Comparing extended versus standard time window for thrombectomy: caseload, patient characteristics, treatment rates and outcomes-a prospective single-centre study.

PURPOSE: New guidelines recommend thrombectomy up to 24 h in selected patients; however, the workload and benefit of extending time window are not known. We conducted a prospective single-centre study to determine the caseload, imaging and interventional need of extended time window. METHODS: All consecutive ischemic stroke patients within 24 h from onset in an 11-month period were included. Thrombectomy eligibility in the 0-6 h time window was based on current guidelines; in the 6-24 h time window, it was based on a combination of DEFUSE 3 and DAWN study criteria using MRI to identify target mismatch. Clinical outcome in treated patients was assessed at 3 months. RESULTS: Within 24 h of onset, 437 patients were admitted. In the 0-6 h time window, 238 patients (54.5%) arrived of whom 221 (92.9%) underwent CTA or MRA, 82 (34.5%) had large vessel occlusion (LVO), 30 (12.6%) had thrombectomy and 11 (36.6%) became independent (mRS ≤ 2). In the extended 6-24 h time window, 199 patients (45.5%) arrived of whom 127 (63.8%) underwent CTA or MRA, 44 (22.1%) had LVO, 8 (4%) had thrombectomy and 4 (50%) became independent. CONCLUSION: Extending the time window from 6 to 24 h results in a 26.7% increase in patients receiving thrombectomy and a 36.4% increase of independent clinical outcome in treated patients at the price of a significantly increased burden of clinical and imaging screening due to the similar caseload but a smaller proportion of treatment eligible patients in the extended as compared with the standard time window.

[N-methyl-D-aspartate receptor antibody encephalitis: the Janus-faced disorder]. / N-metil-D-aszpartát receptor ellenes antitest okozta enkefalitisz: a Janus-arcú betegség.

The recognition of the antibody-mediated encephalitis as a separate entity among the immune disorders of the central nervous system was one of the greatest breakthroughs of the last two decades in neurology. Unlike viral or tumor-related encephalitis, the antibody-mediated form has a good response to immunotherapy, which gives a special clinical importance to the discovery. Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the first fully characterized antibody-mediated encephalitises. This article attempts to summarize the clinical features of this complex neuropsychiatric disorder with the aim to help its early recognition and to report the clinical course and the outcome of our six seropositive anti-NMDAR cases. The disease appears typically in young females and often combined with ovarian teratoma. However, the antibody production could develop without any malignancy. The course of the illness is usually monophasic, but 10% of the cases are relapsing. The anti-NMDAR encephalitis is the result of disturbed glutamatergic neurotransmission due to the internalization of the receptor-antibody complexes. The disease usually develops after a common viral infection, but recent data proved that anti-NMDAR encephalitis could also develop after herpes simplex virus-1 encephalitis. The Janus-faced clinical course of the disease is the obstacle of the early recognition. Psychiatric symptoms - like delusion, hallucination and agitation - dominate in the first, cortical phase of the illness, which are indistinguishable from the signs of primary psychosis. The true nature of the disease only reveals later, with the appearance of the basal ganglia territory and brainstem sings, such as perioral hyperkinesia and bradycardia. Further delays the diagnosis that the leading symptoms of the second phase could be interpreted as the side effects of the initial treatment. According to expert psychiatrists, the unusual dynamic of the psychotic symptoms and the lack of response to the neuroleptic drugs could lead toward the idea of the anti-NMDAR encephalitis. The final diagnosis depends on the detection of the anti-NMDAR antibody from the cerebrospinal fluid or the serum, respectively. Haloperidol is the most potent drug to treat the psychotic symptoms of the cortical phase; however due to its antidopaminergic side effect atypical neuroleptics are recommended by the experts. The immunological treatment is the administration of intravenous corticosteroid combined with plasma exchange or with intravenous IgG infusion. The immunotherapy in most of the cases is successful, but the recovery is long and it requires strong cooperation between the psychiatrists, neurologists and intensive care therapists.

[Experience with infection surveillance at a neurological intensive care unit]. / Aktív fertozésfelügyeleti ("surveillance") tapasztalatok neurológiai intenzív terápiás osztályon.

Infection-surveillance is an important part of the infection control system serving the protection of patients and healthcare workers as well. The continuous surveillance of health care associated infections is among the most important fields of patient safety and quality management. The aim of this study was to evaluate the frequency of the health care associated infections among patients at the neurointensive care unit. Moreover, we aimed to identify specific infection-forms and the most frequently occurring pathogens. We performed the study for a half-year according to the HELICS-method proposed by the National Center of Epidemiology. In this setup we evaluated the infections and risk factors for infection (instrument-use, antibiotic therapy etc.) among the patients who spent at least 48 hours in the neurointensive care unit. During the six-month period, we observed 16 health care associated mono- and polymicrobial infections out of the 88 cases. Mainly Gram-positive pathogens were identified, but we found multidrug-resistant pathogens as well. Clinically diagnosed pneumonia was the most frequent among the infections. These infections were detected by a relatively low microbiological testing rate, which warns to increase sampling frequency to ensure more accurate data on infections. Infection control based on a comparative standardized infection dataset seems to be one of the most important preventive measures.

