Bone marrow-derived MOs/MPs recruited via CCR2 and acting via TGF-β1 are essential for maintaining integrity of the neurovascular unit following brain ischemia. Future therapies should be aimed at enhancing physiological repair functions of CCR2(+) MOs/MPs rather than blocking their hematogenous recruitment.

ObjectiveTo investigate the prevalence of neutralizing antibodies (NAbs) against botulinum neurotoxin type A (BoNT/A) during long-term BoNT/A treatment in different neurologic indications.MethodsIn this monocentric, observational cross-sectional study, 596 outpatients treated with BoNT/A for different indications were tested for BoNT/A binding antibodies by ELISA. Positive samples were investigated for NAbs with the mouse hemidiaphragm test. The prevalence of NAbs was analyzed for different indications: facial hemispasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. Besides the rate of NAb-positive patients overall and per patient subgroup, a Kaplan-Meier analysis of the probability of remaining NAb negative with duration of treatment is provided, and a stepwise binary logistic regression analysis is performed to identify factors significantly contributing to the induction of NAbs.ResultsOverall, 83 of 596 patients (13.9%) had measurable NAbs. The probability of developing NAbs increased with the single and cumulative dose of treatment and was influenced by the BoNT/A formulation, while all other factors analyzed, including disease entity and treatment duration, had no additional influence.ConclusionsWe present the largest study to date of the prevalence of BoNT/A NAbs in a large unbiased cohort of patients including the relevant neurologic indications. Repeated injections of BoNT/A inevitably bear the risk of developing NAbs. However, in addition to avoiding booster injections and providing short intervals between injections, reducing the individual injected doses may diminish the risk of NAb induction independently of the indication for which BoNT/A is used.

The three different botulinum toxin type A (BoNT/A) preparations being licensed in Europe and the U.S. differ in protein content, which seems to be a major factor influencing the antigenicity of BoNT/A. In the present study, several arguments out of our research pool were collected to demonstrate that the clinical response and antigenicity were different for the three BoNT/A preparations: some results of (1) a cross-sectional study on clinical outcome and antibody formation of 212 patients with cervical dystonia (CD) being treated between 2 and 22 years; 2) another cross-sectional study on the clinical aspects and neutralizing antibody (NAB) induction of 63 patients having developed partial secondary treatment under abobotulinum (aboBoNT/A) onabotulinumtoxin (onaBoNT/A) who were switched to incobotulinumtoxin (incoBoNT/A) in comparison to 32 patients being exclusively treated with incoBoNT/A. These results imply that (1) the presence of NAB cannot be concluded from the course of treatment, that (2) an increase in the dose and variability of outcome with treatment duration indicates the ongoing induction of NABs over time, that (3) the higher protein load of BoNT/A goes along with a higher incidence and prevalence of NAB induction and that (4) the best response to a BoNT/A is also dependent on the protein load of the preparation.

BackgroundIn a proportion of stroke patients with acute large vessel occlusion permanent stent implantation is mandatory to achieve successful recanalization. The optimum platelet inhibition strategy after such emergency stenting is unknown. We therefore analyzed the outcome of early glycoprotein (gp) IIb/IIIa inhibitor treatment after emergency stenting in acute stroke.MethodsSixty patients with emergency stenting were identified in our stroke unit registry from 12/2010-06/2014 and analyzed retrospectively. All patients were bridged intravenously with the gpIIb/IIIa antagonist tirofiban immediately after the acute procedure until switching to oral aspirin and clopidogrel was performed. For comparison we studied 135 patients with M1 occlusion undergoing thrombectomy without stent implantation or tirofiban treatment in a propensity score-adjusted analysis.ResultsIn the acute stenting group receiving tirofiban complications with 6 deaths during the hospital stay (10%), 2 reinfarctions (3%), 12 intracerebral hemorrhages (ICH; 20%) and 5 symptomatic ICH (8%) occurred. Thirty-seven patients (62%) reached a moderate outcome of mRS 0–3 after 90 days. In the thrombectomy group without tirofiban administration the rate of deaths within hospital stay, the rate of ICH and outcome at day 90 were not different.ConclusionIn our retrospective study acute stenting with subsequent gpIIb/IIIa inhibition was not associated with an increased risk of ICH or in-hospital death.