CNS Complications Research Articles

Multimodal Analgesia and Outcomes in Hysterectomy Surgery-A Population-Based Analysis.

Objective: We aimed to investigate the impact of multimodal analgesia on postoperative complications and opioid prescription on a national level. Methods: This retrospective cross-sectional study included n = 1,307,923 hysterectomies (01/2006-12/2022, Premier Healthcare claims data). Multimodal analgesia was defined as opioid use with the addition of non-opioid analgesic modes, grouped into four categories: opioid-only and 1, 2, or 3 or more additional non-opioid analgesics. Multivariable regression models measured associations between multimodal categories and outcomes (composite/respiratory/cardiac/gastrointestinal/genitourinary, and CNS complications, oral morphine milligram equivalents [MME], and length of hospital stay [LOS]). Odds ratios (OR) and 95% confidence intervals (CI) are reported. Results: Overall, 84.3% (1,102,812/1,307,923) received multimodal analgesia, of which 58.9%, 28.0%, and 13.1% received 1, 2, or 3 or more additional non-opioid analgesics, respectively. The odds of any composite complication (any ≥1 complication) decreased with the addition of 1, 2, 3, or more analgesic modalities (versus opioid-only): OR 0.66 (CI 0.64; 0.68), OR 0.63 (CI 0.61; 0.66), OR 0.65 (CI 0.62; 0.67), respectively. Similar patterns existed for respiratory, cardiac, and genitourinary complications. Opioid prescription decreased incrementally with 1,2, 3, or more non-opioid analgesic modalities by 9.51 mg (CI 11.16; 7.86) and 15.29 mg (CI 17.21; 13.37) and 29.35 mg (CI 31.79; 26.91) cumulative MME. LOS was reduced by 0.52 days (CI 0.54; 0.51), 0.49 days (CI 0.51; 0.47), and 0.40 days (CI 0.43; 0.38), respectively. Costs were reduced by $765 (CI 817; 714) or $479 (CI 539; 419) with 1 or 2 multimodal modes. Conclusions: These findings suggest substantial benefits of multimodal analgesia, including significant decreases in serious complications (especially respiratory, cardiac, and genitourinary), opioid consumption, and hospitalizations. Multimodal analgesia may facilitate safe and efficient pain management with optimized opioid consumption.

HIV-1 RNA in extracellular vesicles is associated with neurocognitive outcomes

Human immunodeficiency virus type-1 (HIV-1) is responsible for significant mortality and morbidity worldwide. Despite complete control of viral replication with antiretrovirals, cells with integrated HIV-1 provirus can produce viral transcripts. In a cross-sectional study of 84 HIV+ individuals of whom 43 were followed longitudinally, we found that HIV-1 RNAs are present in extracellular vesicles (EVs) derived from cerebrospinal fluid and serum of all individuals. We used seven digital droplet polymerase chain reaction assays to evaluate the transcriptional status of the latent reservoir. EV-associated viral RNA was more abundant in the CSF and correlated with neurocognitive dysfunction in both, the cross-sectional and longitudinal studies. Sequencing studies suggested compartmentalization of defective viral transcripts in the serum and CSF. These findings suggest previous studies have underestimated the viral burden and there is a significant relationship between latent viral transcription and CNS complications of long-term disease despite the adequate use of antiretrovirals.

In-vitro and in-vivo assessment of nirmatrelvir penetration into CSF, central nervous system cells, tissues, and peripheral blood mononuclear cells

Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been shown as viral reservoirs for SARS-CoV-2, yielding a potential hypothesis for CNS effects. Thus, we investigated the CNS pharmacology of orally dosed nirmatrelvir/ritonavir (NMR/RTV). Using both an in vitro and an in vivo rodent model, we investigated CNS penetration and potential pharmacodynamic activity of NMR. Through pharmacokinetic modeling, we estimated the median CSF penetration of NMR to be low at 18.11% of plasma with very low accumulation in rodent brain tissue. Based on the multiples of the 90% maximal effective concentration (EC90) for SARS-CoV-2, NMR concentrations in the CSF and brain do not achieve an exposure level similar to that of plasma. A median of only 16% of all the predicted CSF concentrations in rats were > 3xEC90 (unadjusted for protein binding). This may have implications for viral persistence and neurologic post-acute sequelae of COVID-19 if increased NMR penetration in the CNS leads to decreased CNS viral loads and decreased CNS inflammation.

