Which compartments of the optic nerve and its sheath are associated with intracranial pressure? An exploratory study.

BACKGROUND AND PURPOSE: The optic nerve sheath diameter (ONSD) is a commonly used estimate of intracranial pressure (ICP). The rationale behind this is that pressure changes in the cerebrospinal fluid affect the optic nerve subarachnoid space (ONSAS) thickness. Still, possible effects on other compartments of the optic nerve sheath (ONS) have not been studied. This is the first study ever to analyze all measurable compartments of the ONS for associations with elevated ICP. METHODS: We measured changes in ICP and changes in ONS compartments in 75 patients treated with invasive ICP monitoring at the Karolinska University Hospital. Associations between changes in ICP and changes in ONS compartments were estimated with generalized estimating equations. The potential to identify elevated ICP was assessed with the area under the receiver operating characteristic curve (AUROC) for ONS compartments associated with ICP changes. RESULTS: Both ONSAS and perioptic dura mater thickness were significantly associated with changes in ICP in multivariable modeling. ONSAS was the only compartment that independently predicted changes in ICP, with an AUROC of 0.69 for predicting ICP increase. Still, both the perioptic dura mater thickness and the optic nerve diameter added value in predicting ICP changes in multivariable modeling. CONCLUSIONS: The results from this study challenge the current understanding of the mechanism behind the association between ICP and ONSD. Contrary to the common opinion that ONSAS is the only affected compartment, this study shows a more complex picture. It suggests that all ONS compartments may add value in predicting changes in ICP.

Sex differences in the diagnostic value of optic nerve sheath diameter for assessing intracranial pressure.

The optic nerve sheath diameter (ONSD) can predict elevated intracranial pressure (ICP) but it is not known whether diagnostic characteristics differ between men and women. This observational study was performed at the Karolinska University Hospital in Sweden to assess sex differences in diagnostic accuracy for ONSD. We included 139 patients (65 women), unconscious and/or sedated, with invasive ICP monitoring. Commonly used ONSD derived measurements and associated ICP measurements were collected. Linear regression analyses were performed with ICP as dependent variable and ONSD as independent variable. Area under the receiver operator characteristics curve (AUROC) analyses were performed with a threshold for elevated ICP ≥ 20 mmHg. Analyses were stratified by sex. Optimal cut-offs and diagnostic characteristics were estimated. The ONSD was associated with ICP in women. The AUROCs in women ranged from 0.70 to 0.83. In men, the ONSD was not associated with ICP and none of the AUROCs were significantly larger than 0.5. This study suggests that ONSD is a useful predictor of ICP in women but may not be so in men. If this finding is verified in further studies, this would call for a re-evaluation of the usage and interpretation of ONSD to estimate ICP.

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.

Optic nerve sheath diameter in intracranial hypertension: Measurement external or internal of the dura mater?

BACKGROUND AND PURPOSE: Optic nerve sheath diameter (ONSD) is a promising metric to estimate intracranial pressure (ICP). There is no consensus whether ONSD should be measured external (ONSDext) or internal (ONSDint) of the dura mater. Expert opinion favors ONSDint, though without clear evidence to support this. Adjustments of ONSD for eye diameter (ED) and optic nerve diameter (OND) have been suggested to improve precision. We examined the diagnostic accuracy of ONSDext and ONSDint for estimating ICP, unadjusted as well as adjusted for ED and OND. METHODS: We performed an observational cohort study, measuring ONSDext and ONSDint in patients with invasive ICP monitoring at Karolinska University Hospital in Stockholm, Sweden. We used ONSDext and ONSDint unadjusted as well as adjusted for ED and for OND. We compared the area under the receiver operator characteristics curve (AUROC) for these methods. Thresholds for elevated ICP were set at ≥20 and ≥22 mmHg, respectively. RESULTS: We included 220 measurements from 100 patients. Median ONSDext and ONSDint were significantly different at 6.7 and 5.2 mm (p = .00). There was no significant difference in AUROC for predicting elevated ICP between ONSDext and ONSDint (.67 vs. .64, p = .31). Adjustment for ED yielded better diagnostic accuracy (AUROC, cutoff, sensitivity, specificity) for ONSDext/ED (.76, .29, .81, .62) and ONSDint/ED (.71, .24, .5, .89). CONCLUSIONS: ONSDext and ONSDint differ significantly and are not interchangeable. However, there were no significant differences in diagnostic accuracy between ONSDext and ONSDint. Adjustment for ED may improve diagnostic accuracy of ONSD.

