Beyond Vertigo: Vestibular, Aural, and Perceptual Symptoms in Vestibular Migraine.

PURPOSE: To review the vestibular, aural, and perceptual symptoms of vestibular migraine (VM) that may present alongside vertigo. RECENT FINDINGS: Increased research attention to the wide spectrum of symptoms presenting in VM patients has improved understanding of this disorder, with recent identification of five different VM phenotypes. Research into the clinical overlap between VM and other chronic vestibular syndromes such as persistent postural-perceptual dizziness and mal-de-debarquement syndrome reveals a range of vestibular symptoms and hints at pathophysiological connections between migraine and vestibular dysfunction. Studies of migraine treatment for hearing loss suggest patients presenting with aural symptoms may have an underlying diagnosis of migraine and deserve a trial of migraine preventives. Research into the neurologic basis of the perceptual disorder Alice in Wonderland syndrome has revealed brain areas that are likely involved and may help explain its prevalence in VM patients. VM is a sensory processing disorder that presents with more than just vertigo. Understanding the range of potential symptoms improves diagnosis and treatment for migraine patients whose diagnosis may be missed when only the symptoms identified in the diagnostic criteria are considered.

Mal de Débarquement Syndrome in Children: A Case Series.

Currently, mal de débarquement syndrome (MdDS) has been reported only among adults. This case series describes 3 pediatric patients with MdDS. MdDS presentation in children is similar to that of adults, although the frequency of comorbid conditions is greater. Diagnostic delays are common and likely due to under-recognition of MdDS among children.

Transcranial Alternating Current Stimulation Reduces Network Hypersynchrony and Persistent Vertigo.

OBJECTIVES: Persistent oscillating vertigo that occurs after entrainment to periodic motion is known as Mal de Débarquement Syndrome (MdDS). Down-modulation of this oscillating vertigo is associated with reduction in long-range resting-state functional connectivity between fronto-parieto-occipital regions. In order to determine the association between this oscillating vertigo and hypersynchrony as measured by the auditory steady-state response (ASSR), we investigated the differences in ASSR between individuals with MdDS and healthy controls as well as the change in ASSR in individuals with MdDS before and after treatment with transcranial alternating current stimulation (tACS). MATERIALS AND METHODS: Individuals with treatment refractory MdDS lasting at least six months received single administrations of fronto-parieto-occipital tACS in an "n-of-1" double-blind randomized design: alpha-frequency in-phase, alpha-frequency antiphase, and gamma frequency antiphase control. The treatment protocol that led to the most acute reduction in symptoms and improved balance was administered for 10-12 sessions given over three days (each session 20-min at 2-4 mA). RESULTS: Twenty-four individuals with MdDS participated (mean age 53.0 ± 11.8 years [range: 22-66 years, median: 57.0 years]; mean duration of illness 38.6 ± 53.4 months [range: 6-240 months, median: 18.0 months]). Individuals with MdDS had elevated ASSR compared to healthy controls at baseline (t11 = 5.95, p < 0.001). There was a significant decrease in the 40 Hz-ASSR response between responders compared to nonresponders to tACS (t-test, t15 = -2.26, p = 0.04). Both in-phase and anti-phase alpha tACS lead to symptom improvement but only antiphase alpha-tACS led to a significant decrease of 40 Hz-ASSR (t-test, t12 = -9.6, p < 0.001). CONCLUSIONS: Our findings suggest that tACS has the potential to reduce network-level hypersynchrony and pathological susceptibility to entrainment by sensory input. To the best of our knowledge, this is the first successful demonstration of desynchronization by noninvasive brain stimulation leading to reduced vertigo. Other disease states associated with pathological functional coupling of neuronal networks may similarly benefit from this novel approach.

Electrophysiological Signatures of Intrinsic Functional Connectivity Related to rTMS Treatment for Mal de Debarquement Syndrome.

