Online Questionnaire with Fibromyalgia Patients Shows Negative Correlations between Disease Severity and Adherence to Mediterranean Diet.

Fibromyalgia (FM) is a multidimensional disorder in which intense chronic pain is accompanied by a variety of psychophysical symptoms that impose a burden on the patients' quality of life. Despite the efforts and the recent advancement in research, FM pathogenesis and effective treatment remain unknown. Recently, the possible role of dietary patterns and/or components has been gaining attention. The current study aimed to investigate a potential correlation between adherence to the Mediterranean diet (MedDiet) and FM severity in a sample of Italian FM patients. An online survey was designed, composed of customized questions and validated questionnaires with the aim of investigating the intensity and type of pain, the presence of other psychophysical symptoms, the overall impact of FM, general food and lifestyle habits, and adherence to the MedDiet. The collected responses were analyzed for descriptive statistics, linear regression, and propensity score analyses. The results show that, despite considerable use of pharmaceuticals and supplements, FM participants suffered from a high-severity grade disease. However, those with good adherence to the MedDiet experienced a lower pain intensity and overall FM impact. A propensity score analysis indicates a positive influence of the MedDiet against FM severity, thus unveiling the need for well-designed intervention studies to evaluate the therapeutic potential of different dietary patterns.

Fibromyalgia in Pregnancy: Neuro-Endocrine Fluctuations Provide Insight into Pathophysiology and Neuromodulation Treatment.

Fibromyalgia (FM) is a chronic pain disorder with unclear pathophysiological mechanisms, which leads to challenges in patient management. In addition to pain, the disorder presents with a broad range of symptoms, such as sleep disruption, chronic fatigue, brain fog, depression, muscle stiffness, and migraine. FM has a considerable female prevalence, and it has been shown that symptoms are influenced by the menstrual cycle and periods of significant hormonal and immunological changes. There is increasing evidence that females with FM experience an aggravation of symptoms in pregnancy, particularly during the third trimester and after childbirth. In this perspective paper, we focus on the neuro-endocrine interactions that occur between progesterone, allopregnanolone, and cortisol during pregnancy, and propose that they align with our previously proposed model of FM pathogenesis based on GABAergic "weakening" in a thalamocortical neural loop system. Based on our hypothesis, we introduce the possibility of utilizing transcranial direct current stimulation (tDCS) as a non-invasive treatment potentially capable of exerting sex-specific effects on FM patients.

Mal de Debarquement Syndrome explained by a vestibulo-cerebellar oscillator.

Mal de Debarquement Syndrome (MdDS) is a puzzling central vestibular disorder characterized by a long-lasting perception of oscillatory postural instability that may occur after sea travels or flights. We have postulated that MdDS originates from the post-disembarking persistence of an adaptive internal oscillator consisting of a loop system, involving the right and left vestibular nuclei, and the Purkinje cells of the right and left flocculonodular cerebellar cortex, connected by GABAergic and glutamatergic fibers. We have formulated here a mathematical model of the vestibulo-cerebellar loop system and carried out a computational analysis based on a set of differential equations describing the interactions among the loop elements and containing Hill functions that model input-output firing rates relationships among neurons. The analysis indicates that the system acquires a spontaneous and permanent oscillatory behavior for a decrease of threshold and an increase of sensitivity in neuronal input-output responses. These results suggest a role for synaptic plasticity in MdDS pathophysiology, thus reinforcing our previous hypothesis that MdDS may be the result of excessive synaptic plasticity acting on the vestibulo-cerebellar network during its entraining to an oscillatory environment. Hence, our study points to neuroendocrine pathways that lead to increased synaptic response as possible new therapeutic targets for the clinical treatment of the disorder.

Online Questionnaire with Fibromyalgia Patients Reveals Correlations among Type of Pain, Psychological Alterations, and Effectiveness of Non-Pharmacological Therapies.

