Effect of clinical features on antiseizure medication doses in patients with newly diagnosed epilepsy.

Objective: We evaluate the effect of distinct clinical features on anti-seizure medication (ASM) doses in seizure-free and not seizure-free patients aged ≥16 years with new-onset epilepsy. Materials and methods: This study included 459 patients with a validated diagnosis of epilepsy. The most prescribed ASMs were oxcarbazepine (OXC; n = 307), followed by valproic acid (VPA; n = 115), carbamazepine (CBZ; n = 81), and lamotrigine (LTG; n = 67). The seizure freedom rate with their first or subsequent ASM was 88.0%. A retrospective analysis of patient records was performed to determine any association between doses of ASMs and patient characteristics. Results: The median OXC dose in seizure-free patients aged >60 years was 600 mg compared to 900 mg in younger patients. When controlling for age but not in an unadjusted model, the median dose of OXC was lower (300 mg, p = 0.018) for seizure-free patients compared to non-seizure-free patients, and the median dose of OXC was also 300 mg lower among older patients aged >60 years (p < 0.001). The median OXC doses for men aged ≤60 years were 300 mg higher than for women aged >60 years (900 mg vs. 600 mg, p = 0.021). The median dose of VPA was 400 mg higher in men than in women (p < 0.001) and 400 mg higher in not seizure-free patients compared to seizure-free patients only when adjusting for sex (p < 0.001). Higher median doses for CBZ were registered with FAS compared with FBTCS (difference in median doses of 200 mg; p = 0.017). Conclusion: Significant OXC dose differences were detected between age groups, whereas VPA dosing was different in men and women. Moreover, CBZ doses were dependent on some seizure types. These data allow for the individualization of the initial target dosing based on key clinical characteristics.

Indications for the use of intravenous second-line antiseizure medications in an emergency room setting.

BACKGROUND: Second-line iv antiseizure medications (ASMs) are used to treat status epilepticus (SE), but in the emergency room setting, there might be other intended and unintended indications for administration. We wanted to explore these different indications and assess the actual usage of first- and second-line ASMs for SE with reference to other uses, such as for SE mimics. METHODS: In this retrospective study, we searched the electronic patient registry with the following terms: "epilepsy", "SE", and "seizure", during 2015. Patients at least 16 years old and treated with iv second-line ASMs were further analysed. We reassessed the indications for the use of iv ASMs based on clinical features and examinations performed. RESULTS: A total of 166 episodes from 136 patients with a median age of 66 years were evaluated, constituting the following indication categories: ongoing SE (48.2%), recurrent seizures (19.3%), postictal (12.1%), seizure mimics (10.2%) and prophylactic use of ASMs (10.2%). Ongoing SE included the following subgroups: convulsive SE, focal aware SE, nonconvulsive SE (NCSE) and NCSE with coma. The seizure mimics group had a preexisting epilepsy diagnosis more often than the ongoing SE group (73% vs. 44%, p = 0.039). Ischaemic stroke was the most frequent seizure mimic. EEG was performed during hospital admission in 78% of patients with ongoing SE, 50% of patients with recurrent seizures, 75% of patients with postictal state, 53% of seizure mimic episodes and 12% of the prophylactic group. In NCSE and comatose NCSE, the diagnosis was made, and treatment was initiated only after an EEG in 52% and 30% of cases, respectively. The use of newer second-line ASMs (levetiracetam and lacosamide) was frequent in our study population. Immediate side effects of ASMs were infrequent. CONCLUSIONS: Even though most of the use of ASMs was justified and administered for SE, it is a diagnostic challenge where a prior diagnosis of epilepsy can be a misleading factor, and EEG is an essential tool when clinical features are often overlapping with other acute seizure disorders. Side effects of the newer second-line ASMs after a single dose are infrequent.

Prescribed antiseizure medication doses and their relation to defined daily doses for achieving seizure freedom in newly diagnosed patients with epilepsy.

