How enoxaparin underdosing and sex contribute to achieving therapeutic anti-Xa levels.

Introduction: Anti-Xa serves as a clinical surrogate for assessing the efficacy and bleeding risk in patients treated with enoxaparin for thromboembolic events. Evidence from the literature and empirical observations suggest that patients are underdosed in clinical practice to avoid bleeding complications. This study aimed to investigate such underdosing of enoxaparin and its potential impact on achieving therapeutic anti-Xa levels. Methods: This multicentric, retrospective, observational study included patients with acute ischemic stroke due to atrial fibrillation. All patients received enoxaparin in the therapeutic setting with subsequent anti-Xa measurements. The one-sample, one-tailed Wilcoxon signed-rank test was used to identify a significant difference between the doses administered and the recommended daily dose. Logistic regression model analysis was performed to identify additional predictors affecting achievement of the therapeutic anti-Xa target range. Stepwise forward-backward selection with Akaike's information criterion as metric was applied to refine the logistic regression model. Results: A total of 145 patients from the university hospitals of St. Pölten and Tulln in Lower Austria were included. The median daily enoxaparin dose administered was 1.23 mg/kg, resulting in an overall target range achievement rate of 66%. As compared to recommended therapeutic doses, significant underdosing of enoxaparin was evident in both participating centers (p < 0.001). The calculated threshold dose to achieve the therapeutic target range with a 90% probability was 1.5 mg/kg enoxaparin daily. Female sex was found to be a strong independent predictor of achieving a therapeutic target range (OR 9.44; 95% CI 3.40-30.05, p < 0.001). Conclusion: Despite the underdosing observed in both centers, therapeutic anti-Xa levels were achieved with lower than recommended doses of enoxaparin, and women required even lower doses than men. These findings warrant further confirmation by prospective studies.

Anti-Ri paraneoplastic neurological syndrome presenting with bilateral cranial nerve VI palsy and jaw dystonia-a distinctive syndrome within the anti-Ri spectrum? : Case report and literature review.

OBJECTIVE: Paraneoplastic neurological syndromes (PNS) are rare disorders associated with various onconeuronal antibodies. Anti-Ri antibodies (ANNA-2) are typically found in patients with opsoclonus myoclonus syndrome (OMS) and ataxia. CASE REPORT: We present an anti-Ri antibody-positive 77-year-old woman with subacute progressive bilateral cranial nerve VI palsy, gait disturbance and jaw dystonia. MRI of the brain showed hyperintense signals on T2 bitemporal without contrast enhancement. Cerebrospinal fluid (CSF) examination exhibited mild pleocytosis of 13 cells/µl and positive oligoclonal bands. CSF was overall inconspicuous for a malignant or inflammatory etiology. Immunofluorescence analysis revealed anti-Ri antibodies in both serum and CSF. Subsequent diagnostic work up resulted in a newly diagnosed ductal carcinoma of the right breast. PNS in this case partially responded to the anti-tumor therapy. CONCLUSION: This case shows similarities with recently published anti-Ri syndromes, which might form a distinct triad within the anti-Ri spectrum.

Perioperative levetiracetam for seizure prophylaxis in seizure-naive brain tumor patients with focus on neurocognitive functioning.

INTRODUCTION: In seizure-naive brain tumor patients, the efficacy of perioperative prophylactic antiepileptic drug treatment remains controversial. In case of administration, the common preferred drug is levetiracetam (LEV) because of its favorable pharmacological profile. Research to date has not sufficiently determined how LEV affects cognition in the short term, as is the case in the perioperative period. The objective of this prospective study was to examine the neurocognitive functioning of seizure-naive brain tumor patients after receiving LEV perioperatively. METHODS: Fortythree patients with supratentorial brain tumor scheduled for surgery received LEV three days before until six days after surgery as seizure prophylaxis. Cognitive functioning (NeuroCogFX), LEV plasma-levels, hematotoxicity, side-effects, as well as health-related quality of life (HRQoL, Qolie31), were recorded preoperatively before (Baseline) and after onset of LEV (Pre-Op), 4-6 days postoperatively (Post-Op) and 21 days postoperatively (Follow-Up). RESULTS: No significant changes in cognitive functioning and HRQoL were seen after onset of preoperative LEV. There was a significant improvement of NeuroCogFX total-score at Follow-Up (p = 0.004) compared to Baseline. The overall-score Qolie31 showed simultaneous improvement patterns as cognitive functioning (p < 0.001). The most frequent side effect related to study drug was somnolence (in 28.6% of patients). CONCLUSIONS: A significant improvement of cognitive functioning, as well as an improvement in HRQoL, were detected postoperatively. This is presumably due to the debulking effect of the surgery. Nevertheless, LEV has no detrimental effect on cognitive functioning in the perioperative phase in seizure-naive brain tumor patients. TRIAL REGISTRATION: This study was registered prospectively (Date: 25/11/2015; EudraCT: 2015-003,916-19).