To determine intrinsic functional connectivity (IFC) related to symptom changes induced by rTMS in mal de debarquement syndrome (MdDS), a motion perceptual disorder induced by entrainment to oscillating motion. Twenty right-handed women (mean age: 52.9 ± 12.6 years; mean duration illness: 35.2 ± 24.2 months) with MdDS received five sessions of rTMS (1 Hz right DLPFC, 10 Hz left DLPFC) over consecutive days. High-density (128-channel) resting-state EEG were recorded prior to and following treatment sessions and analyzed using a group-level independent component (IC) analysis. IFC between 19 ICs was quantified by inter-IC phase coherence (ICPC) in six frequency bands (delta, theta, low alpha, high alpha, beta, gamma). Correlational analyses between IFCs and symptoms were performed. Symptom improvement after rTMS was significantly correlated with (1) an increase in low alpha band (8-10 Hz) IFC but a decrease of IFC in all other bands, and (2) high baseline IFC in the high alpha (11-13 Hz) and beta bands (14-30 Hz). Most treatment related IFC changes occurred between frontal and parietal regions with a linear association between the degree of symptom improvement and the number of coherent IFC changes. Frequency band and region specific IFC changes correlate with and can predict symptom changes induced by rTMS over DLPFC in MdDS. MdDS symptom response correlates with high baseline IFC in most frequency bands. Treatment induced increase in long-range low alpha IFC and decreases in IFC in other bands as well as the proportion of coherent IFC changes correlate with symptom reduction.

Assessing the synergistic effectiveness of intermittent theta burst stimulation and the vestibular ocular reflex rehabilitation protocol in the treatment of Mal de Debarquement Syndrome: a randomised controlled trial.

INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is a rare central vestibular disorder characterised by a constant sensation of motion (rocking, swaying, bobbing), which typically arises after motion experiences (e.g. sea, air, and road travel), though can be triggered by non-motion events. The current standard of care is non-specific medications and interventions that only result in mild-to-moderate improvements. The vestibular ocular reflex (VOR) rehabilitation protocol, a specialised form of rehabilitation, has shown promising results in reducing symptoms amongst people with MdDS. Accumulating evidence suggests that it may be possible to augment the effects of VOR rehabilitation via non-invasive brain stimulation protocols, such as theta burst stimulation (TBS). METHODS: The aim of this randomised controlled trial was to evaluate the effectiveness of intermittent TBS (iTBS) over the dorsolateral prefrontal cortex in enhancing the effectiveness of a subsequently delivered VOR rehabilitation protocol in people with MdDS. Participants were allocated randomly to receive either Sham (n = 10) or Active (n = 10) iTBS, followed by the VOR rehabilitation protocol. Subjective outcome measures (symptom ratings and mental health scores) were collected 1 week pre-treatment and for 16 weeks post-treatment. Posturography (objective outcome) was recorded each day of the treatment week. RESULTS: Significant improvements in subjective and objective outcomes were reported across both treatment groups over time, but no between-group differences were observed. DISCUSSION: These findings support the effectiveness of the VOR rehabilitation protocol in reducing MdDS symptoms. Further research into iTBS is required to elucidate whether the treatment has a role in the management of MdDS. TRN: ACTRN12619001519145 (Date registered: 04 November 2019).

Guideline for standardized approach in the treatment of the Mal de Debarquement syndrome.

Introduction: Mal de Debarquement Syndrome (MdDS) is a debilitating neuro-otological disorder. Patients experience almost continuously a perception of self-motion. This syndrome can be motion-triggered (MT-MdDS), such as on a boat, or occur spontaneously or have other triggers (SO-MdDS) in the absence of such motion. Because the pathophysiological mechanism is unknown, treatment options and symptom management strategies are limited. One available treatment protocol involves a readaptation of the vestibular ocular reflex (VOR). This study assesses the effectiveness of vestibulo-ocular reflex (VOR) readaptation in 131 consecutive patients with a fixed protocol. Methods: We administered 131 treatments involving optokinetic stimulation (OKS) paired with a fixed head roll at 0.167 Hz over two to five consecutive days. Each day, four-minute treatment blocks were scheduled twice in the morning and afternoon. Treatment effectiveness was evaluated through questionnaires and posturography. Results: We observed significant improvements in the visual analog scale (VAS), MdDS symptom questionnaire, and posturography measures from pre- to post-treatment. No significant differences were found in outcome variables between MT- and SO-MdDS onsets. Conclusion: Symptoms improved subjectively and objectively in patients' post-treatment. The overall success rate was 64.1%, with no significant difference between MT (64.2%) and SO (63.3%). This study supports the conclusion that VOR readaptation treatment provides relief for two-thirds of MdDS patients, irrespective of the onset type. Based on consistency in the findings, we propose a standardized method for treatment of MdDS based on the OKS with head roll paradigm.

