Search

Abstract Background Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. Results In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e’), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF

Abstract Pulmonary hypertension (PH) is a progressive and invalidating condition despite available therapy. Addressing complications such as left main coronary artery compression (LMCo) due to the dilated pulmonary artery (PA) may improve symptoms and survival. Nevertheless, clear recommendations are lacking. The aim of this study is to analyze the prevalence, characteristics, predictive factors and impact of LMCo in a heterogenous precapillary PH population in a single referral center. Two hundred sixty‐five adults with various etiologies of precapillary PH at catheterization were reviewed. Coronary angiography (CA) was performed for LMCo suspicion. Revascularization was performed in selected cases. Outcomes were assessed at a mean follow‐up of 3.9 years. LMCo was suspected in 125 patients and confirmed in 39 (31.2%), of whom 21 (16.8%) had 50%–90% stenoses. Nine revascularizations were performed, with clinical improvement. The only periprocedural complication was a stent migration. LMCo was associated with PH etiology (p 0.003), occuring more frequently in congenital heart disease‐associated PH (61.5% of all LMCo cases, 66.6% of LMCo ≥ 50%). Predictors of LMCo ≥50% were PA ≥ 37.5 mm (Sn 81%, Sp 74%) and PA‐to‐aorta ≥1.24 (Sn 81%, Sp 69%), with increased discrimination when considering RV end‐diastolic area. LMCo ≥ 50% without revascularization presented clinical deterioration and worse survival (p 0.019). This analysis of a heterogeneous pre‐capillary PH population provides LMCo prevalence estimation, predictive factors (PA size, PA‐to‐aorta, RV end‐diastolic area and PH etiology) and long‐term impact. While LMCo impact on survival is inconclusive, untreated LMCo ≥ 50% has worse prognosis. LMCo revascularization may be performed safely and with good outcomes.

Este consenso de nomenclatura y clasificación para la válvula aórtica bicúspide congénita y su aortopatía está basado en la evidencia y destinado a ser utilizado universalmente por médicos (tanto pediatras como de adultos), médicos ecocardiografistas, especialistas en imágenes avanzadas cardiovasculares, cardiólogos intervencionistas, cirujanos cardiovasculares, patólogos, genetistas e investigadores que abarcan estas áreas de investigación clínica y básica. Siempre y cuando se disponga de nueva investigación clave y de referencia, este consenso internacional puede estar sujeto a cambios de acuerdo con datos basados en la evidencia1.

Immunosenescence, the gradual deterioration of immune function with age, holds profound implications for our understanding and management of multiple sclerosis (MS), a chronic autoimmune disease affecting the central nervous system. Traditionally diagnosed in young adults, advancements in disease-modifying therapies and increased life expectancy have led to a growing number of older individuals with MS. This demographic shift underscores the need for a deeper investigation into how age-related alterations in immune function shape the course of MS, influencing disease progression, treatment effectiveness, and overall patient outcomes. Age-related immunosenescence involves changes such as shifts in cytokine profiles, the accumulation of senescent immune cells, and compromised immune surveillance, collectively contributing to a state known as “inflammaging”. In the context of MS, these immunological changes disturb the intricate balance between inflammatory and regulatory responses, thereby impacting mechanisms of central immune tolerance and peripheral regulation. This paper stands out by combining the most recent advancements in immunosenescence with both pathophysiological and treatment perspectives on multiple sclerosis, offering a cohesive and accessible discussion that bridges theory and practice, while also introducing novel insights into underexplored concepts such as therapy discontinuation and the latest senolytic, neuroprotective, and remyelination therapies. Enhancing our understanding of these complexities will guide tailored approaches to MS management, ultimately improving clinical outcomes for affected individuals.

BackgroundPatent foramen ovale (PFO) is a prevalent cardiac remnant of fetal anatomy that may pose a risk factor for stroke in some patients, while others can present with asymptomatic white matter (WM) lesions. The current study aimed to test the hypothesis that patients with a PFO who have a history of stroke or transient ischemic attack, compared to those without such a history, have a different burden and distribution of cerebral WM hyperintensities. Additionally, we tested the association between PFO morphological characteristics and severity of shunt, and their impact on the occurrence of ischemic cerebral vascular events and on the burden of cerebral WM lesions.Patients and methodsRetrospective, case–control study that included patients with PFO confirmed by transesophageal echocardiography. Right-to-left shunt size was assessed using transcranial Doppler ultrasound. Cerebral MRIs were analyzed for all participants using the semi-automated Quantib NDTM software for the objective quantification of WM lesions. WM lesions volume was compared between patients with and without a history of stroke. Additionally, the anatomical characteristics of PFOs were assessed to explore their relation to stroke occurrence and WM lesions volume.ResultsOf the initial 264 patients diagnosed with PFO, 67 met the inclusion criteria and were included in the analysis. Of them, 62% had a history of PFO-related stroke/TIA. Overall burden of WM lesions, including stroke volume, was not significantly different (p = 0.103). However, after excluding stroke volume, WM lesions volume was significantly higher in patients without stroke (0.27 cm3, IQR 0.03–0.60) compared to those with stroke/TIA (0.08 cm3, IQR 0.02–0.18), p = 0.019. Patients with a history of PFO-related stroke/TIA had a tendency to larger PFO sizes by comparison to those without, in terms of length and height, and exhibited greater right-to-left shunt volumes.DiscussionWe suggest that PFO may be associated with the development of two distinct cerebrovascular conditions (stroke and “silent” WM lesions), each characterized by unique imaging patterns. Further studies are needed to identify better the “at-risk” PFOs and gain deeper insights into their clinical implications.

Background/Objectives: Dystonia is a neurological movement disorder characterized by involuntary muscle contractions that lead to abnormal movements and postures; it has a major impact on patients’ health-related quality of life (HRQoL). The aim of this study was to examine the HRQoL of Romanian patients with dystonia using the EQ-5D-5L instrument. Methods: Responses to the EQ-5D-5L and the visual analogue scale (VAS) were collected alongside demographic and clinical characteristics. Health profiles were analyzed via the metrics of the EQ-5D-5L, severity levels, and age groups. Using Shannon’s indexes, we calculated informativity both for patients’ health profile as a whole and each individual dimension. Level sum scores (LSS) of the EQ-5D-5L were calculated and compared with scores from the EQ-5D-5L index and VAS. The HRQoL measures were analyzed through demographic and clinical characteristics. Descriptive statistics, Spearman correlation, and non-parametric tests (Mann–Whitney U or Kruskall–Wallis H) were used. The level of agreement between HRQoL measures was assessed using their intraclass correlation coefficient (ICC) and Bland–Altman plots. Results: A sample of 90 patients was used, around 75.6% of whom were female patients, and the mean age at the beginning of the survey was 58.7 years. The proportion of patients reporting “no problems” in all five dimensions was 10%. The highest frequency reported was “no problems” in self-care (66%), followed by “no problems” in mobility (41%). Shannon index and Shannon evenness index values showed higher informativity for pain/discomfort (2.07 and 0.89, respectively) and minimal informativity for self-care (1.59 and 0.68, respectively). The mean EQ-5D-5L index, LSS, and VAS scores were 0.74 (SD = 0.26), 0.70 (SD = 0.24), and 0.61 (SD = 0.21), respectively. The Spearman correlations between HRQoL measures were higher than 0.60. The agreement between the EQ-5D-5L index and LSS values was excellent (ICC = 0.970, 95% CI = 0.934–0.984); the agreement was poor-to-good between the EQ-5D-5L index and VAS scores (ICC = 683, 95% CI = 0.388–0.820), and moderate-to-good between the LSS and VAS scores (ICC = 0.789, 95% CI = 0.593–0.862). Conclusions: Our results support the utilization of the EQ-5D-5L instrument in assessing the HRQoL of dystonia patients, and empirical results suggest that the EQ-5D-5L index and LSS measure may be used interchangeably. The findings from this study highlight that HRQoL is complex in patients with dystonia, particularly across different age groups.

