Frontiers in Neurology最新文献

Background: Intermittent Theta Burst Stimulation (iTBS), a non-invasive brain stimulation technique, is recognized for its ability to modulate cortical neuronal activity. However, its effects over time and the dynamics following stimulation are less well understood. Understanding the temporal dynamics of iTBS effects is essential for optimizing the timing and frequency of stimulation in therapeutic applications.

Objective: This study investigated the temporal changes in protein expression induced by iTBS in Neuro-2a cells.

Methods: We analyzed protein expression in retinoic acid-differentiated Neuro-2a cells at multiple time points - 0.5, 3, 6, 12, and 24 hours post-iTBS - using Western blot and immunocytochemistry techniques.

Results: Our findings reveal a significant early increase in neurotransmitter receptor subunits, neurotrophic factors, and cytoskeletal proteins within the first 0.5 hour following iTBS. Notably, proteins such as mGLuR1, NMDAR1, GABBR2, and β-tubulin III showed substantial increase in expression. However, the effects of iTBS on protein expression was not sustained at later timepoints.

Conclusion: Our results suggest that iTBS can transiently alter the expression of specific proteins in Neuro-2a cells. Future research should investigate the potential benefits of repeated stimulations within the early time window to refine iTBS interventions, potentially expanding their research and clinical applications.

Background: Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems. We have developed an animal model of this human condition in the Mongolian Gerbil that uses surgically created SSCD to induce the condition. A feature that is unique in this model is that spontaneous resurfacing of the dehiscence occurs via osteoneogenesis without a subsequent intervention. In this study, we completed our assessment of this model to include reversible asymmetrical vestibular impairments that interfere with balance.

Methods: Adult Mongolian gerbils (N = 6) were trained to complete a balance beam task. They were also trained to perform a Rotarod task. After 10 days of training, preoperative ABR and c+VEMP testing was followed by a surgical fenestration of the left superior semicircular canal. Balance beam testing recommenced at postoperative day 6 and continued through postoperative day 15 at which point final ABR and c+VEMP testing was carried out.

Results: Behavioral comparison of preoperative and postoperative performance show a significant decrease in Rotarod performance, increased rates of falling, and an increase in time to cross the balance beam. Impairments were the most significant at postoperative day 7 with a return toward preoperative performance by postoperative day 14. This behavioral impairment was correlated with residual impairments to auditory thresholds and vestibular myogenic amplitudes at postoperative day 14.

Conclusion: These results confirm that aberrant asymmetric vestibular output in our model of SSCD results in reversible balance impairments. The level of these behavioral impairments is directly correlated with severity of the vestibular dysfunction as we have previously reported for peripheral ear physiology and cognition.

Introduction: Neurosonology is a vital paraclinical investigation in modern neurology. However, access to education and certification in neurosonology for neurology residents and young specialists in Europe is challenging, and comprehensive data regarding this topic are scarce. Information regarding difficulties in neurosonology training across Europe may help bring this topic under the spotlight and act as a call for the harmonization of curricula across the continent.

Methods: We performed an online survey targeting European neurology residents and young specialists, focusing on neurosonology training and certification. The survey was conducted between May and September 2023 and received responses from 282 participants representing 37 European countries.

Results: There were disparities in neurosonology training during residency, with 6 (16.2%) out of 37 countries reporting a dedicated curriculum. The respondents expressed an overall lack of satisfaction with theoretical knowledge (rating their experience as very poor 28.0%, poor 20.2%, neutral 25.9%, good 19.3%, and very good 6.6%) and practical skills gained during their training (rating their experience as very poor 30.9%, poor 18.9%, neutral 22.6%, good 18.1%, and very good 9.5%). A total of 282 respondents (5.7%), 16 held a national certification in neurosonology, claiming obstacles such as high costs of certification and a limited number of certifying centers.

