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Background. Hemiballismus is a rare hyperkinetic movement disorder characterized by irregular, poorly patterned, highamplitude involuntary movements of the limbs on one side of the body. While being usually a consequence of subthalamic nucleus lesions, hemiballismus is uncommonly associated with stroke in adults. Moreover, many debates remain regarding the physiopathology behind post-stroke hemiballismus and its optimal treatment. Case reports. In this context, the article aims to present two intriguing cases of hemiballismus arising from ischemic stroke, illustrating the intricate interplay between vascular pathology and movement disorders. Case 1 involves a 72-yearold female presenting with sudden onset left hemiballismus following incomplete right middle cerebral artery infarction, who received intravenous thrombolysis and had a good outcome. Case 2, an 80-year-old female presenting with abrupt onset right hemiballismus, with a suboptimal therapeutic response but self-remission after three months. Considering the inconclusive imaging results, this case highlights the diagnostic challenges and dilemmas encountered in the management of post-stroke hemiballismus. Conclusions. The authors propose a discussion by comparing the selected case reports with currently available data from the literature, focusing on the diagnosis and possible therapeutic strategies. These two cases underscore the importance of early recognition and tailored management of post-stroke hemiballismus, enriching the understanding of this movement disorder.

Introduction. Neurological manifestations secondary to Hymenoptera stings are rare. However, the literature describes cases of severe central and peripheral nervous system damage. Suspected pathophysiological mechanisms include hypoxic-ischemic damage, demyelination, and the direct neurotoxic effect of venoms. In this context, bee stings could be a possible atypical causative factor for Guillan–Barré syndrome and chronic inflammatory demyelinating polyneuropathy. Case report. We present the case of a 32-year-old patient who declared the presence of a bee sting two weeks before the onset of neurological manifestations (flaccid quadriparesis, predominantly distal, with paresthesia at the same level) that were initially diagnosed as a Guillain Barré syndrome. Despite the treatment with immunoglobulins in the acute phase, the worsening of the motor deficit after one month required a new course of immunoglobulins, associating corticosteroids, with initially favorable evolution. However, the presence of a new relapse after eight weeks, correlated with changes such as albumin-cytological dissociation in the examination of the cerebrospinal fluid and the appearance of active denervation on the electroneuromyography study, established the final diagnosis of chronic inflammatory demyelinating polyneuropathy. Conclusions. We consider the presented case proof of the relationship between the Hymenoptera sting and various peripheral nervous system pathologies. Inflammatory and demyelinating changes common to Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy appear to be the primary pathophysiological mechanism to explain this uncommon correlation.

This paper describes the process of producing chemosensors based on hybrid nanostructures obtained from Al2O3, as well as ZnO ceramic nanotubes and the following conducting polymers: poly(3-hexylthiophene), polyaniline emeraldine-base (PANI-EB), and poly(3, 4-ethylenedioxythiophene)-polystyrene sulfonate. The process for creating ceramic nanotubes involves three steps: creating polymer fiber nets using poly(methyl methacrylate), depositing ceramic films onto the nanofiber nets using magnetron deposition, and heating the nanotubes to 600 °C to burn off the polymer support completely. The technology for obtaining hybrid nanostructures from ceramic nanotubes and conducting polymers is drop-casting. AFM analysis emphasized a higher roughness, mainly in the case of PANI-EB, for both nanotube types, with a much larger grain size dimension of over 5 μm. The values of the parameter Rku were close or slightly above 3, indicating, in all cases, the formation of layers predominantly characterized by peaks and not by depressions, with a Gaussian distribution. An ink-jet printer was used to generate chemiresistors from ceramic nanotubes and PANI-EB structures, and the metallization was made with commercial copper ink for printed electronics. Calibration curves were experimentally generated for both sensing structures across a wider range of NH3 concentrations in air, reaching up to 5 ppm. A 0.5 ppm detection limit was established. The curve for the ZnO:PANI-EB structure presented high linearity and lower resistance values. The sensor could be used in medical diagnosis for the analysis of breath ammonia and biomarkers for predicting CKD in stages higher than 1. The threshold value of 1 ppm represents a feasible value for the presented sensor, which can be defined as a simple, low-value and robust device for individual use, beneficial at the patient level.

