Mal De Debarquement

Neurological Disorder MONDO:0016217 Pathograph 10 Show in embeddings browser

Mal de débarquement syndrome (MdDS) is a chronic central vestibular disorder in which a persistent illusion of self-motion - described as rocking, bobbing or swaying - outlasts the passive motion that provoked it, classically a sea voyage but also air, road or rail travel. It is a disorder of the perception of motion rather than of the vestibular end organ: inner-ear function, audiometry and structural brain imaging are characteristically normal, and the diagnosis is made on the clinical pattern rather than on any test. The defining and diagnostically decisive feature is paradoxical: symptoms temporarily *remit* on re-exposure to passive motion, so patients feel better while driving and worse when the car stops. That single observation separates MdDS from persistent postural-perceptual dizziness, in which motion and visual complexity make things worse, and it is also the clue to the mechanism - the brain state is not a deficit but a maladaptive adaptation that the triggering stimulus transiently satisfies. The leading mechanistic account, developed from roll-while-rotating conditioning in monkeys and reproduced in humans in NASA rotating-room experiments, is that prolonged passive oscillatory motion maladapts the vestibulo-ocular reflex through velocity storage, the central integrator that extends the vestibular response beyond the cupula's own time constant. Formalized as a three-dimensional dynamical system, the lesion is cross-axis coupling - off-diagonal terms misaligning the yaw eigenvector from the head-vertical and gravity axes - which is experienced as a continuous pull or rocking. Downstream, functional imaging finds a limbic focus of entorhinal and amygdala hypermetabolism with increased coupling to posterior visual-vestibular areas and reduced frontal connectivity, and resting EEG frames the disorder as entrainment to oscillating motion rather than a focal lesion. The therapy that follows from this account - rolling the head while viewing a full-field rotating stimulus, to readapt the reflex in the opposite direction - is unusual in that it is simultaneously the treatment and the clearest test of the mechanism. MdDS falls disproportionately on women in the fourth to sixth decades, often around the perimenopausal transition, and carries high migraine comorbidity. Population prevalence is not known.

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1
Definitions
5
Pathophys.
10
Phenotypes
1
Gaps
10
Pathograph
5
Medical Actions
3
Differentials
1
Models
1
Deep Research
📘

Definitions

1
Bárány Society diagnostic criteria for MdDS
The International Classification of Vestibular Disorders case definition. Criteria A-D must all be met and E excludes better explanations: (A) non-spinning vertigo of oscillatory character, continuous or most of the day; (B) onset within 48 hours of the end of passive motion exposure; (C) temporary reduction of symptoms on re-exposure to passive motion; (D) duration beyond 48 hours; (E) not better accounted for by another disorder. Criterion C is the discriminating one - it is what separates MdDS from the disorders it most resembles.
DIAGNOSTIC_CRITERIA
Show evidence (2 references)
PMID:32986636 SUPPORT DIRECT Other
"1] Non-spinning vertigo characterized by an oscillatory perception ('rocking,' 'bobbing,' or 'swaying') present continuously or for most of the day; 2] Onset occurs within 48 hours after the end of exposure to passive motion, 3] Symptoms temporarily reduce with exposure to passive motion (e.g...."
States the four positive diagnostic criteria verbatim.
PMID:32986636 SUPPORT DIRECT Other
"there are demographic and prognostic differences between the common short-term unsteadiness that happens immediately after landing and the syndrome that can last well beyond 48 hours"
Justifies the 48-hour threshold: brief post-disembarkation unsteadiness is near-universal and non-pathological, so the criterion is what makes MdDS a disorder rather than a normal after-effect.
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Discussions and Knowledge Gaps

1
Is motion-moderated oscillatory vertigo without a motion trigger the same disease as motion-triggered MdDS, a variant of PPPD, or a third entity?
KNOWLEDGE GAP OPEN mdds_non_motion_triggered_variant
Attached to
pathophysiology#Prolonged Passive Oscillatory Motion Exposure differential_diagnoses#Persistent postural-perceptual dizziness (PPPD)
The consensus criteria require onset within 48 hours of passive motion, yet the same committee records an otherwise indistinguishable presentation arising with no motion trigger - typically after another vestibular disorder, a medical illness, psychological stress or metabolic disturbance - and states that its terminology has varied because it has features of both MdDS and PPPD. This is not a naming quibble: the entire mechanistic account in this entry begins with an oscillatory conditioning stimulus, so a presentation without one either reaches the same velocity-storage state by another route or is a different disease wearing the same symptoms. The entry curates the motion-triggered form, which is what the criteria define, and does not silently extend its mechanism to the non-triggered presentation. Resolving this needs the phenomenological and mechanistic comparison the committee itself calls for.
Show evidence (2 references)
PMID:32986636 SUPPORT DIRECT Other
"Terminology for this non-motion triggered presentation has been varied as it has features of both MdDS and PPPD."
The consensus committee's own statement that the boundary is unresolved and needs further research.
PMID:30410464 SUPPORT DIRECT Human Clinical
"The Motion-Triggered group responded better to treatment than the Spontaneous group."
A differential response to a mechanism-directed therapy is the first concrete discriminator between the two presentations, and bears directly on this question: if the readaptation protocol works less well without a motion trigger, that is evidence the two do not share the same lesion.
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Pathophysiology

5
Prolonged Passive Oscillatory Motion Exposure
The initiating exposure: hours of passive, periodic, oscillatory motion - a ship, aircraft, car or train, but also a swaying building, a waterbed or moving exercise equipment. What matters mechanistically is the oscillatory or periodic character of the stimulus coupled with a minimum duration on the order of hours, not the mode of transport. A concurrent physical or psychological stressor during the exposure is commonly reported, and perimenstrual or perimenopausal hormonal state at the time of exposure has been proposed as a risk factor. Notably the triggering journey is not otherwise remarkable - it need not involve seasickness or illness.
Downstream
Velocity Storage Cross-Axis Maladaptation Sustained periodic vestibular input during head movement conditions the central velocity-storage integrator into a maladapted configuration.
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"The key features of the triggers are an oscillatory or periodic stimulus coupled with some minimal duration of exposure, generally on the order of hours."
Identifies the mechanically relevant properties of the trigger.
Velocity Storage Cross-Axis Maladaptation
The core lesion. Velocity storage is the central vestibular integrator that prolongs the response to rotation well beyond the cupula's own time constant; roll-while-rotating conditioning maladapts the vestibulo-ocular reflex through it. The dependence on velocity storage is not assumed - in the monkey experiments the maladaptation appeared only in animals with long VOR time constants and not when the time constant approached the cupula's, which is what implicates the central integrator rather than the periphery. Modelled as a three-by-three dynamical system, normal upright orientation gives a diagonal system matrix whose yaw eigenvector aligns with gravity; in MdDS off-diagonal terms appear, representing cross-axis coupling and a misalignment between the yaw eigenvector and the head vertical, which is experienced as a directional pull. No GO term is bound here because none describes the vestibulo-ocular reflex.
Animal models
Roll-while-rotating conditioned rhesus monkey Monkey recapitulates Reproduces the proposed lesion by applying the proposed cause, and the equivalent conditioning was subsequently produced in humans in rotating-room experiments, which bridges the species gap.
Downstream
Persistent Oscillatory Self-Motion Perception The maladapted reflex is read centrally as continuing self-motion after the physical motion has stopped.
Limbic-Vestibular Network Reorganization Sustained abnormal motion signalling entrains a distributed cortical and limbic network.
Show evidence (2 references)
PMID:25076935 SUPPORT INDIRECT Model Organism
"This only occurred in monkeys with long VOR time constants, and was not present when the VOR time constant was close to that of the cupula"
The observation that localizes the lesion to central velocity storage rather than the periphery. Graded INDIRECT because it is conditioning in monkeys, from which the human mechanism is inferred.
PMID:41122084 SUPPORT INDIRECT Computational
"A pull sensation of MdDS has been expressed with a system matrix with off-diagonal elements representing cross-axis coupling and interpreted as a misalignment between the yaw eigenvector and the head vertical."
Formalizes the lesion as cross-axis coupling in the velocity-storage matrix. INDIRECT because it is a mathematical model of the mechanism, not a measurement of it.
Persistent Oscillatory Self-Motion Perception
The cardinal symptom and the state that defines the disease: a continuous non-spinning perception of rocking, bobbing or swaying, present most or all of the day, persisting for months or years after a motion exposure of hours. Its signature behaviour is that it is transiently nulled by re-exposure to passive motion and rebounds when that motion stops - the percept behaves as though the brain has adopted a model of the world in which the motion is still happening.
Downstream
Functional Impairment and Secondary Affective Burden A continuous unrelenting motion illusion drives fatigue, impaired concentration and secondary anxiety and depression.
Show evidence (2 references)
PMID:33746890 SUPPORT DIRECT Other
"Symptoms are described as a “rocking,” “bobbing,” or “swaying” perception that is nulled by exposure to passive motion such as driving/riding in a car or returning to the triggering stimulus."
States the percept and its defining nulling behaviour.
PMID:25076935 SUPPORT DIRECT Human Clinical
"Physical findings included body oscillation at 0.2 Hz, oscillating vertical nystagmus when the head was rolled from side-to-side in darkness, and unilateral rotation during the Fukuda stepping test."
The objective correlates of the subjective percept, and the only described examination sign of the disorder.
Limbic-Vestibular Network Reorganization
Downstream of the maladapted reflex, functional imaging shows a limbic focus of hypermetabolism in the left entorhinal cortex and amygdala, increased functional connectivity from that focus to posterior visual and vestibular processing areas including motion-sensitive MT/V5, and reduced connectivity to frontal and temporal cortices. Resting-state EEG frames the same state as entrainment to oscillating motion, with treatment response tracking inter-regional alpha-band phase coherence. This is a network-level dysrhythmia rather than a focal lesion, which is consistent with structural imaging being normal.
Show evidence (3 references)
PMID:23209584 SUPPORT DIRECT Human Clinical
"MdDS subjects showed increased metabolism in the left entorhinal cortex and amygdala (z>3.3)."
The primary FDG-PET finding, in 20 patients against 20 matched controls.
PMID:33746890 SUPPORT DIRECT Other
"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"
Synthesis of the connectivity pattern across imaging studies.
PMID:30099627 SUPPORT DIRECT Human Clinical
"a motion perceptual disorder induced by entrainment to oscillating motion"
Frames the disorder electrophysiologically as motion entrainment.
Functional Impairment and Secondary Affective Burden
The clinical endpoint. Beyond the motion illusion itself, patients develop spatial disorientation, visual motion intolerance, chronic fatigue, impaired cognition, insomnia, and exacerbation of headache, anxiety and depression. Whether the affective symptoms are secondary to a relentless perceptual disturbance or share the limbic substrate is not resolved; the imaging studies covaried for mood and anxiety precisely because of that ambiguity.
Show evidence (1 reference)
PMID:32364688 SUPPORT DIRECT Human Clinical
"Chronic fatigue, anxiety, and depression are frequently associated with primary symptoms."
Documents the secondary symptom burden accompanying the core percept.
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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Mal De Debarquement Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

