Imaging Triage of Patients with Late-Window (6-24 Hours) Acute Ischemic Stroke: A Comparative Study Using Multiphase CT Angiography versus CT Perfusion.

BACKGROUND AND PURPOSE: The role of collateral imaging in selecting patients for endovascular thrombectomy beyond 6 hours from onset has not been established. To assess the comparative utility of collateral imaging using multiphase CTA in selecting late window patients for EVT. MATERIALS AND METHODS: We used data from a prospective multicenter observational study in which all patients underwent imaging with multiphase CT angiography as well as CTP. Two blinded reviewers evaluated patients' eligibility for endovascular thrombectomy using published collateral imaging (multiphase CTA) criteria compared with CTP using the selection criteria of the Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) and Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE-3) trials. CTP images were processed using automated commercial software. The outcomes of patients eligible for endovascular thrombectomy according to multiphase CTA, DAWN, or DEFUSE-3 criteria were compared using multivariable logistic regression modeling. Model characteristics were compared using the C-statistic for the receiver operating characteristic curve, the Akaike information criterion, and the Bayesian information criterion. RESULTS: Eighty-six patients presented beyond 6 hours from onset/last known well (median, 9.6 hours; interquartile range, 4.1 hours). Thirty-five patients (40.7%) received endovascular thrombectomy, of whom good functional outcome (90-day mRS, 0-2) was achieved in 16/35 (47%). Collateral-based imaging paradigms significantly modified the treatment effect of endovascular thrombectomy on 90-day mRS 0-2 (P interaction = .007). The multiphase CTA-based regression model best fit the data for the 90-day outcome (C-statistic, 0.86; 95% CI, 0.77-0.94) and was associated with the least information loss (Akaike information criterion, 95.7; Bayesian information criterion, 114.9) compared with CTP-based models. CONCLUSIONS: The collateral-based imaging paradigm using multiphase CTA compares well with CTP in selecting patients for endovascular thrombectomy in the late time window.

Inter-rater Agreement in Three Perfusion-Computed Tomography Evaluation Methods before Endovascular Therapy for Acute Ischemic Stroke.

PURPOSE: There is ongoing debate on which method of perfusion computed tomography (PCT) evaluation in ischemic stroke is the most appropriate for improved selection of patients for endovascular treatment. We sought to test different assessment methods for inter-rater reliability. METHODS: Twenty-six patients were enrolled prospectively before endovascular therapy for acute anterior circulation ischemic stroke. Three raters experienced in stroke imaging and blinded to other imaging and clinical information independently analyzed 22 technically successful PCT scans according to 3 prespecified assessment methods applied to cerebral blood flow (CBF)/cerebral blood volume (CBV) and time-to-peak (TTP) maps: (1) visual mismatch estimate (VME), (2) Alberta Stroke Program Early CT Score perfusion method (ASPECTS-PCT), and (3) quantitative perfusion ratios (qPRs): RCBF, RCBV, RTTP. Inter-rater agreement was assessed with Cohen's kappa, intraclass correlation coefficients (ICC), Bland-Altman plots, and global and descriptive statistics. RESULTS: Significant differences between raters were found with VME and ASPECTS-PCT (P < .001) but with qPRs only for CBV (P = .03). Inter-rater agreement for VME was at best moderate by kappa statistics (.51); moderate by ICC for all parametric maps of ASPECTS-PCT (.56-.62), strong for RTTP (.76), and excellent for RCBF (.92) and RCBV (.86). Pairwise comparisons revealed less scattering of individual values with qPRs and less deviation of mean differences from 0, suggesting minor systematic deviation by any 1 rater as compared with VME or ASPECTS-PCT. CONCLUSION: PCT evaluation methods used before endovascular therapy for acute anterior circulation stroke are subject to substantial inter-rater disagreement. QPRs in PCT evaluation had better inter-rater reliability than the often used VME and ASPECTS-PCT assessment.

Diffusion tensor imaging abnormalities in photosensitive juvenile myoclonic epilepsy.

