Intraoperative contrast-enhanced cone beam CT allows visualization of the 'dark side' of the clot and improves mechanical thrombectomy performance.

BACKGROUND: Visualization of the clot is key to the endovascular treatment of ischemic stroke, but identification of the distal part of the clot and distal arteries during mechanical thrombectomy (MT) remains challenging with conventional intraoperative imaging. We aimed to leverage the potential of contrast-enhanced cone beam CT (CE-CBCT) to better visualize the distality ('dark side') of the clot. METHODS: We retrospectively analyzed all patients treated with MT for medium vessel occlusion (MeVO) guided by three-dimensional (3D) imaging to identify those who underwent either CE-CBCT or 3D rotational angiography (3DRA). Our primary outcome was the visualization of the proximal and distal edges of the clot and the arteries beyond the occlusion on the different types of intraoperative imaging: digital subtraction angiography (DSA), 3DRA, and CE-CBCT. Secondary outcomes included the efficacy, safety, and timing of MT between CE-CBCT versus 3DRA groups. RESULTS: The proximal edge of the clot was well visualized by DSA, 3DRA, and CE-CBCT. However, the distal edge of the clot and distal arteries were significantly better visualized with CE-CBCT (60.0%) than 3DRA (2.7%) and DSA (11.4-13.5%). Moreover, MT efficacy was better with CE-CBCT than 3DRA, with higher first-pass effect (65.7% vs 37.8%) and final recanalization grade (expanded Treatment In Cerebral Infarction (eTICI) 3: 71.4% vs 43.2%). Finally, the visualization of the distal edge of the clot and distal arteries correlated with better collateralization grade. CONCLUSION: CE-CBCT localizes the clot and reveals the underlying vascular anatomy better than 3DRA or DSA, thereby enhancing the efficacy of MT. The improved filling of collaterals with CE-CBCT may explain this better visualization of the 'dark side' of the clot.

Fingerprints of brain disease: connectome identifiability in Alzheimer's disease.

Functional connectivity patterns in the human brain, like the friction ridges of a fingerprint, can uniquely identify individuals. Does this "brain fingerprint" remain distinct even during Alzheimer's disease (AD)? Using fMRI data from healthy and pathologically ageing subjects, we find that individual functional connectivity profiles remain unique and highly heterogeneous during mild cognitive impairment and AD. However, the patterns that make individuals identifiable change with disease progression, revealing a reconfiguration of the brain fingerprint. Notably, connectivity shifts towards functional system connections in AD and lower-order cognitive functions in early disease stages. These findings emphasize the importance of focusing on individual variability rather than group differences in AD studies. Individual functional connectomes could be instrumental in creating personalized models of AD progression, predicting disease course, and optimizing treatments, paving the way for personalized medicine in AD management.

Specific Reversal Agents for Direct Oral Anticoagulants in Acute Stroke.

Direct oral anticoagulants (DOACs) changed stroke prevention and decreased the risk of ischemic and hemorrhagic complications in patients on oral anticoagulation (OAC) therapy. The numbers of patients prescribed DOACs has increased rapidly. Availability of specific reversal agents opened new avenues in the prevention and management of DOAC complications. An ideal specific reversal agent for a DOAC in acute stroke is an agent which lacks safety concerns and immediately reverses DOAC anticoagulation activity, thereby enabling effective treatment. Reversal of anticoagulant activity is mandatory in patients with acute ischemic stroke (AIS) before performing therapeutic procedures such as intravenous thrombolysis (IVT) and neurosurgery in intracranial hemorrhage (ICH) in order to improve clinical outcomes. In this manuscript we pursue an interdisciplinary approach in discussing advantages and concerns of specific reversal agents in acute stroke DOAC-treated patients in everyday clinical practice.

Experimental comparison of first-pass effect between direct thromboaspiration and combined thrombectomy in the setting of distal basilar occlusion.

