Insulin resistance is a condition characterized by the attenuated biological response in the presence of normal or elevated insulin level and therefore is characterized by the impaired sensitivity to insulin and impaired glucose disposal and utilization. Insulin resistance in brain/Brain insulin resistance (BIR) is accompanied by the various manifestations including alteration in glucose sensing by hypothalamic neurons, impaired sympathetic outflow in response to hypoglycemia, increased ROS production, impaired mitochondrial oxygen consumption in the brain, cognitive deficits and neuronal cell damage. It has been reported that the disrupted insulin signaling is accompanied by the reduced expression of insulin receptor (IR)/insulin receptor substrate 1 (IRS1)/PI3K/AKT and IGF-1 receptor (IGF-1R)/IRS2/PI3K pathways. Insulin resistance and impaired insulin signaling interferes with the degradation and transportation of Aβ leading to Aβ deposition. Aβ promotes the hyperphosphorylation of tau, accumulation of neurofibrillary tangles and the later promotes the neuro-inflammation, apoptosis, oxidative stress, impairments of energy metabolism, synaptic disconnections, and hippocampus atrophy. Therefore, the impaired insulin signaling and the insulin promote cognitive deficits and neuronal cell death in the affected individuals. BIR is mainly responsible for the cognitive deficits and the neuronal damage in the patients of Alzheimer's disease (AD). In the present work, authors describe the BIR, and its role in the emergence of cognitive deficits and neurodegeneration. Further, the emphasis has been given on the pharmacological agents that may alleviate the BIR and its deleterious effects.

IntroductionRecent studies suggest a link between gut microbiota and neurological diseases, implicating the microbiome’s role in neurological health. However, the specific alterations in the microbiome associated with migraine remain underexplored. This study aims to systematically review the existing literature to determine whether migraine patients are associated with changes in gut microbiota composition.MethodsA systematic review was conducted in accordance with the PRISMA statement. We included original empirical studies investigating the microbiome in migraine patients. Data extracted included study design, participant demographics, microbiome differences at various taxonomic levels, and measures of microbial diversity (alpha and beta diversity). The search and selection process involved four independent reviewers who assessed abstracts and full texts to ensure eligibility. The gut microbiota was evaluated using relative abundance and diversity indices.ResultsSix studies, encompassing various regions including China, Korea, and Italy, were included in the analysis. The results indicated significant differences in gut microbiota between migraine patients and controls. Key findings include a reduction in Faecalibacterium, a genus known for its anti-inflammatory properties, in migraine patients, including those with chronic migraine. Conversely, Veillonella exhibited elevated abundance compared to controls. Other taxa, such as Prevotella and Parabacteroides, showed variable associations with migraine across different studies, suggesting a dysbiotic gut environment in migraine patients.ConclusionThis review highlights that migraines are associated with specific alterations in gut microbiota, including decreased microbial diversity and changes in the abundance of key taxa. These findings suggest that gut microbiota dysbiosis may play a role in migraine pathophysiology. Further research is needed to explore the potential causal relationships and therapeutic implications, particularly targeting the microbiome in migraine management.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13760-025-02779-y.

BackgroundSpinal Muscular Atrophy (SMA) is a genetic neuromuscular disorder causing progressive motor function loss, respiratory and swallowing impairments, and significant limitations in activities of daily living (ADLs) and social participation. While gene therapies have enhanced life expectancy, functional management remains crucial. Despite the International Classification of Functioning Disability and Health for Children and Youth (ICF-CY) being a valuable framework for patient-centered care, its integration in setting multidisciplinary rehabilitation goals for SMA patients is underexplored.ObjectiveThis study aimed to assess the use of the ICF-CY framework in developing multidisciplinary intervention goals for SMA patients.MethodsA cross-sectional study involving 6 SMA patients was conducted at a pediatric neurorehabilitation hospital. Data were collected using a standardized ICF-CY-based case record form and analysed to identify patterns of impairment, activity limitations, and environmental factors.ResultsResults demonstrated the multifaceted nature of SMA, with significant impairments in motor function, respiratory function, and swallowing, as well as limitations in activities of daily living and social participation. Environmental factors, particularly social support and accessibility, emerged as crucial determinants of overall well-being.ConclusionsThe study underscores the importance of a multidisciplinary approach and the use of ICF-CY framework for developing comprehensive and patient-centered care plans for SMA patients.

