Inclusion body myositis, viral infections, and TDP-43: a narrative review.

The ubiquitous RNA-processing molecule TDP-43 is involved in neuromuscular diseases such as inclusion body myositis, a late-onset acquired inflammatory myopathy. TDP-43 solubility and function are disrupted in certain viral infections. Certain viruses, high viremia, co-infections, reactivation of latent viruses, and post-acute expansion of cytotoxic T cells may all contribute to inclusion body myositis, mainly in an age-shaped immune landscape. The virally induced senescent, interferon gamma-producing cytotoxic CD8+ T cells with increased inflammatory, and cytotoxic features are involved in the occurrence of inclusion body myositis in most such cases, in a genetically predisposed host. We discuss the putative mechanisms linking inclusion body myositis, TDP-43, and viral infections untangling the links between viruses, interferon, and neuromuscular degeneration could shed a light on the pathogenesis of the inclusion body myositis and other TDP-43-related neuromuscular diseases, with possible therapeutic implications.

The effect of multiple sclerosis therapy on gut microbiota dysbiosis: a longitudinal prospective study.

Gut microbiota has complex immune functions, related to different pathologies, including multiple sclerosis (MS).This study evaluated the influence of treatments on gut microbiota in people with MS (PwMS). The research comprised 60 participants, including 39 PwMS and 21 healthy controls (HC). Among the PwMS, 20 were prescribed a disease-modifying therapy (DMT), either interferon beta1a or teriflunomide, while 19 received a combination of classical DMT and an immunoglobulin Y (IgY) supplement. For each participant, two sets of gut samples were collected: one at the study's outset and another after two months. Alpha and beta diversity analyses revealed no significant differences between groups. In comparison to the HC, the MS group exhibited an increase in Prevotella stercorea and a decrease in Faecalibacterium prausnitzii. Following treatment, individuals with MS showed enrichment in Lachnospiraceae and Streptococcus. The second sample, compared to the first one, demonstrated an increase in Bifidobacterium angulatum and a decrease in Oscillospira for individuals with MS. Gut microbiota diversity in PwMS is not significantly different to HC.However, specific taxonomic changes indicate the presence of a dysbiosis state. The use of DMTs and immunoglobulin Y supplements may contribute to alterations in microbial composition, potentially leading to the restoration of a healthier microbiome.

Brain-Derived Neurotrophic Factor in Multiple Sclerosis Disability: A Prospective Study.

Multiple sclerosis (MS) is a demyelinating central nervous system disease that leads to neurological disability. Brain-derived neurotrophic factors (BDNFs) are neurotrophins involved in neurodegenerative disorders. This study analysed the relationship between serum BDNF, neurological disability and different MS treatments. We included 63 people with MS (PwMS), with relapsing-remitting MS or clinically isolated syndrome, and 16 healthy controls (HCs). We analysed the serum levels of BDNF and MS specific disability tests (Expanded Disability Status Scale, timed 25-foot walk test, nine-hole peg test), at baseline (V0) and after one year of interferon beta1a or teriflunomide treatment (V1). Baseline BDNF values were not different between the PwMS and HCs (p = 0.85). The BDNF levels were higher in PwMS vs. HCs after treatment (p = 0.003). BDNF was not related to last-year relapses or by the disease duration (all p > 0.05). The overall values for the PwMS decreased after one year (p < 0.001). Both treatments implied a similar reduction. BDNF was not related to neurological disability (p > 0.05). BDNF values were not influenced by the lesion burden, active lesions, or new lesions on MRI (p > 0.05). In our cohort, the PwMS had higher BDNF levels compared to the HCs after one year of treatment. BDNF was not related to clinical or paraclinical disease severity signs.

Dysbiosis in Multiple Sclerosis: Can Immunoglobulin Y Supplements Help?

The role of gut microbiota in autoimmune disorders like multiple sclerosis is gaining attention. Multiple sclerosis is characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Alterations in gut microbiota have been linked to multiple sclerosis development, with decreased beneficial bacteria and increased harmful species. The gut-brain axis is a complex interface influencing bidirectional interactions between the gut and the brain. Dysbiosis, an imbalance in gut microbiota, has been associated with autoimmune diseases. The influence of gut microbiota in multiple sclerosis is reversible, making it a potential therapeutic target. Probiotics, prebiotics, and fecal microbiota transplantation have shown promise in multiple sclerosis treatment, with positive effects on inflammation and immune regulation. Immunoglobulin Y (IgY) supplements derived from chicken egg yolk have potential as nutraceuticals or dietary supplements. IgY technology has been effective against various infections, and studies have highlighted its role in modulating gut microbiota and immune responses. Clinical trials using IgY supplements in multiple sclerosis are limited but have shown positive outcomes, including reduced symptoms, and altered immune responses. Future research directions involve understanding the mechanisms of IgY's interaction with gut microbiota, optimal dosage determination, and long-term safety assessments. Combining IgY therapy with other interventions and investigating correlations between microbiota changes and clinical outcomes are potential avenues for advancing multiple sclerosis treatment with IgY supplements.

