Search Results (6,427)

Background: Behçet’s Disease (BD) was traditionally classified according to the International Study Group (ISG), where oral ulcers were mandatory. The International Team for the Revision of the International Criteria for BD (ICBD) introduced a scoring system instead. Our aim was to assess (a) sensitivity, (b) concordance between ISG and ICDB criteria in global and severe BD cases (ocular, vascular, and neurological), and (c) evaluate their clinical implications. Methods: Retrospective cohort study including 142 BD patients diagnosed in a well-defined population in Northern Spain, between January 1980 and November 2023. Both ISG and ICBD criteria were compared, sensitivity and concordance were assessed using Prevalence-Adjusted and Bias-Adjusted Kappa (PABAK) and the unadjusted Kappa. Results: A total of 142 BD patients diagnosed by expert rheumatologists (73 men; mean age of 36.4) were studied. Among them, 84 met ISG criteria, while 116 fulfilled ICBD criteria. Sensitivity of ISG and ICBD criteria in the overall cohort was (59.1% and 81.6%), respectively. Among patients with severe manifestations (ocular, vascular, or neurological), sensitivity increased to 71.2% for ISG and 92.5% for ICBD. Overall concordance was moderate (Kappa = 0.490), with 70.4% of patients classified identically. When adjusting prevalence and bias, concordance improved slightly (PABAK = 0.549). Of the 32 patients classified as BD exclusively by ICBD, 7 were receiving anti-TNF therapy, and 2 were receiving apremilast. Conclusions: The ICBD criteria demonstrated higher sensitivity than the traditional ISG criteria in classifying BD, particularly in severe cases. Classifying these additional patients under ICBD facilitated the initiation of on-label biologic treatments, potentially enhancing BD management, especially for severe cases. Full article

Pediatric palliative care (PPC) aims to enhance the quality of life of children with life-limiting conditions and their families through individualized, interdisciplinary support. Among this population, children with neurological diseases represent a substantial and growing group, often facing prolonged disease courses, cognitive impairment, and high prognostic uncertainty. Effective communication is central to PPC; however, it remains deeply influenced by cultural, religious, and spiritual frameworks that shape family perceptions of illness, suffering, and decision-making. This narrative review explores communication strategies in PPC, with a specific focus on children with neurological conditions, highlighting conceptual foundations, cross-cultural variations, and emerging best practices. Key findings highlight the importance of culturally humble approaches, family-centered communication models, and structured tools, such as co-designed advance care planning and dignity therapy, to enhance communication. Additionally, the review highlights the presence of ethical and interdisciplinary challenges, particularly in neonatal and neurology settings, where misaligned team messaging and institutional hesitancy may compromise trust and timely referral to palliative care. Future research, policy, and clinical education priorities should advocate for models that are inclusive, ethically grounded, and tailored to the unique trajectories of neurologically ill children. Integrating cultural competence, team alignment, and family voices is essential for delivering equitable and compassionate PPC across diverse care settings. Full article

Ischemic stroke is a primary cause of cerebrovascular diseases and continues to be one of the leading causes of death and disability among patients worldwide. Pathological processes caused by vascular damage due to stroke occur in a time-dependent manner and are classified into three categories: acute, subacute, and chronic. Current treatments for ischemic stroke are limited to effectiveness in the early stages. In this study, we investigated the therapeutic effect of an oriental medicine, Gosha-jinki-gan (TJ107), on improving chronic ischemic stroke using the mouse model with middle cerebral artery occlusion (MCAO). The changes in the intracerebral inflammatory response (macrophages (F4/80), TLR2•4, IL-23, IL-17, TNF-α, and IL-1β) were examined using real-time RT-PCR. The MCAO mice showed the increased expression of glial fibrillary acidic protein (GFAP) and of F4/80, TLR2, TLR4, IL-1β, TNF-α, and IL-17 in the brain tissue from the MCAO region. This suggests that they contribute to the expansion of the ischemic stroke infarct area and to the worsening of the neurological symptoms of the MCAO mice in the chronic phase. On the other hand, the administration of TJ107 was proven to reduce the infarct area, with decreased GFAP expression, suppressed macrophage infiltration in the brain, and reduced TNF-α, IL-1β, and IL-17 production compared with the MCAO mice. This study first demonstrated Gosha-jinki-gan’s therapeutic effects on the chronic ischemic stroke. Full article

Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article

Brain organoid technology has revolutionized in vitro modeling of human neurodevelopment and disease, providing unprecedented insights into cortical patterning, neural circuit assembly, and pathogenic mechanisms of neurological disorders. Critically, human brain organoids uniquely recapitulate human-specific developmental processes—such as the expansion of outer radial glia and neuromelanin—that are absent in rodent models, making them indispensable for studying human brain evolution and dysfunction. However, a major bottleneck persists: Extended culture periods (≥6 months) are empirically required to achieve late-stage maturation markers like synaptic refinement, functional network plasticity, and gliogenesis. Yet prolonged conventional 3D culture exacerbates metabolic stress, hypoxia-induced necrosis, and microenvironmental instability, leading to asynchronous tissue maturation—electrophysiologically active superficial layers juxtaposed with degenerating cores. This immaturity/heterogeneity severely limits their utility in modeling adult-onset disorders (e.g., Alzheimer’s disease) and high-fidelity drug screening, as organoids fail to recapitulate postnatal transcriptional signatures or neurovascular interactions without bioengineering interventions. We summarize emerging strategies to decouple maturation milestones from rigid temporal frameworks, emphasizing the synergistic integration of chronological optimization (e.g., vascularized co-cultures) and active bioengineering accelerators (e.g., electrical stimulation and microfluidics). By bridging biological timelines with scalable engineering, this review charts a roadmap to generate translationally relevant, functionally mature brain organoids. Full article

Dopamine transporter (DAT) mutations are associated with neurological and psychiatric diseases, and DAT gene knockout in rats (DAT-KO) provides an opportunity to evaluate the DAT role in pathological conditions. We analyzed DAT expression and co-expression with other genes in the substantia nigra and striatum in public transcriptomic data represented in the GEO repository and then estimated the identified DAT co-expression pattern in DAT-KO rats by RT-PCR. In silico analysis confirmed DAT expression in the substantia nigra and absence of DAT mRNA in the striatum. Also, DAT is co-expressed with genes involved in dopamine signaling, but these associations are disrupted in dopamine neuron-damaging conditions. To estimate this co-expression pattern when DAT expression is lost, we evaluate it in the substantia nigra of DAT-KO rats. However, in DAT-KO rats the associations between genes involved in dopamine signaling were not disturbed compared to wild-type littermates, and tyrosine hydroxylase expression upregulation in the substantia nigra of these animals may be considered as compensation for the loss of dopamine reuptake. Further studies of expression regulation in dopamine neurons of DAT-KO rats may provide valuable information for compensatory mechanisms in substantia nigra dopaminergic neurons. Full article

Background/Objectives: Wilson’s disease (WD) is a rare autosomal recessive disorder of copper metabolism that results in hepatic, neurological, and psychiatric manifestations. Despite being described globally, data from the Middle East remains limited. This study presents the first comprehensive national cohort analysis of WD in Oman, examining clinical features, diagnostic challenges, treatment patterns, and long-term outcomes. Methods: A retrospective cohort study was conducted on 36 Omani patients diagnosed with WD between 2013 and 2020 at Sultan Qaboos University Hospital using AASLD diagnostic criteria. Clinical presentation, biochemical parameters, treatment regimens, and progression-free survival were analyzed. Results: The median age at diagnosis was 14.5 years, with a slight female predominance (55.6%). Clinical presentation varied: 25% had hepatic symptoms, 22.2% had mixed hepatic-neurological features, and 16.7% presented with neurological symptoms alone. Asymptomatic cases identified via family screening accounted for 33.3%. Diagnostic delays were most pronounced among patients presenting with neurological symptoms. A positive family history was reported in 88.9% of cases, suggesting strong familial clustering despite a low rate of consanguinity (5.6%). Regional distribution was concentrated in Ash Sharqiyah North and Muscat. Chelation therapy with trientine or penicillamine, often combined with zinc, was the mainstay of treatment. Treatment adherence was significantly associated with improved progression-free survival (p = 0.012). Conclusions: WD in Oman is marked by heterogeneous presentations, frequent diagnostic delays, and strong familial clustering. Early detection through cascade screening and sustained treatment adherence are critical for favorable outcomes. These findings support the need for national screening policies and structured long-term care models for WD in the region. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder that primarily affects young adults and is frequently accompanied by psychiatric comorbidities such as depression and anxiety, both of which significantly diminish patients’ quality of life (QoL). This study investigated the effect of two oral disease-modifying therapies (DMTs), fingolimod and cladribine, on mental health and QoL in patients with relapsing-remitting MS (RRMS). The aim of the study was to compare levels of depression, anxiety, and health-related quality of life (HRQoL) in RRMS patients treated with fingolimod or cladribine, and to evaluate their associations with clinical and radiological parameters. Materials and Methods: Eighty RRMS patients aged 18 to 50 years with Expanded Disability Status Scale (EDSS) scores of 3.0 or less, no recent disease relapse, and no history of antidepressant use were enrolled. Forty patients were treated with fingolimod and forty with cladribine. Depression and anxiety were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). QoL was evaluated using the Multiple Sclerosis QoL-54 (MSQOL-54) instrument. Additional clinical data, including MRI-based lesion burden, EDSS scores, age, disease duration, and occupational status, were collected. Results: No statistically significant differences were observed between the two groups regarding HDRS and HARS scores (p > 0.05). However, patients treated with fingolimod had significantly higher scores in the Energy/Fatigue subdomain (7.55 ± 2.02 vs. 6.56 ± 2.57, p = 0.046) and Composite Mental Health (CMH) score (64.73 ± 15.01 vs. 56.00 ± 18.93, p = 0.029) compared to those treated with cladribine. No significant differences were found in the independent items of the MSQOL-54. A negative correlation was identified between total lesion load and QoL scores. Conclusions: Although fingolimod and cladribine exert comparable effects on depression and anxiety levels, fingolimod may be associated with better mental health outcomes and reduced fatigue in RRMS patients. Furthermore, lesion burden and clinical parameters such as age and EDSS score may independently influence QoL, regardless of the DMT used. Full article

