European Journal of Paediatric Neurology最新文献

This study presents the first reported case of a 3-year-old child with EIF2AK2-related dystonia treated with adjunctive luteolin supplementation. EIF2AK2-related dystonia, characterized by exacerbations during infections, is associated with disruptions in the integrated stress response (ISR). The ISR, a cellular signaling pathway activated in response to stress, culminates in the phosphorylation of eIF2α, which modulates protein synthesis and can induce cell death. Pathogenic variants in EIF2AK2 disrupt this pathway, contributing to the development of dystonia. Luteolin, a flavonoid possessing anti-inflammatory and neuroprotective properties, was hypothesized to modulate the ISR, thereby attenuating infection-induced dystonic exacerbations. The patient, exhibiting early-onset dystonia with clinical worsening during febrile episodes, harbored a de novo pathogenic variant in EIF2AK2. Following initial clinical improvement with trihexyphenidyl, adjunctive luteolin therapy was initiated, resulting in further clinical enhancements. Quantitative assessment using dystonia rating scales (UDRS, MSS, DSS) demonstrated sustained improvement, characterized by a reduction in the severity and frequency of infection-triggered relapses. The proposed mechanism of action involves luteolin disrupting the PACT-PKR interaction, a critical step in ISR activation, thus preventing excessive eIF2α phosphorylation and subsequent cellular dysfunction. This mechanism, supported by in vitro studies utilizing relevant disease models, suggests luteolin's potential to stabilize cellular homeostasis under stress. This case report indicates that luteolin may serve as a promising adjunctive therapeutic strategy for patients with infection-sensitive dystonic phenotypes, such as EIF2AK2-related dystonia. Further randomized controlled trials are warranted to validate these findings and establish the optimal dosing regimen and long-term safety profile of luteolin in vivo.

Background: Glucose Transporter Type 1 Deficiency Syndrome (GLUT1DS) is a rare genetic disorder caused by mutations in the SLC2A1 gene. Core symptoms include epilepsy, movement disorders, and neurocognitive impairment. While ketogenic dietary therapies remain the gold standard for treatment, challenges persist in ensuring adherence, with varying responses across patients. Limited knowledge exists regarding the broader impact of GLUT1DS on patients and caregivers, highlighting the need for a patient-centered care approach.

Methods: In collaboration with the Italian GLUT1DS Association, a survey was developed to assess Patient-Centered Outcomes, covering demographic data, symptoms, daily life challenges and treatment experiences. The survey was distributed online to patients and caregivers, yielding 83 responses. Data were analyzed using descriptive statistics, t-tests, and chi-square analyses to explore the relationship between core symptoms and broader life impacts.

Results: Movement disorders were identified as a major barrier to daily activities, particularly leisure and social engagement. Cognitive impairments were linked to academic struggles, and speech/language impairments, especially dysarthria, emerged as a significant burden. Sleep disturbances were common, with restless sleep in younger patients and excessive daytime sleepiness in older ones. Although ketogenic therapies improved energy and memory, challenges in patient autonomy persisted. Delayed disease awareness and difficulty with educational and occupational transitions were also reported.

Conclusion: GLUT1DS has a broad impact beyond core symptoms. A comprehensive, multidisciplinary care approach is essential for optimizing quality of life. These findings offer critical insights for refining clinical management strategies and shaping future research on patient-reported outcomes in GLUT1DS.