Improved Stroke Care in a Primary Stroke Centre Using AI-Decision Support.

BACKGROUND: Patient selection for reperfusion therapies requires significant expertise in neuroimaging. Increasingly, machine learning-based analysis is used for faster and standardized patient selection. However, there is little information on how such software influences real-world patient management. AIMS: We evaluated changes in thrombolysis and thrombectomy delivery following implementation of automated analysis at a high volume primary stroke centre. METHODS: We retrospectively collected data on consecutive stroke patients admitted to a large university stroke centre from two identical 7-month periods in 2017 and 2018 between which the e-Stroke Suite (Brainomix, Oxford, UK) was implemented to analyse non-contrast CT and CT angiography results. Delivery of stroke care was otherwise unchanged. Patients were transferred to a hub for thrombectomy. We collected the number of patients receiving intravenous thrombolysis and/or thrombectomy, the time to treatment; and outcome at 90 days for thrombectomy. RESULTS: 399 patients from 2017 and 398 from 2018 were included in the study. From 2017 to 2018, thrombolysis rates increased from 11.5% to 18.1% with a similar trend for thrombectomy (2.8-4.8%). There was a trend towards shorter door-to-needle times (44-42 min) and CT-to-groin puncture times (174-145 min). There was a non-significant trend towards improved outcomes with thrombectomy. Qualitatively, physician feedback suggested that e-Stroke Suite increased decision-making confidence and improved patient flow. CONCLUSIONS: Use of artificial intelligence decision support in a hyperacute stroke pathway facilitates decision-making and can improve rate and time of reperfusion therapies in a hub-and-spoke system of care.

Methylene Blue Bridges the Inhibition and Produces Unusual Respiratory Changes in Complex III-Inhibited Mitochondria. Studies on Rats, Mice and Guinea Pigs.

Methylene blue (MB) is used in human therapy in various pathological conditions. Its effects in neurodegenerative disease models are promising. MB acts on multiple cellular targets and mechanisms, but many of its potential beneficial effects are ascribed to be mitochondrial. According to the "alternative electron transport" hypothesis, MB is capable of donating electrons to cytochrome c bypassing complex I and III. As a consequence of this, the deleterious effects of the inhibitors of complex I and III can be ameliorated by MB. Recently, the beneficial effects of MB exerted on complex III-inhibited mitochondria were debated. In the present contribution, several pieces of evidence are provided towards that MB is able to reduce cytochrome c and improve bioenergetic parameters, like respiration and membrane potential, in mitochondria treated with complex III inhibitors, either antimycin or myxothiazol. These conclusions were drawn from measurements for mitochondrial oxygen consumption, membrane potential, NAD(P)H steady state, MB uptake and MB-cytochrome c oxidoreduction. In the presence of MB and complex III inhibitors, unusual respiratory reactions, like decreased oxygen consumption as a response to ADP addition as well as stimulation of respiration upon administration of inhibitors of ATP synthase or ANT, were observed. Qualitatively identical results were obtained in three rodent species. The actual metabolic status of mitochondria is well reflected in the distribution of MB amongst various compartments of this organelle.

Effects of COVID-19 pandemic on acute ischemic stroke care. A single-centre retrospective analysis of medical collateral damage. / A COVID-19-pandémia hatása az akut ischaemiás stroke ellátásra. A járulékos egészségügyi veszteségek retrospektív, egycentrumos felmérése (A COVID-19-pandémia orvosszakmai kérdései).

INTRODUCTION: Early international observations report decreased number of acute ischemic stroke admissions and prolonged onset-to-treatment times during COVID-19 pandemic. AIM: Our goal was to assess the effect of COVID-19 pandemic on Hungarian acute ischemic stroke care. METHOD: We compared demographical and clinical characteristics, rate of intravenous and endovascular therapies and therapeutic time parameters of acute ischemic strokes admitted to a university stroke centre in a COVID-epidemic period (01/03/2020-30/04/2020) and an identical period of 2019. RESULTS: 86 patients were admitted during the COVID-period and 97 in the control period. Demographical and clinical characteristics of these periods were well-balanced. In the COVID-period, the proportion of patients arriving beyond 24 hours after onset increased by 13% (p = 0.046), the rate of endovascular interventions remained unchanged (8%), the rate of intravenous thrombolysis decreased from 26% to 16%, the mean onset-to-treatment time of thrombolysis increased by 20 minutes, while the mean door-to-treatment time increased by only 5 minutes. Behind the shift of arrival time categories, multivariable (year of examination, NIHSS, age) logistic regression shows that the year of examination might play a leading role (p = 0.096). CONCLUSION: In the COVID-period, admissions for acute ischemic strokes decreased by 11% and the proportion of cases certainly untreatable by reperfusion therapies (arriving beyond 24 hours after onset) increased significantly. While the rate of endovascular interventions remained unchanged, the absolute rate of intravenous thrombolysis decreased by 10% and the mean onset-to-treatment time showed a tendency to increase. In these changes, the COVID-epidemic itself and related out-of-hospital factors might play a leading role. Orv Hetil. 2020; 161(34): 1395-1399.