Fibromyalgia (FM) is a chronic pain syndrome with an unclear etiology. In addition to pain, FM patients suffer from a diverse array of symptoms and comorbidities, encompassing fatigue, cognitive dysfunction, mood disorders, sleep deprivation, and dizziness. Due to the complexity of FM, the diagnosis and treatment of it are highly challenging. The aim of the present work was to investigate some clinical and psychological characteristics of FM patients, and to uncover possible correlations with pharmacological and non-pharmacological therapies. We conducted a cross-sectional, questionnaire-based study aimed at evaluating pain, psychological traits, and the self-perceived effectiveness of pharmacological and non-pharmacological treatments in an Italian population of FM patients. Descriptive statistics, correlation, and inference analyses were performed. We found a prevalence of a neuropathic/nociplastic type of pain, which correlated with psychological traits such as anxiety, low mood, psychophysical discomfort, and the inability to relax. The pain type and psychological traits proved to play a role in determining the self-perceived effectiveness of therapeutic interventions. Patients revealed a better response to non-pharmacological therapies, particularly dietary interventions, relaxation techniques, and psychotherapy rather than pharmacological interventions. The sum of our data indicates that for better outcomes, the type of pain and psychological traits should be considered for tailor-made treatments considering non-pharmacological protocols as a complement to the use of drugs.

Visual disorders and mal de debarquement syndrome: a potential comorbidity questionnaire-based study.

Aim: Mal de debarquement syndrome (MdDS) is a neurological condition characterized by a constant sensation of self-motion; onset may be motion-triggered (MT) or non-motion-triggered/spontaneous (NMT/SO). People with MdDS experience similar symptoms to those with vertical heterophoria, a subset of binocular visual dysfunction. Hence, we aimed to explore potential visual symptom overlaps. Methods: MdDS patients (n = 196) and controls (n = 197) completed a visual health questionnaire. Results: Compared with controls, the MdDS group demonstrated higher visual disorder scores and visual complaints. NMT/SO participants reported unique visual symptoms and a higher prevalence of mild traumatic brain injury. Conclusion: Our findings suggest visual disorders may coexist with MdDS, particularly the NMT/SO subtype. The difference in visual dysfunction frequency and medical histories between subtypes, warrants further investigation into differing pathophysiological mechanisms.

Vestibular Disability/Handicap in Fibromyalgia: A Questionnaire Study.

Fibromyalgia (FM) is a poorly understood, central pain processing disorder characterized by a broad range of symptoms, such as chronic pain, sleep disruption, chronic fatigue, and psychosomatic symptoms. In addition, recent studies have shown that FM patients also experience dizziness. We aimed to establish a prevalence rate of vestibular symptoms in a population of FM patients through a battery of questionnaires investigating socio-demographic, clinical and psychological characteristics, combined with the Dizziness Handicap Inventory (DHI) and the Situational Vertigo Questionnaire (SVQ). A total of 277 respondents, officially diagnosed with FM, completed the full study, while 80 controls were also included for DHI and SVQ questionnaires. We found that FM participants were significantly affected by vestibular symptoms, which correlated with FM-associated pain and non-pain symptoms. The dizziness reported by FM participants showed peculiar features suggesting an FM-intrinsic mechanism of vestibular dysfunction, possibly linked to migraine and dysautonomia conditions. Correlations between dizziness and depressive mood (or neuroticism), revealed an impact of dizziness on psychological status, leading to depressive reactions and interpersonal difficulties, and possibly involving a noxious, self-sustained stress condition. In conclusion, data showed a manifesting dizziness condition in FM patients that warrants careful clinical attention due to its possible inherent role in the syndrome.

Thalamocortical bistable switch as a theoretical model of fibromyalgia pathogenesis inferred from a literature survey.

