Brain Sciences最新文献

Background: Childhood-onset progressive ataxias are rare neurodegenerative disorders characterized by cerebellar signs, sometimes associated with other neurological or extra-neurological features. The autosomal dominant forms, known as spinocerebellar ataxias (SCAs), linked to trinucleotide (i.e., CAG) repeat disorders, are ultra-rare in children. We describe three patients from two unrelated families affected by spinocerebellar ataxia type 2 (SCA2) and present a literature review of pediatric cases. Methods: The patients' clinical and genetic data were collected retrospectively. Results: The first case was a 9.5-year-old boy, affected by ataxia with oculomotor apraxia and cerebellar atrophy, subcortical myoclonus, and peripheral axonal sensitive polyneuropathy caused by a pathologic expansion in ATXN2, inherited from his asymptomatic father. Two brothers with familial SCA2 presented neurodegeneration leading to early death in one case and progressive ataxia, parkinsonism, and epilepsy with preserved ambulation at age 18 years in the second. To date, 19 pediatric patients affected by SCA2 have been reported, 3 of whom had a phenotype consistent with progressive ataxia with shorter CAG repeats, while 16 had more severe early-onset encephalopathy, with longer alleles. Conclusions: Although they are ultra-rare, trinucleotide repeat disorders must be considered in differential diagnosis of hereditary progressive ataxias in children, especially considering that they require targeted genetic testing and can manifest even before a parental carrier becomes symptomatic. Thus, they must also be taken into account with negative family history and when Next-Generation Sequencing (NGS) results are inconclusive. Notably, the association between cerebellar ataxia and other movement disorders should raise suspicion of SCA2 among differential diagnoses.

Background/Objectives: The main objective of this systematic review was to explore the role of magnetoencephalography (MEG) in the diagnosis, assessment, and monitoring of mild traumatic brain injury (mTBI) and post-concussion syndrome (PCS). We aimed to evaluate the potential of some MEG biomarkers in detecting subtle brain abnormalities often missed by conventional imaging techniques. Methods: A systematic review was conducted using 25 studies that administered MEG to examine mTBI and PCS patients. The quality of the studies was assessed based on selection, comparability, and outcomes. Studies were analyzed for their methodology, evaluated parameters, and the clinical implications of using MEG for mTBI diagnosis. Results: MEG detected abnormal brain oscillations, including increased delta, theta, and gamma waves and disruptions in functional connectivity, particularly in the default mode and frontoparietal networks of patients suffering from mTBI. MEG consistently revealed abnormalities in mTBI patients even when structural imaging was normal. The use of MEG in monitoring recovery showed significant reductions in abnormal slow-wave activity corresponding to clinical improvements. Machine learning algorithms applied to MEG data demonstrated high sensitivity and specificity in distinguishing mTBI patients from healthy controls and predicting clinical outcomes. Conclusions: MEG provides a valuable diagnostic and prognostic tool for mTBI and PCS by identifying subtle neurophysiological abnormalities. The high temporal resolution and the ability to assess functional brain networks make MEG a promising complement to conventional imaging. Future research should focus on integrating MEG with other neuroimaging modalities and standardizing MEG protocols for clinical use.

Background/Objectives: Recent research suggests that video games may serve as cognitive training tools to enhance visual working memory (VWM) capacity. However, the effectiveness of game-based cognitive training remains debated, and the underlying neural mechanisms, as well as the relationship between training efficacy and game design factors, are unclear. This study aimed to evaluate the impact of video game training on VWM capacity and explore its neural correlates. Methods: Two groups underwent 56 daily 20 min training sessions with two distinct video games targeting different cognitive skills: a reaction-time training game and a VWM-specific training game. Behavioral assessments included accuracy, hit response times, correct rejection response times, and Cowan's K values. Neural correlates were measured through Negative Slow Wave (NSW) activity using EEG. Decision tree classification analyses were applied to NSW data across sessions and set sizes to identify patterns linked to VWM capacity. Results: Preliminary results are that both groups showed improvements in behavioral measures (accuracy, response times, and Cowan's K values). NSW analyses revealed a main effect of set size in both groups, and classification results indicated that NSW patterns differed between groups, across sessions, and set sizes, supporting the relationship between NSW and VWM capacity. Conclusions: These findings contribute to understanding NSW as a neurophysiological correlate of VWM capacity, demonstrating its plasticity through video game training. Simple video games could effectively enhance behavioral and neural aspects of VWM, encouraging their potential as accessible cognitive training tools.