Association between Acute and Chronic Inflammatory States: A Case-Control Study.

BACKGROUND: Fever is the hallmark of efficient acute inflammatory response, which may be disrupted in chronic inflammatory conditions. The "continuum theory" proposes that the return of acute inflammatory states with high fever predicts improvement in chronic diseases during treatment. Our objective was to investigate the observation made, during classical homeopathic treatment, that such an association exists between chronic inflammation and efficient acute inflammation. METHODS: In a case-control study, the reports of patients diagnosed with chronic inflammatory conditions with at least 6 months of follow-up under homeopathic treatment were retrospectively sampled from homeopathic medical practices from Greece, India, Romania and Russia. Twenty patients who improved under homeopathic treatment and 20 age-matched controls of those who did not improve were selected. The occurrence of common acute infectious diseases with fever during the follow-up period was investigated. RESULTS: The average age of the cases and controls was 28.4 (SD: 16.64) and 27.9 (SD: 17.19) years respectively. 18/20 cases and 4/20 controls developed common infectious diseases with fever. Cramer's V co-efficient value was found to be 0.551 (p < 0.01), indicating that improvement was more in patients with fever than without. Odds ratio of improving with respect to development of acute infectious diseases was 36.0 (95% CI: 5.8 to 223.5). The binary logistic regression model indicated significant contribution of occurrence of acute infections with fever as a predictor for improvement in chronic inflammatory disease. CONCLUSIONS: Classical homeopathic clinical observations indicate an association between chronic inflammatory status in the body and the ability to mount efficient acute inflammation. In this case-control study, the occurrence of common infections with fever during treatment heralded improvement in chronic inflammatory disease. Further powered studies are necessary to substantiate this finding.

Cognitive Dysfunction and Affective Mood Disorder Screening in Patients With Chronic Inflammatory Bowel Disease: Protocol for a Prospective Case-Control Study.

BACKGROUND: Mild cognitive impairment (MCI) and Alzheimer's disease (AD) might be more frequent in patients with inflammatory bowel disease (IBD), but the relationship between these 2 entities is yet to be entirely established. Certain blood biomarkers (eg, serum amyloid A [SAA] and serum homocysteine [Hcy], which increase in IBD and MCI; brain-derived neurotrophic factor [BDNF], which decreases in MCI and AD but is not clearly modified in IBD; and S100 calcium-binding protein B [S100B], which increases in the blood-brain barrier and neuronal lesions) might predict the stage of MCI or dementia or progression to a further state. The gut-brain axis (GBA) might be the key to the development of MCI in patients with IBD, along with systemic inflammation and the possible and unknown adverse effects of disease-modifying medication. OBJECTIVE: The aim of this study is to investigate whether GBA interactions play a role in MCI development in patients with IBD. METHODS: A case-control study will be conducted on at least 100 patients diagnosed with IBD, matched with 100 healthy individual controls. The matching will include sex, age, and education. Patients will be fully examined, and a full interview and a neurological and cognitive examination will be performed. The primary clinical outcomes will be cognitive test scores (Montreal Cognitive Assessment, Trail Making Test, Digit Symbol Substitution Test, forward and backward digit span testing). Depression, stress, and anxiety screening will also be performed. Blood samples from all participants will be collected, and aliquots will be immediately stored in a biobank. Primary laboratory outcomes will include serum levels of presumed cognitive dysfunction blood biomarkers SAA, Hcy, S100B, and BDNF. Follow-up will be performed at 12, 24, 36, and 48 months. RESULTS: Data collection started in December 2021 and is ongoing. So far, 53 patients with IBD have been recruited and 50 HC matched. Data collection should end in January 2030. Intermediary analysis will be performed in April 2024. We expect patients with IBD to have lower scores on cognitive testing and a positive correlation between disease length and cognitive impairment level. In addition, the levels of stress, anxiety, and depression should be higher in the IBD group. The serum levels of the 4 biomarkers could correlate or anticorrelate with cognitive scores and serve as predictive factors for MCI or dementia development. A higher level of education, a younger age, the absence of malabsorption, and good disease control might serve as protectors against MCI. CONCLUSIONS: GBA interactions, along with systemic inflammation and the adverse effects of medication, might be a cause of MCI and AD development in patients with IBD. Serum biomarkers could prove cheap and useful predictors of MCI development. TRIAL REGISTRATION: ClinicalTrials.gov NCT05760729; https://clinicaltrials.gov/study/NCT05760729. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50546.

