Augmented reality for teaching anatomy.

Successive waves of the coronavirus (COVID-19) pandemic lockdowns resulted in significant reduction in face-to-face teaching, with an adverse effect especially on sectors requiring direct skill acquisition. Despite the fact that augmented reality (AR) presents an equitable, cost-effective solution which reduces crowding in the confined spaces of the dissection theater, the benefits of AR-supported undergraduate medical education have been poorly investigated. We conducted a validated survey to explore the value of AR in the dissection theater and assess its impact from the learner's perspective. Further to a validated pilot (n = 30), a larger scale study (n = 130) was conducted to assess the introduction of AR across three different learning domains: retaining anatomy detail, perception of spatial anatomical relations, and speed of learning. A response rate of 85.4% was reported. Our results suggest that the use of AR technology leads to a significant enhancement of spatial relations, faster detailed material assimilation and assistance in understanding of key concepts. In addition, most participants opt to recommend AR as a valuable tool in the learning process. In view of the proposed added value of AR technology in various teaching aspects, we recommend that AR should be introduced as a standard practice in both pre- and postgraduate medical curricula and suggest further research regarding the use of this technology.

Sella turcica bridging: a systematic review.

PURPOSE: Sella turcica bridging (STB) has significant implications during neurosurgery, since it alters regional anatomy; however, no studies have investigated the global prevalence of STB. Our systematic review aimed to establish the global prevalence of STB, in specimens/individuals with and without comorbidities, in males and females, and of partial, complete, unilateral, and bilateral bridging. METHODS: A literature search was conducted in MEDLINE/PubMed, ScienceDirect, and Google Scholar with various key words relating to Sella turcica bridging. Quantitative data were extracted and statistically analysed. RESULTS: Eighty-two studies satisfied our inclusion criteria. The mean prevalence of STB was 26.54%, and most prevalent in Europe. STB was detected more frequently using radiological investigations. STB was less prevalent in healthy individuals (21.12%) when compared to individuals with comorbidities (33.31%). Partial STB was found to be the more prevalent in both individuals with (41.06%) and without (21.55%) comorbidities. The prevalence of unilateral and bilateral STB was only studied in healthy individuals, with unilateral bridging being the more prevalent (6.26% vs 3.84%). CONCLUSION: The global overall prevalence of Sella turcica bridging in the general population was found to be higher than previously thought. Anatomical and embryological textbooks should consider including information on STB in their texts, due to its considerable prevalence and effects to the regional anatomy.

Central axons preparing to myelinate are highly sensitive [corrected] to ischemic injury.

OBJECTIVE: Developing central white matter is subject to ischemic-type injury during the period that precedes myelination. At this stage in maturation, central axons initiate a program of radial expansion and ion channel redistribution. Here we test the hypothesis that during radial expansion axons display heightened ischemic sensitivity, when clusters of Ca(2+) channels decorate future node of Ranvier sites. METHODS: Functionality and morphology of central axons and glia were examined during and after a period of modeled ischemia. Pathological changes in axons undergoing radial expansion were probed using electrophysiological, quantitative ultrastructural, and morphometric analysis in neonatal rodent optic nerve and periventricular white matter axons studied under modeled ischemia in vitro or after hypoxia-ischemia in vivo. RESULTS: Acute ischemic injury of central axons undergoing initial radial expansion was mediated by Ca(2+) influx through Ca(2+) channels expressed in axolemma clusters. This form of injury operated only in this axon population, which was more sensitive to injury than neighboring myelinated axons, smaller axons yet to initiate radial expansion, astrocytes, or oligodendroglia. A pharmacological strategy designed to protect both small and large diameter premyelinated axons proved 100% protective against acute ischemia studied under modeled ischemia in vitro or after hypoxia-ischemia in vivo. INTERPRETATION: Recent clinical data highlight the importance of axon pathology in developing white matter injury. The elevated susceptibility of early maturing axons to ischemic injury described here may significantly contribute to selective white matter pathology and places these axons alongside preoligodendrocytes as a potential primary target of both injury and therapeutics.

LITT for biopsy proven radiation necrosis: A qualitative systematic review.

