Long-term Neurological Complications Research Articles

An ensemble-based machine learning model for predicting type 2 diabetes and its effect on bone health

BackgroundDiabetes is a chronic condition that can result in many long-term physiological, metabolic, and neurological complications. Therefore, early detection of diabetes would help to determine a proper diagnosis and treatment plan.MethodsIn this study, we employed machine learning (ML) based case-control study on a diabetic cohort size of 1000 participants form Qatar Biobank to predict diabetes using clinical and bone health indicators from Dual Energy X-ray Absorptiometry (DXA) machines. ML models were utilized to distinguish diabetes groups from non-diabetes controls. Recursive feature elimination (RFE) was leveraged to identify a subset of features to improve the performance of model. SHAP based analysis was used for the importance of features and support the explainability of the proposed model.ResultsEnsemble based models XGboost and RF achieved over 84% accuracy for detecting diabetes. After applying RFE, we selected only 20 features which improved the model accuracy to 87.2%. From a clinical standpoint, higher HDL-Cholesterol and Neutrophil levels were observed in the diabetic group, along with lower vitamin B12 and testosterone levels. Lower sodium levels were found in diabetics, potentially stemming from clinical factors including specific medications, hormonal imbalances, unmanaged diabetes. We believe Dapagliflozin prescriptions in Qatar were associated with decreased Gamma Glutamyltransferase and Aspartate Aminotransferase enzyme levels, confirming prior research. We observed that bone area, bone mineral content, and bone mineral density were slightly lower in the Diabetes group across almost all body parts, but the difference against the control group was not statistically significant except in T12, troch and trunk area. No significant negative impact of diabetes progression on bone health was observed over a period of 5-15 yrs in the cohort.ConclusionThis study recommends the inclusion of ML model which combines both DXA and clinical data for the early diagnosis of diabetes.

Brain exposure to SARS-CoV-2 virions perturbs synaptic homeostasis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with short- and long-term neurological complications. The variety of symptoms makes it difficult to unravel molecular mechanisms underlying neurological sequalae after coronavirus disease 2019 (COVID-19). Here we show that SARS-CoV-2 triggers the up-regulation of synaptic components and perturbs local electrical field potential. Using cerebral organoids, organotypic culture of human brain explants from individuals without COVID-19 and post-mortem brain samples from individuals with COVID-19, we find that neural cells are permissive to SARS-CoV-2 to a low extent. SARS-CoV-2 induces aberrant presynaptic morphology and increases expression of the synaptic components Bassoon, latrophilin-3 (LPHN3) and fibronectin leucine-rich transmembrane protein-3 (FLRT3). Furthermore, we find that LPHN3-agonist treatment with Stachel partially restored organoid electrical activity and reverted SARS-CoV-2-induced aberrant presynaptic morphology. Finally, we observe accumulation of relatively static virions at LPHN3-FLRT3 synapses, suggesting that local hindrance can contribute to synaptic perturbations. Together, our study provides molecular insights into SARS-CoV-2-brain interactions, which may contribute to COVID-19-related neurological disorders.

Neuropathic pain after orthopaedic surgery with continuous peripheral nerve block.

Continuous peripheral nerve blocks (cPNBs) have shown favourable post-operative pain control results but may be associated with a risk for long-term neurological complications. This study sought to examine factors associated with persistent post-operative pain and potential neuropathy after orthopaedic lower-limb surgery with the use of post-operative cPNB. Patients who underwent lower limb orthopaedic procedures with cPNBs between November 2021 to May 2022 were included. Patient demographics and perioperative data were noted. At discharge, patients completed the PainDetect (PD) questionnaire and were followed up six months after discharge. Seventy-seven patients with a total of 171 catheters completed the follow up. The median time to follow-up was 214 days after catheter removal, and 18 patients (23%) had a PD score ≥ 13. Univariate analysis showed that multiple variables were associated with a PD score ≥ 13 at the six-month follow-up. Multiple logistic regression showed that a high PD score at discharge, high BMI and longer duration of cPNBs were associated with higher risk of having a PD score ≥ 13 at the six-month follow-up. Several factors were associated with a higher risk of having possible neuropathy after six months. BMI, duration of catheter and PD score at discharge were correlated with risk of possible neuropathic pain. None. The study was a quality control project and therefore did not require registration under Danish law.

