003 and 2013. The proportion of patients with death or dependency at 3 months (mRS 3-6) was observed for each score point and compared with the predicted proportion according to the risk scores. Predictive performance was assessed using the AUC of the receiver operating characteristic. The ASTRAL showed an AUC of 0.790 (95% CI, 0.786–0.795) and the DRAGON an AUC of 0.774 (95% CI, 0.769–0.779). We concluded that the ASTRAL and DRAGON scores show an acceptable predictive performance and may have a role for prognostication of outcome after acute ischaemic stroke. Study 3. We aimed to assess the predictive value of various models based on baseline NIHSS sub-items, ranging from simple to more complex models, for predicting large arterial occlusions (LAO) in anterior circulation stroke. Patients registered in the SITS-ISTR with clinically defined anterior circulation stroke, and available NIHSS and radiological arterial occlusion data were analysed. We compared 1975 patients harbouring an LAO with 2036 patients having no/distal occlusions. Using binary logistic regression, we developed models ranging from a simple 1 NIHSS-sub-item to full NIHSS-sub-items models. Sensitivities and specificities of the models for predicting LAO were examined. The model with highest predictive value included all NIHSS subitems as well as other relevant parameters for predicting LAO (AUC 0.78), yielding a sensitivity and specificity of 74% and 72% respectively. The simplest model included only deficits in arm motor-function (AUC 0.72) for predicting LAO, yielding a sensitivity and specificity of 69% and 70% respectively. Differences between the models were not large. We concluded that assessing grade of arm-dysfunction along with an established strokediagnosis model may serve a surrogate measure of LAO status, thereby assisting in triage decisions. Study 4. Assessment of long-term functional outcome is lacking in many settings. We aimed to investigate whether automatic assessment of the mRS based on a mobile phone questionnaire may serve as an alternative to mRS assessments at clinical visits after stroke. We enrolled 62 acute stroke patients admitted to our stroke unit during March to May 2014. Forty- eight patients completed the study. During the hospital stay, patients and/or caregivers were equipped with a mobile phone application in their personal mobile phones. Three months after inclusion, the mobile phone application automatically prompted the study participants to answer an mRS questionnaire in the mobile phones. A few days later, a study personnel performed a clinical visit mRS assessment. The 2 assessments were compared using quadratic weighing κ-statistics. We found a 62.5% agreement between clinical visit and mobile mRS assessment, weighted kappa 0.89 (95% CI 0.82–0.96), and unweighted kappa 0.53 (95% CI 0.36– 0.70). Mobile phone–based automatic assessments of mRS performed well in comparison with clinical visit mRS and may serve a supplementary role to traditional assessments, especially in settings where clinical follow-up visits are scarce because of economic and time-restraining factors

Minor stroke due to large artery occlusion. When is intravenous thrombolysis not enough? Results from the SITS International Stroke Thrombolysis Register

Purpose: Beyond intravenous thrombolysis, evidence is lacking on acute treatment of minor stroke caused by large artery occlusion. To identify candidates for additional endovascular therapy, we aimed to determine the frequency of non-haemorrhagic early neurological deterioration in patients with intravenous thrombolysis-treated minor stroke caused by occlusion of large proximal and distal cerebral arteries. Secondary aims were to establish risk factors for non-haemorrhagic early neurological deterioration and report three-month outcomes in patients with and without non-haemorrhagic early neurological deterioration. Method: We analysed data from the SITS International Stroke Thrombolysis Register on 2553 patients with intravenous thrombolysis-treated minor stroke (NIH Stroke Scale scores 0–5) and available arterial occlusion data. Non-haemorrhagic early neurological deterioration was defined as an increase in NIH Stroke Scale score ≥4 at 24 h, without parenchymal hematoma on follow-up imaging within 22–36 h. Findings: The highest frequency of non-haemorrhagic early neurological deterioration was seen in 30% of patients with terminal internal carotid artery or tandem occlusions (internal carotid artery + middle cerebral artery) (adjusted odds ratio: 10.3 (95% CI 4.3–24.9), p < 0.001) and 17% in extracranial carotid occlusions (adjusted odds ratio 4.3 (2.5–7.7), p < 0.001) versus 3.1% in those with no occlusion. Proximal middle cerebral artery-M1 occlusions had non-haemorrhagic early neurological deterioration in 9% (adjusted odds ratio 2.1 (0.97–4.4), p = 0.06). Among patients with any occlusion and non-haemorrhagic early neurological deterioration, 77% were dead or dependent at three months. Conclusions: Patients with minor stroke caused by internal carotid artery occlusion, with or without tandem middle cerebral artery involvement, are at high risk of disabling deterioration, despite intravenous thrombolysis treatment. Acute vessel imaging contributes usefully even in minor stroke to identify and consider endovascular treatment, or intensive monitoring at a comprehensive stroke centre, for patients at high risk of neurological deterioration