INTRODUCTION: With the widespread use of stereotactic radiosurgery (SRS), post-radiation treatment effects (PTREs) are increasing in prevalence. Radiation necrosis (RN) is a serious PTRE which carries a poor prognosis. Since 2012, laser interstitial thermal therapy (LITT) has been used to treat RN. However, reviews have attempting to generalise the efficacy of LITT against biopsy-proven RN are limited. In this systematic review, patient demographic characteristics and post-LITT clinical outcomes are characterised. METHODS: A systematic literature search was conducted in four major databases for cohort studies and case reports published between 2012 and 2022, following the PRISMA 2020 checklist. Data was extracted and descriptively analysed. Quality of reporting was assessed using the PROCESS criteria and reporting bias was evaluated using the ROBINS-I scoring system. RESULTS: Eleven studies met our inclusion criteria, with an overall moderate risk of reporting bias being observed. Mean pre-LITT target lesion volume was 6.75 cm3, and was independent of gender, time since SRS, age and number of interventions prior to LITT. DISCUSSION AND CONCLUSION: LITT is a versatile treatment option which may be used to treat a vast range of patients with refractory biopsy-proven RN. However, neurosurgeons should exercise caution when selecting patients for LITT due to insufficient data on the treatment's efficacy against biopsy-proven RN. This warrants further studies to unequivocally determine the safety and clinical outcomes.

Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature.

Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K(+) channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1(V408A/+)). Here, we investigated the neuromuscular transmission of Kv1.1(V408A/+) ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve-muscle from Kv1.1(+/+) and Kv1.1(V408A/+) mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca(2+) signals that occurred abnormally only in preparations dissected from Kv1.1(V408A/+) mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca(2+) homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K(+) channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during fatigue or ischemic insult.

Closed loop deep brain stimulation: A systematic scoping review.

BACKGROUND: At the turn of the 21st century, closed-loop deep brain stimulation (CL-DBS) systems have emerged as promising neuromodulatory treatment strategies, that integrate real-time feedback based on the brain's condition to fine-tune the stimulation being applied. CL-DBS promises numerous advantages over open-loop deep brain stimulation (OL-DBS) systems. However, no up-to-date review articles are available which characterise the clinical outcomes of CL-DBS therapy. METHODS: A systematic literature search was conducted in seven major databases with various keywords relating to CL-DBS, for non-randomised cohort studies, finalised clinical trials, case reports, and nonrandomised control trials published between 2011 and 2021. RESULTS: Seven studies satisfied our inclusion criteria. Six investigated the use of CL-DBS therapy for neurological disorders, while one investigated its use for psychiatric disorders. The average patient age was 61 years (range: 27 - 78), and the mean disease duration before CL-DBS therapy was 15 years (range: 4 - 47). Patients included with essential tremor (ET) (n = 11) were older than patients with freezing of gait (FoG) in Parkinson's disease (PD) (n = 6) (p = 0.009), albeit insignificantly longer disease duration (p = 0.199). Following CL-DBS intervention, patients with ET (n = 11), major depressive disorder (n = 1) and Tourette syndrome (n = 1) had improvements in clinical outcomes, while PD patients had heterogeneous outcomes (n = 7). CL-DBS systems utilised by the included studies demonstrated a mean of 51.94 % (range: 36.62 - 68) energy-saving capacity over OL-DBS systems. CONCLUSIONS: To date, there is insufficient evidence that CL-DBS offers significant superior clinical outcomes over OL-DBS. Our scoping review suggests that CL-DBS can improve symptoms of specific neurological and psychiatric disorders, whilst demonstrating improved energy-saving capacity which has the potential to decrease battery replacement surgeries. Real-time adjustment of patients' symptoms using CL-DBS may improve patients' overall quality of life. Further studies are required to validate our observations.

New Trends in Immunohistochemical Methods to Estimate the Time since Death: A Review.