Charcot-Marie-Tooth disease type 1 A (CMT1A) is the major subtype of hereditary peripheral neuropathies and arises from a 1.5 megabase (Mb) tandem duplication in chromosome 17p11.2-p12 that contains the complete peripheral myelin protein 22 (PMP22) gene. Patients commonly present with progressive weakness and atrophy of the distal muscles, accompanied by hyperalgesia, decreased or absent tendon reflexes, and foot deformities. Current clinical management relies on multidisciplinary supportive care. Recent preclinical studies targeting potential therapeutic strategies for CMT1A have focused on correcting the gene-dose imbalance of PMP22. Notably, PXT3003 has shown phase III clinical efficacy in relieving symptoms and reducing neuropathy, and is expected to be the earliest CMT1A-targeted drug on the market. Gene editing approaches have also shown therapeutic promise in animal models, but off-target effects remain a concern. In addition, the rapid development of induced pluripotent stem cell (iPSC) technology has paved the way for stem cell therapies, which may be a promising therapeutic approach. This article reviews the existing literature on therapeutic strategies for CMT1A and aims to provide a valuable reference for the clinical treatment of CMT1A.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13760-025-02881-1.

Recent evidence indicates that statins have anti-inflammatory and antioxidant effects, leading to several investigations of whether statins have a neuroprotective effect and may benefit patients with Parkinson's disease (PD). However, the potential mechanisms of this class of medications as modifiers of the course of PD in already diagnosed patients is still unclear. To assess the effectiveness of statins as modifiers of established PD. Two investigators systematically searched for randomized clinical trials and observational studies comparing PD patients treated with statins versus those treated without statins. The search was conducted in PubMed, Embase, Cochrane, and Web of Science. The outcome of interest was the change in the MDS-UPDRS III (Movement Disorder society-Unified Parkinson's Disease Rating Scale Part III) and UPDRS III scores from baseline. Statistical analysis was performed using R Studio 4.3.2. Four studies, totaling 472 patients, were included. The standardized mean difference for the MDS-UPDRS Part III and UPDRS Part III scales between statin and non-statin groups was - 0.13 (95% CI - 0.44 to 0.17; p = 0.39; I2 = 58%), and there was no statistical significant difference regarding this outcome. There was no statistical significance for the potential clinical benefit of statins as modifiers of the disease course in PD patients.

Infantile spasms syndrome is a severe form of infantile epilepsy. It is commonly treated with hormonal therapies or vigabatrin, either alone or in combination. This study aimed to assess the efficacy of these treatment modalities and explore associations with aetiology, and pre-existing developmental delay. Patients diagnosed with and treated for infantile spasms syndrome at the University Hospital of Leuven between 1 January 2018 and 23 November 2022, were identified. Retrospective clinical data were analysed descriptively. Short-term and long-term outcomes determined the efficacy of the current treatments, with seizure freedom and sustained normal development at 6 and 12 months after treatment initiation as primary treatment goals. The study included 26 patients. No single treatment modality demonstrated clear superiority in terms of both short-term and long-term outcomes. Patients with unknown aetiology showed better developmental outcomes after 12 months than those with proven aetiology (30.77% with normal development versus 7.69%.) Another clear difference in treatment efficacy emerged between patients with and without pre-existing developmental issues, with only 6.67% achieving normal development after 12 months compared to 36.36%, respectively. No single treatment modality demonstrated clear superiority. Associations were found between treatment efficacy and aetiology as well as pre-existing developmental delay, suggesting these as potential prognostic indicators.

The purpose of this meta-analysis was to conduct a comparative study by systematically examining and analyzing trials that studied the impacts of levodopa and bromocriptine, either separately or together, in treating Parkinson's disease (PD). An extensive literature search was conducted across PubMed (Medline), Scopus, and Web of Science databases, using targeted keywords for studies published up to October 2024. The methodological quality of included RCTs was assessed with the Cochrane Risk of Bias 2 (RoB 2) tool, and bias evaluation was performed using RevMan (version 5). Statistical analyses were conducted in STATA version 17, applying random-effects models. The overall quality of evidence was evaluated using the GRADE approach. The thorough evaluation identified 12 randomized controlled trials with a total of 4,060 participants, 1,956 in the intervention group and 2,104 in the comparison group, all diagnosed with PD. A combined effect size of 0.18 (SMD: 0.18; 95% CI: -0.03, 0.39) was found through quantitative analysis of motor scales for the Unified Parkinson's Disease Rating Scale (UPDRS). An effect size of 0.50 (OR: 0.50; 95% CI: 0.31, 0.80) was determined for dyskinesia. Dystonia occurrences showed a significant effect size of 0.44 (OR: 0.44; 95% CI: 0.24, 0.81; I2: 87.28%; P value: 0.0001). Hallucination and dizziness occurrences showed effect sizes of 0.91 (OR: 0.91; 95% CI: 0.36, 2.30) and 1.36 (OR: 1.36; 95% CI: 0.91, 2.04) overall, respectively. Quality assessment revealed high-certainty evidence for dyskinesia and dystonia reduction with bromocriptine, while other outcomes showed low to very low certainty. Meta-regression analyses showed no significant correlation between population characteristics and outcomes. This thorough meta-analysis offers an understanding of how bromocriptine compares in effectiveness to levodopa and other treatments for managing PD.