Virtual reality application matches the most established treatment for Mal de Debarquement Syndrome: A non-inferiority, randomized, open clinical trial.

Mal de Debarquement Syndrome (MdDS) is a debilitating neuro-otological disorder where individuals consistently feel self-motion, often triggered by motion like being on a boat (MT-MdDS). Due to the unknown pathophysiological mechanism, available treatment options for managing symptoms are limited. Our objective was to develop a virtual reality application (VRA) to simulate the full field optokinetic stimulation (OKS) booth and evaluate its efficacy compared to the standard treatment. In our randomized, open, non-inferiority clinical trial with 30 â€‹MT-MdDS patients, 15 received the OKS booth and 15 the new VRA over four consecutive days. Two 4-min treatment blocks were scheduled in the morning and afternoon, with a total of four blocks. Treatment effectiveness was evaluated through questionnaires and posturography. Our findings suggest that the choice of modality does not significantly differ in achieving an overall improvement in symptoms. We advocate that the VRA can be used as an accessible alternative to the booth method worldwide, effectively mitigating MdDS symptoms and enhancing the QoL of numerous MdDS patients.

Mal De Debarquement Syndrome: An Often Unrecognized and Unreported Condition.

Mal de debarquement syndrome (MdDS), also known as "the sickness of disembarkment," is characterized by a persistent bobbing, rocking, or swaying sensation reported by patients long after they have completed travel on a boat or other forms of extended transportation. A detailed patient history, focusing on specific inquiries about recent boat or ship travel, is crucial for a timely diagnosis. The syndrome is unique in that reintroducing similar movements, such as driving, swinging, or returning to the boat, alleviates symptoms temporarily. We describe the case history of a 28-year-old male who experienced a persistent illusion of ground movement for six months following a fishing expedition. The patient reported alleviated symptoms when re-exposed to movements such as driving or swinging. The patient had undergone extensive medical workups and imaging tests under multiple physicians before being diagnosed with MdDS. MdDS is a commonly misdiagnosed, underdiagnosed, unreported, and unrecognized condition. Diagnosing MdDS requires a detailed medical and travel history, accompanying an understanding that the symptoms improve upon re-exposure to the same or similar motion.

Rocking dizziness and headache: a two-way street.

BACKGROUND: Chronic rocking dizziness, often described as the feeling of being on a boat, is classically triggered by prolonged exposure to passive motion. Patients with this motion-triggered sensation of rocking, which is also known as MAL DE DEBARQUEMENT SYNDROME , often develop new onset headaches along with the dizziness. Chronic rocking dizziness has also been noted in vestibular migraine, occurring without a motion trigger. We sought to clarify the association between both motion-triggered (MT) and non-motion-triggered (non-MT) chronic rocking dizziness and headache history. METHODS: Our methods included questionnaire and interview study of subjects with either MT or non-MT chronic rocking dizziness. RESULTS: Onset of headaches was earlier in patients with non-MT rocking dizziness (median 26 years: MT; 16 years: non-MT). In MT subjects, there was a bimodal peak of age of onset of headache (20-29 years and 40-49 years). Most headache met criteria for migraine in both groups. By the time that chronic dizziness occurred, both groups had a comparable prevalence of migraine headache (41%: MT; 46%: non-MT). Pre-existing headache usually worsened after the onset of dizziness. DISCUSSION: Though rocking dizziness does not meet current criteria for vestibular migraine, migraine physiology may predispose to, develop in, or worsen with the onset of chronic rocking dizziness.

