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Additional file 5: Table S4. Transcriptomic datasets used in this study.

Additional file 1: Figure S1. Functional enrichment analysis and largest connected component of the six CRISPR-Cas9-based SARS-CoV-2 host factor datasets. Figure S2. Network proximity results using different numbers of top genes from the CRISPR-Cas9-based SARS-CoV-2 host factor datasets. Figure S3. Single-cell level expression of AD blood markers in the PBMC samples of COVID-19 patients. Figure S4. Expression spectrum of the SARS-CoV-2 entry factors in the entorhinal cortex from Alzheimer’s disease patients and controls. Figure S5. Expression spectrum of the SARS-CoV-2 entry factors in individuals with different APOE genotypes. Figure S6. Expression of the key SARS-CoV-2 entry factors in different tissues. Figure S7. Expression of the key SARS-CoV-2 entry factors in different brain regions. Figure S8. Cumulative degree distribution of 964 innate immune genes, 14267 brain expressed genes, and 3383 brain specific genes.

NeuroQuant (NQ) is an FDA approved software that performs automatic MRI quantitative volumetric analysis. There is a paucity of literature investigating its clinical utility in a real patient population. This study aims to compare the accuracy of NQ relative to neuroradiologists in detecting MRI signs of hippocampal sclerosis (HS). Methods: We included 144 adult patients with no prior brain surgery, who underwent a temporal lobe resection for epilepsy at Cleveland Clinic from 2010 to 2017. The “gold standard” for the presence of HS was defined by pathology (as confirmed by expert neuropathologist review). Nonspecific findings on pathology were classified as no HS. MRI was acquired on a 3T scanner. An epilepsy neuroradiologist reviewed the pre-operative MRI and classified patients as having HS or not. Questionable signs of HS were classified as no-HS. After de-identifying the MRIs, we used NQ to quantify the volume of the eventually resected hippocampus. The results were given in percentile (based on age- and gender-matched normative cohort controls). Percentiles below 5 were considered abnormal. We used a McNemar’s paired proportions test to compare the specificity and sensitivity of identifying HS between NQ and neuroradiologist reports. Results: There were no differences between the HS group versus no-HS defined by pathology, but for age (Table 1). Distribution of hippocampus volumes (in percentile) is described in table 1. Sensitivity, specificity, positive predictive values, and negative predictive values are presented in Table 2. We found that NQ has the same specificity (p=1) but lower sensitivity when compared to neuroradiologists (69% vs 93%; p

Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japanese-ancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64×10-15; Cleveland: P = 2.85×10-4; Finnish-ancestry Epi25: P = 1.80×10-4) or population controls (Epi25: P = 2.35×10-70; Cleveland: P = 1.43×10-7; Finnish-ancestry Epi25: P = 3.11×10-4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99×10-4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74×10-19; Cleveland: P = 1.69×10-6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish European cohorts (Epi25: P = 2.60×10-15; Cleveland: P = 1.39×10-2). We conclude that common variant risk associated with epilepsy is significantly enriched in multiple cohorts of patients with epilepsy compared to controls-in particular for generalized epilepsy. As sample sizes and PRS accuracy continue to increase with further common variant discovery, PRS could complement established clinical biomarkers and augment genetic testing for patient classification, comorbidity research, and potentially targeted treatment.

The American Epilepsy Society Meeting in New Orleans attracted more than 5900 attendees. There was a lively exchange of new science, innovation, education, clinical practice, and many other items related to epilepsy. Educational symposia were a major part of the meeting and explored varying topics of interest for all types of epilepsy professionals. This article reviews highlights of the meeting presented in major symposia. Topics ranged from how to treat varying aspects of epilepsy as a consultant in the hospital to finding the scientific underpinning of the interaction between sleep and epilepsy. Pros and cons of novel antiseizure medications, dietary, and stimulation treatments were discussed. Epilepsy may impair memory and we need to learn what is the pathophysiologic relationship. Febrile status epilepticus may have severe consequences for a later life with seizures. Epilepsy professionals should be very well aware of the ethical implications of devasting seizures and their associated disability. These are just a few select topics of the many that we need to study further to archive the final goal to improve the lives of patients with epilepsy.

This workshop addressed challenges of clinical research in neurosurgery. Randomized controlled clinical trials (RCTs) have high internal validity, but often insufficiently generalize to real-world practice. Observational studies are inclusive but often lack sufficient rigor. The workshop considered possible solutions, such as (1) statistical methods for demonstrating causality using observational data; (2) characteristics required of a registry supporting effectiveness research; (3) trial designs combining advantages of observational studies and RCTs; and (4) equipoise, an identified challenge for RCTs. In the future, advances in information technology potentially could lead to creation of a massive database where clinical data from all neurosurgeons are integrated and analyzed, ending the separation of clinical research and practice and leading to a new "science of practice."