OBJECTIVES: To investigate the antiseizure medication (ASM) doses required to achieve seizure freedom and their correlation with the World Health Organization's defined daily doses (DDDs) in patients aged 16 years or older with newly diagnosed epilepsy. METHODS: The study included 459 patients with a validated diagnosis of new-onset epilepsy. Patient records were retrospectively analyzed to determine the ASM doses in patients with or without seizure freedom during follow-up. The DDD of the relevant ASM was then retrieved. RESULTS: The seizure-freedom rate with first and subsequent ASMs was 88% (404/459 patients) during the follow-up. The mean prescribed doses (PDDs) and PDD/DDD ratio of the most commonly used ASMs, ie, oxcarbazepine (OXC), carbamazepine (CBZ), and valproic acid (VPA), differed significantly between seizure-free and non-seizure-free status (992 mg and 0.99 vs 1132 mg and 1.13; 547 mg and 0.55 vs 659 mg and 0.66; and 953 mg and 0.64 vs 1260 mg and 0.84, respectively). The effect of the OXC dose as the first failed ASM on the possibility of achieving seizure freedom was significant (Fisher's exact test, p = 0.002). Thirty-four of 43 patients (79%) in which an OXC dose of ≤900 mg failed became seizure-free, as compared with 24 of 54 patients (44%) with a failed OXC dose >900 mg. SIGNIFICANCE: The present study provides new insights into the doses of the commonly used ASMs such as OXC, CBZ, and VPA that can lead to seizure freedom as monotherapy or as combination therapy. The higher PDD/DDD ratio of OXC (0.99) than that of CBZ or VPA renders a generalized PDD/DDD comparison highly problematic.

Long-term effectiveness of enzyme replacement therapy in Fabry disease with the p.Arg227Ter variant: Fabry disease in Ostrobothnia (FAST) study.

Fabry disease (FD) is an X chromosome-linked, life-threatening lysosomal disease caused by one of more than 1000 currently known variants in the α-galactosidase A (GLA) gene. The follow-up part of the Fabry Disease in Ostrobothnia (FAST) study reports the long-term effect of enzyme replacement therapy (ERT) on a prospectively collected cohort of 12 patients, 4 males and 8 females, mean age 46 years (SD 16), with the classical variant c.679C > T p.Arg227Ter, which is one of the most common FD variants worldwide. In the natural history period of the FAST study, half of the patients in both sexes had at least one major event, of which 80% were of cardiac origin. During 5 years of ERT, four patients had a total of six major clinical events consisting of one silent ischemic stroke, three ventricular tachycardias and two increased left ventricular mass indexes. In addition, four patients developed minor cardiac events, four patients minor renal events, and one patient a minor neurological event. ERTs may delay but not prevent the progression of the disease in most patients with the variant Arg227Ter. This variant might be suitable for investigating the efficacy of second-generation ERTs compared to the currently used ERTs regardless of sex.

Response to subsequent antiseizure medications after first antiseizure medication failure in newly diagnosed epilepsy.

Objective: There is a lack of studies using the International League Against Epilepsy (ILAE) recommendation to define drug-resistant epilepsy (DRE). This study evaluated the seizure freedom rates of substitution or add-on and subsequent antiseizure medication (ASM) therapies using different proposed definitions of DRE or ASM trials in patients with a failed first ASM. We also identified prognostic factors for 1-year seizure freedom. Methods: This study included 459 patients with epilepsy of whom 151 were not seizure-free after the first ASM. Multilevel mixed-effects logistic regression was used to examine the correlation between observations from the same patient. Results: The overall seizure freedom rate with the first and subsequent ASMs was 88.0% (404/459). The rate of DRE when defined as the failure of two ASMs for any reason was 20.0%, and according to the ILAE definition of DRE, it was 16.3%. After failing the first ASM, 63.6% of patients (96/151) became seizure free with subsequent ASMs and tried an average of 1.9 ASMs (range 1-5). Of the patients who achieved 1-year seizure freedom, 10.1% (41/404) were taking polytherapy and there was no difference between substitution and add-on. All the patients with generalized epilepsy were seizure-free. A favorable prognostic factor was age >60 years and an EEG without epileptiform activity. The efficacies of the different ASMs were largely similar, but drugs that enhanced GABA-mediated inhibitory neurotransmission had the lowest seizure freedom rate. Significance: In adults with newly-diagnosed epilepsy, 1-year seizure freedom was achieved for almost 90% of the patients. After failing the first ASM, two-thirds of the patients responded to subsequent ASM regimens. Our results support the feasibility and applicability of the ILAE concept of an adequate ASM trial and the failure of two ASMs as a definition of DRE.

Clinical utility of a video/audio-based epilepsy monitoring system Nelli.