CNS Demyelination Syndromes Following COVID-19 Vaccination: A Case Series

ABSTRACT Background and Objectives: Although immunization against coronavirus disease 2019 (COVID-19) is ongoing, adverse reactions to these vaccinations have been observed in isolated cases. We aimed to report different neurological complications developed after COVID-19 vaccination. Materials and Methods: In our case series study, we report all cases of CNS demyelination following COVID-19 immunization. Clinical evaluation, brain MRI, and CSF analysis for oligoclonal bands and IgG index were performed for all patients. Other investigations were performed for selected patients, including spine MRI, EEG, VEP, and aquaporin-4. Results: Eighteen patients (eight males and ten females) with no history of COVID-19 infection had neurological manifestations (vertigo, ataxia, recurrent attacks of loss of consciousness, optic neuritis, and myelitis) starting within 14 days after Pfizer (n = 12) and AstraZeneca (n = 6) vaccination. MRI was obtained during the acute stage of the disease. The most common presenting symptoms were optic neuritis and hemiparesis. Sixteen patients had altered signal intensity and multiple variable-sized, round to ill-defined oval lesions suggestive of MS. Two showed findings compatible with transverse myelitis Conclusion: This study identified CNS demyelination complications after COVID-19 vaccination. The COVID-19 vaccination could result in CNS complications, possibly connected to a post-vaccination inflammatory process. We recommend continuous post-marketing monitoring for adverse reactions in individuals who received the vaccines to establish a connection and guarantee the long-term safety of COVID-19 vaccines.

A Systematic Review of the COVID Vaccine's Impact on the Nervous System.

The objective of this study was to conduct a systematic review of research pertaining to the COVID-19 vaccine and its association with neurological complications. We performed a comprehensive search of the literature using Google Scholar, PubMed, and NCBI databases from December 2021 to December 2022. For Google Scholar, PubMed, and NCBI databases we used the following key search terms: "neurological adverse effects", "COVID-19 vaccination", "SARS-CoV-2", CNS complications, and CNS adverse effects. Two reviewer authors individually searched and assessed the titles and abstracts of all articles. The third reviewer resolved the disagreement between them. Data were documented regarding title, study location, type of study, type of COVID-19 vaccine, type of neurological complications/adverse effects, and sample size. From our findings, it is confirmed that these neurological complications like GuillainBarre syndrome (23.6%), Neuromyelitis Optica spectrum disorder (5.5%), Neuropathy (6.9%), Transverse Myelitis (8.3%) and Acute disseminated Encephalomyelitis (4.1%) are majorly affected in most of the people. The increase in risks associated with SARS-CoV-2 infection far outweighs any previously reported associations with vaccination. We found no safety signal was observed between COVID-19 vaccines and the immune-mediated neurological events. Before assuming a causal relationship, the side effects of the COVID-19 vaccine should first be carefully examined to rule out known associated factors. Symptom onset was within two weeks of vaccination in the majority of cases; as such, this seems to be a high-risk period warranting vigilance.

A Systematic Review and Clinical Presentation of Central Nervous System Complications of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospitalized Pediatric Patients During the Coronavirus Disease 2019 Pandemic in Israel

BackgroundCoronavirus disease-associated central nervous system complications (CNS-C) in hospitalized children, especially during the Omicron wave, and in comparison with influenza associated CNS-C, are not well understood. MethodsThe study population included 755 children aged <18 years hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Sheba Medical Center, during March 2020 to July 2022. A comparative cohort consisted of 314 pediatric patients with influenza during the 2018-2019 and 2019-2020 influenza seasons. ResultsOverall, 5.8% (n = 44) of patients exhibited CNS-C. Seizures at presentation occurred in 33 patients with COVID-19 (4.4%), with 2.6% (n = 20) experiencing nonfebrile seizures, 1.1% (n = 8) febrile seizures, and 0.7% (n = 5) status epilepticus. More patients with CNS-C experienced seizures during the Omicron wave versus the pre-Omicron period (77.8% vs 41.2%, P = 0.03). Fewer patients were admitted to the intensive care unit in the Omicron wave (7.4%) versus prior waves (7.4% vs 41.2%, P = 0.02). Fewer patients with SARS-CoV-2 experienced CNS-C (5.8%) versus patients with influenza (9.9%), P = 0.03. More patients with SARS-CoV-2 experienced nonfebrile seizures (2.6% vs 0.6%, P = 0.06), whereas more patients with influenza experienced febrile seizures (7.3% vs 1.1%, P < 0.01). ConclusionsThe Omicron wave was characterized by more seizures and fewer intensive-care-unit admissions than previous waves. Pediatric patients with SARS-CoV-2 experienced fewer CNS-C and more nonfebrile seizures compared with patients with influenza.

Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology

Propionic acidemia (PA) is an autosomal recessive condition (OMIM #606054), wherein pathogenic variants in PCCA and PCCB impair the activity of propionyl-CoA carboxylase. PA is associated with neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorder (ASD); however, the correlates and mechanisms of these outcomes remain unknown. Using data from a subset of participants with PA enrolled in a dedicated natural history study (n = 33), we explored associations between neurodevelopmental phenotypes and laboratory parameters. Twenty (61%) participants received an ID diagnosis, and 12 of the 31 (39%) who were fully evaluated received the diagnosis of ASD. A diagnosis of ID, lower full-scale IQ (sample mean = 65 ± 26), and lower adaptive behavior composite scores (sample mean = 67 ± 23) were associated with several biomarkers. Higher concentrations of plasma propionylcarnitine, plasma total 2-methylcitrate, serum erythropoietin, and mitochondrial biomarkers plasma FGF21 and GDF15 were associated with a more severe ID profile. Reduced 1-13C-propionate oxidative capacity and decreased levels of plasma and urinary glutamine were also associated with a more severe ID profile. Only two parameters, increased serum erythropoietin and decreased plasma glutamine, were associated with ASD. Plasma glycine, one of the defining features of PA, was not meaningfully associated with either ID or ASD. Thus, while both ID and ASD were commonly observed in our PA cohort, only ID was robustly associated with metabolic parameters. Our results suggest that disease severity and associated mitochondrial dysfunction may play a role in CNS complications of PA and identify potential biomarkers and candidate surrogate endpoints.

The Efficacy and Safety of the Third Generation TKI Olverembatinib in Adult Ph+ Acute Lymphoblastic Leukemia with Relapsed Disease or Persistent MRD Bridging to Allo-HSCT: A Case Series from a Single Center

Background The value of achieving hematology remission and MRD negativity before HSCT is substantial for ph+ALL patients. Olverembatinib, a novel third-generation TKI developed in China, has been approved in CML with T315I mutation since 2021. In this study, we report a retrospective analysis of the efficacy and safety of the Olverembatinib-involved regimen in adult Ph/BCR-ABL1+ ALL with relapsed disease or persistent MRD prior to allo-HSCT. Herein, we report our preliminary results. Method In this retrospective analysis, all enrolled ph+ALL patients with relapsed disease or persistent MRD were treated with Olverembatinib involving regimen, before bridging to HSCT. The Olverembatinib involving regimen included: Olverembatinib and Venetoclax in combination with VP based low intensive chemotherapy (Vindesine /Prednisone), Olverembatinib+Blinatumomab, Olverembatinib + INO. Efficacy was assessed by complete remission (CR) rate, MRDneg (&amp;lt;0.01%) rate by flow cytometry, and CMR (BCR-ABL1 transcript&amp;lt;10-4) rate by real-time quantitative polymerase chain reaction (RT-qPCR). Safety events were also monitored. Result From April 2022 to February 2023, 13 Ph+ ALL pts were treated with Olverembatinib involving therapy due to disease recurrence (n=2) and persistently molecular positive (n=11). The median age was 40 years (range, 23-56), and 9/13 were males. BCR::ABL1 p190 and p210 fusion were found in 7 and 6 patients, respectively. Three patients had T315I mutations, and one had G250E mutation. Three patients had IKZF mutations. Four patients had received 2 types of TKIs previously. One patient relapsed with both BM and CNS involved. The median time from diagnosis of Relapse or molecular positive to the administration of Olverembatinib was 181 (range, 51-1284) days. Totally, ten patients achieved CMR, and the overall CMR by PCR rate was 76.92%, while the MRDneg rate by flow cytometry was 100%. All patients with T315I mutations achieved CMR. Among patients with hematology relapse, the hematology remission rate and CMR rate reached both 100% after only one cycle of Olverembatinib involved regimen, including Olverembatinib + Blinatumomab, Olverembatinib + INO, respectively. For patients with persistent molecular diseases, eight patients achieved CMR. With respect to the different olverembatinib involving regimen, the CMR in olverembatinib+Venetoclax+ VP, olverembatinib+Blinatumomab, olverembatinib + INO, were 71.43%. 75% and 100%, respectively. The median regimen cycle times were 2 (range 1-3). All patients succeeded to bridge to allo-HSCT. With a median follow-up of 249（60-376）days post-HSCT, the estimated one-year overall survival (OS), and relapse-free survival (RFS) were 92.3±7.39% and 92.3±7.39%, respectively. One patient died of severe infection and CNS complications. Meanwhile, the Olverembatinib-based therapy was well tolerated. Only one patient reported gastrointestinal symptoms, such as nausea and vomiting. One patient complained about dizziness due to hypertension. No drug-related death or permanent discontinuation was reported due to toxicity. Conclusion This work suggests that Olverembatinib showed a profound response rate and was well tolerated in MRD clearance prior to allo-HSCT in Ph+ALL with disease recurrence and persistently MRD positive. Larger prospective studies are needed.