Neurological disorders with general overheating of the body (scientific and literary review)

Based on the understanding of the pathophysiology of heat stroke, it has been suggested that heat stroke can be considered as a form of hyperthermia that is associated with a systemic inflammatory response leading to a syndrome of multiple organ dysfunction in which encephalopathy predominates. Mechanisms of neuronal injury in heat stroke include: cellular effects (damage to membranes, mitochondria, and DNA, stimulation of excitotoxic mechanisms, protein denaturation), local effects (ischemia, inflammatory changes, edema, cytokine release, vascular damage), systemic effects (changes in cerebral blood flow, endotoxemia, translocation of bacteria through a dysfunctional gastrointestinal tract). Neurological manifestations of heat stroke develop in 3 stages according to the time of occurrence: acute, convalescent and late. In the acute stage, cerebral dysfunction prevails. Overheating of the body directly caused polyetiological cerebral dysfunction with deep suppression of consciousness in the acute stage; circulatory shock, hypoxia and cerebral ischemia, excessive accumulation of cytotoxic free radicals and oxidant brain damage developed. During the convalescence stage, cerebral dysfunction gradually decreases. This stage is characterized by transient cerebellar dysfunction. For the late stage, long-term neurological and cardiovascular complications with a constant risk of death are typical. When late stage with permanent neurologic deficits develop, cerebellar dysfunction is the most common symptom. The delayed onset of degeneration and deafferentation suggests that the syndrome is not caused by the primary lesion itself but may be a consequence of postsynaptic hypersensitivity or secondary reorganization of the involved pathways.

Neurologic Complications in Adult Cancer Survivorship.

Over the past decade, the improvement in cancer diagnostics and therapeutics has extended the overall survival of patients diagnosed with cancer including brain cancer. However, despite these unprecedented medical successes, patients continue to experience numerous neurologic complications after treatment that interfere with their independence, functionality, and overall quality of life. These include, among others, cognitive impairment, endocrinopathies, peripheral and cranial neuropathies, and vasculopathy. This article describes the long-term neurologic complications cancer survivors commonly experience to increase awareness of these complications and discuss treatments when available. Further research is necessary to understanding of mechanisms of neurologic injury and advance diagnosis and treatment. Effective patient education, monitoring, and managing neurologic issues after cancer treatment may improve independence, functionality, and quality of life during survivorship.

Brain Health After COVID-19, Pneumonia, Myocardial Infarction, or Critical Illness

