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David J Seiffge - Top 30 Publications

Serum Neurofilament Light Chain in Patients with Acute Cerebrovascular Events.

Serum Neurofilaments are markers of axonal injury. We addressed their diagnostic and prognostic role in acute ischemic stroke (AIS) and TIA.

Non-office-hours admission affects intravenous thrombolysis treatment times and clinical outcome.

Intravenous Thrombolysis in Patients with Stroke Taking Rivaroxaban Using Drug Specific Plasma Levels: Experience with a Standard Operation Procedure in Clinical Practice.

Standard operating procedures (SOP) incorporating plasma levels of rivaroxaban might be helpful in selecting patients with acute ischemic stroke taking rivaroxaban suitable for IVthrombolysis (IVT) or endovascular treatment (EVT).

Author response: Early start of DOAC after ischemic stroke: Risk of intracranial hemorrhage and recurrent events.

Acute Ischemic Stroke in Nonconvulsive Status Epilepticus-Underestimated? Results from an Eight-Year Cohort Study.

Outcome of intracerebral hemorrhage associated with different oral anticoagulants.

In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non-vitamin K antagonist oral anticoagulation-related ICH (NOAC-ICH) and vitamin K antagonist-associated ICH (VKA-ICH).

Early start of DOAC after ischemic stroke: Risk of intracranial hemorrhage and recurrent events.

In patients with recent acute ischemic stroke (AIS) and atrial fibrillation, we assessed the starting time of direct, non-vitamin K antagonist oral anticoagulants (DOACs) for secondary prevention, the rate of intracranial hemorrhage (ICH), and recurrent ischemic events during follow-up.

Frequency and Determinants of Adherence to Oral Anticoagulants in Stroke Patients with Atrial Fibrillation in Clinical Practice.

Vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs) are beneficial in patients with stroke and atrial fibrillation (AF). However, little is known about frequency and determinants of adherence to NOACs/VKAs in clinical practice.

Feasibility of rapid measurement of Rivaroxaban plasma levels in patients with acute stroke.

Plasma levels of Rivaroxaban (RivLev) might be useful to guide therapeutic decisions in patients with acute stroke under Rivaroxaban. A prerequisite for the potential clinical usefulness is their rapid availability in emergency situations. Single-center explorative analysis from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (NOACISP, We included consecutive patients with acute ischemic or hemorrhagic stroke under Rivaroxaban (last intake <48 h) in which RivLev determined by an automated anti-factor Xa-based chromogenic assay (Hyphen-Biomed, France) are available. Primary endpoint was the turnaround time (TAT), defined as time from registration of the blood sample in the lab to first result published. Furthermore, we studied, whether TAT is influenced by (1) on- and off-hour-measurements and (2) early versus later patient arrival (cut-off: 270 min after symptom onset). Thirty-eight patients met the eligibility criteria (mean age 77 years, 44 % female). TAT was 34 min (IQR 29-65 min). TATs were similar for on- (n = 14; median 34 min; IQR 30-56 min) and off-hours-TATs (n = 24; median 35 min; IQR 29-75 min) as well as for early (n = 16; median 33 min; IQR 30-40 min) and late patient arrival (n = 22, median 34 min, IQR 28-58 min; all nonsignificant.). Taking into account RivLev in the decision process about the use of intravenous thrombolysis, three patients received intravenous thrombolysis on an individualized basis, none of them with bleeding complications. Emergency measurement of RivLev among patients with acute stroke is available within a median of 34 min and therefore feasible for ED use. Due to the rapid availability, further research to evaluate the role of RivLev in order to guide acute treatment decisions is warranted.

Intravenous Thrombolysis in Patients Dependent on the Daily Help of Others Before Stroke.

We compared outcome and complications in patients with stroke treated with intravenous thrombolysis (IVT) who could not live alone without help of another person before stroke (dependent patients) versus independent ones.

Serum Neurofilament Light Chain Levels Are Associated with Clinical Characteristics and Outcome in Patients with Cervical Artery Dissection.

