In 1988, two seminal studies were published almost simultaneously in the same scientific journal. Both spurred the field of brain energy metabolism research in new directions, culminating in a long-lasting debate that appeared to split its practitioners into two factions that seem unwilling to agree on what metabolic processes are fueling the active brain with adenosine triphosphate (ATP). The first study used rat hippocampal slices to demonstrate the ability of lactate to support neuronal function as the sole oxidative mitochondrial substrate. The second study demonstrated that upon brain stimulation, glucose consumption is not accompanied by respective oxygen consumption, but a non-oxidative glucose utilization or what has become known as "aerobic glycolysis". Consequently, for almost four decades, researchers in this field have been divided between those who profess that brain activity is supported by oxidative lactate metabolism and those who insist that non-oxidative glucose metabolism supports it. Hypotheses for both concepts were offered, "The Astrocyte Neuron Lactate Shuttle Hypothesis" and "The Efficiency Tradeoff Hypothesis," respectively. To bridge the gap between the two groups, a recent editorial, authored by over twenty leading investigators, was published. The editorial received two separate responses from investigators who supported the non-oxidative glucose consumption as the main process supporting neural activity, signaling that the gap between the two groups remained. The present perspective highlights the principal disagreements that divide this utmost important field of research. It argues that the main reason for these disagreements is rooted in the assumption that pyruvate is the end-product of aerobic glycolysis, even when many among those who adhere to this assumption accept that in the active brain glycolysis is the main provider of the necessary ATP and the end-product is lactate under aerobic conditions. The consideration of a paradigm shift, according to which lactate is the real end-product of glycolysis, independent of the presence or absence of oxygen, could bridge the great divide between those who separate glycolysis into two outcomes and those who profess that there is only one, prefix-less glycolytic pathway that always ends with the production of lactate.

Neonates undergoing surgery for congenital heart disease (CHD) are at high risk for brain function impairment. Reliable early predictors of postoperative neurological complications are lacking. We examined a retrospective cohort of 55 surgically treated CHD neonates systematically monitored by concomitant conventional electroencephalography (cEEG) and amplitude-integrated EEG (aEEG). Neonates underwent cEEG/aEEG at three time points: T0 (preoperative, duration: 90-120 min); T1 (24-48 h after cardiac surgery, duration: ≥11 h); and T2 (7-10 days post-surgery, duration: 90-120 min). For each patient, aEEG background activity was evaluated and scored, and clinical and surgical data were retrieved to establish short-term post-surgical outcomes. Patients with normal T0 monitoring had significantly higher aEEG bandwidths in T1. A lower Aristotle basic score was associated with an improvement in aEEG at T1. Inversely, a narrower aEEG bandwidth in T1 was associated with post-surgical neurological deterioration. The aEEG bandwidth accurately predicted short-term neurological outcome; in particular, a minimal aEEG amplitude above 17.5 µV excluded poor neurological outcome with a negative predictive value of 81.48%. Our results demonstrated that aEEG bandwidth and trend dynamics may be associated with surgical complexity and neurological outcomes. aEEG background trend monitoring may provide relevant prognostic information on neurological outcomes in surgically treated CHD neonates.

Remote ischaemic conditioning (RIC) is a promising treatment for neurological disorders. It involves cycles of temporary ischaemic stimulus, usually applied to a limb, and has shown significant improvement in neurological function in many trials. This review focuses on identifying and summarising the biomarkers of RIC that can enhance clinical practice and understanding of its mechanisms. A search was conducted in MEDLINE and EMBASE up to August 2025 using terms related to ischaemic conditioning. Studies were included if they were RCTs involving cerebrovascular disease, used RIC as treatment, and measured mechanistic biomarkers. We extracted and summarised data on study design, participant characteristics, RIC intervention protocols (including timing, frequency, duration, and pressure), biomarker types and measurement methods, timing of biomarker assessment, and main findings relating biomarker changes to clinical outcomes. The review identified twenty-one RCTs examining biomarkers, including serum biomarkers, imaging markers, and other physiological indicators. Key biomarkers identified include systemic inflammatory cytokines and various imaging markers such as cerebral blood flow (CBF), white matter hyperintensities (WMH), and brachial artery flow-mediated dilation (BA-FMD). The evidence suggests that RIC modulates various biomarkers linked to neuroprotection and recovery. Reliable biomarkers of RIC would enhance the understanding of its mechanisms and improve targeted therapies. The clinical utility of these biomarkers requires further validation through large-scale trials. Standardised protocols and longitudinal studies are essential for optimising RIC therapy and improving patient outcomes in stroke and cerebral small vessel disease. Future research should focus on expanding our understanding of these biomarkers and their interactions with RIC, leading to more personalised and effective treatments.