Psychological assessment of individuals with Mal de Débarquement Syndrome.

OBJECTIVE: To report on the psychological, personality, and behavioral profiles of individuals with persistent Mal de Débarquement Syndrome (MdDS). MATERIALS AND METHODS: Individuals with MdDS who participated in neuromodulation clinical trials between May 2013 and June 2019 completed a series of standardized psychological questionnaires and underwent the Structural Clinical Interview for DSM-IV-TR (SCID) for specific psychiatric diagnoses. All data reported are from baseline assessments prior to any study interventions. Scores were compared to population norms for adult women. RESULTS: Complete datasets were available for 55 women. Mean age of onset of MdDS was 49.0 ± 11.9 years (range 22-69 years) and median duration of illness of 22 months (6 months-20 years). SCID results were as follows: healthy (48.1%), any lifetime Major Depressive Disorder (35.2%, 7.4% current); any lifetime history of anxiety disorder (11.1%); any lifetime substance use disorders (18.5%, 0% current). Compared to population norms, the MdDS group scored significantly higher on the Patient Health Questionnaire-9 depression scale and the Generalized Anxiety Disorder 7 (GAD-7) anxiety scale, but only the GAD-7 correlated with symptom severity. The NEO-Five Factor Inventory for personality, Positive and Negative Affect Schedule, Behavioral Inhibition System/Behavioral Activation System Scale, and the Empathy Quotient metrics did not correlate with duration of illness. Disability assessed by the 12-item World Health Organization Disability Assessment Schedule 2.0 was 25.7 ± 6.7, comparable to reports for concussion. Disability correlated with severity of depression, anxiety, neuroticism, and affect but not to severity of MdDS. CONCLUSIONS: Psychological profiles of MdDS relate to disability but not to duration of illness.

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.

The Interconnections of Mal de Débarquement Syndrome and Vestibular Migraine.

OBJECTIVES/HYPOTHESIS: Mal de débarquement syndrome (MDDS) is characterized by a persistent rocking sensation, as though on a boat. It may occur following exposure to passive motion (motion-triggered MDDS [MT-MDDS]), or spontaneously (spontaneous-onset MDDS [SO-MDDS]). This study investigated the characteristics of MDDS patients with vestibular migraine (MDDS-VM) to those without (MDDS-O). STUDY DESIGN: Retrospective review. METHODS: Retrospective, single-center study of 62 patients with MDDS. Clinical characteristics, Dizziness Handicap Inventory (DHI), Migraine Disability Assessment Score (MIDAS), job impact, and optimal treatment(s) were studied. RESULTS: There were 23 MDDS-O (19 women), and 39 MDDS-VM (35 women) patients. Comparisons between MDDS-VM and MDDS-O showed significant differences in age of onset (41 vs. 52 years, P = .005), interictal visually induced dizziness (89.7% vs. 30.4%, P < .001), interictal head motion-induced dizziness (87.2% vs. 47.8%, P = .001), other vestibular sensations (59% vs. 13%, P < .001), interictal aural symptoms (25.6% vs. 0%, P = .008), number of interictal symptoms (4.3 vs. 2.3, P < .001), total DHI score (54.9 vs. 38.1, P = .005), DHI-P (physical domain) score (16.1 vs. 10, P = .004), DHI-F (functional domain) score (20.9 vs. 15.7, P = .016 MIDAS (4.6 vs. 32, P = .002), and job resignations (23.2% vs. 5%, P = .016). On the other hand, between-group comparisons for MT-MDDS and SO-MDDS did not reveal any significant differences whatsoever. For optimal treatment, venlafaxine was the most used (27.3%) in all groups. For MDDS-VM, antiepileptic drugs and migraine preventive vitamins were also useful in relieving symptoms. CONCLUSIONS: MDDS-VM patients appear to be more disabled than MDDS-O, in terms of severity of dizziness, job impact, and number of symptoms, but have good potential for improvement, particularly with migraine prophylactic treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E1653-E1661, 2021.

