AIMS
We aimed at evaluating the relative role of Optical coherence tomography (OCT) next to serum neurofilament light chain (sNfL) and magnetic resonance imaging (MRI), for assessing cognitive and physical disability in multiple sclerosis (MS).
METHODS
Cross-sectional study with 100 MS patients (63 female, age: 50.4±11.5 years(y); disease duration: 18.7± 9.8y; education: 14.1±3.3y, 80% with relapsing remitting MS) and 52 matched healthy controls (HC; 34 female, age: 51.4±13.7y; education: 16.0±3.3y). All subjects underwent an OCT to assess the mean peripapillary retinal nerve fiber layer (pRNFL) thickness, and the volume of the ganglion cell-inner plexiform- (GCIPL) and inner nuclear layers (INL). For patients with prior optic neuritis, we included only the non-affected eye and for the rest, we took the average OCT measures of both eyes. Brief International Cognitive Assessment for Multiple Sclerosis and the Expanded Disability Status Scale (EDSS) were used to quantify cognitive and physical disability. sNfl levels were measured and T2 lesion volume (T2LV) and brain parenchymal fraction (BPF) were assessed on MRI, using GruSEG and FreeSurfer respectively.
RESULTS
Compared to HC, patients had lower mean pRNFL thickness (p< 0.001) and GCIPL volume (p< 0.001), but INL volume did not differ (p= 0.093).
After correction for age, vision and education, pRNFL thickness was associated with the symbol digit modalities test (SDMT) in patients (β= 0.2, p= 0.030). In a multivariate analysis including sNfL, BPF and T2LV, pRNFL (β= 0.19, p= 0.044) and T2LV (β= -0.24, p= 0.023) were the only predictors that remained associated with the SDMT.
Mean pRNFL thickness and GCIPL volume showed associations with the EDSS (β= -0.37, p< 0.001 and β= -0.46, p< 0.001). In a multivariate analysis including sNfL, BPF, and T2LV, GCIPL volume was the strongest predictor of the EDSS (β= -0.32, p< 0.001), followed by sNfL (β= 0.18, p= 0.024).
CONCLUSIONS
OCT measures, as markers of neuroaxonal loss, are associated with cognitive and physical disability in MS patients independently of serum- (sNfL) and MRI- (BPF, T2LV) markers. Furthermore, GCIPL was the strongest predictor of physical disability. With the advantage of being a quick, patient-friendly examination, needing only minimal post-processing, OCT can play a major role in the stratification of MS patients at risk of higher cognitive and physical disability.

Aims
Current guidelines recommend to treat refractory status epilepticus (RSE) with continuous intravenous anesthetic drugs (IVAD) to achieve a electroencephalographic (EEG) burst attenuation/suppression pattern (BS). However, the evidence for the benefit of BS and its appropriate extent and duration is scarce. This study investigated the frequency of therapeutically induced BS and its association with clinical outcome in adult RSE patients receiving IVAD as antiseizure treatment.

Methods
Retrospective analysis of all adult patients treated for RSE with continuous IVAD in an intensive care unit of a Swiss academic tertiary medical center between 2011 and 2019. BS was visually assessed during the first two minutes of each one-hour epoch of EEG monitoring. BS with ≥ 50 % suppression percent was defined according to the American Clinical Neurophysiology Society’s (ACNS) Standardized Critical Care EEG Terminology 2021, whereas a BS with a suppression percent between 20 – 49 % was defined as incomplete BS. The primary outcome was the frequency of induced EEG burst-suppression during IVAD treatment. Secondary outcomes were the association of clinical courses and outcomes of RSE patients with the presence of BS or incomplete BS. Logistic regression was performed for outcome analysis.

Results
Of 526 adult patients with status epilepticus (SE) between 2011 and 2019, 147 RSE patients with IVAD as antiseizure treatment were identified (median 63 years, 44 % female). Thereof, 85 (58 %) patients had presumed fatal etiology. Among RSE patients with IVAD, 34 (23 %) attained BS and 25 (17 %) incomplete BS at least at one time point during EEG monitoring. The univariable comparison between patients with and without persistent termination of RSE did not show an association with the presence of BS (p = 0.13), incomplete BS (p = 0.41) or absence of any BS (p = 0.43). Likewise, the univariable comparison between surviving and non-surviving patients did not show any association with BS (p = 0.83), incomplete BS (p = 0.47) or absence of BS (p = 0.71). In contrast, presumed fatal etiology was significantly associated with absence of RSE termination (p = 0.006) and death (p = 0.001).

Conclusion
Our results underscore the challenges of achieving EEG BS as recommended during IVAD treatment in patients with RSE. Furthermore, in contrast to SE etiology, our analysis did not find evidence that achievement of BS influences persistent RSE termination or survival.

Myasthenia gravis is an autoimmune disorder defined by muscle weakness and fatigability associated with antibodies against proteins of the neuromuscular junction (NMJ). The most common autoantibody target is the acetylcholine receptor (AChR). Three mechanisms have been postulated by which autoantibodies might interfere with neurotransmission: direct blockade of acetylcholine binding to receptor, complement-mediated damage of the postsynaptic membrane, and enhanced internalization of the receptor. It is very likely that more than one of these mechanisms operate in parallel, and therefore dissecting the mechanisms of autoantibody-mediated pathology requires patient-derived, monoclonal antibodies.
Using membrane antigen capture activated cell sorting (MACACS) we isolated AChR-specific B cells from patients with myasthenia gravis, and produced and studied recombinant antibodies. All six cloned AChR-antibodies were hypermutated, but of varying isotypes (IgG1, IgG3, IgG4) and recognizing the four different chains of the AChR. Despite strong binding to the receptor, none of the individual antibodies had a strong influence on neuromuscular signal transmission as measured in an in vitro neuromuscular synapse model. They also did not activate complement or induce myasthenic signs in vivo. However, combinations of antibodies induced strong complement activation in vitro, and severe muscle weakness in a passive transfer myasthenia gravis rat model, associated with NMJ destruction and complement activation in muscle. The strongest complement activation was mediated by combinations of antibodies targeting disparate subunits of the AChR, and such combinations also induced the formation of large clusters of AChR on the surface of live cells in vitro. We propose that this synergy between antibodies of different epitope specificities is a fundamental feature of the disease, that can explain the well-known discrepancy between serum anti-AChR titers and clinical severity. This model also has implications for therapeutic strategies currently under investigation.

Background: Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH), but there is no comprehensive classification of ICH subtypes according to different SVD phaenotypes. We aimed to develop an MRI-based classification for SVD-related ICH and assess association with outcomes.
Methods: We performed a retrospective study of prospectively collected data of patients enrolled in the national, multicenter Swiss Stroke Registry from 2013-2019. We included consecutive patients with non-traumatic, SVD-related ICH and available MRI. Patients were classified according to a novel MRI-based classification using haemorrhagic (microbleeds, cortical siderosis) and non-haemorrhagic (white matter hyperintensities, lacunes, perivascular spaces) MRI markers and haematoma location as cerebral amyloid angiopathy (CAA), deep perforator arteriopathy (DPA), mixed SVD or undetermined SVD. The primary clinical outcomes were recurrent ICH or ischemic stroke at 3 months. We performed a Firth penalized logistic regression and competing risk analysis according to Fine and Gray.
Results: We enrolled 1180 patients (age (IQR) 73 (62-80) years, baseline NIHSS 6 (2-12), 538/1180 (45.6%) lobar hematoma location, systolic blood pressure on admission 166 (145-185) mmHg). During follow-up 57 patients had 58 events (29 ICH, 29 ischemic strokes, event rate 4.8%). The rate of recurrent ICH and ischaemic stroke at 3 months was 4%/1% for CAA, 0.7%/2.6% for DPA, 2.7%/2.9% for mixed SVD and 3.8%/3.4% for undetermined SVD, respectively, without a statistically significant difference between groups.
Discussion: This new MRI-based SVD-ICH phaenotype classification based on objective radiological markers is feasible and may improve classification and reporting of ICH subtypes in clinical practice and research.

Introduction
In patients with Multiple Sclerosis (pwMS), specific disease modifying treatments (DMTs) may compromise immune response following SARS-CoV-2 vaccination. Limited information is available, whether levels of anti-SARS-CoV-2 antibodies are linked to the risk of breakthrough infections in pwMS.
Aims
To determine the rate of Omicron breakthrough infection and severity of COVID-19 in a cohort of MS patients treated with different DMTs and to estimate the impact of SARS-CoV-2-specific antibody levels on breakthrough infection risk.
Methods
This study is nested within the Swiss MS Cohort, a nationwide multicenter study that has recruited 1585 pwMS. Patients who received two doses of SARS-CoV-2 vaccines before Omicron became the dominant variant in Switzerland on Dec-15, 2021 and had a follow-up thereafter were included. Data on SARS-CoV-2 infections, severity of COVID-19 according to the WHO scale and SARS-CoV-2 vaccines were collected by questionnaires. Anti-SARS-CoV-2-S antibody levels were measured after the second vaccine dose. Incidence of infections grouped by antibody level after second vaccination was visualized using Kaplan-Meier curves. Cox regression models were used to estimate the impact of antibody levels on the hazard of breakthrough infection during follow-up.
Results
242 pwMS (median age 49 years, 162 (67 %) female, 36 (15 %) with progressive disease, median EDSS 2.5) were included. 22 (9 %) had SARS-CoV-2 infection and 137 (57 %) at least one additional vaccine dose prior to Omicron start. Since then, 57 breakthrough infections were reported. Severity of breakthrough disease on WHO scale ranged from 1-10. 7 were asymptomatic, 46 were symptomatic as outpatients, 3 were hospitalized and 1 died. Patients with antibody levels > 150 U/ml (n = 95) after second vaccination had a 64 % reduced risk for Omicron breakthrough-infection compared to patients with antibody levels < 0.7 U/ml (n = 81) (HR 0.36, 95 % CI = 0.18-0.71, p < 0.01). This effect was maintained after adjustment for DMT at vaccination and time since second vaccination.
Conclusions
Humoral immune response after second SARS-CoV-2 vaccination is associated with Omicron breakthrough infection rate, a finding contrasting general populations, where antibody levels seem to have little impact on protecting from Omicron infection. Most breakthrough infections in our cohort were mild. Analyses on the effect of booster vaccinations on serology and infection rates will follow.

Background/Aims: Signs of upper motor neurons (UMN) dysfunction can be elusive and difficult to identify in amyotrophic lateral sclerosis (ALS) (1), but are important for timely diagnosis (2). One of the core macro-pathological features of ALS, the spinal cord lateral tract (SCLT) sclerosis, was described by Charcot and shaped the name of the disease (3). Histopathologically, these areas are characterized by axonal loss and diffuse astrocytic gliosis (4, 5). Averaged Magnetization Inversion Recovery Acquisitions (rAMIRA) is a novel MRI approach enabling spinal cord (SC) gray and white matter (WM) imaging with high contrast in clinically feasible acquisition times at 3 Tesla (T) (6, 7). The aims of the study were to define and validate the SCLT sign and to investigate its sensitivity and specificity in patients with ALS, other lower-motor neuron (LMN) diseases, and healthy controls (HC).
Methods: 38 patients with an established diagnosis of ALS (Gold Coast criteria), 60 HC, 25 patients with post-polio syndrome (PPS, March of Dimes criteria), and 10 patients with 5q-spinal muscular atrophy (SMA) were investigated by axial 2D rAMIRA imaging at the intervertebral disc levels C2/C3 - C5/C6 (3T-PRISMA, Siemens). Clinical and demographic data of all participants were obtained. The SCLT sign was defined and validated in a multi-step process by 4 independent raters in subsets of participants and its sensitivity and specificity in detecting ALS were calculated.
Results: The SCLT sign, defined as evenly spread, uni-or bilateral hyperintensities in the SC WM dorsolaterally to the anterior horns, was present in ALS patients in 50 %, 49 %, 54 % and 46 % at the respective levels C2/C3-C5/C6, and in up to 89 % of ALS patients with UMN predominance. In the HC, PPS and SMA groups, the sign was present in 3 %, 8 %, and 0 %, respectively, thus rendering a sensitivity of 58 % and specificity of 98 % at C3/C4 to identify ALS cases. The sign was detectable irrespective of disease duration and persisted on serial imaging over 2 years.
Conclusion: The SCLT sign shows a high specificity in distinguishing patients with ALS from HC and patients with other LMN disorders. Further investigations of patients early in the disease course, particularly those without clinical signs of UMN dysfunction, and of patients with other UMN disorders are necessary next steps to estimate the potential of this novel imaging marker to improve the ALS diagnostic process.

Background: There is an urgent need for valid and reliable imaging biomarkers to reduce the diagnostic delay, to monitor the disease course, and to evaluate drug efficacy in upcoming trials in amyotrophic lateral sclerosis (ALS). The novel AMIRA (Averaged Magnetization Inversion Recovery Acquisitions) method enables high resolution MR-imaging with improved contrast of spinal cord (SC) gray matter (GM) and white matter in clinically feasible acquisition times at 3 Tesla.(1,2)

The aims of this study were to compare cervical SC GM areas between patients with a diagnosis of ALS and healthy, age- and sex-matched control subjects (HC) and to assess the association of cervical SC GM area and established measures of clinical disability, the revised ALS functional rating scale and of respiratory impairment, the sniff nasal inspiratory pressure (SNIP) in ALS.