CMS121 Partially Attenuates Disease Progression in Mouse Models of Huntington's Disease.

There are currently no drugs that meaningfully slow down the progression of Huntington's disease (HD). Moreover, drug candidates against a single molecular target have not had significant success. Therefore, a different approach to HD drug discovery is needed. Previously we showed that the flavonol fisetin is efficacious in mouse and fly models of HD (Hum. Mol. Gen. 20:261, 2011). It is also effective in animal models of Alzheimer's disease (AD), ischemic stroke, and the CNS complications of diabetes, all of which share some pathological features with HD. Potent derivatives of fisetin with improved pharmacology were made that maintain its multiple biological activities (J. Med. Chem. 55:378, 2012). From 160 synthetic fisetin derivatives, one, CMS121, was selected for further study in the context of HD based on pharmacological parameters and its efficacy in animal models of AD. Both R6/2 and YAC128 mouse models of HD were used in these studies. We examined motor function using multiple assays as well as survival. In the R6/2 mice, we also looked at the effects of CMS121 on striatal gene expression. In both models, we found a slowing of motor dysfunction and an increase in median life span. Interestingly, in the YAC128 mice, the effects on the slowing in motor function loss became increasingly more pronounced as the mice aged. CMS121 also reduced HD-driven changes in the expression of genes associated with the proteasome and oxidative phosphorylation. Overall, these results suggest that CMS121 could provide some benefits for HD patients, particularly with regard to increasing health span.

Repurposing the in-house generated Alzheimer's disease targeting molecules through computational and preliminary in-vitro studies for the management of SARS-coronavirus-2.

Covid-19 was declared a world pandemic. Recent studies demonstrated that Covid-19 impairs CNS activity by crossing the blood-brain barrier and ensuing cognitive impairment. In this study, we have utilized Covid-19 main protease (Mpro) as a biological target to repurpose our previously reported multifunctional compounds targeting Alzheimer's disease. Molecular docking, spatial orientation, molecular dynamics simulation, MM-GBSA energy calculation, and DFT studies were carried out with these molecules. Among all the compounds, F27, F44, and F56 exhibited higher binding energy (-8.03, -8.65, and -8.68kcal/mol, respectively) over the co-crystal ligand O6K (-7.00kcal/mol). In MD simulation, compounds F27, F44, and F56 could make a stable complex with Mpro target throughout the simulation. The compounds were synthesized following reported methods and subjected for cytotoxicity, and assessment of their capability to cross the blood-brain barrier in PAMPA assay, and antioxidant property evaluation through DPPH assay. The compounds F27, F44, and F56 exhibited cytocompatibility with the SiHA cell line and also displayed significant antioxidant properties with IC50 = 45.80 ± 0.27μM, 44.42 ± 0.30μM, and 42.74 ± 0.23μM respectively. In the PAMPA assays, the permeability coefficient (Pe) value of F27, F44, and F56 lies in the acceptable range (Pe > 4). The results of the computational and preliminary in-vitro studies strongly corroborate the potential of F27, F44, and F56 as a lead for further optimization in treating the CNS complications associated with Covid-19.