Abstract Background Fluid overload and venous congestion are associated with morbi-mortality in the ICU (intensive care unit). Administration of diuretics to correct the fluid balance is common, although there is no strong relationship between the consequent fluid loss and clinical improvement. The aim of the study was to evaluate the ability of the portal pulsatility index, the renal venous impedance index, and the VEXUS score (venous ultrasound congestion score) to predict appropriate diuretic-induced fluid depletion. Methods The study had a prospective, observational, single-center observational design and was conducted in a university-affiliated medico-surgical ICU. Adult patients for whom the clinician decided to introduce loop diuretic treatment were included. Hemodynamic and ultrasound measurements (including the portal pulsatility index, renal venous impedance index and VEXUS score) were performed at inclusion and 2 hours after the initiation of the diuretics. The patients’ characteristics were noted at inclusion, 24 h later, and at ICU discharge. The appropriate diuretic-induced fluid depletion was defined by a congestive score lower than 3 after diuretic fluid depletion. The congestive score included clinical and biological parameters of congestion. Results Eighty-one patients were included, and 43 (53%) patients presented with clinically significant congestion score at inclusion. Thirty-four patients (42%) had an appropriate response to diuretic-induced fluid depletion. None of the left- and right-sided echocardiographic parameters differed between the two groups. The baseline portal pulsatility index was the best predictor of appropriate response to diuretic-induced fluid depletion (AUC = 0.80, CI95%:0.70–0.92, p = 0.001), followed by the renal venous impedance index (AUC = 0.72, CI95% 0.61–0.84, p = 0.001). The baseline VEXUS score (AUC of 0.66 CI95% 0.53–0.79, p = 0.012) was poorly predictive of appropriate response to diuretic-induced fluid depletion. Conclusion The portal pulsatility index and the renal venous impedance index were predictive of the appropriate response to diuretic-induced fluid depletion in ICU patients. The portal pulsatility index should be evaluated in future randomized studies.

Burning Mouth Syndrome (BMS) is a chronic condition characterized by a burning sensation in the oral mucosa, lasting more than 2 hours daily for more than 3 months, without clinical and/or laboratory evidence. BMS is often comorbid with mood, and psychiatric disorders, and a complex pathophysiology and interaction between impairments in nociceptive processing and psychologic function is occurring. In this work, we aimed to define the neuropsychological profile specific for BMS patients for a better management of this complex disease. We conducted a case–control study comparing 120 BMS patients and 110 non-BMS individuals (CTRL). Sociodemographic data and lifestyle habits, were collected, along with data regarding quality of life (SF-36 scale), stress (PSS), depression and anxiety (MADRS and HADS scales), sleep quality (PSQI scale), and cognitive functions (MoCA, SVF and PVF tests). The statistical analysis revealed a lower general quality of life (p

IntroductionRight ventricular (RV) dysfunction and pulmonary hypertension (PH) have been previously associated with unfavorable outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI), but little is known about the effect of right ventricle (RV) to pulmonary artery (PA) coupling. Our study aimed to evaluate the determinant factors and the prognostic value of RV-PA coupling in patients undergoing TAVI.MethodsOne hundred sixty consecutive patients with severe AS were prospectively enrolled, between September 2018 and May 2020. They underwent a comprehensive echocardiogram before and 30 days after TAVI, including speckle tracking echocardiography (STE) for myocardial deformation analysis of the left ventricle (LV), left atrium (LA), and RV function. Complete data on myocardial deformation was available in 132 patients (76.6 ± 7.5 years, 52.5% men) who formed the final study population. The ratio of RV free wall longitudinal strain (RV-FWLS) to PA systolic pressure (PASP) was used as an estimate of RV-PA coupling. Patients were analyzed according to baseline RV-FWLS/PASP cut-off point, determined through time-dependent ROC curve analysis, as follows: normal RV-PA coupling group (RV-FWLS/PASP ≥0.63, n = 65) and impaired RV-PA coupling group (RV-FWLS/PASP

Alzheimer’s disease is a neurodegenerative condition marked by the progressive deterioration of cognitive abilities, memory impairment, and the accumulation of abnormal proteins, specifically beta-amyloid plaques and tau tangles, within the brain. Despite extensive research efforts, Alzheimer’s disease remains without a cure, presenting a significant global healthcare challenge. Recently, there has been an increased focus on antibody-based treatments as a potentially effective method for dealing with Alzheimer’s disease. This paper offers a comprehensive overview of the current status of research on antibody-based molecules as therapies for Alzheimer’s disease. We will briefly mention their mechanisms of action, therapeutic efficacy, and safety profiles while addressing the challenges and limitations encountered during their development. We also highlight some crucial considerations in antibody-based treatment development, including patient selection criteria, dosing regimens, or safety concerns. In conclusion, antibody-based therapies present a hopeful outlook for addressing Alzheimer’s disease. While challenges remain, the accumulating evidence suggests that these therapies may offer substantial promise in ameliorating or preventing the progression of this debilitating condition, thus potentially enhancing the quality of life for the millions of individuals and families affected by Alzheimer’s disease worldwide.

Background and Objectives: Noncommunicable diseases (NCDs) are a group of non-transmissible conditions that tend to be of long duration and are the result of a combination of genetic, physiological, environmental, and behavioral factors. Although an association between oral disorders and NCDs has been suggested, the relationship between Burning Mouth Syndrome (BMS) and NCDs and their associated risk factors has not been deeply investigated. In this study, we aim to identify associations between BMS and NCDs in the Romanian population. Materials and Methods: Ninety-nine BMS patients and 88 age-matched controls (aged 50 and over) were clinically evaluated for the presence of eight noncommunicable diseases (NCDs) and their most common risk factors, including hypertension, dyslipidemia, smoking, and obesity. Results: The results of our study showed that the BMS in the Romanian population seems to be significantly associated with cardiovascular diseases (CVDs) (p < 0.001) and two of their risk factors, hypertension (p < 0.001) and dyslipidemia (p < 0.001). Moreover, evaluating the Framingham Risk Score (FRS) in the individuals not affected by CVDs (73 CTRL and 38 BMS), we found that 13.2% of BMS patients reported a moderate risk of developing CVDs in ten years, compared to the controls, all of whom presented a low risk (p = 0.002). Conclusions: Our findings suggest that a multidisciplinary clinical approach, which also includes a cardiovascular evaluation, is essential for the successful management of BMS. Moreover, these data highlighted the importance of introducing an integrated strategy for the prevention and care of NCDs in BMS patients.