Methods: Using axial 2D radial (r)AMIRA imaging(1) at the cervical intervertebral disc level C3/C4 acquired at a 3T PRISMA scanner (Siemens healthineers) and a semi-automated segmentation approach (JIM7, www.xinapse.com), we compared SC GM areas of 36 patients diagnosed with ALS according to the Gold Coast criteria(3) (mean age 61.7 yrs, 14 women, with bulbar and spinal onset, mean disease duration 32.9 months) and 36 age- and sex-matched HC. The associations between SC GM area and disability metrics (ALSFRS-R(4) and SNIP(5)) were assessed by multivariable regression analyses with adjustment for age and sex.

Results: SC GM area at the level C3/C4 was significantly reduced in patients with ALS compared to HC (mean GM area in mm2 (SD): ALS 16.6 (2.3); HC 19.65 (2.7); relative reduction 15.4%, p < 0.0001). In multivariable regression analyses adjusting for age and sex, GM area at C3/C4 explained 36.1% of ALSFRS-R variance (p = 0.0001) and 32.2% of SNIP variance in patients with ALS, respectively.

Conclusions: Cervical SC GM area in ALS patients shows significant atrophy compared to HC and correlates with established measures of clinical disability and respiratory impairment, namely ALSFRS-R and SNIP. Further longitudinal investigations, particularly of patients early in the disease course, are necessary next steps to evaluate the potential of this novel and easy to assess imaging marker for monitoring and predicting the disease course, and its potential as a surrogate in upcoming drug trials.

Aims
The risk of herpes zoster (HZ) is associated with a decline in the immune system function, linked to aging and/or in individuals who are immunocompromised or immunosuppressed due to disease or therapy. In this post-hoc analysis, we describe the incidence and burden of HZ pain in immunocompetent patients ≥ 50 years of age (YOA) and in hematopoietic stem cell transplantation (HSCT) recipients aged ≥ 18 YOA.

Methods
ZOE-50 (NCT01165177), ZOE-70 (NCT01165229) and ZOE-HSCT (NCT01610414) were phase III, observer-blind, placebo-controlled, randomized studies conducted in immunocompetent adults ≥ 50 YOA (ZOE-50) and ≥ 70 YOA (ZOE-70); and in HSCT recipients aged ≥ 18 YOA, respectively. Studies were conducted between August 2010 and July 2015, and between July 2012 and February 2017 for the ZOE-50/ZOE-70 and ZOE-HSCT studies, respectively. The participants received 1 or 2 doses of the adjuvanted recombinant zoster vaccine or placebo, 1 to 2 months apart. The analysis was performed on unvaccinated/placebo subjects who had a confirmed HZ episode during the original studies. HZ pain and interference with activities of daily living was assessed by the Zoster Brief Pain Inventory instrument.

Results
Overall, 280 HZ confirmed patients aged ≥ 50 YOA, 240 HZ patients aged ≥ 70 YOA, and 172 HZ patients aged ≥ 18 YOA were included in the placebo groups for the ZOE-50, ZOE-70 and ZOE-HSCT studies, respectively. The incidence of HZ was 9.1/1000 person years in both the ZOE-50 and ZOE-70 placebo groups and 95.6/1000 person years in the ZOE-HSCT study placebo group. In the 3 studies, the majority of individuals with HZ experienced severe pain, with approximately 90% of individuals reporting clinically significant pain. Descriptive statistics on the location of the rash, number of dermatomes involved, the presence of pain and pain intensity will be presented by study group.

Conclusion
Our assessments show that the incidence and burden of HZ is high in immunocompetent adults aged ≥ 50 YOA and even more so in HSCT recipients aged ≥ 18 YOA.

Background: Emerging evidence suggests that long-term blood pressure variability (BPV) may contribute to cerebral small vessel disease progression and cognitive impairment beyond the deleterious effects of elevated blood pressure. (1,2) We investigated whether BPV is associated with white matter (WM) microstructural integrity and cognitive decline in elderly individuals with cerebral amyloid angiopathy (CAA), a well-characterized cerebral small vessel disease.

Methods: We recruited 131 non-demented individuals (73.3 ± 7.0 y, 33/101 female/male, MMSE 27.5 ± 2.0) from the Massachusetts General Hospital memory-clinic cohort with and without CAA (24/50 possible/probable CAA) according to modified Boston criteria. Participants underwent detailed neuropsychological testing and a 3 T research MRI. Visit-to-visit BPV was assessed using the coefficient of variation derived from serial BP measures during a 5-year interval. A novel diffusion tensor imaging marker – peak width of skeletonized mean diffusivity (PSMD) – was used to evaluate the WM integrity. (3) We used linear regression models to assess the association between BPV with PSMD and domain-specific cognitive decline. Models were adjusted for mean BP, age, sex, hypertension, antihypertensive medication, diabetes, smoking, and body mass index.

Results: We found a strong association between loss of WM integrity and high systolic BPV (β = 0.43, P < 0.001). The association remained significant in the adjusted regression model (β = 0.41, P < 0.001). Furthermore, the association of BPV with WM integrity was stronger when CAA was present (β = 9.33, P for interaction < 0.023). Higher BPV was associated with decline in global cognition (β = -0.24, P = 0.035) and processing speed (β = -0.30, P = 0.022). BPV also had a weak association with decline in executive function (β = -0.19, P = 0.106), and memory (β = -0.19, P = 0.095).

Conclusions: Our findings show that long-term BPV is associated with microstructural vascular white matter injury that may contribute to domain-specific cognitive decline in older adults. The association between BPV and white matter integrity may in part be driven by CAA-related vascular dysfunction. Better control of BPV could be a novel therapeutic target to slow cognitive decline over time. As a next step, we will use BP telemonitoring technologies to evaluate whether real-world BP fluctuations contribute to vascular brain injury and vascular cognitive impairment.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurological disease and patients present with symptoms, which can occur as relapses or as progressive neurological deterioration. Comprehensive, standardized clinical neurological assessment is the gold standard to evaluate activity and to track disability over time. The Neurostatus-eEDSS® is the standard assessment deployed in MS randomized clinical trials (RCT), typically serving as the primary endpoint. COVID-19 pandemic has impacted conduct clinical studies. This opened opportunities to adapt the data capture systems in clinical trials i.e. conducting neurological assessments on phone or video. We have developed a new version of Neurostatus-eEDSS® for trained non-neurologist healthcare professionals (HCP) to perform these assessments. . This Neurostatus-SMARTCARE (“smartly modernized assessment: recorded, telemedical, care professional-assisted, remotely evaluated”) assessment is video recorded, allowing neurologists to review and re-assess the ratings for quality control as needed.
AIM: to assess the concordance between Neurostatus-SMARTCARE, performed by HCPs, and Neurostatus-EDSS®, performed by neurologists.
METHODS: A multicentre randomized cross-over study in Switzerland with 100 MS patients that have consented to participate are randomized 1:1 to group A or group B. Group A undergoes first Neurostatus-EDSS® and afterwards Neurostatus-SMARTCARE - group B starts with Neurostatus-SMARTCARE and finishes with Neurostatus-EDSS®. At the next regular visit –i.e. 6 or12 months- the reverese order is applied. The HCP and neurologist performing the evaluations are blinded to each others findings and assessment scores. . All examinations are entered into an electronical case report form and video recorded.
CONCLUSION: The combination of a video recorded system and an expert assessment presents a unique opportunity for innovation in MS RCTs. In addition, Neurostatus-SMARTCARE may be extended to clinical care settings by allowing home based assessment by MS HCPs, thereby reducing the burden on patients and caregivers. Furthermore it offers the potential for more frequent remote assessments and reducing the costs.

Background: Brain fog is a common and highly disturbing symptom for patients with neuropathic postural tachycardia syndrome (POTS). Cognitive deficits have been measured exclusively in the upright body position and mainly comprised impairments of higher cognitive functions. The cause of brain fog is still unclear today. This study aimed to investigate whether increased autonomic activation might be an underlying mechanism for the occurrence of brain fog in neuropathic POTS. We therefore investigated cognitive function in patients with neuropathic POTS and a healthy control group depending on body position and in relation to norepinephrine release as a sensitive indicator of acute stress. The second aim was to test the effect of water intake on cardiovascular regulation, orthostatic symptoms, cognitive function and norepinephrine release.
Methods: Thirteen patients with neuropathic POTS and 15 healthy control subjects were included. All participants completed a total of four rounds of cognitive testing: two before and two after the intake of 500 ml still water, each first in the supine position and then during head-up tilt. At the end of each cognitive test, a blood sample was collected for determination of plasma norepinephrine. After each head-up tilt phase participants were asked to rate their current symptoms on a visual analogue scale.
Results: Working memory performance in the upright body position was impaired in patients, which was associated with self-reported symptom severity. Patients had elevated plasma norepinephrine independent of body position and water intake that increased excessively in the upright body position. The excessive increase of plasma norepinephrine was related to heart rate and symptom severity. Water intake in patients decreased norepinephrine levels and heart rate, and improved symptoms as well as cognitive performance.
Conclusion: Brain fog and symptom severity in neuropathic POTS are paralleled by an excessive norepinephrine secretion. Bolus water drinking down regulates norepinephrine secretion and improves general symptom severity including brain fog.

Objective
To demonstrate that there are interindividual differences in the response of upper limb bradykinesia to subthalamic deep brain stimulation (STN-DBS) in patients with Parkinson’s disease (PD) depending on the stimulation frequency used.

Background
There is evidence that increasing stimulation frequency of STN-DBS beyond the standard settings of 130 Hz may improve tremor, whereas lower frequencies "< 100 Hz" are more beneficial for axial motor symptoms. There are also indications that the improvement of upper limb motor symptoms varies between patients depending on the frequency used.
Methods
A kinematic analysis of a finger-tapping train for 20 sec. was assessed in 13 PD patients (median: 63 ears; range 56-71 years) with chronic ("> 3" months) bilateral STN-DBS after overnight PD drug withdrawal. Frequencies were varied in intervals of 10 Hz from 60-180 Hz (randomized sequence), while the TEED was kept stable. Every train of finger-tapping was performed twice for each frequency five minutes after the frequency had been changed. The decrement of the amplitude of the finger taps (i.e. distance between index finger and thumb) was measured by means of a kinematic system and estimated by fitting a regression line to the amplitude values. The regression coefficients were compared statistically.
Results
As expected the amplitude decrement of finger taps improved under DBS compared to the state off DBS ("p < 0.001"). The optimal stimulation frequency with the least decrement varied from patient to patient. There was no consistent peak frequency across patients. Similar observations were made for the worst stimulation frequencies which in a few patients resulted in an even worse motor performance than off DBS
Conclusions
Our results indicate that the effect of DBS on upper limb bradykinesia varies across individuals depending on the frequency used. The standard frequency of 130 Hz may not yield the best motor response to DBS in all individuals. We propose that evaluating different stimulation frequencies may contribute to an optimisation of the DBS effect, whereas the concept of “one frequency fits all” should be abolished.

Aims:
Treatment of pericallosal aneurysms (PeriAy), whether endovascular or surgical, relies more on the neurovascular team experience than on evidence-based guidelines. This study aims to compare endovascular and surgical treatments of PeriAy, ruptured and unruptured.


Methods:
All data were extracted from the Pericallosal Aneurysm Study Group data base, an multicentric international cohort collecting data on patients treated for at least one PeriAy, ruptured and unruptured. Outcomes were compared by endovascular versus surgical treatments, and by rupture status. The primary outcome was the mRS at 12 months. Secondary outcomes were the aneurysmal complete occlusion at 12 months, the rate of complications, and vasospasms requiring invasive treatment.


Results:
One hundred and sixteen treated pericallosal aneurysms were included, 31 (26.7%) were treated endovascularly and 85 (73.3%) were treated surgically. Fifty-three treatments concerned ruptured PeriAy (21 endovascular (67.7%), 32 surgical (37.6%) (p < 0.001)). Demographics were similar between groups.

No difference regarding the mRS at 12 months was observed between the treatment groups (endovascular and surgical groups respectively (median): all 0 [Q1:0, Q3:2], 0 [Q1:0, Q3:1]; unruptured 0 [Q1:0, Q3:1], 0 [Q1:0, Q3:1]; ruptured 0 [Q1:0, Q3:2], 0 [Q1:0.5, Q3:2]).

No residual perfusion of the PeriAy was observed in the surgical treatment group, whereas 44.4% of the endovascularly-treated aneurysms were found to have residual perfusion (p < 0.001). The need of invasive treatment for vasospasm was significantly lower in the surgical group (12.5%) compared to the endovascular group (38.1%, p = 0.04). No difference was observed regarding the complication rate (endovascular 29%, surgical 16.5%, p = 0.19).

Conclusion:
Although surgical treatment reduces the risk of aneurysmal residual perfusion and the need of invasive treatment for vasospasms, ruptured PeriAy are more often treated endovascularly. PeriAy should be considered for surgical treatment, especially if ruptured. Endovascular treatment should be reserved for morbid patients with surgical risk. Multicentric data collection is still ongoing.

Aims: Recently, ‘don’t eat me’-signals like CD47 have emerged as novel innate immune checkpoints, enabling cancer cells to evade clearance by phagocytes such as monocyte-derived macrophages (MdM) or microglia (MG). Here, we aim at defining the role of inhibitory Siglec-9 in human and its mouse homologue Siglec-E in MG-centered immunotherapy against GBM.

Methods: We employed a CT-2A orthotopic GBM mouse model with MG specific (Sall1-CreERT2 x Siglece-flox) and whole innate-compartment (Cx3cr1-CreERT2 x Siglece-flox) spatio-temporal deletion of Siglece. We applied multi-color flow cytometry, transcriptomics and proteomics analysis to decipher the immune response upon Siglece knockout.

