Neurology International最新文献

Background: Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by progressive lower-limb spasticity and weakness. SPAST mutations are the most common cause of autosomal dominant HSP (SPG4). However, many pathogenic SPAST variants are unique and genetic data from underrepresented communities remain limited.

Methods: Whole-exome sequencing (WES) was performed on the index patient with HSP. Variant annotation tools included Ensembl VEP, LOFTEE, CADD, SIFT, PolyPhen-2, MutationTaster, and SpliceAI. Variant interpretation followed ACMG/AMP guidelines. Clinical evaluation and family history supported phenotypic correlation and segregation.

Results: A novel heterozygous frameshift variant in SPAST (c.339delG; p.Glu114Serfs*47) was identified. The variant was predicted to cause nonsense-mediated decay, resulting in loss of the microtubule-interacting and AAA ATPase domains of spastin. It was absent from population databases (gnomAD, TOPMed, 1000 Genomes) and public variant repositories (ClinVar, HGMD). The variant segregated with disease in two affected siblings and could be classified as likely pathogenic.

Conclusions: This novel SPAST frameshift variant expands the mutational spectrum of SPG4-HSP and highlights the importance of including isolated or minority communities in genomic research to improve variant interpretation.

Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, and progressive cognitive decline. Recent evidence has highlighted the role of blood-brain barrier (BBB) dysfunction in the early stages of AD pathology. Objective: We sought to explore the histological structure and physiological function of the blood-brain barrier, and to identify the shared pathological mechanisms between BBB disruption and Alzheimer's disease progression. Methods: This narrative review was conducted through a comprehensive search of peer-reviewed literature from 1997 to 2024, using databases such as PubMed, Elsevier, Scopus, and Google Scholar. Results: Multiple histological and cellular components-including endothelial cells, pericytes, astrocytes, and tight junctions-contribute to BBB integrity. The breakdown of this barrier in AD is associated with chronic inflammation, oxidative stress, vascular injury, pericyte degeneration, astrocyte polarity loss, and dysfunction of nutrient transport systems like Glucose Transporter Type 1 (GLUT1). These alterations promote neuroinflammation, amyloid-β (Aβ) accumulation, and progressive neuronal damage. Conclusions: BBB dysfunction is not merely a consequence of AD but may act as an early and active driver of its pathogenesis. Understanding the mechanisms of BBB breakdown can lead to early diagnostic markers and novel therapeutic strategies aimed at preserving or restoring barrier integrity in Alzheimer's disease.

Background: Stroke is a major cerebrovascular disease characterized by disrupted cerebral blood flow, leading to neuronal damage and significant physical, cognitive, and emotional sequelae. While advancements in acute stroke management have improved survival rates, long-term complications such as cognitive impairment and depression continue to hinder recovery. This study addresses these dimensions within the context of ischemic stroke.

Aim: The aim of this study was to analyze the cognitive status, functionality, and depressive symptoms in patients with ischemic stroke, exploring interrelations between cognitive, functional, and emotional outcomes to prioritize clinical interventions.

Design: This was an analytical, observational, cohort, and prospective study.

Methods: The study included 81 subjects diagnosed with ischemic stroke admitted to the Neurology Department of Lucus Augusti University Hospital. Data were collected at three time points-admission, discharge, and follow-up-using validated instruments such as the National Institutes of Health Stroke Scale, Mini-Mental State Examination, Barthel Index, and Beck Depression Inventory. Statistical analyses included Spearman's correlation, Kruskal-Wallis, and Mann-Whitney tests.

Results: Patients with greater cognitive impairment at admission showed poorer functional recovery and higher depressive symptoms during follow-up. Depressive symptoms remained minimal in most cases, but correlations with cognitive and functional deficits were significant. NIHSS scores at admission strongly predicted both functional and emotional recovery, reinforcing its value in early prognosis and therapeutic planning.

Conclusions: This study highlights the importance of integrating cognitive, functional, and emotional dimensions into stroke care protocols to optimize patient recovery and improve long-term outcomes.