Clinical selection strategies to identify ischemic stroke patients with large anterior vessel occlusion: results from SITS-ISTR (Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry)

Background and Purpose—The National Institutes of Health Stroke Scale (NIHSS) correlates with presence of large anterior vessel occlusion (LAVO). However, the application of the full NIHSS in the prehospital setting to select patients eligible for treatment with thrombectomy is limited. Therefore, we aimed to evaluate the prognostic value of simple clinical selection strategies. Methods—Data from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry (January 2012–May 2014) were analyzed retrospectively. Patients with complete breakdown of NIHSS scores and documented vessel status were included. We assessed the association of prehospital stroke scales and NIHSS symptom profiles with LAVO (internal carotid artery, carotid-terminus or M1-segment of the middle cerebral artery). Results—Among 3505 patients, 23.6% (n=827) had LAVO. Pathological finding on the NIHSS item best gaze was strongly associated with LAVO (adjusted odds ratio 4.5, 95% confidence interval 3.8–5.3). All 3 face–arm–speech–time test (FAST) items identified LAVO with high sensitivity. Addition of the item gaze to the original FAST score (G-FAST) or high scores on other simplified stroke scales increased specificity. The NIHSS symptom profiles representing total anterior syndromes showed a 10-fold increased likelihood for LAVO compared with a nonspecific clinical profile. If compared with an NIHSS threshold of ≥6, the prehospital stroke scales performed similarly or even better without losing sensitivity. Conclusions—Simple modification of the face–arm–speech–time score or evaluating the NIHSS symptom profile may help to stratify patients’ risk of LAVO and to identify individuals who deserve rapid transfer to comprehensive stroke centers. Prospective validation in the prehospital setting is required

Association of cholesterol levels with hemorrhagic transformation and cerebral edema after reperfusion therapies

[Background] The association between cholesterol levels and cerebral edema (CED) or hemorrhagic transformation (HT) as an expressions of blood-brain barrier (BBB) dysfunction after ischemic stroke is not well established. The aim of this study is to determine the association of total cholesterol (TC) levels with the incidence of HT and CED after reperfusion therapies.[Methods] We analyzed SITS Thrombolysis and Thrombectomy Registry data from January 2011 to December 2017. We identified patients with data on TC levels at baseline. TC values were categorized in three groups (reference group ⩾200 mg/dl). The two primary outcomes were any parenchymal hemorrhage (PH) and moderate to severe CED on follow up imaging. Secondary outcomes included death and functional independence (mRS 0–2) at 3 months. Multivariable logistic regression analysis adjusted for baseline factors including statin pretreatment was used to assess the association between TC levels and outcomes.[Results] Of 35,314 patients with available information on TC levels at baseline, 3372 (9.5%) presented with TC levels ⩽130 mg/dl, 8203 (23.2%) with TC 130–200 mg/dl and 23,739 (67.3%) with TC ⩾ 200 mg/dl. In the adjusted analyses, TC level as continuous variable was inversely associated with moderate to severe CED (OR 0.99, 95% CI 0.99–1.00, p = 0.025) and as categorical variable lower TC levels were associated with a higher risk of moderate to severe CED (aOR 1.24, 95% CI 1.10–1.40, p = 0.003). TC levels were not associated with any PH, functional independence, and mortality at 3 months.[Conclusions] Our findings indicate an independent association between low levels of TC and higher odds of moderate/severe CED. Further studies are needed to confirm these findings.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The SITS registry is financed directly and indirectly by grants from Karolinska Institutet, Stockholm County Council, the Swedish Heart-Lung Foundation, as well as from an unrestricted sponsorship from Boehringer-Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, and conducted studies supported by EVER Pharma and Ferrer Internacional, as well as in collaboration with Karolinska Institutet, supported by Stryker, Covidien, and Phenox. SITS is currently conducting studies supported by Boehringer-Ingelheim and Biogen. N Ahmed is supported by Stockholm County Council and Swedish Heart-lung Foundation. Irene Escudero-Martínez has received a grant from “Fundación Progreso y Salud, Junta de Andalucía” (grant EF-0437-2018).Peer reviewe

Post-stroke epilepsy in an ischemic stroke cohort-Incidence and diagnosis.