Results: TCGA RNA-sequencing data revealed a significant correlation between high expression of immunoinhibitory SIGLEC9 and poor survival in GBM patients (log-rank p = 0.02). In the MG specific spatio-temporal deletion of Siglece (Sall1-CreERT2 xSiglece-flox), we observed high MG-proliferation upon Siglec-E knockout (Ki-67+ MG 14.8% in Cre- vs. 34.9% in Cre+, p < 0.0001) accompanied by an enhanced microglial GBM-cell uptake (5.6% in Cre- vs. 12.3% in Cre+, p < 0.001). By extending the Siglece knockout to the MdM compartment in our glioma mouse model (Cx3cr1-CreERT2 x Siglece-flox) we observed a significantly prolonged survival in the Cx3cr1-Cre+ population (21d in Cre- vs. 27d post-tumor injection in Cre+, p = 0.018), which could be further promoted by combining Siglece knockout with CD47 blockade (11% long-term remission in Cre+ + anti-CD47). Proteomics analysis revealed increased antigen processing and presentation capabilities of Siglece knockout MdMs which was confirmed by ex-vivo OT-1 cross-presentation assays. This increased T cell priming upon MdM Siglece knockout was further boosted by addition of anti-PD1 antibody to the Siglece knockout + anti-CD47 combination. Resulting in 23% of animals experiencing long-term remission in the triple treatment arm, even after tumor re-challenge. By genetically targeting sialic acids, the ligand for Siglec receptors, on CT-2A cells (GNE-KO), we observed a strong innate and adaptive immune response with increased GBM-cell phagocytosis by MG and MdMs and less exhausted tumor-infiltrating CD8+ T cells (14.8% in WT vs. 5.9% in GNE-KO, p = 0.003).

Conclusion: These data identify the sialic-acid-Siglec-E pathway as an anti-phagocytic signal in a pre-clinical GBM model, and demonstrate its therapeutic potential in GBM immunotherapy.

Background: Clinical trials of systemic T cell checkpoint blockade in GBM patients showed only disappointing results. This may be attributed in part to the immunosuppressive components of the GBM immune tumor microenvironment (iTME). Therefore, major efforts have been undertaken to describe the GBM iTME on a single cell level. However, human data on the composition of the iTME in different tumor regions (contrast enhancing tumor center versus peripheral infiltration zone) remain scarce.

Methods: Here, we performed high-depth single-cell RNA sequencing (scRNA-seq) on patient-matched biopsies from tumor center and the peripheral infiltration zone of five primary GBM patients. Additionally, peripheral blood mononuclear cells (PBMC) of the same patients were included in the analysis to explore the transcriptional changes occurring during tumor infiltration of circulating immune cells. Main findings of the transcriptional analysis were confirmed by flow cytometry.

Results: Through analysis of > 45’000 cells, we revealed a distinct regional transcriptional profile of microglia (MG) and monocyte-derived macrophages (MdM), a non-reactive/exhausted MG subcluster in the GBM iTME and an impaired interferon-response signature in the tumor-peripheral cytotoxic cell compartment. Comparing CD8+ T cells from the tumor periphery to PBMC-derived CD8+ T cells of the same patient revealed CX3CR1high and CX3CR1int CD8+ T cell populations with effector and memory phenotype, respectively. These cells were enriched in the PBMC but lacking in the tumor periphery. Tumor peripheral CD8+ T cells shared features with tissue-resident memory CD8+ T-cells with exhausted effector functions.

Conclusion: Our analysis provides a large-scale dissection of GBM-associated cell types complemented by patient-matched PBMCs, serving as a high dimensional reference map of the human GBM iTME.

Aim
Resorption of bone flap after reimplantation following decompressive hemicraniectomy is a well-known problem. Due to mostly short follow-up after reimplantation, the event is likely underreported in the literature. We aim at quantifying the risk of bone flap resorption within the first two years after reimplantation and currently provide a single-site interim-analysis of screening- and study data.

Methods
So far, we screened 192 patients that underwent decompressive hemicraniectomy in our institution between Sept 2014 and April 2022 as well as the clinical and radiological follow up one resp. two years after reimplantation of the autologous bone flap. Patients after reimplantation were prospectively enrolled. We performed a 1 resp. 2 year follow up including clinical examination and CT scan. Resorption was classified using a score taking into account clinical (palpable dehiscence, instable flap) and radiological (thickness of flap and dislocation on CT scan) findings. Furthermore, facial symmetry was optically evaluated.

Results
• Out of 192 hemicraniectomies, 129 (67%) got reimplanted.
• Mortality after decompressive hemicraniectomy: 25.5%
• 102 patients (53%) agreed to participate in the study. Of those, 65 fulfilled their 12 Mo F/U, whereas 21 (32%) showed bone flap resorption at 12 months after reimplantation. Amongst those who completed the 24 Mo F/U (53 patients), 21 patients (40%) presented with significant bone flap resorption.
• Mean patient age: 52.4 y
• Mean duration to reimplantation: 2.9 month
• Indication: CVI (39 patients), SAB (44), aSDH (64), ICB (16), others (29)
• Complications amongst survivors: 6.9% surgical site infections, 2.3% hydrocephalus, 5.6% postoperative hematoma

Conclusio
Decompressive Hemicraniectomy is a treatment of last resort, which explains the high mortality rate. Amongst survivors, cumulated complication rates after reimplantation of the bone flap are 14.8% (surgical site infections, hydrocephalus, postoperative hematoma). 32% of patients show bone flap resorption 1 year after implantation. This results in an overall complication rate of 46.8% within one year after reimplantation.
Use of CAD-based patient specific implants instead of autologous bone flaps is a viable alternative after decompressive hemicaniectomy, especially in patients of younger age or in case of segmented bone-flaps due to an even more frequent resorption of the bone flap reported in the literature, requiring additional surgery in the future

Aims. Blood Oxygenation Level Dependent (BOLD) is by far the most used contrast for functional MRI [1, 2]. However, its spatial specificity can be biased by altered neurovascular coupling, which is typical in patients who are candidate for neurosurgery [3-6]. Arterial Spin Labelling (ASL) is a non-invasive MRI technique for a direct and quantitative measurement of the cerebral blood flow. It can be used for functional imaging as an alternative to the standard BOLD. This work aims to assess the spatial specificity of functional-ASL (fASL) in respect to BOLD and in comparison with Transcranial Magnetic Stimulation (TMS) in healthy subjects, for and before translating fASL in the clinical pre-surgical workflow.
Methods. Thirty healthy volunteers ([18-31; 40-65] years old, 15 females) performed a motor and somatosensory task in a 3T MRI, while BOLD and ASL were simultaneously acquired. TMS for the representation of ‘hand’ in the brain was performed in a separate session. For each subject and each hand, the coordinates of the global maxima for BOLD and fASL were collected at individual level and then compared with TMS (assumed as ‘gold standard’). To detect systematic shift in the localization, paired-t-tests were performed: i) between the two MRI modalities; ii) between TMS and each MRI modality.
Results. For the motor task: i) fASL localized significantly more anteriorly and deeper than BOLD (p < 0.05) and ii) fASL was significant closer than BOLD to TMS (p < 0.05), along the posterior-anterior and ventral-dorsal directions. For the somatosensory task, at a group level, fASL localized: i) more towards the midline; ii) more anteriorly; iii) deeper than BOLD.
Conclusion. Our results are concordant with the literature which used used different types and techniques of analysis [7,8]. The validation step on a selected clinical population will enrich our investigation of fASL spatial accuracy given the availability on perioperative monitoring. In the future, fASL could be a valid and more specific substitution of BOLD, particularly for clinical localization of eloquent cortex to be preserved during brain surgery.

References
1. Ogawa S et al,1992. PMID: 1631079
2. Kwong KK et al,1992. PMID: 1608978
3. Jacobs J et al, 2009. PMID: 19349236
4. Carusone LM et al, 2002. PMID: 12169483
5. Pittau, F et al, 2013. PMID: 23793553
6. Agarwal S et al, 2016. PMID: 26201672
7. Lascano AM et al, 2014. PMID: 24463494
8. Diekhoff S et al, 2011. PMID: 20533563

Background: Glioblastomas with methylation of the promotor region of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene exhibit increased sensitivity to alkylating chemotherapy. Quantitative assessment of the MGMT promotor methylation status might provide additional prognostic information. The aim of our study was to determine a quantitative methylation threshold for better survival among patients with isocitrate dehydrogenase (IDH) wildtype glioblastomas.
Methods: We included consecutive patients "≥ 18" years treated at our department between 11/2010 and 08/2018 for a glioblastoma, IDH wildtype undergoing quantitative MGMT promotor methylation analysis. Quantitative MGMT promotor methylation analysis was performed using a primer extension-based method adapted to formalin-fixed paraffin-embedded tissues. Six diagnostically relevant CpG dinucleotides are mapped with this assay. The primary endpoint was overall survival. In a secondary analysis including only tumors exposed to temozolomide (TMZ), the percentage of methylation of each tumor was plotted on a ROC curve using survival "> 13.0" months, referring to a historical cohort treated by radiotherapy only, as outcome parameter.
Results: 321 patients were included. Mean age was 64.1 years (± 11.4). Median overall survival was 12.6 months. Kaplan-Meier and adjusted Cox regression analysis showed better survival for the groups with 16–30% (p=0.010), 31–60% ("p < 0.001"), and 61–100% ("p < 0.001") methylation. In contrast, survival in the group with 1–15% methylation was similar to that with unmethylated promotor regions (p=0.204). The secondary analysis confirmed this threshold with a maximal Youden index at "≥ 16%" methylation.
Conclusion: Better survival is seen in patients with glioblastomas with "≥ 16%" methylation of the MGMT promotor region than with "< 16%" methylation. Survival with tumors with 1–15% methylation is similar to with unmethylated tumors. Above 16% methylation, we found no additional benefit with increasing methylation. We suggest using the 16% threshold of MGMT methylation for selecting patients in clinical trials and for prognostic counseling.

Aims: Patients with Parkinson’s disease (PD) suffer from symptoms that have been linked to increased beta-oscillatory activity (13–35 Hz) in the basal ganglia. Current state-of-the-art treatments include dopamine replacement therapy and deep brain stimulation (DBS). While these approaches reduce pathological beta-oscillatory activity concomitantly with improving motor performance, we set out to explore deep brain-computer interfaces that exploit neurofeedback to modulate pathological deep brain activity. Neurofeedback has emerged as a promising technique enabling the self-regulation of cortical (EEG neurofeedback) or subcortical brain activity (rt-fMRI neurofeedback). However, while the latter allows subcortical brain modulation, it is inherently slow as it relies on the BOLD response.

Methods: We present a much faster method, namely deep brain electrical neurofeedback, which uses implanted DBS electrodes. These measure local field potentials within the subthalamic nucleus that can instantly be processed to provide real-time visual neurofeedback of pathological subthalamic beta activity.

Results: All PD patients in this study (n = 8) were able to reduce on-going beta-oscillatory activity within as little as 6 minutes of neurofeedback training (p = 0.00092) as compared to their resting beta-activity. We also observed improvement over three consecutive neurofeedback blocks, assessed by a stronger reduction of beta-oscillatory activity by the end of a single training session over one hour as well as accelerated hand movements. Lastly, control over deep brain activity was possible even after removing visual neurofeedback (p = 0.0156), suggesting that neurofeedback-acquired strategies to control deep brain oscillations are retained.

Conclusion: In summary, we show that deep brain electrode-guided neur- ofeedback is an efficient way to reduce pathological deep brain activity as well as bradykinesia and that the modulatory effect improves with training and can even be retained once neurofeedback is no longer provided. Further improvement of deep brain neurofeedback might benefit patients with PD by improving symptom control or even patients that suffer from other diseases that DBS is currently tested for.

Objective : To describe a cheap simulation model used to reduce the learning curve of the interlaminar full-endoscopic discectomy.

Background : The very difficult learning curve remains one of the main obstacles against the widespread diffusion of interlaminar full endoscopic lumbar discectomy (ILFED). One solution to overcome this learning curve is training with deliberate practice. As realistic models are relatively expensive and cadaver workshops not readily available, we developped a simple and cheap model to train the key steps of the procedure.

Methods : A simple and cheap model was designed. It consists of a king oyster mushroom stalk, a glove finger, a sponge and cotton wool. In order to fix the model to the table and to simulate the level of the patient’s skin whereupon the hand of the surgeon relies, a wooden holding device was also used.

Results
The model has been tested by colleagues attending an advanced ILFED training course on expensive realistic models. A step-by-step learning method with key steps was used. All colleagues evaluated the model as comparable and enough realistic to train key steps in order to reduce the learning curve and training costs.

Conclusion
We present an affordable, simple and reproducible training model, which allows for deliberate practice of the key steps of the ILFED procedure. The model may be used by surgeons starting with spinal endoscopy before practicing on more expensive training material, such as realistic models or cadavers.

Objective
Over the recent decades, the number of different manufacturers and models of cerebrospinal fluid shunt valves constantly increased. Proper identification of shunt valves on x-ray images is crucial to neurosurgeons and radiologists to derive further details of a specific shunt valve, such as opening pressure settings and MR scanning conditions. The main aim of this pilot study is to evaluate the feasibility of an AI-assisted shunt valve detection system.

Methods
The dataset used contains 1444 anonymized images of five different, commonly used shunt valve types from a single institution. All images were acquired from skull x-rays or scout CT-images and were cropped in a random size containing the shunt valve. In detail, the dataset contains images of 359 Miethke proGAV 1, 394 Miethke proGAV 2, 308 Codman Hakim Programmable, 304 Medtronic PS Medical Strata and 80 Integra DP valves. The images were randomly split into a 80% training and 20% validation set. An implementation in Python with the FastAi library (Howard J. et al. 2020) was used to resize all images to 460x460 pixels and to train a convolutional neural network with 101 layers using a transfer learning method on a pre-trained model.