Background: Alzheimer’s disease (AD), along with other neurodegenerative disorders, remains a challenge for clinicians, mainly because of the incomplete knowledge surrounding its etiology and inefficient therapeutic options. Considering the central role of amyloid beta (Aβ) in the onset and evolution of AD, Aβ-targeted therapies are among the most promising research directions. In the context of decreased Aβ elimination from the central nervous system in the AD patient, the authors propose a novel therapeutic approach based on the “Cerebrospinal Fluid Sink Therapeutic Strategy” presented in previous works. This article aims to demonstrate the laborious process of the development and testing of an effective nanoporous ceramic filter, which is the main component of an experimental device capable of filtrating Aβ from the cerebrospinal fluid in an AD mouse model. Methods: First, the authors present the main steps needed to create a functional filtrating nanoporous ceramic filter, which represents the central part of the experimental filtration device. This process included synthesis, functionalization, and quality control of the functionalization, which were performed via various spectroscopy methods and thermal analysis, selectivity measurements, and a biocompatibility assessment. Subsequently, the prototype was implanted in APP/PS1 mice for four weeks, then removed, and the nanoporous ceramic filter was tested for its filtration capacity and potential structural damages. Results: In applying the multi-step protocol, the authors developed a functional Aβ-selective filtration nanoporous ceramic filter that was used within the prototype. All animal models survived the implantation procedure and had no significant adverse effects during the 4-week trial period. Post-treatment analysis of the nanoporous ceramic filter showed significant protein loading, but no complete clogging of the pores. Conclusions: We demonstrated that a nanoporous ceramic filter-based system that filtrates Aβ from the cerebrospinal fluid is a feasible and safe treatment modality in the AD mouse model. The presented prototype has a functional lifespan of around four weeks, highlighting the need to develop advanced nanoporous ceramic filters with anti-biofouling properties to ensure the long-term action of this therapy.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized in its typical presentation by a combination of lower and upper motor neuron symptoms, with a progressive course and fatal outcome. Due to increased recognition of the non-motor symptoms, it is currently considered a multisystem disorder with great heterogeneity, regarding genetical, clinical, and neuropathological features. Often underestimated, autonomic signs and symptoms have been described in patients with ALS, and various method analyses have been used to assess autonomic nervous system involvement. The aim of this paper is to offer a narrative literature review on autonomic disturbances in ALS, based on the scarce data available to date.

Burning mouth syndrome (BMS) is a chronic disease characterized by the presence of persistent oral mucosa pain, mainly burning sensation without any detectable clinical cause or modified general investigations. Coronavirus infections, in some patients, caused sensations of oral burning, of a neuropathic nature, which mimicked the symptoms of BMS. In addition, the psychiatric manifestations associated with the COVID-19 pandemic have exacerbated the symptoms of patients already diagnosed with burning mouth syndrome. Based on these observations, we conducted a longitudinal study to assess the changes in depressive and anxiety symptoms in BMS patients during the pandemics. We recruited two groups of age and gender-matched BMS patients. The first group included patients with BMS diagnosed with coronavirus infection and the second one without coronavirus infection. The study concluded that in patients with coronavirus infection there was an intensification of anxiety-depressive symptoms more pronounced in the first 6 months after infection (duration being associated with the infection severity and long-COVID symptoms), followed by a recurrence or even decrease in symptoms compared to the initial examination. Oral symptomatology had a similar evolution, the intensity being determined by the severity of the COVID-19 infection episode and by the prolonged use of antivirals. The lack of a larger number of studies and patients with BMS and COVID-19 infection limited the possibility of comparative analyses.

Background and Objectives: The COVID-19 pandemic triggered significant delays in the treatment of people with movement disorders who depend on face-to-face clinic encounters for receipt of their regular botulinum toxin injections. Against this background, it was the aim of this study to look into pandemic-related characteristics of patients with dystonia and hemifacial spasm treated with botulinum toxin at a tertiary centre in Romania and identify potential correlations between delays in treatment and health perceptions. Materials and Methods: A cross sectional, questionnaire-based, study was conducted between May-September 2021 on the 175 patients in the centre’s botulinum toxin database. Results: Of the 90 patients who qualified for inclusion most were late middle-aged females with long-standing dystonia, of which torticollis and blepharospasm were the most common phenotypes. Treatment was delayed by an average of 8.5 months, whereas the overall quality-of-life health score was 61.1, with 60% of respondents rating themselves above 50. No statistically significant correlation was identified between delays in treatment and overall health scores. Instead, statistically significant differences were uncovered based on type of disorder (dystonia vs. hemifacial spasm). Conclusion: The results of this study may go on to show that, in the event of similar pandemic surges, patient micromanagement by type of disorder may be part of a well-balanced restriction-cum-access health policy.

BackgroundWhile stroke is one of the most dissected topics in neurology, the primary prevention of PFO-related stroke in young patients is still an unaddressed subject. We present a study concerning clinical, demographic, and laboratory factors associated with stroke and transient ischemic attack in patients with patent foramen ovale (PFO), as well as comparing PFO-patients with and without cerebrovascular ischemic events (CVEs).Patients and methodsConsecutive patients with PFO-associated CVEs were included in the study; control group was selected from patients with a PFO and no history of stroke. All participants underwent peripheral routine blood analyses, as well as, on treating physician's recommendations, screening for thrombophilia.ResultsNinety-five patients with CVEs and 41 controls were included. Females had a significantly lower risk of CVEs than males (p = 0.04). PFO size was similar between patients and controls. Patients with CVEs had more often hypertension (n = 33, 34.7%), p = 0.007. No significant differences were found between the two groups with regard to routine laboratory tests and thrombophilia status. Hypertension and gender were identified in a binomial logistic regression model as independent predictors for CVEs, but with an area under the ROC curve of 0.531, suggesting a very poor level of discrimination between the two groups.Discussion and conclusionsThere is little difference between patients with PFO with and without CVEs in terms of PFO size and routine laboratory analyses. While still a controversial topic in the specialty literature, classic first-level thrombophilic mutations are not a risk factor for stroke in patients with PFO. Hypertension and male gender were identified as factors associated with a higher risk of stroke in the setting of PFO.

Autoimmune encephalitis is a complex and multifaceted pathology that involves immune-mediated inflammation of the brain. It is characterized by the body’s immune system attacking the brain tissue, leading to a cascade of inflammatory processes. What makes autoimmune encephalitis vast is the wide range of causes, mechanisms, clinical presentations, and diagnostic challenges associated with the condition. The clinical presentations of autoimmune encephalitis are broad and can mimic other neurological disorders, making it a challenging differential diagnosis. This diverse clinical presentation can overlap with other conditions, making it crucial for healthcare professionals to maintain a high level of suspicion for autoimmune encephalitis when evaluating patients. The diagnostic challenges associated with autoimmune encephalitis further contribute to its vastness. Due to the variable nature of the condition, there is no definitive diagnostic test that can confirm autoimmune encephalitis in all cases. In this context, personalized patient management is crucial for achieving favorable outcomes. Each patient’s treatment plan should be tailored to their specific clinical presentation, underlying cause, and immune response. Our objective is to raise awareness about the frequent yet underdiagnosed nature of autoimmune encephalitis by sharing five cases we encountered, along with a brief literature review.