Background: Pathophysiological models of pediatric bipolar disorder (PBD) are lacking. Multimodal approaches may provide a comprehensive description of the complex relationship between the brain and behavior. Aim: To assess behavioral, neuropsychological, neurophysiological, and neuroanatomical alterations in youth with PBD. Methods: Subjects with PBD (n = 23) and healthy controls (HCs, n = 23) underwent (a) clinical assessments encompassing the severity of psychiatric symptoms, (b) neuropsychological evaluation, (c) analyses of event-related potentials (related to the passive viewing of fearful, neutral, and happy faces during electroencephalography recording, and (d) cortical thickness and deep gray matter volume measurement using magnetic resonance imaging. Canonical correlation analyses were used to assess the relationships between these dimensions. Results: Youth with PBD had higher levels of anxiety (p < 0.001) and borderline personality features (p < 0.001), greater commission errors for negative stimuli (p = 0.003), delayed deliberation time (p < 0.001), and smaller risk adjustment scores (p = 0.002) than HCs. Furthermore, they showed cortical thinning in the frontal, parietal, and occipital areas (all p < 0.001) and greater P300 for happy faces (p = 0.29). In youth with PBD, cortical thickening and P300 amplitude positively correlated with more commission errors for negative stimuli, longer deliberation times, reduced risk adjustment, higher levels of panic and separation anxiety, and greater levels of negative relationships, whereas they negatively correlated with levels of depression (overall loadings > or <0.3). Limitations: Small sample size, cross-sectional design, and limited variables investigated. Conclusions: This preliminary work showed that multimodal assessment might be a viable tool for providing a pathophysiological model that unifies brain and behavioral alterations in youth with PBD.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and interaction, along with restricted and repetitive patterns of behavior, interests, or activities. ASD encompasses a wide spectrum of clinical presentations and functional impairments, ranging from mild to severe. Despite its prevalence, the underlying physiopathological mechanisms of ASD remain largely unknown, resulting in a lack of effective targeted therapeutic interventions, contributing to significant financial and emotional burdens on affected families and the healthcare system. Emerging evidence suggests that dysfunction in the tetrahydrobiopterin (BH4) pathway may impair the activity of monoaminergic and nitric oxide (NO)-dependent neurons in individuals with ASD. To explore this potential mechanism, we conducted a systematic review to analyze such impairments to gather information on whether the off-label use of BH4 could represent a novel pharmacological approach for managing ASD. Following the PRISMA 2020 guidelines, we systematically reviewed the literature from four databases: PubMed, Virtual Health Library, Cochrane Library, and SciELO, from January 1967 to December 2021. The quality of the included studies was assessed using the Newcastle-Ottawa scale. The inclusion criteria for this systematic review focused on identifying articles published in English that contained the following keywords, used in various combinations: autism, ASD, autism spectrum disorder, BH4, tetrahydrobiopterin, neopterin, NO, nitric oxide. The analysis was performed between December 2020 and December 2021. The collected data demonstrated that BH4 metabolism was altered in individuals with ASD. Lower levels of BH4 were reported in biological samples from ASD-affected individuals compared to age- and sex-matched controls. Additionally, neopterin levels were elevated in plasma and urine, but decreased in cerebrospinal fluid, while nitric oxide levels were consistently reported to be higher across studies. Treatment with BH4 has shown potential in improving ASD-related symptoms. The reported increase in neopterin in biological fluids indicates inflammation, while the reduction in BH4 levels suggests a potential shift in its metabolic role. Specifically, BH4 may be diverted from its primary role in neurotransmitter synthesis to function as an antioxidant or to perpetuate inflammation through NO production. Given that BH4 is a critical cofactor in monoaminergic neurotransmission, its dysfunction highlights the molecule's therapeutic potential. BH4, already FDA-approved for other conditions, emerges as a promising off-label candidate to alleviate ASD symptomatology.

Background/Objectives Studies in rodents indicate that disruptions in both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling pathways are involved in the development of hyperactive behavior. We examined whether vinpocetine, a phosphodiesterase type 1 inhibitor that enhances brain cAMP and cGMP levels, could mitigate locomotor hyperactivity in mice exposed to lead during early development. Methods Swiss mice were exposed to 90 ppm of lead in their drinking water throughout gestation and the first ten postnatal days. At postnatal day 10 (PN10), blood lead levels (BLLs) were about 30 µg/dL. At PN30, animals either received vinpocetine (20 mg/kg, i.p.) or a vehicle 4 h before the evaluation of locomotor activity in the open field. Results Lead-exposed males did not display differences in locomotor activity compared to controls, while lead-exposed females showed a significant increase in locomotion. Vinpocetine treatment significantly reversed the lead-induced hyperactivity in females. Conclusions These findings suggest that the cAMP and cGMP signaling pathways play a role in the hyperactivity induced by lead exposure.

Multiple sclerosis (MS) is an autoimmune disease classified as neurodegenerative because it can be associated with the more or less progressive development of neurological symptoms and cognitive deficits. In recent years, various studies have started to investigate eye movements in relation to cognitive impairment in persons with MS by means of eye-tracking equipment. However, the high heterogeneity of the paradigms used in different studies, as well as the different methodologies included, makes it difficult to provide a complete and precise picture of this important research and clinical issue. The purpose of the present in-depth scoping review was to map the existing literature in this field to determine which metrics may be relevant when dealing with the neurocognitive profile of people with MS. From the analyses of the included studies, the anti-saccade latency and errors were the most frequently proposed metrics. Correlation analyses between these metrics and cognitive measures showed significant associations between them, calling for a deeper investigation of this promising research and clinical field. The results of the present scoping review strongly suggest that eye tracking may play a crucial role in clinical practice during the early detection of neurocognitive disorders. There is a great need for primary research that addresses the full complexity of MS in its different phenotypes and the disease-related variables from a multidisciplinary perspective. Future research should clarify whether oculomotor dysfunction in MS follows or precedes cognitive deficits.