To access publisher's full text version of this article click on the hyperlink belowOBJECTIVES: Stroke is a common cause of adult-onset epilepsy (post-stroke epilepsy, PSE). Despite an increasing awareness, there is a concern for underdiagnosis of the condition. We aimed to study the adherence to the latest updated epilepsy definition, as well as the incidence and diagnosis of PSE in an ischemic stroke cohort admitted to a tertiary University Hospital. MATERIALS AND METHODS: We retrospectively investigated the occurrence and diagnosis of unprovoked seizures and PSE in all ischemic stroke patients admitted to Karolinska University Hospital in Stockholm during 2015 and registered in the Swedish Stroke Register. Patient records were scrutinized for the presence of post-stroke seizures/epilepsy. RESULTS: A total of 240 patients fulfilling the inclusion criteria were surveyed. Median follow-up time was 1062 days (IQR 589-1195 days). Thirteen patients were diagnosed with PSE according to the study criteria, the incidence of PSE 23/1000 person-years (95% CI 13-38/1000 person-years). Median time to PSE from stroke-onset was 237 days (IQR 33-688). Eleven of 13 PSE patients received an epilepsy diagnosis, eight patients after one unprovoked seizure, and three patients after two. CONCLUSIONS: The majority of PSE patients were given a correct epilepsy diagnosis and treated with antiepileptic drugs. However, this study suggests that there still is potential for improvement in the adherence to the latest updated epilepsy definition. The incidence of PSE in a Swedish ischemic stroke cohort using updated epilepsy definitions is similar to previous studies. Larger studies are needed to confirm our findings on the incidence of PSE

Incidence of osmotic demyelination syndrome in Sweden: A nationwide study.

To access publisher's full text version of this article click on the hyperlink belowOBJECTIVE: To report the incidence rate of osmotic demyelination syndrome (ODS), associated risk factors, treatment, and long-term outcomes in a nationwide cohort. METHODS: We conducted a retrospective study of individuals diagnosed with central pontine myelinolysis (ICD-10 code G37.2) in the Swedish National Patient Register during 1997-2011. RESULTS: During the study period, we identified 83 individuals with ODS, 47 women and 36 men. Median age at diagnosis was 55 years. The incidence rate of ODS for the entire study period was 0.611 (95% CI: 0.490-0.754) per million person-years and increased during the study period from 0.271 (95% CI: 0.147-0.460) in 1997-2001 to 0.945 (95% CI: 0.677-1.234) individuals per million person-years in 2007-2011. Most cases (86.7%) were hyponatremic with a median sodium level at admission of 104 mmol/L. All hyponatremic cases were chronic. The cause of hyponatremia was multifactorial, including drugs (56.9%), polydipsia (31.9%), and vomiting or diarrhea (41.7%). A majority of patients (69.9%) were alcoholics. Hyponatremic patients were predominantly treated with isotonic saline (93.1%) and only 4.2% with hypotonic fluids. The median correction rate was 0.72 mmol/L/h. Only six patients were corrected in accordance with national guidelines (≤8 mmol/L/24/h). At three months, 7.2% had died and 60.2% were functionally independent (modified Rankin Scale 0-2). INTERPRETATION: We found an increasing incidence during the study period, which could partly be explained by increased access to magnetic resonance imaging. ODS occurs predominantly in patients with extreme chronic hyponatremia which is corrected too fast with isotonic saline. Most patients survived and became functionally independent

Identification of pregnancies at increased risk of brachial plexus birth palsy - the construction of a weighted risk score

Objective: Since it is difficult to identify women at increased risk of fetal brachial plexus birth palsy (BPBP) during labor and delivery, we aimed to construct and validate a risk score. Methods: A retrospective case-control study was undertaken in 2001 and 2006 in an urban context in Malmo, Sweden. A risk score was constructed for all women who had received routine municipal maternal health care at Skane University Hospital (n = 10 459). The model was validated among all pregnant women with BPBP and controls in Sweden between 2006 and 2007. Results: The likelihood of BPBP increased as the risk score rose: 3.1% of the women studied had a risk score >= 5, including 32.1% of the BPBP cases, where the risk showed a 38-fold increase, as compared to those with a risk score <= 1 (2/3 of the population). Conclusion: Our findings indicate that it is possible to identify women at increased risk of having a child with BPBP by using variables observable in advance of delivery