Intranasal application of secretin, similarly to intracerebroventricular administration, influences the motor behavior of mice probably through specific receptors.

Secretin and its receptors show wide distribution in the central nervous system. It was demonstrated previously that intravenous (i.v.) and intracerebroventricular (i.c.v.) application of secretin influenced the behavior of rat, mouse, and human. In our previous experiment, we used a special animal model, Japanese waltzing mice (JWM). These animals run around without stopping (the ambulation distance is very limited) and they do not bother with their environment. The i.c.v. secretin attenuated this hyperactive repetitive movement. In the present work, the effect of i.c.v. and intranasal (i.n.) application of secretin was compared. We have also looked for the presence of secretin receptors in the brain structures related to motor functions. Two micrograms of i.c.v. secretin improved the horizontal movement of JWM, enhancing the ambulation distance. It was nearly threefold higher in treated than in control animals. The i.n. application of secretin to the left nostril once or twice a day or once for 3 days more effectively enhanced the ambulation distance than i.c.v. administration. When secretin was given twice a day for 3 days it had no effect. Secretin did not improve the explorative behavior (the rearing), of JWM. With the use of in situ hybridization, we have found very dense secretin receptor labeling in the cerebellum. In the primary motor cortex and in the striatum, only a few labeled cells were seen. It was supposed that secretin exerted its effect through specific receptors, mainly present in the cerebellum.

Quantitative relationship between inhibition of respiratory complexes and formation of reactive oxygen species in isolated nerve terminals.

In this study reactive oxygen species (ROS) generated in the respiratory chain were measured and the quantitative relationship between inhibition of the respiratory chain complexes and ROS formation was investigated in isolated nerve terminals. We addressed to what extent complex I, III and IV,respectively, should be inhibited to cause ROS generation. For inhibition of complex I, III and IV, rotenone, antimycin and cyanide were used, respectively, and ROS formation was followed by measuring the activity of aconitase enzyme. ROS formation was not detected until complex III was inhibited by up to 71 +/- 4%, above that threshold inhibition, decrease in aconitase activity indicated an enhanced ROS generation. Similarly, threshold inhibition of complex IV caused an accelerated ROS production. By contrast, inactivation of complex I to a small extent (16 +/- 2%) resulted in a significant increase in ROS formation, and no clear threshold inhibition could be determined. However, the magnitude of ROS generated at complex I when it is completely inhibited is smaller than that observed when complex III or complex IV was fully inactivated. Our findings may add a novel aspect to the pathology of Parkinson's disease, showing that a moderate level of complex I inhibition characteristic in Parkinson's disease leads to significant ROS formation. The amount of ROS generated by complex I inhibition is sufficient to inhibit in situ the activity of endogenous aconitase.

The production of reactive oxygen species in intact isolated nerve terminals is independent of the mitochondrial membrane potential.

Dependence on mitochondrial membrane potential (deltapsim) of hydrogen peroxide formation of in situ mitochondria in response to inhibition of complex I or III was studied in synaptosomes. Blockage of electron flow through complex I by rotenone or that through complex III by antimycin resulted in an increase in the rate of H2O2 generation as measured with the Amplex red assay. Membrane potential of mitochondria was dissipated by either FCCP (250 nM) or DNP (50 microM) and then the rate of H2O2 production was followed. Neither of the uncouplers had a significant effect on the rate of H2O2 production induced by rotenone or antimycin. Inhibition of the F0F1-ATPase by oligomycin, which also eliminates deltapsim in the presence of rotenone and antimycin, respectively, was also without effect on the ROS formation induced by rotenone and only slightly reduced the antimycin-induced H2O2 production. These results indicate that ROS generation of in situ mitochondria in nerve terminals in response to inhibition of complex I or complex III is independent of deltapsim. In addition, we detected a significant antimycin-induced H2O2 production when the flow of electrons through complex I was inhibited by rotenone, indicating that the respiratory chain of in situ mitochondria in synaptosomes has a substantial electron influx distal from the rotenone site, which could contribute to ROS generation when the complex III is inhibited.

Initiation of neuronal damage by complex I deficiency and oxidative stress in Parkinson's disease.

Oxidative stress and partial deficiencies of mitochondrial complex I appear to be key factors in the pathogenesis of Parkinson's disease. They are interconnected; complex I inhibition results in an enhanced production of reactive oxygen species (ROS), which in turn will inhibit complex I. Partial inhibition of complex I in nerve terminals is sufficient for in situ mitochondria to generate more ROS. H2O2 plays a major role in inhibiting complex I as well as a key metabolic enzyme, alpha-ketoglutarate dehydrogenase. The vicious cycle resulting from partial inhibition of complex I and/or an inherently higher ROS production in dopaminergic neurons leads over time to excessive oxidative stress and ATP deficit that eventually will result in cell death in the nigro-striatal pathway.