Association among VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs11676382 polymorphisms and acute ischemic stroke.

Acute ischemic stroke is a major cause of morbidity and mortality worldwide, and genetic factors play a role in the risk of stroke. Single nucleotide polymorphisms (SNPs) in the VKORC1, CYP4F2, and GGCX genes have been linked to clinical outcomes, such as bleeding and cardiovascular diseases. This study aimed to investigate the association between specific polymorphisms in these genes and the risk of developing the first episode of acute ischemic stroke in patients without a known embolic source. This retrospective, cross-sectional, observational, analytical, case-control study included adult patients diagnosed with acute ischemic stroke. The SNPs in VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs11676382 genes were genotyped and analyzed together with the demographic and clinical factors of the 2 groups of patients. The presence of SNPs in VKORC1 or CYP4F2 genes significantly increased the risk of ischemic stroke in the context of smoking, arterial hypertension, and carotid plaque burden. The multivariate logistic model revealed that smoking (odds ratio [OR] = 3.920; P < .001), the presence of carotid plaques (OR = 2.661; P < .001) and low-density lipoprotein cholesterol values >77 mg/dL (OR = 2.574; P < .001) were independently associated with stroke. Polymorphisms in the VKORC1 and CYP4F2 genes may increase the risk of ischemic stroke in patients without a determined embolic source. Smoking, the presence of carotid plaques, and high low-density lipoprotein cholesterol levels were reconfirmed as important factors associated with ischemic stroke.

Serum levels of neurofilament light chains in pediatric multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis is a neuro-inflammatory disease that affects adults and children and causes somatic and cognitive symptoms. Diagnosis after the first clinical symptoms is challenging, involves laboratory and magnetic resonance imaging work-up and is often inconclusive unless subsequent clinical attacks occur. Neurofilament light chains are structural proteins within neurons. Levels of this marker in cerebrospinal fluid, plasma and serum are consistently higher in patients with an initial clinical demyelinating attack that later go on to develop multiple sclerosis. Evidence concerning serum levels of this biomarker in children with multiple sclerosis is scarce. Our aim is to review and analyze the evidence available for patients with multiple sclerosis, under the age of 18. METHODS: We conducted a systematic search of PubMed/Medline, Embase, Cochrane Database, and ProQuest. Human studies that provided data on serum levels of Neurofilament light chains in pediatric patients with MS, measured at the time of the first demyelinating attack and before treatment were included in meta-analysis. RESULTS: Three studies satisfied the inclusion criteria. 157 pediatric patients with multiple sclerosis and 270 hospital-based controls that did not present with this condition were included in the analysis. A fixed effects meta-analysis showed that the standardized mean difference between patients and controls is 1.82, with a 95% confidence interval of [1.56-2.08]. CONCLUSION: Pediatric patients with multiple sclerosis show higher levels of serum neurofilament light chains at their first clinical demyelinating attack compared to pediatric hospital-based controls.

The psychological impact of the COVID-19 pandemic on people with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that leads to neurological impairment and disability, mostly in young-aged people. Depression and anxiety are important associated mental disorders for people with MS (PwMS), which influence their life quality. During the COVID-19 pandemic, fear and stress levels enhanced dramatically for the general population, but mostly in progressive chronic pathologies such as MS. AIM: This study aimed to analyze the dynamic of psychological aspects in PwMS pre-pandemic and during pandemic, their connection with clinical outcomes, and with the coronavirus disease. METHODS: We included 95 PwMS with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS), who were first evaluated 4 years before the pandemic outbreak and the second time 2 years after. They completed a series of psychological tests for depression, anxiety, negative automatic thoughts, and stress: Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Endler Multidimensional Anxiety Scales (EMAS), Automatic Thoughts Questionnaire (ATQ). A neurologist evaluated the Expanded Disability Status Scale (EDSS) and a COVID-19 survey was completed by 78 patients. RESULTS: During the pandemic, depression was encountered in 9.47% of PwMS, only 1.05% with a severe form, and 6.3% with suicidal thoughts, while anxiety was more frequent (39% of cases). Compared to the pre-pandemic period, depression levels remained stable over time (p = 0.55), anxiety was reduced (p<0.001), and stress levels significantly increased (p = 0.001). Some social aspects, such as having sufficient income, reduced the risk for psychological comorbidities. There was a mild correlation between emotional well-being and neurological disability. Of all patients who responded to the survey, 53.84% had previous COVID-19 infections, no patient was hospitalized and 69.23% were vaccinated. There was no relationship between the COVID-19 infection and psychological test results. CONCLUSION: During the pandemic, in the MS population depression remained stable, anxiety decreased, and stress levels were enhanced compared to the pre-pandemic period. Psychiatric comorbidities were not influenced by the coronavirus infection.