Fibromyalgia (FM) is an unsolved central pain processing disturbance. We aim to provide a unifying model for FM pathogenesis based on a loop network involving thalamocortical regions, i.e., the ventroposterior lateral thalamus (VPL), the somatosensory cortex (SC), and the thalamic reticular nucleus (TRN). The dynamics of the loop have been described by three differential equations having neuron mean firing rates as variables and containing Hill functions to model mutual interactions among the loop elements. A computational analysis conducted with MATLAB has shown a transition from monostability to bistability of the loop behavior for a weakening of GABAergic transmission between TRN and VPL. This involves the appearance of a high-firing-rate steady state, which becomes dominant and is assumed to represent pathogenic pain processing giving rise to chronic pain. Our model is consistent with a bulk of literature evidence, such as neuroimaging and pharmacological data collected on FM patients, and with correlations between FM and immunoendocrine conditions, such as stress, perimenopause, chronic inflammation, obesity, and chronic dizziness. The model suggests that critical targets for FM treatment are to be found among immunoendocrine pathways leading to GABA/glutamate imbalance having an impact on the thalamocortical system.

Influence of sex hormones on vestibular disorders.

PURPOSE OF REVIEW: Vestibular disorders are gender distributed with a higher prevalence in women. Although research has increased in this field, the mechanisms underlying this unbalance is unclear. This review summarises recent advances in this research sphere, and briefly discusses sex hormone effects on various vestibular conditions and highlights some recent theories. RECENT FINDINGS: Recent work has identified a direct link between aberrant gonadal hormone levels and vestibular dysfunction. Benign paroxysmal positional vertigo research suggests that the disorder may be linked to the rapid decrease in oestrogen, observed in menopausal women, which disrupts otoconial metabolism within the inner ear. A successful hormonal therapeutic intervention study has advanced our knowledge of hormonal influences in the inner ear in Ménière's disease. Also, several studies have focused on potential mechanisms involved in the interaction between Vestibular Migraine, Mal de Debarquement Syndrome, and gonadal hormones. SUMMARY: In females, gonadal hormones and sex-specific synaptic plasticity may play a significant role in the underlying pathophysiology of peripheral and central vestibular disorders. Overall, this review concludes that clinical assessment of female vestibular patients requires a multifaceted approach which includes auditory and vestibular medicine physicians, gynaecologists and/or endocrinologists, in conjunction with hormonal profile evaluations.

Diagnostic accuracy and usability of the EMBalance decision support system for vestibular disorders in primary care: proof of concept randomised controlled study results.

BACKGROUND: Dizziness and imbalance are common symptoms that are often inadequately diagnosed or managed, due to a lack of dedicated specialists. Decision Support Systems (DSS) may support first-line physicians to diagnose and manage these patients based on personalised data. AIM: To examine the diagnostic accuracy and application of the EMBalance DSS for diagnosis and management of common vestibular disorders in primary care. METHODS: Patients with persistent dizziness were recruited from primary care in Germany, Greece, Belgium and the UK and randomised to primary care clinicians assessing the patients with (+ DSS) versus assessment without (- DSS) the EMBalance DSS. Subsequently, specialists in neuro-otology/audiovestibular medicine performed clinical evaluation of each patient in a blinded way to provide the "gold standard" against which the + DSS, - DSS and the DSS as a standalone tool (i.e. without the final decision made by the clinician) were validated. RESULTS: One hundred ninety-four participants (age range 25-85, mean = 57.7, SD = 16.7 years) were assigned to the + DSS (N = 100) and to the - DSS group (N = 94). The diagnosis suggested by the + DSS primary care physician agreed with the expert diagnosis in 54%, compared to 41.5% of cases in the - DSS group (odds ratio 1.35). Similar positive trends were observed for management and further referral in the + DSS vs. the - DSS group. The standalone DSS had better diagnostic and management accuracy than the + DSS group. CONCLUSION: There were trends for improved vestibular diagnosis and management when using the EMBalance DSS. The tool requires further development to improve its diagnostic accuracy, but holds promise for timely and effective diagnosis and management of dizzy patients in primary care. TRIAL REGISTRATION NUMBER: NCT02704819 (clinicaltrials.gov).

Brain Correlates of Persistent Postural-Perceptual Dizziness: A Review of Neuroimaging Studies.