BACKGROUND: Studies investigating endovascular therapy in vertebro-basilar stroke have led to controversial results in the past, but recent randomized trials seem to show an effectiveness superiority of endovascular therapy versus best medical treatment. However, uncertainty remains concerning many aspects of thrombectomy in acute basilar artery occlusion, notably technical considerations. This study compared the first-pass effect of direct thromboaspiration and combined thrombectomy in the setting of distal basilar occlusion. METHODS: An in-vitro experimental set-up was used, consisting of a vascular phantom model and thrombus analogs of different consistencies to mimic human clots. Thrombus analogs were injected into the model through the vertebral artery and flowed to the basilar distal third to mimic a distal basilar occlusion. Ten procedures were performed for each thrombus analog stiffness and technique (direct thromboaspiration versus combined thrombectomy). RESULTS: Direct thromboaspiration showed an overall first-pass effect rate of 83.3% (25/30) and was particularly effective for ultra-soft and soft clot analogs, but decreased for hard clot analogs. Combined thrombectomy had an overall first-pass effect rate of 56.7% (17/30). The effect rate for ultra-soft and soft clot analogs was 60% and 50% for hard clot analogs. In the softer clot analogs, the stent-retriever device used for the combined thrombectomies tended to deviate the clot analog from a co-axial trajectory with the aspiration catheter. CONCLUSIONS: In the context of distal basilar occlusion, our in-vitro results showed that higher first-pass effect rates were achieved with direct thromboaspiration compared to combined thrombectomy in all types of thrombus analogs.

Current and Future Applications of Arterial Spin Labeling MRI in Cerebral Arteriovenous Malformations.

Arterial spin labeling (ASL) has emerged as a promising noninvasive tool for the evaluation of both pediatric and adult arteriovenous malformations (AVMs). This paper reviews the advantages and challenges associated with the use of ASL in AVM assessment. An assessment of the diagnostic workup of AVMs and their variants in both adult and pediatric populations is proposed. Evaluation after treatments, whether endovascular or microsurgical, was similarly examined. ASL, with its endogenous tracer and favorable safety profile, offers functional assessment and arterial feeder identification. ASL has demonstrated strong performance in identifying feeder arteries and detecting arteriovenous shunting, although some studies report inferior performance compared with digital subtraction angiography (DSA) in delineating venous drainage. Challenges include uncertainties in sensitivity for specific AVM features. Detecting AVMs in challenging locations, such as the apical cranial convexity, is further complicated, demanding careful consideration due to the risk of underestimating total blood flow. Navigating these challenges, ASL provides a noninvasive avenue with undeniable merits, but a balanced approach considering its limitations is crucial. Larger-scale prospective studies are needed to comprehensively evaluate the diagnostic performance of ASL in AVM assessment.

Can micro-guidewire advancement forces predict clot consistency and location to assist the first-line technique for mechanical thrombectomy?

BACKGROUND: The identification of specific clot characteristics before mechanical thrombectomy (MTB) might allow the selection of the most effective first-line technique, thus potentially improving the procedural outcome. We aimed to evaluate if the microwire push forces could extrapolate information on clot consistency and extension before MTB, based on clot mechanical properties. METHODS: We measured in vitro the forces exerted on the proximal extremity of the guidewire during the advancement and retrieval of the guidewire through clot analogs of different compositions. In addition, we analyzed the forces exerted on the guidewire to extrapolate information about the location of the proximal and distal extremities of the clot analogs. RESULTS: The maximum forces recorded during the whole penetration phase were significantly different for hard and soft clots (median values, 55.6 mN vs 15.4 mN, respectively; P<0.0001). The maximum slope of the force curves recorded during the advancement of the guidewire for the first 3 s of penetration also significantly differentiated soft from hard clot analogs (7.6 mN/s vs 23.9 mN/s, respectively; P<0.0001). In addition, the qualitative analysis of the shape of the force curves obtained during the advancement and retrieval of the guidewire showed a good potential for the identification of the proximal and distal edges of the clot analogs. CONCLUSION: Our results demonstrated that it was possible to differentiate between soft and hard clot analogs. Furthermore, force measurements could give important information about the location of the clot extremities. Such an approach might support the selection of the first-line MTB technique, with the potential to improve the outcome.

