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.

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.

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.

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.

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.

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.