Persistent postural-perceptual dizziness (PPPD), defined in 2017, is a vestibular disorder characterized by chronic dizziness that is exacerbated by upright posture and exposure to complex visual stimuli. This review focused on recent neuroimaging studies that explored the pathophysiological mechanisms underlying PPPD and three conditions that predated it. The emerging picture is that local activity and functional connectivity in multimodal vestibular cortical areas are decreased in PPPD, which is potentially related to structural abnormalities (e.g., reductions in cortical folding and grey-matter volume). Additionally, connectivity between the prefrontal cortex, which regulates attentional and emotional responses, and primary visual and motor regions appears to be increased in PPPD. These results complement physiological and psychological data identifying hypervigilant postural control and visual dependence in patients with PPPD, supporting the hypothesis that PPPD arises from shifts in interactions among visuo-vestibular, sensorimotor, and emotional networks that overweigh visual over vestibular inputs and increase the effects of anxiety-related mechanisms on locomotor control and spatial orientation.

Telemedicine Across the Globe-Position Paper From the COVID-19 Pandemic Health System Resilience PROGRAM (REPROGRAM) International Consortium (Part 1).

Coronavirus disease 2019 (COVID-19) has accelerated the adoption of telemedicine globally. The current consortium critically examines the telemedicine frameworks, identifies gaps in its implementation and investigates the changes in telemedicine framework/s during COVID-19 across the globe. Streamlining of global public health preparedness framework that is interoperable and allow for collaboration and sharing of resources, in which telemedicine is an integral part of the public health response during outbreaks such as COVID-19, should be pursued. With adequate reinforcement, telemedicine has the potential to act as the "safety-net" of our public health response to an outbreak. Our focus on telemedicine must shift to the developing and under-developing nations, which carry a disproportionate burden of vulnerable communities who are at risk due to COVID-19.

Mal de Debarquement Syndrome: A Matter of Loops?

Introduction: Mal de Debarquement Syndrome (MdDS) is a poorly understood neurological disorder affecting mostly perimenopausal women. MdDS has been hypothesized to be a maladaptation of the vestibulo-ocular reflex, a neuroplasticity disorder, and a consequence of neurochemical imbalances and hormonal changes. Our hypothesis considers elements from these theories, but presents a novel approach based on the analysis of functional loops, according to Systems and Control Theory. Hypothesis: MdDS is characterized by a persistent sensation of self-motion, usually occurring after sea travels. We assume the existence of a neuronal mechanism acting as an oscillator, i.e., an adaptive internal model, that may be able to cancel a sinusoidal disturbance of posture experienced aboard, due to wave motion. Thereafter, we identify this mechanism as a multi-loop neural network that spans between vestibular nuclei and the flocculonodular lobe of the cerebellum. We demonstrate that this loop system has a tendency to oscillate, which increases with increasing strength of neuronal connections. Therefore, we hypothesize that synaptic plasticity, specifically long-term potentiation, may play a role in making these oscillations poorly damped. Finally, we assume that the neuromodulator Calcitonin Gene-Related Peptide, which is modulated in perimenopausal women, exacerbates this process thus rendering the transition irreversible and consequently leading to MdDS. Conclusion and Validation: The concept of an oscillator that becomes noxiously permanent can be used as a model for MdDS, given a high correlation between patients with MdDS and sea travels involving undulating passive motion, and an alleviation of symptoms when patients are re-exposed to similar passive motion. The mechanism could be further investigated utilizing posturography tests to evaluate if subjective perception of motion matches with objective postural instability. Neurochemical imbalances that would render individuals more susceptible to developing MdDS could be investigated through hormonal profile screening. Alterations in the connections between vestibular nuclei and cerebellum, notably GABAergic fibers, could be explored by neuroimaging techniques as well as transcranial magnetic stimulation. If our hypothesis were tested and verified, optimal targets for MdDS treatment could be found within both the neural networks and biochemical factors that are deemed to play a fundamental role in loop functioning and synaptic plasticity.

Combined Optokinetic Treatment and Vestibular Rehabilitation to Reduce Visually Induced Dizziness in a Professional Ice Hockey Player After Concussion: A Clinical Case.