Disruption of histone acetylation homeostasis triggers cognitive dysfunction in experimental diabetes

Epigenetic mechanisms related to diabetes-afflicted CNS complications are largely unknown. The present study investigated the role of histone acetylation mechanisms triggering cognitive dysfunction in the Type 1 and 2 diabetic mice model. Dynamic changes in diabetic parameters like fasting blood glucose levels, glucose tolerance test, and insulin levels were observed after the induction of diabetes. Cognitive performance was significantly diminished in T1D and T2D mice examined by the Morris water maze, novel object recognition test, and Y Maze as compared to controls. Histone profiling revealed a significant reduction in H3K9/14 and H4K12 acetylation in the cortex and hippocampus of T1D and T2D mice vs Controls. While histone deacetylase (HDAC) activity was significantly elevated in brain regions of T1D and T2D mice, the histone acetyltransferase (HAT) activity remain unchanged. Significantly increased HDAC 2, HDAC 3 protein and mRNA expression observed in T1D and T2D brain regions may corroborate for increased HDAC activity. No significant change was observed in protein and mRNA expression of HDAC 1, 5, 6, and 7 in diabetic brains. Reduced H3K9/14 and H4K12 acetylation paralleled transcriptional repression of memory-related markers BDNF, SYP, and PSD-95 in the cortex and hippocampus of T1D and T2D. Pharmacological inhibition of HDAC activity by Trichostatin A enhanced the cognitive changes observed in T1D and T2D by ameliorating BDNF, SYP, Psd-95. The present study provides a better insight into molecular mechanisms related to diabetes-dependent memory changes that can help to generate new advances for therapeutics to be developed in this area.

A Comparison of the Charlson and Elixhauser Methods for Predicting Nursing Indicators in Gastrectomy with Gastric Cancer Patients

Background: Comorbidity indices such as Charlson’s (CCI) and Elixhauser’s (ECI) are used to adjust the patient’s care, depending on the severity of their condition. However, no study has compared these indices’ ability to predict nursing-sensitive outcomes (NSOs). We compared the performance of CCI and ECI in predicting NSOs in gastric cancer patients’ gastrectomy. Methods: Gastric cancer patients with gastrectomy, aged 19 years or older and admitted between 2015 and 2016, were selected from the Korea Insurance Review and Assessment Service database. We examined the relationships between NSOs and CCI or ECI while adjusting patient and hospital characteristics with logistic regression. Results: The ECI item model was the best in view of the C-statistic and Akaike Information Criterion for total NSO, physiologic/metabolic derangement, and deep vein thrombosis, while the Charlson item model was the best for upper gastrointestinal tract bleeding. For the C-statistic, the ECI item model was the best for in-hospital mortality, CNS complications, shock/cardiac arrest, urinary tract infection, pulmonary failure, and wound infection, while the CCI item model was the best for hospital-acquired pneumonia and pressure ulcers. Conclusions: In predicting 8 of 11 NSOs, the ECI item model outperformed the others. For other NSOs, the best model varies between the ECI item and CCI item model.

A multicentric study on Clinical, microbiological and psychological aspects of human toxoplasmosis in pregnant women of South-East regions of India

Introduction: Serological tests based on the detection of specific IgG and IgM antibodies are the primary diagnostic methods for Toxoplasma infection. Prompt diagnosis of maternal seroconversion during pregnancy is necessary to prevent transmission to the foetus, by means of specific treatment, and also to permit close monitoring of at-risk foetuses and neonates. Material and Methods: This prospective multicentric study was conducted to evaluate the seroprevalence of T. gondii in humans and to determine various risk factors and psychiatry comorbidity associated with the disease. During the study, samples were collected from randomly selected pregnant women at various centres. Sera were sent to laboratory for antibody detection by ELISA. Proper history was recorded and psychiatry evaluation was done. Results: Most of patients belonged to 31-40 years (28.3%) followed by 21-30 years (21.6%), 41-50 years (18.3%) and least were belongs to 15-20 years (15%). Most of the patients showed Fever,Lymphadenopathy, Abdominal pain as presenting symptoms. In our study, women reported higher scores of somatizations, depression and phobic anxiety. Eating of raw or undercooked meat and inappropriately washed vegetables were identified as two important risk factors for maternal toxoplasmosis. Conclusion: Although most immunocompetent individuals infected with toxoplasmosis remain asymptomatic throughout life, this parasite can cause many complications in immunocompromised patients and in pregnant women. Newborns presenting with congenital toxoplasmosis can be asymptomatic but can also developretinochoroiditis and serious CNS complications. So, if women conceive, they should be educated regarding their eating habits and the value of good hygiene at the first visit for antenatal care. Health education for women of childbearing age is extremely important to prevent maternal toxoplasmosis.

Neuro-Psychological Outcome of ICU-Admitted COVID-19 Patients Presenting With CNS Complications.