Background/Objectives: The approval of disease-modifying therapies has significantly improved outcomes for patients with spinal muscular atrophy (SMA), yet their long-term safety profiles remain under continuous evaluation. This study aimed to assess trends in the reporting of suspected adverse drug reactions (ADRs) associated with nusinersen, onasemnogene abeparvovec, and risdiplam across the European Union. Methods: We conducted a secondary analysis of annual suspected ADR data reported to EudraVigilance from 2017 to 2024 for the three approved disease-modifying therapies for SMA. On top of general reporting trend, specific adverse reactions of interest included post-lumbar puncture syndrome for nusinersen, liver toxicity and elevated serum troponin for onasemnogene abeparvovec, and respiratory and gastrointestinal reactions for risdiplam. Joinpoint regression analysis was used to evaluate annual percent changes and identify statistically significant trend segments for each medicine. Results: The reporting of suspected ADRs for nusinersen showed an initial increase, followed by a significant decline after 2019. Onasemnogene abeparvovec exhibited a continued but decelerating increase in suspected ADRs, while risdiplam demonstrated a consistent upward trend across all reported reactions. Conclusions: Diverging patterns in adverse reaction reporting suggest a stabilizing safety profile for nusinersen and potential emerging safety signals for risdiplam and onasemnogene abeparvovec, underscoring the need for ongoing continued pharmacovigilance (e.g., post-authorization studies and spontaneous reporting).

Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating skeletal muscle weakness. Myasthenic crisis (MCr), a severe and potentially life-threatening complication, presents with respiratory failure and requires intensive care and rapid immunomodulatory intervention. Conventional MCr treatments-such as plasma exchange (PLEX), intravenous immunoglobulin (IVIG), and intravenous methylprednisolone (IVMP)-remain standard treatments; however, they present significant limitations, including delayed onset of action, adverse effects, and inconsistent efficacy. Recent therapeutic advances have led to the development of molecularly targeted therapies based on MG pathophysiology, particularly neonatal Fc receptor (FcRn) inhibitors and complement inhibitors, which have shown efficacy in refractory or maintenance settings. This review explores the potential application of these agents in MCr. We review published case reports involving FcRn inhibitors (efgartigimod, efgartigimod-SC, rozanolixizumab) and complement inhibitors (eculizumab, ravulizumab, zilucoplan), highlighting their rapid onset of action and safety profiles in MCr. While efgartigimod and eculizumab are the most commonly reported agents in MCr, data remain limited to small case series. Emerging evidence suggests these agents may offer effective alternatives to conventional therapies, with favorable safety and potential for rapid symptom resolution. We also discuss strategic considerations for therapy selection, including antibody subtype, coexisting autoimmune conditions, genetic factors, and transition to long-term maintenance. Though the current evidence is promising, large-scale randomized studies are needed to establish definitive roles for these therapies in MCr management.

Background and objectives: Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder with autosomal dominant forms most often linked to MAPT, GRN, and C9orf72. We aimed to evaluate the prevalence of pathogenic variants in these genes in a hospital-based cohort of FTD patients assessed at a tertiary referral center in southeastern Serbia.

Methods: We studied 58 consecutive patients with FTD spectrum syndromes evaluated at a tertiary referral center. All underwent standardized neurological, neuropsychological, and imaging assessments, and family history was recorded. Genetic testing included validated assays for C9orf72 repeat expansions and next-generation sequencing of MAPT and GRN.

Results: Women comprised 53.45% of the cohort. The mean age was 67.88 years, with mean onset at 61.70 years. Behavioral variant FTD predominated (75.87%), while language forms were less frequent. Positive family history was present in 16 patients (27.59%). Pathogenic variants were identified in three individuals (5.17%): two unrelated carriers of the intronic MAPT mutation c.1920+16C>T and one patient with a C9orf72 expansion. No GRN variants were detected. Mutation frequency was 18.75% in familial cases, while none were found among sporadic patients (p = 0.018). Four of nine relatives were asymptomatic MAPT mutation carriers.

Conclusions: This first genetic study of FTD in southeastern Serbia revealed a lower mutation frequency than in Northern and Western Europe, but similar to cohorts from Southeastern Europe. The detection of MAPT c.1920+16C>T in two unrelated families extends the geographic range of this splice-site variant and underscores the importance of systematic genetic testing and larger collaborative studies in the Balkans.

Background: Parkinson's disease (PD) is a neurodegenerative disorder affecting men more frequently than women, a difference that might be due to many factors, including sexual hormones. Estrogens seem to confer a protective effect on the nigrostriatal pathway in experimental studies but their effects on cognition in patients with PD are unknown.

Aim: To investigate the impact of the exogenous and endogenous estrogens on cognitive impairment in women with PD.

Methods and materials: We recruited and consecutively interviewed outpatient women affected by PD. Each patient underwent a cognitive assessment via the Montreal Cognitive Assessment scale (MoCA), an anamnestic collection of the reproductive lifespan variables and clinical features. We investigated if some of the reproductive lifespan variables investigated could predict cognition outcomes in post-menopausal women with PD.