Results
Overall, our model achieved an F1-score of 0.98 to predict the correct shunt valve model. Breaking down the performance metric for each shunt valve, we could achieve an F1-score of 0.97 for the Codman Hakim Programmable, 0.97 for the Medtronic PS Medical Strata, 0.98 for the Miethke proGAV 1, 0.98 for the Miethke proGAV 2 and 1.0 for the Integra DP shunt valve on our validation set.

Conclusion
This technology has the potential to automatically detect different shunt valve models in a fast and precise way and may facilitate the identification of an unknown shunt valve on X-ray or CT scout images. Our results are in line with recent publications (Sujit et al. 2021) demonstrating the feasibility of AI-assisted shunt valve identification. The current model is able to distinguish between five different shunt valve types. A larger dataset including the most common shunt valve models is required to make proper use of this technology in daily routine.

BACKGROUND. Glioblastoma (GBM) is the most aggressive and common brain tumor. Despite multimodal therapy which consists of complete tumor removal, chemo- and radiation therapy in most patients, the tumor recurs, and the overall survival of only 14 months remains very poor. To identify tumor-induced immune evasion and treatment resistance mechanisms induced during GBM recurrence, we aimed at characterizing the immunological/molecular changes in patient-matched treatment-naïve and recurrent GBM samples.
MATERIAL AND METHODS. Proteins and total RNA were extracted from 16 patient-matched treatment-naïve (primary) and recurrent GBM fresh frozen tumor samples. The expression of genes involved in brain immune responses were compared using Nanostring panels encompassing Cancer and Neuroinflammation genes. Proteomic was conducted using 6 patient-matched primary and recurrent tumor samples. Immunostaining was performed on a tissue microarray containing matched primary and recurrent tumor samples to identify tumor cells and microglia in order to assess spatial transcriptome of these specific cell types in situ using GeoMX technology. Moreover, correlation analysis of differentially genes and proteins with time to relapse was performed.
RESULTS. Genes significantly differentially expressed between primary and recurrent tumors revealed genes overexpressed in recurrent tumors belonging to “FCGR-mediated Phagocytosis” and “synapse pruning” pathways. Proteomic confirmed the synaptic signalling considering overexpressed proteins. Correlation studies with the time to relapse indicated that higher expression of FCG receptors, complement molecules and synaptic components correlate with shorter time to relapse, sharing similarities with neurodegenerative/cognitive disorders such as schizophrenia and Alzheimer disease. The source for these molecules is under evaluation with the spatial transcriptomic analysis.
CONCLUSION. Upregulation of specific proteins such as FCG receptors, complement and synaptic components may result in more favourable conditions for tumor regrowth and may therefore be identified as negative predictors patient outcome. Interfering with these molecules may represent novel therapeutic options after initial GBM surgery.

Aims: Endovascular treatment (EVT) of large vessel occlusion in acute ischemic stroke is the current gold standard. EVT using a magnetic steerable catheter (MSC) is a potential alternative to well-established manual guidewire-based EVTs to directly steer the MSC with a magnetic field. Robotic magnetic navigation systems (MNS) can simplify catheter navigation and allow for remote intervention. This has the potential to reduce procedure time and costs and also provide treatment in remote areas without specially trained medical staff.
Method: A diagnostic MSC was developed and tested in combination with established thrombectomy devices (TD) from Medtronic, Stryker, and Microvention. The catheter has two magnets at the tip and was operated with an MNS and a motorized advancer unit. In-vivo experiments were performed in vivo on a 45 kg pig. The catheter position was tracked with a Philipps Allura Xper FD20 angiography system.

Results: The navigation of the MSC and the TD deployment were successfully tested in this in-vivo feasibility study. The MSC has been successfully navigated to different arterial branches of the extracranial vasculature and the TDs have been successfully deployed. Technically, the generated magnetic torque was sufficient to reliably navigate while low enough to avoid arterial damage.

Conclusion: This in-vivo study demonstrates the feasibility of MSC navigation in small vessels and the successful deployment of different TDs in an in-vivo model. Future studies need to incorporate remote operation functionality including the remote control of the patient bed and fluoroscope to make this technology suitable for clinical use.

Aims: A newly developed magnetic steerable micro-catheter (MSM) controlled by an electromagnetic navigation system (eMNS) offers remote control and high navigability in small and distal vessels.
Currently, endovascular therapy (EVT) of distal vessel occlusion (DVO) in acute ischemic stroke (AIS) is increasingly performed (1). Endovascular treatment of DVO requires a high degree of technical expertise and is not without risk.
Here, we present a novel concept of MSM that can be applied to AIS patients with DVO using intra-arterial thrombolysis (IAT).

Method: A 2Fr micro-catheter with magnetic tip was navigated through the small branches of the external carotid artery (ECA) of a 45 kg pig in vivo. The MSM tip was controlled with means of external magnetic fields generated by an (eMNS) and advanced by a motorized advancer. The operator interacted with the system via a hand-held controller. The MSM was imaged using a mono-planar angiography system (Philipps Allura Xper FD20). Once the target site was reached, a IAT mimicking contrast agent solution (50:50 Iopamiro 300) was injected.

Results: The MSM was successfully navigated in small diameter, tortuous vessels (small branches of the ECA). An injection of contrast agent was performed at multiple target sites imitating IAT application. The magnetic catheter showed high controllability for selecting multiple millimetre-sized arteries.

Conclusion: We demonstrated the feasibility of MSM using eMNS in small vessels in a porcine model. Due to the ease of use of this novel technique, MSM has the potential to facilitate EVT in AIS patients by reaching more distant vessel occlusions and addressing complex anatomical situations.

Aims
Epilepsy research has recently undergone a paradigm shift: from epilepsy as focal cortical disease towards epilepsy as network disease. This is motivated by new evidence of widespread brain activity in seizure initiation and maintenance, and by promising results of brain stimulation for drug-resistant cases. However, a thorough understanding of the network-rooted epileptic dynamics is still missing, and the details of the stimulation procedures do not account for the variable brain network dynamics between patients.

Methods
We develop personalized dynamical models of epileptic networks, based on EEG in an entirely data-driven manner. A dynamic connectivity matrix, simultaneously capturing the dominant spatial and temporal modes in the epileptic network, is extracted for steady-state EEG dynamics. The considered population includes 30 patients with frequent epileptiform discharges ("active EEG"). The dynamical properties of the active and inactive EEG states are compared.

Results
Our model accurately reproduces the clinically relevant properties of the recorded EEG dynamics: spectral power, channel coherence and amplitude variation. We find the dominant coherent structures for each epileptic network state. In addition, the models allow to simulate the effects of external network stimulation. By comparing the two types of brain dynamics, the model is used to predict targeted interventions to transition from pathological to healthy states.

Conclusion
We developed personalized EEG-driven models of epileptic network dynamics. We demonstrated their accuracy for patients with active EEG. The models can be readily used to predict the optimal localization and stimulation parameters of patient-specific interventions and help resolve the pathological epileptic network states.

Due to its connectivity profile and its potential role in the subcortical propagation of seizures, the Anterior Nucleus of the Thalamus (ANT) is chosen as the stimulation target in Deep Brain Stimulation (DBS) for drug-resistant epilepsy (DRE). We aimed to analyze how the ANT interacts with the neocortex and to explore the electrophysiological mechanisms underlying the effectiveness of this method.
Electroencephalograms (EEG) and ANT Local Field Potential (LFP) have been recorded parallelly during the intra-operative phase of ANT-DBS bilateral implantation in 15 subjects. High-frequency test stimulations in the ANT have been delivered, while EEG was recorded.
Firstly, by analyzing the electrophysiological properties of the ANT in the spectral domain, we found that the major difference among thalami (T=30) was observed in the theta and low alpha range. The same result was found along the implantation trajectory. A sweet-spot of a higher theta power was found at approximately 1.5 to 3.5 mm post-entry. The strongest connectivity (wpli-debiased) between the scalp and ANT bilaterally was found in the theta band (N-way ANOVA, p < 0.01), with F3/F4 channels most strongly connected to left/right ANT respectively. Importantly, the depth of recording of the ANT along the implantation trajectory did not affect the profile of connectivity to the cortical regions. We analyzed EEG properties with (“ON”) and without (“OFF”) stimulation (paired t-test). A significant decrease (p < 0.05) in high beta and gamma power was found and spread throughout the scalp, counteracted by a trend towards an increase in lower frequencies. Scalp Connectivity showed a statistically significant increase (ON-condition) in the theta band and in the gamma band (p < 0.001).
We finally explored how these measures correlated to subjective responsiveness to therapy, computed as the reduction in seizure frequency 6 months post-implantation. We divided our cohort of patients into Responders (N=9) and Non Responders (N=6). We found that Responders presented a significantly stronger scalp and ANT theta power, both in OFF and ON conditions. Moreover, the average ANT to scalp theta connectivity was stronger in Responders than in Non Responders, with a focus on fronto-central areas. In conclusion, this study represents an unprecedented characterization of the dynamical interactions between the ANT and the cortex in the context of ANT DBS for DRE, providing crucial information to optimize this therapy.

Background
In focal epilepsy, seizures result from subnetworks of abnormally high cortical excitability (CE) within a relatively normal brain. Practical means of monitoring CE in the human brain, for example to assess the effects of anti-seizure medications are currently lacking. We asked whether directly probing the brain with minute electrical pulses and recording cortico-cortical evoked potentials (CCEPs) may help quantify CE before and after administration of a benzodiazepine (BZD).

Methods
In seven epilepsy patients undergoing cortical recordings for diagnostic reasons (median number of electrode contacts: 68 [48, 111]), we probed CE with repeated single pulses (median N= 168 [151, 204]) systematically varying in intensity (0.2 – 12mA). All brain responses, before and after administration of clonazepam (0.75-1mg) were clustered into subnetworks using NMF (Non-negativity matrix factorization) based on the dynamics of CCEPs. CE in each subnetwork was quantified by the magnitude of the NMF activation coefficients.

Results
Across patients, NMF delineated a total of 20 subnetworks that encompassed a collection of brain areas with shorter- and longer-range connections responding conjointly to the administered probing stimulations with CCEPs. Across these subnetworks, CE was significantly decreased after BZD administration (Wilcoxon signed-rank test: p = 0.0003).

Conclusion
Combining probing neurostimulations with unsupervised pattern recognition algorithms, we introduce a novel method to quantify CE in the human brain. As a proof-of-principle, we apply this method to uncover the network effects of a well-known GABA agonist on CE. Applying such methods over longer durations, may help monitor non-linear dynamics in the human cortex, including in epilepsy.

Objectives. In this retrospective single-center study, we examined the impact of delay of anti-seizure medication (ASM) introduction on outcomes for patients with new-onset epilepsy (NOE), starting in the emergency department (ED).

Methods. All patients ( ≥ 16 years) with NOE between 1.3.2010 and 1.3.2017 were included in the present study. The diagnostic protocol included routine EEG, brain CT/MRI, long-term overnight EEG (LT-EEG) and specialized consultations, which were launched as soon as the patient arrived in the ED. Patients were followed for 5 years. The effect of the delay of treatment introduction on the relapse rate was investigated using Cox proportional hazard models. Potential confounded variables such as as the presence of a tumor, the type of epilepsy, the sex, etc. were controlled for in the models.

Results. 487 patients suffered from NOE. If treatment was initiated ≤ 48 h, relapses were less likely as compared to patients with ASM introduction > 48 h (39.4% vs 68.1%, respectively, p < 0.001). Patients with a history of anterior events (p < 0.001), male sex (p = 0.003), younger patients (p = 0.04) and focal epilepsy p = 0.04) were more likely to relapse. Despite these variables controlled for, the effect of treatment delay remained highliy significant, and if only patients with full treatment by 6 months were considered, the effect remained significant as well (p < 0.001).

Conclusions. Our results suggest the benefit of swift work-up and introduction of ASM therapy within 48 h after the first seizure. ASM therapy within 48h was associated with better prognosis up to 5 years after the index event. Patients may benefit of first-seizure units, similar to stroke units, activated upon arrival in the ED as well the development of more ASM allowing rapid up-titration.

Patrick Stancu, Pia De Stefano, Maria Vargas*, Eric Menetre, Emmanuel Carrera%,
Andreas Kleinschmidt, Margitta Seeck

Neurology Division and *Neuroradiology Division, University Hospital of Geneva, Switzerland


Objective :
Hippocampal sclerosis (HS) is a prominent biomarker of epilepsy. If acquired later in life, it usually occurs in the context of degenerative or acute inflammatory-infectious disease. Conversely, acute symptomatic seizures (ASS) are considered a risk factor for developing post-stroke epilepsy but other factors remain unrecognized. Here, we hypothesize that silent hippocampal injury contributes to the development of post-stroke epilepsy.

Methods :
We performed a retrospective observational study of patients hospitalized between 1/2007 and 12/2018 with an acute stroke in the Stroke Center of the Geneva University Hospital. Patients were included if they had a documented normal hippocampal complex at onset and a control MRI at ≥ 2 years interval without new lesion in the meantime.

Results :
162 patients fulfilled our inclusion criteria. ASS during the first week (p < 0.0001) and epileptiform abnormalities in electroencephalography (EEG; p = 0.02) were more frequently associated with the development of epilepsy. Hemorrhagic stroke was strongly associated to both ASS and future focal epilepsy (p = .00097). Three patients (1.8%) developed hippocampal sclerosis ipsilateral to the cerebrovascular event between 2 and 5 years, all with ASS and hemorrhagic stroke.