Background and Objectives: Although available therapies have changed the natural evolution of multiple sclerosis (MS), in time some patients assume a progressive course and no longer respond to treatment. There is no definitive clinical or laboratory parameter to certify MS progression from relapsing remitting MS (RRMS) to secondary progressive MS (SPMS) in early phases of transition. Our study aims to evaluate the value of clinical parameters and serum neurofilament light chain levels (sNfLs) as early warning signs of conversion to SPMS. Materials and Methods: The Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), 25-foot walk test (25FWT) and Symbol Digit Modalities Test (SDMT) were evaluated at 12 months apart in a cohort of 83 RRMS treated patients. sNfLs were evaluated at the second time point. Results: sNfLs correlate with EDSS and SDMT, with EDSS change and disease duration. Clinical parameters correlate among themselves and perform well in supporting the diagnosis of SPMS in logistic regression and ROC curves analysis. Eighty percent of the RRMS patients in our study (of which 65% are treated with high-efficacy disease-modifying drugs) showed some type of progression independent of relapses (PIRA) after 12 months, with one in five patients experiencing isolated cognitive worsening and almost two-thirds some type of motor worsening. We found no differences in terms of progression between patients treated with platform drugs versus high-efficacy drugs. Conclusions: An elevated level of progression independent of relapses (PIRA) was found in our cohort, with high-efficacy drugs providing no supplementary protection. As sNfL levels were correlated with the progression of EDSS (the main clinical progression marker), they may be considered potential prognostic markers, but further studies are necessary to precisely define their role in this direction. The lack of early sensitive markers for risk of progression may contribute to therapeutic delay and failure.

This paper describes a process to obtain magnetite functionalized with carboxymethylcellulose via coprecipitation by means of a preliminary stabilization of magnetite in citric acid. The magnetite assemblies successfully passed in vitro and in vivo tests of bio-compatibility. The measured values for the dielectric loss factor are remarkably high, a prerequisite for the assemblies’ potential use as contrast agents. Broadband THz spectroscopy analysis was performed to identify the most relevant frequency bands (here, 3.2–4 THz) where the signal difference between normal cells and cancer cells is relevant for the particles’ potential use as contrast agents for THz imaging, with applications in oncology.

This paper describes the process of producing chemiresistors based on hybrid nanostructures obtained from graphene and conducting polymers. The technology of graphene presumed the following: dispersion and support stabilization based on the chemical vapor deposition technique; transfer of the graphene to the substrate by spin-coating of polymethyl methacrylate; and thermal treatment and electrochemical delamination. For the process at T = 950 °C, a better settlement of the grains was noticed, with the formation of layers predominantly characterized by peaks and not by depressions. The technology for obtaining hybrid nanostructures from graphene and conducting polymers was drop-casting, with solutions of Poly(3-hexylthiophene (P3HT) and Poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-bithiophene] (F8T2). In the case of F8T2, compared to P3HT, a 10 times larger dimension of grain size and about 7 times larger distances between the peak clusters were noticed. To generate chemiresistors from graphene–polymer structures, an ink-jet printer was used, and the metallization was made with commercial copper ink for printed electronics, leading to a structure of a resistor with an active surface of about 1 cm2. Experimental calibration curves were plotted for both sensing structures, for a domain of CH4 of up to 1000 ppm concentration in air. A linearity of the curve for the low concentration of CH4 was noticed for the graphene structure with F8T2, presenting a sensitivity of about 6 times higher compared with the graphene structure with P3HT, which makes the sensing structure of graphene with F8T2 more feasible and reliable for the medical application of irritable bowel syndrome evaluation.

Alzheimer’s disease, the most common type of dementia worldwide, lacks effective disease-modifying therapies despite significant research efforts. Passive anti-amyloid immunotherapies represent a promising avenue for Alzheimer’s disease treatment by targeting the amyloid-beta peptide, a key pathological hallmark of the disease. This approach utilizes monoclonal antibodies designed to specifically bind amyloid beta, facilitating its clearance from the brain. This review offers an original and critical analysis of anti-amyloid immunotherapies by exploring several aspects. Firstly, the mechanisms of action of these therapies are reviewed, focusing on their ability to promote Aβ degradation and enhance its efflux from the central nervous system. Subsequently, the extensive history of clinical trials involving anti-amyloid antibodies is presented, from initial efforts using first-generation molecules leading to mixed results to recent clinically approved drugs. Along with undeniable progress, the authors also highlight the pitfalls of this approach to offer a balanced perspective on this topic. Finally, based on its potential and limitations, the future directions of this promising therapeutic strategy for Alzheimer’s disease are emphasized.