Introduction: Vestibular migraine (VM) is a frequent but underdiagnosed cause of episodic vertigo, characterized by vestibular symptoms often accompanied by migrainous features. Despite its relatively high prevalence, diagnosis remains clinically challenging and may differ depending on the diagnostic criteria used. This systematic review evaluates VM prevalence and clinical features across age groups to improve recognition and guide age-appropriate management. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO. This research was conducted using PubMed, Google Scholar, Cochrane, Web of Science, Wiley Online Library, and Embase. Two independent reviewers screened studies by title and abstract, and a separate pair screened full texts. Eligible studies were observational and reported prevalence or clinical features of VM. Results: A total of 874 publications were identified, leading to the review of 21 studies. Prevalence of VM varied widely, ranging from 6% to 35% in children and 2.7% to 40.9% in adults. Pooled prevalence across studies was 19% overall, 25% in children, and 14% in adults. Among patients with vertigo, the pooled prevalence was higher at 26%, with 33% in children and 18% in adults. Vertigo was the most consistent symptom in both age groups, and female predominance was observed in all age groups. Prevalence variability likely reflects diversity in applied diagnostic criteria and study design across included studies. Conclusion: VM is a common cause of vertigo, particularly in pediatric populations. Age-specific clinical features highlight the need for tailored diagnostic and management strategies. Future research should focus on large-scale prospective studies.

While typical benign paroxysmal positional vertigo (BPPV) presents with reproducible patterns of nystagmus and vertigo during positional testing, atypical variants often deviate from typical patterns, making diagnosis more complex. Recognizing atypical BPPV is crucial to avoid misdiagnosis and inappropriate management. This study aims to describe the clinical spectrum of atypical BPPV, differentiate it from central positional vertigo, and provide practical diagnostic guidance for clinicians. A narrative review was conducted to explore the clinical spectrum of atypical BPPV. Findings indicate that it may present with vertigo without nystagmus, conflicting torsional components in bilateral cases, or persistent symptoms despite repositioning maneuvers. Canal switch and pseudo-spontaneous nystagmus have also been described. Although these variants may mimic central etiologies, the absence of consistent neurological signs supports a peripheral mechanism. Diagnosis relies on detailed assessment of nystagmus characteristics—such as latency, /duration, and direction—as well as the exclusion of red flags, like direction-changing nystagmus without head movement, vomiting, or non-positional ocular motor abnormalities. Atypical BPPV remains a diagnostic challenge and requires careful bedside assessment and clinical testing. Understanding these variants is essential for timely and appropriate treatment. When doubt persists and resolution with treatment does not occur, neuroimaging should be considered to exclude central pathology.

Lumbar intervertebral disc herniation is a common cause of low back and radicular leg pain, traditionally managed with a combination of conservative therapies and, when indicated, surgical discectomy. An intriguing phenomenon observed in many patients is the spontaneous resorption of herniated disc material over time, often correlating with significant symptom improvement. This article is presented as a narrative review synthesizing experimental, imaging, and clinical literature relevant to spontaneous disc resorption and its implications for clinical decision-making. This paper provides a comprehensive overview of spontaneous disc herniation resorption, exploring the underlying pathophysiological mechanisms and the factors that predict which herniations are likely to regress without surgery. Key mechanisms include inflammatory-mediated degradation of disc fragments, neovascularization with macrophage infiltration and phagocytosis of extruded nucleus pulposus tissue, and biological processes such as enzymatic matrix breakdown and cellular apoptosis that collectively lead to shrinkage of the herniated mass. Patient and disc characteristics that favour spontaneous resorption are identified, such as younger age, extruded or sequestered fragment type, larger initial herniation size, and robust inflammatory response on imaging, whereas certain chronic degenerative changes may reduce this likelihood. We also review current clinical guidelines and expert recommendations on when surgical intervention is warranted versus when conservative management and observation are appropriate. Understanding the probability of natural disc fragment resolution is critical in guiding treatment decisions. In the absence of severe neurological deficits or intractable pain, a period of non-operative management can often be pursued safely, given that the majority of patients experience substantial relief within a few months as discs regress. Conversely, timely surgery is advised for those with neurological compromise or refractory symptoms. By synthesizing the latest evidence on spontaneous disc herniation resorption and its predictors, this review aims to assist neurosurgeons and spine specialists in optimizing patient selection for conservative care and identifying the proper timing for surgical intervention to achieve the best clinical outcomes. Given the narrative design, conclusions are based on synthesis of heterogeneous evidence rather than formal comparative analysis.