10
Ear 3
Persistent Oscillatory Vertigo OBLIGATE Non-spinning vertigo HP:4000033 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Non-spinning oscillatory vertigo, annotated with Non-spinning vertigo (HP:4000033), qualified as temporality chronic. HP:4000033 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"Non-spinning vertigo characterized by an oscillatory perception (‘rocking,’ ‘bobbing,’ or ‘swaying’) present continuously or for most of the day"
Criterion A of the case definition, hence OBLIGATE - a patient without it does not have the diagnosis.
Visual Motion Intolerance Abnormal vestibular function HP:0001751 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Visual motion intolerance, annotated with Abnormal vestibular function (HP:0001751). HP:0001751 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety."
Names visual motion intolerance as a co-existing symptom. Bound to the general vestibular-function term because HPO has no specific class for visual motion intolerance.
Spatial Disorientation Abnormal vestibular function HP:0001751 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Spatial disorientation, annotated with Abnormal vestibular function (HP:0001751). HP:0001751 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety."
Names spatial disorientation as a co-existing symptom.
Eye 1
Head-Roll Induced Nystagmus HP:0000639 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Nystagmus (HP:0000639). HP:0000639 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:25076935 SUPPORT DIRECT Human Clinical
"oscillating vertical nystagmus when the head was rolled from side-to-side in darkness"
Documents the examination sign linking the symptom to the reflex lesion.
Nervous System 5
Gait Imbalance HP:0002141 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Gait imbalance (HP:0002141). HP:0002141 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:25076935 SUPPORT DIRECT Human Clinical
"Physical findings included body oscillation at 0.2 Hz"
Quantifies the postural oscillation accompanying the percept.
Impaired Cognition Cognitive impairment HP:0100543 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Impaired cognition, annotated with Cognitive impairment (HP:0100543). HP:0100543 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:25076935 SUPPORT DIRECT Human Clinical
"it is associated with many other disturbing symptoms, including disorientation, impaired cognition, fatigue, ataxia, insomnia, headache, anxiety, and depression"
Names impaired cognition among the accompanying symptom burden.
Depression HP:0000716 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Depression (HP:0000716). HP:0000716 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32364688 SUPPORT DIRECT Human Clinical
"Chronic fatigue, anxiety, and depression are frequently associated with primary symptoms."
Documents depression as a frequent accompanying feature.
Anxiety HP:0000739 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anxiety (HP:0000739). HP:0000739 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32364688 SUPPORT DIRECT Human Clinical
"Chronic fatigue, anxiety, and depression are frequently associated with primary symptoms."
Documents anxiety as a frequent accompanying feature.
Headache Exacerbation HP:0002315 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Headache (HP:0002315). HP:0002315 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety."
Names exacerbation of headache among the co-existing symptoms.
Constitutional 1
Chronic Fatigue HP:0012378 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fatigue (HP:0012378), qualified as temporality chronic. HP:0012378 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety."
Lists fatigue among the recognized co-existing symptoms.
💊

Medical Actions

5
Vestibulo-Ocular Reflex Readaptation (Optokinetic Roll Protocol)
Action: RehabilitationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Rehabilitation (NCIT:C15315). NCIT:C15315 is a clinical intervention from the NCI Thesaurus. NCIT:C15315
Platform: Behavioral / lifestyle
The one disease-specific therapy, and the clearest test of the mechanism: the patient rolls the head side to side while viewing a rotating full-field visual stimulus, driving reflex adaptation in the direction opposite to the maladapted components. In the original series 17 of 24 patients had complete or substantial recovery sustained about a year, six relapsed after initial benefit and one did not respond. Its rationale is not empirical - it was predicted from the velocity-storage account and then tested, so its success is itself evidence for the mechanism.
Mechanism Target:
Velocity Storage Cross-Axis Maladaptation — Acts directly on the proposed lesion by readapting the reflex, rather than on symptoms downstream of it.
Show evidence (3 references)
PMID:25076935 SUPPORT DIRECT Human Clinical
"Seventeen of the 24 subjects had a complete or substantial recovery on average for approximately 1 year."
The primary efficacy result, in an uncontrolled series of 24 patients.
PMID:25076935 SUPPORT INDIRECT Human Clinical
"We conclude that the adaptive processes associated with roll-while-rotating are responsible for producing MdDS"
The authors' inference from treatment response back to mechanism. Graded INDIRECT because it reasons from a therapeutic result to the mechanism that therapy targets.
PMID:30410464 SUPPORT DIRECT Human Clinical
"No placebo effect was recorded with any changes in postural data and VAS scale."
A sham exposure produced no change. This matters more than the response rate for the entry's argument: if treatment response is offered as evidence for the mechanism, the absence of a placebo effect is what stops that argument resting on expectation alone.
Repetitive Transcranial Magnetic Stimulation over Left DLPFC
Action: Transcranial Magnetic StimulationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Transcranial Magnetic Stimulation (NCIT:C116655). NCIT:C116655 is a clinical intervention from the NCI Thesaurus. NCIT:C116655
Platform: Device
10 Hz rTMS over the left dorsolateral prefrontal cortex, targeting the cortico-limbic node implicated by imaging rather than the vestibular lesion. A small double-blind sham-controlled crossover trial in eight women reported improvement in dizziness and in mood and anxiety persisting beyond the treatment period. Evidence is limited and the effect sizes modest: a scoping review of TMS across chronic vestibular disorders found statistically significant improvement on the Dizziness Handicap Inventory in a minority of studies (3 of 7) and no clinically significant improvement at all, with the authors cautioning that methodological limitations bear on how the results are read.
Mechanism Target:
Limbic-Vestibular Network Reorganization — Targets the prefrontal node of the reorganized network rather than the upstream velocity-storage lesion.
Show evidence (2 references)
PMID:27176615 SUPPORT DIRECT Human Clinical
"Our study provides evidence that the dizziness, mood and anxiety symptoms of MdDS can be improved with 10 Hz rTMS over left DLPFC beyond the treatment period in selected individuals"
The controlled trial result. Note the authors' own qualifier, "in selected individuals" - this is eight patients, not a general indication.
PMID:40228811 SUPPORT INDIRECT Human Clinical
"Statistically significant improvements were noted on the Dizziness Handicap Inventory (3/7 studies) but clinically significant improvements were not observed."
Bounds the claim rather than supporting it straightforwardly. Across chronic vestibular disorders as a class, TMS reached statistical significance on the Dizziness Handicap Inventory in a minority of studies and clinical significance in none, which is why this treatment is recorded as limited rather than established. Graded INDIRECT because the review covers chronic vestibular disorders generally rather than this disease specifically.
Intermittent Theta Burst Stimulation as an Adjunct to VOR Rehabilitation
Action: Transcranial Magnetic StimulationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Transcranial Magnetic Stimulation (NCIT:C116655). NCIT:C116655 is a clinical intervention from the NCI Thesaurus. NCIT:C116655
Platform: Device
Tested as a way to augment the readaptation protocol. It did not work: in a randomised sham-controlled trial of 20 patients both arms improved and there was no between-group difference, so the benefit was attributable to the rehabilitation and not to the stimulation. Recorded because a negative controlled result is more informative here than the positive uncontrolled ones, and because it bounds what neuromodulation adds.
Show evidence (1 reference)
PMID:38345630 REFUTE DIRECT Human Clinical
"Significant improvements in subjective and objective outcomes were reported across both treatment groups over time, but no between-group differences were observed."
Refutes an additive benefit of iTBS over VOR rehabilitation alone. The shared improvement in both arms simultaneously supports the rehabilitation protocol.
Transcranial Direct Current Stimulation over DLPFC
Action: Transcranial Direct Current StimulationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Transcranial Direct Current Stimulation (NCIT:C129862). NCIT:C129862 is a clinical intervention from the NCI Thesaurus. NCIT:C129862
Platform: Device
Anodal left / cathodal right DLPFC tDCS, delivered at home following rTMS in a randomised single-blind sham-controlled study of 23 patients. Those receiving real tDCS improved on the MdDS Balance Rating Scale and on anxiety by week 4. Included because it is the neuromodulation arm with a positive controlled result, alongside the iTBS trial that was negative.
Mechanism Target:
Limbic-Vestibular Network Reorganization — Targets the same prefrontal node as rTMS rather than the upstream velocity-storage lesion.
Show evidence (1 reference)
PMID:27117283 SUPPORT DIRECT Human Clinical
"Those who received real tDCS after rTMS showed significant improvements in the degree of rocking perception as measured by the MdDS Balance Rating Scale and anxiety ratings by Week 4"
The controlled efficacy result for adjunctive tDCS.
Vestibular Migraine Prophylaxis
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Platform: Small molecule
Given the high migraine comorbidity, an institutional vestibular-migraine protocol - lifestyle modification plus verapamil, nortriptyline, topiramate or a combination - benefited 11 of 15 patients in one series. Symptomatic rather than mechanism-directed, and it presupposes the migraine phenotype. There is no drug approved specifically for MdDS.
Show evidence (1 reference)
PMID:27730651 SUPPORT DIRECT Human Clinical
"Eleven patients (73%) responded well to management with a vestibular migraine protocol, which included lifestyle changes, as well as pharmacotherapy with verapamil, nortriptyline, topiramate, or a combination thereof"
The response rate to migraine prophylaxis in a 15-patient series.
🌍