The importance of burnout amongst medical staff was highlighted by various papers, showing that this issue implies job demands and job resources. The current challenge of SARS-CoV-2 pandemic also raised many concerns about its impact on healthcare sector. A new survey after 4 years from the previous study of the Bucharest College of Physicians is coming with new data, containing the effect of COVID-19 on the psychological wellbeing of its members. The increasing of burnout was found in all categories, and the most frequently solutions claimed by the respondents were related to decreasing of workload and bureaucracy, and an important number of physicians identify the need for specialized psychological assistance. The COVID-19 pandemic period exacerbated the system related factors that contribute to the phenomenon of burnout.

Abstract Cardiac amyloidosis is a restrictive cardiomyopathy determined by the accumulation of amyloid, which is represented by misfolded protein fragments in the cardiac extracellular space. The main classification of systemic amyloidosis is determined by the amyloid precursor proteins causing a very heterogeneous disease spectrum, but the main types of amyloidosis involving the heart are light chain (AL) and transthyretin amyloidosis (ATTR). AL, in which the amyloid precursor is represented by misfolded immunoglobulin light chains, can involve almost any system carrying the worst prognosis among amyloidosis patients. This has however dramatically improved in the last few years with the increased usage of the novel therapies such as proteasome inhibitors and haematopoietic cell transplantation, in the case of timely diagnosis and initiation of treatment. The treatment for AL is directed by the haematologist working closely with the cardiologist when there is a significant cardiac involvement. Transthyretin (TTR) is a protein that is produced by the liver and is involved in the transportation of thyroid hormones, especially thyroxine and retinol binding protein. ATTR results from the accumulation of transthyretin amyloid in the extracellular space of different organs and systems, especially the heart and the nervous system. Specific therapies for ATTR act at various levels of TTR, from synthesis to deposition: TTR tetramer stabilization, oligomer aggregation inhibition, genetic therapy, amyloid fibre degradation, antiserum amyloid P antibodies, and antiserum TTR antibodies. Treatment of systemic amyloidosis has dramatically evolved over the last few years in both AL and ATTR, improving disease prognosis. Moreover, recent studies revealed that timely treatment can lead to an improvement in clinical status and in a regression of amyloid myocardial infiltration showed by imaging, especially by cardiac magnetic resonance, in both AL and ATTR. However, treating cardiac amyloidosis is a complex task due to the frequent association between systemic congestion and low blood pressure, thrombo‐embolic and haemorrhagic risk balance, patient frailty, and generally poor prognosis. The aim of this review is to describe the current state of knowledge regarding cardiac amyloidosis therapy in this constantly evolving field, classified as treatment of the cardiac complications of amyloidosis (heart failure, rhythm and conduction disturbances, and thrombo‐embolic risk) and the disease‐modifying therapy.

Amyloid beta peptide is an important biomarker in Alzheimer’s disease, with the amyloidogenic hypothesis as one of the central hypotheses trying to explain this type of dementia. Despite numerous studies, the etiology of Alzheimer’s disease remains incompletely known, as the pathological accumulation of amyloid beta aggregates cannot fully explain the complex clinical picture of the disease. Or, for the development of effective therapies, it is mandatory to understand the roles of amyloid beta at the brain level, from its initial monomeric stage prior to aggregation in the form of senile plaques. In this sense, this review aims to bring new, clinically relevant data on a subject intensely debated in the literature in the last years. In the first part, the amyloidogenic cascade is reviewed and the possible subtypes of amyloid beta are differentiated. In the second part, the roles played by the amyloid beta monomers in physiological and pathological (neurodegenerative) conditions are illustrated based on the most relevant and recent studies published on this topic. Finally, considering the importance of amyloid beta monomers in the pathophysiology of Alzheimer’s disease, new research directions with diagnostic and therapeutic impacts are suggested.

Abstract Background Hypertrophic cardiomyopathy (HCM) is a genetic disorder mostly caused by sarcomeric gene mutations, but almost 10% of cases are attributed to inherited metabolic and neuromuscular disorders. First described in 2008 in an American-Italian family with scapuloperoneal myopathy, FHL1 gene encodes four-and-a-half LIM domains 1 proteins which are involved in sarcomere formation, assembly and biomechanical stress sensing both in cardiac and skeletal muscle, and its mutations are responsible for a large spectrum of neuromuscular disorders (mostly myopathies) and cardiac disease, represented by HCM, either isolated, or in conjunction with neurologic and skeletal muscle impairment. We thereby report a novel mutation variant in FHL1 structure, associated with HCM and type 6 Emery-Dreifuss muscular dystrophy (EDMD). Case presentation We describe the case of a 40 year old male patient, who was referred to our department for evaluation in the setting of NYHA II heart failure symptoms and was found to have HCM. The elevated muscular enzymes raised the suspicion of a neuromuscular disease. Rigid low spine and wasting of deltoidus, supraspinatus, infraspinatus and calf muscles were described by the neurological examination. Electromyography and muscle biopsy found evidence of chronic myopathy. Diagnosis work-up was completed by next-generation sequencing genetic testing which found a likely pathogenic mutation in the FHL1 gene (c.157-1G > A, hemizygous) involved in the development of X-linked EDMD type 6. Conclusion This case report highlights the importance of multimodality diagnostic approach in a patient with a neuromuscular disorder and associated hypertrophic cardiomyopathy by identifying a novel mutation variant in FHL1 gene. Raising awareness of non-sarcomeric gene mutations which can lead to HCM is fundamental, because of diagnostic and clinical risk stratification challenges.

IntroductionTwo parallel paradigms of cardiovascular efficiency and haemodynamic optimisation coexist in haemodynamic research. Targeting ventriculo-arterial (VA) coupling [i.e., the ratio between arterial and ventricular elastance (EV)] and electromechanical coupling are two promising approaches in acute circulatory failure. However, validation of the parameters of electromechanical coupling in critically ill patients is ongoing. Furthermore, a unifying link between VA and electromechanical coupling may exist, as EV is correlated with different times of the cardiac cycle.Materials and MethodsThis study was a retrospective analysis of a prospectively collected observational database from one tertiary center ICU. We analyzed the relationship between electromechanical dyssynchrony and acute circulatory failure hemodynamics before and after treatment (i.e., fluid expansion, dobutamine, or norepinephrine infusion). The relationship between electromechanical coupling and VA coupling was also investigated. Adult patients with haemodynamic instability were included. Haemodynamic parameters, including arterial pressure, cardiac index, VA coupling, stroke work index/pressure–volume area (SWI/PVA), t-IVT, and Tei's index, were collected before and after treatment. A t-IVT of >12 s/min was classified as intraventricular dyssynchrony.ResultsWe included 54 patients; 39 (72.2%) were classified as having intraventricular dyssynchrony at baseline. These patients with baseline dyssynchrony showed a statistically significant amelioration of t-IVT (from 18 ± 4 s to 14 ± 6 s, p = 0.001), left ventricular EV [from 1.1 (0.72–1.52) to 1.33 (0.84–1.67) mmHg mL−1, p = 0.001], VA coupling [from 2 (1.67–2.59) to 1.80 (1.40–2.21), p = 0.001], and SWI/PVA [from 0.58 (0.49–0.65) to 0.64 (0.51–0.68), p = 0.007]. Patients without baseline dyssynchrony showed no statistically significant results. The improvement in VA coupling was mediated by an amelioration of EV. All patients improved their arterial pressure and cardiac index with treatment. The haemodynamic treatment group exhibited no effect on changing t-IVT.ConclusionAcute circulatory failure is associated with electromechanical dyssynchrony. Cardiac electromechanical coupling was improved by haemodynamic treatment only if altered at baseline. The improvement of cardiac electromechanical coupling was associated with the improvement of markers of cardiocirculatory efficacy and efficiency (i.e., SWI/PVA and VA coupling). This study was the first to demonstrate a possible link between cardiac electromechanical coupling and VA coupling in patients with acute circulatory failure.