Real-time monitoring of intravenous thrombolysis in acute ischemic stroke using rotational thromboelastometry: a feasibility pilot study.

INTRODUCTION: Rotational thromboelastometry (ROTEM) records whole blood coagulation in vitro. Data on dynamic changes of clot patterns during intravenous thrombolysis (IVT) in acute ischemic stroke is scarce. We investigated the feasibility of ROTEM as a potential point-of-care assessment tool for IVT. METHODS: In this prospective pilot study, patients with acute stroke symptoms received IVT. Whole blood coagulation was tracked on the ROTEM analyzer. Blood samples were analyzed before, and then 2, 15, 30 and 60 min after beginning IVT. In vitro clots (iCLs) were described by their maximum clot firmness (MCF), the time needed to reach MCF (MCF-t), as well as the area under the curve (AR10). National Institutes of Health Stroke Scale (NIHSS) was used as early clinical outcome parameter. RESULTS: We analyzed 288 iCLs from 12 patients undergoing IVT. In all iCLs, an early fibrinolysis (91% within the first 10 min) was detected during IVT. Three different curve progression patterns were observed: a low-responder pattern with a continuous clot increase, a high-responder pattern with a sustained clot decrease or total clotting suppression and an intermediate-responder pattern with alternating clot characteristics. There was a difference among these groups in early clinical outcome (AR10 and MCF each p = 0.01, MCF-t p = 0.02, Kruskal-Wallis Test). CONCLUSION: The fibrinolysis patterns determined using ROTEM allow for the monitoring of IVT in patients with acute ischemic stroke. This pilot study found a correlation between the in vitro fibrinolysis patterns and early clinical outcomes. These findings support a potential for individualization of IVT in the future.

Multimodal assessment of disease activity in glioblastoma : A single center experience.

BACKGROUND: Assessment of disease activity in glioblastoma (GBM) can be challenging due to several clinical and radiological pitfalls. Besides MRI, FET-PET and neurocognitive assessment (NA) are used in several neuro-oncological centers in order to improve the specificity of response assessment. We performed a retrospective study to investigate whether the assessment by RANO (Response Assessment in NeuroOncology) corresponds to FET-PET imaging and NA results. Moreover, the concordance of RANO with a final recommendation of an interdisciplinary neuro-oncological tumor board recommendation (TBR) was analyzed. METHODS: We enrolled 25 consecutive patients with newly diagnosed histologically confirmed GBM in a pilot study, accounting for 81 multimodal test results. All patients were selected after undergoing consecutive follow-up comprising MRI, FET-PET, and NA with a subsequent TBR. Results were analyzed for correlations between RANO, FET-PET and NA. An additional consistency analysis was performed to elucidate the impact of RANO on decision making. RESULTS: A highly statistically significant correlation was found between RANO and FET-PET and NA results (all P < 0.01); however, 26% of follow-up tests exhibited inconsistent results in multimodal assessment, among which RANO was only 48% in accordance with the final TBR. The concordance of NA and FET-PET with the final TBR was 67% and 86%, respectively. CONCLUSION: The RANO proved its value in the context of multimodal assessment of disease activity in GBM; however, because the implementation of multimodal assessment showed a considerably high percentage of inconsistent results, further studies are required to investigate the relationship between different assessment techniques, in addition to their overall significance to response rating.

Migraine and vertigo--a prospective diary study.

The objective of the study was to examine migrainous vertigo prospectively by means of a diary. We included 146 patients with at least one migraine attack per month. All patients underwent a semistructured interview, completed questionnaires on depression, anxiety and quality of sleep and kept a diary covering detailed information on headache, vertigo and dizziness over a period of 30 days. A completed diary was returned by 116 patients (79.5%). Based on the diary migrainous vertigo (MV) was diagnosed in 18 patients (15.5%) and non-migrainous vertigo or dizziness (non-MV) in 35 patients (30.2%). MV was present on 65 of 3477 patient days (1.9%) and non-MV on 145 days (4.2%). MV occurred more often on days with headache (P < 0.001). Its median duration was 3 h and it lasted longer on days with headache than on days without headache (P < 0.001). The most prominent specific feature of MV was head motion intolerance. Patients with MV showed anxiety more often (P < 0.001) and tended to have worse quality of sleep and higher depression scores. In conclusion, vertigo and dizziness are frequent symptoms in migraineurs. The 1-month prevalence of MV is 16% and that of non-MV 30% in patients with at least one migraine attack per month. Frequency of MV is higher and duration longer on days with headache. MV is a risk factor for co-morbid anxiety.