Serum neurofilament light chain (sNfL) levels represent a promising marker of neuroaxonal injury. They are elevated in several neurological conditions, but their importance in cerebrovascular diseases remains unclear. In a proof of concept study, we compared sNfL levels with clinical characteristics and outcome in patients with cervical artery dissection (CeAD).

Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome.

We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC).

Symptomatic intracranial hemorrhage after stroke thrombolysis: comparison of prediction scores.

Several prognostic scores have been developed to predict the risk of symptomatic intracranial hemorrhage (sICH) after ischemic stroke thrombolysis. We compared the performance of these scores in a multicenter cohort.

Dose-related effects of statins on symptomatic intracerebral hemorrhage and outcome after thrombolysis for ischemic stroke.

The aim of our study was to assess whether statins have dose-dependent effects on risk of symptomatic intracerebral hemorrhage (sICH) and outcome after intravenous thrombolysis for ischemic stroke.

IV thrombolysis and renal function.

To investigate the association of renal impairment on functional outcome and complications in stroke patients treated with IV thrombolysis (IVT).

Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?

We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis.

Validation of the DRAGON score in 12 stroke centers in anterior and posterior circulation.

The DRAGON score predicts functional outcome in the hyperacute phase of intravenous thrombolysis treatment of ischemic stroke patients. We aimed to validate the score in a large multicenter cohort in anterior and posterior circulation.

Relationship between onset-to-door time and door-to-thrombolysis time: a pooled analysis of 10 dedicated stroke centers.

Inverse relationship between onset-to-door time (ODT) and door-to-needle time (DNT) in stroke thrombolysis was reported from various registries. We analyzed this relationship and other determinants of DNT in dedicated stroke centers.

Long-term outcome in stroke patients treated with IV thrombolysis.

Data on long-term outcome after IV thrombolysis (IVT) are sparse. Our goals were to 1) estimate annual survival, and 2) evaluate determinants for an unfavorable long-term outcome after IVT for stroke.

Improvement of oxygen supply by an artificial carrier in combination with normobaric oxygenation decreases the volume of tissue hypoxia and tissue damage from transient focal cerebral ischemia.

Tissue hypoxia may play an important role in the development of ischemic brain damage. In the present study we investigated in a rat model of transient focal brain ischemia the neuroprotective effects of increasing the blood oxygen transport capacity by applying a semifluorinated alkane (SFA)-containing emulsion together with normobaric hyperoxygenation (NBO). The spread of tissue hypoxia was studied using pimonidazole given prior to filament-induced middle cerebral artery occlusion (MCAO, 2 h). Treatment consisted of intravenous injection of saline or the SFA-containing emulsion (0.5 or 1.0 ml/100g body weight; [SFA(0.5) or SFA(1.0)]) either upon establishing MCAO (early treatment) or after filament removal (delayed treatment). After injection NBO was administered for 8 h (early treatment) or 6 h (delayed treatment). Experiments were terminated 8 or 24 h after MCAO. In serial brain sections tissue hypoxia and irreversible cell damage were quantitatively determined. Furthermore, we studied hypoxia-related gene expression (VEGF, flt-1). Early treatment significantly (p<0.05) reduced the volumes of tissue damage (8 h after MCAO: SFA(1.0), 57±34 mm³; controls, 217±70 mm³; 24 h after MCAO: SFA(1.0), 189±82 mm³; controls, 317±60 mm³) and of P-Add immunoreactivity (8 h after MCAO: SFA(1.0), 261±37 mm³; controls, 339±26 mm³; 24h after MCAO: SFA(1.0), 274±47 mm³; controls, 364±46 mm³). Delayed treatment was comparably successful. The volume of the hypoxic penumbra was not decreased by the treatment. Similarly, VEGF and flt-1 mRNA levels did not differ between the experimental groups. From these data we conclude that increasing the blood oxygen transport capacity in the plasma compartment provides a neuroprotective effect by alleviating the severity of hypoxia to a level sufficient to prevent cells from transition into irreversible damage.