Neurology International最新文献

Patent foramen ovale (PFO) is present in roughly one quarter of adults and is over-represented among younger patients with cryptogenic ischemic stroke. The past decade has produced compelling evidence from randomized trials showing that PFO closure is beneficial than medical therapy in preventing recurrent ischemic stroke in appropriately selected patients. Despite this, anticoagulation continues to be used when closure is not feasible, declined, contraindicated, or considered after recurrent events. The observation that some patients experience "breakthrough" stroke or transient ischemic attack (TIA) despite therapeutic anticoagulation raises a critical question: why does medical therapy fail in PFO-associated stroke, and why does closure appear superior? This narrative review synthesizes the latest evidence on the pathophysiology of PFO-associated stroke, with attention to mechanisms that remain incompletely addressed by anticoagulation. It analyzes randomized trial data comparing antiplatelet therapy, anticoagulation, and transcatheter closure. It examines the role of high-risk PFO anatomical characteristics, the Risk of Paradoxical Embolism (RoPE) score, and the PFO-Associated Stroke Causal Likelihood (PASCAL) classification in understanding medical therapy failure. Additionally, the review explores whether PFO "type" predicts anticoagulation failure and highlights future research directions needed to further optimize therapy. In conclusion, in appropriately selected patients with high-risk PFO features, closure provides greater stroke risk reduction than medical therapy alone, albeit with small absolute risk differences and a procedural risk of atrial fibrillation.

Background: Standard ketogenic diets (KD) and fish oil have established efficacy for drug-resistant epilepsy (DRE), but adherence and variability remain challenging. Objective: The objective of this study is to provide the first systematic evaluation of clinical evidence for emerging dietary interventions for epilepsy-specifically those other than standard KD and fish oil-and to rigorously evaluate their effectiveness and certainty of evidence to address the current gap in dietary management literature. Unlike prior reviews focused on standard KD or carbohydrate-modified versions, this study is the first to synthesize evidence for "non-standard" interventions-including olive oil-based KDs, probiotics, and restrictive gluten/glutamate-free diets-which are typically excluded from traditional dietary meta-analyses. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Web of Science, Cochrane, and Google Scholar up to March 2025. Randomized Controlled Trials (RCTs) and Non-Randomized Studies of Interventions (NRSIs) were included, with quality assessed using RoB 2 and ROBINS-I tools. Results: Eight studies (total n = 675) were identified, comprising 2 RCTs and 6 NRSIs. These included olive oil-based KDs (n = 1), probiotic/synbiotic supplementation (n = 2), medium-chain triglyceride (MCT) additions (n = 2), and gluten-free (n = 1) or glutamate-free (n = 1) diets. Evidence quality is generally low, with 75% of studies at high risk of bias. Preliminary responder rates reached 83.1% in uncontrolled olive oil-based KD studies, whereas the only RCT evaluating a low-glutamate diet showed no significant seizure reduction (p = 0.57). Conclusion: Evidence for emerging dietary interventions beyond standard KD is nascent and of low certainty. Interpretation: While preliminary signals exist for olive oil-based KDs and probiotics, current data are insufficient for clinical recommendation; this review identifies these as promising exploratory targets requiring validation through rigorous, blinded RCTs.

Background: Botulism is a rare but potentially fatal neuroparalytic illness caused by Clostridium botulinum neurotoxins (BoNTs). While adult cases usually result from foodborne exposure or wound infection, intestinal colonization is exceedingly uncommon. Diagnosis can be delayed by overlap with other neuromuscular syndromes, and confirmation requires specialized assays. Anti-GQ1b antibodies, classically associated with Miller-Fisher syndrome (MFS), have rarely been reported in confirmed botulism, raising questions about shared pathophysiology. Case Presentation: We describe an adult patient with acute dyspnea, xerostomia, and cranial neuropathies. No foodborne source was identified, but intestinal colonization of BoNT/B toxigenic Clostridium botulinum was confirmed by stool enrichment and mouse lethality bioassay. The patient improved promptly following heptavalent antitoxin. Unexpectedly, anti-GQ1b antibodies were detected during recovery, a finding typically linked to MFS rather than botulism. Discussion: This case illustrates the diagnostic challenges of sporadic cases of botulism, especially when respiratory compromise and autonomic dysfunction dominate the initial presentation. The autoantibodies finding raises the possibility of molecular mimicry, whereby toxin-ganglioside interactions expose neuronal epitopes and trigger an immune response. While causality cannot be proven, the overlap between botulism and GQ1b-positive neuropathies merits further investigation. Conclusions: Clinicians should maintain high suspicion for botulism in adults with acute dyspnea, especially when associated with cranial neuropathies, even in the absence of foodborne exposure. Anti-ganglioside antibodies in this context should be interpreted with caution, as they do not exclude botulism but may highlight immunological overlap with autoimmune neuropathies.