Brain health is most likely compromised after hospitalization for COVID-19; however, long-term prospective investigations with matched control cohorts and face-to-face assessments are lacking. To assess whether long-term cognitive, psychiatric, or neurological complications among patients hospitalized for COVID-19 differ from those among patients hospitalized for other medical conditions of similar severity and from healthy controls. This prospective cohort study with matched controls was conducted at 2 academic hospitals in Copenhagen, Denmark. The case cohort comprised patients with COVID-19 hospitalized between March 1, 2020, and March 31, 2021. Control cohorts consisted of patients hospitalized for pneumonia, myocardial infarction, or non-COVID-19 intensive care-requiring illness between March 1, 2020, and June 30, 2021, and healthy age- and sex-matched individuals. The follow-up period was 18 months; participants were evaluated between November 1, 2021, and February 28, 2023. Hospitalization for COVID-19. The primary outcome was overall cognition, assessed by the Screen for Cognitive Impairment in Psychiatry (SCIP) and the Montreal Cognitive Assessment (MoCA). Secondary outcomes were executive function, anxiety, depressive symptoms, and neurological deficits. The study included 345 participants, including 120 patients with COVID-19 (mean [SD] age, 60.8 [14.4] years; 70 men [58.3%]), 125 hospitalized controls (mean [SD] age, 66.0 [12.0] years; 73 men [58.4%]), and 100 healthy controls (mean [SD] age, 62.9 [15.3] years; 46 men [46.0%]). Patients with COVID-19 had worse cognitive status than healthy controls (estimated mean SCIP score, 59.0 [95% CI, 56.9-61.2] vs 68.8 [95% CI, 66.2-71.5]; estimated mean MoCA score, 26.5 [95% CI, 26.0-27.0] vs 28.2 [95% CI, 27.8-28.6]), but not hospitalized controls (mean SCIP score, 61.6 [95% CI, 59.1-64.1]; mean MoCA score, 27.2 [95% CI, 26.8-27.7]). Patients with COVID-19 also performed worse than healthy controls during all other psychiatric and neurological assessments. However, except for executive dysfunction (Trail Making Test Part B; relative mean difference, 1.15 [95% CI, 1.01-1.31]), the brain health of patients with COVID-19 was not more impaired than among hospitalized control patients. These results remained consistent across various sensitivity analyses. This prospective cohort study suggests that post-COVID-19 brain health was impaired but, overall, no more than the brain health of patients from 3 non-COVID-19 cohorts of comparable disease severity. Long-term associations with brain health might not be specific to COVID-19 but associated with overall illness severity and hospitalization. This information is important for putting understandable concerns about brain health after COVID-19 into perspective.

Designing a Multiepitope Vaccine against Eastern Equine Encephalitis Virus: Immunoinformatics and Computational Approaches.

Eastern equine encephalitis virus (EEEV) is a significant threat to human and animal populations, causing severe encephalitis, often leading to long-term neurological complications and even mortality. Despite this, no approved antiviral treatments or EEEV human vaccines currently exist. In response, we utilized immunoinformatics and computational approaches to design a multiepitope vaccine candidate for EEEV. By screening the structural polyprotein of EEEV, we predicted both T-cell and linear B-cell epitopes. These epitopes underwent comprehensive evaluations for their antigenicity, toxicity, and allergenicity. From these evaluations, we selected ten epitopes highly suitable for vaccine design, which were connected with adjuvants using a stable linker. The resulting vaccine construct demonstrated exceptional antigenic, nontoxic, nonallergenic, and physicochemical properties. Subsequently, we employed molecular docking and molecular dynamics simulations to reveal a stable interaction pattern between the vaccine candidate and Toll-like receptor 5. Besides, computational immune simulations predicted the vaccine's capability to induce robust immune responses. Our study addresses the urgent need for effective EEEV preventive strategies and offers valuable insights for EEEV vaccine development. As EEEV poses a severe threat with potential spread due to climate change, our research provides a crucial step in enhancing public health defenses against this menacing zoonotic disease.

Long-term neurological implications of severe acute respiratory syndrome coronavirus 2 infections in neonates: Innate immune memory and chronic neuroinflammation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause long-term neurological complications in adults. However, the mechanisms by which early-life SARS-CoV-2 infection increases the risk of abnormal neurodevelopment remain unknown.Recent studies have shown an association with chronic proinflammatory cytokine/chemokine production in the central nervous system (CNS). Therefore, it was hypothesised that innate immune activation and induction of innate immune memory may play a potential role in the neonatal brain. Haematopoietic stem cells in the bone marrow are exposed to SARS-CoV-2, SARS-CoV-2 envelope protein (E protein), lipopolysaccharide (LPS)-bound spike proteins (S1 and S2 proteins), and damage-associated molecular patterns (DAMPs). Myeloid progenitors enter the stroma of the choroid plexus and are further directed to incessantly supply the brain parenchyma with resident innate immune cells. The S proteins-LPS complex can cross the blood–brain barrier and plays an important role in microglial and astrocytic inflammatory responses and innate immune memory. Persistently activated microglia with memory release pro-inflammatory cytokines/chemokines which contribute to abnormal synaptic development in the frontal lobe and cerebellum, potentially leading to long-term neurological complications, similar to those observed in autism spectrum disorder (ASD). In addition, this hypothesis suggests that bacterial and fungal products may act as adjuvants to S proteins and may also explain why S proteins alone are insufficient to induce neuroinflammation in neonates.