Environmental Factors

1
Prolonged exposure to passive oscillatory motion (sea, air, road or rail travel)
exposure to passive oscillatory motion during travel ECTO:6000033 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is exposure to passive oscillatory motion during travel, annotated with exposure to travel (ECTO:6000033). ECTO:6000033 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
ECTO:6000033 `exposure to travel` is the closest available term and is deliberately imperfect: the mechanically relevant property is passive oscillatory motion of some hours' duration, not travel as such, and the same trigger is reported from swaying buildings, waterbeds and moving exercise equipment, which are not travel at all. Bound rather than left free-text because the overwhelming majority of triggers are journeys, with the mismatch recorded here rather than hidden.
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"Typical triggers include transportation vessels such as boats, airplanes, automobiles, and trains but can also include swaying buildings, waterbeds, exercise equipment and other platforms that passively move the individual"
Enumerates the reported trigger exposures, including the non-travel ones.
Mechanism Target:
TRIGGERS Velocity Storage Cross-Axis Maladaptation — The exposure is the conditioning stimulus itself: periodic vestibular input sustained across head movements is what maladapts the reflex.
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"Onset occurs within 48 hours after the end of exposure to passive motion"
The tight temporal coupling between exposure and onset is what makes this a trigger rather than an association.
🔬

Diagnosis

1
Clinical diagnosis with normal vestibular and structural testing
There is no confirmatory test. Vestibular function testing, audiometry and structural brain imaging are characteristically normal, and their normality is part of the diagnostic picture rather than a failure to find the lesion - the disorder is one of central motion perception, not of the end organ. The imaging abnormalities that do exist are group-level research findings, not clinical assays.
Show evidence (1 reference)
PMID:32364688 SUPPORT DIRECT Human Clinical
"We found normal inner-ear function, non-related abnormalities and normal brain imaging"
Documents the expected normal work-up in a clinical case series.
📈

Progression

3
MdDS in evolution
Symptoms ongoing but the observation period is under one month, so the course cannot yet be assigned. A staging designation, not a distinct disease.
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"MdDS in evolution: symptoms are ongoing but the observation period has been less than 1 month"
Defines the provisional staging category.
Transient MdDS
Symptoms resolve at or before one month. Diagnosable only in retrospect, since it is defined by remission having occurred.
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"Transient MdDS: symptoms resolve at or before 1 month and the observation period extends at least to the resolution point"
Defines the remitting course.
Persistent MdDS
Symptoms beyond one month. This is the clinically burdensome form; reported cohorts have median durations of many months to years.
Show evidence (3 references)
PMID:32986636 SUPPORT DIRECT Other
"Persistent MdDS: symptoms last for more than 1 month"
Defines the persistent course.
PMID:23209584 SUPPORT DIRECT Human Clinical
"Twenty subjects with MdDS lasting a median duration of 17.5 months"
Illustrates the typical duration in a persistent-MdDS research cohort.
PMID:27730651 SUPPORT DIRECT Human Clinical
"symptoms that persist beyond 6 months have been described as unlikely to remit"
Records the prognostic threshold beyond which spontaneous remission is described as unlikely - the practical significance of the persistent designation.
📊

Prevalence

1
Worldwide
Unknown Unknown
No population-based prevalence or incidence figure exists. All available numbers come from specialty-clinic case series, not registries or population data, so no rate is recorded here rather than promoting a clinic figure to a population estimate. Brief post-disembarkation unsteadiness under 48 hours is by contrast near-universal and is explicitly not this disorder.
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"Short duration symptoms lasting less than 48 hours are extremely common even among healthy young individuals"
Establishes that the common transient phenomenon is not the disorder, which is why casual prevalence figures are misleading here.
🌍

Epidemiology

2
Female predominance and adult onset
Reported cohorts are overwhelmingly female, with onset typically in the fourth to sixth decades and frequent perimenopausal timing. A sex-hormone mechanism has been proposed for vestibular disorders generally, which would fit the observed pattern, but it is a proposal rather than a demonstration for MdDS specifically. Note these are specialty-clinic series, which carry their own referral bias.
Show evidence (3 references)
PMID:23674832 SUPPORT DIRECT Human Clinical
"Both groups showed a female predominance of more than 80% and an average age of onset of the first lifetime episode of chronic rocking dizziness in the fifth decade"
Establishes both halves of this record's claim - the sex ratio and the age of onset - in one measured cohort.
PMID:32986636 SUPPORT DIRECT Other
"MdDS lasting more than 48 hours and particularly lasting more than 1 month is overwhelmingly represented by women (75–100%)"
The consensus committee's own range across sources, and it ties the female predominance specifically to the persistent form rather than to the common transient after-effect.
PMID:34864753 SUPPORT INDIRECT Other
"In females, gonadal hormones and sex-specific synaptic plasticity may play a significant role in the underlying pathophysiology of peripheral and central vestibular disorders"
Offers a candidate mechanism for the predominance the two items above establish. Graded INDIRECT because it concerns vestibular disorders as a class, not MdDS specifically, and proposes rather than demonstrates.
Migraine comorbidity
Migraine history is common in patients with rocking dizziness, at roughly 41-46% across motion-triggered and non-motion-triggered groups. This is the empirical basis for trialling vestibular-migraine prophylaxis and part of the vestibular-migraine differential; it was previously asserted in this entry without a citation.
41.0–46.0 percent of patients with a migraine history
Show evidence (1 reference)
PMID:23674832 SUPPORT DIRECT Human Clinical
"both groups had a comparable prevalence of migraine headache (41%: MT; 46%: non-MT)"
Quantifies migraine comorbidity, and notably finds it comparable between the motion-triggered and non-motion-triggered groups.
⚖️

Clinical Burden

High
A continuous, unrelenting motion illusion lasting months to years, with no confirmatory test, no approved drug, and a mechanism-directed therapy available at few centres. Occupational impact is documented and scales with exposure: symptom severity increases with flight time and with age across all measured subfactors.
Show evidence (1 reference)
PMID:40296474 SUPPORT DIRECT Human Clinical
"As flight time and age increased, the severity of the symptoms of MdDS increased for all subfactors"
Documents a dose-response between motion exposure and symptom severity in an occupationally exposed group.
🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Mal De Debarquement:

Persistent postural-perceptual dizziness (PPPD)
Overlapping Features The closest mimic and the most important distinction. Both are chronic functional vestibular disorders, but the response to motion is opposite: MdDS symptoms transiently improve on re-exposure to passive motion, whereas PPPD is aggravated by motion and by complex visual environments. The non-motion-triggered presentation of oscillatory vertigo is where the two genuinely blur.
Show evidence (1 reference)
PMID:32986636 SUPPORT DIRECT Other
"Features that distinguish MdDS from vestibular migraine, motion sickness, and persistent postural perceptual dizziness (PPPD) are reviewed."
Establishes PPPD as a formally addressed differential in the consensus criteria.
Vestibular migraine
Overlapping Features Shares the female predominance and a high rate of migraine history, and overlaps enough that some MdDS patients respond to migraine prophylaxis. Distinguished by the episodic character of vestibular migraine against the continuous percept of MdDS, and by the absence of the passive-motion trigger and nulling response.
Motion sickness and visually induced motion sickness
Overlapping Features Occur during rather than after motion exposure and resolve on its cessation, the reverse of the MdDS temporal pattern.
🐁