The identification of a reliable and accurate post-mortem interval (PMI) is a major challenge in the field of forensic sciences and criminal investigation. Several laboratory techniques have recently been developed that offer a better contribution to the estimation of PMI, in addition to the traditional physical or physico-chemical (body cooling, lividity, radiocarbon dating, rigor mortis), chemical (autolysis), microbiological (putrefaction), entomological, as well as botanical parameters. Molecular biology (degradation pattern of macromolecules such as proteins, DNA, RNA), biochemical analysis of biological fluids (such as blood, cerebrospinal fluid, and vitreous humor), and immunohistochemistry are some of the most recent technological innovations. A systematic review of the literature was performed with the aim of presenting an up-to-date overview on the correlation between the immunohistochemical (IHC) expression of specific antigenic markers at different PMIs. The systematic review was performed according to PRISMA guidelines. Scopus and PubMed were used as search engines from January 1, 1998 to March 1, 2022 to evaluate the effectiveness of immunohistochemistry in estimating PMI. The following keywords were used: (immunohistochemical) OR (immunohistochemistry) AND (time since death) OR (post-mortem interval) OR (PMI). A total of 6571 articles were collected. Ultimately, 16 studies were included in this review. The results of this systematic review highlighted that IHC techniques, in association with traditional methods, add, in Bayesian terms, additional information to define a more accurate time of death and PMI. However, current IHC results are numerically limited and more data and studies are desirable in the near future.

Neurological disorders vis-à-vis climate change.

Climate change is one of the biggest challenges humanity is facing in the 21st century. Two recognized sequelae of climate change are global warming and air pollution. The gradual increase in ambient temperature, coupled with elevated pollution levels have a devastating effect on our health, potentially contributing to the increased rate and severity of numerous neurological disorders. The main aim of this review paper is to shed some light on the association between the phenomena of global warming and air pollution, and two of the most common and debilitating neurological conditions: stroke and neurodegenerative disorders. Extreme ambient temperatures induce neurological impairment and increase stroke incidence and mortality. Global warming does not participate in the etiology of neurodegenerative disorders, but it exacerbates symptoms of dementia, Alzheimer's disease (AD) and Parkinson's Disease (PD). A very close link exists between accumulated levels of air pollutants (principally particulate matter), and the incidence of ischemic rather than hemorrhagic strokes. People exposed to air pollutants have a higher risk of developing dementia and AD, but not PD. Oxidative stress, changes in cardiovascular and cerebrovascular haemodynamics, excitotoxicity, microglial activation, and cellular apoptosis, all play a central role in the overlap of the effect of climate change on neurological disorders. The complex interactions between global warming and air pollution, and their intricate effect on the nervous system, imply that future policies aimed to mitigate climate change must address these two challenges in unison.

Neuropeptides' Hypothalamic Regulation of Sleep Control in Children Affected by Functional Non-Retentive Fecal Incontinence.

Functional non-retentive fecal incontinence (FNRFI) is a common problem in pediatric age. FNRFI is defined as unintended loss of stool in a 4-year-old or older child after organic causes have been excluded. FNRFI tends to affects up to 3% of children older than 4 years, with males being affected more frequently than females. Clinically, children affected by FNRFI have normal intestinal movements and stool consistency. Literature data show that children with fecal incontinence have increased levels of separation anxiety, specific phobias, general anxiety, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder. In terms of possible relationship between incontinence and sleep, disorders of sleep organization have been observed in the pathogenesis of enuresis so generating the hypothesis that the orexinergic system may have a crucial role not only for the sleep organization per se but also for the sphincterial control in general. This study aimed to focus on specific neurophysiological aspects to investigate on the possible relationship between sleep organizational abnormalities and FNRFI. Specifically, we aimed to measure orexin serum levels in children with FNRFI and assess their polysomnographic sleep macrostructure patterns. Two study groups were considered: FNFRI (n = 45) and typically developed (TD) (n = 45) group. In both groups, sleep patterns and respiratory events were assessed by polysomnographic recordings (PSG) during a period of two nights at least, and plasma levels of Orexin-A were measured in each participant. The findings of this initial investigation seem to support a major role of Orexin-A in sleep organization alterations in children with FNFRI. Also, our data suggest that sleep habits evaluation should be considered as screening and complementary tool for the diagnosis of fecal incontinence in children.

High-Fat Diet Induces Neuroinflammation and Mitochondrial Impairment in Mice Cerebral Cortex and Synaptic Fraction.