Double Stent Retriever Technique for Mechanical Thrombectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Mechanical thrombectomy using a double stent retriever technique has recently been described for the treatment of acute ischemic stroke, but its efficacy and safety are not well-established. PURPOSE: The aim of this systematic review and meta-analysis was to evaluate reports of the use of a double stent retriever technique during the endovascular treatment of patients with ischemic stroke. DATA SOURCES: The PubMed, EMBASE, Web of Science, and Scopus databases were searched to identify all studies (clinical trials, cohort series, and case reports) investigating the utility of a double stent retriever technique for the treatment of stroke. The study is reported in accordance with PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD42023482691). STUDY SELECTION: Seventeen studies involving a total of 128 patients with large-vessel occlusions predominantly in the anterior circulation (93.0%) were identified. DATA ANALYSIS: Outcomes of interest were the prevalence of successful recanalization (modified TICI ≥2b) and a first-pass effect following the double stent retriever technique as well as complications such as iatrogenic dissections and SAH. Data were pooled using a random effects model. DATA SYNTHESIS: The double stent retriever technique was used as a rescue strategy in occlusions refractory to conventional endovascular treatment in 68.7% (88/128) of patients and as a first-line strategy in 31.3% (40/128) of patients. The double stent retriever technique achieved an overall final modified TICI ≥2b in 92.6% cases, with a first-pass effect of 76.6%. The complication rate remained low, with 0.37% dissection and 1.56% SAH. LIMITATIONS: Limitations of the study include the following: 1) a large number of case reports or small series, 2) a meta-analysis of proportions with no statistical comparison with a control group, and 3) the lack of access to patient-level data. CONCLUSIONS: Our findings suggest that double stent retriever thrombectomy may be safe and associated with good recanalization outcomes, but prospective comparative studies are needed to determine which patients may benefit from this endovascular procedure.

Persistence and emergence of new neuropsychological deficits following SARS-CoV-2 infection: A follow-up assessment of the Geneva COVID-COG cohort.

Background: Despite numerous observations of neuropsychological deficits immediately following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, little is known about what happens to these deficits over time and whether they are affected by changes in fatigue and any psychiatric symptoms. We aimed to assess the prevalence of neuropsychological deficits at 6-9 months and again at 12-15 months after coronavirus disease 2019 (COVID-19) and to explore whether it was associated with changes in fatigue and psychiatric symptoms. Methods: We administered a series of neuropsychological tests and psychiatric questionnaires to 95 patients (mean age = 57.12 years, standard deviation (SD) = 10.68; 35.79% women) 222 (time point 1 (T1)) and 441 (time point 2 (T2)) days on average after infection. Patients were categorised according to the severity of their respiratory COVID-19 symptoms in the acute phase: mild (no hospitalisation), moderate (conventional hospitalisation), and severe (hospitalisation in intensive care unit (ICU) plus mechanical ventilation). We ran Monte-Carlo simulation methods at each time point to generate a simulated population and then compared the cumulative percentages of cognitive disorders displayed by the three patient subgroups with the estimated normative data. We calculated generalised estimating equations for the whole sample to assess the longitudinal associations between cumulative neuropsychological deficits, fatigue, and psychiatric data (anxiety, depressive symptoms, posttraumatic stress disorder, and apathy). Results: Most participants (>50%) exhibited a decrease in their neuropsychological impairments, while approximately 25% showed an escalation in these cognitive deficits. At T2, patients in the mild subgroup remained free of accumulated neuropsychological impairments. Patients with moderate severity of symptoms displayed a decrease in the magnitude of cumulative deficits in perceptual and attentional functions, a persistence of executive, memory and logical reasoning deficits, and the emergence of language deficits. In patients with severe symptoms, perceptual deficits emerged and executive deficits increased, while attentional and memory deficits remained unchanged. Changes in executive functions were significantly associated with changes in depressive symptoms, but the generalised estimating equations failed to reveal any other significant effect. Conclusion: While most cumulative neuropsychological deficits observed at T1 persisted and even worsened over time in the subgroups of patients with moderate and severe symptoms, a significant proportion of patients, mainly in the mild subgroup, exhibited improved performances. However, we identified heterogeneous neuropsychological profiles both cross-sectionally and over time, suggesting that there may be distinct patient phenotypes. Predictors of these detrimental dynamics have yet to be identified.

High-dose glucocorticoids in COVID-19 patients with acute encephalopathy: clinical and imaging findings in a retrospective cohort study.