Animal Models

1
Roll-while-rotating conditioned rhesus monkey
Not a genetic model but a conditioning paradigm, and the experiment that generated the whole mechanistic account. Monkeys rolled side to side while rotating in darkness for several hours developed vertical and horizontal nystagmus in addition to ocular torsion, with the vertical component oscillating in phase with head roll - the same maladapted reflex signature later found in patients. Crucially the effect appeared only in animals with long VOR time constants, which is what implicates central velocity storage.
Species
Monkey
Genotype
Wild type
Publication
PMID:25076935
Pathograph links
Velocity Storage Cross-Axis Maladaptation recapitulates fidelity: moderate Reproduces the proposed lesion by applying the proposed cause, and the equivalent conditioning was subsequently produced in humans in rotating-room experiments, which bridges the species gap.
Limitations: The model reproduces the reflex maladaptation, not the disease: conditioned monkeys are not reported to develop a persistent self-motion percept, and the perceptual and limbic components of MdDS have no counterpart here. What it models is the initiating vestibular lesion alone.
Readouts
Oscillating vertical nystagmus on head roll
Direction: INCREASED
Interpretation: The oculomotor read-out of reflex maladaptation, and the same sign found on examination in patients.
Show evidence (1 reference)
PMID:25076935 SUPPORT DIRECT Model Organism
"The vertical nystagmus oscillated as they rolled from side-to-side, with upward slow phases when the animals were on one side and downward slow phases on the other side."
Reports the conditioned nystagmus measurement behind this readout.
Show evidence (1 reference)
PMID:25076935 SUPPORT INDIRECT Model Organism
"The alteration in the eye movements indicated that the vestibulo-ocular reflex (VOR) had been maladapted."
Supports treating the conditioned monkey as informative for the human lesion. INDIRECT because the human mechanism is inferred from it.
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Source YAML

click to show 
name: Mal De Debarquement
creation_date: "2026-08-29T00:00:00Z"
category: Neurological Disorder
description: >-
  Mal de débarquement syndrome (MdDS) is a chronic central vestibular disorder
  in which a persistent illusion of self-motion - described as rocking, bobbing
  or swaying - outlasts the passive motion that provoked it, classically a sea
  voyage but also air, road or rail travel. It is a disorder of the perception
  of motion rather than of the vestibular end organ: inner-ear function,
  audiometry and structural brain imaging are characteristically normal, and
  the diagnosis is made on the clinical pattern rather than on any test.

  The defining and diagnostically decisive feature is paradoxical: symptoms
  temporarily *remit* on re-exposure to passive motion, so patients feel better
  while driving and worse when the car stops. That single observation separates
  MdDS from persistent postural-perceptual dizziness, in which motion and
  visual complexity make things worse, and it is also the clue to the
  mechanism - the brain state is not a deficit but a maladaptive adaptation
  that the triggering stimulus transiently satisfies.

  The leading mechanistic account, developed from roll-while-rotating
  conditioning in monkeys and reproduced in humans in NASA rotating-room
  experiments, is that prolonged passive oscillatory motion maladapts the
  vestibulo-ocular reflex through velocity storage, the central integrator that
  extends the vestibular response beyond the cupula's own time constant.
  Formalized as a three-dimensional dynamical system, the lesion is
  cross-axis coupling - off-diagonal terms misaligning the yaw eigenvector from
  the head-vertical and gravity axes - which is experienced as a continuous
  pull or rocking. Downstream, functional imaging finds a limbic focus of
  entorhinal and amygdala hypermetabolism with increased coupling to posterior
  visual-vestibular areas and reduced frontal connectivity, and resting EEG
  frames the disorder as entrainment to oscillating motion rather than a focal
  lesion. The therapy that follows from this account - rolling the head while
  viewing a full-field rotating stimulus, to readapt the reflex in the opposite
  direction - is unusual in that it is simultaneously the treatment and the
  clearest test of the mechanism.

  MdDS falls disproportionately on women in the fourth to sixth decades, often
  around the perimenopausal transition, and carries high migraine comorbidity.
  Population prevalence is not known.
disease_term:
  preferred_term: mal de débarquement syndrome
  term:
    id: MONDO:0016217
    label: mal de Debarquement
synonyms:
- MdDS
- mal de débarquement syndrome
- disembarkment syndrome
- sickness of disembarkment
- landsickness
notes: >-
  Ontology note. The central mechanism of this entry is maladaptation of the
  vestibulo-ocular reflex, and no adequate GO term for that process exists: GO
  has no vestibulo-ocular reflex class, and GO:0060013 - which the deep-research
  report offered under that name - is `righting reflex`, a different process.
  The mechanism nodes therefore carry no GO binding rather than a
  near-miss one, and name the process in prose instead. See the wider term note
  in the PR.