Tourette syndrome (TS), or Tourette's, is a tic disorder (TD) belonging to a group of neuropsychiatric conditions marked by recurrent motor movements or vocalizations known as tics. TD, including TS, typically begins in childhood between 4 and 18 years of age and affects approximately 3% of children and adolescents. The etiology and pathogenesis of TD are multifactorial, involving genetic, immunologic, psychological, and environmental factors. Evidence suggests that neurotransmitter dysregulation, particularly within the cortical dopaminergic networks of the basal ganglia and limbic system, which support motor control and cognition, may be involved in the development of TD. Nutritional factors may modulate TD through various mechanisms, including effects on neurotransmitter synthesis and metabolism, neurodevelopment, neural architecture, and neuroimmune activity. This review integrates current evidence on the roles of vitamins D, B6, and A, as well as iron, magnesium, zinc, and copper, in TD. For each micronutrient, its physiological and neurobiological functions are discussed, along with possible mechanistic links to TD pathophysiology. Additionally, we summarize the impact of nutrient deficiencies and assess available evidence regarding their potential therapeutic potential role in TD management. Overall, this synthesis highlights how nutritional status may influence TD onset and symptom severity, suggesting that nutrient-based interventions could potentially serve as valuable adjunctive strategies in treatment.

Background/Objectives: Beyond respiratory problems, COVID-19 can cause a variety of symptoms, such as neurological disorders caused by biological and psychological factors. Brain fog (BF), a post-illness cognitive impairment that many patients report, can be evaluated with reaction time (RT) testing. Response latency is measured by RT, which can be either simple (sRT) or complex (cRT). This study focuses on how COVID-19 affects cognitive function, with particular attention on RT changes, BF prevalence, and implications for daily life. Methods: The study included 599 participants from Bosnia and Herzegovina, Croatia and Serbia. RT was measured using PsyToolkit and participants completed a COVID-19-associated BF questionnaire. Participants who experienced BF after their latest COVID-19 infection rated its severity using a visual analogue scale (VAS). Additional clinical data were obtained from medical records. Results: BF was reported by 40% of participants post-COVID-19. Men reported it less frequently but found it more disruptive. RT progressively declined post-infection, reaching peak impairment at 15 weeks, following recovery, with RT normalizing by six months. Conclusions: COVID-19 is linked to temporary RT impairment, peaking at 15 weeks post-infection and resolving by six months, independent of BF presence. This study emphasizes the need for a biopsychosocial approach to BF management. Easily available RT assessments should be incorporated into routine clinical practice.

Background/Objectives: The circadian regulator, circadian locomotor output cycles kaput (CLOCK), is well-established in maintaining sleep-wake rhythms, yet its cell-type-specific functions in sleep regulation remain largely unexplored. While ventromedial hypothalamic (VMH) prodynorphin (PDYN)-expressing (VMH^PDYN+) neurons are known to modulate homeostatic and motivational processes, their potential role in circadian sleep regulation has not been investigated. Methods: To address this, we developed mice with PDYN neuron-specific functional suppression of CLOCK activity (mClkΔ19) by interfering with their internal clock through Adeno-Associated Virus (AAV)-mediated overexpression of dominant-negative CLOCKΔ19 in PDYN-Cre mice. Results: We found that mClkΔ19 mice exhibited reduced locomotor activity during the dark phase, earlier activity peaks, and impaired rhythmicity of rapid eye movement (REM) and non-REM (NREM) sleep. Sleep analysis in mClkΔ19 mice showed selective reductions and fragmentation of light-phase REM sleep, more frequent sleep-wake transitions, and shorter REM cycles during the dark phase, indicating disrupted REM sleep timing. EEG spectral analysis in mClkΔ19 mice revealed decreased gamma activity during REM sleep in the light phase and an increase in delta activity coupled with decreased gamma during wakefulness in the dark phase. Conclusions: These findings suggest that the CLOCK activity in VMH^PDYN+ neurons is vital for circadian accuracy, REM sleep stability, and brain oscillations during sleep-wake cycles.

Primary Brain Calcification (PBC) is a neurodegenerative disorder of unknown etiology that results in bilateral calcifications within the brain. PBC symptoms vary, including Parkinsonian symptoms and psychiatric symptoms. Abnormalities in phosphate metabolism within the brain are hypothesized to be a mechanism underlying the onset of PBC, but the precise pathophysiological mechanism remains unclear. Furthermore, no fundamental treatment or therapeutic agent for PBC has been established. Previous studies have reported SLC20A2, PDGFB, PDGFRB, XPR1, MYORG, JAM2, CMPK2, and NAA60 as causative genes for familial PBC. Elucidating the pathophysiological mechanisms of PBC and developing treatments and therapeutic agents requires appropriate experimental disease models. Knockout mice and mutant mice targeting familial causative genes have been reported to be useful as in vivo models of PBC. Furthermore, several disease-specific iPS cells for PBC have been reported, suggesting their potential utility as PBC models. This paper reviews each familial causative gene and current PBC models, including genetically modified animals and disease-specific iPS cells, and examines their usefulness for understanding disease mechanisms and advancing therapeutic research.