Coexistence of mutations of Gilbert’s syndrome and Crigler-Najjar syndrome in an infant with unconjugated hyperbilirubinemia—a case report

BackgroundJaundice in the newborn period is a very common entity; rare inherited causes are often forgotten. Persistent unconjugated hyperbilirubinemia in the intermediate levels with non-hemolytic features must prompt the necessity for evaluating for genetic defects in bilirubin metabolism.Case presentationThree-and-a-half-month-old first-born girl of consanguineous marriage presented with jaundice from day 5 of life. Dark yellow color urine or pale stools were not present. Antenatal and birth history was normal. She had mild pallor and icterus and no hepatosplenomegaly. Total serum bilirubin was 8.2 mg/dl, and direct was 0.4 mg/dl. Workup for hemolytic anemia, thyroid function test, and sonography of abdomen was normal. Syrup phenobarbitone was started, and bilirubin levels after dropped to 2 mg/dl. Crigler-Najjar type II syndrome (CN II) or Gilbert’s syndrome (GS) was suspected. Next-generation sequencing for UGT1A1 gene mutation showed homozygous missense mutation consistent with CN II and 7 TA repeats in the promoter region consistent with GS. Bilirubin levels gradually fell after starting oral phenobarbitone syrup, and at 5 years of age, a trial of withholding phenobarbitone was given, and bilirubin levels remained lower, and she is asked to follow-up with bilirubin levels every 15 days to assess the need for reintroducing the therapy. Parents are planning for a second pregnancy, and a preconception genetic counseling has been done.ConclusionGenetic confirmation of coexistence of mutations causing GS and CN II have an implication on long-term neurological complications of unconjugated hyperbilirubinemia in stress or crisis situations. Prenatal diagnostic testing must be advised for detecting homozygous UGT1A1 mutations to diagnose CN II and Gilbert mutations for each of the future pregnancies. Considering the side effects of long-term phenobarbitone therapy, the decision can be taken on case-to-case basis of stopping the therapy while monitoring TSB levels.

Cardiotocography, Hypoxia, and Feto-Neonatal Neurological Damage

Complications occurring at any level of fetal oxygen supply can result in hypoxemia, which may ultimately lead to hypoxia/acidosis and neurological damage. Hypoxic-ischemic encephalopathy (HIE) is the short-term neurological dysfunction caused by intrapartum hypoxia/acidosis. This diagnosis requires the presence of several findings, including confirmation of newborn metabolic acidosis, low Apgar scores, early imaging evidence of cerebral edema, and the appearance of clinical signs of neurological dysfunction in the first 48 hours of life. Cerebral palsy (CP) comprises a heterogeneous group of nonprogressive movement and posture disorders, often accompanied by cognitive and sensory impairments, epilepsy, nutritional deficiencies, and secondary musculoskeletal lesions. Although CP is the most common long-term neurological complication associated with intrapartum hypoxia/acidosis, over 80% of cases are caused by other factors. Data on minor long-term neurological deficits are limited, but they suggest that less severe intellectual and motor impairments may result from intrapartum hypoxia/acidosis. Birth asphyxia is a broad term referring to intrapartum asphyxia severe enough to cause neurological damage in some newborns and, rarely, intrapartum or neonatal death. Cerebral palsy and long-term neurological complications such as learning difficulties and motor impairments may have causes other than birth asphyxia. Several intrapartum events can lead to asphyxia (i.e., hypoxia and metabolic acidosis), increasing the likelihood of neurological injury. The cardiotocograph (CTG) is a screening tool used to assess fetal well-being during labor and to identify the possibility of asphyxia. An abnormal CTG, sometimes severe enough to be described as a pathological trace, is commonly referred to as “fetal distress”, although many fetuses with such traces may not have hypoxia and metabolic acidosis. In current practice, these events are appropriately termed “pathological CTG trace” or “acidotic pH” rather than “fetal distress”. Accurate interpretation of the CTG is essential, and it is important to recognize a fetus displaying a pathological CTG in labor, which may imply possible hypoxia and birth asphyxia. Considering the broader clinical context when interpreting the CTG and taking timely and appropriate action based on the findings may help prevent birth asphyxia.