BACKGROUND AND PURPOSE: Multiple structural white matter abnormalities have been described in patients with juvenile myoclonic epilepsy (JME). In the present study, the question of whether microstructural variations exist between the two subgroups of JME, with and without photoparoxysmal responses (PPR positive and negative), was addressed using diffusion tensor imaging. METHODS: A selection of 18 patients (eight PPR positive) from a tertiary epilepsy center diagnosed with JME and 27 healthy controls was studied. The following regions of interest were investigated: the ascending reticular activating system, lateral geniculate nucleus, genu of the internal capsule, ventromedial thalamus and inferior cerebellar peduncle. RESULTS: Widespread white matter microstructural abnormalities in JME and in particular in PPR positive cases were identified. PPR positive patients demonstrated increased fractional anisotropy in the ascending reticular activating system and ventromedial thalamus compared to PPR negative patients and healthy controls. Reduced fractional anisotropy of the lateral geniculate nucleus was observed in the entire JME group compared to healthy controls. CONCLUSIONS: Several microstructural variations between PPR positive and negative JME patients have been identified. Our findings highlight the pivotal role of the thalamus in the pathophysiology of primary generalized seizures and suggest that thalamo-premotor connections are both an essential part of epileptic networks and important in the pathogenesis of photosensitivity.

Comparing perfusion CT evaluation algorithms for predicting outcome after endovascular treatment in anterior circulation ischaemic stroke.

AIM: To analyse perfusion CT (PCT) evaluation algorithms for their predictive value for outcome after endovascular therapy (ET) in acute ischaemic stroke. MATERIALS AND METHODS: Twenty-six patients were prospectively enrolled to undergo endovascular therapy for moderate to severe [National Institute of Health Stroke Scale (NIHSS) score of ≥5] anterior circulation stroke ≤6 h of onset. PCT datasets were evaluated according to three algorithms: visual mismatch estimate (VME), Alberta Stroke Programme Early CT Score (ASPECTS) perfusion, and quantitative perfusion ratios (QPRs: RCBF, RCBV) of cerebral blood flow (CBF) and volume (CBV). Results were correlated with outcome measures [NIHSS score at discharge, NIHSS score change until discharge (ΔNIHSSA/D), mRS at 90 days (mRS90d)] and compared with a matched control group. RESULTS: Recanalization was achieved in 73%, median NIHSS score decreased from 14 to 5 at discharge. The treatment and control group did not differ by VME and ASPECTS perfusion, nor did VME correlate with any of the three outcome measures. ASPECTS perfusion was not predictive of any outcome measure in the ET group. RCBF and RCBV were associated with ΔNIHSSA/D in controls and, inversely, the ET group, but not with mRS90d. Receiver operating characteristic (ROC) analysis of RCBF (and RCBV) showed a positive predictive and negative predictive value of 87% (78%) and 74% (73%), respectively, for discriminating major neurological improvement (ΔNIHSSA/D <7 versus ≥7). CONCLUSIONS: Implementation of QPRs for CBF and CBV are superior to clinically used VME and ASPECTS perfusion evaluation methods for predicting early outcome after ET for anterior circulation stroke.

["Time is brain". Optimizing prehospital stroke management]. / "Zeit ist Hirn". Optimierung des prähospitalen Schlaganfallmanagements.

Acute stroke is one of the main causes of death and chronic disability. Thrombolysis, achieved by administering recombinant tissue plasminogen activator within 4.5 h, is an effective therapeutic option for ischemic stroke. However, less than 2-12 % of patients receive this treatment and a major reason is that most patients reach the hospital too late. Several time-saving measures should be implemented. Firstly, optimized and continual public awareness campaigns for patients should be initiated to reduce delays in notifying the emergency medical service. Secondly, emergency medical service personnel should develop protocols for prenotification of the receiving hospital. Other suggested measures involve educating emergency medical service personnel to systematically use scales for recognizing the symptoms of stroke and to triage patients to experienced stroke centers. In the future, administering treatment at the emergency site (mobile stroke unit concept) may allow more than a small minority of patients to benefit from available recanalization treatment options.