OBJECTIVE: The aim of this study was to evaluate the clinical utility of a semi-automated hybrid video/audio-based epilepsy monitoring system (Nelli®) in a home setting. METHODS: In this retrospective study, 104 consecutive patients underwent Nelli-registration for an average of 29 days at their home. The seizure-related data obtained from the registration were assessed to investigate the utility of the Nelli-registration regarding clinical decision-making. RESULTS: Of 104 patients, Nelli® hybrid system was able to recognize clinically relevant events in 83 (80%) patients: epileptic seizures in 67 (65%) and nonepileptic events in 16 (15%). A total of 2767 epileptic seizures of different seizure types were captured and identified. These seizures included not only tonic-clonic seizures but also other complex or simple motor seizures. For the outcomes regarding clinical decision-making, a need for a new therapeutic intervention was recognized in 54 (51.9%) patients based on the number and severity of seizures captured by Nelli-registration. In 12 (11.5%) patients, the need to change the treatment plan was excluded because no evidence of suspected epileptic seizures was found. Nelli-registration aided in confirming the therapeutic efficacy of modifications of antiseizure medications (ASMs) or neuromodulation therapies in 13 (12.5%) patients. Nelli-registration enabled to determine the change in seizure classification and facilitated to reach clear diagnostic conclusions in 11 (10.6%) patients. In 14 (13.5%) patients, there was no change in clinical outcome, as Nelli-registration was unable to infer any clinical decision either due to inconclusive results or lack of typical events. Seizures detected during Nelli-registration aided in decision-making for therapeutic interventions in 71 (68%) patients. Altogether, 44 (42%) patients had adjustment of ASMs, and in 9 (9%) patients, Nelli-registrations led to the change in the settings of vagus nerve stimulation (VNS) or deep brain stimulation (DBS) treatment. Additionally, 18 (17%) patients were referred to presurgical evaluation or established a baseline seizure frequency before surgical implantation for neuromodulation treatment with VNS or DBS, while 33 (32%) patients had no change in therapy. Nine patients (8.7%) were referred to video-EEG monitoring (VEM), as Nelli-recorded events highlighted the need for presurgical evaluation in 6 patients or further diagnostic evaluation in 3 patients. CONCLUSION: This study confirms the clinical utility of the video/audio monitoring system Nelli® in home settings. Home monitoring with Nelli® hybrid system provides a new alternative for the assessment of frequency and type of epileptic seizures as well as for a recognition of nonepileptic events. Thus, Nelli-registration can facilitate the optimization of seizure monitoring and management in clinical practice, complementing existing methods such as VEM and ambulatory EEG recordings.

Pulmonary manifestations and the effectiveness of enzyme replacement therapy in Fabry Disease with the p. Arg227Ter (p.R227*) mutation.

BACKGROUND: Fabry disease (FD) is caused by a defect in α-galactosidase A gene (GLA) which leads to a progressive accumulation of neutral shingolipids, mainly globotriaosylceramide and its metabolites in several organs. Pulmonary manifestations of FD mimic chronic obstructive pulmonary disease and are disproportionate to smoking status. The effect of enzyme replacement therapy (ERT) on pulmonary function is inconclusive. We studied the effect of ERT on pulmonary function in FD with a mutation p. Arg227Ter (p.R227*) which is one of the most common mutations causing classical FD in Finland and worldwide. METHODS: Patients were annually examined by multidisciplinary team. Based on the maximal pulmonary oxygen consumption at the baseline, either cardiopulmonary exercise test or combination of spirometry and 6-minute walking test were performed annually during 5-year follow-up. RESULTS: Four males and eight females met the criteria for ERT and were included in this study. Three of 12 patients had obstruction by GOLD criterion before ERT, and one had a borderline obstruction. In 5 years, five patients were classified as obstructive, although the real change in FEV1/FVC was unchanged in the whole cohort. Only one patient was an active smoker. CONCLUSION: In nonsmokers, pulmonary manifestations in classical FD are mild and might be stabilized by ERT.

Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients.

BACKGROUND: Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. OBJECTIVES: To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. METHODS: In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. RESULTS: Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. CONCLUSIONS: SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.

Response to first antiseizure medication in patients diagnosed with epilepsy.