Multi-omics reveal neuroprotection of Acer truncatum Bunge Seed extract on hypoxic-ischemia encephalopathy rats under high-altitude

Hypoxic-ischemic encephalopathy (HIE) at high-altitudes leads to neonatal mortality and long-term neurological complications without effective treatment. Acer truncatum Bunge Seed extract (ASO) is reported to have effect on cognitive improvement, but its molecular mechanisms on HIE are unclear. In this study, ASO administration contributed to reduced neuronal cell edema and improved motor ability in HIE rats at a simulated 4500-meter altitude. Transcriptomics and WGCNA analysis showed genes associated with lipid biosynthesis, redox homeostasis, neuronal growth, and synaptic plasticity regulated in the ASO group. Targeted and untargeted-lipidomics revealed decreased free fatty acids and increased phospholipids with favorable ω-3/ω-6/ω-9 fatty acid ratios, as well as reduced oxidized glycerophospholipids (OxGPs) in the ASO group. Combining multi-omics analysis demonstrated FA to FA-CoA, phospholipids metabolism, and lipid peroxidation were regulated by ASO treatment. Our results illuminated preliminary metabolism mechanism of ASO ingesting in rats, implying ASO administration as potential intervention strategy for HIE under high-altitude.

Neurological Manifestations in Hospitalized Geriatric Patients With COVID-19 at King Abdulaziz Medical City in Jeddah, Western Region, Saudi Arabia From 2020 to 2021: A Cross-Sectional Study.

Introduction COVID-19 involvement in the nervous system has been reported in many cases.Viral neuroinvasion has multiple routes of entry.Neurological manifestations of COVID-19 can be divided into ones of the central nervous system (CNS), such as headache, dizziness, altered mental status, ataxia, and seizure, and of theperipheral nervous system (PNS), including ageusia, anosmia, acute illness demyelinating polyneuropathy, and neuralgia. Aim and objectives This study aims to observe and report the neurological manifestations in geriatric patients who were diagnosed with COVID-19 at KAMC-J and report the duration of admission to the in-patient and ICU wards. Methods This was a cross-sectional study conducted on admitted geriatric patients with PCR-confirmed COVID-19 from April 1, 2020 to June 30, 2021 at KAMC-J. Using Raosoft®, the sample size was estimated with a CI of 95% and a 36.4%prevalence of neurological symptoms in COVID-19 patients to be 289. Convenience sampling was used, and the data were collected from BESTCare EMRs. IBMSPSSStatistics for Windows, Version 20 (Released 2011) was used for descriptive and inferential statistical analysis. Results In this study, a total of 290 patients' data were collected, 161 (55.5%) of which were males. In addition, the median age was 71 (Q1-Q3: 65-78) years; furthermore, the median body mass index (BMI) was 30(Q1-Q3: 25-34) kg/m2. In descending order, the most prevalent comorbidities were hypertension (HTN) (70.3%), diabetes mellitus (DM) (68.6%), cardiac disease (42.1%), chronic kidney disease(26.6%), neurological disease (23.6%), cancer malignancy (13.1%), and finally chronic respiratory disease (11.4%).Regarding typical COVID-19 manifestations, 181 patients claimed to have experienced cough(62.4%), dyspnea by 164 (56.7%), fever by 154 (53.5%), fatigue by 93 (32.3%), a reading of anoxia by 68 (23.4%), abdominal pain by 58 (20.0%), diarrhea by 56 (19.4%), and finally throat pain by 19 (6.6%). Manifestations and pathologies of the CNS included headache (25.4%), dizziness (21.5%), impaired consciousness (17.2%), delirium (6.6%), ischemic stroke (4.1%), focal cranial nerve dysfunction(2.8%), seizure (2.8%), intracerebral hemorrhage (ICH) (0.3%), and ataxia (0.3%). Moreover, pathologies of the PNS manifested as taste impairment in 46 patients (15.9%), smell impairment in 33 (11.4%), nerve pain in 7 (24%), visual impairment in 5 (1.7%), Bell's palsy in 2 (0.7%), and Guillain-Barre syndrome in 1 (0.3%). Moreover, the majority of patients who developed an ischemic stroke or ICH, or required admission to the ICU had either DM or HTN. In addition, 17 (25.4%) of the 67 patients admitted to the ICU developed impaired consciousness. All-cause mortality in our study was 31 (10.71%) cases. Conclusion Neurological manifestations of COVID-19 are common and can result in serious complications if not detected and managed early, especially in the elderly. These complications are mostly seen in severely ill patients and may be the only symptoms in COVID-19 patients. In addition,patients' clinical conditions could deteriorate rapidly and result in significant morbidity and mortality. Therefore, a high index of suspicion is required among healthcare providers when dealing with such cases. Moreover, we recommend systematically collecting data on the short- and long-term neurological complications of COVID-19 globally and documenting the functional long-term outcomes after these complications.