  Scope note. The three temporal designations in the Bárány criteria - `in
  evolution`, `transient` and `persistent` - are observation-window
  qualifiers on one disease, not distinct entities, so they are curated as
  `progression` phases rather than as `has_subtypes`. The genuine subtype axis
  is motion-triggered versus non-motion-triggered onset, and that one is
  contested; see the discussion attached to the trigger node.
definitions:
- name: Bárány Society diagnostic criteria for MdDS
  definition_type: DIAGNOSTIC_CRITERIA
  derivation_basis: ESTABLISHED_CRITERIA
  description: >-
    The International Classification of Vestibular Disorders case definition.
    Criteria A-D must all be met and E excludes better explanations: (A)
    non-spinning vertigo of oscillatory character, continuous or most of the
    day; (B) onset within 48 hours of the end of passive motion exposure; (C)
    temporary reduction of symptoms on re-exposure to passive motion; (D)
    duration beyond 48 hours; (E) not better accounted for by another disorder.
    Criterion C is the discriminating one - it is what separates MdDS from the
    disorders it most resembles.
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "1] Non-spinning vertigo characterized by an oscillatory perception ('rocking,' 'bobbing,' or 'swaying') present continuously or for most of the day; 2] Onset occurs within 48 hours after the end of exposure to passive motion, 3] Symptoms temporarily reduce with exposure to passive motion (e.g. driving), and 4] Symptoms persist for >48 hours."
    explanation: States the four positive diagnostic criteria verbatim.
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "there are demographic and prognostic differences between the common short-term unsteadiness that happens immediately after landing and the syndrome that can last well beyond 48 hours"
    explanation: >-
      Justifies the 48-hour threshold: brief post-disembarkation unsteadiness is
      near-universal and non-pathological, so the criterion is what makes MdDS a
      disorder rather than a normal after-effect.
pathophysiology:
- name: Prolonged Passive Oscillatory Motion Exposure
  biological_scale: ORGANISM
  description: >-
    The initiating exposure: hours of passive, periodic, oscillatory motion -
    a ship, aircraft, car or train, but also a swaying building, a waterbed or
    moving exercise equipment. What matters mechanistically is the oscillatory
    or periodic character of the stimulus coupled with a minimum duration on
    the order of hours, not the mode of transport. A concurrent physical or
    psychological stressor during the exposure is commonly reported, and
    perimenstrual or perimenopausal hormonal state at the time of exposure has
    been proposed as a risk factor. Notably the triggering journey is not
    otherwise remarkable - it need not involve seasickness or illness.
  downstream:
  - target: Velocity Storage Cross-Axis Maladaptation
    description: >-
      Sustained periodic vestibular input during head movement conditions the
      central velocity-storage integrator into a maladapted configuration.
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "The key features of the triggers are an oscillatory or periodic stimulus coupled with some minimal duration of exposure, generally on the order of hours."
    explanation: Identifies the mechanically relevant properties of the trigger.
- name: Velocity Storage Cross-Axis Maladaptation
  biological_scale: ORGANISM
  description: >-
    The core lesion. Velocity storage is the central vestibular integrator that
    prolongs the response to rotation well beyond the cupula's own time
    constant; roll-while-rotating conditioning maladapts the vestibulo-ocular
    reflex through it. The dependence on velocity storage is not assumed - in
    the monkey experiments the maladaptation appeared only in animals with long
    VOR time constants and not when the time constant approached the cupula's,
    which is what implicates the central integrator rather than the periphery.
    Modelled as a three-by-three dynamical system, normal upright orientation
    gives a diagonal system matrix whose yaw eigenvector aligns with gravity;
    in MdDS off-diagonal terms appear, representing cross-axis coupling and a
    misalignment between the yaw eigenvector and the head vertical, which is
    experienced as a directional pull. No GO term is bound here because none
    describes the vestibulo-ocular reflex.
  downstream:
  - target: Persistent Oscillatory Self-Motion Perception
    description: >-
      The maladapted reflex is read centrally as continuing self-motion after
      the physical motion has stopped.
  - target: Limbic-Vestibular Network Reorganization
    description: >-
      Sustained abnormal motion signalling entrains a distributed cortical and
      limbic network.
  evidence:
  - reference: PMID:25076935
    reference_title: "Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: MODEL_ORGANISM
    snippet: "This only occurred in monkeys with long VOR time constants, and was not present when the VOR time constant was close to that of the cupula"
    explanation: >-
      The observation that localizes the lesion to central velocity storage
      rather than the periphery. Graded INDIRECT because it is conditioning in
      monkeys, from which the human mechanism is inferred.
  - reference: PMID:41122084
    reference_title: "Potential lesson from a model-based exploration on treatment effect heterogeneity of mal de débarquement syndrome."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: COMPUTATIONAL
    snippet: "A pull sensation of MdDS has been expressed with a system matrix with off-diagonal elements representing cross-axis coupling and interpreted as a misalignment between the yaw eigenvector and the head vertical."
    explanation: >-
      Formalizes the lesion as cross-axis coupling in the velocity-storage
      matrix. INDIRECT because it is a mathematical model of the mechanism, not
      a measurement of it.
- name: Persistent Oscillatory Self-Motion Perception
  biological_scale: ORGANISM
  description: >-
    The cardinal symptom and the state that defines the disease: a continuous
    non-spinning perception of rocking, bobbing or swaying, present most or all
    of the day, persisting for months or years after a motion exposure of
    hours. Its signature behaviour is that it is transiently nulled by
    re-exposure to passive motion and rebounds when that motion stops - the
    percept behaves as though the brain has adopted a model of the world in
    which the motion is still happening.
  downstream:
  - target: Functional Impairment and Secondary Affective Burden
    description: >-
      A continuous unrelenting motion illusion drives fatigue, impaired
      concentration and secondary anxiety and depression.
  evidence:
  - reference: PMID:33746890
    reference_title: "Neuroimaging Markers of Mal de Débarquement Syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Symptoms are described as a “rocking,” “bobbing,” or “swaying” perception that is nulled by exposure to passive motion such as driving/riding in a car or returning to the triggering stimulus."
    explanation: States the percept and its defining nulling behaviour.
  - reference: PMID:25076935
    reference_title: "Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Physical findings included body oscillation at 0.2 Hz, oscillating vertical nystagmus when the head was rolled from side-to-side in darkness, and unilateral rotation during the Fukuda stepping test."
    explanation: >-
      The objective correlates of the subjective percept, and the only described
      examination sign of the disorder.
- name: Limbic-Vestibular Network Reorganization
  biological_scale: TISSUE
  description: >-
    Downstream of the maladapted reflex, functional imaging shows a limbic focus
    of hypermetabolism in the left entorhinal cortex and amygdala, increased
    functional connectivity from that focus to posterior visual and vestibular
    processing areas including motion-sensitive MT/V5, and reduced connectivity
    to frontal and temporal cortices. Resting-state EEG frames the same state as
    entrainment to oscillating motion, with treatment response tracking
    inter-regional alpha-band phase coherence. This is a network-level
    dysrhythmia rather than a focal lesion, which is consistent with structural
    imaging being normal.
  evidence:
  - reference: PMID:23209584
    reference_title: "Metabolic and functional connectivity changes in mal de debarquement syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "MdDS subjects showed increased metabolism in the left entorhinal cortex and amygdala (z>3.3)."
    explanation: The primary FDG-PET finding, in 20 patients against 20 matched controls.
  - reference: PMID:33746890
    reference_title: "Neuroimaging Markers of Mal de Débarquement Syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "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"
    explanation: Synthesis of the connectivity pattern across imaging studies.
  - reference: PMID:30099627
    reference_title: "Electrophysiological Signatures of Intrinsic Functional Connectivity Related to rTMS Treatment for Mal de Debarquement Syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "a motion perceptual disorder induced by entrainment to oscillating motion"
    explanation: Frames the disorder electrophysiologically as motion entrainment.
- name: Functional Impairment and Secondary Affective Burden
  biological_scale: ORGANISM
  description: >-
    The clinical endpoint. Beyond the motion illusion itself, patients develop
    spatial disorientation, visual motion intolerance, chronic fatigue,
    impaired cognition, insomnia, and exacerbation of headache, anxiety and
    depression. Whether the affective symptoms are secondary to a relentless
    perceptual disturbance or share the limbic substrate is not resolved; the
    imaging studies covaried for mood and anxiety precisely because of that
    ambiguity.
  evidence:
  - reference: PMID:32364688
    reference_title: "[Mal de débarquement syndrome – “sickness of disembarkment”]."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Chronic fatigue, anxiety, and depression are frequently associated with primary symptoms."
    explanation: Documents the secondary symptom burden accompanying the core percept.
phenotypes:
- category: Neurological
  name: Persistent Oscillatory Vertigo
  description: >-
    Continuous non-spinning rocking, bobbing or swaying self-motion perception,
    present continuously or for most of the day. The defining symptom.
  frequency: OBLIGATE
  phenotype_term:
    preferred_term: Non-spinning oscillatory vertigo
    term:
      id: HP:4000033
      label: Non-spinning vertigo
    temporality: CHRONIC
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Non-spinning vertigo characterized by an oscillatory perception (‘rocking,’ ‘bobbing,’ or ‘swaying’) present continuously or for most of the day"
    explanation: >-
      Criterion A of the case definition, hence OBLIGATE - a patient without it
      does not have the diagnosis.
- category: Neurological
  name: Gait Imbalance
  description: Unsteadiness and body oscillation, measurable at about 0.2 Hz.
  phenotype_term:
    preferred_term: Gait imbalance
    term:
      id: HP:0002141
      label: Gait imbalance
  evidence:
  - reference: PMID:25076935
    reference_title: "Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Physical findings included body oscillation at 0.2 Hz"
    explanation: Quantifies the postural oscillation accompanying the percept.
- category: Neurological
  name: Head-Roll Induced Nystagmus
  description: >-
    Oscillating vertical nystagmus elicited by side-to-side head roll in
    darkness - the one described objective examination sign, and the direct
    read-out of the maladapted reflex.
  phenotype_term:
    preferred_term: Nystagmus
    term:
      id: HP:0000639
      label: Nystagmus
  evidence:
  - reference: PMID:25076935
    reference_title: "Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "oscillating vertical nystagmus when the head was rolled from side-to-side in darkness"
    explanation: Documents the examination sign linking the symptom to the reflex lesion.
- category: Constitutional
  name: Chronic Fatigue
  description: Persistent fatigue, one of the most burdensome accompanying symptoms.
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
    temporality: CHRONIC
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety."
    explanation: Lists fatigue among the recognized co-existing symptoms.
- category: Neurological
  name: Visual Motion Intolerance
  description: >-
    Intolerance of complex or moving visual environments. Named in the consensus
    criteria as a co-existing symptom and previously present in this entry only
    as prose in a pathophysiology description.
  phenotype_term:
    preferred_term: Visual motion intolerance
    term:
      id: HP:0001751
      label: Abnormal vestibular function
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety."
    explanation: >-
      Names visual motion intolerance as a co-existing symptom. Bound to the
      general vestibular-function term because HPO has no specific class for
      visual motion intolerance.
- category: Neurological