[Endovascular treatment of acute ischemic stroke under conscious sedation compared to general anesthesia - safety, feasibility and clinical and radiological outcome]. / Endovaskuläre Therapie des akut ischämischen Schlaganfalls unter Analgosedierung im Vergleich zur Intubationsnarkose - Durchführbarkeit, periprozedurale Sicherheit, klinisches und radiologisches Outcome.

PURPOSE: Vessel recanalization is an important predictor of clinical outcome in the treatment of acute ischemic stroke. Endovascular therapies are used with increasing frequency. There is no general agreement on the policy of anesthesia during endovascular therapy, ranging from general anesthesia (GA) to local anesthesia at the puncture site with conscious sedation (CS) as needed. The aim of the study was to evaluate the safety and feasibility and radiological and clinical outcome of endovascular stroke therapy under CS. MATERIALS AND METHODS: We retrospectively included all patients with acute ischemic stroke who were treated with endovascular therapy over a five-year period. Data was evaluated with respect to type of sedation, conversion from CS to GA, recanalization rate, infarct volume and peri- and post-procedural complications. RESULTS: There was a technical failure in 7 patients. Of the remaining 124 patients (mean age 68.8 ± 14.6 years), 65 were female (52 %). The site of occlusion was located in the anterior circulation in 94 patients (76 %) and in the posterior circulation in 30 cases (24 %). 105 patients (85 %) were treated under CS and 16 cases (13 %) primarily under GA. In 3 cases (2 %) peri-procedural conversion to GA was necessary. Primary intra-arterial thrombolysis, mechanical recanalization only, and combination therapy were performed in 60 (48 %), 27 (22 %) and 37 (30 %) patients, respectively. There were no significant differences for recanalization rate and complications between GA and CS. The mean procedure time was significantly shorter in patients treated under CS (p < 0.01). CONCLUSION: Endovascular stroke therapy with CS is feasible, can be performed safely and is faster than with GA.

[Diffusion-weighted MRI - how many B-values are necessary?]. / Diffusionsgewichtete MRT - wie viele Diffusionsfaktoren sind notwendig?

PURPOSE: Diffusion-weighted imaging (DWI) has become an important component in modern stroke imaging. This MR technique detects diffusion abnormalities, which can be quantified by computing apparent diffusion coefficient (ADC) maps. ADC values are typically calculated from a set of MR images obtained with varying degrees of diffusion weighting (b-values) using nonlinear regression. However, there is no agreement concerning the number of images needed for ADC calculation. The aim of our study was to determine how many b-values are necessary to reliably calculate ADC maps. MATERIALS AND METHODS: In 100 consecutive patients with clinical signs of acute ischemic stroke, 6 identically oriented and centered diffusion data sets with different b-values were acquired. ROI analysis was performed for DWI-positive lesions, normal-appearing gray and white matter, CSF, and background noise. ADC values for each ROI were calculated using a nonlinear regression model. Additionally, the CNR and SNR were calculated for each ROI. RESULTS: Acquisition time was 0:39 min for 2 b-values and up to 2:49 min for a sequence with 7 b-values. The mean ADC (× 10(-3) mm2/s) for ischemic lesions was 58.29, 58.47, 57.83, 57.81, 57.58 and 54.51 using 2, 3, 4, 5, 6, and 7 b-values. Ischemic lesions had significantly different mean ADC values only for high b-values (b = 2000 s/mm2). CONCLUSION: ADC values can be reliably calculated using 2 b-values. Radiologists may use the more time-efficient 2-point method for reliably estimating ADC values and detecting ischemic lesions in the daily clinical routine.

Long-term health-related quality of life after decompressive hemicraniectomy in stroke patients with life-threatening space-occupying brain edema.