Optic nerve sheath diameter is associated with outcome in severe Covid-19.

Neurological symptoms are common in Covid-19 and cerebral edema has been shown post-mortem. The mechanism behind this is unclear. Elevated intracranial pressure (ICP) has not been extensively studied in Covid-19. ICP can be estimated noninvasively with measurements of the optic nerve sheath diameter (ONSD). We performed a cohort study with ONSD ultrasound measurements in severe cases of Covid-19 at an intensive care unit (ICU). We measured ONSD with ultrasound in adults with severe Covid-19 in the ICU at Karolinska University Hospital in Sweden. Patients were classified as either having normal or elevated ONSD. We compared ICU length of stay (ICU-LOS) and 90 day mortality between the groups. 54 patients were included. 11 of these (20.4%) had elevated ONSD. Patients with elevated ONSD had 12 days longer ICU-LOS (95% CI 2 to 23 p = 0.03) and a risk ratio of 2.3 for ICU-LOS ≥ 30 days. There were no significant differences in baseline data or 90 day mortality between the groups. Elevated ONSD is common in severe Covid-19 and is associated with adverse outcome. This may be caused by elevated ICP. This is a clinically important finding that needs to be considered when deciding upon various treatment strategies.

Can Quantitative Pupillometry be used to Screen for Elevated Intracranial Pressure? A Retrospective Cohort Study.

BACKGROUND: Elevated intracranial pressure (ICP) is a serious complication in brain injury. Because of the risks involved, ICP is not monitored in all patients at risk. Noninvasive screening tools to identify patients with elevated ICP are needed. Anisocoria, abnormal pupillary size, and abnormal pupillary light reflex are signs of high ICP, but manual pupillometry is arbitrary and subject to interrater variability. We have evaluated quantitative pupillometry as a screening tool for elevated ICP. METHODS: We performed a retrospective observational study of the association between Neurological Pupil index (NPi), measured with the Neuroptics NPi-200 pupillometer, and ICP in patients routinely monitored with invasive ICP measurement in the intensive care unit. We performed a nonparametric receiver operator curve analysis for ICP ≥ 20 mm Hg with NPi as a classification variable. We performed a Youden analysis for the optimal NPi cutoff value and recorded sensitivity and specificity for this cutoff value. We also performed a logistic regression with elevated ICP as the dependent variable and NPi as the independent variable. RESULTS: We included 65 patients with invasive ICP monitoring. A total of 2,705 measurements were analyzed. Using NPi as a screening tool for elevated ICP yielded an area under receiver operator curve of 0.72. The optimal mean NPi cutoff value to rule out elevated ICP was ≥ 3.9. The probability of elevated ICP decreased with increasing NPi, with an odds ratio of 0.55 (0.50, 0.61). CONCLUSIONS: Screening with NPi may inform high stakes clinical decisions by ruling out elevated ICP with a high degree of certainty. It may also aid in estimating probabilities of elevated ICP. This can help to weigh the risks of initiating invasive ICP monitoring against the risks of not doing so. Because of its ease of use and excellent interrater reliability, we suggest further studies of NPi as a screening tool for elevated ICP.

Optic nerve sheath diameter measurement by ultrasound: Evaluation of a standardized protocol.

