An Online Single-Session Cognitive Behavioral Therapy for Depression and Anxiety Associated with Multiple Sclerosis-Pilot Study.

Background: Multiple sclerosis (MS) is one of the most debilitating neurodegenerative diseases in youth, significantly affecting all life domains. Therefore, a strong association between MS, depression and anxiety symptoms has been established. The objective of the present interventional one-group pretest-posttest study is to assess the feasibility of an online single-session intervention (SSI) based on a cognitive behavioral therapy protocol targeting depressive and anxiety symptoms, psychological mechanisms, fatigue and overall health status. Methods: In this pilot study, 31 patients with MS (Mage = 42 years, SD = 12.2) received the online CBT SSI. The impact of the intervention was assessed using validated instruments two weeks after the intervention and after a two-month follow-up period. Results: Statistically significant effects were observed for the reduction of depression, with B = -7.58, 95% CI (-12.84, -2.31) and p < 0.01, and anxiety, with B = -15.17, 95% CI (-18.31, -12.02) and p < 0.001, at post-test and follow-up screening. Additionally, positive outcomes were seen for irrational beliefs at post-test, with B = -25.86, 95% CI (-46.10, -5.61), along with negative automatic thoughts, with B = -4.47, 95% CI (-10.65, 1.71), which were preserved at follow-up. Despite the health status also improving, no significant changes were observed for dysfunctional attitudes and fatigue. Conclusions: This research proves that the online CBT SSI was efficient for decreasing mild to moderate symptoms of depression and anxiety and reducing the intensity of dysfunctional psychological mechanisms in our sample.

The Path from Personality to Anxiety and Depression Is Mediated by Cognition in Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative immunological disease causing significant impairment in all life areas. Therefore, personality changes are observed and associated with higher prevalence of depression and anxiety disorders. Considering this relationship, we hypothesized that clinical symptoms and personality disorders are more prevalent in MS and that dysfunctional psychological mechanisms mediate the path from personality disorders to clinical symptoms. METHODS: The study sample consisted of 43 patients with MS (age M = 41.9, SD = 11.5) and 31 controls (age M = 39.8, SD = 10.3). Measures of personality, anxiety, depression, fatigue, health status, and dysfunctional psychological mechanisms were conducted. RESULTS: The prevalence of clinical symptoms was increased in MS patients as compared to controls. Also, dependent and schizoid personality traits (PTs) were observed in the patient sample. Negative automatic thoughts (NATs) were found to mediate the association between dependent PT and clinical symptoms. Along with schizoid PT, all dysfunctional psychological mechanisms impacted clinical symptoms. DISCUSSION: The results of our research are in line with previous studies showing that anxiety, depression, and dysfunctional personality traits are more prevalent in MS as compared to controls. CONCLUSIONS: PTs and dysfunctional psychological mechanisms predicted depression, anxiety, fatigue, and health status in MS patients. Cognition acts as a strong mediator between PTs and psychopathology in MS. Hence, integrative personalized psychological treatment is recommended to improve the quality of care in MS.

GFAP as Astrocyte-Derived Extracellular Vesicle Cargo in Acute Ischemic Stroke Patients-A Pilot Study.

The utility of serum glial fibrillary acidic protein (GFAP) in acute ischemic stroke (AIS) has been extensively studied in recent years. Here, we aimed to assess its potential role as a cargo protein of extracellular vesicles (EVs) secreted by astrocytes (ADEVs) in response to brain ischemia. Plasma samples from eighteen AIS patients at 24 h (D1), 7 days (D7), and one month (M1) post-symptoms onset, and nine age, sex, and cardiovascular risk factor-matched healthy controls were obtained to isolate EVs using the Exoquick ULTRA EV kit. Subsets of presumed ADEVs were identified further by the expression of the glutamate aspartate transporter (GLAST) as a specific marker of astrocytes with the Basic Exo-Flow Capture kit. Western blotting has tested the presence of GFAP in ADEV cargo. Post-stroke ADEV GFAP levels were elevated at D1 and D7 but not M1 compared to controls (p = 0.007, p = 0.019, and p = 0.344, respectively). Significant differences were highlighted in ADEV GFAP content at the three time points studied (n = 12, p = 0.027) and between D1 and M1 (z = 2.65, p = 0.023). A positive correlation was observed between the modified Rankin Scale (mRS) at D7 and ADEV GFAP at D1 (r = 0.58, p = 0.010) and D7 (r = 0.57, p = 0.013), respectively. ADEV GFAP may dynamically reflect changes during the first month post-ischemia. Profiling ADEVs from peripheral blood could provide a new way to assess the central nervous system pathology.

Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of motor neurons. Emerging evidence suggests a potential link between metabolic dysregulation and ALS pathogenesis. This study aimed to investigate the relationship between metabolic hormones and disease progression in ALS patients. A cross-sectional study was conducted involving 44 ALS patients recruited from a tertiary care center. Serum levels of insulin, total amylin, C-peptide, active ghrelin, GIP (gastric inhibitory peptide), GLP-1 active (glucagon-like peptide-1), glucagon, PYY (peptide YY), PP (pancreatic polypeptide), leptin, interleukin-6, MCP-1 (monocyte chemoattractant protein-1), and TNFα (tumor necrosis factor alpha) were measured, and correlations with ALSFRS-R, evolution scores, and biomarkers were analyzed using Spearman correlation coefficients. Subgroup analyses based on ALS subtypes, progression pattern of disease, and disease progression rate patterns were performed. Significant correlations were observed between metabolic hormones and ALS evolution scores. Insulin and amylin exhibited strong correlations with disease progression and clinical functional outcomes, with insulin showing particularly robust associations. Other hormones such as C-peptide, leptin, and GLP-1 also showed correlations with ALS progression and functional status. Subgroup analyses revealed differences in hormone levels based on sex and disease evolution patterns, with male patients showing higher amylin and glucagon levels. ALS patients with slower disease progression exhibited elevated levels of amylin and insulin. Our findings suggest a potential role for metabolic hormones in modulating ALS progression and functional outcomes. Further research is needed to elucidate the underlying mechanisms and explore the therapeutic implications of targeting metabolic pathways in ALS management.

A Potential Role of Interleukin-5 in the Pathogenesis and Progression of Amyotrophic Lateral Sclerosis: A New Molecular Perspective.

Cumulative data suggest that neuroinflammation plays a prominent role in amyotrophic lateral sclerosis (ALS) pathogenesis. The purpose of this work was to assess if patients with ALS present a specific peripheral cytokine profile and if it correlates with neurological disability assessed by ALSFRS-R, the rate of disease progression, and the pattern of disease progression (horizontal spreading [HSP] versus vertical spreading [VSP]). We determined the levels of 15 cytokines in the blood of 59 patients with ALS and 40 controls. We identified a positive correlation between levels of pro-inflammatory cytokines (interleukin [IL]-17F, IL-33, IL-31) and the age of ALS patients, as well as a positive correlation between IL-12p/70 and survival from ALS onset and ALS diagnosis. Additionally, there was a positive correlation between the ALSFRS-R score in the upper limb and respiratory domain and IL-5 levels. In our ALS cohort, the spreading pattern was 42% horizontal and 58% vertical, with patients with VSP showing a faster rate of ALS progression. Furthermore, we identified a negative correlation between IL-5 levels and the rate of disease progression, as well as a positive correlation between IL-5 and HSP of ALS. To the best of our knowledge, this is the first study reporting a "protective" role of IL-5 in ALS.

Characteristics of Developmental and Epileptic Encephalopathy Associated with PACS2 p.Glu209Lys Pathogenic Variant-Our Experience and Systematic Review of the Literature.

BACKGROUND: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of PACS2 gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published. METHODS: We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic PACS2 gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology. RESULTS: A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs' involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date. CONCLUSIONS: It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.

Sociodemographic and Clinical Determinants of Fatigue in Multiple Sclerosis.

