Immediate high-dose intravenous immunoglobulins followed by direct thrombin-inhibitor treatment is crucial for survival in Sars-Covid-19-adenoviral vector vaccine-induced immune thrombotic thrombocytopenia VITT with cerebral sinus venous and portal vein thrombosis

Graf T, Thiele T, Klingebiel R, Greinacher A, Schäbitz W-R, Greeve I. Immediate high-dose intravenous immunoglobulins followed by direct thrombin-inhibitor treatment is crucial for survival in Sars-Covid-19-adenoviral vector vaccine-induced immune thrombotic thrombocytopenia VITT with cerebral sinus venous and portal vein thrombosis. Journal of Neurology. 2021;268(12):4483-4485

Interferon-inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication.

International audienceHypermutations in hepatitis B virus (HBV) DNA by APOBEC3 cytidine deaminases have been detected in vitro and in vivo, and APOBEC3G (A3G) and APOBEC3F (A3F) have been shown to inhibit the replication of HBV in vitro, but the presumably low or even absent hepatic expression of these enzymes has raised the question as to their physiological impact on HBV replication. We show that normal human liver expresses the mRNAs of APOBEC3B (A3B), APOBEC3C (A3C), A3F, and A3G. In primary human hepatocytes, interferon alpha (IFN-alpha) stimulated the expression of these cytidine deaminases up to 14-fold, and the mRNAs of A3G, A3F, and A3B reached expression levels of 10%, 3%, and 3%, respectively, relative to GAPDH mRNA abundance. On transfection, the full-length protein A3B(L) inhibited HBV replication in vitro as efficiently as A3G or A3F, whereas the truncated splice variant A3B(S) and A3C had no effect. A3B(L) and A3B(S) were detected predominantly in the nucleus of uninfected cells; however, in HBV-expressing cells both proteins were found also in the cytoplasm and were associated with HBV viral particles, similarly to A3G and A3F. Moreover, A3G, A3F, and A3B(L), but not A3B(S), induced extensive G-to-A hypermutations in a fraction of the replicated HBV genomes. In conclusion, the editing enzymes A3B(L), A3F, and most markedly A3G, which are expressed in liver and up-regulated by IFN-alpha in hepatocytes, are candidates to contribute to the noncytolytic clearance of HBV

Clinical and Computerized Volumetric Analysis of Posterior Fossa Decompression for Space-Occupying Cerebellar Infarction

Goulin Lippi Fernandes E, Ridwan S, Greeve I, Schäbitz W-R, Grote A, Simon M. Clinical and Computerized Volumetric Analysis of Posterior Fossa Decompression for Space-Occupying Cerebellar Infarction. Frontiers in Neurology . 2022;13: 840212.Background and Purpose: Surgical decompression of the posterior fossa is often performed in cases with a space-occupying cerebellar infarction to prevent coma and death. In this study, we analyzed our institutional experience with this condition. We specifically attempted to address timing issues and investigated the role of cerebellar necrosectomy using imaging data and conducting volumetric analyses.; Methods: We retrospectively studied pertinent clinical and imaging data, including computerized volumetric analyses (preoperative/postoperative infarction volume, necrosectomy volume, and posterior fossa volume), from all 49 patients who underwent posterior fossa decompression surgery for cerebellar infarction in our department from January 2012 to January 2021.; Results: Thirty-five (71%) patients had a Glasgow Coma Scale (GCS) of 14-15 at admission vs. only 14 (29%) before vs. 41 (84%) following surgery. Seven (14%) patients had preventive surgery (initial GCS 14-15, preoperative GCS change ≤ 1). Only 18 (37%) patients had an mRS score of 0-3 at discharge. Estimated overall survival was 70.5% at 1 year. Interestingly, 18/20 (90%) surviving cases had a modified Rankin Scale (mRS) outcome of 0-3 (mRS 0-2: 12/20 [60%]) 1 year after surgery. Surgical timing, including preventive surgery and mass effect of the infarct, in the posterior fossa assessed semi-quantitatively (Kirollos grade) and with volumetric parameters that were not predictive of the patients' (functional) outcomes.; Conclusion: Posterior fossa decompression for cerebellar infarction is a life-saving procedure, but rapid recovery of the GCS after surgery does not necessarily translate into good functional outcome. Many patients died during follow-up, but long-term mRS outcomes of 4-5 are rare. Surgery should probably aim primarily at pressure relief, and our clinical as well as volumetric data suggest that the impact of removing an infarcted tissue may be limited. It is presumably relatively safe to initially withhold surgery in cases with a GCS of 14-15. Copyright © 2022 Goulin Lippi Fernandes, Ridwan, Greeve, Schabitz, Grote and Simon

Case report: Cerebral amyloid angiopathy-related inflammation in a patient with granulomatosis with polyangiitis

