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Background: interleukin 23 (IL-23) is an important factor involved in the survival and proliferation of T helper 17 cells (Th17), known for their implication in multiple sclerosis (MS). By contrast, IL-27 regulates and modulates the function of T lymphocytes, in particular as a suppressor of Th17 differentiation. The aims of the study were i) to test the association of cytokines with the clinical and genetic characteristics in each of the multiple sclerosis groups (CIS - clinically isolated syndrome, RRMS - relapsing-remitting MS and SPMS – Secondary progressive MS) and ii) to evaluate the association between serum levels of IL-23 and IL-27 with T4730C (IL-27), A964G (IL-27) and R381Q (IL-23) gene polymorphisms in RRMS patients. Methods: Blood samples were obtained from 82 patients diagnosed with MS under treatment with glatiramer acetate (GA), interferon beta (IFN) 1 A and 1 B. IL-23 and IL-27 serum concentrations were measured by enzyme-linked immunosorbant assay (ELISA). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used in order to determine the genotypes for R381Q (IL-23) polymorphisms, T4730C (IL-27) and A964G (IL-27). Results: Patients with SPMS, RRMS and CIS respectively differed significantly regarding age distribution (p = 0.003) but the studied MS groups were similar regarding age at disease onset (p = 0.528) and treatment type (p = 0.479). A significant increase of mean serum IL-27 was noticed in cases with early onset (age at disease onset 0.05) in the CIS and SPMS group respectively but a significant correlation between IL-23 and the duration of disease-modifying treatment was noticed only in the SPMS group. Conclusions: The results of the current study suggest an association between IL-23 levels and the R381Q gene polymorphism and also a relationship between IL-27 serum levels and early age at disease onset in RRMS patients.

Traumatic brain injury (TBI) is a significant public health concern, often leading to long-lasting impairments in cognitive, motor and sensory functions. The rapid development of non-invasive systems has revolutionized the field of TBI rehabilitation by offering modern and effective interventions. This narrative review explores the application of non-invasive technologies, including electroencephalography (EEG), quantitative electroencephalography (qEEG), brain–computer interface (BCI), eye tracking, near-infrared spectroscopy (NIRS), functional near-infrared spectroscopy (fNIRS), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) in assessing TBI consequences, and repetitive transcranial magnetic stimulation (rTMS), low-level laser therapy (LLLT), neurofeedback, transcranial direct current stimulation (tDCS), transcranial alternative current stimulation (tACS) and virtual reality (VR) as therapeutic approaches for TBI rehabilitation. In pursuit of advancing TBI rehabilitation, this narrative review highlights the promising potential of non-invasive technologies. We emphasize the need for future research and clinical trials to elucidate their mechanisms of action, refine treatment protocols, and ensure their widespread adoption in TBI rehabilitation settings.

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.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), affecting mostly young-aged people. As a chronic incurable disease, in most cases, it can lead to progressive neurological impairment and severe disability. Depression and anxiety are major distress factors for MS patients, being considerably aggravating elements for their functional capacity. In this study, we analysed the mood disorder distribution and the possible correlations between depression, anxiety, automatic negative thoughts, and MS disability. We took into consideration 146 MS patients, who completed a series of questionnaires: Beck Depression Inventory II (BDI-II), Endler Multidimensional Anxiety Scales-State (EMAS-S), and Automatic Thoughts Questionnaire (ATQ). The Expanded Disability Status Scale (EDSS) was used to measure the neurological disability. Of all patients, 30.1% had symptoms for depression and 11% presented suicidal thoughts. After analysing the correlation index between each variable, we found that there is a mild positive correlation between depression and the EDSS score and between anxiety and the EDSS score. A difference is found in the test scores according to the type of the MS disease. Also, automatic negative thoughts are strongly correlated with depression and anxiety, but do not mediate the path between psychological comorbidities and neurological impairment. Sociodemographic features and interferon-beta treatment were not related to the intensity of the mood disorders. The study suggests that depression and anxiety are frequently encountered among MS patients and these mental disfunctions have an impact on their disability. A proper identification of these risk factors may improve the quality of life for these patients.