Pelle, Juliette MD1; Nedelec, Thomas PhD2; Marois, Clémence MD1,3; on behalf of the Coco Neurosciences study group Collaborators Delorme, Cecile; Corvol, Jean-Christophe; Delattre, Jean-Yves; Carvalho, Stephanie; Sagnes, Sandrine; Dubois, Bruno; Navarro, Vincent; Louapre, Celine; Stojkovic, Tanya; Idbaih, Ahmed; Rosso, Charlotte; Grabli, David; Gales, Ana Zenovia; Millet, Bruno; Rohaut, Benjamin; Bayen, Eleonore; Dupont, Sophie; Bruneteau, Gaelle; Lehericy, Stephane; Seilhean, Danielle; Durr, Alexandra; Lamari, Foudil; Houot, Marion; Brochard, Vanessa Batista; Lubetzki, Catherine; Seilhean, Danielle; Pradat-Diehl, Pascale; Rosso, Charlotte; Hoang-Xuan, Khe; Fontaine, Bertrand; Naccache, Lionel; Fossati, Philippe; Arnulf, Isabelle; Durr, Alexandra; Carpentier, Alexandre; Edel, Yves; Robain, Gilberte; Thoumie, Philippe; Degos, Bertrand; Sharshar, Tarek; Alamowitch, Sonia; Apartis-Bourdieu, Emmanuelle; Peretti, Charles-Siegried; Ursu, Renata; Dzierzynski, Nathalie; Bourron, Kiyoka Kinugawa; Belmin, Joel; Oquendo, Bruno; Pautas, Eric; Verny, Marc; Samson, Yves; Leder, Sara; Leger, Anne; Deltour, Sandrine; Baronnet, Flore; Bombois, Stephanie; Touat, Mehdi; Idbaih, Ahmed; Sanson, Marc; Dehais, Caroline; Houillier, Caroline; Laigle-Donadey, Florence; Psimaras, Dimitri; Alenton, Agusti; Younan, Nadia; Villain, Nicolas; Grabli, David; del Mar Amador, Maria; Bruneteau, Gaelle; Louapre, Celine; Mariani, Louise-Laure; Mezouar, Nicolas; Mangone, Graziella; Meneret, Aurelie; Hartmann, Andreas; Tarrano, Clement; Bendetowicz, David; Pradat, Pierre-François; Baulac, Michel; Sambin, Sara; Pichit, Phintip; Chochon, Florence; Hesters, Adele; Herlin, Bastien; Nguyen, An Hung; Procher, Valerie; Demoule, Alexandre; Morawiec, Elise; Mayaux, Julien; Faure, Morgan; Ewenczyk, Claire; Coarelli, Giulia; Heinzmann, Anna; Stojkovic, Tanya; Masingue, Marion; Bassez, Guillaume; Navarro, Vincent; An, Isabelle; Worbe, Yulia; Lambrecq, Virginie; Debs, Rabab; Musat, Esteban Munoz; Lenglet, Timothee; Lambrecq, Virginie; Hanin, Aurelie; Chougar, Lydia; Shor, Nathalia; Pyatigorskaya, Nadya; Galanaud, Damien; Leclercq, Delphine; Demeret, Sophie; Rohaut, Benjamin; Cao, Albert; Marois, Clemence; Weiss, Nicolas; Gassama, Salimata; Guennec, Loic Le; Degos, Vincent; Jacquens, Alice; Similowski, Thomas; Morelot-Panzini, Capucine; Rotge, Jean-Yves; Saudreau, Bertrand; Millet, Bruno; Pitron, Victor; Sarni, Nassim; Girault, Nathalie; Maatoug, Redwan; Leu, Smaranda; Bayen, Eleonore; Thivard, Lionel; Mokhtari, Karima; Plu, Isabelle; Gonçalves, Bruno; Bottin, Laure; Yger, Marion; Ouvrard, Gaelle; Haddad, Rebecca; Ketz, Flora; Lafuente, Carmelo; Oasi, Christel; Megabarne, Bruno; Herve, Dominique; Salman, Haysam; Rametti-Lacroux, Armelle; Chalançon, Alize; Herve, Anais; Royer, Hugo; Beauzor, Florence; Maheo, Valentine; Laganot, Christelle; Minelli, Camille; Fekete, Aurelie; Grine, Abel; Biet, Marie; Hilab, Rania; Besnard, Aurore; Bouguerra, Meriem; Goudard, Gwen; Houairi, Saida; Al-Youssef, Saba; Pires, Christine; Oukhedouma, Anissa; Siuda-Krzywicka, Katarzyna; Malkinson, Tal Seidel; Agguini, Hanane; Said, Safia; Houot, Marion Author Information

Machine Learning Approaches to Understand Cognitive Phenotypes in People With HIV.