Clinical manifestations of peripheral vegetative insufficiency in children and adolescents with type 1 diabetes mellitus (retrospective and prospective investigations)

The variety of complications of type 1 diabetes mellitus (DM) in children and adolescents are often observed in clinical practice. Among them, damage to the central and peripheral nervous system prevails. The term «peripheral vegetative insufficiency» (PVI) refers to a complex of vegetative manifestations that occur in the peripheral (segmental) part of the VNS against the DM background.
 Objective — to determine the clinical typology of PVN in children with type 1 DM during the period of the years 1980—1990 (retrospective investigation) and in the period of the years 2012—2022 (prospective study).
 Materials and methods. The study was conducted on the basis of the Department of Endocrinology of the SI «Institute of Child and Adolescent Health of the NAMS of Ukraine». Examinations involved 605 pediatric patients: 285 patients (126 children and 159 adolescents) in the retrospective study, and 320 subjects (186 children and 134 adolescents) in the group of prospective study. All patients underwent somatic, neurological, and clinical examinations.
 Results and discussion. It haі been determined that in children and adolescents with type 1 diabetes mellitus, PVI clinical manifestations were present in all physiological body systems and often occur under the mask of various somatic diseases. The most typical PVI clinical syndromes in pediatric patients with DM included orthostatic hypotension, tachycardia at rest, hypohidrosis, gastroparesis, constipation, and urinary incontinence. The incidence of PVI syndromes in the groups of patients in the prospective study (years 2012-2022) was lower than in the retrospective study (years 1980—1990) owing to the use of the novel technologies for the DM treatment.
 Conclusions. The labile, severe course of type 1 diabetes mellitus in children often triggers the development of autonomic disorders, which are predictors and manifestations of neurological disorders. As the overall duration of the disease increases and carbohydrate metabolism is not compensated properly, the number of functional organic neurological complications increases. Damage to immature brain structures affects their further development and forms the basis for the long-term neurological complications in older age.

Long-term neurological complications in COVID-19 survivors: study protocol of a prospective cohort study (NeurodegCoV-19)

BackgroundEvidence suggests an association between SARS-CoV-2 infection and worse performance on cognitive tests, and a higher risk of Parkinson’s disease (PD) and dementia up to 6 and 12 months after...

Hyperglycaemic Metabolic Complications of Ischemic Brain: Current Therapeutics, Anti-Diabetics and Stem Cell Therapy.