Interpretation :
ASS and epileptiform EEG abnormalities are strong predictors of post-stroke epilepsy. HS develops in a minority of patients after hemorrhagic lesions, leading to focal epilepsy. Prospective studies are required, including systematic follow-up with EEG and if characterized by epileptiform discharges, with MRI, to determine the true frequency of HS and predictors of post-stroke epilepsy (AAS, stroke type, HS), and eventually, its impact on stroke recovery.

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsies. While TLE is characterized by the presence of an epileptic focus (EF) that is held to be responsible for triggering seizures and driving interictal activities, recent studies showed that epileptogenic networks (EN) and brain alterations are widely distributed, even in well diagnosed focal epilepsies. The pathologic mechanisms that drive the development of the EN are unclear, leaded us to investigate two possibilities: does the EF pathological activities disrupted distant brain regions and trigger the EN formation or, does the EN development started as soon as the initial insult, and so, before the first apparition of focal epileptic activities.
Using multisite chronic mSEEG recordings and chemogenetic tools in the unilateral intra-hippocampal kainate (KA) mouse of TLE (IHK), we propose to characterize in detail the emergence of epileptic activities in the EF and in remote regions and evaluate the role of the primary epileptogenic region for the development of the large-scale EN. Interestingly, we found that the different types of epileptiform activities, i.e. the various types of ictal, ictal-like or interictal patterns, starts to appear in the very early stage of the epileptogenesis (i.e. at least 72h after KA injection) in both the EF and the contralateral hippocampus and evolve to become typical epileptic events (seizures, fast-ripples, generalized spikes, etc.). We investigate precisely these network dynamics with high spatial and temporal precision using systematic unbiased detection of pathological activities. Such a detailed description of the pathological activities during this period is fundamental to understand how neuronal networks alterations emerge in lesioned (sclerotic injected hippocampus) and apparently non-lesioned regions. Beyond these important descriptive aspects, we hope to further identify key mechanisms of epileptic neuronal networks development.

In Alzheimer’s disease, cortical tau deposition has been associated to synaptic density loss, neurodegeneration, and cognitive decline. A deficit in gamma oscillations has been observed on EEG of AD patients. Loss of gamma oscillations is considered a marker of GABAergic interneuron dysfunction and synaptic loss. We explored the correlation between alterations of gamma oscillations and cortical tau deposition in AD patients.
We selected 18 patients from the Geneva Memory Center dataset who underwent tau-PET, amyloid-PET and a 25-electrode scalp resting-state EEG. We estimated the power spectral density on 30 epochs of one second and power in the gamma frequency band (30-100 Hz). We compared the average gamma power between subjects with and without significant cortical tau deposition. We correlated the localization of tau standardized uptake value ratio (SUVr) with power distribution of gamma oscillations in both groups.
Of the 18 included patients, 9 had positive tau-PET and amyloid-PET scans. Of these, 5 (56%) showed a more prominent tau burden in the left temporal and parietal lobes, with the remaining 4 (44%) having a bilateral distribution. Of the 9 negative tau-PET patients, only one had a positive amyloid-PET. We observed a statistically significant decrease of total gamma power in tau-positive compared to tau-negative patients (p=0.038). In tau-positive patients, regional analyses showed a non-significant inverse relationship between tau burden and gamma power (i.e. with increasing tau burden, gamma power decreased). This tendency was strongest in the precuneus, parietal and temporal lobes of the most affected hemisphere on molecular imaging. A non-significant positive correlation was observed in the same lobes of the contralateral hemisphere in tau-positive patients and in both hemispheres of tau-negative patients (i.e. with increasing tau burden, gamma power increased).
Alterations in gamma oscillations could be a biomarker for cortical tau deposition in AD. The opposite relationship between tau burden and gamma oscillations observed in the different hemispheres might represent a large-scale compensatory mechanism in the least affected one. Indeed, recent studies found an increase in beta and gamma oscillations in frontal regions of subjects showing signs of degeneration on FDG-PET. In conclusion, alterations of gamma oscillations might be a promising electrophysiological marker for early diagnosis and possibly follow-up of Alzheimer’s disease.

During surgical resection of supratentorial mass lesions, motor deficits might be caused by different patterns of injury: mechanical (damage of primary motor cortex / corticospinal tract), ischemic (coagulation of perforator arteries, vasospasm), or lesion of associative motor areas. Recently, we performed a scoping review to asses intraoperative motor evoked potentials (MEP) warning criteria (1). Here we present the data of a subgroup of patients, with focus on the pattern of injury.
A systematic search of the literature using PubMed, Embase, Scopus, CINAHL and the Cochrane Library was undertaken. Inclusion criteria were intraoperative electrically elicited MEP with predefined alarm criterion in anesthetized patients undergoing supratentorial brain surgery with quantitative report of motor outcome. For this subgroup analyses we focused on supratentorial parenchymal lesions.
Of the 68 included papers, 54.8 % described the different intraoperative injury patterns. For permanent deficits, 2 groups described exclusive mechanical injury, 6 exclusive vascular and 8 mixed patterns. For transient deficits, 3 groups described exclusive mechanical injury, 1 exclusive vascular and 3 mixed patterns. Of 1551 cases, there were 7.8 % of permanent motor deficits (3.2 % mechanical, 2.6 % vascular, and 1.9 % of unclear cause). For mechanical injury 38, 6 and 4 cases had irreversible, reversible and no change of MEP, respectively; whereas for vascular injury the corresponding numbers were 30, 5, and 5. For transient motor deficits, 27 cases were due to mechanical injury, of which 9 had irreversible, 1 reversible and 17 no change of MEP. For vascular injuries (12 cases) the corresponding numbers were 4, 5 and 3, respectively, with more reversible changes in vascular than mechanical cases (P = 0.01 – Chi square test).
In the group of patients with transient postoperative motor deficits, the subgroup with vascular injury had significantly more reversible MEP changes than the mechanical injury patients. This suggests that an MEP alert may reduce permanent motor deficits caused by vasospasm / transient ischemia. In the whole group, we observed a slight predominance of mechanical injury. Thus, additional subcortical mapping strategies may improve surgical guidance. Deeper understanding of the mechanisms of injury could help to develop a strategy for a faster and more effective detection of an intraoperative lesion, as well as the suggested methodology to avoid permanent deficits.

Introduction
We describe two recent cases of peripheral neuropathy reported after vaccination with mRNA SARS-CoV2 vaccine (Moderna®).

Methods
The first patient developed a neuralgic amyotrophy, the second patient a radial neuropathy.

Results
A 67-year-old man with hypertension and hyperlipidemia developed acute and severe neuropathic shoulder pain 8 days after the second vaccination dose of COVID-19 vaccine in the ipsilateral deltoid muscle. A causative trauma and other differential diagnoses were denied. NSAIDs showed no effect, but corticosteroids improved the pain. Subsequently paresis of the left proximal shoulder muscles occurred, and EMG showed axonal damage. A 60-year-old female with no medical history developed weakness of left hand extension 4 days after the first vaccination dose of COVID-19 vaccine in the ipsilateral deltoid muscle. Neurological examination showed a mild paresis of the radial innervated muscles in the forearm and reduced sensitivity of the dorso-radial area of her hand. Nerve-conduction-studies demonstrated a conduction block of the radial nerve proximal to the elbow, concomitant with focal swelling detected by high-resolution nerve ultrasound.

Conclusion
The two cases show a temporal and local association (ipsilateral injection) of peripheral neuropathies after vaccination with mRNA COVID-19 vaccine (Moderna®). Similar case reports are published. However, temporal association is not equal to causal association and can ideally be investigated by prospective randomized trials, which is unethical in the pandemic situation. Therefore, prospective register studies, case series and case reports must act as a substitute. However, due to underreporting or insufficient timely data processing a large body of information is missing.

Objectives: The aim of this research was to determine the differences in blink reflex latencies as a diagnostic tool for unilaterally idiopathic TN compared with pain-free health volunteers.
Methods. A prospective cohort study was conducted over 2 years. The final subgroup TN-Subgroup included 15 patients (mean age / SD 62.3±10,7 years; 10 (66,7%) female). Blink-eliciting stimuli were performed by surface electrodes to stimulate the supraorbital nerve at the forehead. Pain-free and healthy volunteers as a HV-Subgroup (mean age / SD: 30,8±8.1 years; 12 (75%) female) were recruited from asymptomatic students of dental medicine.
Diagnostic parameters were determined by measuring latency (in ms) to the onset of the reflex components from electric stimulation. The shortest latency values obtained were taken into account. They were composed of homolateral early response R1 and bilateral late response R2 (homolateral response), and R2c (contralaterally expressed response), the occurrence of ipsilateral/contralateral R3/R3c component, and side-to-side difference for R1, R2 and R2c latencies. The level of anxiety was evaluated by Spielberger’s psychological measuring instrument State-Trait Anxiety Inventory.
Results: A strictly unilateral TN was diagnosed on the right side in 53% patients. There was no difference in sex distribution between NT and HV subgroups (Fischer's exact test p = 0.4815). The following anxiety scores with statistically significance were found comparing TN-subgroup / HV subgroup – STAI 1: 45.06 ± 8.90 / 31.94 ± 10.25 and STAI 2: 43.12 ± 9.30 / 35.00 ± 10.11 respectively (p=0.0001 / p=0.009). Blink reflex latencies of stimulation values left and right side together between subgroups were significantly higher for latencies values R1, R2, R2c at TN-subgroup (p < 0.05). Other blink reflex parameters were analysed, such as the absence of R1 latency, and the presence of R1c, R3, and R3c latencies.
Conclusion. Nociceptive blink reflex is a non-invasive and painless method with the purpose of objectifying neuropathic pain in different groups of patients. Blink-reflex parameters (R1, R2 and R2c) were significantly abnormal not only upon comparing TN-patients with healthy volunteers. The R3 component of the reflex was related to noxious stimuli, likewise by innocuous stimuli.

Background
There is extensive and growing evidence about the role of inflammation in Parkinson’s disease (PD). In addition to neuroinflammatory processes occurring in the brain, elevated levels of pro-inflammatory factors are also present in the plasma of PD. Extracellular vesicles (EVs), secreted membrane particles involved in cell-to-cell communication, carry important information on immunity and its dysregulations. Thus, we hypothesize that plasmatic inflammatory EVs may have a functional role in disease initiation and progression.
Methods
Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated for 22h with PD vs. healthy control (HC) circulating EVs previously labeled with the lipophilic dye DiR. A panel of 14 specific antigens was used to identify more than 12 subpopulations of PBMC by FACS analysis. For each subpopulation, we dissected the differential EV internalization and immune activation. PBMCs were also treated with LPS to mimic an inflammatory condition; the differential EV internalization and immune activation of PBMCs receiving EVs from PD and HC in inflammatory conditions was evaluated. Finally, with a cytokine array on PBMCs media treated with EVs from PD or HC, we evaluated the differential secretion.
Results
The exposition with EVs from PD induced an increase in NKT CD80+ cells. In inflammatory conditions, we observed an increased of CD16+ cells in PBMCs treated with EVs from PD. Finally, the exposure to EVs from PD or HC induced a differential release of cytokine by PBMCs.
Conclusion
The differential response of PBMCs to EVs derived from PD or HC peripheral blood suggest a differential message carried by EVs. A deep plasma-derived EVs functional analysis may shed light on the role of inflammatory dysregulation in causing PD.

Introduction:
Visual Snow Syndrome (VSS) is a migraine-related perceptual disorder. The main symptom is “visual snow (VS)” resembling the view of TV-static in the entire visual field.(1) There are additional visual symptoms such as enhanced entoptic phenomena, palinopsia, photophobia and nyctalopia. The diagnosis as established in the ICDH3(2)-criteria is based solely on patient history. Here we propose an objective marker supporting the diagnosis and quantifying VS symptom intensity.

Methods
Fourteen subjects (9 VSS, 5 matched healthy controls) participated in a web-based, object recognition task, in which images of common objects were masked with black and white noise, which approximates the quality of VS as reported by the patients. At the beginning of each of the ten trials, the added noise covered the entire image, making object recognition impossible. Over time the noise level was automatically reduced until subjects signalized that they recognized the image embedded in the noise via a button press. To control for correct identification subjects had to select the answer from five alternatives presented on the screen. The primary endpoint was the mean noise level at the moment of recognition. This was compared between the two groups using an independent t-test.

Results
Comparing the mean detection performance between VSS patients and matched healthy controls, we found a significant difference over all stimuli (p = .026; d = 1.05). Overall detection performance was lower in VSS (mean noise level = 34.27) than in healthy controls (mean noise level = 37.48), demonstrating that people suffering from VSS require a lower level of noise to successfully recognize objects than people without VSS.