OBJECTIVES: Acute encephalopathy (AE) has been described as a severe complication of COVID-19. Inflammation has been suggested as a pathogenic mechanism, with high-dose glucocorticoids (GC) showing a beneficial effect. Here, we retrospectively analyzed the clinical and radiological features in a group of COVID-19 AE patients who received GC treatment (GT) and in a non-treated (NT) group. METHOD: Thirty-six patients with COVID-19 AE (mean age 72.6 ± 11 years; 86.11% men) were evaluated for GC treatment. Twelve patients (mean age 73.6 ± 4.5 years; 66.67% men) received GC, whereas 24 patients who showed signs of spontaneous remission were not treated with GC (mean age 70.1 ± 8.6 years; 95.83% men). Differences in clinical characteristics and correlations with imaging features were explored. RESULTS: The GT group showed signs of vulnerability, with a longer hospitalization (p = 0.009) and AE duration (p = 0.012) and a higher hypertensive arteriopathy (HTNA) score (p = 0.022), when compared to NT group. At hospital discharge, the two groups were comparable in terms of clinical outcome (modified Rankin scale; p = 0.666) or mortality (p = 0.607). In our whole group analyses, AE severity was positively correlated with periventricular white matter hyperintensities (p = 0.011), deep enlarged perivascular spaces (p = 0.039) and HTNA score (p = 0.014). CONCLUSION: This study suggests that, despite signs of radiological vulnerability and AE severity, patients treated by high-dose GC showed similar outcome at discharge, with respect to NT patients. Imaging features of cerebral small vessel disease correlated with AE severity, supporting the hypothesis that brain structural vulnerability can impact AE in COVID-19.

Insights into single-timepoint ASL hemodynamics: what visual assessment and spatial coefficient of variation can tell.

PURPOSE: Arterial spin labeling (ASL) represents a noninvasive perfusion biomarker, and, in the study of nonvascular disease, the use of the single-timepoint ASL technique is recommended. However, the obtained cerebral blood flow (CBF) maps may be highly influenced by delayed arterial transit time (ATT). Our aim was to assess the complexity of hemodynamic information of single-timepoint CBF maps using a new visual scale and comparing it with an ATT proxy, the "coefficient of spatial variation" (sCoV). MATERIAL AND METHODS: Individual CBF maps were estimated in a memory clinic population (mild cognitive impairment, dementia and cognitively unimpaired controls) and classified into four levels of delayed perfusion based on a visual rating scale. Calculated measures included global/regional sCoVs and common CBF statistics, as mean, median and standard deviation. One-way ANOVA was performed to compare these measures across the four groups of delayed perfusion. Spearman correlation was used to study the association of global sCoV with clinical data and CBF statistics. RESULTS: One hundred and forty-four participants (72 ± 7 years, 53% women) were included in the study. The proportion of maps with none, mild, moderate, and severe delayed perfusion was 15, 20, 37, and 28%, respectively. SCoV demonstrated a significant increase (p < 0.05) across the four groups, except when comparing none vs mild delayed perfusion groups (pBonf > 0.05). Global sCoV values, as an ATT proxy, ranged from 67 ± 4% (none) to 121 ± 24% (severe delayed) and were significantly associated with age and CBF statistics (p < 0.05). CONCLUSION: The impact of ATT delay in single-time CBF maps requires the use of a visual scale or sCoV in clinical or research settings.

Time-of-flight and black-blood MRI to study intracranial arteries in rats.

Intracranial aneurysms (IAs) are usually incidentally discovered by magnetic resonance imaging (MRI). Once discovered, the risk associated with their treatment must be balanced with the risk of an unexpected rupture. Although clinical observations suggest that the detection of contrast agent in the aneurysm wall using a double-inversion recovery black-blood (BB) sequence may point to IA wall instability, the exact meaning of this observation is not understood. Validation of reliable diagnostic markers of IA (in)stability is of utmost importance to deciding whether to treat or not an IA. To longitudinally investigate IA progression and enhance our understanding of this devastating disease, animal models are of great help. The aim of our study was to improve a three-dimensional (3D)-time-of-flight (TOF) sequence and to develop a BB sequence on a standard preclinical 3-T MRI unit to investigate intracranial arterial diseases in rats. We showed that our 3D-TOF sequence allows reliable measurements of intracranial artery diameters, inter-artery distances, and angles between arteries and that our BB sequence enables us to visualize intracranial arteries. We report the first BB-MRI sequence to visualize intracranial arteries in rats using a preclinical 3-T MRI unit. This sequence could be useful for a large community of researchers working on intracranial arterial diseases.Relevance statement We developed a black-blood MRI sequence to study vessel wall enhancement in rats with possible application to understanding IAs instability and finding reliable markers for clinical decision-making.Key points• Reliable markers of aneurysm stability are needed for clinical decision.• Detection of contrast enhancement in the aneurysm wall may be associated with instability.• We developed a black-blood MRI sequence in rats to be used to study vessel wall enhancement of IAs.