Background: Currently, there is a considerable number of studies addressing vagus nerve stimulation (VNS) for the treatment of different stroke-related outcomes. We aimed to promote a broad view of the outcomes studied and what are the opportune outcomes to be studied involving this therapeutic strategy for the treatment of post-stroke complications. Methods: This is a scoping review that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two investigators conducted independent searches on PubMed/MEDLINE, Scopus, and Embase till July 2025. Randomized clinical trials and preclinical studies using invasive or non-invasive vagus nerve stimulation conducted with a population diagnosed with stroke were included. Results: Forty-one experimental studies and sixteen clinical trials were included. The outcomes found were neuroprotection; motor, functional, and cognitive rehabilitation; dysphagia; comparison of different stimulation intensities; safety, efficacy, and feasibility of the non-invasive approach; comparison between transcutaneous auricular vagus nerve stimulation (taVNS) and transcutaneous cervical vagus nerve stimulation (tcVNS); and comparison between two models of ischemia (permanent and transient). Preclinical studies mostly investigated molecular elements involved in neuroprotection, neuroinflammation, and cellular apoptosis, while clinical studies evaluating the effectiveness of this technique used for rehabilitation and its comparison or combination with other techniques remain scarce. Conclusions: Most studies investigating the effects of VNS on different post-stroke outcomes are experimental studies. Clinical studies are still scarce and with limited analysis of outcomes.

Duropathies encompass a spectrum of disorders linked to spinal dural tears and cerebrospinal fluid (CSF) leaks, resulting in significant neurological manifestations. This review synthesizes the current literature on duropathies, focusing on their anatomical and pathophysiological aspects, including conditions such as superficial siderosis, spontaneous intracranial hypotension, and spinal cord herniation. The methodologies employed include comprehensive evaluations through neuroimaging techniques such as MRI and CT myelography, alongside clinical assessments of symptoms like ataxia, hearing loss, and cognitive impairment. Key findings highlight the prevalence of dural defects in patients with superficial siderosis and the association of persistent CSF leaks with various neurological impairments. The review emphasizes the need for a standardized diagnostic and therapeutic approach to enhance patient management and improve outcomes. By addressing the interrelated nature of these conditions, the study underscores the importance of early intervention to mitigate long-term neurological consequences. Overall, the findings advocate for further research to elucidate the mechanisms underlying duropathies and the development of effective treatment strategies, ultimately aiming to improve the quality of life for affected individuals.

Since its introduction, the construct of executive functions (EFs) has been associated with a set of tests to assess these functions and a brain network centered in the associative frontal brain regions. While the majority of perspectives have endorsed these associations, some studies have started casting doubts on them. In this article, the association between the construct of EFs, the tests used to assess them, and the involvement of frontal regions is examined. A sample of 28 patients with brain injuries was divided into three subgroups according to the region of the injury (anterior, posterior, antero-posterior). Patients were assessed with a battery of tests, including 25 measures of EFs and 6 control measures. A series of regression models revealed no significant differences in performance across the three groups. Findings indicate that the EF tests are not specific enough to differentiate EFs and brain injuries. The alleged reference of EFs to the frontal areas of the brain should attribute a higher role to other associative areas. The present study provides recommendations about how the EFs concept could be improved through methodological refinements and/or its dissemination.

Different neurodegenerative diseases display varying etiologies and phenotypes, reflecting region-specific neurodegeneration [...].