COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, a novel betacoronavirus discovered in December 2019 and closely related to the SARS coronavirus (CoV). Both viruses use the human ACE2 receptor for cell entry, recognizing it with the Receptor Binding Domain (RBD) of the S1 subunit of the viral spike (S) protein.The S2 domain mediates viral fusion with the host cell membrane. Experience with SARS and MERS coronavirus has shown that potent monoclonal neutralizing antibodies against the RBD can inhibit the interaction with the virus cellular receptor (ACE2 for SARS) and block the virus cell entry. Assuming that a similar strategy would be successful against SARS-CoV-2, we used phage display to select from the human naïve universal antibody gene libraries HAL9/10 anti SARS2 spike antibodies capable of inhibiting interaction with ACE2. 309 unique fully human antibodies against S1 were identified. 17 showed more than 75% inhibition of spike binding to cells expressing ACE2, assessed by flow cytometry and several antibodies showed even an 50% inhibition at a molar ratio of the antibody to spike protein or RBD of 1:1. Furthermore, these antibodies neutralized active SARS-Cov-2 virus infection of VeroE6 cells. All 17 were all able to bind the isolated RBD, four of them with sub-nanomolar EC50. Epitope analysis of the antibodies revealed that six bind at the RBD-ACE2 interface and two on the opposite side of the domain. Universal libraries from healthy donors offer the advantage that antibodies can be generated quickly and independent from the availability of material from recovered patients in a pandemic situation. 4/34 Main textIn 2015 Menachery et al. wrote: "Our work suggests a potential risk of SARS-CoV reemergence from viruses currently circulating in bat populations." 1 . Four years later, a novel coronavirus causing a severe pneumonia was discovered and later named SARS-CoV-2. The outbreak started on a sea food market in Wuhan, Hubei province (China) at the end of 2019. The disease was named COVID-19 (coronavirus disease 2019) by the World Health Organization (WHO). Sequencing showed high identity to bat corona viruses (CoV, in particular RaTG13), beta-CoV virus causing human diseases like SARS and MERS and, to a lesser extent, the seasonal CoV hCoV-OC43 and HCov-HKU1 2,3 . The spike (S) protein of SARS-CoV-2, as well as SARS-CoV, binds to the human zinc peptidase angiotensin-converting enzyme 2 (ACE2) which is expressed on lung cells, heart, kidney and intestine cells and acts as receptor for virus entry. S protein consists of the N-terminal S1 subunit, which includes the receptor binding domain (RBD), and the Cterminal S2 subunit which is anchored to the viral membrane and is required for trimerization and fusion of the virus and host membrane 4-6 . The membrane bound host protease TMPRSS2 is responsible for S protein priming by cleavage of specific sites between S1 and S2. In addition to proteolytic activation of the S2' site, conformational changes and viral entry 7-10 .Antibodies against the...

Background: Angioedema (AE) in stroke has been reported exclusively after thrombolysis with recombinant tissue-type plasminogen activator (rtPA). Previous studies proposed the insular cortex to play a specific role in the development of AE after stroke. We evaluated the incidence of AE in acute stroke and tried to identify the predominantly involved brain structures. Methods: We performed a retrospective search of our stroke database for patients with an AE. MRI data were analyzed by adapting the images to a standard size and superimposing the infarctions. The areas of overlap were assumed to represent the areas of interest. Results: 865 of 4,789 (18.1%) consecutive patients with acute stroke received IV rtPA, 20 of them (2.3%) developed AE. One patient developed AE without prior thrombolysis. The odds ratio for AE after rtPA was 93 (95% CI: 12-693). Of the 21 AE patients, 15 (71.4%) had ACE-inhibitor treatment (ACEi) and 7 (33.3%) had diabetes. In all but one patient, AE was clearly lateralized; then the AE was contralateral to the side of the ischemia in 18 of 20 patients (90.0%). An insular/peri-insular involvement was detected in 17/21 (81.0%). About 80.0% of the patients had a suspected MCA branch occlusion. Conclusions: In contrast to AE in other conditions, AE in stroke seems to feature a unique cerebral pathology because it is mostly lateralized (contralateral to an infarction), is associated with a distinct brain area, may even occur without rtPA, and is far more frequent than after thrombolysis for other indications. rtPA is the major risk factor. Similar to prior studies, we identified ACEi to be another risk factor, and a diabetic autonomic instability might further increase the risk. Central pathways involving the insular and peri-insular cortex seem to play a major role in the pathophysiology of AE in stroke.

Fourteen consecutive patients with segmental dystonia underwent chronic deep brain stimulation (DBS) surgery in the frame of a prospective study protocol. Twelve patients received chronic pallidal stimulation, while 2 patients with prominent dystonic tremor received chronic thalamic ventrointermediate nucleus stimulation. Twelve patients had primary dystonia, and 2 patients secondary dystonia. The Burke-Fahn-Marsden dystonia rating scale (BFM motor) showed a mean relative improvement of 57.3% at the first follow-up (FU1, mean 7 months) and 57.8% at the second follow-up (FU2, mean 16 months). The mean BFM scores were 34.9 ± 17.7 preoperatively, 14.9 ± 11.7 at FU1, and 14.8 ± 10.3 at FU2. Scores of the disability subscale improved by 43% at FU1 and 36% at FU2. Improvement was comparatively less in those patients with secondary dystonia. Dysarthria was a limitation of DBS in 4 patients when using high voltage. Overall, chronic DBS is a very effective treatment option for medically refractory segmental dystonia.

Since the beginning oft he Covid-19 pandemic we have observed an increased incidence of transient global amnesia, possibly related to emotional stress as a trigger factor.

<b><i>Background:</i></b> Transient global amnesia (TGA) is a syndrome featuring acute anterograde amnesia as the most striking clinical symptom. Its etiology is still a matter of debate. Most neurological guidelines allow the diagnosis on the basis of clinical criteria only; a more extensive evaluation is recommended only for patients with “red flags” like severe headache, nausea or vomiting, or metabolic abnormalities. The aim of our study was to assess the frequency of a severe underlying disease or alternative diagnoses (mimics) in patients fulfilling the clinical criteria. <b><i>Methods:</i></b> We evaluated the medical records and the imaging data of an unselected consecutive cohort of patients with suspected TGA over a 7-year period. All patients were hospitalized and received a neurological workup including brain imaging, color-coded duplex sonography of the brain supplying arteries, electroencephalography, and laboratory studies of blood and (in selected cases) cerebrospinal fluid. <b><i>Results:</i></b> 163 patients with 166 episodes of suspected TGA were hospitalized (3 patients twice). After the workup, the diagnosis of TGA was confirmed in 148/166 (89.2%) episodes (“simple TGA”). Eighteen patients (10.8%) either had an alternative diagnosis or a severe comorbidity that was assumed to have had an impact on the occurrence of the amnestic episode (“complicated TGA/mimic”). The most important differential diagnosis was stroke (11 patients, 6.6% of all TGA suspects and 61.1% of the complicated TGA/mimic group). Other mimics were transient epileptic amnesia (2 patients) and steroid-induced delirium (1 patient). Important comorbidities that had not been obvious at the time of presentation were severe sleep apnea (2 patients), triptan overuse (1 patient), and an involuntary amlodipine intoxication during TGA. <b><i>Conclusion:</i></b> As approximately every tenth patient with suspected TGA either had an alternative diagnosis or a severe comorbidity, which had not been obvious at the time of admission, we consider in-patient treatment of all suspected TGA cases as appropriate, preferably in the setting of a stroke unit, as ischemic stroke was the by far most important diagnosis mimicking TGA.

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