Cognitive disorders are prevalent in people with HIV (PWH) despite antiretroviral therapy. Given the heterogeneity of cognitive disorders in PWH in the current era and evidence that these disorders have different etiologies and risk factors, scientific rationale is growing for using data-driven models to identify biologically defined subtypes (biotypes) of these disorders. Here, we discuss the state of science using machine learning to understand cognitive phenotypes in PWH and their associated comorbidities, biological mechanisms, and risk factors. We also discuss methods, example applications, challenges, and what will be required from the field to successfully incorporate machine learning in research on cognitive disorders in PWH. These topics were discussed at the National Institute of Mental Health meeting on "Biotypes of CNS Complications in People Living with HIV" held in October 2021. These ongoing research initiatives seek to explain the heterogeneity of cognitive phenotypes in PWH and their associated biological mechanisms to facilitate clinical management and tailored interventions.

Encephalomyelitis in a patient with monkeypox: an unusual complication

A new outbreak of monkeypox has been reported worldwide with CNS complications like encephalitis or myelitis being extremely rare. We present a case of a 30-year-old man with PCR-confirmed diagnosis of monkeypox who developed rapid neurological deterioration with extensive inflammatory involvement of the brain and spinal cord on MRI. Because of the clinical and radiological resemblance to acute disseminated encephalomyelitis (ADEM), it was decided to indicate treatment with high-dose corticosteroids for 5 days (without concomitant antiviral management due to lack of availability in our country). Given the poor clinical and radiological response, 5 days of immunoglobulin G were administered. During follow-up the patient’s clinical condition improved, physiotherapy was started and all associated medical complications were controlled. To our knowledge, this is the first reported monkeypox case with severe CNS complications treated with steroids and immunoglobulin in the absence of specific antiviral treatment.

CNS Complications Following COVID-19 Vaccines: an Egyptian Case Series.

CNS Complications Following COVID-19 Vaccines: an Egyptian Case Series.

Review of first 60 pituitary adenoma cases of a skull base team, one center experience

Background: Endoscopic endonasal transsphenoid approach of pituitary gland is being effectively replacing microscopic approach. This approach need a lot of training and stepwise learning to reach perfection. This study discuss the experience and pitfalls of an evolving skull base team in one institute. Aim of the work: Analysis of first sixty pituitary adenomas patients operated by an evolving skull base teams in one institute, and highlighting modifications introduced in their technique. Methodology: This is a retrospective analytical study of the medical records of first 60 pituitary adenoma patients who had presented to one center and had endoscopic trans-nasal trans-sphenoidal approach by conjoined skull base team. Results: There were 60 cases of pituitary adenoma; 23 males, and 37 females. Mean age were 46 years old. 37 cases (61%) had temporal field defect, 22 cases had visual acuity loss, 41 patients (68%) had nonfunctioning adenomas, and 18% were prolactinomas. Fifty two cases (86.6%) were macroadenoma, and 2 patients (3.3%) were microadenoma. 48 cases (80%) had suprasellar extension, while 19 cases (19%) had parasellar extension. Three cases (5%) were recurrent. Trans-nasal cavity approach was adopted in 58 cases (96.6%). 4 cases needed middle turbinate resection. Mean operative time was 3 hours. Gross total removal of the tumor were achieved in 49 cases (81.6%). Intraoperative CSF leakage occurred in 31 patients (51%). Failure of reconstruction occurred in 4 cases (6.6%). Mean duration of hospital, and ICU stay was 8, 2 days respectively. Postoperative temporary diabetes insipidus occurred in 35 cases (58.3%), 5 of them (8.3%) had permanent DI. Major CNS complications occurred in 2 cases (3%). Conclusion: The more experience gained the more modifications introduced to improve surgical outcome; more gross total resection rate, less morbidity, and mortality rates, less operative time, better quality of life of patients and less time and effort exhaustion of the team work.

SARS-CoV-2 infection increases risk of intracranial hemorrhage.