Introduction: The SARS CoV-2 infection, responsible for COVID-19, has spread worldwide start-ing with the end of 2019, with major impact in the years 2020 and 2021, especially through the alpha, beta, and delta strains respectively. These strains have also been associated with the de-velopment of symptoms of anosmia and ageusia, even after overcoming the acute form of the disease, as part of the post-COVID-19 sequalae that make up the so-called “long-Covid”. [1] The purpose of this systematic literature review was to study these disabling symptoms in the con-text of long-COVID syndrome. Material and methods: In order to accomplish this review, we used the method Preferred Re-porting Items for Systematic Reviews and Meta-Analyses (acronym - PRISMA) to filter and select the articles of interest that appeared in the period 1/01/2021-31/12/2022, in the international med-ical databases: Elsevier, NCBI/ PubMed,NCBI/ PMC and PEDro (= Physiotherapy Evidence Data-base classification), as well as ISI Web of Knowledge (Institute for Scientific Information - ex Thomson Reuters - Clarivate Analytics). We used the keywords for the selection: "COVID-19" / "viral neuroinfections" + "smell" /”olphactory” + "taste" /”gustatory”+ "anosmia" + 'ageusia' +'recovery'+'rehabilitation'. Results and discussion: After applying indirect and then direct quantitative and qualitative fil-tering, 25 articles remained that met the selection criteria (noted in order of relevance in table 1, at the end of the article). We also added a number of freely identified papers, considered relevant to our topic. We studied aspects of the "long-COVID" syndrome, mainly related to neu-ro-psychiatric symptoms - especially taste and smell disorders (anosmia/ageusia), risk factors, predictors for this status, pathophysiology, their intricate mechanism of action, frequency of symptoms, neuroanatomy imaging correlated with clinical aspects, effect of anosmia and ageu-sia on quality of life, recovery from such sequelae, favorable/unfavorable prognostic factors in this regard. Conclusions: Smell and taste are more than just simple sensations/perceptions and anosmia/ ageusia does not always recover spontaneously. The category of patients who are left with such permanent qualitative/quantitative alterations requires in-depth study in order to establish standardized and more effective methods of diagnosis, evaluation and treatment and recovery, than those available at the moment. The chosen topic represents a partially studied niche in the current well of knowledge, which will allow us, following the theoretical and practical deepen-ing of the subject, some possible elements of future contribution.

Sensory ganglionopathies (SG) are a rare but distinct clinical subgroup of peripheral neuropathies characterized by damage to dorsal root ganglia. Typical manifestations include early gait and limb ataxia, widespread diminished or absent deep tendon reflexes accompanied by Romberg sign and pseudoathetoid movements.The diagnosis of SG is valuable since it may prompt towards early recognition of an underlying malignancy or autoimmune disorder. We report the case of a female diagnosed with mixed connective tissue disease (MCTD) along with severe SG. To our knowledge, such disease association has not been reported yet. The pathophysiology in cases linked to MCTD is unclear and asks for further studies. Moreover, the important degree of disability associated with this condition highlights the need for effective therapies’ development.

Recent advances in understanding the pathogenesis of multiple sclerosis (MS) have brought into the spotlight the major role played by reactive astrocytes in this condition. Response Gene to Complement (RGC)-32 is a gene induced by complement activation, growth factors, and cytokines, notably transforming growth factor β, that is involved in the modulation of processes such as angiogenesis, fibrosis, cell migration, and cell differentiation. Studies have uncovered the crucial role that RGC-32 plays in promoting the differentiation of Th17 cells, a subtype of CD4+ T lymphocytes with an important role in MS and its murine model, experimental autoimmune encephalomyelitis. The latest data have also shown that RGC-32 is involved in regulating major transcriptomic changes in astrocytes and in favoring the synthesis and secretion of extracellular matrix components, growth factors, axonal growth molecules, and pro-astrogliogenic molecules. These results suggest that RGC-32 plays a major role in driving reactive astrocytosis and the generation of astrocytes from radial glia precursors. In this review, we summarize recent advances in understanding how RGC-32 regulates the behavior of Th17 cells and astrocytes in neuroinflammation, providing insight into its role as a potential new biomarker and therapeutic target.