  name: Spatial Disorientation
  description: Impaired sense of spatial orientation accompanying the motion illusion.
  phenotype_term:
    preferred_term: Spatial disorientation
    term:
      id: HP:0001751
      label: Abnormal vestibular function
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety."
    explanation: Names spatial disorientation as a co-existing symptom.
- category: Neurological
  name: Impaired Cognition
  description: >-
    Impaired concentration and cognitive slowing, reported by patients as "brain
    fog" and among the more disabling accompanying features.
  phenotype_term:
    preferred_term: Impaired cognition
    term:
      id: HP:0100543
      label: Cognitive impairment
  evidence:
  - reference: PMID:25076935
    reference_title: "Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "it is associated with many other disturbing symptoms, including disorientation, impaired cognition, fatigue, ataxia, insomnia, headache, anxiety, and depression"
    explanation: Names impaired cognition among the accompanying symptom burden.
- category: Psychiatric
  name: Depression
  description: Depressed mood accompanying the chronic perceptual disturbance.
  phenotype_term:
    preferred_term: Depression
    term:
      id: HP:0000716
      label: Depression
  evidence:
  - reference: PMID:32364688
    reference_title: "[Mal de débarquement syndrome – “sickness of disembarkment”]."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Chronic fatigue, anxiety, and depression are frequently associated with primary symptoms."
    explanation: Documents depression as a frequent accompanying feature.
- category: Psychiatric
  name: Anxiety
  description: >-
    Anxiety, frequently accompanying the primary symptoms. Curated as an
    associated feature rather than a cause; imaging studies treat mood and
    anxiety as covariates for this reason.
  phenotype_term:
    preferred_term: Anxiety
    term:
      id: HP:0000739
      label: Anxiety
  evidence:
  - reference: PMID:32364688
    reference_title: "[Mal de débarquement syndrome – “sickness of disembarkment”]."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Chronic fatigue, anxiety, and depression are frequently associated with primary symptoms."
    explanation: Documents anxiety as a frequent accompanying feature.
- category: Neurological
  name: Headache Exacerbation
  description: >-
    Worsening of pre-existing headache, notable given the high migraine
    comorbidity and the responsiveness of some patients to migraine prophylaxis.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety."
    explanation: Names exacerbation of headache among the co-existing symptoms.
environmental:
- name: Prolonged exposure to passive oscillatory motion (sea, air, road or rail travel)
  exposure_term:
    preferred_term: exposure to passive oscillatory motion during travel
    term:
      id: ECTO:6000033
      label: exposure to travel
  notes: >-
    ECTO:6000033 `exposure to travel` is the closest available term and is
    deliberately imperfect: the mechanically relevant property is passive
    oscillatory motion of some hours' duration, not travel as such, and the
    same trigger is reported from swaying buildings, waterbeds and moving
    exercise equipment, which are not travel at all. Bound rather than left
    free-text because the overwhelming majority of triggers are journeys, with
    the mismatch recorded here rather than hidden.
  influences_mechanisms:
  - target: Velocity Storage Cross-Axis Maladaptation
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      The exposure is the conditioning stimulus itself: periodic vestibular
      input sustained across head movements is what maladapts the reflex.
    evidence:
    - reference: PMID:32986636
      reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
      supports: SUPPORT
      directness: DIRECT
      evidence_source: OTHER
      snippet: "Onset occurs within 48 hours after the end of exposure to passive motion"
      explanation: >-
        The tight temporal coupling between exposure and onset is what makes
        this a trigger rather than an association.
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Typical triggers include transportation vessels such as boats, airplanes, automobiles, and trains but can also include swaying buildings, waterbeds, exercise equipment and other platforms that passively move the individual"
    explanation: Enumerates the reported trigger exposures, including the non-travel ones.
progression:
- phase: MdDS in evolution
  notes: >-
    Symptoms ongoing but the observation period is under one month, so the
    course cannot yet be assigned. A staging designation, not a distinct
    disease.
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "MdDS in evolution: symptoms are ongoing but the observation period has been less than 1 month"
    explanation: Defines the provisional staging category.
- phase: Transient MdDS
  notes: >-
    Symptoms resolve at or before one month. Diagnosable only in retrospect,
    since it is defined by remission having occurred.
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Transient MdDS: symptoms resolve at or before 1 month and the observation period extends at least to the resolution point"
    explanation: Defines the remitting course.
- phase: Persistent MdDS
  notes: >-
    Symptoms beyond one month. This is the clinically burdensome form; reported
    cohorts have median durations of many months to years.
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Persistent MdDS: symptoms last for more than 1 month"
    explanation: Defines the persistent course.
  - reference: PMID:23209584
    reference_title: "Metabolic and functional connectivity changes in mal de debarquement syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Twenty subjects with MdDS lasting a median duration of 17.5 months"
    explanation: Illustrates the typical duration in a persistent-MdDS research cohort.
  - reference: PMID:27730651
    reference_title: "Management of mal de debarquement syndrome as vestibular migraines."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "symptoms that persist beyond 6 months have been described as unlikely to remit"
    explanation: >-
      Records the prognostic threshold beyond which spontaneous remission is
      described as unlikely - the practical significance of the persistent
      designation.
epidemiology:
- name: Female predominance and adult onset
  description: >-
    Reported cohorts are overwhelmingly female, with onset typically in the
    fourth to sixth decades and frequent perimenopausal timing. A sex-hormone
    mechanism has been proposed for vestibular disorders generally, which would
    fit the observed pattern, but it is a proposal rather than a demonstration
    for MdDS specifically. Note these are specialty-clinic series, which carry
    their own referral bias.
  evidence:
  - reference: PMID:23674832
    reference_title: "Rocking dizziness and headache: a two-way street."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Both groups showed a female predominance of more than 80% and an average age of onset of the first lifetime episode of chronic rocking dizziness in the fifth decade"
    explanation: >-
      Establishes both halves of this record's claim - the sex ratio and the age
      of onset - in one measured cohort.
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "MdDS lasting more than 48 hours and particularly lasting more than 1 month is overwhelmingly represented by women (75–100%)"
    explanation: >-
      The consensus committee's own range across sources, and it ties the female
      predominance specifically to the persistent form rather than to the common
      transient after-effect.
  - reference: PMID:34864753
    reference_title: "Influence of sex hormones on vestibular disorders."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: OTHER
    snippet: "In females, gonadal hormones and sex-specific synaptic plasticity may play a significant role in the underlying pathophysiology of peripheral and central vestibular disorders"
    explanation: >-
      Offers a candidate mechanism for the predominance the two items above
      establish. Graded INDIRECT because it concerns vestibular disorders as a
      class, not MdDS specifically, and proposes rather than demonstrates.
- name: Migraine comorbidity
  description: >-
    Migraine history is common in patients with rocking dizziness, at roughly
    41-46% across motion-triggered and non-motion-triggered groups. This is the
    empirical basis for trialling vestibular-migraine prophylaxis and part of
    the vestibular-migraine differential; it was previously asserted in this
    entry without a citation.
  minimum_value: 41.0
  maximum_value: 46.0
  unit: percent of patients with a migraine history
  evidence:
  - reference: PMID:23674832
    reference_title: "Rocking dizziness and headache: a two-way street."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "both groups had a comparable prevalence of migraine headache (41%: MT; 46%: non-MT)"
    explanation: >-
      Quantifies migraine comorbidity, and notably finds it comparable between
      the motion-triggered and non-motion-triggered groups.
diagnosis:
- name: Clinical diagnosis with normal vestibular and structural testing
  description: >-
    There is no confirmatory test. Vestibular function testing, audiometry and
    structural brain imaging are characteristically normal, and their normality
    is part of the diagnostic picture rather than a failure to find the lesion -
    the disorder is one of central motion perception, not of the end organ. The
    imaging abnormalities that do exist are group-level research findings, not
    clinical assays.
  evidence:
  - reference: PMID:32364688
    reference_title: "[Mal de débarquement syndrome – “sickness of disembarkment”]."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "We found normal inner-ear function, non-related abnormalities and normal brain imaging"
    explanation: Documents the expected normal work-up in a clinical case series.
differential_diagnoses:
- name: Persistent postural-perceptual dizziness (PPPD)
  description: >-
    The closest mimic and the most important distinction. Both are chronic
    functional vestibular disorders, but the response to motion is opposite:
    MdDS symptoms transiently improve on re-exposure to passive motion, whereas
    PPPD is aggravated by motion and by complex visual environments. The
    non-motion-triggered presentation of oscillatory vertigo is where the two
    genuinely blur.
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Features that distinguish MdDS from vestibular migraine, motion sickness, and persistent postural perceptual dizziness (PPPD) are reviewed."
    explanation: Establishes PPPD as a formally addressed differential in the consensus criteria.
- name: Vestibular migraine
  description: >-
    Shares the female predominance and a high rate of migraine history, and
    overlaps enough that some MdDS patients respond to migraine prophylaxis.
    Distinguished by the episodic character of vestibular migraine against the
    continuous percept of MdDS, and by the absence of the passive-motion
    trigger and nulling response.
- name: Motion sickness and visually induced motion sickness
  description: >-
    Occur during rather than after motion exposure and resolve on its cessation,
    the reverse of the MdDS temporal pattern.
treatments:
- name: Vestibulo-Ocular Reflex Readaptation (Optokinetic Roll Protocol)
  description: >-
    The one disease-specific therapy, and the clearest test of the mechanism:
    the patient rolls the head side to side while viewing a rotating full-field
    visual stimulus, driving reflex adaptation in the direction opposite to the
    maladapted components. In the original series 17 of 24 patients had complete
    or substantial recovery sustained about a year, six relapsed after initial
    benefit and one did not respond. Its rationale is not empirical - it was
    predicted from the velocity-storage account and then tested, so its success
    is itself evidence for the mechanism.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: Rehabilitation
    term:
      id: NCIT:C15315
      label: Rehabilitation
  target_mechanisms:
  - target: Velocity Storage Cross-Axis Maladaptation
    description: >-
      Acts directly on the proposed lesion by readapting the reflex, rather than
      on symptoms downstream of it.
  evidence:
  - reference: PMID:25076935
    reference_title: "Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Seventeen of the 24 subjects had a complete or substantial recovery on average for approximately 1 year."
    explanation: The primary efficacy result, in an uncontrolled series of 24 patients.
  - reference: PMID:25076935
    reference_title: "Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "We conclude that the adaptive processes associated with roll-while-rotating are responsible for producing MdDS"
    explanation: >-
      The authors' inference from treatment response back to mechanism. Graded
      INDIRECT because it reasons from a therapeutic result to the mechanism
      that therapy targets.
  - reference: PMID:30410464