The role of multiple sclerosis therapies on the dynamic of human gut microbiota.

Gut microbiota, the total microorganisms in our gastrointestinal tract, might have an implication in multiple sclerosis (MS), a demyelinating neurological disease. Our study included 50 MS patients and 21 healthy controls (HC). Twenty patients received a disease modifying therapy (DMT), interferon beta1a or teriflunomide, 19 DMT combined with homeopathy and 11 patients accepted only homeopathy. We collected in total 142 gut samples, two for each individual: at the study enrolment and eight weeks after treatment. We compared MS patients' microbiome with HC, we analysed its evolution in time and the effect of interferon beta1a, teriflunomide and homeopathy. There was no difference in alpha diversity, only two beta diversity results related to homeopathy. Compared to HC, untreated MS patients had a decrease of Actinobacteria, Bifidobacterium, Faecalibacterium prauznitzii and increased Prevotella stercorea, while treated patients presented lowered Ruminococcus and Clostridium. Compared to the initial sample, treated MS patients had a decrease of Lachnospiraceae and Ruminococcus and an increased Enterococcus faecalis. Eubacterium oxidoreducens was reduced after homeopathic treatment. The study revealed that MS patients may present dysbiosis. Treatment with interferon beta1a, teriflunomide or homeopathy implied several taxonomic changes. DMTs and homeopathy might influence the gut microbiota.

3D Ultrasound Reconstructions of the Carotid Artery and Thyroid Gland Using Artificial-Intelligence-Based Automatic Segmentation-Qualitative and Quantitative Evaluation of the Segmentation Results via Comparison with CT Angiography.

The aim of this study was to evaluate the feasibility of a noninvasive and low-operator-dependent imaging method for carotid-artery-stenosis diagnosis. A previously developed prototype for 3D ultrasound scans based on a standard ultrasound machine and a pose reading sensor was used for this study. Working in a 3D space and processing data using automatic segmentation lowers operator dependency. Additionally, ultrasound imaging is a noninvasive diagnosis method. Artificial intelligence (AI)-based automatic segmentation of the acquired data was performed for the reconstruction and visualization of the scanned area: the carotid artery wall, the carotid artery circulated lumen, soft plaque, and calcified plaque. A qualitative evaluation was conducted via comparing the US reconstruction results with the CT angiographies of healthy and carotid-artery-disease patients. The overall scores for the automated segmentation using the MultiResUNet model for all segmented classes in our study were 0.80 for the IoU and 0.94 for the Dice. The present study demonstrated the potential of the MultiResUNet-based model for 2D-ultrasound-image automated segmentation for atherosclerosis diagnosis purposes. Using 3D ultrasound reconstructions may help operators achieve better spatial orientation and evaluation of segmentation results.

Circadian Rhythm and Risk of Hemorrhagic Transformation after Acute Ischemic Stroke Treated with Intravenous Thrombolysis - A Systematic Review.