BackgroundPatients with hypertrophic cardiomyopathy (HCM) have an increased prevalence of atrial fibrillation (AF) compared to the general population, and left atrium (LA) remodeling is strongly correlated with the risk of AF. This prospective, monocentric study aimed to assess the role of LA electrocardiographic and echocardiographic (structural and functional) parameters in predicting the risk for incident AF in patients with HCM.Methods and ResultsThe study population consisted of 126 HCM patients in sinus rhythm (52.6 ± 16.2 years, 54 men), 118 of them without documented AF. During a median follow-up of 56 (7–124) months, 39 (30.9%) developed a new episode of AF. Multivariable analysis showed that LA booster pump function (assessed by ASr, HR = 4.24, CI = 1.84–9.75, and p = 0.038) and electrical dispersion (assessed by P wave dispersion – Pd, HR = 1.044, CI = 1.029–1.058, and p = 0.001), and not structural parameters (LA diameter, LA volume) were independent predictors of incident AF. Seventy-two patients had a LA diameter < 45 mm, and 16 of them (22.2%) had an AF episode during follow-up. In this subgroup, only Pd emerged as an independent predictor for incident AF (HR = 1.105, CI = 1.059–1.154, and p = 0.002), with good accuracy (AUC = 0.89).ConclusionLeft atrium booster pump function (ASr) and electrical dispersion (Pd) are related to the risk of incident AF in HCM patients. These parameters can provide further stratification of the risk for AF in this setting, including in patients considered at lower risk for AF based on the conventional assessment of LA size.

Introduction: Cognitive decline, correlating with hippocampal atrophy, characterizes several neurodegenerative disorders having a background of low-level chronic inflammation and oxidative stress. Methods: In this cross-sectional study, we examined how cognitive decline and hippocampal subfields volume are associated with the expression of redox and inflammatory genes in peripheral blood. We analyzed 34 individuals with different cognitive scores according to Mini-Mental State Examination, corrected by age and education (adjMMSE). We identified a group presenting cognitive decline (CD) with adjMMSE Results: Our findings indicate that hippocampal segment volumes correlate positively with adjMMSE and negatively with the blood transcript levels of 19 genes, mostly redox genes correlating especially with the left subiculum and presubiculum. A strong negative correlation between hippocampal subfields atrophy and Sulfiredoxin-1 ( SRXN1) redox gene was emphasized. Conclusions: Concluding, these results suggest that SRXN1 might be a valuable candidate blood biomarker for non-invasively monitoring the evolution of hippocampal atrophy in CD patients.

Introduction : Cognitive decline, correlating with hippocampal atrophy, characterizes several neurodegenerative disorders having a background of low-level chronic inflammation and oxidative stress. Methods : In this cross-sectional study, we examined how cognitive decline and hippocampal subfields volume are associated with the expression of redox and inflammatory genes in peripheral blood. We analyzed 34 individuals with different cognitive scores according to Mini-Mental State Examination, corrected by age and education (adjMMSE). We identified a group presenting cognitive decline (CD) with adjMMSE Results : Our findings indicate that hippocampal segment volumes correlate positively with adjMMSE and negatively with the blood transcript levels of 19 genes, mostly redox genes correlating especially with the left subiculum and presubiculum. A strong negative correlation between hippocampal subfields atrophy and SRXN1 redox gene is emphasized. Conclusions: Concluding, these results suggest that SRXN1 might be a valuable candidate blood biomarker for non-invasively monitoring the evolution of hippocampal atrophy in CD patients.

Myxomatous mitral valve disease (MVD) is a common disorder in which the entire mitral valve apparatus seems to be involved. Mitral valve repair is nowadays the method of choice for the correction of mitral regurgitation but the optimal shape and flexibility of the annuloplasty ring remain controversial. Considering that myxomatous MVD covers a wide spectrum from limited fi bro-elastic deficiency to extensive Barlow disease, we presume that the mitral annulus morphological and functional changes are likely different in different types of myxomatous MVD. We analyze the 3-dimensional geometry and the dynamics of the mitral annulus in 110 patients with significant mitral regurgitation due to different types of myxomatous mitral valve disease and 40 normal subjects using 3D transesophageal echocardiography. The mitral annulus differs in patients with limited MVD, extensive MVD and in normal controls in terms of size, shape, and dynamics. Patients with limited MVD have larger, flatter, dysfunctional and more mobile mitral annulus compared to normal, while patients with extensive MVD have even larger, flatter and more dysfunctional mitral annulus, with reduced mobility. The non-planar dynamics has different patterns during systole, according to the extension of MV disease. Our data may be important for the appropriate choose of annuloplasty mitral annulus in mitral valve repair, the current trend being to choose the ring according to the underlying pathology.

Coarctation of the aorta (CoA) is a relatively frequent congenital defect. Its natural evolution is marked by serious complications including aortic dissection, heart failure, coronary artery disease, infective endocarditis, or cerebral haemorrhages. Correction of CoA before complications arise is associated with a favorable long-term outcome. Timely diagnosis of CoA is therefore of utmost importance in the prognosis of these patients. Non-invasive imaging techniques, ranging from chest radiography to echocardiography, Cardiac Computed Tomography (CCT), and Cardiac Magnetic Resonance (CMR) have evolved to the extent where they can not only suggest but also precisely characterize the lesion and guide further management. We present a series of 3 case reports, highlighting the diagnostic approach and treatment for this pathology.

We present a complex Marfan case, with previous type A aortic dissection, subsequent progressing aortic arch aneurysm, type B chronic aortic dissection, and Barlow disease with severe mitral regurgitation, all expressions of the same phenotype, all needing staged complex surgical therapies. (Level of Difficulty: Intermediate.)

(1) Background: Early disability accrual in RRMS patients is frequent and is associated with worse long-term prognosis. Correctly identifying the patients that present a high risk of early disability progression is of utmost importance, and may be aided by the use of predictive biomarkers. (2) Methods: We performed a prospective cohort study that included newly diagnosed RRMS patients, with a minimum follow-up period of one year. Biomarker samples were collected at baseline, 3-, 6- and 12-month follow-ups. Disability progression was measured using the EDSS-plus score. (3) Results: A logistic regression model based on baseline and 6-month follow-up sNfL z-scores, RNFL and GCL-IPL thickness and BREMSO score was statistically significant, with χ2(4) = 19.542, p < 0.0001, R2 = 0.791. The model correctly classified 89.1% of cases, with a sensitivity of 80%, a specificity of 93.5%, a positive predictive value of 85.7% and a negative predictive value of 90.62%. (4) Conclusions: Serum biomarkers (adjusted sNfL z-scores at baseline and 6 months) combined with OCT metrics (RNFL and GCL-IPL layer thickness) and the clinical score BREMSO can accurately predict early disability progression using the EDSS-plus score for newly diagnosed RRMS patients.