BACKGROUND: Although randomized clinical trials have reported significant improvement in mortality and functional outcome as measured with modified Rankin Scale (mRS) or Barthel index (BI) in stroke patients with space-occupying anterior circulation infarctions treated with hemicraniectomy, many clinicians are still concerned about the long-term health-related quality of life (HRQoL). AIM: Assessment of HRQoL after hemicraniectomy to holistically reevaluate clinical outcome. METHODS: Eleven patients (6 men, 5 women; mean age 48 (SD 5.8) years) were examined at 9-51 months after hemicraniectomy. Test batteries comprised NIH stroke scale, BI, mRS, neuropsychological tests (Visual Object and Space Perception Battery and clock test), and HRQoL-scales (Short Form 36 Health Survey (SF-36), Nottingham Health Profile (NHP), Questions on Life Satisfaction, Hospital Anxiety and Depression Scale and EQ-5D). RESULTS: Median values for NIHSS, BI and mRS were 11.5, 55 and 3.5. In HRQoL-scales, subscales related to physical mobility and functioning were consistently severely impaired, while subscales related to psychological well-being were impaired to a lesser extent. Mean scores for physical functioning and physical role were 10.5 and 12.5 in the SF-36, and 61.3 and 43.3 for physical mobility and energy in the NHP; emotional role and mental health scored 63.3 and 66.4 (SF-36), scores for emotional reaction and social isolation were 18.9 and 16.0 (NHP), respectively. CONCLUSION: Although, physical components of HRQoL are highly impaired, these stroke patients achieved a satisfying level of psychological well-being which was endorsed by a nearly unanimous retrospective appraisal of life-saving hemicraniectomy.

CT-angiographic collateralization predicts final infarct volume after intra-arterial thrombolysis for acute anterior circulation ischemic stroke.

BACKGROUND: Final infarct volume after thrombolysis for acute ischemic stroke depends on time to, and degree of reperfusion and residual blood flow, which is influenced by leptomeningeal collateralization. We evaluated the role of collateralization in the ischemic territory as a predictor of infarct size. METHODS: Twenty-five patients (17 women, 8 men, mean age: 67.6 ± 12.4 years) selected by non-contrast-enhanced CT and CT angiography (CTA) underwent intra-arterial thrombolysis (iaT) within 6 h after symptom onset (mean 4.1 ± 1.3 h) for middle cerebral and terminal internal carotid artery (MCA/ICA) stroke. CTA was evaluated for collateralization using thick-slice coronal and axial maximum-intensity projection reconstructions according to a simple score, the CTA collateralization score (CTA-cs): 0 = no collateral filling, 1 = ≤50%, 2 = >50% but <100%, and 3 = 100% collateral filling. We analyzed the association between the final infarct volume on CT 5 days after the intervention and the CTA-cs, successful reperfusion (Thrombolysis in Myocardial Infarction, TIMI, grades 2 and 3) and time to treatment in a prospective study approved by our institutional review board, with informed consent from all patients. RESULTS: Reperfusion was achieved in 72%. Asymptomatic and symptomatic parenchymal hemorrhage occurred in 2 patients (8%) each and hemorrhagic transformation in 4 (16%). CTA-cs (r = -0.63; p < 0.001) and postinterventional TIMI grade (r = -0.403; p = 0.046) were inversely associated with final infarct volume. After multiple regression analysis, CTA-cs and reperfusion remained as independent predictors of final infarct volume whereas time to treatment and initial stroke severity did not. CONCLUSION: The extent of collateralization and reperfusion are independent predictors of final infarct volume in acute MCA/ICA stroke treated with iaT. Time to treatment and stroke severity had no independent effect on final infarct volume.

A case of hippocampal laminar necrosis following complex partial status epilepticus.

Cortical laminar necrosis (CLN) is a metabolic injury pattern usually observed after cerebral hypoxia, hypoglycemia, or ischemia. We report serial magnetic resonance imaging findings in a patient with complex partial status epilepticus (SE) developing a band-like, T1-hyperintense lesion consistent with CLN along the surface of the left hippocampus without concurrent other causes of CLN. This observation suggests a direct pathogenetic link between SE and CLN involving combined damage to neurons and glia.

[Stroke: epidemiology, risk factors, and genetics]. / Schlaganfall: Epidemiologie, Risikofaktoren und Genetik.