Results: A total of 90 women with PD were recruited. Women with MoCA ≥ 26 (n = 27) had a lower median age at menarche (11 [11,12] vs. 13 [12-14], p < 0.0001), lower disease duration in years (8.3 [6.1-12.7] vs. 9.4 [6-12.7], p = 0.6), and less advanced disease (1 [1,2] vs. 2 [1-3], p = 0.02). Among all the reproductive life-span variables, only earlier age at menarche significantly predicted higher scores on MoCA (aOR = 0.5 [0.3-0.8], p = 0.005). No other clinical and reproductive factors have been shown to have an influence on cognitive scores.

Conclusions: Age at menarche correlated with cognitive outcomes. Our study suggests that earlier exposure to endogenous estrogens during a phase of development and plasticity of the brain might preserve women with PD from cognitive decline.

Background: Monitoring brain activity through electroencephalography (EEG) has led to significant advancements in the study of brain microstates and their relationship with cognitive processes, such as memory. Objective: A systematic literature review was conducted following the PRISMA methodology, with the aim of identifying and analyzing potential biomarkers of memory functions derived from EEG microstate analysis. Methods: Searches were performed in five major databases (PubMed, Scopus, Web of Science, Springer, and institutional registers), covering studies published between 2019 and 2024. The initial search retrieved 179 records; after removing duplicates and ineligible works, 18 full-text articles were evaluated. Finally, 10 original studies met the inclusion criteria. Although primarily focused on other pathologies or baseline conditions, these studies reported relevant findings related to memory processes. This allowed for an exploratory synthesis of the potential role of EEG microstates as indirect biomarkers of memory. Results: The findings revealed that microstates, particularly microstates C and D, show significant alterations in their duration, coverage, and occurrence in various pathologies, such as Alzheimer's disease, schizophrenia, and attention disorders, highlighting their potential as noninvasive biomarkers. Conclusions: Although methodological variability across studies represents a limitation, this review provides a solid foundation for future research aimed at standardizing the use of EEG microstates in clinical applications, improving diagnostic accuracy in memory-related diseases. Overall, EEG microstates hold great promise in both neuroscientific research and clinical practice.

Background: Stroke is a leading cause of seizures and epilepsy, both of which are linked to increased mortality, disability, and hospital readmissions. Early recognition and management of seizures in acute stroke are crucial for improving outcomes. Electroencephalogram (EEG) is not routinely used for post-stroke seizure monitoring and is typically initiated only after clinical suspicion arises, making bedside recognition essential. This scoping review aimed to map the existing literature on clinical methods used for identifying and observing early post-stroke seizures (EPSSs) at the bedside. Methods: We included literature involving adults with acute ischaemic stroke or primary intracerebral haemorrhage who were diagnosed or suspected of having inpatient EPSS. Searches were conducted in Medline, CINAHL, Embase, and the Cochrane Library for English-language publications up to April 2023. Eligible sources included primary research, case reports, systematic reviews, clinical guidelines, consensus statements, and expert opinion. Reference lists of included articles were also reviewed. Data were charted and synthesised to assess the scope, type, and gaps in the evidence. Results: Thirty papers met inclusion criteria: 17 research studies, six expert opinions, four case reports, and three clinical guidelines. Empirical evidence on clinical methods for seizure recognition and monitoring in acute stroke was limited. No studies evaluated the effectiveness of different approaches, and existing recommendations lacked detail and consensus. Conclusions: Accurate EPSS diagnosis is vital due to its impact on outcomes. This review highlights inconsistency in monitoring methods and a clear need for targeted research into effective clinical identification strategies in acute stroke care.

Deep brain stimulation (DBS) is an evolving neurosurgical treatment, originally developed for movement disorders such as Parkinson's disease, essential tremor, and dystonia. In recent years, it has been increasingly applied to psychiatric and cognitive disorders. This review aimed to summarize the psychological and neuroethical dimensions of DBS, with particular attention to cognitive, emotional, and personality-related outcomes. While DBS can significantly enhance quality of life, it may also lead to subtle or overt changes in cognition, affect, and self-perception, especially in patients with neuropsychiatric comorbidities. Comprehensive psychological evaluation, both pre- and post-operatively, is essential. Findings from recent trials highlight a balance of potential risks and benefits that must be communicated transparently to patients. From a neuroethical perspective, DBS raises important questions regarding personal identity and autonomy, concerns that will become increasingly relevant as the technology advances. This paper underscores the need for more systematic research and the development of personalized care protocols that address not only motor outcomes but also psychosocial well-being.