Fatigue is the most common and disabling symptom in patients with multiple sclerosis (PwMS), representing one of the main determinants of reduced quality of life among PwMS due to its interference with social activities and work capacity. This study aimed to identify the sociodemographic determinants of fatigue in a cohort of 150 PwMS and 100 healthy controls (HCs). Fatigue was assessed using one of the most suitable and appropriate tools for measuring the degree of fatigue: the Modified Fatigue Impact Scale (MFIS). By comparing the median scores for the MFIS, we observed that the PwMS group had significantly higher MFIS scores than the HCs (p = 0.0001). In PwMS, MFIS scores correlated positively with age, total number of relapses, total disease duration, disability status, and Beck Depression Inventory-II score and negatively with cognitive performance. Patients with relapsing-remitting MS had significantly lower fatigue levels than those with secondary progressive MS (p = 0.0010). Fatigue levels were significantly lower among male than female PwMS (p = 0.0120). Other determinant factors of fatigue in our study proved to be the marital and occupational status, as well as the presence of children, but in a linear multivariate regressions analysis with MFIS score as the dependent variable, the fatigue levels were influenced only by sex, occupational status, marital status, children status, and BDI-II test results. Considering the significant impact of fatigue on the quality of life of PwMS, clinicians must diagnose fatigue as early as possible, identify its modifiable determinants, and manage it effectively to increase their quality of life.

The Occurrence of Acute Disseminated Encephalomyelitis in SARS-CoV-2 Infection/Vaccination: Our Experience and a Systematic Review of the Literature.

BACKGROUND: The neurological complications of coronavirus disease 2019 (COVID-19) infection and the side effects of vaccination include immune-mediated diseases of the central nervous system (CNS) such as acute disseminated encephalomyelitis (ADEM). It is an acute-onset demyelinating disease that involves a rapid evolution and multifocal neurological deficits that develops following a viral or bacterial infection or, less frequently, following vaccination. Acute hemorrhagic leukoencephalitis (AHLE) is the hemorrhagic variant of ADEM that presents a more severe evolution which can be followed by coma and death. The objectives of this study consist in evaluating the diagnosis, clinical characteristics, imaging and laboratory features, evolution, and treatment of ADEM and AHLE following COVID-19 infection or vaccination. METHODS: We performed a systematic review of the medical literature according to PRISMA guidelines that included ADEM cases published between 1 January 2020 and 30 November 2022 following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination and also included our own clinical experience regarding this pathology. RESULTS: A total number of 74 patients were diagnosed with ADEM, 45 following COVID-19 infection and 29 after a SARS-CoV-2 vaccine. A total of 13 patients (17.33%) presented AHLE. The moderate form of COVID-19 presented a positive correlation with AHLE (r = 0.691, p < 0.001). The existence of coma and AHLE was correlated with poor outcomes. The following more aggressive immunomodulatory therapies applied in severe cases were correlated with poor outcomes (major sequelae and death): therapeutic plasma exchange (TPE) treatment (r = 382, p = 0.01) and combined therapy with corticosteroids and TPE (r = 0.337, p = 0.03). CONCLUSIONS: Vaccinations are essential to reduce the spread of the COVID-19 pandemic, and the monitoring of adverse events is an important part of the strategic fight against SARS-CoV-2. The general benefits and the overall good evolution outweigh the risks, and prompt diagnosis is associated with a better prognosis in these patients.

Serum Fatty Acids Are Associated with a Higher Risk of Ischemic Stroke.

Stroke prevention, a significant public-health concern, begins with recognizing and addressing risk factors. Interventions targeted at modifiable risk factors can effectively prevent ischemic stroke, while Omega-3 fatty acids have been shown to improve stroke outcomes. Our study aimed to investigate the relationship between ischemic-stroke risk factors and fatty acids using a prospective observational study with 274 patients. We collected clinical data on risk factors and measured fatty-acid levels using high-performance liquid chromatography coupled with mass spectrometry. We found that several risk factors, including age, sex, smoking, atrial fibrillation, dyslipidemia, and previous stroke history, had a direct relationship with fatty acids. Of these, smoking had the most significant impact, negatively impacting levels of docosahexaenoic and eicosapentaenoic acid. Conversely, dyslipidemia and atrial fibrillation positively correlated with fatty acids, particularly in female patients and those with recurrent strokes. Age was found to directly correlate with other risk factors and variations in fatty-acid ratios. The stroke rate was higher in males than females before the age of 70, but this trend reversed. Our findings suggest that better management of risk factors, particularly modifiable lifestyle factors, could improve fatty-acid profiles and the balance of Omega-3 and Omega-6 in patients with ischemic stroke.