The incidence and prevalence of cardiac and cerebrovascular diseases are constantly increasing, with chronic coronary syndrome and ischemic stroke as the leading causes of morbidity and mortality worldwide. According to current knowledge, the heart–brain axis is more than a theoretical concept, with many common pathophysiological mechanisms involved in the onset and evolution of both coronary and cerebral ischemia. Moreover, the focus is on the prevention and early intervention of risk factors in searching for targeted and personalized medical treatment. In this context, this narrative review aims to offer, in a didactic and practice-oriented manner, an up-to-date overview of the role played by lipid-derived biomarkers (from low-density lipoprotein cholesterol to oxylipin and apolipoproteins) in chronic coronary syndrome and ischemic stroke. Firstly, the authors highlight, via relevant epidemiological data, the significant burden of chronic coronary syndrome and ischemic stroke in the general population, thus explaining the need for updated information on this topic. Subsequently, the most important lipid-derived biomarkers and their multiple roles in the pathogenesis of these two disorders are listed. Currently available and experimental targeted therapies based on these lipid-derived biomarkers are presented in the final part of this paper, representing this manuscript’s original and novel input.

Multiple sclerosis (MS), the most common autoimmune neurological disease of young people, is a significant burden for the patient, significantly decreasing the quality of life. Besides motor deficits, sensory problems, and vision loss, in recent years, neurologists have focused also on the cognitive impairment related to this condition. The early detection of cognitive disturbances is currently an essential part of MS patients’ follow-ups, as any worsening suggests the inefficiency of the applied treatment and the need for a therapeutic switch. In this regard, this review aims to highlight the importance of cognitive screening tests in the periodical evaluation of MS patients. While in the first part, the most frequently used cognitive screening tests in Romania are presented in a detailed manner, in the second part of the article, the clinical impact of these tests is highlighted, based on the results of the most relevant randomized clinical trials published during the last 10 years. Finally, the authors suggest future research directions to improve cognitive screening testing in MS patients after exposing the limitations of currently used screening batteries.

Neurodegenerative disorders, particularly Alzheimer’s disease (AD), remain a great challenge regarding the finding of effective treatment, one main reason being the incomplete understanding of their etiology. With many intensely debated hypotheses, a newer approach based on the impact of iron imbalance in sustaining neurodegeneration in the central nervous system becomes increasingly popular. Altered iron homeostasis leads to increased iron accumulation in specific brain areas, explaining the clinical picture of AD patients. Moreover, growing evidence sustains the significant impact of iron metabolism in relationship to other pathological processes encountered in the AD-affected brain, such as the amyloidogenic pathway, chronic inflammation, or oxidative stress. In this context, this mini-review aims to summarize the novel data from the continuously expanding literature on this topic in a didactic manner. Thus, in the first part, the authors briefly highlight the most relevant aspects related to iron absorption, transport, regulation, and elimination at the cerebral level, focusing on the role of the blood-brain barrier and the newer concept of ferroptosis. Subsequently, currently available iron chelation therapies are discussed, including an overview of the most relevant clinical trials on this topic. In the final part, based on the latest results from in vitro and in vivo studies, new research directions are suggested to enhance the development of effective antidementia therapies.

Post-stroke aphasia is an important topic in clinical rehabilitation neurology, affecting a significant number of stroke patients worldwide each year. Although the anatomical basis of aphasia has been explored for over a century, a revision of disease classification has led to a broader understanding of the subject and has stimulated the field of drug development to yield novel therapies. In this context, the authors commence the current narrative review by presenting the widely accepted aphasia classifications and the corresponding management practices. Subsequently, speech-language therapies are presented, with a focus on the widely preferred patient-centered approach. We conclude with a brief discussion regarding adjunctive treatment options such as pharmacological intervention, non-invasive brain stimulation techniques, and virtual reality rehabilitation.

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.