BACKGROUND AND PURPOSE: Treatment of elevated intracranial pressure (ICP) is central to neurocritical care, but not all patients are eligible for invasive ICP-monitoring. A promising noninvasive option is ultrasound measurement of the optic nerve sheath diameter (ONSD). However, meta-analyses of ONSD for elevated ICP show wide confidence intervals. This might be due to baseline variations, inter-rater variability, and varying measurement methods. No standardized protocol has been validated. Corrections for eyeball diameter (ED) and optic nerve diameter (OND) may compensate for baseline variations. We evaluated a protocol and compared two different measurement methods for ONSD ultrasound. METHODS: Two operators, blinded to each other's measurements, measured ONSD, ED, and OND twice in 20 patients. ONSD was measured with two different methods in use: internal (ONSDint) or external (ONSDext) of the dura mater. Intra-class correlation (ICC) was calculated for inter-rater and intra-rater reliability. RESULTS: ICCs for inter-rater reliability of ONSDext and ONSDint (95% confidence interval) were 0.96 (0.93, 0.98) and 0.88 (0.79, 0.94), respectively. ICCs for intra-rater reliability of ONSDext and ONSDint were 0.97 (0.94, 0.99) and 0.93 (0.87, 0.96), respectively. There was no significant bias or difference in intra-rater reliability between operators. CONCLUSIONS: ONSD can be measured with an excellent inter- and intra-rater reliability and low risk of inter-rater bias, when using this protocol. ONSDext yields a higher inter- and intra-rater reliability than ONSDint. Corrections for ED and OND can be performed reliably.

Association between systolic blood pressure course and outcomes after stroke thrombectomy.

BACKGROUND: Systolic blood pressure (SBP) after endovascular thrombectomy (EVT) for large artery occlusive stroke is dynamic, requiring adaptable early prediction tools for improving outcomes. We investigated if post-EVT SBP course was associated with outcomes. METHODS: EVT-treated patients who had a stroke at Karolinska University Hospital, Stockholm, Sweden, were included in the study during 12 February 2018-11 February 2020. SBP was recorded during the first 24 hours after EVT. Primary outcome was functional independence defined by a Modified Rankin Scale score of 0-2 at 3 months. Secondary outcomes were death by 3 months, symptomatic intracranial haemorrhage and any intracranial haemorrhage. Patients with favourable outcomes were used as a reference SBP course in mixed linear effects models and compared with SBP courses of patients with unfavourable outcomes using the empirical best linear unbiased predictor, measuring deviations from the reference SBP course using the random effects. We tested model predictive stability for SBP measurements of only 18, 12 or 6 hours after EVT. RESULTS: 374 patients were registered, with mean age 71, median NIHSS score of 15, and 53.2% men. Deviating from a linear SBP course starting at 130 mm Hg and decreasing to 123 mm Hg at 24 hours after EVT was associated with lower chances of functional independence (adjusted OR 0.53, 95% CI 0.29 to 0.88, for reaching either 99 or 147 mm Hg at 24 hours after EVT). All SBP course models for the remaining outcomes did not show statistical significance. Functional independence models showed stable predictive values for all time periods. CONCLUSION: Deviating from a linear SBP course was associated with lower chances of 3-month functional independence.

Stroke Etiology and Outcomes after Endovascular Thrombectomy: Results from the SITS Registry and a Meta-Analysis.