Conclusion
The preliminary data show that subjects with VSS can be identified by their reduced performance in a masked object recognition task. The presented test provides the first attempt to quantify the severity of VS by an objective measure. In the future, such a test might be used as a diagnostic tool or, to monitor the success of therapeutic interventions, or in research projects

Aims: According to some guidelines for health insurance reimbursement, ineffective use of one aCGRP mAb (monoclonal antibody targeting the CGRP pathway), defined by not reaching a reduction of monthly migraine days (MMD) by 50% compared to baseline after 6 months of treatment, excludes reimbursement of another aCGRP mAb. The aim of this preliminary analysis is to quantify the effectiveness of switching between aCGRP mAbs due to lack of efficacy of previous aCGRP mAb treatment.
Methods: FINESSE is a multicenter, two-country (Germany, Austria) prospective non-interventional study (NIS) in which effectiveness and tolerability of fremanezumab in adults with EM and CM are evaluated in routine clinical practice. Medical history of patients is documented at baseline, including past preventive treatment (PPT) with another aCGRP mAb (erenumab or galcanezumab). This preliminary subgroup analysis (cut-off date 14.05.21) focused on preventive migraine treatments with other aCGRP mAbs prior to initiation of fremanezumab. Distribution of patients with and without ineffective PPT with another aCGRP mAb was analysed for the primary endpoint of FINESSE, the proportion of patients reaching ≥50% reduction in MMD that was evaluated during the 6-month period after the first dose of fremanezumab.
Results: 574 patients with fully documented baseline visit were included (89.4% female, 45.7 ± 12.2 years of age); 58.4% had EM, 41.6% CM. Of those, 308 had completed the 6-month visit, 241 without and 67 with prior exposure to another aCGRP mAb. The main reason for discontinuation of prior aCGRP mAb therapy was, according to the patients at baseline visit, lack of efficacy in 57 patients (85.1%) and other reasons in 10 patients (14.9%). In total 150 of 308 patients (48.7%) achieved the primary endpoint of ≥50% reduction from baseline in MMD at month 6 after the first dose of fremanezumab. In the subgroup of patients with lack of efficacy of prior aCGRP mAbs, 18 of 57 (31.6%) reached the primary endpoint and 129 of 241 in patients without prior aCGRP mAb treatment (53.5%).
Conclusion: This preliminary data provides prospective real-world evidence that treatment with fremanezumab is effective in about 30% of patients with prior ineffective aCGRP mAb treatment. For these patients, a switch should not be withheld since it can be a promising treatment option.

ComPAIN
Communication of pain in patients with headache

E.Eicher (1), S.Räz (1), M.Stattmann (1), E.Neumann (1), H.Pohl (1), Y.Ilg (2), A.Maatz (3), S.Wegener (1)

1 Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland
2 Department of German Studies, University of Zurich, Switzerland
3 Centre for Social Psychiatry, Psychiatric Hospital, University of Zurich, Switzerland

Aim: Primary headaches are a common debilitating health condition, affecting more than 1 billion people worldwide. Proper diagnosis and treatment depend on com-munication. We want to reveal differences in pain communication depending on headache disorder as well as individual patient factors, including sex. Furthermore, we would like to analyze patients’ satisfaction with our consultations and evaluate if there is a correlation with communication.

Methods: Patients with suspected primary headaches visiting our headache unit were asked to participate. Up to now, we included 18 patients: 10 of them diag-nosed with migraine, 3 with tension type headaches (TTH), 3 with both (migraine and tension type headaches (M+TTH)) and 1 with cluster headache. The patients were asked to fill in a questionnaire before entering their consultation, after finishing the consultation and a third questionnaire 6 months later (sent home via mail). We recorded the consultations on video and audio tapes for linguistic analyses.

Results: On average, migraine patients used more words to characterize their pain: 22.67 vs. 9 in TTH patients (p=0.286). Migraine patients also tended to use the first-person narrative more often (50% vs. 30% in TTH patients, p=0.648), and showed a slightly better satisfaction with the consultation overall (90.68% vs. 80.93% in TTH patients, p=0.168). However, due to the small patient groups at the current stage these trends were not significant.

Conclusion: Our preliminary results suggest that communication of headache dif-fers depending on headache diagnosis and individual patient characteristics. More in depth analysis of a larger patient cohort will be presented at the conference. We hope to make an important contribution to the understanding of our future patients with headache, ultimately leading to better treatments and patient satisfaction.

BACKGROUND:
Central Nervous System(CNS) vasculitis is a rare disease that cause inflammation in the vessels of the CNS without evidence of vasculitis outside the CNS. It presents clinical features motor weakness, cognitive problems, and difficulties controlling bladder and bowel incontinence and symptom of neurogenic bowel makes quality of life lower in patients with this diseases. Here, we introduce a case that improved through biofeedback treatment in addition to oral medications for constipation in the young patient with neurogenic bowel who was diagnosed with CNS vasculitis.

CASE REPORT:
A 28-year-old male represented symptoms of dizziness, gait disturbance, visual disturbance, and dysphagia and was diagnosed with CNS vasculitis with brain MRI. He came to the rehabilitation unit due to worsened dysphagia and gait disturbance. His Modified Barthel Index score was 29 and Mini Mental Status Examination score was 28. Also he complained severe constipation and difficulty with evacuation. There were a lot of feces in large intestine and rectum on his abdominal x-ray. Although several drug such as oral osmotic or stimulant laxatives and bisacodyl suppository were used, symptoms did not improve. Manometry was performed to differentiate colon transit disorder, and there were no specific findings in colon transit time. We regard his symptom as an anorectal function disorder and recommend the biofeedback treatment. During the 1st time of biofeedback treatment, the patient showed problems with increasing the abdominal pressure or relaxation of external anal sphincter muscle but after 4 times of treatments, he showed improvement in controlling the abdominal pressure and anal sphincter. After that he said it was much easier to defecate and was able to reduce the number of oral medications he took for neurogenic bowel. Afterwards, the patient continues physical, occupational therapy and biofeedback therapy.

Conclusion
Bowel biofeedback is a conservative method for neurogenic bowel that brings behavioral changes in the patients with functional chronic constipation or dyssynergic pattern of defecation. Otherwise, there were few reports with biofeedback in stroke or CNS vasculitis patients. If the patient's cognitive function and cooperation are adequate, biofeedback could be an effective treatment option for neurogenic bowel in patients with stroke or central vasculitis.

Aims:
Ischemic stroke (IS) is the leading cause of epilepsy in elderly patients. Blood biomarkers acquired in the acute phase may contribute to early prediction and risk stratification for post stroke epilepsy (PSE), thus identifying vulnerable patients that are most likely to benefit of antiepileptic treatment. Increased permeability of blood-brain barrier and neuro-inflammation are crucial in the process of epileptogenesis. Elevation of S100-B serum levels is a marker of cell damage, studies with murine models and with large collectives of human patients have been already proposed this protein as a prognostic biomarker for PSE. We aim to assess and validate the predictive value for PSE of S100-B using a large well characterized acute IS cohort.
Methods:
Within the multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) study (ClinicalTrial.gov NCT02274727), we consecutively included 1161 ischemic stroke patients at the stroke center of the university hospital of Zurich 24 hours of symptom onset. Clinical work-up during the hospitalization included medical history, physical examination, clinical risk scoring using NIHSS, routine laboratory tests & imaging (CT and /or MRI) and aetiology work up (ECG, Echocardiography, Ultrasound). Blinded S100-B measurement was performed within 24 hours of symptom onset. The primary endpoint late seizure more than 7 days after stroke and secondary endpoint was any seizure, during a long follow up period (follow-up median duration 5 year, Q1 5 years, Q3 6 years). Logistic regression models were fitted to estimate odds ratio (OR) and 95% confidence interval (CI) for the association between log-S-100B and the outcome, while extreme gradient boosting techniques were used to assess optimal, predictive multivariable models.
Results
Among 1161 acute IS patients, 69 developed late seizure and 101 developed any seizure. After adjusting for demographic and vascular risk factors there was no significant association between log-S100B levels neither with late nor with any seizure during the follow up. Machine learning approaches led to the same conclusions.
Conclusions
Despite previous pilot studies in this large cohort study we were not able to find a significant association between levels of S-100B and development of PSE. Other candidate biomarkers should be further evaluated for this important clinical question.

Background
CRAO is a serious condition leading to monocular blindness. Re-establishing retinal perfusion might prevent irreversible damage. Data about thrombolysis in CRAO are promising but good evidence is still lacking. Among others this is due to important prehospital delays. The aim of this study ist to describe the current practice in patients with CRAO treated in Stroke Centers/Units (SCs/SUs) in Switzerland and the prehospital delays and pathways compared to patients with ischemic stroke based on the data from the Swiss Stroke Register (SSR)

Methods
We analysed registered cases with CRAO and ischemic stroke between January 2014 and Dezember 2019. We describe and compare the prehospital pathways. Patients with CRAO were categorized into two groups: those receiving thrombolysis and those with standard of care treatment.

Results
397 CRAO and 32’816 ischemic stroke cases were registered from 2014 until 2019 in 20 SC/ in Switzerland. The mean age was 71.8 (13.7) and 72.4 (13.7) years, respectively.
Most of the CRAO Patients (41,0%) were referred from another hospital and had a lower rate of emergency referrals (5.9%). For CRAO-patients receiving thrombolysis, emergency referrals doubled (11.6%) at the expense of referrals from the GP (14.0%). Most of the CRAO patients (83.0%) used private transportation, and only 16.6% came by emergency services. This contrast the number of stroke patients arriving at the hospital by the emergency services (65,3%). Hence, the symptom-to-door time was significantly longer in CRAO compared to stroke (852min. vs 300min).
The thrombolysis rate was 13.2% for CRAO patients (8.9% systemic-and 4.3% intra-arterial thrombolysis), which is significantly lower than the observed thrombolysis rate in stroke patients (30.9%). Among CRAO patients with a symptom-to-door time of less than 4 hours (26,0%), the thrombolysis rate was 45%. Of the remaining patients who arrived beyond 4 hours after symptom onset, only 1,7% of the patients were thrombolysed.

Conclusions
The prehospital delays seems to be the main reason for withholding thrombolysis from patients with CRAO. Although CRAO is a serious condition affecting multiple aspects of daily living and the quality of life, specific prehospital pathways to improve symptom to door time are not defined. Reducing prehospital delays will increase thrombolysis rate and facilitate enrolment of patients in clinical trials in order to improve the poor outcome of CRAO

Aims: Effective control of cardiovascular risk factors is the prerequisite to prevent cardiovascular disease. It is increasingly clear that non-traditional cardiovascular risk factors (nt-cvrf) such as stress significantly add to cardiovascular risk arising from traditional cardiovascular risk factors (t-cvrf). To determine sex-specific changes and 10-year trends in prevalence of t-cvrf and nt-cvrf in Switzerland.
Methods: We obtained anonymized data from 22’134 participants (51% women) of the governmental Swiss Health Survey, performed every five years (2007, 2012, and 2017). Epidemiological parameters, t-cvrf and nt-cvrf were analyzed in a cross-sectional approach and observational study design. Temporal trends in epidemiological parameters, t-cvrf (e.g. hypertension, diabetes, hypercholesterolemia, alcohol/nicotine consumption, physical activity, smoking), and nt-cvrf (e.g. stress at work, feeling exhausted at work, working despite illness, locus of control, energy and vitality, sleep disorders, major depression) were matched by sex.
Results: Over the observation period, the number of women having full-time jobs increased considerably (2007: 38%, 2012: 39%, 2017: 44%). This was accompanied by a substantial rise in the prevalence of nt-cvrf including stress at work (2007: not available, 2012: 59%, 2017: 66%), reduced feeling of energy and vitality (2007: not available, 2012: 23%, 2017: 29%), and sleep disorders (2007: 26%, 2012: 24%, 2017: 29%) in women. This trend was less pronounced in men. Amongst t-cvrf, only the prevalence of obesity and hypercholesterolemia increased over time in both sexes, while other t-cvrf remained stable (hypertension [27%], diabetes [5%]) or decreased (smoking [9.4 cigarettes/day]).
Conclusion: A rise in women’s economic participation alongside a pronounced increase in nt-cvrf in the female Swiss population emphasizes the need to improve cardiovascular risk stratification and implement effective preventive measures for neuro- and cardiovascular disease.

Background and aims: Lipoprotein (a) (Lp (a)) serum levels are mainly genetically determined and contribute to atherogenesis. High Lp (a) levels are associated with an increased cardiovascular morbidity. Recently, serum Lp (a) levels have been associated with large artery atherosclerosis stroke (LAAS) aetiology. We aimed to validate this association in an independent cohort.

Methods: We included acute ischemic stroke patients from a prospective cohort study from the University Hospital Bern (Inselspital), Switzerland. Lp (a) serum levels were measured in serum, drawn within 24 hours after symptom onset. Stroke subtype was determined according to the TOAST classification. We assessed the association of Lp (a) with LAAS in univariate and multivariate analysis, adjusting for traditional LAAS risk factors.

Results: Overall, 746 patients were included, of which 105 had a LAA stroke (14%). Lp (a) was higher in patients with LAAS compared to patients with non-LAAS (23.0 nmol/l [IQR:9.8-80.0] versus 16.3 nmol/l [IQR:5.8-57.0], p=0.01). In univariate analysis, patients with LAAS were significantly more often men, suffered more often from Dyslipidaemia, Arterial Hypertension, Diabetes and had a higher BMI than patients with non-LAAS. In a multivariable logistic regression model, elevated Log10(Lp(a)) was associated with LAAS with a OR of 1.50 (95%CI 1.02-2.21).

Conclusions: Among ischemic stroke patients, we could validate the independent association of higher Lp (a) levels with LAAS aetiology, also after adjusting for traditional cardiovascular risk factors. Independent validation of biomarkers, especially with the aim to guide secondary prevention, is essential. These findings are relevant in view of randomised clinical trials investigating the effect of specific Lp (a) lowering agents in reducing major adverse cardiovascular events.

Background
CRAO is a serious condition leading to monocular blindness. Re-establishing retinal perfusion might prevent irreversible damage. Data about thrombolysis in CRAO are promising but good evidence is still lacking. Among others this is due to important prehospital delays. The aim of this study was to assess the level of awareness of CRAO symptoms and handling of these patients amongst the general population, general practitioners (GPs) and ophthalmologists in Eastern Switzerland.