Abstract: Introduction. Osteoid osteoma represents about 3% of all primary bone tumors and 11% of all benign bone tumors. Data from the literature suggest that a neuromuscular rehabilitation program after osteoid osteoma surgery is very beneficial and improves the general quality of life. Material and methods. A 30-year-old male patient with intermittent right shoulder pain radiating to the right hand, and recurrent myalgias in the past year presented to our neuro-logical department. The neurological examination highlighted limitation of the abduction of the right upper limb. The paraclinical investigations included plain radiography of the right upper limb and electroneurography, which were normal, and native cervical MRI which revealed discrete C5 disc overflow, without visible signs of compression. The patient presented limited initial response to NSAIDs, so his treatment was changed to corticoster-oid therapy. Further, the patient was guided to undergo a rheumatological examination where a musculoskeletal ultrasound was performed, showing no any specific modifica-tion. Additionally, we indicated a native right shoulder MRI, which revealed a signal mod-ification of the proximal humeral diaphysis. We further indicated an MRI scan with con-trast of the upper right limb, which revealed a nidus at the top one-third of the humerus. Additionally, a CT scan with contrast of the same region displayed images that were high-ly suggestive of osteoma. The patient was referred to the orthopedics department, where a complete resection of the tumor was performed, and the pathology report confirmed the fi-nal diagnosis of osteoid osteoma. Conclusions. Recovery after osteoid osteoma surgery is more beneficial if the neuromuscu-lar rehabilitation program, that has an important role in increasing muscle strength, is combined with orthopedic devices and pain medication.

BackgroundMalnutrition is common after stroke and can affect rehabilitation and healthcare costs. A comprehensive overview of stroke patients' nutritional condition from the hyperacute to the chronic phase is lacking. This systematic review aimed to investigate the prevalence of impaired nutritional condition (INC) across the continuum of care in specific phases after stroke.MethodsCAB ABSTRACTS, Embase, MEDLINE, were used to collect studies published between 01-01-1999 and 26-08-2020. Primary and secondary outcomes were prevalence of INC and prevalence of malnutrition, respectively. Exploratory outcomes were prevalence of INC at follow-up, nutritional examination methods, prevalence of dysphagia, stroke severity, adverse events, and continent-specific prevalence of INC. A random-effects meta-analysis model was used to estimate the phase-specific pooled prevalence of INC and malnutrition.ResultsThe dataset consisted of 78 study groups selected over a total of 1,244 identified records. The pooled prevalence of INC and malnutrition were 19% (95%CI:7–31) (N = 4) and 19% (95%CI:9–29) (N = 3), 34% (95%CI:25–43) (N = 34) and 26% (95%CI:18–35) (N = 29), 52% (95%CI:43–61) (N = 34) and 37% (95%CI:28–45) (N = 31), 21% (95%CI:12–31) (N = 3) and 11% (95%CI:0–24) (N = 3) and 72% (95%CI:41–100) (N = 3) and 30% (95%CI:0–76) (N = 2) in the hyperacute, acute, early subacute, late subacute, and chronic phase, respectively.ConclusionINC and malnutrition are highly prevalent in all stages of stroke care. Since malnutrition has been shown to negatively affect clinical outcomes, mortality, and overall healthcare expenditure in stroke survivors, it is essential to examine and monitor the nutritional status of stroke patients throughout their care journey to guide and plan, timely nutritional support and dietary modification.

