Pedunculopontine nucleus stimulation for gait and postural disorders in Parkinson's disease

The pedunculopontine nucleus (PPN) is a reticular collection of neurons at the junction of midbrain and pons. The PPN in animal models appears topographically organised and functionally related to locomotion and arousal. In Parkinson’s disease, the PPN degenerates and is susceptible to abnormal basal ganglia output. In patients with Parkinson’s disease, low frequency PPN stimulation is proposed to improve gait freezing and postural instability. However, the therapeutic mechanisms, optimal clinical application and precise effects on gait and posture of PPN stimulation are unclear. Here, a topographic arrangement of the PPN was supported by local field potential recordings in parkinsonian patients. In the PPN region, beta oscillations were recorded rostrally and alpha oscillations caudally. Alpha oscillations, consistent with their putative role in allocating attention, correlated with gait performance and attenuated with gait freezing. Thus the caudal PPN subregion may be the most relevant target for gait disorders. Accordingly, an unblinded clinical study suggested that stimulation of the caudal PPN subregion was beneficial for gait freezing, postural instability and falls. In a double-blinded study using spatiotemporal gait analysis, caudal PPN stimulation reduced triggered gait freezing, with bilateral stimulation more effective than unilateral. However, akinesia including akinetic gait did not improve with PPN stimulation. Accordingly, dopaminergic medication requirements did not change. Mechanisms underlying gait freezing and PPN stimulation were explored with reaction time experiments. Parkinsonian patients with severe gait freezing and postural instability demonstrated a ‘block’ to pre-programmed movement. This was evidenced by prolonged simple reaction times and the absence of ‘StartReact’, whereby pre-prepared responses are normally accelerated by loud acoustic stimuli. PPN stimulation improved simple reaction time and restored Startreact. The relief of this ‘motor block’ with PPN stimulation may therefore explain the associated improvement in gait freezing and postural instability, as these tend to occur in circumstances requiring triggered, pre-prepared adjustments.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Association between different acute stroke therapies and development of post stroke seizures

Abstract Background Epilepsy is a major complication of stroke. We aimed to establish whether there is an association between intravenous thrombolysis, intra-arterial thrombolysis and post stroke seizure (PSS) development. Improved understanding of the relationship between reperfusion therapies and seizure development may improve post-stroke monitoring and follow-up. Methods This was a retrospective, multicentre cohort study conducted at the Royal Melbourne Hospital and Jingling Hospital Nanjing. We included patients with anterior circulation ischemic stroke admitted 2008–2015. Patients were divided into four treatment groups 1. IV-tPA only, 2. Intra-arterial therapies (IAT) only, 3. IAT + IV-tPA and 4. stroke unit care only (i.e. no IV-tPA or IAT). To assess the association between type of reperfusion treatment and seizure incidence we used multivariable logistic regression models adjusted for age, stroke severity, 3-month functional outcome and prognostic factors. Results There were 1375 stroke unit care-only patients, of whom 28 (2%) developed PSS. There were 363 patients who received only IV-tPA, of whom 21 (5.8%) developed PSS. There were 93 patients who received IAT only, of whom 12 (12.9%) developed PSS and 112 that received both IV-tPA + IAT, of which 5 (4.5%) developed PSS. All reperfusion treatments were associated with seizure development compared to stroke unit care-only patients: IV-tPA only adjusted odds ratio (aOR) 3.7, 95%CI 1.8–7.4, p < 0.0001; IAT aOR 5.5, 95%CI 2.1–14.3, p < 0.0001, IAT + IV-tPA aOR 3.4, 95% CI 0.98–11.8, p = 0.05. These aORs did not differ significantly between treatment groups (IV-tPA + IAT versus IV-tPA p = 0.89, IV-tPA + IAT versus IAT, p = 0.44). Conclusions Patients receiving thrombolytic or intra-arterial reperfusion therapies for acute ischemic stroke are at higher risk of epilepsy and may benefit from longer follow-up. No evidence for an additive or synergistic effect of treatment modality on seizure development was found

Left-Ventricular Unloading With Impella During Refractory Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis

OBJECTIVES: Extracorporeal cardiopulmonary resuscitation (ECPR) is the implementation of venoarterial extracorporeal membrane oxygenation (VA-ECMO) during refractory cardiac arrest. The role of left-ventricular (LV) unloading with Impella in addition to VA-ECMO ("ECMELLA") remains unclear during ECPR. This is the first systematic review and meta-analysis to characterize patients with ECPR receiving LV unloading and to compare in-hospital mortality between ECMELLA and VA-ECMO during ECPR.DATA SOURCES: Medline, Cochrane Central Register of Controlled Trials, Embase, and abstract websites of the three largest cardiology societies (American Heart Association, American College of Cardiology, and European Society of Cardiology).STUDY SELECTION: Observational studies with adult patients with refractory cardiac arrest receiving ECPR with ECMELLA or VA-ECMO until July 2023 according to the Preferred Reported Items for Systematic Reviews and Meta-Analysis checklist.DATA EXTRACTION: Patient and treatment characteristics and in-hospital mortality from 13 study records at 32 hospitals with a total of 1014 ECPR patients. Odds ratios (ORs) and 95% CI were computed with the Mantel-Haenszel test using a random-effects model.DATA SYNTHESIS: Seven hundred sixty-two patients (75.1%) received VA-ECMO and 252 (24.9%) ECMELLA. Compared with VA-ECMO, the ECMELLA group was comprised of more patients with initial shockable electrocardiogram rhythms (58.6% vs. 49.3%), acute myocardial infarctions (79.7% vs. 51.5%), and percutaneous coronary interventions (79.0% vs. 47.5%). VA-ECMO alone was more frequently used in pulmonary embolism (9.5% vs. 0.7%). Age, rate of out-of-hospital cardiac arrest, and low-flow times were similar between both groups. ECMELLA support was associated with reduced odds of mortality (OR, 0.53 [95% CI, 0.30-0.91]) and higher odds of good neurologic outcome (OR, 2.22 [95% CI, 1.17-4.22]) compared with VA-ECMO support alone. ECMELLA therapy was associated with numerically increased but not significantly higher complication rates. Primary results remained robust in multiple sensitivity analyses.CONCLUSIONS: ECMELLA support was predominantly used in patients with acute myocardial infarction and VA-ECMO for pulmonary embolism. ECMELLA support during ECPR might be associated with improved survival and neurologic outcome despite higher complication rates. However, indications and frequency of ECMELLA support varied strongly between institutions. Further scientific evidence is urgently required to elaborate standardized guidelines for the use of LV unloading during ECPR.</p

Additional file 1: of Association between different acute stroke therapies and development of post stroke seizures

Table S1. Univariate logistic regression with baseline risk factors (age, NIHSS and mRS02 at 90 days) and treatment for seizure outcome. Table S2. Logistic regression model with treatment groups plus age for seizure outcome. Table S3. Logistic regression model with treatment groups plus NIHSS for seizure outcome. Table S4. Logistic regression model with treatment groups plus mRS02 for seizure outcome. Table S5. Logistic regression model with treatment groups unadjusted. Table S6. Logistic regression model with treatment groups adjusted for age, NIHSS and mRS02. Table S7. Median (IQR) of the baseline NIHSS and number (percentage) of mRS (0–2) in the sensitivity analysis NIHSS ≥ 6. Table S8. Median (IQR) of the baseline NIHSS and number (percentage) of mRS (0–2) in the sensitivity analysis NIHSS > 8. (DOCX 63 kb