Background: The appropriate detection and therapy of concussion symptoms are of great importance to avoid long-term impairment and absence from pre-concussive activities, such as sport, school or work. Post-traumatic headache and dizziness are known as risk factors of persistent symptoms after a concussion. Dizziness has even been classified as a predictor for symptom persistence. One type of dizziness, which has never been considered is visually induced dizziness (VID) often develops as a consequence of vestibular impairment. This manuscript presents the clinical case of a 25-year-old male, professional ice hockey player, whereby a therapeutic approach to VID after concussion is demonstrated. Case: A detailed interdisciplinary clinical and laboratory-assisted neurological, neurovestibular and ocular-motor examination was performed 20 days post-concussion, which indicated VID symptoms. Thus, the player qualified for a 5-day combined vestibular, balance and optokinetic therapy, which aimed to reduce the player's increased sensitivity to visual information. Each treatment day consisted of two sessions: vestibular/ocular-motor training and exposure to optokinetic stimuli combined with postural control exercises. The optokinetic stimulus was delivered in the form of a rotating disk. VID symptoms were recorded daily via posturography and a visual analog scale prior to the optokinetic sessions. The player improved over the course of each treatment day and was able to return to ice hockey 15 days after the final treatment session. Three months later the player reported no symptoms in the follow up questionnaire. Conclusion: The combination of vestibular, balance and optokinetic therapy led to remission of VID symptoms in a professional ice hockey player after multiple concussions, within a short time frame after his last concussion. Thus, this case study highlights the significant benefit of treating post-concussive VID symptoms utilizing a multi-modal approach.

[The Mal de Débarquement Syndrome]. / Syndrome du mal de débarquement.

The Mal de Débarquement Syndrome (MdDS) is characterized by a persistent (> 1 month) sensation of self-motion, most of the time initially motion-triggered (i.e. boat, car, airplane travel). The symptoms are markedly diminished during a new exposure to passive motion. Female are more often affected. The vestibular functional assessment and cerebral imaging are normal. Chronic fatigue, headache, hypersensitivity to visual stimuli are other classical features of MdDS. The impact of MdDS on quality of life is significant. Maladaptation of the vestibulo-ocular reflex, abnormal functional connectivity as well as gonadal hormones imbalance are possible causes of the MdDS. Exposure to optokinetic stimulations, and transcranial magnetic stimulations open therapeutic perspectives.

Le syndrome du mal de débarquement (MdDS) est caractérisé par la persistance d'une sensation de mouvement (> 1 mois), souvent suite à un déplacement en moyen de transport. Les symptômes sont nettement diminués lors d'une nouvelle exposition à un mouvement passif. Les femmes sont plus fréquemment atteintes. Le bilan fonctionnel vestibulaire et l'imagerie cérébrale sont normaux. La fatigue chronique, les céphalées, l'hypersensibilité aux stimuli visuels sont également caractéristiques du MdDS. L'impact sur la qualité de vie est significatif. Une mauvaise adaptation du réflexe vestibulo-oculaire, un trouble de la connectivité fonctionnelle ainsi qu'un dérèglement des hormones gonadiques pourraient être à l'origine du MdDS. L'exposition à des stimulations optocinétiques et la stimulation magnétique transcrânienne ouvrent des perspectives thérapeutiques.

Pilot study on patients with Mal de Debarquement syndrome during pregnancy.

AIM: To evaluate if patients with Mal de Debarquement syndrome (MdDS) demonstrate different symptom levels or symptom type during pregnancy. MATERIALS & METHODS: 18 MdDS patients that were or had been pregnant during their condition were recruited to complete a retrospective online questionnaire. Respondents answered questions regarding their basic clinical data, diagnosis, triggers and differences in symptom level and symptom type during pregnancy and before pregnancy. RESULTS: A total of 81.3% reported that their symptoms were reduced during pregnancy compared with before pregnancy. Respondents also reported a different perception of motion and experienced less dizziness while being pregnant. CONCLUSION: The physiological changes that occur during pregnancy improve the symptoms of patients with MdDS, and this is potentially attributable to the rise in estrogen and progesterone.