Brain network effects by continuous theta burst stimulation in mal de débarquement syndrome: simultaneous EEG and fMRI study.

Objective. Heterogeneous clinical responses to treatment with non-invasive brain stimulation are commonly observed, making it necessary to determine personally optimized stimulation parameters. We investigated neuroimaging markers of effective brain targets of treatment with continuous theta burst stimulation (cTBS) in mal de débarquement syndrome (MdDS), a balance disorder of persistent oscillating vertigo previously shown to exhibit abnormal intrinsic functional connectivity.Approach.Twenty-four right-handed, cTBS-naive individuals with MdDS received single administrations of cTBS over one of three stimulation targets in randomized order. The optimal target was determined based on the assessment of acute changes after the administration of cTBS over each target. Repetitive cTBS sessions were delivered on three consecutive days with the optimal target chosen by the participant. Electroencephalography (EEG) was recorded at single-administration test sessions of cTBS. Simultaneous EEG and functional MRI data were acquired at baseline and after completion of 10-12 sessions. Network connectivity changes after single and repetitive stimulations of cTBS were analyzed.Main results.Using electrophysiological source imaging and a data-driven method, we identified network-level connectivity changes in EEG that correlated with symptom responses after completion of multiple sessions of cTBS. We further determined that connectivity changes demonstrated by EEG during test sessions of single administrations of cTBS were signatures that could predict optimal targets.Significance.Our findings demonstrate the effect of cTBS on resting state brain networks and suggest an imaging-based, closed-loop stimulation paradigm that can identify optimal targets during short-term test sessions of stimulation.ClinicalTrials.gov Identifier:NCT02470377.

Remotely Monitored Home-Based Neuromodulation With Transcranial Alternating Current Stimulation (tACS) for Mal de Débarquement Syndrome.

Objective: To determine whether remotely-monitored transcranial alternating current stimulation (tACS) may be a viable and safe treatment option for Mal de Débarquement Syndrome (MdDS). Background: Mal de Débarquement Syndrome is a neurotological disorder characterized by persistent oscillating vertigo that is triggered by entrainment to passive oscillatory motion such as occurs during water-based travel. Treatment options for MdDS are limited, variably effective, and can be undone by further travel. Design and Methods: This was a remotely-monitored open-label optional extension phase of a double-blind randomized onsite study of tACS for medically refractory MdDS. The primary goal was to determine safety, feasibility, and blinded participant feedback. The secondary goal was to determine efficacy. Thirteen participants (all women), aged 22-67 years, experiencing a duration of illness of 11-72 months, were a subset of 24 individuals who participated in an on-site study of tACS. They had either not responded to the on-site protocol or had relapsed after travel home. Treatment accessories and a tablet controlled tACS stimulator (Pulvinar XCSITE-100) were mailed to participants. Three teaching sessions were performed via webcam followed by on-going remote monitoring of treatment logs and participants' reports through a daily on-line diary and weekly questionnaires. Treatment continued until an effective protocol was administered for 4 weeks and then tapered over 4 weeks. Participants completed a blinded feedback survey and a debriefing interview at the completion of the entire study. Results: Treatment duration ranged from 4 to 31 weeks followed by a 4-week taper accounting for 578 verified sessions. Of the 13 total participants, seven agreed or agreed strongly in the blinded survey that tACS treatment was beneficial; 2) Twelve were comfortable utilizing tACS on their own; 3) Eleven preferred stimulation above their individual alpha frequency; 4) Side effects were generally mild and typical of tACS. In the debriefing interview completed 2-9 months after the last stimulation, five participants reported doing "great," with no to minimal symptoms, four reported doing "good," with moderate symptoms, and four reported no change compared to pre-study baseline. Conclusion: Remotely-monitored tACS may be a safe treatment option for MdDS with the potential for lasting outcomes, increased accessibility, and reduction in travel-related treatment reversal.

Neuroimaging Markers of Mal de Débarquement Syndrome.