Stroke is the leading cause of morbidity and mortality in diabetic patients. Diabetes alters the endothelial function and disrupts brain pathways, resulting in a variety of systemic metabolic complications. Diabetics not only have impaired neurotransmission, but also have progressive neurodegeneration, which leads to long-term neurological complications. Diabetes risk factors and physiology alter the frequency and severity of cardiovascular and cerebrovascular events, necessitating more hospitalizations. Stroke and diabetes have a mutually reinforcing relationship that worsens their outcomes. Diabetes has far-reaching systemic consequences for human physiology as a metabolic syndrome. As a result, diabetic stroke patients require dual-therapeutics with dual protection. Scientific researchers have made tremendous progress in diabetes-related stroke and its therapeutics over the last few decades. We have summarised diabetic brain and associated risk factors, co-morbidities, biomarkers, and hyperglycemia-associated neurovascular insult and cognitive demur. In addition to providing an overview of the effects of hyperglycaemia on brain physiology, this article aims to summarise the evidence from current glucose-lowering treatment, recent advances in stroke therapeutics as well as exploring stem cell therapy in the management of diabetes-associated stroke.

The thick-borne encephalitis caused by alimentary transmission - case series report.

Tick-borne encephalitis (TBE) is a central nervous system zoonotic disease transmitted by ticks. Tick-borne encephalitis virus (TBEV) is one of the main causes of lymphocytic meningitis in the areas of its endemic occurrence. A mode of transmission of TBEV which is rarely observed in clinical practice is an alimentary transmission through consumption of unpasteurised dairy products from infected animals. The following article contains detailed description of the clinical course of TBE among five family members, for whom the occurrence of TBE was temporarily associated with the consumption of unpasteurised goat's milk from the same source. The epidemiological outbreak presented in this article is the fifth ever described case of the milk-borne TBE in Poland. More so, the clinical course of the disease has shown differences from the typical course characterised so far in the literature. Clinical cases of TBE described in this study were similar to infections caused by tick bites in humans. The following article discusses available methods of preventing TBE, with emphasis on alimentary transmission of TBEV, since possibility of serious detrimental long-term neurological complications resulting from TBE was stressed in prior literature.

Out-of-hospital cardiac arrest: Do we have to perform coronary angiography?

Out-of-hospital cardiac arrest (OHCA) remains a leading cause of global mortality, while survivors are burdened with long-term neurological and cardiovascular complications. OHCA management at the hospital level remains challenging, due to heterogeneity of OHCA presentation, the critical status of OHCA patients reaching the return of spontaneous circulation (ROSC), and the demands of post ROSC treatment. The validity and optimal timing for coronary angiography is one important, yet not fully defined, component of OHCA management. Guidelines state clear recommendations for coronary angiography in OHCA patients with shockable rhythms, cardiogenic shock, or in patients with ST-segment elevation observed in electrocardiography after ROSC. However, there is no established consensus on the angiographic management in other clinical settings. While coronary angiography may accelerate the diagnostic and therapeutic process (provided OHCA was a consequence of coronary artery disease), it might come at the cost of impaired post-resuscitation care quality due to postponing of intensive care management. The aim of the current statement paper is to discuss clinical strategies for the management of OHCA including the stratification to invasive procedures and the rationale behind the risk-benefit ratio of coronary angiography, especially with patients in critical condition.

209 What Happens to Brain Outside the Thermal Ablation Zones? An Assessment of Needle-Based Therapeutic Ultrasound in Survival Swine