Sham-Controlled Study of Optokinetic Stimuli as Treatment for Mal de Debarquement Syndrome.

Introduction: Mal de Debarquement Syndrome (MdDS) is a condition characterized by a perception of self-motion in the absence of a stimulus, with two onset types: Motion-Triggered and Spontaneous. Currently, the pathophysiology is unknown and consequently, the therapeutic options are limited. One proposed treatment protocol, developed by Dai and colleagues is based on optokinetic stimulation, which aims to re-adapt the vestibular ocular reflex. This study aimed to reproduce the treatment protocol developed by Dai and colleagues and to assess if a placebo effect is present in the treatment protocol and lastly, aimed to further investigate the treatment on MdDS patient outcomes. Method: Twenty-five MdDS patients (13 Motion-Triggered and 12 Spontaneous) were exposed to 5 consecutive days of optokinetic treatment (consisting of exposure to optokinetic stimuli with head movements). Eleven of these 25 patients were also exposed to 2 days of a sham treatment prior to the OKN treatment. Posturography measurements and reported symptoms [e.g., using the visual analog scale (VAS)] of patients were assessed throughout the treatment. Posturography data of the patients was compared with the data of 20 healthy controls. Results: No placebo effect was recorded with any changes in postural data and VAS scale. After the optokinetic treatment, a significant improvement in postural control was observed in 48% of patients, of whom 70% were of the Motion-Triggered subtype (p-values: Area under the Curve-Anterior Posterior < 0.001; Area under the Curve-Medio Lateral p < 0.001, Confidence Ellipse Area (CEA) < 0.001, Velocity < 0.001). Conclusion: The protocol was effective in approximately half of the MdDS patients that took part in the study, with no placebo effect recorded. The Motion-Triggered group responded better to treatment than the Spontaneous group. In addition to this, this study indicates that the greatest postural changes occur within the first 3 days of treatment, suggesting that a shorter protocol is possible. Overall, these findings support what was previously observed in Dai's studies, that optokinetic stimulation can reduce and ease self-motion perception in those with MdDS. Thus, validating the reproducibility of this protocol, suggesting that a consistent and uncomplicated implementation across treatment centers is possible.

A new theory on GABA and Calcitonin Gene-Related Peptide involvement in Mal de Debarquement Syndrome predisposition factors and pathophysiology.

INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is a condition characterized by a sensation of motion in the absence of a stimulus, which presents with two subtypes depending on the onset: Motion-Triggered, and Spontaneous or Non-Motion Triggered. MdDS predominantly affects women around 40-50 years of age and a high number of patients report associated disorders, such as migraine and depression. The pathophysiology of MdDS is unclear, as is whether there are predisposing factors that make individuals more vulnerable to developing the condition. Hormonal changes in women similarly to what observed in migraineous patients, as well as depression disorder, have been examined as potential key factors for developing MdDS. Studies on migraine and depression have revealed correlations with hormonal fluctuations in females as well as aberrant levels of some key neurotransmitters such as Gamma-Aminobutyric Acid (GABA) and inflammatory neuropeptides like Calcitonin Gene-Related Peptide (CGRP). Consequently, this manuscript aims to propose a new hypothesis on the predisposing factors for MdDS and a new concept that could contribute to the understanding of its pathophysiology. NEW HYPOTHESIS: Recent findings have demonstrated a role for hormonal influences in MdDS patients, similar to previous observations in patients with depression and migraine. We hypothesize the involvement of gonadal hormones and aberrant neurotransmitter levels, including the GABAergic and serotonergic systems, in MdDS pathophysiology. Our theory is that certain individuals are more vulnerable to develop MdDS during specific gonadal hormonal phases. Furthermore, we hypothesize that it may be possible to identify these individuals by measurement of an existing imbalance of these neurotransmitters or inflammatory neuropeptides like CGRP. FURTHER EVALUATION OF THE HYPOTHESIS: According to one theory, MdDS is considered as a maladaptation of the Vestibular Ocular Reflex (VOR) and velocity storage. When considering this theory, it is essential to highlight that the brainstem nuclei involved in the VOR and the velocity storage include GABAb sensitive neurons, which appear to produce inhibitory control of velocity storage. Responses of these GABAb sensitive neurons are also modulated by CGRP. Thus an alteration of the GABAergic network by imbalances of inhibitory neurotransmitters or CGRP could influence signal integration in the velocity storage system and therefore be directly involved in MdDS pathophysiology. CONSEQUENCE OF THE HYPOTHESIS AND FUTURE STUDIES: A hormonal and neurotransmitter imbalance may act to predispose individuals in developing MdDS. Future studies should focus on the hormonal influences on neurotransmitters (e.g. GABA) and on the trial of CGRP antagonist drugs for the treatment of MdDS patients.