    reference_title: "Sham-Controlled Study of Optokinetic Stimuli as Treatment for Mal de Debarquement Syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "No placebo effect was recorded with any changes in postural data and VAS scale."
    explanation: >-
      A sham exposure produced no change. This matters more than the response
      rate for the entry's argument: if treatment response is offered as
      evidence for the mechanism, the absence of a placebo effect is what stops
      that argument resting on expectation alone.
- name: Repetitive Transcranial Magnetic Stimulation over Left DLPFC
  description: >-
    10 Hz rTMS over the left dorsolateral prefrontal cortex, targeting the
    cortico-limbic node implicated by imaging rather than the vestibular lesion.
    A small double-blind sham-controlled crossover trial in eight women reported
    improvement in dizziness and in mood and anxiety persisting beyond the
    treatment period. Evidence is limited and the effect sizes modest: a scoping
    review of TMS across chronic vestibular disorders found statistically
    significant improvement on the Dizziness Handicap Inventory in a minority of
    studies (3 of 7) and no clinically significant improvement at all, with the
    authors cautioning that methodological limitations bear on how the results
    are read.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: Transcranial Magnetic Stimulation
    term:
      id: NCIT:C116655
      label: Transcranial Magnetic Stimulation
  target_mechanisms:
  - target: Limbic-Vestibular Network Reorganization
    description: >-
      Targets the prefrontal node of the reorganized network rather than the
      upstream velocity-storage lesion.
  evidence:
  - reference: PMID:27176615
    reference_title: "Double-Blind Sham-Controlled Crossover Trial of Repetitive Transcranial Magnetic Stimulation for Mal de Debarquement Syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our study provides evidence that the dizziness, mood and anxiety symptoms of MdDS can be improved with 10 Hz rTMS over left DLPFC beyond the treatment period in selected individuals"
    explanation: >-
      The controlled trial result. Note the authors' own qualifier, "in selected
      individuals" - this is eight patients, not a general indication.
  - reference: PMID:40228811
    reference_title: "Transcranial magnetic stimulation use with chronic vestibular disorders: A scoping review."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Statistically significant improvements were noted on the Dizziness Handicap Inventory (3/7 studies) but clinically significant improvements were not observed."
    explanation: >-
      Bounds the claim rather than supporting it straightforwardly. Across chronic
      vestibular disorders as a class, TMS reached statistical significance on the
      Dizziness Handicap Inventory in a minority of studies and clinical
      significance in none, which is why this treatment is recorded as limited
      rather than established. Graded INDIRECT because the review covers chronic
      vestibular disorders generally rather than this disease specifically.
- name: Intermittent Theta Burst Stimulation as an Adjunct to VOR Rehabilitation
  description: >-
    Tested as a way to augment the readaptation protocol. It did not work: in a
    randomised sham-controlled trial of 20 patients both arms improved and there
    was no between-group difference, so the benefit was attributable to the
    rehabilitation and not to the stimulation. Recorded because a negative
    controlled result is more informative here than the positive uncontrolled
    ones, and because it bounds what neuromodulation adds.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: Transcranial Magnetic Stimulation
    term:
      id: NCIT:C116655
      label: Transcranial Magnetic Stimulation
  evidence:
  - reference: PMID:38345630
    reference_title: "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."
    supports: REFUTE
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Significant improvements in subjective and objective outcomes were reported across both treatment groups over time, but no between-group differences were observed."
    explanation: >-
      Refutes an additive benefit of iTBS over VOR rehabilitation alone. The
      shared improvement in both arms simultaneously supports the rehabilitation
      protocol.
- name: Transcranial Direct Current Stimulation over DLPFC
  description: >-
    Anodal left / cathodal right DLPFC tDCS, delivered at home following rTMS in
    a randomised single-blind sham-controlled study of 23 patients. Those
    receiving real tDCS improved on the MdDS Balance Rating Scale and on anxiety
    by week 4. Included because it is the neuromodulation arm with a positive
    controlled result, alongside the iTBS trial that was negative.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: Transcranial Direct Current Stimulation
    term:
      id: NCIT:C129862
      label: Transcranial Direct Current Stimulation
  target_mechanisms:
  - target: Limbic-Vestibular Network Reorganization
    description: >-
      Targets the same prefrontal node as rTMS rather than the upstream
      velocity-storage lesion.
  evidence:
  - reference: PMID:27117283
    reference_title: "Randomized Single Blind Sham Controlled Trial of Adjunctive Home-Based tDCS after rTMS for Mal De Debarquement Syndrome: Safety, Efficacy, and Participant Satisfaction Assessment."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Those who received real tDCS after rTMS showed significant improvements in the degree of rocking perception as measured by the MdDS Balance Rating Scale and anxiety ratings by Week 4"
    explanation: The controlled efficacy result for adjunctive tDCS.
- name: Vestibular Migraine Prophylaxis
  description: >-
    Given the high migraine comorbidity, an institutional vestibular-migraine
    protocol - lifestyle modification plus verapamil, nortriptyline,
    topiramate or a combination - benefited 11 of 15 patients in one series.
    Symptomatic rather than mechanism-directed, and it presupposes the migraine
    phenotype. There is no drug approved specifically for MdDS.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:27730651
    reference_title: "Management of mal de debarquement syndrome as vestibular migraines."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Eleven patients (73%) responded well to management with a vestibular migraine protocol, which included lifestyle changes, as well as pharmacotherapy with verapamil, nortriptyline, topiramate, or a combination thereof"
    explanation: The response rate to migraine prophylaxis in a 15-patient series.
animal_models:
- name: Roll-while-rotating conditioned rhesus monkey
  species: Monkey
  genotype: Wild type
  description: >-
    Not a genetic model but a conditioning paradigm, and the experiment that
    generated the whole mechanistic account. Monkeys rolled side to side while
    rotating in darkness for several hours developed vertical and horizontal
    nystagmus in addition to ocular torsion, with the vertical component
    oscillating in phase with head roll - the same maladapted reflex signature
    later found in patients. Crucially the effect appeared only in animals with
    long VOR time constants, which is what implicates central velocity storage.
  publication: PMID:25076935
  modeled_mechanisms:
  - target: Velocity Storage Cross-Axis Maladaptation
    relationship: RECAPITULATES
    fidelity: MODERATE
    description: >-
      Reproduces the proposed lesion by applying the proposed cause, and the
      equivalent conditioning was subsequently produced in humans in rotating-room
      experiments, which bridges the species gap.
    limitations: >-
      The model reproduces the reflex maladaptation, not the disease: conditioned
      monkeys are not reported to develop a persistent self-motion percept, and
      the perceptual and limbic components of MdDS have no counterpart here.
      What it models is the initiating vestibular lesion alone.
    readouts:
    - name: Oscillating vertical nystagmus on head roll
      target: Velocity Storage Cross-Axis Maladaptation
      direction: INCREASED
      interpretation: >-
        The oculomotor read-out of reflex maladaptation, and the same sign found
        on examination in patients.
      evidence:
      - reference: PMID:25076935
        reference_title: "Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome."
        supports: SUPPORT
        directness: DIRECT
        evidence_source: MODEL_ORGANISM
        snippet: "The vertical nystagmus oscillated as they rolled from side-to-side, with upward slow phases when the animals were on one side and downward slow phases on the other side."
        explanation: Reports the conditioned nystagmus measurement behind this readout.
    evidence:
    - reference: PMID:25076935
      reference_title: "Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome."
      supports: SUPPORT
      directness: INDIRECT
      evidence_source: MODEL_ORGANISM
      snippet: "The alteration in the eye movements indicated that the vestibulo-ocular reflex (VOR) had been maladapted."
      explanation: >-
        Supports treating the conditioned monkey as informative for the human
        lesion. INDIRECT because the human mechanism is inferred from it.
clinical_burden:
  burden_level: HIGH
  rationale: >-
    A continuous, unrelenting motion illusion lasting months to years, with no
    confirmatory test, no approved drug, and a mechanism-directed therapy
    available at few centres. Occupational impact is documented and scales with
    exposure: symptom severity increases with flight time and with age across
    all measured subfactors.
  evidence:
  - reference: PMID:40296474
    reference_title: "Investigation of Mal de Debarquement Syndrome in Pilots Based on Flight Time."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "As flight time and age increased, the severity of the symptoms of MdDS increased for all subfactors"
    explanation: >-
      Documents a dose-response between motion exposure and symptom severity in
      an occupationally exposed group.
prevalence:
- population: Worldwide
  measure_type: UNKNOWN
  prevalence_class: UNKNOWN
  notes: >-
    No population-based prevalence or incidence figure exists. All available
    numbers come from specialty-clinic case series, not registries or
    population data, so no rate is recorded here rather than promoting a clinic
    figure to a population estimate. Brief post-disembarkation unsteadiness
    under 48 hours is by contrast near-universal and is explicitly not this
    disorder.
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Short duration symptoms lasting less than 48 hours are extremely common even among healthy young individuals"
    explanation: >-
      Establishes that the common transient phenomenon is not the disorder,
      which is why casual prevalence figures are misleading here.
discussions:
- discussion_id: mdds_non_motion_triggered_variant
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Prolonged Passive Oscillatory Motion Exposure
  - differential_diagnoses#Persistent postural-perceptual dizziness (PPPD)
  prompt: >-
    Is motion-moderated oscillatory vertigo without a motion trigger the same
    disease as motion-triggered MdDS, a variant of PPPD, or a third entity?
  rationale: >-
    The consensus criteria require onset within 48 hours of passive motion, yet
    the same committee records an otherwise indistinguishable presentation
    arising with no motion trigger - typically after another vestibular
    disorder, a medical illness, psychological stress or metabolic disturbance -
    and states that its terminology has varied because it has features of both
    MdDS and PPPD. This is not a naming quibble: the entire mechanistic account
    in this entry begins with an oscillatory conditioning stimulus, so a
    presentation without one either reaches the same velocity-storage state by
    another route or is a different disease wearing the same symptoms. The
    entry curates the motion-triggered form, which is what the criteria define,
    and does not silently extend its mechanism to the non-triggered
    presentation. Resolving this needs the phenomenological and mechanistic
    comparison the committee itself calls for.
  evidence:
  - reference: PMID:32986636
    reference_title: "Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: OTHER
    snippet: "Terminology for this non-motion triggered presentation has been varied as it has features of both MdDS and PPPD."
    explanation: >-
      The consensus committee's own statement that the boundary is unresolved
      and needs further research.
  - reference: PMID:30410464
    reference_title: "Sham-Controlled Study of Optokinetic Stimuli as Treatment for Mal de Debarquement Syndrome."
    supports: SUPPORT
    directness: DIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "The Motion-Triggered group responded better to treatment than the Spontaneous group."
    explanation: >-
      A differential response to a mechanism-directed therapy is the first
      concrete discriminator between the two presentations, and bears directly
      on this question: if the readaptation protocol works less well without a
      motion trigger, that is evidence the two do not share the same lesion.
📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (2)