Methods
The survey was carried out between March 2019 and July 2020. The population-level was assessed with an 16 questions questionnaire about demographic data, recognition of CRAO warning signs, underlying causes, and approach in case of acute unilateral visual loss as well as in case of stroke symptoms. GPs and ophthalmologist filled out an online 16 and 11 questions questionnaire, respectively, regarding symptoms of CRAO, differential diagnosis, etiology, approach in case of persistent and temporary acute visual loss, therapy options, and time windows.

Results
350 people participated in the population survey. 28,6% identified an unilateral, sudden loss of vision as a symptom of CRAO. CRAO was considered a medical emergency by 63.1% of them. 55.4% would go to the hospital in case of acute visual loss compared to 89.9% with stroke symptoms. 69.7% identified a temporary visual loss as potentially harmful and would consult a doctor.
66 of 67 (98.5%) surveyed ophthalmologists recognise CRAO as a medical emergency, and 64.2% of them would transfer their patients to a stroke center. Only 23.9% would consider systemic thrombolysis and 41.8 % intra-arterial thrombolysis as a beneficial therapy. All GPs (102) recognise CRAO as an emergency and 88.2 % recognised a sudden unilateral loss of vision as the typical symptom in CRAO. 59,8% of them would transfer the patient to the next stroke center. 55,3% and 37,3% consider intra-arterial and systemic thrombolysis respectively as potentially effective.

Conclusions
Awareness on population level of symptoms and urgency of CRAO is rather low in Eastern Switzerland. Although the symptoms recognition among GPs and ophthalmologist is good the acceptance of thrombolysis as a possible treatment option is low.
Current delays in the prehospital phase in case of CRAO represent the main obstacle for reperfusion therapies/studies. Information campaigns are needed to benefit from the existing prehospital organizational models for stroke.

BACKGROUND - We assessed the efficacy and safety of mechanical thrombectomy (MT) in adult stroke patients with anterior circulation large vessel occlusion (LVO) presenting in the late window who did not fulfill the DEFUSE-3 and DAWN inclusion criteria.

METHODS - Cohort study of adults with LVO admitted between 6 and 24 hours after last seen well at five participating Swiss Stroke Centers between 2014 and 2021. Mismatch was assessed by CT or MRI perfusion with an automated software (RAPID or OLEA). We excluded patients meeting DEFUSE-3 and DAWN inclusion criteria and compared those who underwent MT with those receiving best medical treatment alone (BMT) by inverse probability of treatment weighting (IPTW) using the propensity score. The primary efficacy endpoint was a favorable functional outcome at 90 days, defined as a modified Rankin Scale (mRS) score of 0-2, or a mRS shift toward lower categories. The primary safety endpoint was symptomatic intracranial hemorrhage (sICH).

RESULTS - Among 278 patients with LVO presenting in the late window, 190 (68%) did not meet the DEFUSE-3 and DAWN inclusion criteria and thus were included in the analyses. Of those, 102 (54%) received MT. In the IPTW analysis, patients in the MT group had higher odds of favorable outcomes compared to the BMT group (mRS 0-2: aOR 1.57 [1.02-2.44], p=0.04; mRS shift: cOR 0.68 [0.47-0.99], p=0.045). There were no significant differences in sICH (MT vs BMT: 5% vs 2%, p=0.63) or all-cause death within 90 days (aOR 0.68 [0.43-1.08], p=0.10).

CONCLUSION - Two out of three patients with LVO presenting in the late window did not meet the DEFUSE-3 and DAWN inclusion criteria. In these patients, MT was associated with higher odds of favorable functional outcomes without increased rates of sICH. These findings support the enrolment of patients into ongoing randomized trials on MT in the late window with more permissive inclusion criteria.

Aims: Adverse childhood events (ACE) such as maltreatment or neglect during childhood can have an imprinting effect on child development and adult mental health. It is assumed that early programming of the stress response system is a mediating factor between ACE and later stress associated disorders like depression. In addition, ACE may have an impact on bonding style. The aim of this study was to examine, whether maternal ACE have an impact on the risk for postpartum depression and the quality of mother-infant bonding. And if so, whether hypothalamus-pituitary-adrenal (HPA) axis activity as reflected by hair steroids were involved in this association.
Methods: Thirty-six pregnant women (M=33.3 years, SD=4.4) were recruited in an out-patient setting. At study inclusion (before 32 weeks gestation), ACE were assessed with the Childhood Trauma Questionnaire Short Form (CTQ-SF). At 12 weeks postpartum, levels of hair cortisol and hair cortisone, degrees of depression (HAMD, EPDS), anxiety (STAI), insomnia (ISI), perceived stress (PSS, PSI), and impairment of mother-infant bonding (PBQ) were assessed.
Results: Inconsistency experiences during maternal childhood correlated positively with impaired bonding (r = .646, p = .002), rejection and anger to the child (r = .632, p = .002), and anxiety about caring for the child (r = .538, p = .012). Moreover inconsistency experiences were related to higher scores of depression (r = .690, p < .001) at 12 weeks postpartum. Furthermore, impaired bonding (r = .631, p = .003) and anxiety about caregiving (r = .538, p = .012) positively influenced the association between inconsistency experiences and postpartum depression. Further, no significant association was shown between cortisol (r = .310, p = .242) or cortisone (r = .477, p = .061) and inconsistency experiences. However, hair cortisol (r = .750, p = .001) as well as hair cortisone (r = .701, p = .004) positively influenced the association between inconsistency experiences and postpartum depression.
Conclusion: Inconsistency experiences in childhood were related to both, impaired mother-infant bonding as well as a higher risk of postpartum depression. Furthermore, the magnitude of the association between inconsistency experiences and postpartum depression was influenced by both, poor bonding as well as by increased levels of hair cortisol and cortisone, which indicate an increased HPA activity.

Aim
High experienced stress correlates to accelerated biological aging and adverse health outcome. As an aging indexer, shortening leukocyte telomere length (LTL) may be associated to activating the hypothalamic-pituitary-adrenal (HPA) axis putative to stress. Hair cortisol concentration (HCC) has risen to be a standard of the HPA axis activation. Due to a lack of biological measures of chronic biological stress, the investigation between long-term stress and cellular aging has been challenging.
This study aimed to assess the association between HCC and LTL of young adults to examine the relationship between chronic biological stress and LTL in the content of aging.
Methods
This study was conducted in a highly strained, at-risk sample of young adults with previous residential child welfare placement. The study size consisted of 92 participants (38 % women and 62 % men). For the Cortisol measurement, 2 cm of hair was utilised (approx. eight weeks of cortisol excretion). LTL was assessed with quantitative PCR in whole blood samples. Polynomial and linear regression were used for the correlation analysis between LTL and HCC.
Results
Between HCC and LTL a negative correlation (rho/r = -0.68, p < 0.001) was found indicating that higher HCCs are linked to shorter LTL. HCC explained about 50 % of the variance to LTL. A curvilinear relationship showed a strong negative association with lower cortisol concentration (0-10 pg/mg). Still, the analysis demonstrated no correlation at higher cortisol levels (>10 pg/ml) in the polynomial regression models.
Conclusion
This study is the first to examine the correlation between HCCs and LTL. This study demonstrated that higher HCCs were associated with a shorter LTL in humans, thereby potentially involving the HPA axis by prolonged cortisol secretion to telomere length. Consequently, HCC might be a potential indicator for investigating chronic stress linked with aging-related processes. Further clarification of this association, a more extensive and diverse sample is needed.

Background: Adolescents with externalizing behavioral issues such as aggressive behavior and callous-unemotional traits pose a challenge both for their individual psychosocial development and for the society. By contrast, traits of empathy might counterbalance adverse behavior. Further, there is some, but inconsistent research as regards the predictive value of objective sleep parameters for future psychological functioning. We addressed this issue and asked, if and to what extent longitudinally behavior and objective sleep at the age of five years could predict dimensions of callous-unemotional behavior and empathy. Cross-sectionally, we asked, if subjective sleep and stress were associated with callous-unemotional behavior and empathy.
Methods: At total of 80 preschoolers (mean age: five years) underwent objective sleep-EEG recordings. Their parents completed the Strengths and Difficulties Questionnaire (SDQ). At the age of 14 years, that is, nine years later, participants completed a series of self-rating questionnaires on callous-unemotional behavior, empathy, subjective sleep, and stress perception.
Results: Cross-sectionally, higher scores for insomnia were associated with higher scores for callous-unemotional behavior, and lower scores for empathy. Higher stress scores were associated with higher callous-unemotional behavior. Longitudinally, at the age of five years, lower sleep-EEG-assessed sleep efficiency indices, a longer sleep-onset latency and a shorter sleep duration predicted higher scores for callous-unemotional behavior at the age of 14 years. Further, At the age of five years, higher externalizing problems and higher hyperactivity scores predicted higher scores for callous-unemotional behavior. At the age of five years, higher negative peer relations and lower prosocial behavior predicted lower scores for empathy at the age of 14 years.
Conclusions: Data suggest that objectively measured sleep indices and behavioral issues, as rated by parents, at preschool age have the power to predict dimensions of emotion regulation at the age of 14 years. Current subjective sleep quality and stress may confound or intensify these patterns of association.

Background: Individuals scoring high in Dark Triad traits (psychopathy, narcissism, Machiavellianism) also report higher scores on sociosexual orientation. Further, among successful professional athletes, physical activity performance was associated to a lower 2D:4D-ratio: the length of the index finger is shorter compared to the length of the ring finger; this is understood as a proxy of increased perinatal exposure to testosterone. Here, we investigated the associations between Dark Triad traits, 2D:4D-ratio, sociosexual orientation, and current and past physical activity patterns among a sample of young non-athlete adults.
Method: A total of 90 adults (mean age: 23 years; 55.2% males) took part in this study. They completed a series of self-rating questionnaires covering demographic information, Dark Triad traits, sociosexual orientation, and current and past physical activity patterns. Further, participants provided a scan of the palm of their right hand.
Results: Compared to female participants, male participants had a lower 2D:4D-ratio and reported higher scores on sociosexual orientation. A lower 2D:4D-ratio was associated with higher current and past physical activity patterns. While the current physical activity pattern was associated with higher Dark Triad traits, higher past physical activity patterns were associated with lower Dark Triad traits. Higher current physical activity patterns were associated with a higher sociosexual orientation, male gender and higher Dark Triad scores,
Conclusions: The current pattern of results suggests that individuals prenatally exposed to higher testosterone concentrations might benefit from this programmed physiological pattern, once they are adults.

Background: Nowadays, physical inactivity is a global health problem and negatively associated with physical and mental health. In contrast, excessive training is also associated with physical and mental risks. We tested the hypothesis that there is a so-called „sweet spot“. “Sweet spot” refers to an optimal amount of sports activity in which mental health reaches an optimal level. In a second hypothesis, it was assumed that people who are very active in sports must compromise on more things than people who do less sports. Research should also be carried out into the main things these people have to renounce.
Methods: A total of 197 people (average age: 28 years; 64% women) participated in the online survey. Participants answered questions regarding the use of their daily time budget, motivation for exercising, mental health, and the sacrifices they must make because of exercising. They were divided into five categories: category 0 (< 1 h sport/day), category 1 (1 h sport/day), category 2 (2 h sport/day), category 3 (3 h sport/day), and category 4 (≥ 4 h sport/day).
Results: Mental health indices increased to a “sweet point” of 2-3h/d, while a higher amount of daily exercising (4+h/d) was associated with more health issues. In the group of +4h/d, time budget was shortened to keeping social contacts with family members, peers and peers at work. Importantly, very high exercisers rated the decrease of social contacts as particularly unpleasant.
Conclusions: The patterns of results suggests that the “sweet point” is about 2-3h of daily physical activity and exercising. A higher duration and intensity of physical activity and exercising is related to shortened time budget for keeping social contacts with family members, and peers. Importantly, the relative lack of social contacts was understood as particularly unpleasant.

Background: Emotional competencies are understood as the appropriate management of one’s own emotions. As such, emotional competencies are also crucial for successful social interactions. However, among individuals with multiple sclerosis (MS), emotional competencies have not been investigated. Given this, the first aim of the present study was to compare the scores for emotional competencies between individuals with MS, adults of the general population, and adults with major depressive disorder. The second aim was to investigate the association of emotional competencies with MS-related symptoms of insomnia, depression, fatigue, and paresthesia. The third aim was to identify possible predictors of emotional competencies, including intolerance of uncertainty and mental toughness.
Methods: A total of 1135 individuals with MS (mean age: 34.56 years; 74.32% females; median EDSS: 2; range: 0 - 5) completed a series of self-rating questionnaires covering sociodemographic and MS-related information, emotional competencies, insomnia, depression, fatigue, paresthesia, and intolerance of uncertainty and mental toughness. Participants’ emotional competencies were compared with adults of general population and major depressive disorder.
Results: Compared to general population, individuals with MS reported worse emotional competencies (small to large effect sizes). Compared to individuals with major depressive disorders, individuals with MS reported similar scores (trivial to small effect sizes). Higher scores for emotional competencies were associated with lower symptoms of insomnia, depression, fatigue, paresthesia, and intolerance of uncertainty, and with higher scores for mental toughness. Lower scores for depression and higher scores for mental toughness predicted higher emotional competencies. Higher scores for mental toughness statistically moderated associations between higher scores for depression and lower scores for emotional competencies.
Conclusions: Individuals with MS scored low in emotional competencies, and such scores were related with a broad range of MS-related symptoms, including intolerance of uncertainty. Mental toughness appeared to counterbalance the association between low emotional competencies and symptoms of depression. As such, it is conceivable that specific psychotherapeutic interventions may improve emotional competencies via improved mental toughness and decreased symptoms of depression.