Mal de Debarquement Syndrome: A Retrospective Online Questionnaire on the Influences of Gonadal Hormones in Relation to Onset and Symptom Fluctuation.

INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is a condition characterized by a persistent perception of self-motion, in most cases triggered from exposure to passive motion (e.g., boat travel, a car ride, flights). Patients whose onset was triggered in this way are categorized as Motion-Triggered (MT) subtype or onset group. However, the same syndrome can occur spontaneously or after non-motion events, such as childbirth, high stress, surgery, etc. Patients who were triggered in this way are categorized as being of the Spontaneous/Other (SO) subtype or onset group. The underlying pathophysiology of MdDS is unknown and there has been some speculation that the two onset groups are separate entities. However, despite the differences in onset between the subtypes, symptoms are parallel and a significant female predominance has been shown. To date, the role of gonadal hormones in MdDS pathophysiology has not been investigated. This study aimed to evaluate the hormonal profile of MdDS patients, the presence of hormonal conditions, the influence of hormones on symptomatology and to assess possible hormonal differences between onset groups. In addition, the prevalence of migraine and motion sickness and their relation to MdDS were assessed. METHOD: Retrospective online surveys were performed in 370 MdDS patients from both onset groups. Data were analyzed using Fisher's exact test or Fisher-Freeman-Hanlon exact test. When possible, data were compared with normative statistical data from the wider literature. RESULTS: From the data collected, it was evident that naturally cycling female respondents from the MT group were significantly more likely to report an aggravation of MdDS symptoms during menses and mid-cycle (p < 0.001). A few preliminary differences between the onset groups were highlighted such as in regular menstrual cycling (p = 0.028), reporting menses during onset (p < 0.016), and migraine susceptibility after onset (p = 0.044). CONCLUSION: These results demonstrate a potential relation between hormone fluctuations and symptom aggravation in the MT group. This study is an important first step to suggest a hormonal involvement in the pathophysiology of MdDS and provides a base for further hormonal investigation. Future prospective studies should expand upon these results and explore the implications for treatment.

Chest Ultrasonography in Modern Day Extreme Settings: From Military Setting and Natural Disasters to Space Flights and Extreme Sports.

Chest ultrasonography (CU) is a noninvasive imaging technique able to provide an immediate diagnosis of the underlying aetiology of acute respiratory failure and traumatic chest injuries. Given the great technologies, it is now possible to perform accurate CU in remote and adverse environments including the combat field, extreme sport settings, and environmental disasters, as well as during space missions. Today, the usage of CU in the extreme emergency setting is more likely to occur, as this technique proved to be a fast diagnostic tool to assist resuscitation manoeuvres and interventional procedures in many cases. A scientific literature review is presented here. This was based on a systematic search of published literature, on the following online databases: PubMed and Scopus. The following words were used: "chest sonography," " thoracic ultrasound," and "lung sonography," in different combinations with "extreme sport," "extreme environment," "wilderness," "catastrophe," and "extreme conditions." This manuscript reports the most relevant usages of CU in the extreme setting as well as technological improvements and current limitations. CU application in the extreme setting is further encouraged here.