Drosophila melanogaster is one of the most known and used organisms worldwide, not just to study general biology problems but above all for modeling complex human diseases. During the decades, it has become a central tool to understand the genetics of human disease, how mutations alter the behavior and health of cells, tissues, and organs, and more recently to test new compounds with a potential therapeutic use. But how did this small insect become so crucial in genetics? And how is it currently used in the study of human conditions affecting millions of people? In this review, we retrace the historical origins of its adoption in genetics laboratories and list all the advantages it provides to scientific research, both for its daily usage and for the fine tuning of gene regulation through genetic engineering approaches. We also provide some examples of how it is used to study human diseases such as cancer, neurological and infectious diseases, and its importance in drug discovery and testing. Full article

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

Background: Charcot–Marie–Tooth disease (CMT) is a genetically and phenotypically heterogeneous hereditary neuropathy. Axonal CMT type 2 (CMT2) subtypes often exhibit overlapping clinical features, which makes molecular genetic analysis essential for accurate diagnosis and subtype differentiation. Methods: This retrospective study included five pediatric patients who presented with gait disturbance, muscle weakness, and foot deformities and were subsequently diagnosed with axonal forms of CMT. Clinical data, electrophysiological studies, neuroimaging, and genetic analyses were evaluated. Whole exome sequencing (WES) was performed in three sporadic cases, while targeted CMT gene panel testing was used for two siblings. Variants were interpreted using ACMG guidelines, supported by public databases (ClinVar, HGMD, and VarSome), and confirmed by Sanger sequencing when available. Results: All had absent deep tendon reflexes and distal muscle weakness; three had intellectual disability. One patient was found to carry a novel homozygous frameshift variant (c.2568_2569del) in the IGHMBP2 gene, consistent with CMT2S. Other variants were identified in the NEFH (CMT2CC), DYNC1H1 (CMT2O), and MPV17 (CMT2EE) genes. Notably, a previously unreported co-occurrence of MPV17 mutation and congenital heart disease was observed in one case. Conclusions: This study expands the clinical and genetic spectrum of pediatric axonal CMT and highlights the role of early physical examination and molecular diagnostics in detecting rare variants. Identification of a novel IGHMBP2 variant and unique phenotypic associations provides new insights for future genotype–phenotype correlation studies. Full article

The popularity of bioactive compounds extracted from sea cucumbers is growing due to their wide application in the pharmaceutical industry, particularly in the development of drugs for neurological disorders. Different types of compounds, such as saponins, phenolic compounds, cerebrosides, and glucocerebrosides, are being studied intensively for their efficacy in assessing the treatment of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and brain tumors, among others. Positive results have been observed in the upregulation in the content of p-CREB, p-PL3K, BDNF, SOD, and MDA. Furthermore, the neuroprotective mechanism of the compounds against Alzheimer’s disease revealed that suppressing the phosphorylation of tau protein by the PI3K/Akt/GSK3β pathway leads to improved synaptic plasticity and reduced nerve fiber tangles. This comprehensive review explores recent findings on the therapeutic potential of sea cucumber bioactives in the treatment of brain-related disorders. Full article

Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities. Objectives/Methods: This study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review. Results: Enzyme activity, molecular data, and phenotypic assessments are described to explore genotype–phenotype correlations and identify diagnostic challenges. Conclusions: These findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members. Full article

Background/Objectives: Traumatic brain injury is one of the leading causes of death and disability. When traumatic brain injury is repeated over time, it can lead to the development of Chronic Traumatic Encephalopathy, a chronic neurodegenerative disease commonly observed in individuals who engage in contact sports or military personnel involved in activities with a high risk of repeated head trauma. At autopsy, the examination of the brain reveals regional atrophy, corresponding to high concentrations of glutamate receptors. Microscopically, the primary findings are the deposition of neurofibrillary tangles and neuropil threads. The aim of this study is to highlight the clinical and histopathological characteristics of Chronic Traumatic Encephalopathy, providing diagnostic support to forensic pathologists. Additionally, it seeks to aid in the differential diagnosis of similar conditions. Methods: A review of literature was conducted following the PRISMA criteria. Of 274 articles, 7 were selected. Results: According to these papers, most patients were male and exhibited neurological symptoms and neuropsychiatric impairments, and a proportion of them committed suicide or had aggressive behavior. Conclusions: Chronic Traumatic Encephalopathy remains largely underdiagnosed during life. The definitive diagnosis of Chronic Traumatic Encephalopathy is established post-mortem through the identification of pathognomonic tauopathy lesions. Early and accurate antemortem recognition, particularly in at-risk individuals, is highly valuable for its differentiation from other neurodegenerative conditions, thereby enabling appropriate clinical management and potential interventions. Full article