OBJECTIVES: To investigate the interaction among the efficacy, tolerability and overall effectiveness of the first antiseizure medication in patients 16 years or older with newly diagnosed epilepsy. MATERIALS AND METHODS: The study included 584 patients who were referred to the Tampere University Hospital between 1 January 1995 and 31 December 2005 and were diagnosed with epilepsy. All individuals were retrospectively followed up until 31 December 2006, until reaching at least one year of seizure freedom, or until death if before the cut-off date. RESULTS: Overall, after thorough validation of the epilepsy diagnosis 459 patients comprised the study cohort; among these patients, 73% of males and 60% of females became seizure-free for at least one year with the first antiseizure medication. The seizure freedom rate for focal epilepsy was 67%. There was no significant difference in focal epilepsy to achieve seizure freedom between oxcarbazepine, carbamazepine or valproic acid. The seizure freedom rate among patients above 60 years of age was 67%. For patients with structural and unknown aetiology, seizure freedom rates were 61.5% and 75.3%, respectively. Additionally, epileptiform activity on EEG in patients with focal epilepsy decreased odds of seizure freedom in adjusted logistic regression models (OR 0.55, p=0.036). CONCLUSIONS: This study provides a more positive prediction of seizure freedom compared with previous studies with the onset of epilepsy at 16 years or older with an overall estimation that two-thirds of patients with new-onset epilepsy obtain seizure freedom with the first antiseizure medication.

Natural course of Fabry disease with the p. Arg227Ter (p.R227*) mutation in Finland: Fast study.

BACKGROUND: Fabry disease is caused by a deficient or an absent alfa-galactosidase A activity and is an X-linked disorder that results in organ damage and a shortened life span, especially in males. The severity of the disease depends on the type of mutation, gender, skewed X-chromosome inactivation, and other still unknown factors. METHODS: In this article, we describe the natural course of a common classic Fabry disease mutation, p.Arg227Ter or p.R227*, in Finland. RESULTS: Four males and ten females belonged to two extended families. The mean age was 46 years (SD 18.4). Six patients (43%) had cardiac hypertrophy, three patients (21%) had ischemic stroke, and none had severe kidney dysfunction. Three patients had atrial fibrillation; two patients who had atrial fibrillation also had pacemakers. All males over 30 years of age had at least one of the following manifestations: cardiac hypertrophy, stroke, or proteinuria. In females, the severity of Fabry disease varied from classic multiorgan disease to a condition that mimicked the attenuated cardiac variant. No one was totally asymptomatic without any signs of Fabry disease. Cardiac magnetic resonance imaging was performed on nine of 14 patients was the most sensitive for detecting early cardiac manifestations. Five patients (55%) had late gadolinium enhancement-positive segments. CONCLUSION: Cardiac involvement should be effectively detected in females before considering them asymptomatic mutation carriers.

Internal Carotid Artery and the Proximal M1 Segment Are Optimal Targets for Mechanical Thrombectomy.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is an established treatment of acute anterior circulation stroke caused by large vessel occlusion (LVO). We compared the clinical outcome (3-month modified Rankin Scale, mRS) in hyperacute (<3h from the onset of symptoms) ischemic stroke between an MT and an intravenous thrombolysis (IVT) cohort in proximal (ICA and the proximal M1 segment of the middle cerebral artery) and distal (the distal M1 and the M2 segment) LVOs. METHODS: We prospectively reviewed 67 patients who underwent MT with newer-generation stent retrievers. The IVT cohort consisted of 98 patients who received IVT without MT. We recorded baseline clinical, procedural and imaging variables, technical outcome, 24-h imaging outcome, and the clinical outcome. Differences between the groups were studied with theoretically appropriate statistical tests and binary logistic regression analysis. RESULTS: The proportion of patients who had a proximal LVO and experienced good (mRS ≤2) or excellent (mRS ≤1) clinical outcome was significantly larger in the MT group (62 vs. 7%, p < 0.001; 47 vs. 3%, p < 0.001, respectively). In a regression model including relevant confounding variables, good clinical outcome was seen significantly more often among patients with proximal occlusions (OR = 6.0, CI 95% 1.9-18.3, p = 0.002). In a similar model, no statistically significant differences were observed in patients with more distal occlusions. CONCLUSIONS: MT is superior to IVT in achieving good clinical outcome in hyperacute anterior circulation stroke in the most proximal occlusions (ICA and proximal M1 segment). In the distal M1 and M2 segments neither of these therapies clearly outperforms the other.