Background/objectives: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRP-mAbs) are effective injectable medications for the treatment of migraine. This study aimed to evaluate continuation, resumption, and withdrawal rates of CGRP-mAb treatment under real-world clinical conditions.

Methods: Treatment-naïve patients with at least 3 months of follow-up after starting CGRP-mAb treatment were included. The decision to continue, discontinue, or resume CGRP-mAb treatment was made freely by the patients. Headache Impact Test-6 (HIT-6) and the Migraine-Specific Quality of Life Questionnaire (MSQ) were administered before starting treatment and one month after each CGRP-mAb injection. The endpoints were as follows: continuation rates of CGRP-mAb treatment after treatment initiation; resumption rate; withdrawal rate; changes in HIT-6 and MSQ scores; and differences in background factors between the resumption and withdrawal groups.

Results: Of the 1162 migraine patients, 146 were included in the analysis. Continuation rates of CGRP-mAb treatment at 3, 6, 9, 12, 18, and 24 months were 93.2%, 80.2%, 68.9%, 58.8%, 55.4%, and 51.7%, respectively. For the patients who discontinued, the resumption rate was 76.8%, and the withdrawal rate was 20.7%. HIT-6 and MSQ scores were significantly decreased at all assessment points compared with before CGRP-mAb treatment. There were no significant differences in factors between the resumption and withdrawal groups.

Conclusions: Under real-world clinical conditions in which patients were free to choose their own treatment, the continuation rate of CGRP-mAb treatment 12 months after treatment initiation was 58.8%, and more than half of patients remained on treatment after 24 months. The resumption rate was 76.8% and the withdrawal rate was 20.7%.

Multiple sclerosis (MS) affects approximately 2.9 million people in the world, exerting a significant economic and societal burden. The disease is increasingly identified among populations considered as uncommonly affected. MS is reported in all regions of the World Health Organization (WHO) member states in Africa, the Americas, South-East Asia, Europe, the Eastern Mediterranean and the Western Pacific, affecting all ethnicities while exhibiting substantially variable prevalences. Countries with high MS prevalence and some with moderate frequencies generally have economically better structured healthcare systems. Nevertheless, health disparities in these countries are accentuated by suboptimal accessibility of care for their minorities, immigrants and other underserved populations. Social Determinants of Health (SDOH) might have an impact on morbidity and higher rates of disability. Large segments of the world population (i.e., African, Latin American, people from the Middle East and Southeast Asia) do not have access to adequate MS diagnostic procedures, compounded by reduced availability of neurologists. Healthcare disparities exist practically in every country of the world. Active wars and a large number of refugees resulting from conflict augments the challenges to healthcare systems. These global factors constitute obstacles to the adequate management of MS. A collective international path is required to facilitate access to highly effective, albeit onerous treatments, some already approved and being utilized, i.e., monoclonal antibodies and B-lymphocyte depletory agents, and others foreseen in the future as advanced therapeutic molecules continue to develop.

The blood-brain barrier (BBB) is essential for maintaining cerebral homeostasis, and its dysfunction is increasingly recognized as an active driver of epilepsy. This review explores the mechanisms by which BBB disruption contributes to seizures and the development of chronic epilepsy. Potentially epileptogenic insults, including traumatic brain injury, stroke, and status epilepticus, induce acute and often persistent BBB leakage. This breach permits the extravasation of serum albumin, which activates transforming growth factor-beta (TGF-β) signaling in astrocytes. This cascade leads to astrocytic dysfunction, impaired potassium buffering, neuroinflammation, and synaptic remodeling, collectively fostering neuronal hyperexcitability. Furthermore, BBB disruption facilitates the infiltration of peripheral immune cells, amplifying neuroinflammation and propagating a pathologic cycle of BBB damage and seizure activity. BBB damage is mediated by multiple processes, including the activation of the plasminogen activation (PA) system. Furthermore, these processes of BBB disruption and neuroinflammation provide a shared pathological basis for neuropsychiatric disorders like depression and anxiety, which are common comorbidities of epilepsy, through shared mechanisms of neuroinflammation and neurovascular unit (NVU) dysregulation. BBB dysfunction can also contribute to the resistance to antiepileptic drugs. Finally, we discuss the therapeutic potential of stabilizing the BBB as a viable strategy for developing disease-modifying therapies for epilepsy.