Stroke constitutes a major global challenge for health policy and healthcare economics. Reducing stroke burden requires extensive knowledge of risk factors and, if applicable, preventive control. Risk factors may be categorized in non-modifiable biological factors, such as age, gender, race/ethnicity; proatherosclerotic/prothrombotic factors (hypertension, diabetes, dyslipidaemia, other serologic and haemostasis factors); cardiac comorbidity (CAD, CHF, atrial fibrillation); lifestyle factors, which play an increasing role, e.g. smoking, physical inactivity, alcohol consumption. These traditional risk factors are extended by rapidly growing efforts in elucidating genetic backgrounds for stroke. Genetic polymorphisms of functionally or pathophysiologically important proteins are investigated in the setting of case-control-studies for their role as candidate genes. Meta-analyses have corroborated the association of the factor V-Leiden arg506gln, MTHFR-C677T, and ACE-insertion-deletion polymorphisms with stroke. Current population-based, genome-wide linkage analyses face high expectations for identifying new genetic risk factors.

Predictors of hemorrhage in patients with untreated brain arteriovenous malformation.

BACKGROUND: Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been established, but their relevance for the risk of subsequent AVM hemorrhage remains unclear. METHODS: The authors analyzed follow-up data on 622 consecutive patients from the prospective Columbia AVM database, limited to the period between initial AVM diagnosis and the start of treatment (i.e., any endovascular, surgical, or radiation therapy). Univariate and multivariate logistic regression and Cox proportional hazard models were applied to analyze the effect of patient age, gender, AVM size, anatomic location, venous drainage pattern, and associated arterial aneurysms on the risk of intracranial hemorrhage at initial presentation and during follow-up. RESULTS: The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio [HR] 1.05, 95% CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95% CI 2.64 to 10.96), deep brain location (HR 3.25, 95% CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95% CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9% for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4% for those harboring all three risk factors. CONCLUSIONS: Hemorrhagic arteriovenous malformation (AVM) presentation, increasing age, deep brain location, and exclusive deep venous drainage appear to be independent predictors for AVM hemorrhage during natural history follow-up. The risk of spontaneous hemorrhage may be low in AVMs without these risk factors.

Immunophenotypic patterns of T-cell activation in neuroinflammatory diseases.

OBJECTIVES: We aimed to gain insights into the pathogen-specific differences in early adaptive immune responses following central nervous system infections with Borrelia burgdorferi and viral pathogens by studying the immunophenotypic patterns of T-cell activation. Moreover, we wished to determine whether the expression of T-cell activation markers reflects disease activity in multiple sclerosis (MS). METHODS: Proportions of cerebrospinal fluid T-cells expressing the markers HLA-DR, CD25 and CD38 were determined in patients with MS (n = 40), acute viral meningomyeloradiculoneuritis (VID, n = 26), early neuroborreliosis (NB, n = 23) and non-inflammatory neurologic diseases (n = 51) by using flow cytometry. In relapsing-remitting MS, disease activity was assessed by clinical examination and magnetic resonance imaging. RESULTS: For each of the surface markers that were examined, significant differences in T cell proportions were found between patient groups. The proportion of HLA-DR+ T cells was higher and that of CD25+ T cells lower in NB compared with VID. These differences were attributable only to the early phase of the disease (< or = 6 days after symptom onset). Among MS patients, there was a trend for higher proportions of T cells expressing activation markers in patients with gadolinium-enhancing lesions. CONCLUSIONS: The decreased CD25 expression in NB may reflect immunomodulatory effects of B. burgdorferi facilitating persistent infection. Larger prospective studies of T-cell activation markers for ascertaining the association between cellular markers and clinical surrogates of disease activity in MS are warranted.

Association of infratentorial brain arteriovenous malformations with hemorrhage at initial presentation.