Quality of acute stroke care in Romania: Achievements and gaps between 2017 and 2022.

Romania has one of the highest incidences of stroke and one of the highest mortality rates in Europe. The mortality rate due to treatable causes is also very high and is associated with the lowest public spending on healthcare in the European Union. Nonetheless, significant achievements in acute stroke care have been made in Romania in the last 5 years, most notably the increase of the national thrombolysis rate from 0.8% to 5.4%. Numerous educational workshops and constant communication with the stroke centers led to a solid and active stroke network. Due to the joint efforts of this stroke network and the ESO-EAST project, the quality of stroke care has significantly improved. However, Romania still faces many problems: a major lack of specialists in interventional neuroradiology and consequently a low number of stroke patients treated by thrombectomy and carotid revascularization procedures, a low number of neuro-rehabilitation centers and a country-wide lack of neurologists.

Prognostic Factors of Survival in Glioblastoma Multiforme Patients-A Retrospective Study.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive brain tumor that occurs in adults. In spite of prompt diagnosis and rapidly administered treatment, the survival expectancy is tremendously poor. Extensive research has been performed in order to establish factors to predict the outcome of GBM patients; however, worldwide accepted prognostic markers are still lacking. METHODS: We retrospectively assessed all adult patients who were diagnosed with primary GBM and underwent surgical treatment during a three-year period (January 2017-December 2019) in the Neurosurgery Department of the Emergency Clinical County Hospital of Târgu Mureș, Romania. Our aim was to find any statistically relevant connections between clinical, imagistic, and histopathological characteristics and patients' survival. RESULTS: A total of 75 patients were eventually included in our statistical analysis: 40 males and 35 females, with a median age of 61 years. The mean tumor dimension was 45.28 ± 15.52 mm, while the mean survival rate was 4 ± 6.75 months. A univariate analysis demonstrated a statistically significant impact of tumor size, pre-, and postoperative KPSI on survival rate. In addition, a Cox multivariate assessment strengthened previous findings regarding postoperative KPSI (regression coefficient -0.03, HR 0.97, 95% CI (HR) 0.96-0.99, p = 0.002) as a favorable prognostic factor and GBM size (regression coefficient 0.03, HR 1.03, 95% CI (HR) 1.01-1.05, p = 0.005) as a poor prognostic marker for patients' survival. CONCLUSIONS: The results of our retrospective study are consistent with prior scientific results that provide evidence supporting the importance of clinical (quantified by KPSI) and imagistic (particularly tumor dimensions) features as reliable prognostic factors in GBM patients' survival.

Fatty Acids and Lipid Paradox-Neuroprotective Biomarkers in Ischemic Stroke.

Stroke is the primary cause of death and disability worldwide, with ischemic stroke up to 80% of the total cases. Lipid profile was established as a major risk factor for stroke, but recent studies show a paradoxical relationship between serum values and the outcome of stroke patients. Our study aims to analyze the impact of the classic extended lipid profile, including fatty acids as potential neuroprotective biomarkers for the outcome of ischemic stroke patients. We included 298 patients and collected clinical, paraclinical, and outcome parameters. We used a method consisting of high-performance liquid chromatography coupled with mass spectrometry to quantify serum fatty acids. We observed a negative correlation between National Institutes of Health Stroke Scale (NIHSS) at admission and total cholesterol (p = 0.040; r = -0.120), respectively triglycerides (p = 0.041; r = -0.122). The eicosapentaenoic to arachidonic acid ratio has a negative correlation, while the docosahexaenoic to eicosapentaenoic acid ratio positively correlates with all the prognostic parameters, showing a potential neuroprotective role for eicosapentaenoic acid in preventing severe ischemic stroke. The impact of the lipid profile paradox and the dependency relationship with the fatty acids represent a significant predictive factor for the functional and disability prognostic of ischemic stroke patients.

The Importance of Small Extracellular Vesicles in the Cerebral Metastatic Process.