Seifert RM, Rauch M, Klingebiel R, et al. Case report: Cerebral amyloid angiopathy-related inflammation in a patient with granulomatosis with polyangiitis. Frontiers in Neurology. 2023;14. **Background** Cerebral amyloid angiopathy-related inflammation (CAA-ri) defines a subacute autoimmune encephalopathy, which is presumably caused by increased CSF concentrations of anti-Aβ autoantibodies. This autoinflammatory reaction is temporally and regionally associated with microglial activation, inflammation and radiological presence of vasogenic edema. Clinical characteristics include progressive demential development as well as headache and epileptic seizures. In the absence of histopathologic confirmation, the criteria defined by Auriel et al. allow diagnosis of probable resp. possible CAA-ri. CAA-ri shows responsiveness to immunosuppressive therapies and a possible coexistence with other autoinflammatory diseases. **Methods** We present a case report and literature review on the diagnosis of CAA-ri in a patient with known granulomatosis with polyangiitis (GPA). **Results** Initially, the presented patient showed neuropsychiatric abnormalities and latent arm paresis. Due to slight increase in CSF cell count, an initial antiviral therapy was started. MR tomography showed a pronounced frontotemporal edema as well as cerebral microhemorrhages, leading to the diagnosis of CAA-ri. Subsequent high-dose steroid treatment followed by six intravenous cyclophosphamide pulses resulted in decreased CSF cell count and regression of cerebral MRI findings. **Conclusion** The symptoms observed in the patient are consistent with previous case reports on CAA-ri. Due to previously known GPA, we considered a cerebral manifestation of this disease as a differential diagnosis. However, absence of pachymeningitis as well as granulomatous infiltrations on imaging made cerebral GPA less likely. An increased risk for Aβ-associated pathologies in systemic rheumatic diseases is discussed variously. </p

Antimyelin antibodies as predictors of disability after clinically isolated syndrome

There is controversy whether determination of antibodies against myelin, myelin oligodendrocyte glycoprotein, and myelin basic protein in serum from patients with a first episode suggestive of multiple sclerosis is of prognostic value. We evaluated whether detection of antimyelin antibodies in serum indicates a worse course with earlier time to a second relapse and increased progression of disability. We conducted a prospective study at the Department of Neurology, Inselspital Bern, Switzerland from 2004 to 2008 in patients presenting with a clinically isolated syndrome (CIS) and a follow-up of at least 4 months. Antimyelin antibodies were assessed by Western blot. Results were correlated with clinical course and sex. Among 93 consecutive patients with a CIS, 74 (80%) were positive for either one or both antimyelin antibodies. A relapse occurred in 49 (53%) and the median EDSS was 2 (range 1-3.5) after a mean observation period of 20 months. Presence of antimyelin antibodies at CIS neither increased the risk for a second relapse nor for progression of disability. Stratification for gender did not reveal differences for any of the clinical surrogates. The sole determination of antimyelin antibodies in serum is of limited prognostic value for the identification of patients with different short-term course

Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source during 3 Years of Prolonged Monitoring with an Implantable Loop Recorder

Kitsiou A, Rogalewski A, Kalyani M, et al. Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source during 3 Years of Prolonged Monitoring with an Implantable Loop Recorder. Thrombosis and Haemostasis. 2021;121(06):826-833.Background: Undocumented atrial fibrillation (AF) is suspected as a main stroke cause in patients with embolic stroke of undetermined source (ESUS), but its prevalence is largely unknown. This prospective study therefore aimed at delineating the prevalence of AF in patients with ESUS using continuous cardiac monitoring by implantable loop recorder (ILR) with daily remote interrogation over a period of 3 years and its clinical consequences, including recurrent stroke. Methods: In consecutive patients with an ESUS diagnosis after complete work-up, an ILR was implanted and followed by daily remote monitoring until AF was detected or a follow-up of at least 3 years was completed. Additionally, the ILR was interrogated in-hospital in 6-month intervals. Results: A total of 123 patients (74 male, mean age 65 ± 9 years) were enrolled and completed the 3 years study period. AF was detected in 51 patients (41.4%). In 43 of the 51 AF positive patients (84%) oral anticoagulation was established. Recurrent strokes occurred in 18 patients (14.6%) of this ESUS population, 9 of these patients being AF positive (17.6% of the AF-positive patients) and 9 being AF negative (12.5% of AF-negative patients). Patients with AF were slightly older than patients without AF (63.1 ± 8.8 vs. 67.5 ± 9.6 years, p = 0.12). Other parameters such as CHA2DS2-VASc score, infarct localization, micro- and macroangiopathy, carotid or aortic plaques, or stroke recurrence were not significantly different between groups. Conclusion In ESUS patients, early implantation of an ILR with cardiac monitoring and remote transmission over a 3-year period detected AF in 41.4% and resulted in oral anticoagulation in 84% of these patients

Detection of Atrial Fibrillation on Stroke Units: Comparison of Manual versus Automatic Analysis of Continuous Telemetry