The SH-SY5Y cell line is a simple and inexpensive in vitro experimental model for studying Parkinson disease (PD). This experimental model is a useful tool for elucidating pathophysiological mechanisms of PD and in the development of new pharmacological therapies. In this review, we aim to summarize current protocols for SH-SY5Y cell culturing and differentiation and PD experimental designs derived from the SH-SY5Y cell line. The most efficient protocol for differentiation of the SH-SY5Y cell line into dopaminergic neurons seems to be the addition of retinoic acid to the growth medium, followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) addition in a low concentration of fetal bovine serum. PD pathological changes, such as neuronal apoptosis and the intraneuronal alpha-synuclein aggregation, can be reproduced in the SH-SY5Y cell line either by the use of neurotoxic agents [such as rotenone, 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine] or by genetic modification (transfection of the alpha-synuclein wild-type or mutant gene, genetic manipulation of other genes involved in PD). In addition, compounds with a potential neuroprotective role may be tested on neurotoxicity-induced SH-SY5Y models. The cell line can also be used for testing PD pathophysiological mechanisms such as the prion-like neuronal transmission of alpha-synuclein or the microbiota influence in PD. In conclusion, the use of the SH-SY5Y cell line represents a basic but consistent first step in experiments related to PD, but which must be followed by the confirmation of the results through more complex in vitro and in vivo experimental models.

Abstract Purpose The present study evaluated how heart failure (HF) negatively impacts health-related quality of life (HRQoL) in hypertrophic cardiomyopathy (HCM) patients and explored the major clinical determinants associated with HRQoL impairment in this population. Methods This was a cross-sectional single-center study of health-related HRQoL that included 91 consecutive patients with HCM. Evaluation was performed based on a comprehensive protocol that included the recommended diagnostic studies, as well as administration of the translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ) (CV Outcomes Inc) as a health status measure. Results The cohort included 52 (57%) males, median age 58 (20–85) years. The median global KCCQ score was 67 (12.5–100) corresponding to a moderate impairment in HRQoL. There was an inverse correlation between the median global KCCQ score and NYHA class (Kendall’s tau b coefficient r − 0.33, p = 0.001). Patients with pulmonary hypertension (PHT), defined as resting pulmonary artery systolic pressure of ≥ 45 mmHg, presented a significantly worse HRQoL as compared to those without PHT (median KCCQ score 56.2 vs 77.5, p = 0.013). The KCCQ score mildly correlated with age (r − 0.18, p = 0.014), history of syncope (r − 0.18, p = 0.045), estimated glomerular filtration rate (eGFR) (r 0.31, p

Introduction: Cognitive decline, correlating with hippocampal atrophy, characterizes several neurodegenerative disorders having a background of low-level chronic inflammation and oxidative stress. Methods: In this cross-sectional study, we examined how cognitive decline and hippocampal subfields volume are associated with the expression of redox and inflammatory genes in peripheral blood. We analyzed 34 individuals with different cognitive scores according to Mini-Mental State Examination, corrected by age and education (adjMMSE). We identified a group presenting cognitive decline (CD) with adjMMSE

IntroductionThe determination of ventriculo-arterial coupling is gaining an increasing role in cardiovascular and sport medicine. However, its relevance in critically ill patients is still under investigation. In this study we measured the association between ventriculo-arterial coupling and oxygen consumption (VO2) response after hemodynamic interventions in cardiac surgery patients with acute circulatory instability.Material and MethodsSixty-one cardio-thoracic ICU patients (67 ± 12 years, 80% men) who received hemodynamic therapeutic interventions (fluid challenge or norepinephrine infusion) were included. Arterial pressure, cardiac output, heart rate, arterial (EA), and ventricular elastances (EV), total indexed peripheral resistances were assessed before and after hemodynamic interventions. VO2 responsiveness was defined as VO2 increase >15% following the hemodynamic intervention. Ventriculo-arterial coupling was assessed measuring the EA/EV ratio by echocardiography. The left ventricle stroke work to pressure volume area ratio (SW/PVA) was also calculated.ResultsIn the overall cohort, 24 patients (39%) were VO2 responders, and 48 patients had high ventriculo-arterial (EA/EV) coupling ratio with a median value of 1.9 (1.6–2.4). Most of those patients were classified as VO2 responders (28 of 31 patients, p = 0.031). Changes in VO2 were correlated with those of indexed total peripheral resistances, EA, EA/EV and cardiac output. EA/EV ratio predicted VO2 increase with an AUC of 0.76 [95% CI: 0.62–0.87]; p = 0.001. In principal component analyses, EA/EV and SW/PVA ratios were independently associated (p < 0.05) with VO2 response following interventions.ConclusionsVO2 responders were characterized by baseline high ventriculo-arterial coupling ratio due to high EA and low EV. Baseline EA/EV and SW/PVA ratios were associated with VO2 changes independently of the hemodynamic intervention used. These results underline the pathophysiological significance of measuring ventriculo-arterial coupling in patients with hemodynamic instability, as a potential therapeutic target.

Introduction: Cognitive decline, correlating with hippocampal atrophy, characterizes several neurodegenerative disorders having a background of low-level chronic inflammation and oxidative stress. Methods: In this cross-sectional study, we examined how cognitive decline and hippocampal subfields volume are associated with the expression of redox and inflammatory genes in peripheral blood. We analyzed 34 individuals with different cognitive scores according to Mini-Mental State Examination, corrected by age and education (adjMMSE). We identified a group presenting cognitive decline (CD) with adjMMSE

Abstract Objective Neurodegeneration is thought to be the primary cause of neurological disability in multiple sclerosis (MS). Dysfunctional RNA‐binding proteins (RBPs) including their mislocalization from nucleus to cytoplasm, stress granule formation, and altered RNA metabolism have been found to underlie neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia. Yet, little is known about the role of dysfunctional RBPs in the pathogenesis of neurodegeneration in MS. As a follow‐up to our seminal finding of altered RBP function in a single case of MS, we posited that there would be evidence of RBP dysfunction in cortical neurons in MS. Methods Cortical neurons from 12 MS and six control cases were analyzed by immunohistochemistry for heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and TAR‐DNA‐binding protein‐43 (TDP‐43). Seven distinct neuronal phenotypes were identified based on the nucleocytoplasmic staining of these RBPs. Statistical analyses were performed by analyzing each phenotype in relation to MS versus controls. Results Analyses revealed a continuum of hnRNP A1 and TDP‐43 nucleocytoplasmic staining was found in cortical neurons, from neurons with entirely nuclear staining with little cytoplasmic staining in contrast to those with complete nuclear depletion of RBPs concurrent with robust cytoplasmic staining. The neuronal phenotypes that showed the most nucleocytoplasmic mislocalization of hnRNP A1 and TDP‐43 statistically distinguished MS from control cases (P

Introduction: Tuberous sclerosis complex (TSC) is a genetic disorder with a heterogenous clinical phenotype, with possible involvement of virtually any organ. Although recent advancement in genetics has allowed a better understanding of the pathophysiology of TSC, enabling a genetic diagnosis, TSC is primarily diagnosed on clinical grounds. Neurological manifestations amount to over 90% of people with TSC. Ensuing surveillance and treatment of TSC imply a multidisciplinary team of specialists. Case reports: We report 2 cases of TSC, both admitted to our Neurology Department on account of poor seizure control. One was diagnosed early in his infancy having a typical onset with infantile spasms and subsequent generalised seizures whereas the other was diagnosed with TSC in our department, at 56 years of age. They both also have skin and renal involvement as major clinical features. Conclusion: Recognition of the clinical hallmarks of TSC, albeit variable, is important for early diagnosis and subsequent multidisciplinary management. Neurological involvement, as illustrated in our case reports, is frequent and is largely responsible for morbidity and mortality in TSC.