CADMUS: A Novel MRI-Based Classification of Spontaneous Intracerebral Hemorrhage Associated With Cerebral Small Vessel Disease

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. METHODS: We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. RESULTS: The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. DISCUSSION: CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.

MRI characterization of in vitro clots at 3T and 7T: A technical note.

In acute ischemic stroke, the composition of the occlusive clot can be associated with the underlying pathophysiology and the response to treatment. For these reasons, it is important to characterize the clot composition from clinical scans. We examine the ability of 3T and 7T MRI to distinguish the composition of in vitro clots, using quantitative T1 and T2*, alternatively R2*, mapping. When comparing the two field strengths, we found a tradeoff between sensitivity for clot composition and confidence in the clot depiction associated with spatial resolution. The loss of sensitivity at 7T can be mitigated by combining the T1 and T2* signals.

Effectiveness of the preventive administration of vasoactive amines in counterbalancing significant patient blood pressure drops following nimodipine administration during mechanical thrombectomy procedures.

BACKGROUND: Focal vasospasm (FV) of the occluded vessel can occur during the endovascular treatment of acute ischemic stroke (AIS). Nimodipine is commonly used to treat vasospasm and can play a role in distinguishing it from artery narrowing due to iatrogenic dissection or residual clot. However, nimodipine administration can result in arterial hypotension and subsequent enlargement of the ischemic core. OBJECTIVE: To assess the efficacy of preventive and continuous vasoactive amine infusion to counterbalance nimodipine-induced hypotension. METHODS: We reviewed data from a prospective registry of patients treated for AIS between January 2019 and January 2022 who were administered nimodipine. All patients were equipped with an arterial cannula for invasive blood pressure measurement and given vasoactive amines preemptively before general anesthesia and throughout the procedure. Data obtained from invasive monitoring of mean arterial blood pressure (MABP) in a time-lapse of 25 min before and after nimodipine administration were analyzed. RESULTS: MABP significantly decreased after nimodipine administration but remained within the recommended range (81.79 ± 0.49 mmHg). Nimodipine was effective in reducing FV caused by stent retriever passage in 76.3% of cases. Furthermore, it proved valuable in diagnosing iatrogenic dissection (9.2%), residual clot (10.5%), or intracranial stenosis (4%). CONCLUSIONS: Infusion of vasoactive amines effectively counteracted the intraarterial nimodipine effect, thus avoiding frank arterial hypotension during endovascular treatment. Nimodipine has been useful in differentiating the diagnosis of FV resulting from mechanical thrombectomy and other potential causes, such as iatrogenic dissection or residual clot.

Obstructive sleep apnea: a major risk factor for COVID-19 encephalopathy?

BACKGROUND: This study evaluates the impact of high risk of obstructive sleep apnea (OSA) on coronavirus disease 2019 (COVID-19) acute encephalopathy (AE). METHODS: Between 3/1/2020 and 11/1/2021, 97 consecutive patients were evaluated at the Geneva University Hospitals with a neurological diagnosis of COVID-19 AE. They were divided in two groups depending on the presence or absence of high risk for OSA based on the modified NOSAS score (mNOSAS, respectively ≥ 8 and < 8). We compared patients' characteristics (clinical, biological, brain MRI, EEG, pulmonary CT). The severity of COVID-19 AE relied on the RASS and CAM scores. RESULTS: Most COVID-19 AE patients presented with a high mNOSAS, suggesting high risk of OSA (> 80%). Patients with a high mNOSAS had a more severe form of COVID-19 AE (84.8% versus 27.8%), longer mean duration of COVID-19 AE (27.9 versus 16.9 days), higher mRS at discharge (≥ 3 in 58.2% versus 16.7%), and increased prevalence of brain vessels enhancement (98.1% versus 20.0%). High risk of OSA was associated with a 14 fold increased risk of developing a severe COVID-19 AE (OR = 14.52). DISCUSSION: These observations suggest an association between high risk of OSA and COVID-19 AE severity. High risk of OSA could be a predisposing factor leading to severe COVID-19 AE and consecutive long-term sequalae.