BACKGROUND AND PURPOSE: The influence of stroke etiology on outcomes after endovascular thrombectomy (EVT) is not well understood. We aimed to investigate whether stroke etiology subgrouped as large artery atherosclerosis (LAA) and cardiac embolism (CE) influences outcomes in large artery occlusion (LAO) treated by EVT. METHODS: We included EVT treated LAO stroke patients registered in the Safe Implementation of Treatment in Stroke (SITS) thrombectomy register between January 1, 2014 and September 3, 2019. Primary outcome was successful reperfusion (modified Treatment in Cerebral Infarction 2b-3). Secondary outcomes were symptomatic intracranial hemorrhage (SICH), 3-month functional independence (modified Ranking Scale 0-2) and death. Multivariable logistic regression models were used for comparisons. In addition, a meta-analysis of aggregate data from the current literature was conducted (PROSPERO, ID 167447). RESULTS: Of 7,543 patients, 1,903 (25.2%) had LAA, 3,214 (42.6%) CE, and 2,426 (32.2%) unknown, other, or multiple etiologies. LAA patients were younger (66 vs. 74, P<0.001) and had lower National Institutes of Health Stroke Scale score at baseline (15 vs. 16, P<0.001) than CE patients. Multivariable analyses showed that LAA patients had lower odds of successful reperfusion (odds ratio [OR], 0.70; 95% confidence interval [CI], 0.57 to 0.86) and functional independence (OR, 0.74; 95% CI, 0.63 to 0.85), higher risk of death (OR, 1.44; 95% CI, 1.21 to 1.71), but no difference in SICH (OR, 1.09; 95% CI, 0.71 to 1.66) compared to CE patients. The systematic review found 25 studies matching the criteria. The meta-analysis did not find any difference between etiologies. CONCLUSIONS: From the SITS thrombectomy register, we observed a lower chance of reperfusion and worse outcomes after thrombectomy in patients with LAA compared to CE etiology, despite more favorable baseline characteristics. In contrast, the meta-analysis did not find any difference between etiologies with aggregate data.

Noise induced quiescence of epileptic spike generation in patients with epilepsy.

Clinical scalp electroencephalographic recordings from patients with epilepsy are distinguished by the presence of epileptic discharges i.e. spikes or sharp waves. These often occur randomly on a background of fluctuating potentials. The spike rate varies between different brain states (sleep and awake) and patients. Epileptogenic tissue and regions near these often show increased spike rates in comparison to other cortical regions. Several studies have shown a relation between spike rate and background activity although the underlying reason for this is still poorly understood. Both these processes, spike occurrence and background activity show evidence of being at least partly stochastic processes. In this study we show that epileptic discharges seen on scalp electroencephalographic recordings and background activity are driven at least partly by a common biological noise. Furthermore, our results indicate noise induced quiescence of spike generation which, in analogy with computational models of spiking, indicate spikes to be generated by transitions between semi-stable states of the brain, similar to the generation of epileptic seizure activity. The deepened physiological understanding of spike generation in epilepsy that this study provides could be useful in the electrophysiological assessment of different therapies for epilepsy including the effect of different drugs or electrical stimulation.

Safety and early outcomes after intravenous thrombolysis in acute ischemic stroke patients with prestroke disability.

BACKGROUND: There are limited data on intravenous thrombolysis treatment in ischemic stroke patients with prestroke disability. AIM: We aimed to evaluate safety and outcomes of intravenous thrombolysis treatment in stroke patients with prestroke disability. METHODS: We analyzed 88,094 patients treated with intravenous thrombolysis, recorded in the Safe Implementation of Treatments in Stroke (SITS) International Thrombolysis Register between January 2003 and December 2017, with available NIHSS data at stroke-onset and after 24 h. Of them, 4566 patients (5.2%) had prestroke disability, defined as a modified Rankin Scale score of 3-5. Safety outcome measures included Symptomatic Intracerebral Hemorrhage, any type of parenchymal hematoma on 24 h imaging scans irrespective of clinical symptoms, and death within seven days. Early outcome measures were 24-h NIHSS improvement (≥4 from baseline to 24 h). RESULTS: Patients with prestroke disability were older, had more severe strokes, and more comorbidities than patients without prestroke disability. When comparing patients with prestroke disability with patients without prestroke disability, there was however no significant increase in adjusted odds for symptomatic intracerebral hemorrhage (adjusted odds ratio 0.83 (95% CI 0.60-1.15) (absolute difference in proportion 1.17% vs. 1.27%)) or for parenchymal hemorrhage (adjusted odds ratio 0.96 (0.83-1.11) (7.51% vs. 6.34%)). The prestroke disability group had a significantly lower-adjusted odds ratio for a 24-h NIHSS improvement (adjusted odds ratio 0.79 (0.73-0.85) (45.95% vs. 48.45%)) and a higher adjusted odds ratio for seven-day mortality (aOR 1.40 (1.21-1.61) (10.40% vs. 4.93%)). CONCLUSIONS: Intravenous thrombolysis in acute ischemic stroke patients with prestroke disability was not associated with an increased risk of symptomatic intracerebral hemorrhage or parenchymal hemorrhage. Prestroke disability was however associated with a higher risk of early mortality compared to patients without prestroke disability.