Stroke is a leading cause of disability and mortality, resulting in substantial socio-economic burden for healthcare systems. With advances in artificial intelligence, visual image information can be processed into numerous quantitative features in an objective, repeatable and high-throughput fashion, in a process known as radiomics analysis (RA). Recently, investigators have attempted to apply RA to stroke neuroimaging in the hope of promoting personalized precision medicine. This review aimed to evaluate the role of RA as an adjuvant tool in the prognosis of disability after stroke. We conducted a systematic review following the PRISMA guidelines, searching PubMed and Embase using the keywords: ‘magnetic resonance imaging (MRI)’, ‘radiomics’, and ‘stroke’. The PROBAST tool was used to assess the risk of bias. Radiomics quality score (RQS) was also applied to evaluate the methodological quality of radiomics studies. Of the 150 abstracts returned by electronic literature research, 6 studies fulfilled the inclusion criteria. Five studies evaluated predictive value for different predictive models (PMs). In all studies, the combined PMs consisting of clinical and radiomics features have achieved the best predictive performance compared to PMs based only on clinical or radiomics features, the results varying from an area under the ROC curve (AUC) of 0.80 (95% CI, 0.75–0.86) to an AUC of 0.92 (95% CI, 0.87–0.97). The median RQS of the included studies was 15, reflecting a moderate methodological quality. Assessing the risk of bias using PROBAST, potential high risk of bias in participants selection was identified. Our findings suggest that combined models integrating both clinical and advanced imaging variables seem to better predict the patients’ disability outcome group (favorable outcome: modified Rankin scale (mRS) ≤ 2 and unfavorable outcome: mRS > 2) at three and six months after stroke. Although radiomics studies’ findings are significant in research field, these results should be validated in multiple clinical settings in order to help clinicians to provide individual patients with optimal tailor-made treatment.

Health policies in transitioning health systems are rarely informed by the social burden and the incidence shifts in disease epidemiology. Cerebral venous thrombosis (CVT) is a type of stroke more often affecting younger adults and women, with higher incidences being reported in recent studies. A retrospective, hospital-based population study was conducted at Cluj-Napoca Emergency County Hospital across a 5-year period between 2017 and 2021. The overall incidence and the rates in distinctive gender and age groups were assessed. Length of hospital stay (LHS), modified Rankin score (mRS) and mortality at discharge and at 3 months were calculated. Fifty-three patients were included. The median age was 45 years, and 64.2% were women. In our population of 3,043,998 person-years, 53 CVT cases resulted in an incidence of 1.74 per 100,000 (95% CI 1.30–2.27). CVT incidence was higher in women (2.13 per 100,000, 95% CI 1.47–2.07). There was a statistically significant difference in LHS between patients with different intracranial complications (Kruskal–Wallis, p = 0.008). The discharge mRS correlated with increasing age (rs = 0.334, p = 0.015), transient risk factors (Fisher’s exact test, p = 0.023) and intracranial complications (Fisher’s exact test, p = 0.022). In addition, the mRS at 3 months was statistically associated with increasing age (rs = 0.372, p = 0.006) and transient risk factors (Fisher’s exact test, p = 0.012). In-hospital mortality was 5.7%, and mortality at follow up was 7.5%, with higher rates in women (5.9% and 8.8%, respectively). Our findings may provide insight regarding the epidemiological features of certain patient groups more prone to developing CVT and its complications, informing local and central stakeholders’ efforts to improve standards of care.

Response Gene to Complement 32 (RGC-32) is an important mediator of the TGF-β signaling pathway, and an increasing amount of evidence implicates this protein in regulating astrocyte biology. We showed recently that spinal cord astrocytes in mice lacking RGC-32 display an immature phenotype reminiscent of progenitors and radial glia, with an overall elongated morphology, increased proliferative capacity, and increased expression of progenitor markers when compared to their wild-type (WT) counterparts that make them incapable of undergoing reactive changes during the acute phase of experimental autoimmune encephalomyelitis (EAE). Here, in order to decipher the molecular networks underlying RGC-32’s ability to regulate astrocytic maturation and reactivity, we performed next-generation sequencing of RNA from WT and RGC-32 knockout (KO) neonatal mouse brain astrocytes, either unstimulated or stimulated with the pleiotropic cytokine TGF-β. Pathway enrichment analysis showed that RGC-32 is critical for the TGF-β-induced up-regulation of transcripts encoding proteins involved in brain development and tissue remodeling, such as axonal guidance molecules, transcription factors, extracellular matrix (ECM)-related proteins, and proteoglycans. Our next-generation sequencing of RNA analysis also demonstrated that a lack of RGC-32 results in a significant induction of WD repeat and FYVE domain-containing protein 1 (Wdfy1) and stanniocalcin-1 (Stc1). Immunohistochemical analysis of spinal cords isolated from normal adult mice and mice with EAE at the peak of disease showed that RGC-32 is necessary for the in vivo expression of ephrin receptor type A7 in reactive astrocytes, and that the lack of RGC-32 results in a higher number of homeodomain-only protein homeobox (HOPX)+ and CD133+ radial glia cells. Collectively, these findings suggest that RGC-32 plays a major role in modulating the transcriptomic changes in astrocytes that ultimately lead to molecular programs involved in astrocytic differentiation and reactive changes during neuroinflammation.