Rogalewski A, Plümer J, Feldmann T, et al. Detection of Atrial Fibrillation on Stroke Units: Comparison of Manual versus Automatic Analysis of Continuous Telemetry. Cerebrovascular Diseases. 2020;49(6):647-655.Background: Detection of atrial fibrillation (AF) is one of the primary diagnostic goals for patients on a stroke unit. Physician-based manual analysis of continuous ECG monitoring is regarded as the gold standard for AF detection but requires considerable resources. Recently, automated computer-based analysis of RR intervals was established to simplify AF detection. The present prospective study analyzes both methods head to head regarding AF detection specificity, sensitivity, and overall effectiveness. Methods: Consecutive stroke patients without history of AF or proof of AF in the admission ECG were enrolled over the period of 7 months. All patients received continuous ECG telemetry during the complete stay on the stroke unit. All ECGs underwent automated analysis by a commercially available program. Blinded to these results, all ECG tracings were also assessed manually. Sensitivity, specificity, time consumption, costs per day, and cost-effectiveness were compared. Results: 216 consecutive patients were enrolled (70.7 ± 14.1 years, 56% male) and 555 analysis days compared. AF was detected by manual ECG analysis on 37 days (6.7%) and automatically on 57 days (10.3%). Specificity of the automated algorithm was 94.6% and sensitivity 78.4% (28 [5.0%] false positive and 8 [1.4%] false negative). Patients with AF were older and had more often arterial hypertension, higher NIHSS at admission, more often left atrial dilatation, and a higher CHA2DS2-VASc score. Automation significantly reduced human resources but was more expensive compared to manual analysis alone. Conclusion: Automatic AF detection is highly specific, but sensitivity is relatively low. Results of this study suggest that automated computer-based AF detection should be rather complementary to manual ECG analysis than replacing it

Effect of interferon-beta and atorvastatin on Th1/Th2 cytokines in multiple sclerosis

Beneficial effects by both interferon-beta and statin treatment in patients with multiple sclerosis (MS) may be linked to interference with the Th1/Th2 cytokine balance. We determined patterns of Th1/Th2 cytokines (interleukin (IL)-1beta, IL-2, IL-6, IL-12p70, tumor-necrosis factor (TNF)-alpha and interferon-gamma, and IL-4, IL-5 and IL-10, respectively) in the serum of patients with relapsing-remitting MS treated with 250microg interferon-beta 1b or with interferon-beta plus 40mg atorvastatin. In treatment naïve patients with MS, a trend for lower TNF-alpha serum levels compared to controls was detected (P=0.08). Interferon-beta treatment increased TNF-alpha levels, while a trend for lowering of IL-5 serum levels was found (P=0.07). Addition of atorvastatin raised IL-12p70 serum levels (P<0.05). Mean levels of two Th2 cytokines (IL-4, IL-10) showed a non-significant increase after addition of atorvastatin. We conclude that interferon-beta and atorvastatin exert divergent action on Th1/Th2 serum cytokines levels in MS. Supplemental atorvastatin might promote a Th1-type response by raising IL-12p70. Further studies are required to support a Th2 cytokine shift by atorvastatin in patients with MS

Long-term functional outcome and quality of life 2.5 years after thrombolysis in acute ischemic stroke

Schäbitz M, Möller L, Friedrich A, et al. Long-term functional outcome and quality of life 2.5 years after thrombolysis in acute ischemic stroke. Neurological Research and Practice. 2023;5(1): 62.**Background** Evaluation of outcome after stroke is largely based on assessment of gross function 3 months after stroke onset using scales such as mRS. Cognitive or social functions, level of symptom burden or emotional health are not usually assessed, nor are data available on long-term functional outcomes years after stroke. **Methods** Analysis of 1141 patients with AIS treated with IVT from two major German university hospitals between 2017 and 2020. Patient characteristics and short-term outcome were analysed from patient records. Long-term outcome of 228 patients with prior written informed consent was assessed via telephone survey using mRS and PROMs (EQ-5D-5L, EQ-VAS) 2.5 years after stroke. **Results** Predictors of excellent to good long-term outcome were younger age, event to door time ≤ 2 h, NIHSS ≤ 6 on admission and NIHSS ≤ 6 after IVT. Stroke recurrence was a negative predictor. Predictors of excellent quality of life at 2.5 years included age < 73 years, lower NIHSS after IVT, absence of hypertension. Quality of life was rated in all dimensions with a medium score of 1 and a medium EQ-VAS of 70, representing the good general health status of this stroke population. **Conclusion** Main predictors of an excellent to good long-term outcome and excellent QoL 2.5 years after stroke are younger age, lower NIHSS, and event to door time ≤ 2 h. Research on long-term outcome after disease and treatment is of utmost importance, as it has the ability to reveal the patient true functional outcome and quality of life and to provide information on the status of independence and self-esteem