Benchtop evaluation of a double stent retriever thrombectomy technique for acute ischemic stroke treatment.

BACKGROUND AND PURPOSE: A mechanical thrombectomy technique using a double stent retriever approach has been reported for the treatment of patients with acute ischemic stroke. The purpose of this study was to perform a benchtop evaluation of the mechanism of action and efficacy of a double-stent retriever approach compared to a single-stent retriever approach. MATERIALS AND METHODS: In vitro, mechanical thrombectomy procedures were performed in a vascular phantom reproducing an M1-M2 occlusion with two different clot analog consistencies (soft and hard). We compared the double stent retriever approach to the single stent retriever approach and recorded the recanalization rate, distal embolization, and retrieval forces of each mechanical thrombectomy procedure. RESULTS: The double stent retriever approach achieved a higher recanalization rate and lower embolic complications compared to the single stent retriever approach. This seems to stem from two facts: the greater probability of targeting the correct artery with two stents in the case of bifurcation occlusion, and an improved clot capture mechanism using the double stent retriever approach. However, the double stent retriever was associated with an increased initial retrieval force. CONCLUSIONS: In vitro evaluation of the mechanism of action of the double stent retriever provided explanations that appear to support the high efficacy of such an approach in patient cohorts and could help operators when selecting the optimal mechanical thrombectomy strategy in cases of arterial occlusions difficult to treat with a single stent retriever.

Markers of limbic system damage following SARS-CoV-2 infection.

Alterations of the limbic system may be present in the chronic phase of SARS-CoV-2 infection. Our aim was to study the long-term impact of this disease on limbic system-related behaviour and its associated brain functional connectivity, according to the severity of respiratory symptoms in the acute phase. To this end, we investigated the multimodal emotion recognition abilities of 105 patients from the Geneva COVID-COG Cohort 223 days on average after SARS-CoV-2 infection (diagnosed between March 2020 and May 2021), dividing them into three groups (severe, moderate or mild) according to respiratory symptom severity in the acute phase. We used multiple regressions and partial least squares correlation analyses to investigate the relationships between emotion recognition, olfaction, cognition, neuropsychiatric symptoms and functional brain networks. Six to 9 months following SARS-CoV-2 infection, moderate patients exhibited poorer recognition abilities than mild patients for expressions of fear (P = 0.03 corrected), as did severe patients for disgust (P = 0.04 corrected) and irritation (P < 0.01 corrected). In the whole cohort, these performances were associated with decreased episodic memory and anosmia, but not with depressive symptoms, anxiety or post-traumatic stress disorder. Neuroimaging revealed a positive contribution of functional connectivity, notably between the cerebellum and the default mode, somatosensory motor and salience/ventral attention networks. These results highlight the long-term consequences of SARS-Cov-2 infection on the limbic system at both the behavioural and neuroimaging levels.

Patterns of amyloid accumulation in amyloid-negative cases.

Amyloid staging models showed that regional abnormality occurs before global positivity. Several studies assumed that the trajectory of amyloid spread is homogeneous, but clinical evidence suggests that it is highly heterogeneous. We tested whether different amyloid-ß (Aß) patterns exist by applying clustering on negative scans and investigating their demographics, clinical, cognitive, and biomarkers correlates, and cognitive trajectories. 151 individuals from Geneva and Zurich cohorts with T1-MRI, negative Aß positron emission tomography (PET,centiloid<12) and clinical assessment were included. N=123 underwent tau PET, and N=65 follow-up neuropsychological assessment. We performed k-means clustering using 33 Aß regional Standardized Uptake Vales ratio. Demographics, clinical, cognitive, and biomarkers differences were investigated. Longitudinal cognitive changes by baseline cluster status were estimated using a linear mixed model. The cluster analysis identified two clusters: temporal predominant (TP) and cingulate predominant (CP). TP tau deposition was higher than CP. A trend for a higher cognitive decline in TP compared to CP was observed. This study suggests the existence of two Aß deposition patterns in the earliest phases of Aß accumulation, differently prone to tau pathology and cognitive decline.