Astrocytes are increasingly recognized as critical contributors to multiple sclerosis pathogenesis. We have previously shown that lack of Response Gene to Complement 32 (RGC-32) alters astrocyte morphology in the spinal cord at the peak of experimental autoimmune encephalomyelitis (EAE), suggesting a role for RGC-32 in astrocyte differentiation. In this study, we analyzed the expression and distribution of astrocytes and astrocyte progenitors by immunohistochemistry in spinal cords of wild-type (WT) and RGC-32-knockout (KO) mice with EAE and of normal adult mice. Our analysis showed that during acute EAE, WT astrocytes had a reactive morphology and increased GFAP expression, whereas RGC-32 KO astrocytes had a morphology similar to that of radial glia and an increased expression of progenitor markers such as vimentin and fatty acid binding protein 7 (FABP7). In control mice, GFAP expression and astrocyte density were also significantly higher in the WT group, whereas the number of vimentin and FABP7-positive radial glia was significantly higher in the RGC-32 KO group. In vitro studies on cultured neonatal astrocytes from WT and RGC-32 KO mice showed that RGC-32 regulates a complex array of molecular networks pertaining to signal transduction, growth factor expression and secretion, and extracellular matrix (ECM) remodeling. Among the most differentially expressed factors were insulin-like growth factor 1 (IGF1), insulin-like growth factor binding proteins (IGFBPs), and connective tissue growth factor (CTGF); their expression was downregulated in RGC-32-depleted astrocytes. The nuclear translocation of STAT3, a transcription factor critical for astrogliogenesis and driving glial scar formation, was also impaired after RGC-32 silencing. Taken together, these data suggest that RGC-32 is an important regulator of astrocyte differentiation during EAE and that in the absence of RGC-32, astrocytes are unable to fully mature and become reactive astrocytes.

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version “Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)”. The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.

Vertigo and dizziness are among the most frequent presenting symptoms, not only in neurology, but also in ENT and internal medicine clinics. Vertigo is a spinning sensation or the feeling that the surroundings are spinning. Floating sensation, lightheadiness, forward, backward – and sideward fall sensation, walking instability, gait hesitation or unsteadiness are other type of dizziness. Several clinical pictures of different etiologies include vertigo and dizziness as underlying complaint. Diagnosis should be based on clinical history and neurotological evaluation. A common perspective of neurologists, ENT doctors and general medicine physicians is needed for a better diagnosis and treatment of vertigo and dizziness patients.

Vascular dementia is, in its current conceptual form, a distinct type of dementia with a spectrum of specific clinical and pathophysiological features. However, in a very large majority of cases, these alterations occur in an already aged brain, characterized by a milieu of cellular and molecular events common for different neurodegenerative diseases. The cell signaling defects and molecular dyshomeostasis might lead to neuronal malfunction prior to the death of neurons and the alteration of neuronal networks. In the present paper, we explore some of the molecular mechanisms underlying brain malfunction triggered by cerebrovascular disease and risk factors. We suggest that, in the age of genetic investigation and molecular diagnosis, the concept of vascular dementia needs a new approach.