Discussion: This survey reveals significant variations in neurosonology training across Europe, indicating difficulties in obtaining certification. Despite the increasing importance of neurosonology, many neurologists feel inadequately prepared and lack practical training during residency, emphasizing the need for better and more standardized access.

Conclusion: The survey underscores challenges and disparities in neurosonology training and certification in Europe. Standardization of curricula and increased awareness about available certifications are crucial to address these issues. The interest in European Certification suggests a potential solution for enhancing neurosonology training at the international level.

Background: As targeted drug development in myasthenia gravis (MG) continues to advance, it is important to compare the efficacy of these drugs for better clinical decision-making. However, due to the varied regimens and dosages used in clinical trials for different drugs, a standardized comparison between them is necessary.

Methods: This study enrolled participants in phase II and III trials of innovative targeted drugs for MG. The primary outcome was the change in Quantitative Myasthenia Gravis score (MG-QMG) from baseline. The efficacy of all drugs at four time points was separately analyzed at four time points: initiation 1 week, initiation 4 weeks, maximized response, and post last dose 4 weeks. A network meta-analysis was conducted to compare the results of the different drugs.

Results: A total of 9 drugs, including Efgartigimod, Rozanolixizumab, Batoclimab, Eculizumab, Belimumab, Zilucoplan, Ravulizumab, Nipocalimab, Rituximab, derived from 12 studies were analyzed. At the initiation 1-week time point, three drugs exhibited significant improvement compared to the placebo effect: Efgartigimod, Zilucoplan, Rozanolixizumab. At the initiation 4-week time point, four drugs showed significant improvement compared to the placebo effect: Efgartigimod, Rozanolixizumab, Batoclimab, Zilucoplan. At the maximized response time point, six drugs achieved significant improvement compared to the placebo effect: Efgartigimod, Rozanolixizumab, Batoclimab, Eculizumab, Zilucoplan, Ravulizumab. At the post last dose 4-week point, all drugs statistically showed no significant difference from the placebo.

Conclusion: Although the MG subtypes were not consistent across trials, within the regimen design of each trial, neonatal Fc receptor inhibitors-represented by Efgartigimod, Rozanolixizumab, and Batoclimab-exhibited the most effective response rates when compared to complement and B-cell inhibitor drugs.

Background: Neuronal Intranuclear Inclusion Disease (NIID) is a neurodegenerative disorder characterized by the formation of eosinophilic inclusions in the neurons, visceral and skin cells. The cause is associated with the GGC nucleotide repeat expansion in the NOTCH2NLC gene. The imaging hallmark of NIID is hyperintensities on diffusion-weighted imaging (DWI) at the corticomedullary junction. Clinical manifestations of NIID are highly heterogeneous. Here, we report a case of NIID presenting with acute-onset dementia and cortical edema.

Case presentation: We describe an elderly male patient who presented with sudden dementia within a day. Considering the abrupt onset and the stroke history, we initially diagnosed vascular disease. However, further imaging revealed cortical edema in the temporo-parieto-occipital lobes. Blood and cerebrospinal fluid tests ruled out immunological, metabolic, infectious, or neoplastic etiologies. Genetic testing ultimately confirmed the diagnosis of NIID. Intravenous immunoglobulin (IVIG) therapy did not improve the patient's symptoms; However, about 1 month after treatment, spontaneous improvement was observed. It is noteworthy that 22 months before the onset of cognitive impairment, the patient's MRI for headaches already exhibited the typical imaging lesions of this disease in the cerebellum paravermal region.

Conclusion: Patients with encephalopathy syndrome exhibiting imaging features resembling mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome or Creutzfeldt-Jakob disease should consider the NIID as differential diagnosis. Chronic headaches and symmetric lesions in the cerebellar paravermal region on MRI may be noteworthy indicators of NIID during non-episodic phases.