Introduction: Myotonic dystrophy (DM) type 1 is a genetic disorder, caused by a trinucleotide CTG repeat expansion in the DMPK gene on chromosome 19. The skeletal muscle is the most severely affected organ, patients clinically presenting weakness and myotonia. Additionally, it may affect other organs, transforming it into a multisystemic disease. The pathophysiological mechanism involves RNA toxicity resulting from the expanded repeat in the mutant DM alleles. Phenotypes of DM1 may be classified as congenital, juvenile, classical or late onset. Case Report: We present the case of a 36-year-old male diagnosed with chronic hepatitis B virus infection 4 years ago, admitted to the Neurology Department for progressive weakness of the distal lower limbs and multiple falls without loss of consciousness due to muscle weakness. Considering the clinical evolution, neurological examination and paraclinical investigations, the patient was diagnosed with myotonic dystrophy type 1 and mild sensitive axonal polyneuropathy of the lower limbs. Conclusion: The diagnosis of DM can be established clinically if the patient has typical manifestations and positive family history. Genetic testing for CTG repeat expansion in the DMPK gene is the gold standard in diagnosing DM1. There is no disease-modifying therapy available for DM yet and management is only symptomatic.

Introduction: Post-stroke depression (PSD) has complex pathophysiology determined by various biological and psychological factors. Although it is a long-term complication of stroke, PSD is often underdiagnosed. Given the diagnostic role of quantitative electroencephalography (qEEG) in depression, it was investigated whether a possible marker of PSD could be identified by observing the evolution of the (Delta + Theta)/(Alpha + Beta) Ratio (DTABR), respectively the Delta/Alpha Ratio (DAR) values in post-stroke depressed patients (evaluated through the HADS-D subscale). Methods: The current paper analyzed the data of 57 patients initially selected from a randomized control trial (RCT) that assessed the role of N-Pep 12 in stroke rehabilitation. EEG recordings from the original trial database were analyzed using signal processing techniques, respecting the conditions (eyes open, eyes closed), and several cognitive tasks. Results: We observed two significant associations between the DTABR values and the HADS-D scores of post-stroke depressed patients for each of the two visits (V1 and V2) of the N-Pep 12 trial. We recorded the relationships in the Global (V1 = 30 to 120 days after stroke) and Frontal Extended (V2 = 90 days after stroke) regions during cognitive tasks that trained attention and working memory. For the second visit, the association between the analyzed variables was negative. Conclusions: As both our relationships were described during the cognitive condition, we can state that the neural networks involved in processing attention and working memory might go through a reorganization process one to four months after the stroke onset. After a period longer than six months, the process could localize itself at the level of frontal regions, highlighting a possible divergence between the local frontal dynamics and the subjective well-being of stroke survivors. QEEG parameters linked to stroke progression evolution (like DAR or DTABR) can facilitate the identification of the most common neuropsychiatric complication in stroke survivors.

(1) Background: Cognitive impairment (CI) begins early in the evolution of multiple sclerosis (MS) but may only become obvious in the later stages of the disease. Little data is available regarding predictive biomarkers for early, active cognitive decline in relapse remitting MS (RRMS) patients. (2) Methods: 50 RRMS patients in the first 6 months following diagnosis were included. The minimum follow-up was one year. Biomarker samples were collected at baseline, 3-, 6- and 12-month follow-up. Cognitive performance was assessed at baseline and 12-month follow-up; (3) Results: Statistically significant differences were found for patients undergoing active cognitive decline for sNfL z-scores at baseline and 3 months, CSF NfL baseline values, CSF Aβ42 and the Bremso score as well. The logistic regression model based on these 5 variables was statistically significant, χ2(4) = 22.335, p < 0.0001, R2 = 0.671, with a sensitivity of 57.1%, specificity of 97.4%, a positive predictive value of 80% and a negative predictive value of 92.6%. (4) Conclusions: Our study shows that serum biomarkers (adjusted sNfL z-scores at baseline and 3 months) and CSF biomarkers (CSF NfL baseline values, CSF Aβ42), combined with a clinical score (BREMSO), can accurately predict an early cognitive decline for RRMS patients at the moment of diagnosis.

Background: Alzheimer’s disease has a significant epidemiological and socioeconomic impact, and, unfortunately, the extensive research focused on potential curative therapies has not yet proven to be successful. However, in recent years, important steps have been made in the development and functionalization of nanoporous alumina membranes, which might be of great interest for medical use, including the treatment of neurodegenerative diseases. In this context, the aim of this article is to present the synthesis and biocompatibility testing of a special filtrating nano-membrane, which is planned to be used in an experimental device for Alzheimer’s disease treatment. Methods: Firstly, the alumina nanoporous membrane was synthesized via the two-step anodizing process in oxalic acid-based electrolytes and functionalized via the atomic layer deposition technique. Subsequently, quality control tests (spectrophotometry and potential measurements), toxicity, and biocompatibility tests (cell viability assays) were conducted. Results: The proposed alumina nanoporous membrane proved to be efficient for amyloid-beta filtration according to the permeability studies conducted for 72 h. The proposed membrane has proven to be fully compatible with the tested cell cultures. Conclusions: The proposed alumina nanoporous membrane model is safe and could be incorporated into implantable devices for further in vivo experiments and might be an efficient therapeutic approach for Alzheimer’s disease.