Background/Objectives: To examine if head injury (HI) is associated with age at ALS diagnosis in the United States. Methods: In this cross-sectional populationf-based analysis, we identified patients with ALS who were registered from 2015 to 2023 who completed the Registry's head trauma survey module. The association between HI and age at ALS diagnosis was assessed using multivariate analysis. Results: Of the 3424 respondents, 56.6% had experienced a HI. The adjusted odds ratio (aOR) for an ALS diagnosis before age 60 years for patients with a HI was 1.24 (95% CI, 1.07-1.45). One or two HIs had an aOR of 1.15 (95% CI, 0.97-1.36), and five or more HIs had an aOR of 1.58 (95% CI, 1.19-2.09). HI before age 18 years yielded an aOR of 2.03 (95% CI, 1.53-2.70) as well as HI between the ages of 18 and 30 years (aOR = 1.48, 95% CI: 1.06-2.06)). When narrowing the analysis to patients with HI before age 18 compared with patients with no HI, we found an association with HI that led to an emergency department or hospital visit (aOR = 1.50 (95% CI: 1.21-1.86)). Conclusions: In this cross-sectional analysis of ALS patients, HIs occurring in childhood and early adulthood and the number of HIs increased the odds of being diagnosed before age 60 years. These results suggest that HI continues to be a risk factor for ALS and could be associated with a younger age of diagnosis.

Purpose: Early treatment response assessments are crucial, and the results are known to better correlate with prognosis and survival outcomes. The present study was conducted to differentiate true progression (TP) from pseudoprogression (PsP) in long-term-surviving glioblastoma patients using our previously established multiparametric MRI-based predictive model, as well as to identify clinical factors impacting survival outcomes in these patients. Methods: We report six patients with glioblastoma that had an overall survival longer than 5 years. When tumor specimens were available from second-stage surgery, histopathological analyses were used to classify between TP (>25% characteristics of malignant neoplasms; n = 2) and PsP (<25% characteristics of malignant neoplasms; n = 2). In the absence of histopathology, modified RANO criteria were assessed to determine the presence of TP (n = 1) or PsP (n = 1). The predictive probabilities (PPs) of tumor progression were measured from contrast-enhancing regions of neoplasms using a multiparametric MRI-based prediction model. Subsequently, these PP values were used to define each lesion as TP (PP ≥ 50%) or PsP (PP < 50%). Additionally, detailed clinical information was collected. Results: Our predictive model correctly identified all patients with TP (n = 3) and PsP (n = 3) cases, reflecting a significant concordance between histopathology/modified RANO criteria and PP values. The overall survival varied from 5.1 to 12.3 years. Five of the six glioblastoma patients were MGMT promoter methylated. All patients were female, with a median age of 56 years. Moreover, all six patients had a good functional status (KPS ≥ 70), underwent near-total/complete resection, and received alternative therapies. Conclusions: Multiparametric MRI can aid in assessing treatment response in long-term-surviving glioblastoma patients.

Background/Objectives: Many prison-sentenced individuals exhibit symptoms of mental dysfunctions, including attention deficit hyperactivity disorder (ADHD). The presence of co-occurring mental disorders further complicates their rehabilitation and social reintegration efforts. Given these challenges, understanding the role of specific disorders, such as ADHD, is critical for developing targeted interventions tailored to the needs of incarcerated individuals and improving their outcomes. This research aimed to clarify the relationships among hyperactivity, criminal behavior, and psychological functioning to inform preventative and therapeutic strategies. Methods: This study investigated the complex interplay among attention deficit hyperactivity disorder (ADHD) symptoms, criminal behavior, and various psychological factors in a sample of 391 male inmates from low-security Polish prisons and a control group of non-offending men. Principal component analysis (PCA) and Spearman's rank correlation were used to analyze the relationships among ADHD severity, type of crime (no crime, property crime, crime involving aggression), family functioning, childhood trauma, early maladaptive schemas, and mental health disorders. Results: The results revealed that while traumatic experiences were present across all groups, stronger family cohesion and support were associated with the absence of ADHD symptoms and criminal behavior. As ADHD severity and criminal behavior escalated, particularly in cases involving aggression, family support diminished, and maladaptive schemas, including "disconnection and rejection" and "excessive vigilance and inhibition", became more prominent, alongside increased correlations with mental health issues (anxiety and depression). Conclusions: The findings underscore the crucial role of family environment and early intervention in mitigating the risks associated with ADHD and criminal behavior, highlighting the need for comprehensive interventions targeting maladaptive schemas and providing support for both internalizing and externalizing symptoms. Limitations include the retrospective nature of data collection and the exclusive focus on male inmates in low-security facilities.