Brain mitochondrial dysfunction is involved in the development of neurological and neurodegenerative diseases. Mitochondria specifically located at synapses play a key role in providing energy to support synaptic functions and plasticity, thus their defects may lead to synaptic failure, which is a common hallmark of neurodegenerative diseases. High-Fat Diet (HFD) consumption increases brain oxidative stress and impairs brain mitochondrial functions, although the underlying mechanisms are not completely understood. The aim of our study is to analyze neuroinflammation and mitochondrial dysfunctions in brain cortex and synaptosomal fraction isolated from a mouse model of diet-induced obesity. Male C57Bl/6 mice were divided into two groups fed a standard diet or HFD for 18 weeks. At the end of the treatment, inflammation (detected by ELISA), antioxidant state (measured by enzymatic activity), mitochondrial functions and efficiency (detected by oxidative capacity and Seahorse analysis), and brain-derived neurotrophic factor (BDNF) pathway (analyzed by western blot) were determined in brain cortex and synaptosomal fraction. In HFD animals, we observed an increase in inflammatory parameters and oxidative stress and a decrease in mitochondrial oxidative capacity both in the brain cortex and synaptosomal fraction. These alterations parallel with modulation of BDNF, a brain key signaling molecule that is linking synaptic plasticity and energy metabolism. Neuroinflammation HFD-dependent negatively affects BDNF pathway and mitochondrial activity in the brain cortex. The effect is even more pronounced in the synaptic region, where the impaired energy supply may have a negative impact on neuronal plasticity.

Modafinil and orexin system: interactions and medico-legal considerations.

Modafinil (Mo) is increasingly being used as an enhancement drug rather than for its therapeutic effects. The effects of this drug have been examined in attention deficit disorders, depression, mental fatigue, and in enhancing concentration. The drug possesses wakefulness-promoting properties which are mediated through the interaction of orexinergic system with the activated sympathetic nervous system. Mo exerts a synergistic effect on the orexin system, controls energy expenditure and strengthens the ability of the individual to exercise. Some view Mo as a drug that enhances sports performance, since it induces a prolonged wakefulness and decreasing the sense of fatigue. These characteristics being similar to conventional stimulants have allowed Mo to emerge as a novel stimulant requiring medico-legal considerations. However, more studies are needed to better understand the mid and long-term effects of the drug on user/abuser.

Vesicular glutamate release from central axons contributes to myelin damage.

The axon myelin sheath is prone to injury associated with N-methyl-D-aspartate (NMDA)-type glutamate receptor activation but the source of glutamate in this context is unknown. Myelin damage results in permanent action potential loss and severe functional deficit in the white matter of the CNS, for example in ischemic stroke. Here, we show that in rats and mice, ischemic conditions trigger activation of myelinic NMDA receptors incorporating GluN2C/D subunits following release of axonal vesicular glutamate into the peri-axonal space under the myelin sheath. Glial sources of glutamate such as reverse transport did not contribute significantly to this phenomenon. We demonstrate selective myelin uptake and retention of a GluN2C/D NMDA receptor negative allosteric modulator that shields myelin from ischemic injury. The findings potentially support a rational approach toward a low-impact prophylactic therapy to protect patients at risk of stroke and other forms of excitotoxic injury.

Perceptions of first-year medical students towards learning anatomy using cadaveric specimens through peer teaching.

During the last decade, global interest in the multiple benefits of formal peer teaching has increased. This study aimed to explore the perceptions of first-year medical students towards the use of peer teaching to learn anatomy using cadaveric specimens. A descriptive, cross-sectional, retrospective survey was carried out. Data were collected using an online questionnaire which was administered to all medical students who were in their second year of their medical school curriculum and who had participated in sessions taught by their peers during their first year. Peer teaching was perceived as an effective method of learning anatomy by more than half of the participants. Analysis of mean responses revealed that the peer teachers created a positive, non-intimidating learning environment. Overall, participants gave positive feedback on their peer teachers. Six categories emerged from the responses given by participants as to why they would or would not recommend peer teaching. Ways of improvement as suggested by the respondents were also reported. Variables found to be significantly associated with the perceived benefits of the peer teaching program included sex differences, educational level and recommendations for peer teaching. This study brings to light the merits and demerits of peer teaching as viewed through the eyes of the peer learners. Peer teaching provides a sound platform for teaching and learning anatomy. Further discussions at higher levels are encouraged in order to explore the feasibility of introducing formal peer teaching in the medical curriculum. Anat Sci Educ 11: 346-357. © 2017 American Association of Anatomists.