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

OBJECTIVES: 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.

Blood Pressure After Endovascular Thrombectomy: Modeling for Outcomes Based on Recanalization Status.

Background and Purpose- The optimal level for blood pressure after endovascular thrombectomy in acute ischemic stroke is not well established. We sought to evaluate the association of post-endovascular thrombectomy systolic blood pressure (SBP) levels with clinical outcomes. Methods- We included endovascular thrombectomy-treated patients registered from 2014 to 2017 in the Safe Implementation of Treatments in Stroke International Thrombectomy Registry. The mean 24-hour SBP after endovascular thrombectomy treatment was analyzed both as a continuous variable and in intervals. The primary outcome was 3-month functional independence (modified Rankin Scale score of 0-2). The secondary outcomes were symptomatic intracerebral hemorrhage (SICH) and 3-month mortality. The SBP interval with the highest proportion of functional independence was chosen as reference. All analyses were performed for successful or unsuccessful recanalization (modified Treatment in Cerebral Ischemia score ≥2b or <2b, respectively). The results were adjusted for known confounders in logistic regression models. Results- In the multivariable analyses, a higher SBP value as a continuous variable was associated unfavorably with all outcomes in patients with successful recanalization (n=2920) and with more SICH in patients with unsuccessful recanalization (n=711). SBP interval ≥160 mm Hg was associated with less functional independence (adjusted odds ratio, 0.28 [95% CIs, 0.15-0.53]) and more SICH (adjusted odds ratio, 6.82 [95% CIs, 1.53-38.09]) compared with reference 100 to 119 mm Hg in patients with successful recanalization. SBP ≥160 mm Hg was associated with more SICH (adjusted odds ratio, 6.62 [95% CIs, 1.07-51.05]) compared with reference 120 to 139 mm Hg in patients with unsuccessful recanalization. Conclusions- Higher SBP values were associated with less functional independence at 3 months in patients with successful recanalization and with more SICH regardless of recanalization status.

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

OBJECTIVE: 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.

Safety and Outcome of Intravenous Thrombolysis in Stroke Patients on Prophylactic Doses of Low Molecular Weight Heparins at Stroke Onset.

Background and Purpose- There are limited data on intravenous thrombolysis treatment in patients with ischemic stroke who have received prophylactic doses of low molecular weight heparins (LMWHs). We aimed to evaluate the safety and outcomes of intravenous thrombolysis treatment in stroke patients taking thromboprophylactic doses of LMWH. Methods- We analyzed 109 291patients treated with intravenous thrombolysis, recorded in the Safe Implementation of Treatments in Stroke International Thrombolysis Register between 2003 and 2017 not taking oral anticoagulants or therapeutic doses of heparin at stroke onset. One thousand four hundred eleven patients (1.3%) were on prophylactic LMWH for deep venous thrombosis prevention. Outcome measures were symptomatic intracerebral hemorrhage, parenchymal hematoma, death within 7 days and 3 months, and functional dependency at 3 months. Results- Patients on LMWH were older, had more severe strokes, more prestroke disability, and comorbidities than patients without LMWH. There was no significant increase in adjusted odds ratios (aOR) for symptomatic intracerebral hemorrhage (aOR, 1.02 [95% CI, 0.48-2.17] as per Safe Implementation of Treatments in Stroke -MOST, aOR, 0.95 [0.59-1.53] per ECASS II]), nor for 7-day mortality (aOR, 1.14 [0.82-1.59]), in the prophylactic LMWH group. The LMWH group had a higher aOR for 3-month mortality (aOR, 1.94 [1.49-2.53]) and functional dependency, aOR, 1.44 (1.10-1.90). Propensity score analysis matching patients on baseline characteristics removed differences between groups on all outcomes except 3-month mortality. Conclusions- Intravenous thrombolysis in patients with acute ischemic stroke on treatment with prophylactic doses of LMWH at stroke onset is not associated with an increased risk of symptomatic intracerebral hemorrhage or early death.