Background: Compared to the general population, individuals with multiple sclerosis (MS) report higher levels of insomnia, depression, fatigue, and paresthesia, and lower levels of emotional competencies (understanding emotions in self and others). Available treatments are limited, and novel approaches to reducing symptoms and enhancing emotional competencies in MS are needed. Two potentially beneficial treatments are Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Stress Reduction (MBSR). The aim of the present study was to investigate the impact of ACT and MBSR on symptoms and emotional competencies in patients with MS.
Methods: A total of 76 individuals with MS (81.6% females; mean age: 38.88 years; EDSS median: 2; range: 0-5) were randomly assigned to an 8-week ACT treatment, an 8-week MBSR treatment, or a wait-list control condition. At baseline and study-end (week 8), participants completed a series of questionnaires covering symptoms and emotional competencies. At mid-term (week 4), participants rated their insomnia and depression.
Results: Over time, symptoms of MS decreased and emotional competencies improved, but more so in the MBSR and ACT conditions, compared with the control condition. At study-end, the outcome improvement did not differ between the ACT and MBSR conditions.
Conclusions: Both ACT and MBSR led to reduced symptoms and enhanced emotional competencies. Psychotherapeutic interventions such as these should be considered as a means of decreasing symptoms and increasing emotional competencies among individuals with MS.

Aims:
Stroke is among the leading causes of disability in adults,(1) with over 15’000 new cases per year in Switzerland alone. Around 30% of stroke patients suffer from deficits in executive function, a series of high-order cognitive processes vital for adaptive goal-directed behavior.(2) These deficits often persist in the long-term(3) and interfere significantly with everyday life.(4) Diagnosis of executive deficits requires extensive testing by trained neuropsychologists or cognitive neurologists. However, rather precise screening would be useful to assess the need for and orient the neuropsychological examination. The aim of this study is to assess the validity of a tablet-based and gamified battery Adaptive Cognitive Evaluation (ACE-X) for the screening of executive deficits after stroke.

Methods:
In this cross-sectional study, we included 31 inpatients with unilateral ischemic or hemorrhagic stroke from two neurorehabilitation units at the University Hospital Inselspital Bern, Switzerland. Exclusion criteria were the inability to engage in the tablet-based assessment due to insufficient vision, central visual field, visuospatial attention, comprehension of instructions or distal upper extremity strength. After giving consent, patients underwent ACE-X testing including reaction time, visuospatial working memory, multitasking, cognitive flexibility and cognitive interference. The results were correlated to corresponding neuropsychological tests routinely performed in inpatient neurorehabilitation.

Results:
The mean age at inclusion was 58.6 years, 10 patients were female. 87 % (n = 27) of patients suffered an ischemic stroke and 58 % (n = 18) presented with a right hemispheric lesion. Strong and significant correlations of ACE-X and corresponding neuropsychological tests were found for reaction time, multitasking and cognitive flexibility, while a trend was observed in the correlations for cognitive interference. No significant correlation was detected between the visuospatial working memory tasks.

Conclusion:
The tablet-based closed-loop adaptive video game ACE-X may represent a valid screening battery for executive dysfunction in stroke patients. The motivating video game setting including real-time adaptation and feedback is an unusual yet promising context for cognitive assessment, providing the opportunity for remote screening, also in other neurological and psychiatric conditions such as multiple sclerosis, dementia or schizophrenia.

Introduction: There is some -- but inconsistent -- evidence that sleep and psychological health have deteriorated in the general population as a result of the COVID-19-pandemic and its related social restrictions. In the present study, we investigated whether and to what extent symptoms of insomnia, depression, fatigue, and paresthesia changed from before to during the COVID-19-pandemic among women diagnosed with multiple sclerosis (MS).
Methods: A total of 90 women with MS (mean age; 37.62 (SD = 8.61) years; EDSS score: median: 2.5 (range: 0-6.50)) completed a series of self-rating scales at two time points: Nine months before the COVID-19-outbreak in May 2019 (baseline) and during the COVID-19-pandemic (study end; 12 months after baseline: May 2020). Self-rating questionnaires covered sociodemographic and disease-related information, symptoms of insomnia, depression, fatigue, and paresthesia.
Results: Symptoms of depression increased over time (medium effect size: Cohen’s d = 0.53), while symptoms of insomnia (small effect size: Cohen’s d = 0.43), fatigue (trivial effect size: Cohen’s d = 0.19), and paresthesia (trivial effect size: Cohen’s d = 0.08) did not. The only predictor for insomnia during the COVID-19-pandemic was insomnia before the COVID-19-pandemic (β = 0.36; p = 0.001); the only predictor for depression during the COVID-19-pandemic was insomnia before the COVID-19-pandemic (β = 0.66; p = 0.001);.
Conclusion: Overall, among a sample of female individuals with MS the COVID-19-pandemic and its related social restrictions may have had a modest influence on participants’ core concerns of insomnia, depression, fatigue, and paresthesia.

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥ 85 years.

Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (< 3 months) aged ≥ 85 versus < 85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk.

Results: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥ 85 (HR ≥ 85y = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR < 85y = 0.79, 95%-CI [0.66, 0.95]) in simple (pinteraction = 0.129), adjusted (pinteraction = 0.094) or weighted (pinteraction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous
variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1).

Interpretation: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old.

BACKGROUND: The benefit of mechanical thrombectomy in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) for short-term outcomes is debatable and long-term outcomes remain unknown. This retrospective, monocentric cohort study aimed to assess the association between reperfusion grade and the long-term functional outcome measured with modified Rankin scale as well as the long-term health-related quality of life recorded at the last follow-up in patients according to baseline ASPECTS (0–5 versus 6–10).
METHODS: Deceased patients were identified from the Swiss population register and follow-up telephone interviews were conducted with all surviving patients with stroke treated with mechanical thrombectomy between January 1, 2010, and December 31, 2018. Favorable outcome was defined as modified Rankin scale 0 to 3; health-related quality of life was assessed using the 3-level version of the EuroQol 5-dimensional questionnaire. The EuroQol 5-dimension utility index was calculated for statistical analyses. The reperfusion grade was core laboratory adjudicated using the expanded treatment in cerebral ischemia score. Adjusted odds ratios for the association between the reperfusion grade assessed by expanded treatment in cerebral ischemia and outcomes were calculated from multivariable logistic regression.
RESULTS: Of the 1114 patients with available long-term follow-up records (median follow-up, 3.67 years), 997 were included in the final analysis. Respectively, patients with low ASPECTS more often had complaints regarding mobility (67.1% versus 42.1%, P < 0.001), self-care (53.4% versus 31.2%, P < 0.001), and usual activities (65.8% versus 41.4%, P < 0.001) than patients with high ASPECTS, whereas reported pain/discomfort (65.7% versus 69.9%, P=0.49) and anxiety/depression (71.2% versus 78.9%, P=0.17) did not differ. In patients with low ASPECTS, increasing reperfusion grade was associated with a higher likelihood of long-term favorable functional outcome (adjusted odds ratio, 1.43; 95% CI, 1.09–1.88 [P=0.01]) and health-related quality of life (adjusted linear correlation coefficient, 0.05; 95% CI, 0.02–0.08) despite early extensive infarction.
CONCLUSION: Despite low baseline ASPECTS, a higher reperfusion grade results in better functional outcomes and may improve health-related quality of life in the long term.

Aims: Post-polio syndrome (PPS) is defined by progressive and persistent new muscle weakness or fatigability occurring after a stable interval, decades after the initial viral infection of spinal cord (SC) motor neurons. The aims of this study were to determine if patients with PPS show spinal cord gray matter (SCGM) atrophy using rAMIRA magnetic resonance imaging (MRI) (Wiegel & Bieri, 2018; Weigel et al., 2020) and to assess associations between SCGM atrophy, muscle strength and patient-reported functional decline.

Methods: Twenty patients diagnosed with PPS (March of Dimes criteria, 2002) and twenty age-and sex-matched healthy controls (HC) underwent 3T axial 2D-rAMIRA MRI at the intervertebral disc levels C2/C3–C6/C7, T9/T10 and the lumbar enlargement level (Tmax) (0.5 × 0.5 mm^2 in-plane resolution). SCGM areas were segmented manually by two independent raters. Muscle strength, self-reported fatigue, depression, and pain measures were assessed.

Results: Post-polio syndrome patients showed significantly and preferentially reduced SCGM areas at C2/C3 (p = 0.048), C3/C4 (p = 0.001), C4/C5 (p < 0.001), C5/C6 (p = 0.004) and Tmax (p = 0.041) compared to HC. In patients with PPS, SCGM areas were significantly associated with muscle strength in corresponding myotomes even after adjustment for fatigue, pain, and depression: Adjusted for age and sex, SCGM area at C3/C3 explained 56% of neck flexor strength variance (p = 0.002), SCGM area at C5/C6 explained 32% of wrist extension strength variance (p = 0.032), and SCGM area at Tmax explained 68% of ankle dorsiflexion strength variance (p = 0.006). No associations were found with age at or time since infection. Patients reporting PPS-related decline in arm function showed significant cervical SCGM atrophy compared to stable patients adjusted for initial disease severity.

Conclusion: Patients with PPS show significant SCGM atrophy that correlates with muscle strength in corresponding myotomes and is associated with PPS-related functional decline. Our findings suggest a secondary neurodegenerative process underlying SCGM atrophy in PPS that is not explained by aging or residua of the initial infection alone. These results need to be confirmed by longitudinal studies. The methodology presented here is promising for the development of novel imaging surrogates for diseases involving SCGM.

Unlike other tumours, the anatomical extent of brain tumours is not objectified and quantified through staging. Staging systems are based on understanding the anatomical sequence of tumour progression and its relationship to histopathological dedifferentiation and survival. The aim of this study was to describe the spatiotemporal phenotype of the most frequent brain tumour entities, to assess the association of anatomical tumour features with survival probability and to develop a staging system for WHO grade 2 and 3 gliomas and glioblastoma.

Anatomical phenotyping was performed on a consecutive cohort of 1000 patients with first diagnosis of a primary or secondary brain tumour. Tumour probability in different topographic, phylogenetic and ontogenetic parcellation units was assessed on preoperative MRI through normalization of the relative tumour prevalence to the relative volume of the respective structure. We analysed the spatiotemporal tumour dynamics by cross-referencing preoperative against preceding and subsequent MRIs of the respective patient. The association between anatomical phenotype and outcome defined prognostically critical anatomical tumour features at diagnosis. Based on a hypothesized sequence of anatomical tumour progression, we developed a three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma. This staging system was validated internally in the original cohort and externally in an independent cohort of 300 consecutive patients.

While primary CNS lymphoma showed highest probability along white matter tracts, metastases enriched along terminal arterial flow areas. Neuroepithelial tumours mapped along all sectors of the ventriculocortical axis, while adjacent units were spared, consistent with a transpallial behaviour within phylo-ontogenetic radial units. Their topographic pattern correlated with morphogenetic processes of convergence and divergence of radial units during phylo- and ontogenesis. While a ventriculofugal growth dominated in neuroepithelial tumours, a gradual deviation from this neuroepithelial spatiotemporal behaviour was found with progressive histopathological dedifferentiation. The proposed three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma correlated with the degree of histological dedifferentiation and proved accurate in terms of survival upon both internal and external validation.

Introduction: The choroid plexus (CP) has been proposed as a modulator of MS-related inflammation. We previously showed that the CP is larger in MS than healthy controls (HCs) and neuromyelitis optica spectrum disease. However, data about the correlations between CP volume (CPV) and MS disease characteristics are scarce.
Aim: To investigate the associations between CPV and disease characteristics in RRMS.
Methods: Cross-sectional, retrospective study. We included 109 RRMS patients from the Swiss MS cohort study (Basel center; mean age 46.9 ± 10.9 years; 69 % female; mean disease duration 16 ± 9 years; proportion of patients with a relapse within the previous year = 11%; median EDSS 2.5 [IQR = 2]) and 118 HCs (mean age 44.3 ± 13.4 years; 65% female). The CP of the lateral ventricles was segmented fully automatically using an in-house deep learning algorithm on non-contrast T1-weighted(w) MRI. Serum neurofilament light chain (sNfL) was measured using the latest HDX platform from Quanterix®. We compared the sNfL values of the patients with a large normative database (n > 10,000 HCs) and calculated z-scores using a generalized additive model for location, scale and shape (Benkert et al. Lancet 2022). Associations between CPV and disease characteristics were investigated using multivariable linear regression models.
Results: CP was larger in RRMS than HCs (B = 221; 95% CI: 111-331; Beta = 0.25; p < 0.001; adjusted for age, gender and TIV). In HCs, CPV correlated with the lateral ventricle volume (LVV; B = 0.016; 95% CI: 0.009-0.024; Beta = 0.39; p < 0.001; adjusted for age, gender and TIV). In RRMS, there was no association between CPV and disease duration, log(EDSS), relapses in the last year, sNfL z-score or disease-modifying treatment. However, CPV was associated with volume (B = 10.6; 95% CI: 5.4-15.9; Beta = 0.35; p < 0.001) and number (B = 5.8; 95% CI: 2.5-9.1; Beta = 0.30; p = 0.001) of the T2w lesions adjusted for age, gender and TIV. Every mL increase of T2w lesion volume was associated with a 11μL larger CP. In a multivariable analysis including age, gender, TIV, disease duration, relapse in the last 12 months (yes/no), log(EDSS), disease-modifying treatment, sNfL z-score, T2w lesion volume and LVV, the LVV was the only parameter that was associated with the CPV in RRMS (B = 0.014; 95% CI: 0.009-0.02; Beta = 0.62; p < 0.001).
Conclusion: LVV as a surrogate of brain atrophy is more closely associated to the CPV than the T2w lesion burden in RRMS.