Collateral Circulation Predicts the Size of the Infarct Core and the Proportion of Salvageable Penumbra in Hyperacute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

BACKGROUND: We studied the impact of collateral circulation on CT perfusion (CTP) parametric maps and the amount of salvaged brain tissue, the imaging and clinical outcome at 24 h and at 3 months in a retrospective acute (<3 h) stroke cohort (105 patients) with anterior circulation thrombus treated with intravenous thrombolysis. METHODS: Baseline clinical and imaging information were collected and groups with different collateral scores (CS) were compared. Binary logistic regression analyses using good CS (CS ≥2) as the dependent variable were calculated. RESULTS: CTP Alberta Stroke Program Early CT Score (ASPECTS) was successfully assessed in 58 cases. Thirty patients displayed good CS. Poor CS were associated with more severe strokes according to National Institutes of Health Stroke Scale (NIHSS) at arrival (15 vs. 7, p = 0.005) and at 24 h (10 vs. 3, p = 0.003) after intravenous thrombolysis. Good CS were associated with a longer mean onset-to-treatment time (141 vs. 121 min, p = 0.009) and time to CTP (102 vs. 87 min, p = 0.047), better cerebral blood volume (CBV) ASPECTS (9 vs. 6, p < 0.001), better mean transit time (MTT) ASPECTS (6 vs. 3, p < 0.001), better noncontrast CT (NCCT) ASPECTS (10 vs. 8, p < 0.001) at arrival and with favorable clinical outcome at 3 months (modified Rankin Scale ≤2, p = 0.002). The fraction of penumbra that was salvageable at arrival and salvaged at 24 h was higher with better CS (p < 0.001 and p = 0.035, respectively). In multivariate analysis, time from the onset of symptoms to imaging (p = 0.037, OR 1.04 per minute, 95% CI 1.00-1.08) and CBV ASPECTS (p = 0.001, OR 2.11 per ASPECTS point, 95% CI 1.33-3.34) predicted good CS. In similar multivariable models, MTT ASPECTS (p = 0.04, OR 1.46 per ASPECTS point, 95% CI 1.02-2.10) and NCCT ASPECTS predicted good CS (p = 0.003, OR 4.38 per CT ASPECTS point, 95% CI 1.66-11.55) along with longer time from the onset of symptoms to imaging (p = 0.045, OR 1.03 per minute, 95% CI 1.00-1.06 and p = 0.02, OR 1.05 per minute, 95% CI 1.00-1.09, respectively). CBV ASPECTS had a larger area under the receiver operating characteristic curve for good CS (0.837) than NCCT ASPECTS (0.802) or MTT ASPECTS (0.752) at arrival. CONCLUSIONS: Favorable CBV ASPECTS, NCCT ASPECTS and MTT ASPECTS are associated with good CS along with more salvageable tissue and longer time from the onset of symptoms to imaging in ischemic stroke patients treated with intravenous thrombolysis.

The association of blood pressure and collateral circulation in hyperacute ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUND: The integrity of collateral circulation is a major prognostic factor in ischemic stroke. Patients with good collateral status have larger penumbra and respond better to intravenous thrombolytic therapy. High systolic blood pressure is linked with worse clinical outcome in patients with acute ischemic stroke treated with intravenous thrombolytic therapy. We studied the effect of different blood pressure parameters on leptomeningeal collateral circulation in patients treated with intravenous thrombolytic therapy (<3 h) in a retrospective cohort. METHODS: Anterior circulation thrombus was detected with computed tomography angiography and blood pressure was measured prior to intravenous thrombolytic therapy in 104 patients. Baseline clinical and imaging information were collected. Group comparisons were performed; Collateral Score (CS) was assessed and entered into logistic regression analysis. RESULTS: Fifty-eight patients out of 104 displayed good collateral filling (CS ≥2). Poor CS was associated with more severe strokes according to National Institutes of Health Stroke Scale (NIHSS) at arrival (16 vs. 11, p = 0.005) and at 24 h (15 vs. 3, p < 0.001) after the treatment. Good CS was associated with higher systolic blood pressure (p = 0.03), but not with diastolic blood pressure (p = 0.26), pulse pressure (p = 0.20) or mean arterial pressure (p = 0.07). Good CS was associated with better Alberta Stroke Program Early CT Score (ASPECTS) in 24 h follow-up imaging (p < 0.001) and favorable clinical outcome at three months (mRS ≤2, p < 0.001). Median CS was the highest (CS = 3) when systolic blood pressure was between 170 and 190 mm Hg (p = 0.03). There was no significant difference in the number of patients with good (n = 11) and poor (n = 12) CS who received intravenous antihypertensive medication (p = 0.39) before or during the thrombolytic therapy. In multivariate analysis age (p = 0.02, OR 0.957 per year, 95% CI 0.92-0.99), time from the onset of symptoms to treatment (p = 0.005, OR 1.03 per minute, 95% CI 1.01-1.05), distal clot location (p = 0.02, OR 3.52, 95% CI 1.19-10.35) and systolic blood pressure (p = 0.04, OR 1.03 per unit mm Hg, 95% CI 1.00-1.05) predicted good CS. Higher systolic blood pressure (p = 0.049, OR 0.96 per unit mm Hg, 95% CI 0.93-1.00) and pulse pressure (p = 0.005, OR 0.94 per unit mm Hg, 95% CI 0.90-0.98) predicted unfavorable clinical outcome at three months in multivariate analysis. CONCLUSION: Moderately elevated systolic blood pressure is associated with good collateral circulation in patients treated with intravenous thrombolytic therapy. However, there is an inverse association of systolic blood pressure with the three-month clinical outcome. Diastolic blood pressure, mean arterial pressure and pulse pressure are not statistically and significantly associated with collateral status.