Mal de débarquement syndrome (MdDS) is a motion-induced disorder of oscillating vertigo that persists after the motion has ceased. The neuroimaging characteristics of the MdDS brain state have been investigated with studies on brain metabolism, structure, functional connectivity, and measurements of synchronicity. Baseline metabolism and resting-state functional connectivity studies indicate that a limbic focus in the left entorhinal cortex and amygdala may be important in the pathology of MdDS, as these structures are hypermetabolic in MdDS and exhibit increased functional connectivity to posterior sensory processing areas and reduced connectivity to the frontal and temporal cortices. Both structures are tunable with periodic stimulation, with neurons in the entorhinal cortex required for spatial navigation, acting as a critical efferent pathway to the hippocampus, and sending and receiving projections from much of the neocortex. Voxel-based morphometry measurements have revealed volume differences between MdDS and healthy controls in hubs of multiple resting-state networks including the default mode, salience, and executive control networks. In particular, volume in the bilateral anterior cingulate cortices decreases and volume in the bilateral inferior frontal gyri/anterior insulas increases with longer duration of illness. Paired with noninvasive neuromodulation interventions, functional neuroimaging with functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and simultaneous fMRI-EEG have shown changes in resting-state functional connectivity that correlate with symptom modulation, particularly in the posterior default mode network. Reduced parieto-occipital connectivity with the entorhinal cortex and reduced long-range fronto-parieto-occipital connectivity correlate with symptom improvement. Though there is a general theme of desynchronization correlating with reduced MdDS symptoms, the prediction of optimal stimulation parameters for noninvasive brain stimulation in individuals with MdDS remains a challenge due to the large parameter space. However, the pairing of functional neuroimaging and noninvasive brain stimulation can serve as a probe into the biological underpinnings of MdDS and iteratively lead to optimal parameter space identification.

Readaptation Treatment of Mal de Debarquement Syndrome With a Virtual Reality App: A Pilot Study.

Mal de Debarquement syndrome (MdDS) is composed of constant phantom sensations of motion, which are frequently accompanied by increased sensitivity to light, inability to walk on a patterned floor, the sensation of ear fullness, head pressure, anxiety, and depression. This disabling condition generally occurs in premenopausal women within 2 days after prolonged passive motion (e.g., travel on a cruise ship, plane, or in a car). It has been previously hypothesized that MdDS is the result of maladaptive changes in the polysynaptic vestibulo-ocular reflex (VOR) pathway called velocity storage. Past research indicates that full-field optokinetic stimulation is an optimal way to activate velocity storage. Unfortunately, such devices are typically bulky and not commonly available. We questioned whether virtual reality (VR) goggles with a restricted visual field could effectively simulate a laboratory environment for MdDS treatment. A stripes program for optokinetic stimulation was implemented using Google Daydream Viewer. Five female patients (42 ± 10 years; range 26-50), whose average MdDS symptom duration was 2 months, participated in this study. Four patients had symptoms triggered by prolonged passive motion, and in one, symptoms spontaneously occurred. Symptom severity was self-scored by patients on a scale of 0-10, where 0 is no symptoms at all and 10 is the strongest symptoms that the patient could imagine. Static posturography was obtained to determine objective changes in body motion. The treatment was considered effective if the patient's subjective score improved by at least 50%. All five patients reported immediate improvement. On 2-month follow-ups, symptoms returned only in one patient. These data provide proof of concept for the limited-visual-field goggles potentially having clinical utility as a substitute for full-field optokinetic stimulation in treating patients with MdDS in clinics or via telemedicine.

Mal de Debarquement Syndrome: A Rare Entity.

Mal de debarquement syndrome (MdDS) is a bizarre sensation of continued movement after the termination of motion. It is accompanied by disequilibrium, usually experienced after voyage or travel, however, it is not associated with vertigo. Although most cases resolve spontaneously, middle-aged women sometimes particularly experience protracted symptoms following an ocean cruise, with the persistence of symptoms for many years. We present the case of a young female with no known comorbidities who was misdiagnosed quite a few times before the actual diagnosis of this rare disease was established.