Background. Guillain-Barré syndrome (GBS), the most common cause of flaccid motor deficit with acute or subacute onset, is associated in approximately 2/3 of cases with a history of microbial, predominantly viral, infection. In the context of the current COVID-19 pandemic, the presence of patients with both peripheral nervous system pathology and SARS-CoV-2 viral infection raised questions among researchers whether there may be a possible link between the two entities. Thus, this narrative review aims to provide a clearer perspective on this topic, addressing several issues. Methods. The authors performed independent research of the available literature in the most important electronic databases (PubMed, Google Scholar, and Science Direct). After applying the exclusion criteria, the reviewers focused on the most relevant articles published during the last 18 months, focusing on epidemiological and pathophysiological data regarding GBS and COVID-19. Results. In the first part, a summary of the most important results from the literature on the epidemiological situation in different parts of the world was conducted. Subsequently, possible immunological theories are presented in order to explain the epidemiological association between GBS and COVID-19 infection. Finally, the authors propose new research directions on the topic, discussing the issue of the COVID-19 vaccine, with its short and long term effects, and possible correlations with peripheral nerve pathology. Conclusion. Neurological manifestation in COVID-19 may represent a challenge for the clinician, and with growing numbers of unprecedented cases of peripheral nerve pathology associated with the SARS-CoV-2 virus being reported, further research is urgently needed.

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.

Nowadays, the success of multiple sclerosis therapy does not only mean the absence of relapses or the existence of a stationary clinical status under disease-modifying therapy, but the maintenance of a high quality of life index. Thus, in recent years, the attention of neurologists has focused on the relationship between depression and MS, depression being the most important factor influencing the MS patient’s quality of life. In this regard, the article aims to present a selection of the most important scientific data published during the last 5 years on this topic. Structured in two parts, the initial issue discussed is the etiopathogenesis of depression in MS, with focus on the presentation of theories on the causes of depressive symptoms in demyelinating disease, as well as the intricate relationship between the two clinical entities. Subsequently, the article focuses on capturing the latest developments in currently available pharmacological and non-pharmacological therapeutic means and future prospects for treatment.

Cerebral venous thrombosis in pediatric patient has a varied etiology. The authors present the case of a teenager who, since the debut of SARS-CoV-2 infection, has accused intermittent right side hemicrania, which has become persistent in association with nausea and vomiting since the 5th day of quarantine. She was hospitalized in the 9th day since the debut. Neuroimaging revealed extended venous cerebral thrombosis affecting the right sigmoid sinus, the transverse sinus bilaterally, the confluence of the transverse sinuses and the right internal jugular vein. The evolution was favorable under anticoagulant and symptomatic treatment. Laboratory tests excluded other etiological causes for the cerebral venous thrombosis, thus the authors consider that cerebral thrombosis is a possible complication of SARS-CoV-2 infection in teenagers.

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.

Alzheimer’s disease (AD) is a global health problem, with incidence and prevalence considered to increase during the next decades. However, no currently available effective treatment exists despite numerous clinical trials in progress. Moreover, although many hypotheses are accepted regarding the pathophysiological mechanisms of AD onset and evolution, there are still many unknowns about the disorder. A relatively new approach, based on the amyloid-beta dynamics among different biological compartments, is currently intensely discussed, as it seems to offer a promising solution with significant therapeutic impact. Known as the “cerebrospinal-fluid-sink therapeutic strategy”, part of the “three-sink therapeutic strategy”, this theoretical model focuses on the dynamics of amyloid-beta among the three main liquid compartments of the human body, namely blood, cerebrospinal fluid, and the (brain) interstitial fluid. In this context, this article aims to describe in detail the abovementioned hypothesis, by reviewing in the first part the most relevant anatomical and physiological aspects of amyloid-beta dynamics. Subsequently, explored therapeutic strategies based on the clearance of amyloid-beta from the cerebrospinal fluid level are presented, additionally highlighting their limitations. Finally, the originality and novelty of this work rely on the research experience of the authors, who focus on implantable devices and their utility in AD treatment.