SARS-CoV-2 virus infection causes a dysbalanced and severe inflammatory response, including hypercytokinemia and immunodepression. Systemic inflammation triggered by a viral infection can potentially cause vascular damage, which may lead to cardiovascular and neurovascular events. The aim was to investigate whether CNS complications are related to COVID-19. We examined 21 patients suffering from stroke and intracranial hemorrhage (ICH) and 9 (43%) of them were male. We compared relative frequencies using Fisher's exact test. As we had few observations and many variables, we used principal component analysis (PCA) to reduce data dimensionality. We trained a linear support vector machine (SVM) on the first two PCs of the laboratory data to predict COVID-19. Patients suffering from stroke had either hypertension or SARS-CoV-2 infection, but seldom both (OR = 0.05, p = 0.0075). The presence of SARS-CoV-2 infection was strongly associated with the logarithm of CRP (p = 1.4e-07) and with D-DIMER (p = 1.6e-05) and moderately with PT (p = 0.0024). SARS-CoV-2 infection was not related to any other factor. CRP, D-DIMER, PT, and INR were all related to each other (R 2 ranging from 0.19 to 0.52, p ranging from 0.012 to < 0.0001). The first two PCs covered 96% of the variance in the four variables. Using them, perfect linear discrimination between patients suffering from COVID-19 and other patients could be achieved. SARS-CoV-2 infection causes systemic inflammation, which is suggested as a predictor of the severe course of ICH. SARS-CoV-2 infection is an additional risk factor for vascular complications.

Timing of inpatient medical complications after adult spinal deformity surgery: early ambulation matters

BACKGROUNDThe substantial risk for medical complication after adult spinal deformity (ASD) surgery is well known. However, the timing of medical complications during the inpatient stay have not been previously described. Accurate anticipation of complications and adverse events may improve patient counseling and postoperative management. PURPOSE(1) Describe the rate of medical complication and adverse events by postoperative day after ASD surgery and (2) determine whether early ambulation is protective for complications. STUDY DESIGN/SETTINGSingle institution retrospective cohort study. PATIENT SAMPLETwo hundred thirty-five patients with ASD who underwent posterior-only fusion of the lumbar spine (≥5 levels to the pelvis) between 2013 and 2020. OUTCOME MEASURESMedical complications, categorized per the International Spine Study Group-AO system (cardiopulmonary [CP], gastrointestinal [GI], central nervous system [CNS], infectious [nonsurgical site], and renal) and adverse events (postoperative blood transfusion, urinary retention, and electrolyte abnormalities). METHODSPatients were identified from an institutional ASD database. Outcome measures were classified by the first postoperative day the event was recognized. Demographics, year of surgery, surgical factors, radiographic parameters, surgical invasiveness (ASD-S Index), frailty (Modified Frailty Index-5 [mFI-5]), Charlson Comorbidity Index (CCI), obstructive sleep apnea (OSA), smoking, preoperative opioid use, depression, and post-operative day of ambulation were assessed as risk factors for inpatient medical complications. RESULTSAfter exclusions of patients with incomplete medical chart data, 191 patients were available for analysis, mean age 66±10 y, BMI 28±5 kg/m2, PI-LL 24±20°, T1PA 28±13°. Inpatient medical complications occurred in 55 (28.8%) patients; adverse events occurred in 137 (71.7%). Length of stay was higher in patients with medical complications (mean 8.5±3.8 vs. 5.8±2.3 days, p<.001). However, for patients who had an adverse event, but no medical complication, LOS was comparable (p>.05). Most medical complications occurred by POD3 (58% of all complications). Risk (defined as the proportion of patients with that complication out of all inpatients that day) of CNS, CP, and GI complication peaked early in the postoperative course (CNS on POD1 [2.1% risk]; GI on POD2 [3.7%]; CP on POD3 [2.7%]). Risk for infectious and renal complications (infectious POD8 [2.7%]; renal POD7 [0.9%]) peaked later (Figure 1). On univariate analysis, patients with medical complications had higher rates of OSA (9.1% vs. 2.2%, p=.045), ASD-S (45.9 vs. 40.8, p=.04), max coronal cobb (46.9 vs. 36.7°, p=.003), ASA class (2.5 vs. 2.3, p=.01), and POD of ambulation (1.9 vs. 1.3, p=.01). On multivariate logistic regression (c-statistic 0.78), larger coronal cobb and later POD of ambulation were independent risk factors for complications (OR 1.04, 95% CI 1.01–1.07 and OR 2.3, 95% CI 1.2–4.7, respectively). CONCLUSIONSOur data may inform peri-operative management and patient expectations for hospitalization after ASD surgery. Early ambulation may reduce the risk of complications.