Functional Changes of Orexinergic Reaction to Psychoactive Substances.

It is becoming increasingly apparent the importance of the central nervous system (CNS) as the major contributor to the regulation of systemic metabolism. Antipsychotic drugs are used often to treat several psychiatric disorders, including schizophrenia and bipolar disorder However, antipsychotic drugs prescription, particularly the second-generation ones (SGAs), such as clozapine and olanzapine, is related to a considerable weight gain which usually leads to obesity. The aim of this paper is to assess the influence of orexin A on sympathetic and hyperthermic reactions to several neuroleptic drugs. Orexin A is a neuropeptide which effects both body temperature and food intake by increasing sympathetic activity. Orexin A-mediated hyperthermia is reduced by haloperidol and is blocked by clozapine and olanzapine. Orexin A-mediated body temperature elevation is increased by risperidone. These hyperthermic effects are delayed by quietapine. In this paper, it is discussed the orexinergic pathway activation by neuroleptic drugs and its influence on human therapeutic strategies. With the aim to determine that neuroleptic drugs mediate body temperature control through to the orexinergic system, we summarized our previously published data. Psychiatric disorders increase the risk of developing metabolic disorders (e.g., weight gain, increased blood pressure, and glucose or lipid levels). Therefore, the choice of antipsychotic drug to be prescribed, based on the relevant risks and benefits of each individual drug, has an essential role in human health prevention.

Influence of Football on Physiological Cardiac Indexes in Professional and Young Athletes.

Background: After long-term intensive training, considerable morphological and functional heart changes occur in professional athletes. Such changes arise progressively and regress upon interruption of the physical activity. Morphological and functional alterations on heart are known as "Athlete's heart" condition. Objective: This study aims to compare echocardiographic parameters in two different groups of professional athletes. Furthermore, a prospective study is performed analyzing the echocardiographic changes occurring in 12 professional players in 3 years of follow-up. Materials and Methods: 78 football players were examined from July 2011 to May 2016 (40 enrolled in Group A and 38 in Group B). Twelve players of GROUP A were followed for 3 consecutive seasons. The general clinical examination, the cardiopulmonary evaluation, the ECG, the ergometer stress test, the spirometric examination and the standard cardiac eco color doppler test were recorded. Results: Left ventricle dimensions, left atrium dimensions, and interventricular septum dimensions were higher in A players than in B players. Moreover, following up 12 players for 3 years, a statistically significant increase of such values was observed. Discussion: In A players, higher dimensions of the left chambers and the interventricular septum were observed, compared to B players. No statistically significant difference was found regarding the ejection fraction. The 3 years follow-up showed a statistically significant increase of both left chambers and interventricular septum dimensions, particularly in the second and third year. Conclusions: These findings demonstrated that A players have higher echocardiographic parameters respect to B players. The results of this study support the scientific theory that long-term intensive training influences heart function, inducing "athlete's heart" with morphological adaptations. No significant echocardiographic variation within the examined sample was observed for different roles (goalkeeper, defender, midfielder, or attacker) or skills of individual players.

Adiponectin and Orexin-A as a Potential Immunity Link Between Adipose Tissue and Central Nervous System.

Adipose tissue (AT) is strongly associated with development and progression of immune disorders through adipokines secretion, such as adiponectin. This protein has beneficial energetic properties and is involved in inflammation and immunity processes. Three oligomers of circulating adiponectin with different molecular weight are described: High (HMW), Medium (MMW), and Low (LMW). The HMW is the most biologically active oligomers. On binding to its receptors AdipoR1, AdipoR2, and T-cadherin, adiponectin acts on both innate and acquired immunity. The suppression of NF-κB activation and pro-inflammatory cytokine expression in macrophages is mediated by AdipoR1. AdipoR2 mediates polarization of anti-inflammatory M2 macrophages T-cadherin is essential for the M2 macrophage proliferation. Furthermore, adiponectin reduces T cells responsiveness and B cells lymphopoiesis. The immune system is very sensitive to environmental changes and it is not only interconnected with AT but also with the central nervous system (CNS). Cytokines, which are mediators of the immune system, exercise control over mediators of the CNS. Microglia, which are immunity cells belonging to the macrophage family, are present within the CNS. The nervous system is also involved in immunity through the production of neuropeptides such as orexin-A/hypocretin-1. This neuropeptide is involved in metabolic disorders, inflammation and in the immune response. The relationship between adipokines, immunity, and the nervous system is validated by both the role of orexin-A on fat, food intake, and energy expenditure, as well as by role of adiponectin on the CNS. In this review, we focused on the functions of adiponectin and orexin-A as a potential immunity link between AT and CNS.