INTRODUCTION: For stereotactic radiosurgery, isodense lines must be considered to determine how surrounding tissue is affected. In thermal ablative therapy, such as laser interstitial thermal therapy (LITT) transcranial MR-guided focused ultrasound (tcMRgFUS) and needle-based therapeutic ultrasound (NBTU) how the surrounding area is effected has not been well studies in large animal models. METHODS: Four swine underwent MRgRA NBTU using varying treatment doses. Neurological evaluation of swine was performed up to 30 days post-procedure. Serial MRI images were obtained, and the most representative were overlaid with isodose lines and compared to brain tissue acquired post-mortem which underwent histopathologic analysis. These results were also compared to predicted volumes using a finite element analysis (FEA). RESULTS: NBTU applicator orientation at 360° induced smaller lesion volumes (33.19 mm3; 120 s, 3 W; 30.05 mm3, 180 s, 4 W) versus 180o (77.20 mm3, 120 s, 3 W; 109.29 mm3; 180 s; 4 W). The ablation-zone was characterized by dense macrophage infiltration and glial/neuronal loss as demonstrated by glial fibrillary acidic protein (GFAP) and neurofilament (NF) absence and avid CD163 staining. The transition-zone between lesion and normal brain demonstrated decreased macrophage infiltration and measured ∼345 microns. None of the experimental swine suffered any long-term neurologic or behavioral complications. MRTI/histology overlay demonstrated the boundary of ablation at ∼200 (cumulative equivalent minutes) CEM43 isodose boundary. CONCLUSIONS: We successfully performed MRgRA NBTU ablation in swine and demonstrated minimal histologic changes extended past the ablation-zone. The lesion was characterized by macrophage infiltration and glial/neuronal loss which decreased through the transition-zone. Whether NBTU offers advantage over tcMRgFUS and LITT in this regard warrants further study.

An eye to the future: Acute and long-term neuro-ophthalmological and neurological complications of COVID-19.

COVID-19 has had a significant impact on the global population and has produced compelling evidence of non-pulmonary organ dysfunction, including the nervous system. It is vital that specialists in ophthalmology and neurology are informed of the potential complications of COVID-19 and gain a deeper understanding of how COVID-19 can cause diseases of the nervous system. In this review we detail four possible mechanisms by which COVID-19 infection may result in neurological or neuro-ophthalmological complications: (1) Toxic and metabolic effects of severe pulmonary COVID-19 disease on the neural axis including hypoxia and the systemic hyper-inflammatory state, (2) endothelial dysfunction, (3) dysimmune responses directed again the neuroaxis, and (4) direct neuro-invasion and injury by the virus itself. We explore the pathological evidence for each of these and how they may link to neuro-ophthalmological disorders. Finally, we explore the evidence for long-term neurological and neuro-ophthalmological complications of COVID-19, with a focus on neurodegeneration.

Potential of Nano-Antioxidants and Nanomedicine for Recovery from Neurological Disorders Linked to Long COVID Syndrome.

Long-term neurological complications, persisting in patients who cannot fully recover several months after severe SARS-CoV-2 coronavirus infection, are referred to as neurological sequelae of the long COVID syndrome. Among the numerous clinical post-acute COVID-19 symptoms, neurological and psychiatric manifestations comprise prolonged fatigue, "brain fog", memory deficits, headache, ageusia, anosmia, myalgias, cognitive impairments, anxiety, and depression lasting several months. Considering that neurons are highly vulnerable to inflammatory and oxidative stress damages following the overproduction of reactive oxygen species (ROS), neuroinflammation and oxidative stress have been suggested to dominate the pathophysiological mechanisms of the long COVID syndrome. It is emphasized that mitochondrial dysfunction and oxidative stress damages are crucial for the pathogenesis of neurodegenerative disorders. Importantly, antioxidant therapies have the potential to slow down and prevent disease progression. However, many antioxidant compounds display low bioavailability, instability, and transport to targeted tissues, limiting their clinical applications. Various nanocarrier types, e.g., liposomes, cubosomes, solid lipid nanoparticles, micelles, dendrimers, carbon-based nanostructures, nanoceria, and other inorganic nanoparticles, can be employed to enhance antioxidant bioavailability. Here, we highlight the potential of phytochemical antioxidants and other neuroprotective agents (curcumin, quercetin, vitamins C, E and D, melatonin, rosmarinic acid, N-acetylcysteine, and Ginkgo Biloba derivatives) in therapeutic strategies for neuroregeneration. A particular focus is given to the beneficial role of nanoparticle-mediated drug-delivery systems in addressing the challenges of antioxidants for managing and preventing neurological disorders as factors of long COVID sequelae.