Over the past decade, multiple sclerosis (MS), a chronic neuroinflammatory disease with severe personal and social consequences, has undergone a steady increase in incidence and prevalence rates worldwide. Despite ongoing research and the development of several novel therapies, MS pathology remains incompletely understood, and the prospect for a curative treatment continues to be unpromising in the near future. A sustained research effort, however, should contribute to a deeper understanding of underlying disease mechanisms, which will undoubtedly yield improved results in drug development. In recent years, the blood–brain barrier (BBB) has increasingly become the focus of many studies as it appears to be involved in both MS disease onset and progression. More specifically, neurovascular unit damage is believed to be involved in the critical process of CNS immune cell penetration, which subsequently favors the development of a CNS-specific immune response, leading to the classical pathological and clinical hallmarks of MS. The aim of the current narrative review is to merge the relevant evidence on the role of the BBB in MS pathology in a comprehensive and succinct manner. Firstly, the physiological structure and functions of the BBB as a component of the more complex neurovascular unit are presented. Subsequently, the authors review the specific alteration of the BBB encountered in different stages of MS, focusing on both the modifications of BBB cells in neuroinflammation and the CNS penetration of immune cells. Finally, the currently accepted theories on neurodegeneration in MS are summarized.

The incidence and prevalence of skin cancers is currently increasing worldwide, with early detection, adequate treatment, and prevention of recurrences being topics of great interest for researchers nowadays. Although tumor biopsy remains the gold standard of diagnosis, this technique cannot be performed in a significant proportion of cases, so that the use of alternative methods with high sensitivity and specificity is becoming increasingly desirable. In this context, liquid biopsy appears to be a feasible solution for the study of cellular and molecular markers relevant to different types of skin cancers. Circulating tumor cells are just one of the components of interest obtained from performing liquid biopsy, and their study by complementary methods, such as dielectrophoresis, could bring additional benefits in terms of characterizing skin tumors and subsequently applying personalized therapy. One purpose of this review is to demonstrate the utility of liquid biopsy primarily in monitoring the most common types of skin tumors: basal cell carcinoma, squamous cell carcinoma, and malign melanoma. In addition, the originality of the article is based on the detailed presentation of the dielectrophoretic analysis method of the most important elements obtained from liquid biopsy, with direct impact on the clinical and therapeutic approach of skin tumors.

Alzheimer’s disease (AD), the most common dementia worldwide, remains without an effective treatment to this day despite intensive research conducted during the last decades. In this context, researchers have turned their attention towards the prevention of this pathology, focusing on early detection and better control of the most important risk factors, concomitantly with trying to find potentially protective factors that may delay the onset of AD. From the multitude of factors studied, coffee (especially its main component, caffeine) is a current interesting research topic, taking into consideration the contradictory results of recent years’ studies. On the one hand, much of the evidence from fundamental research suggests the potentially protective trait of caffeine in AD, while other data mainly from human studies lean toward no correlation or even suggesting that caffeine is a veritable risk factor for dementia. Given the methodological heterogeneity of the studies, this review aims to bring new evidence regarding this topic and to try to clearly establish a correlation between the two entities. Thus, in the first part, the authors make a clear distinction between the effects of coffee and the effects of caffeine in AD, presenting a rich basis of clinical trials on both animal models and the human subject. Subsequently, the main pathophysiological mechanisms that would explain the action of caffeine in the etiopathogenesis of AD are reviewed. Finally, the role of computational models is presented, having beneficial impact on both better understanding of the disease mechanism and the development of new therapeutic approaches for AD prevention.

Neoplasia occurs as a result of genetic mutations. Research evaluating the association between gene mutations and skin cancer is limited and has produced inconsistent results. There are no established guidelines for screening skin cancer at molecular level. It should also be noted that the combinations of some mutations may play a role in skin tumors’ biology and immune response. There are three major types of skin cancer, and the originality of this study comes from its approach of each of them.

Here, we reported a study on the detection and electrical characterization of both cancer cell line and primary tumor cells. Dielectrophoresis (DEP) and electrical impedance spectroscopy (EIS) were jointly employed to enable the rapid and label-free differentiation of various cancer cells from normal ones. The primary tumor cells that were collected from two colorectal cancer patients, cancer cell lines (SW-403, Jurkat, and THP-1), and healthy peripheral blood mononuclear cells (PBMCs) were trapped first at the level of interdigitated microelectrodes with the help of dielectrophoresis. Correlation of the cells dielectric characteristics that was obtained via electrical impedance spectroscopy (EIS) allowed evident differentiation of the various types of cell. The differentiations were assigned to a “dielectric phenotype” based on their crossover frequencies. Finally, Randles equivalent circuit model was employed for highlighting the differences with regard to a series group of charge transport resistance and constant phase element for cancerous and normal cells.