BACKGROUND: A circadian pattern for the onset of acute ischemic stroke (AIS) has been described, with a higher risk in the early morning and a lower risk during nighttime. However, data assessing the circadian distribution of hemorrhagic transformation after intravenous thrombolysis (ivT) are still incongruent. OBJECTIVES: This review aimed to evaluate whether the time interval based on AIS onset or ivT time could influence the occurrence of intracranial hemorrhage (ICH) related to ivT and if the circadian rhythm of endogenous production of tissue plasminogen activator (t-PA) favors ICH occurrence. METHODS: We conducted a systematic review following the PRISMA guidelines, searching PubMed and Embase for articles in English using the keywords: 'stroke', 'thrombolysis', and 'circadian'. Articles investigating the AIS onset or ivT time effects on circadian variations of ICH in AIS adult patients treated with ivT were included. Based on ICH's incidence and odds ratio, time intervals associated with higher risk and time intervals associated with lower risk were defined. The Newcastle-Ottawa Scale was used to assess the risk of bias. The resulting data were reported in a qualitative narrative synthesis. RESULTS: From the 70 abstracts returned by electronic literature search, six studies with 33,365 patients fulfilled the inclusion criteria, out of which three were retrospective analysis studies, one case-control study, one prospective study, and one post hoc analysis of a multicentre trial. Some studies assessed the relationship between ICH occurrence and circadian rhythm depending on AIS onset time (n = 2), treatment time (n = 2), or both (n = 4). All studies investigated the patients' comorbidities as confounding variables for the circadian pattern of symptomatic ICH (sICH). Two studies found no association between AIS onset or ivT time and patient risk factors, but the other four found several differences and used multivariate logistic regression models to balance these covariates. The overall score of the Newcastle- Ottawa scale was 83.3%, which might be interpreted as overall high quality. CONCLUSION: ICH occurred after ivT seems to follow a circadian pattern; the 18:00-00:00 time frame was the safest one, and patients with AIS onset or ivT time between these hours had the lowest incidence of any ICH, including sICH. The 06:00-12:00 block was associated with the highest incidence of ICH and sICH. However, the analysis is limited by the small number of included studies and the heterogeneous findings reported. Further homogenized studies using comparable time frames and sICH definitions are needed to demonstrate this circadian pattern. The review protocol was registered in the OSF database under reference UHNF, doi:10.17605/OSF.IO/UHNF6.

The impact of the COVID-19 pandemic on the mental health of patients diagnosed with inflammatory bowel diseases.

Understanding the profound impact of a viral pandemic on the mental health of patients with autoimmune diseases undergoing biological treatment is crucial for future insights. This cross-sectional case-control study aimed to assess the mental health implications of the COVID-19 pandemic on individuals with inflammatory bowel disease (IBD) in Romania, spanning from November 2022 to March 2023. A specialized self-report questionnaire in the Romanian language was developed to measure the multifaceted effects of COVID-19 on the mental well-being of these patients. The findings revealed a significant decline in the mental health of patients with IBD during the pandemic compared to the control group. Patients with IBD exhibited elevated levels of anxiety and concern regarding the virus. Intriguingly, despite the challenges, the vaccination rate was notably higher among patients with IBD, indicating a proactive approach to safeguarding their health. The study also shed light on various coping mechanisms employed by patients with IBD to navigate the pandemic-related restrictions. Engaging in activities such as social media and computer games emerged as effective strategies for managing heightened stress and limitations. In conclusion, the emergence of a novel viral pathogen represents a significant distress factor for patients with autoimmune diseases. Recognizing and comprehending these consequences enhances our understanding of the intricate interplay between physical and mental health and equips authorities with valuable insights to better manage future epidemics or viral outbreaks. This study underscores the importance of tailored support systems and strategies for patients with autoimmune diseases during global health crises.

Paraoxonase 1 and atrial fibrillation: Is there a relationship?

Atrial fibrillation (AF) is associated with oxidative stress and inflammation. Paraoxonase-1 (PON1), circulates in blood bound to high-density lipoproteins and reduces systemic oxidative stress. The aim of this study was to evaluate PON1 serum concentration and PON1 arylesterase activity (AREase) in patients with AF. We studied a group of 67 patients with symptomatic paroxysmal or persistent AF admitted for cardioversion and a control group of 59 patients without AF. Clinical parameters, lipid profile, PON1 concentration and AREase were evaluated. A significant difference in serum PON1 concentration and in AREase was found among the two groups. In a multivariate linear regression model, the presence of AF was associated with low PON1 concentration (P = .022). The body mass index was also independently associated with PON1 values (P < .001). Only the high-density lipoproteins-cholesterol level was independently associated with AREase (P = .002). PON1 serum concentrations and AREase were diminished in patients with AF, and the presence of AF was independently associated with low PON1 values.

Recent Advances on the Roles of PCSK-9 Inhibitors in the Management of Acute Ischemic Stroke Patients.