BACKGROUND AND PURPOSE: The goal of this study was to analyze the association of hemorrhagic presentation with infratentorial brain arteriovenous malformations (AVMs). METHODS: The 623 consecutive, prospectively enrolled patients from the Columbia AVM Databank were analyzed in a cross-sectional study. Clinical presentation (diagnostic event) was categorized as intracranial hemorrhage or nonhemorrhagic presentation. From brain imaging and cerebral angiography, AVM location was classified as either infratentorial or supratentorial. Univariate and multivariate statistical models were applied to test the effect of age, sex, AVM size and location, venous drainage pattern, and associated (ie, feeding artery or intranidal) arterial aneurysms on the likelihood of hemorrhage at initial AVM presentation. RESULTS: Of the 623 patients, 72 (12%) had an infratentorial and 551 (88%) had a supratentorial AVM. Intracranial hemorrhage was the presenting symptom in 283 patients (45%), and infratentorial AVM location was significantly more frequent (18%) among patients who bled initially (6%; odds ratio [OR], 3.60; 95% confidence interval [CI], 2.09 to 6.20). This difference remained significant (OR, 1.99; 95% CI, 1.07 to 3.69) in the multivariate logistic regression model controlling for age, sex, AVM size, deep venous drainage, and associated arterial aneurysms. In the same model, the effect of other established determinants for AVM hemorrhage--ie, AVM size (in 1-mm increments; OR, 0.95; 95% CI, 0.94 to 0.96), deep venous drainage (OR, 3.09; 95% CI, 1.87 to 5.12), and associated aneurysms (OR, 2.78; 95% CI, 1.76 to 4.40)--remained significant. CONCLUSIONS: Our findings suggest that infratentorial AVM location is independently associated with hemorrhagic AVM presentation.

Effect of age on clinical and morphological characteristics in patients with brain arteriovenous malformation.

BACKGROUND AND PURPOSE: The goal of this work was to determine the effect of age at initial presentation on clinical and morphological characteristics in patients with brain arteriovenous malformation (AVM). METHODS: The 542 consecutive patients from the prospective Columbia AVM database (mean+/-SD age, 34+/-15 years) were analyzed. Univariate statistical models were used to test the effect of age at initial presentation on clinical (AVM hemorrhage, seizures, headaches, neurological deficit, other/asymptomatic) and morphological (AVM size, venous drainage pattern, AVM brain location, concurrent arterial aneurysms) characteristics. RESULTS: Hemorrhage was the presenting symptom in 46% (n=247); 29% (n=155) presented with seizures, 13% (n=71) with headaches, 7% (n=36) with a neurological deficit, and 6% (n=33) without AVM-related symptoms. Increasing age correlated positively with intracranial hemorrhage (P=0.001), focal neurological deficits (P=0.007), infratentorial AVMs (P<0.001), and concurrent arterial aneurysms (P<0.001); an inverse correlation was found with seizures (P<0.001), AVM size (P=0.001), and lobar (P<0.001), deep (P=0.008), and borderzone (P=0.014) location. No age differences were found for sex, headache, asymptomatic presentation, and venous drainage pattern. CONCLUSIONS: Our data suggest a significant interaction of patient age and clinical and morphological AVM features and argue against uniform AVM characteristics across different age classes at initial presentation. In particular, AVM patients diagnosed at a higher age show a higher fraction of AVM hemorrhage and are more likely to harbor additional risk factors such as concurrent arterial aneurysms and small AVM diameter. Longitudinal population-based AVM data are necessary to confirm these findings.

[Primary adenocarcinoma of the left atrium mimicking benign myxoma]. / Primäres Adenokarzinom des linken Herzvorhofes. Erst die Histologie führt zur Diagnose Adenokarzinom des Herzens.

Primary tumors of the heart are rare, whereas cardiac metastases, most frequently from adenocarcinomas, occur in up to 20% of malignant tumors. We report about a 61-year-old female patient who was admitted with recurrent stress-induced dizziness, intermittent tachycardia and a fall due to a pre-syncope. Echocardiography showed a left atrial tumor with the typical features of a pediculated myxoma, leading to open heart surgery. However, histopathology revealed a 2.2 x 1.5 cm adenocarcinoma. The subsequent search for a primary tumor, including tumor markers and (18)F-FDG-PET, was unsuccessful, as was a second thorough diagnostic workup half a year later. The tumor was therefore classified as a primary cardiac adenocarcinoma.