Outcome after intravenous thrombolysis in patients with acute lacunar stroke: An observational study based on SITS international registry and a meta-analysis.

BACKGROUND: Intravenous thrombolysis (IVT) for lacunar stroke (LS) is debated, as the underlying pathophysiological mechanism may not be thrombogenic. AIMS: To investigate outcomes after IVT in LS in the SITS International Stroke Thrombolysis Register and perform a meta-analysis. METHODS: LS was identified by both baseline NIHSS-subscores and discharge ICD-10 codes, and contrasted by IVT to non-IVT treated. IVT patients were predominantly from Europe, non-IVT patients predominantly from South America and Asia. Outcome measurements were functional independence (modified Rankin Scale [mRS] score ≤2), excellent outcome (mRS ≤ 1), and mortality at three months. Matched-control comparisons of symptomatic intracerebral hemorrhage (SICH) between IVT-treated LS and IVT-treated non-LS patients were performed. Additionally, we performed a meta-analysis. RESULTS: Median age for IVT-treated LS patients (n = 4610) was 66 years vs. 64 years and NIHSS score was 6 vs. 3, compared to non-IVT-treated LS (n = 1221). Univariate outcomes did not differ; however, IVT-treated LS patients had higher adjusted odds ratios (aOR) for functional independence (aOR = 1.65, 95% CI = 1.28-2.13) but similar mortality at three months (aOR = 0.57, 0.29-1.13) than non-IVT-LS. Propensity-score matched analysis showed that IVT-treated LS patients had a 7.1% higher chance of functional independency than non-IVT LS patients (p < 0.001). IVT-treated LS patients had lower odds for SICH (aOR = 0.33, 0.19-0.58 per SITS, aOR = 0.40, 0.27-0.57 per ECASS-2) than matched non-LS controls, which was mirrored in the meta-analysis. CONCLUSIONS: Our adjusted results show that IVT treatment in LS patients was associated with better functional outcome than non-IVT-treated LS and less SICH than IVT-treated non-LS patients.

Are you suffering from a large arterial occlusion? Please raise your arm!

Background and purpose: Triage tools to identify candidates for thrombectomy are of utmost importance in acute stroke. No prognostic tool has yet gained any widespread use. We compared the predictive value of various models based on National Institutes of Health Stroke Scale (NIHSS) subitems, ranging from simple to more complex models, for predicting large artery occlusion (LAO) in anterior circulation stroke. Methods: Patients registered in the SITS international Stroke Register with available NIHSS and radiological arterial occlusion data were analysed. We compared 2042 patients harbouring an LAO with 2881 patients having no/distal occlusions. Using binary logistic regression, we developed models ranging from simple 1 NIHSS-subitem to full NIHSS-subitems models. Sensitivities and specificities of the models for predicting LAO were examined. Results: The model with highest predictive value included all NIHSS subitems for predicting LAO (area under the curve (AUC) 0.77), yielding a sensitivity and specificity of 69% and 76%, respectively. The second most predictive model (AUC 0.76) included 4-NIHSS-subitems (level of consciousness commands, gaze, facial and arm motor function) yielding a sensitivity and specificity of 67% and 75%, respectively. The simplest model included only deficits in arm motor-function (AUC 0.72) for predicting LAO, yielding a sensitivity and specificity of 67% and 72%, respectively. Conclusions: Although increasingly more complex models yield a higher discriminative performance for predicting LAO, differences between models are not large. Assessing grade of arm dysfunction along with an established stroke-diagnosis model may serve as a surrogate measure of arterial occlusion-status, thereby assisting in triage decisions.

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.