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.

Mal de débarquement syndrome ­ "sickness of disembarkment" / [Mal de débarquement szindróma - "partraszállási betegség"]

Mal de débarquement syndrome is an uncommon vestibular disorder characterized by a constant sensation of swaying or motion after one disembarks from a vehicle such as a ship or plane, however, spontaneous onset also appears. These symptoms temporarily subside when the patient is subjected again to passive motion like driving a car. Chronic fatigue, anxiety, and depression are frequently associated with primary symptoms. The diagnosis is challenging, and often made by the patients themselves. The underlying pathophysiology and definitive therapy are unknown. Exposure to optokinetic stimulations and transcranial magnetic stimulations open therapeutic perspectives. We report a case series of 5 patients who presented with constant rocking, bobbing sensation that had been ongoing for several months. We found normal inner-ear function, non-related abnormalities and normal brain imaging. By presenting our patients' histories, we discuss the different diagnostic issues that help to diagnose this condition. We aimed to report the most recent findings on aetiology and treatment methods and to share our experiences with different therapeutic attempts. Mal de débarquement syndrome is a diagnosis of exclusion and often unrecognized. A thorough clinical history, negative or non-specific clinical findings with a high degree of suspicion are needed for recognizing this disorder. Increasing awareness can lead to early diagnosis and prevent multiple physician visits and unnecessary diagnostic testing. Frequent diagnostic failure has a negative impact on the quality of life, associated with anxiety and depression. Orv Hetil. 2020; 161(20): 846-851.

Neural Correlates of Transient Mal de Debarquement Syndrome: Activation of Prefrontal and Deactivation of Cerebellar Networks Correlate With Neuropsychological Assessment.

Background: Mal de debarquement syndrome (MdDS) is characterized by a subjective perception of self-motion after exposure to passive motion, mostly after sea travel. A transient form of MdDS (t-MdDS) is common in healthy individuals without pathophysiological certainty. In the present cross-sectional study, the possible neuropsychiatric and functional neuroimaging changes in local fishermen with t-MdDS were evaluated. Methods: The present study included 28 fishermen from Buan County in South Korea; 15 (15/28, 53.6%) participants experienced t-MdDS for 1-6 h, and 13 were asymptomatic (13/28, 46.4%). Vestibular function tests were performed using video-oculography, the video head impulse test, and ocular and cervical vestibular-evoked myogenic potentials. Visuospatial function was also assessed by the Corsi block test. Brain imaging comprised structural MRI, resting-state functional MRI, and [18F]FDG PET scans. Results: The results of vestibular function tests did not differ between the fishermen with and those without t-MdDS. However, participants with t-MdDS showed better performance in visuospatial memory function than those without t-MdDS (6.40 vs. 5.31, p-value = 0.016) as determined by the Corsi block test. Structural brain MRIs were normal in both groups. [18F]FDG PET showed a relative hypermetabolism in the bilateral occipital and prefrontal cortices and hypometabolism in the vestibulocerebellum (nodulus and uvula) in participants with t-MdDS compared to those without t-MdDS. Resting-state functional connectivities were significantly decreased between the vestibular regions of the flocculus, superior temporal gyrus, and parietal operculum and the visual association areas of the middle occipital gyrus, fusiform gyrus, and cuneus in participants with t-MdDS. Analysis of functional connectivity of the significant regions in the PET scans revealed decreased connectivity between the prefrontal cortex and visual processing areas in the t-MdDS group. Conclusion: Increased visuospatial memory, altered metabolism in the prefrontal cortex, visual cognition cortices, and the vestibulocerebellum, and decreased functional connectivity between these two functional areas might indicate reductions in the integration of vestibular input and enhancement of visuospatial attention in subjects with t-MdDS. Current functional neuroimaging similarities from transient MdDS via chronic MdDS to functional dizziness and anxiety disorders suggest a shared mechanism of enhanced self-awareness as a kind of continuum or as overlap disorders.