Brain metastases represent more than 50% of all cerebral tumors encountered in clinical practice. Recently, there has been increased interest in the study of extracellular vesicles, and the knowledge about exosomes is constantly expanding. Exosomes are drivers for organotropic metastatic spread, playing important roles in the brain metastatic process by increasing the permeability of the blood-brain barrier and preparing the premetastatic niche. The promising results of the latest experimental studies raise the possibility of one day using exosomes for liquid biopsies or as drug carriers, contributing to early diagnosis and improving the efficacy of chemotherapy in patients with brain metastases. In this review, we attempted to summarize the latest knowledge about the role of exosomes in the brain metastatic process and future research directions for the use of exosomes in patients suffering from brain metastatic disease.

High-dose intravenous immunoglobulins as a therapeutic option in critical illness polyneuropathy accompanying SARS-CoV-2 infection: A case-based review of the literature (Review).

The still ongoing COVID-19 pandemic has exposed the medical community to a number of major challenges. A significant number of patients require admission to intensive care unit (ICU) services due to severe respiratory, thrombotic and septic complications and require long-term hospitalization. Neuromuscular weakness is a common complication in critically ill patients who are treated in ICUs and are mechanically ventilated. This complication is frequently caused by critical illness myopathy (CIM) or critical illness polyneuropathy (CIP) and leads to difficulty in weaning from the ventilator. It is thought to represent an important neurologic manifestation of the systemic inflammatory response syndrome (SIRS). COVID-19 infection is known to trigger strong immune dysregulation, with an intense cytokine storm, as a result, the frequency of CIP is expected to be higher in this setting. The mainstay in the diagnosis of this entity beside the high level of clinical awareness is the electrophysiological examination that provides evidence of axonal motor and sensory polyneuropathy. The present article presents the case of a 54-year-old woman with severe COVID 19 infection who developed neuromuscular weakness, which turned out to be secondary to CIP and was treated successfully with a high dose of human intravenous immunoglobulins. Related to this case, we reviewed the relevant literature data regarding the epidemiology, pathophysiology and clinical features of this important complication and discussed also the treatment options and prognosis.

Guillain-Barré syndrome associated with Covid-19: A close relationship or just a coincidence? (Review).

Several neurological complications affecting the central and peripheral nervous system were described secondary to COVID-19 infection such as hyposmia, headache, nausea, impaired consciousness, psychosis, neurocognitive syndromes and even cerebrovascular accidents. The mechanism of these complications is not fully understood, but heterogenous mechanisms such as cytokine storm, secondary hypercoagulability and direct neurotropism of the virus are thought to be involved. Guillain-Barré syndrome is a heterogeneous disease that frequently follows a bacterial or viral infection. During the ongoing SARS-CoV-2 pandemic, several isolated case reports and case series have suggested an association between this viral infection and the occurrence of Guillain-Barré syndrome. The main mechanism of Guillain-Barré syndrome is probably post-viral dysregulation of the immune system generated by SARS-CoV-2. The clinical characteristics and disease evolution seem to be similar to those observed in Guillain-Barré syndrome secondary to other etiologies. The aim of the present review is to summarize the relevant literature regarding SARS-CoV-2-related Guillain-Barré syndrome.

Dysfunction of the Neurovascular Unit in Ischemic Stroke: Highlights on microRNAs and Exosomes as Potential Biomarkers and Therapy.

Ischemic stroke is a damaging cerebral vascular disease associated with high disability and mortality rates worldwide. In spite of the continuous development of new diagnostic and prognostic methods, early detection and outcome prediction are often very difficult. The neurovascular unit (NVU) is a complex multicellular entity linking the interactions between neurons, glial cells, and brain vessels. Novel research has revealed that exosome-mediated transfer of microRNAs plays an important role in cell-to-cell communication and, thus, is integral in the multicellular crosstalk within the NVU. After a stroke, NVU homeostasis is altered, which induces the release of several potential biomarkers into the blood vessels. The addition of biological data representing all constituents of the NVU to clinical and neuroradiological findings can significantly advance stroke evaluation and prognosis. In this review, we present the current literature regarding the possible beneficial roles of exosomes derived from the components of the NVU and multipotent mesenchymal stem cells in preclinical studies of ischemic stroke. We also discuss the most relevant clinical trials on the diagnostic and prognostic roles of exosomes in stroke patients.