Acute ischemic stroke (AIS) represents an important cause of disability and death. Since only a minor percentage of patients with AIS are eligible for acute therapy, the management of risk factors is mandatory. An important risk factor of AIS is hyperlipemia. The current guidelines recommend a strict correction of it. Statins are recommended as the first-line treatment, while proprotein convertase subtilin/kexin type 9 (PCSK-9) inhibitors are administered as a second or even third option when the goal for a low-density lipoprotein cholesterol (LDL-C) level is not achieved. PCSK-9 inhibitors effectively decrease the LDL-C levels through the inhibition of PCSK-9-LDL-receptor complex formation. The in-depth understanding of the PCSK-9 protein mechanism in the metabolism of LDL-C led to the development of effective targeted approaches. Furthermore, a better understanding of the LDL-C metabolic pathway led to the development of newer approaches, which increased the therapeutic options. This article aims to offer an overview of the PCSK-9 inhibitors and their mechanism in reducing the LDL-C levels. Moreover, we will present the main indications of the current guidelines for patients with hyperlipemia and for those who have suffered an acute ischemic stroke, as well as the importance of LDL-C reduction in decreasing the rate of a recurrence.

The key role of the ophthalmologist in diagnosing botulism: two case reports.

Introduction: Botulinum toxin, the strongest known neurotoxin, is the cause of a rare fatal neuroparalytic disease characterized by the so-called "four Ds": diplopia, dysarthria, dysphagia, dry mouth. If left untreated, botulism may cause paralysis of the respiratory muscles, impairing the respiratory function which can ultimately lead to death. Case report: We describe the cases of two patients who presented, two years apart, with similar ocular symptoms such as blurred vision due to accommodation palsy, diplopia, accompanied by xerostomia and swallowing disorders, which were further confirmed as botulism. Both cases had a similar clinical presentation of the intoxication and a positive response to treatment with botulinum antitoxin, while only the first case had a laboratory confirmation of the disease. Conclusions: The key to diagnose botulism correctly is based on high clinical suspicion and requires a medical multidisciplinary approach and urgent specific treatment. Ophthalmology specialists must be aware of the disease, especially in cases in which ophthalmic manifestation appear at the onset.

N-Pep-12 supplementation after ischemic stroke positively impacts frequency domain QEEG.

BACKGROUND: N-Pep-12 is a dietary supplement with neuroprotective and pro-cognitive effects, as shown in experimental models and clinical studies on patients after ischemic stroke. We tested the hypothesis that N-Pep-12 influences quantitative electroencephalography (QEEG) parameters in patients with subacute to chronic supratentorial ischemic lesions. METHODS: We performed secondary data analysis on an exploratory clinical trial (ISRCTN10702895), assessing the efficacy and safety of 90 days of once-daily treatment with 90 mg N-Pep-12 on neurocognitive function and neurorecovery outcome in patients with post-stroke cognitive impairment against a control group. All participants performed two 32-channel QEEG in resting and active states at baseline (30-120 days after stroke) and 90 days later. Power spectral density on the alpha, beta, theta, delta frequency bands, delta/alpha power ratio (DAR), and (delta+theta)/(alpha+beta) ratio (DTABR) were computed and compared across study groups using means comparison and descriptive methods. Secondarily, associations between QEEG parameters and available neuropsychological tests were explored. RESULTS: Our analysis showed a statistically significant main effect of EEG segments (p<0.001) in alpha, beta, delta, theta, DA, and DTAB power spectral density. An interaction effect between EEG segments and time was noticed in the alpha power. There was a significant difference in theta spectral power between patients with N-Pep-12 supplementation versus placebo at 0.05 alpha level (p=0.023), independent of time points. CONCLUSION: A 90-day, 90 mg daily administration of N-Pep-12 had significant impact on some QEEG indicators in patients after supratentorial ischemic stroke, confirming possible enhancement of post-stroke neurorecovery. Further research is needed to consolidate our findings.

Neurological complications in COVID-19 - a diagnostic challenge.

With the exponential growth of COVID-19 cases, the neurological complications reported during or after the infection became more common. There is limited knowledge regarding the pathophysiological mechanisms that are responsible for these complications. Recent data provides compelling evidence for the neurotropic nature of SARS-CoV-2, based on neurological manifestations reported during the current pandemic, as well as on previous experience with other coronaviruses. We present the case of a patient who developed headaches, motor deficit and dysphasia after respiratory COVID-19. Imaging tests showed heterogeneous central nervous system lesions (multiple subarachnoid hemorrhages and two ischemic strokes). Given the plethora of atypical neurological complications of COVID-19 described in the current literature, establishing a positive diagnosis and deciding on a treatment plan proved to be particularly challenging. We set to discuss some of the possible pathologies, hypothesized to be associated with COVID-19, that could lead to concomitant neurological lesions, similar to those noticed in our patient.