Long Feeding High-Fat Diet Induces Hypothalamic Oxidative Stress and Inflammation, and Prolonged Hypothalamic AMPK Activation in Rat Animal Model.

Scope: The hypothalamus is a key brain region involved in the control of feeding and energy expenditure. Hypothalamic inflammation and oxidative stress are landmarks of both obesity and aging processes, although the molecular mechanisms are still unknown. Therefore, with the aim to understand the neurobiological mechanisms of energy homeostasis during aging, we evaluate the effects of long feeding high-fat diet (HFD) in rats, at different age, on modulation of hypothalamic molecular pathway, oxidative stress, and inflammation. Procedures: Male Wistar rats were divided into two groups: control group, receiving standard diet (CD), and treated group, receiving HFD. Both groups were treated with the appropriate diet for 1, 3, 6, 12, or 18 weeks. We investigated energy balance and body composition, as well as lipid profile, homeostatic model assessment index, and inflammatory state in serum. Furthermore, we also analyzed, at hypothalamic level, inflammation and oxidative stress, and adenosine monophosphate-dependent kinase (AMPK) and pAMPK expression levels. Results: Our data showed that aging and HFD induce increased energy intake and energy efficiency and decreased energy expenditure associated, at hypothalamic level, with inflammation and oxidative stress and activation of AMPK. Conclusion: Our results indicate that the age at which HFD feeding starts and the diet duration are critical in obesity development. The prolonged activation of hypothalamic AMPK may be related to the alterations in energy homeostasis.

Non-Rapid Eye Movement Sleep Parasomnias and Migraine: A Role of Orexinergic Projections.

INTRODUCTION: Sleep and migraine share a common pathophysiological substrate, although the underlying mechanisms are unknown. The serotonergic and orexinergic systems are both involved in the regulation of sleep/wake cycle, and numerous studies show that both are involved in the migraine etiopathogenesis. These two systems are anatomically and functionally interconnected. Our hypothesis is that in migraine a dysfunction of orexinergic projections on the median raphe (MR) nuclei, interfering with serotonergic regulation, may cause Non-Rapid Eye Movement parasomnias, such as somnambulism. HYPOTHESIS/THEORY: Acting on the serotonergic neurons of the raphe nuclei, the dysfunction of orexinergic neurons would lead to a higher release of serotonin. The activation of serotonergic receptors located on the walls of large cerebral vessels would lead to abnormal vasodilatation and consequently increase transmural pressure. This process could activate the trigeminal nerve terminals that innervate vascular walls. As a consequence, there is activation of sensory nerve endings at the level of hard vessels in the meninges, with release of pro-inflammatory peptides (e.g., substance P and CGRP). Within this hypothetical frame, the released serotonin could also interact with trigeminovascular afferents to activate and/or facilitate the release of the neuropeptide at the level of the trigeminal ganglion. The dysregulation of the physiological negative feedback of serotonin on the orexinergic neurons, in turn, would contribute to an alteration of the whole system, altering the sleep-wake cycle. CONCLUSION: Serotonergic neurons of the MR nuclei receive an excitatory input from hypothalamic orexin/hypocretin neurons and reciprocally inhibit orexin/hypocretin neurons through the serotonin 1A receptor (or 5-HT1A receptor). Considering this complex system, if there is an alteration it may facilitate the pathophysiological mechanisms involved in the migraine, while it may produce at the same time an alteration of the sleep-wake rhythm, causing sleep disorders such as sleepwalking. Understanding the complex mechanisms underlying migraine and sleep disorders and how these mechanisms can interact with each other, it would be crucial to pave the way for new therapeutic strategies.