Background and Aim: Remote ischemic conditioning is a procedure purported to reduce the ischemic injury of an organ. This study aimed to explore the efficiency and safety of remote ischemic conditioning in patients with acute ischemic stroke. We hypothesized that remote ischemic conditioning administered from the first day of hospital admission would improve the infarct volume and clinical outcome at 180 days.Material and Methods: We performed a unicentric double-blind randomized controlled trial. We included all patients consecutively admitted to an Emergency Neurology Department with acute ischemic stroke, ineligible for reperfusion treatment, up to 24 hours from onset. All subjects were assigned to receive secondary stroke prevention treatment along with remote ischemic conditioning on the non-paretic upper limb during the first 5 days of hospitalization, twice daily - a blood pressure cuff placed around the arm was inflated to 20 mmHg above the systolic blood pressure (up to 180 mmHg) in the experimental group and 30 mmHg in the sham group. The primary outcome was the difference in infarct volume (measured on brain CT scan) at 180 days compared to baseline, whereas the secondary outcomes included differences in clinical scores (NIHSS, mRS, IADL, ADL) and cognitive/mood changes (MoCA, PHQ-9) at 180 days compared to baseline.Results: We enrolled 40 patients; the mean age was 65 years and 60% were men. Subjects in the interventional group had slightly better recovery in terms of disability, as demonstrated by the differences in disability scores between admission and 6 months (e.g., the median difference score for Barthel was −10 in the sham group and −17.5 in the interventional group, for ADL −2 in the sham group and −2.5 in the interventional group), as well as cognitive performance (the median difference score for MoCA was −2 in the sham group and −3 in the interventional group), but none of these differences reached statistical significance. The severity of symptoms (median difference score for NIHSS = 5 for both groups) and depression rate (median difference score for PHQ-9 = 0 for both groups) were similar in the two groups. The median difference between baseline infarct volume and final infarct volume at 6 months was slightly larger in the sham group compared to the interventional group (p = 0.4), probably due to an initial larger infarct volume in the former.Conclusion: Our results suggest that remote ischemic conditioning might improve disability and cognition. The difference between baseline infarct volume and final infarct volume at 180 days was slightly larger in the sham group.

The blood–brain barrier (BBB) is an essential structure for the maintenance of brain homeostasis. Alterations to the BBB are linked with a myriad of pathological conditions and play a significant role in the onset and evolution of neurodegenerative diseases, including Alzheimer’s disease. Thus, a deeper understanding of the BBB’s structure and function is mandatory for a better knowledge of neurodegenerative disorders and the development of effective therapies. Because studying the BBB in vivo imposes overwhelming difficulties, the in vitro approach remains the main possible way of research. With many in vitro BBB models having been developed over the last years, the main aim of this review is to systematically present the most relevant designs used in neurological research. In the first part of the article, the physiological and structural–functional parameters of the human BBB are detailed. Subsequently, available BBB models are presented in a comparative approach, highlighting their advantages and limitations. Finally, the new perspectives related to the study of Alzheimer’s disease with the help of novel devices that mimic the in vivo human BBB milieu gives the paper significant originality.

Background: Guillain–Barré syndrome (GBS)—a rare condition characterized by acute-onset immune-mediated polyneuropathy—has been registered as a neurological manifestation of COVID-19, suggesting a possible link between these two conditions. Methods: We report a case series of patients with COVID-19-related GBS hospitalized in the Neurology Department of Colentina Clinical Hospital, Bucharest, Romania, between March 2020 and March 2021. Several variables were analyzed, such as the mean interval between the onset of COVID-19 symptoms and neurological ones, clinical features, treatment course, and outcome. Further on, we conducted a thorough literature review based on the PubMed and ScienceDirect scientific databases. Results: A total of 9 COVID-19 patients developed symptoms of GBS, out of which in 7, it manifested as an acute inflammatory demyelinating polyneuropathy (AIDP). Five patients presented respiratory failure, 2 requiring mechanical ventilation. All patients received a course of intravenous immunoglobulins, 2 additionally requiring plasma exchange. Upon discharge, all but 1 patient (who had not regained the ability to walk) had a positive outcome, and 1 died during admission. In the literature review, we analyzed the published sources at the time of writing. Conclusions: A link between COVID-19 and GBS might be possible; therefore, increased vigilance is required in the early identification of these cases for prompt diagnosis and treatment. Some notable differences such as an earlier onset of GBS symptoms, higher respiratory dysfunction, and higher mortality rates in COVID-19 patients have been observed between the presentation of GBS in the context of COVID-19 and GBS of other causes.

Introduction: The emerging Coronavirus Disease (COVID-19) pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious public health issue due to its rapid spreading, high mortality rate and lack of specific treatment. Given its unpredictable clinical course, risk assessment, and stratification for severity of COVID-19 are required. Apart from serving as admission criteria, prognostic factors might guide future therapeutic strategies.Aim: We aimed to compare clinical features and biological parameters between elderly (age ≥ 65 years) and non-elderly (age

Parkinson’s disease (PD) is characterized by alpha-synuclein misfolding with subsequent intraneuronal amyloid formation and accumulation, low grade neuroinflammatory changes, and selective neurodegeneration. Available evidence suggests that the pathology usually begins in the gut and olfactory mucosa, spreading to the brain via the vagus and olfactory nerves, by a prion-like mechanism. A causal relationship has not been established, but gut dysbiosis is prevalent in PD and may lead to intestinal inflammation and barrier dysfunction. Additionally, epidemiological data indicate a link between inflammatory bowel diseases and PD. Calprotectin and zonulin are markers of intestinal inflammation and barrier permeability, respectively. We evaluated their serum and fecal levels in 22 patients with sporadic PD and 16 unmatched healthy controls. Mean calprotectin was higher in PD, both in serum (14.26 mcg/ml ± 4.50 vs. 5.94 mcg/ml ± 3.80, p = 0.0125) and stool (164.54 mcg/g ± 54.19 vs. 56.19 mcg/g ± 35.88, p = 0.0048). Mean zonulin was also higher in PD serum (26.69 ng/ml ± 3.55 vs. 19.43 ng/ml ± 2.56, p = 0.0046) and stool (100.19 ng/ml ± 28.25 vs. 37.3 ng/ml ± 13.26, p = 0.0012). Calprotectin was above the upper reference limit in 19 PD serums and 6 controls (OR = 10.56, 95% CI = 2.17–51.42, p = 0.0025) and in 20 PD stool samples and 4 controls (OR = 30, 95% CI = 4.75–189.30, p = 0.000045). Increased zonulin was found only in the stool samples of 8 PD patients. Despite the small sample size, our findings are robust, complementing and supporting other recently published results. The relation between serum and fecal calprotectin and zonulin levels and sporadic PD warrants further investigation in larger cohorts.

Immune axonal neuropathies are a particular group of immune-mediated neuropathies that occasionally accompany systemic autoimmune rheumatic diseases such as connective tissue dissorders and primary systemic vasculitides. Apart from vasculitis of vasa nervorum, various other mechanisms are involved in their pathogenesis, with possible therapeutic implications. Immune axonal neuropathies have highly heterogeneous clinical presentation and course, ranging from mild chronic distal sensorimotor polyneuropathy to severe subacute mononeuritis multiplex with rapid progression and constitutional symptoms such as fever, malaise, weight loss and night sweats, underpinning a vasculitic process. Sensory neuronopathy (ganglionopathy), small fiber neuropathy (sensory and/or autonomic), axonal variants of Guillain-Barré syndrome and cranial neuropathies have also been reported. In contrast to demyelinating neuropathies, immune axonal neuropathies show absent or reduced nerve amplitudes with normal latencies and conduction velocities on nerve conduction studies. Diagnosis and initiation of treatment are often delayed, leading to accumulating disability. Considering the lack of validated diagnostic criteria and evidence-based treatment protocols for immune axonal neuropathies, this review offers a comprehensive perspective on etiopathogenesis, clinical and paraclinical findings as well as therapy guidance for assisting the clinician in approaching these patients. High quality clinical research is required in order to provide indications and follow up rules for treatment in immune axonal neuropathies related to systemic autoimmune rheumatic diseases.