A male Fabry disease patient treated with intravenous thrombolysis for acute ischemic stroke.

The use of intravenous thrombolytic therapy for acute ischemic stroke is associated with improved outcomes. Fabry disease is an X-linked glycosphingolipid storage disease with vascular endothelial deposits. Affected males with the classic phenotype develop renal, cardiac, and cerebrovascular disease and die prematurely. However, Fabry disease is rare in young men with first ischemic stroke of undetermined cause. We report a 38-year-old man with acute aphasia and a left M2 segment of the middle cerebral artery thrombus with no recanalization who was finally diagnosed with Fabry disease after left ventricular hypertrophy of undetermined cause had been identified. A gene test revealed a R227X mutation typical of Fabry disease with the classical phenotype. To our knowledge our patient is the first reported male Fabry patient who was given intravenous thrombolytic therapy and the first reported Fabry patient who received intravenous thrombolytic therapy between 3 and 4.5 hours of the symptom onset. Despite favorable prognostic indicators on admission imaging, our patient suffered a significant stroke and had an unfavorable clinical outcome. Fortunately, the episode was not complicated by intracranial hemorrhage. Further studies are needed to evaluate the efficacy and safety of intravenous thrombolytic therapy in treating patients with Fabry disease and acute ischemic stroke.

Impact of atrial fibrillation and inadequate antithrombotic management on mortality in acute neurovascular syndrome.

BACKGROUND: The purpose of this study was to observe adherence to antithrombotic management guidelines among atrial fibrillation (AF) patients and to determine prognostic factors for 3-month mortality in both ischemic and hemorrhagic stroke patients with or without AF. METHODS: This was a retrospective observational single stroke center cohort study. In 2007, 380 patients with acute stroke-like symptoms were admitted to Tampere University Hospital as candidates for intravenous thrombolysis. Group comparisons (with or without AF) were performed, and binary logistic regression modeling was used to predict 3-month mortality for different clinical and imaging variables. RESULTS: The prevalence of AF in the acute neurovascular syndrome population was 33%. During hospitalization, the detection rate of previously undiagnosed paroxysmal AF was 8% (17 of 217). Only 26% (18 of 69) of known AF-related ischemic stroke patients had an International Normalized Ratio value above 1.9. National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score at admission in ischemic stroke and intracerebral hemorrhage were significant prognostic factors for 3-month mortality in acute neurovascular syndrome patients with AF according to a multivariable analysis. Inadequate antithrombotic management according to at-the-time and current treatment guidelines was not a risk factor for 3-month mortality. CONCLUSIONS: Patients with AF have more severe stroke and higher mortality than stroke patients without AF. Adherence to the antithrombotic treatment guidelines for the prevention of AF-related cardioembolic strokes is suboptimal. Further studies are needed to evaluate the impact of current antithrombotic treatment guidelines on mortality.

Impact of window setting optimization on accuracy of computed tomography and computed tomography angiography source image-based Alberta Stroke Program Early Computed Tomography Score.