Introduction: As highlighted by the scientific literature, music therapy (MT) represents a significant non-pharmacological intervention within neurorehabilitation programs. MT offers benefits in the recovery process and enhances the quality of life for patients with neurodevelopmental disorders. A review of the literature reveals a lack of MT models focusing on real-time personalized composition using electronic music techniques. Furthermore, studies on MT conducted within a multisensory therapeutic context are limited. Recent literature reviews on MT in telerehabilitation have highlighted that the application of the Euterpe Method (EM) is complex due to limited technical information available and the combined background required for music therapists to replicate the EM protocol.

Methods: This paper presents a manual which specifies the procedures and algorithms of the EM, developed during a research program conducted in a pediatric hospital in Italy. The prerogative of the EM is the use of procedures aimed at creating personalized therapeutic compositions within a multisensory environment.

Discussion: The efficacy and resilience of the EM have been demonstrated in two experimental studies. The first focused on the use of telerehabilitation in children with developmental disorders, while the second involved hospitalized children with cerebral palsy.

Conclusion: This study integrates medicine, neuroscience, and MT to develop personalized interventions in pediatrics, fostering collaboration among specialists and families, enhancing patient well-being, and opening new therapeutic perspectives, while ensuring the replicability of the EM approach.

Background: Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC.

Methods: Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys.

Results: In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%).

Conclusion: We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC.

Background: Multiple sclerosis (MS) is a progressively debilitating disorder that has seen a notable rise in prevalence in recent years. This study examines the burden of MS from 1990 to 2019, providing a detailed analysis by age, sex, and sociodemographic index (SDI) across 204 countries and territories.

Methods: Data on the prevalence, death and disability-adjusted life years (DALYs) attributable to MS were obtained from the publically available Global Burden of Disease 2019 project. The estimates are reported as numbers, percentages, and age-standardized rates per 100,000, accompanied by 95% uncertainty intervals.

Results: In 2019, MS accounted for 1.8 million prevalent cases, 22.4 thousand deaths and 1.2 million DALYs worldwide. There were significant declines in the global age-standardized prevalence, mortality and DALY rates of MS over the period 1990-2019. In 2019, females exhibited a higher global point prevalence and a greater total number of prevalent MS cases than males across all age groups. At the regional level, a non-linear relationship was observed between the age-standardized DALY rate of MS and SDI.

Conclusion: Although the global age-standardized DALY rate of MS decreased between 1990 and 2019, MS continues to account for a considerable number of DALYs and prevalent cases. Integrating MS and its associated risk factors into healthcare planning is vital, especially in areas with high levels of socioeconomic development.

Introduction: Migraine is a prevalent neurological disorder characterized by recurrent attacks, leading to a substantial global disease burden. Recent observational studies have reported the onset and worsening of migraine following COVID-19 infection and vaccination. However, traditional observational study designs have limitations in controlling for confounding factors, potentially resulting in biased and inconsistent conclusions. To address this, we applied Mendelian randomization (MR) to investigate the causal relationship between COVID-19 infection and vaccination with migraine.

Methods: This study utilized summary-level genome-wide association study (GWAS) data from the GWAS catalog and FinnGen database to evaluate the effects of varying degrees of COVID-19 infection and vaccination on migraine. We employed inverse variance weighted (IVW) fixed-effect and random-effect models as the primary methods for MR analysis, with MR-Egger and other approaches as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept regression, and MR-PRESSO, were conducted to ensure robustness of the results.

Results: Our MR analysis revealed no significant causal association between COVID-19 infection and migraine. However, a significant causal association was found between COVID-19 vaccination and migraine (beta = 0.071, P = 0.034). The results were confirmed through a series of sensitivity tests, demonstrating the robustness of the findings.

Discussion: This study provides novel evidence of a significant causal link between COVID-19 vaccination and migraine, while no such association was observed with COVID-19 infection. These findings may have important implications for clinical practice, particularly in planning treatment adjustments and optimizing patient care for individuals with migraines in the context of COVID-19 vaccination.