The use of narrower window width settings on computed tomography (CT) improves sensitivity for detection of early ischemic changes in acute ischemic stroke. This study analyzed the effect of optimization of window settings on the accuracy of Alberta Stroke Program Early Computed Tomography Score (ASPECTS) performed on noncontrast CT (NCCT) and CT angiography source images (CTA-SI). ASPECTS was calculated on NCCT and CTA-SI with standard and optimized window width/center settings in a consecutive series of patients with acute ishcemic stroke. The difference between CT-based ASPECTS and ASPECTS performed on follow-up magnetic resonance imaging (MRI) were calculated to determine the disparity between initial estimates of the extent of ischemia on CT and follow-up lesion imaging by MRI. Forty-four patients were included into the study. The mean difference with respect to follow-up MRI-ASPECTS was 4.1 ± 2.2 for standard NCCT-ASPECTS, 3.7 ± 2.3 for optimized NCCT-ASPECTS, 3.0 ± 2.2 for standard CTA-SI-ASPECTS, and 2.7 ± 2.1 for optimized CTA-SI-ASPECTS. The improvement introduced by the optimization of window settings and use of CTA-SI was statistically significant (P < .01). Our data indicate that the accuracy of ASPECTS is improved with optimized window display settings. This improvement is irrespective of experience or specialty of the rater performing the assessment.

Comparison of 64-row and 16-row multidetector CT in the perfusion CT evaluation of acute ischemic stroke patients receiving intravenous thrombolytic therapy.

INTRODUCTION: Perfusion computed tomography (PCT) is increasingly performed in multimodal CT evaluation of acute ischemic stroke. We compared the technical quality of perfusion studies performed with a 16-row and a 64-row scanner and analyzed the differences between the scanners in their ability to detect perfusion defects. METHODS: We analyzed retrospectively the clinical and imaging data of 140 consecutive acute (<3 h) stroke patients who underwent multimodal CT evaluation and received intravenous rtPA. Alberta Stroke Program Early CT Score (ASPECTS) was assigned to PCT maps. Clinical and imaging parameters were compared between the two scanners. RESULTS: There were more motion artifacts in the 16-row studies (p = 0.04), and the analysis software was able to completely correct significantly fewer of these (p < 0.001). Both ASPECTS levels were optimally covered in only 29% of the 16-row studies, whereas in the 64-row studies, both levels were invariably optimally visualized (p < 0.001). This significantly decreased the sensitivity of the 16-row scanner to detect perfusion defects in the upper ASPECTS level (p = 0.02). The 64-row scanner was able to detect more perfusion defects that were located entirely outside the ASPECTS regions (p = 0.03). There was no significant difference in the 3-month functional outcome. CONCLUSIONS: The 16-row scanner suffered from limited anatomic coverage that decreased the sensitivity to detect perfusion defects in the cranial parts of the middle cerebral artery region. The 16-row studies had poorer technical quality that was in part attributable to higher sampling frequency and smaller slice thickness making the imaging more sensitive to small-scale movement of the patient.

The clot burden score, the Boston Acute Stroke Imaging Scale, the cerebral blood volume ASPECTS, and two novel imaging parameters in the prediction of clinical outcome of ischemic stroke patients receiving intravenous thrombolytic therapy.

INTRODUCTION: Recently two classification methods based on the location and the extent of thrombosis detected with CT angiography have been introduced: the Boston Acute Stroke Imaging Scale (BASIS) and the clot burden score (CBS). We studied the performance of BASIS and CBS in predicting good clinical outcome (mRS ≤ 2 at 90 days) in an acute (< 3 h) stroke cohort treated with intravenous thrombolytic therapy. METHODS: Eighty-three consecutive patients who underwent multimodal CT were analyzed. Binary logistic regression model was used to assess how BASIS, CBS, and cerebral blood volume (CBV) ASPECTS predict favorable clinical outcome. Diagnostic sensitivities and specificities were calculated and compared. RESULTS: Patients with low CBS and CBV ASPECTS scores and major strokes according to BASIS had significantly higher admission NIHSS scores, larger perfusion defects, and more often poor clinical outcome. In logistic regression analysis, CBV ASPECTS, CBS and BASIS were significantly associated with the clinical outcome. The performance of BASIS improved when patients with thrombosis of the M2 segment of the middle cerebral artery were classified as having minor stroke (M1-BASIS). In the anterior circulation, the sum of CBS and CBV ASPECTS (CBSV) proved to be the most robust predictor of favorable outcome. CBV ASPECTS and CBS had high sensitivity but moderate to poor specificity while BASIS was only moderately sensitive and specific. CONCLUSION: CBS, BASIS, and CBV ASPECTS are statistically robust and sensitive but unspecific predictors of good clinical outcome. Two new derived imaging parameters, CBSV and M1-BASIS, share these properties and may have increased prognostic value.