Record notes

Ontology note. The central mechanism of this entry is maladaptation of the vestibulo-ocular reflex, and no adequate GO term for that process exists: GO has no vestibulo-ocular reflex class, and GO:0060013 - which the deep-research report offered under that name - is `righting reflex`, a different process. The mechanism nodes therefore carry no GO binding rather than a near-miss one, and name the process in prose instead. See the wider term note in the PR. Scope note. The three temporal designations in the Bárány criteria - `in evolution`, `transient` and `persistent` - are observation-window qualifiers on one disease, not distinct entities, so they are curated as `progression` phases rather than as `has_subtypes`. The genuine subtype axis is motion-triggered versus non-motion-triggered onset, and that one is contested; see the discussion attached to the trigger node.

Create: Mal De Debarquement · 2026-08-29T15:56:14Z · View source

De-novo curation of mal de Debarquement syndrome, MONDO:0016217, as a Disease. Deep research: OpenScientist, research/Mal_De_Debarquement-deep-research-openscientist.md, 21 citations, 798s, 22/22 references verified with 0 percent confabulation. Mechanism curated as a five-node chain: prolonged passive oscillatory motion exposure, velocity storage cross-axis maladaptation, persistent oscillatory self-motion perception, limbic-vestibular network reorganization, and functional impairment. The Barany Society consensus criteria are curated as a definitions block with derivation_basis ESTABLISHED_CRITERIA, and the three temporal designations are curated as progression phases rather than has_subtypes because they are observation-window qualifiers on one disease. The non-motion-triggered presentation is recorded as an open KNOWLEDGE_GAP rather than folded into the entry, since the entry's mechanism starts from an oscillatory conditioning stimulus that such cases lack. Uses the post-issue-7439 evidence model throughout: supports carries direction only and directness is set separately, with INDIRECT on the monkey conditioning data, the computational velocity-storage model, and the inference from treatment response back to mechanism. One REFUTE item records that iTBS added no benefit over VOR rehabilitation in a randomised trial. No GO term is bound for the vestibulo-ocular reflex: the research report offered GO:0060013 under that name, the report's own term_validation block flagged the label mismatch, and OLS confirms GO:0060013 is righting reflex, so the nodes name the process in prose instead. ECTO:6000033 exposure to travel is bound for the trigger with its imprecision recorded in notes. Validated with just validate-disorders, 32/32 snippets verified, validate-terms, check-entity-refs, check-duplicate-keys, all five snippet gates, a 10-pair reference-title cross-check against the cache, and 15509 structural and conformance tests.

OpenScientist ▸
Mal de Débarquement Syndrome (MdDS): A Comprehensive Disease Characteristics Report
openscientist-autonomous 21 citations 2026-08-29T15:22:48.402018

Mal de Débarquement Syndrome (MdDS): A Comprehensive Disease Characteristics Report

Disease Name: Mal de Débarquement Syndrome (MdDS) Category: Acquired MONDO: "mal de debarquement" (acquired disease term exists in Mondo); MeSH: "Mal de Debarquement" (introduced 2018); ICD-11: foundation term under vestibular/balance disorders; ICD-10: no dedicated code (coded under H81 / R42 "Dizziness and giddiness"); OMIM: none (non-Mendelian); Orphanet: listed among rare vestibular disorders.

Summary

Mal de Débarquement Syndrome (MdDS) is a rare, acquired chronic central/functional vestibular disorder defined by a persistent, non-spinning oscillatory perception of self-motion — described by patients as rocking, bobbing, or swaying — that is present continuously or for most of the day. The hallmark that distinguishes it from other chronic dizziness syndromes is its temporal relationship to passive motion: symptoms begin within 48 hours of ceasing prolonged passive motion (classically a sea cruise, but also air and road travel) and are paradoxically relieved by re-exposure to passive motion (e.g., driving). A non-motion-triggered ("spontaneous") variant also exists, overlapping clinically with persistent postural-perceptual dizziness (PPPD). These features are codified in the 2020 Bárány Society Classification Committee consensus criteria (PMID: 32986636).

Mechanistically, converging evidence supports a model of maladaptive neuroplasticity rather than any structural inner-ear lesion or gene defect. The leading physiological account holds that MdDS results from maladaptation of the vestibulo-ocular reflex (VOR) and the central velocity-storage mechanism to roll of the head during rotation — an inappropriate conditioning of a cross-axis coupling within a dynamical velocity-storage system (PMID: 25076935; PMID: 41122084). Neuroimaging shows a self-sustaining cortico-limbic network signature: hypermetabolism of the left entorhinal cortex and amygdala with altered functional connectivity to posterior sensory-processing and frontal/temporal regions (PMID: 23209584; PMID: 33746890), and high-density EEG frames the condition as a brain state of entrainment to oscillating motion (PMID: 30099627).

MdDS predominates in midlife women (~3:1 to >4:1 female), is highly comorbid with migraine, is diagnosed clinically by exclusion (normal vestibular test battery and structural MRI), and is not life-threatening — but it is frequently chronic and disabling. The most disease-specific therapy is VOR readaptation / optokinetic stimulation (~70% substantial improvement in the original series), supplemented by neuromodulation (rTMS/tDCS over the dorsolateral prefrontal cortex) and migraine-prophylaxis pharmacotherapy. There is no FDA-approved drug, no causal gene, no animal disease model, and no established primary prevention. This report synthesizes 16 confirmed findings across 30 reviewed papers into a complete disease-characteristics entry.

Key Findings

1. Definition and Diagnostic Criteria (F001)

MdDS is a chronic vestibular disorder of persistent oscillatory self-motion. The Bárány Society Classification Committee consensus (PMID: 32986636) provides the authoritative case definition. The criteria specify: "1] Non-spinning vertigo characterized by an oscillatory perception ('rocking,' 'bobbing,' or 'swaying') present continuously or for most of the day; 2] Onset occurs within 48 hours after the end of exposure to passive motion, 3] Symptoms temporarily reduce with exposure to passive motion (e.g. driving), and 4] Symptoms persist for >48 hours."

Temporal qualifiers structure the diagnosis: "in evolution" (<1 month of observation), "transient" (resolves within ≤1 month), and "persistent" (>1 month). A non-motion-triggered variant is recognized, which follows another vestibular disorder, medical illness, psychological stress, or metabolic disturbance and overlaps clinically with PPPD. MdDS is classified within the International Classification of Vestibular Disorders (ICVD) as a chronic functional/central vestibular disorder.

2. Pathophysiology — VOR / Velocity-Storage Maladaptation (F002)

The mechanistic cornerstone is the proposal by Dai, Cohen and colleagues that MdDS arises from maladaptation of the VOR to roll of the head during rotation, derived from both monkey and human data: "Results in monkeys and humans suggested that MdDS was caused by maladaptation of the vestibulo-ocular reflex (VOR) to roll of the head during rotation" (PMID: 25076935). In a cohort of 24 subjects, physical findings included body oscillation at ~0.2 Hz, oscillating vertical nystagmus on side-to-side head roll in darkness, and unilateral rotation on the Fukuda stepping test.

More recent computational modelling formalizes the central velocity-storage mechanism as a 3×3 dynamical system: "A central vestibular neural mechanism known as velocity storage may be inappropriately conditioned in mal de débarquement syndrome (MdDS)" (PMID: 41122084). In this framework, maladapted off-diagonal (cross-axis coupling) elements — a misalignment between the yaw eigenvector and the head-vertical/gravity axis — produce the persistent "pull" / rocking sensation. This is elaborated as "improperly sustained neuroplasticity in the velocity storage mechanism of the central vestibular system" (PMID: 42440785).

3. Neuroimaging — Limbic Hypermetabolism and Altered Connectivity (F003)

Cha et al. studied 20 MdDS subjects (median duration 17.5 months) versus 20 controls using FDG-PET and resting-state fMRI, reporting: "MdDS subjects showed increased metabolism in the left entorhinal cortex and amygdala (z>3.3)" (PMID: 23209584). The same study found relative hypometabolism in the left superior medial/middle frontal gyri, right amygdala, right insula, and temporal gyri, alongside increased connectivity between the entorhinal/amygdala cluster and posterior visual/vestibular processing areas.

A dedicated review synthesizes these imaging findings (PMID: 33746890): "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." Voxel-based morphometry additionally shows decreasing anterior cingulate volume and increasing inferior frontal gyri / anterior insula volume with longer illness duration.

4. Mechanism as an Oscillatory-Entrainment Brain State (F014)

High-density resting-state EEG frames MdDS as "a motion perceptual disorder induced by entrainment to oscillating motion" (PMID: 30099627). In 20 women (mean age 52.9 ± 12.6 y; illness duration 35.2 ± 24.2 mo), rTMS-induced symptom improvement correlated with increased long-range low-alpha (8–10 Hz) inter-regional phase coherence and decreased coherence in other bands, mostly between frontal and parietal regions. High baseline high-alpha/beta coherence predicted treatment response. This electrophysiological signature complements the FDG-PET/fMRI evidence and positions the disorder as a network-level dysrhythmia rather than a focal lesion.

5. Treatment — VOR Readaptation and Optokinetic Stimulation (F004)

The most disease-specific therapy directly targets the proposed velocity-storage maladaptation. Dai et al. treated 24 MdDS subjects by rolling the head side-to-side while viewing a rotating full-field visual stimulus: "Seventeen of the 24 subjects had a complete or substantial recovery on average for approximately 1 year" — approximately 70% response (PMID: 25076935); 6 relapsed and 1 was a non-responder. The authors summarize that "readaptation of the VOR has led to a cure or substantial improvement in 70% of the subjects with MdDS."

The approach has been extended to sham-controlled optokinetic stimulation trials (PMID: 30410464) and translated to audiology-vestibular clinic settings. A case report of a 48-year-old woman treated with the "Roll Readaptation" technique — full-field omnidirectional optokinetic stimulus during rhythmic head roll, three short sessions — produced significant symptom reduction and return to full-time work after nearly 3 months off (PMID: 36323329).

6. Neuromodulation — rTMS, tDCS, iTBS over DLPFC (F010)

Controlled-trial evidence supports neuromodulation as an adjunctive therapy targeting the cortico-limbic network node:

Study Design N Intervention Key result
Cha et al. (PMID: 27176615) Double-blind sham-controlled crossover 8 women 5 days 10 Hz rTMS, left DLPFC Improved DHI at post-weeks 1,3,4 (p<0.05); improved HADS anxiety/depression; no change with sham
Cha et al. (PMID: 27117283) Single-blind sham RCT, home tDCS after rTMS 23 tDCS anode L / cathode R DLPFC Improved MdDS Balance Rating Scale and anxiety by week 4; safe (0 skin burns / 556 sessions)
Browne et al. (PMID: 38345630) RCT, iTBS + VOR rehab vs sham 20 iTBS adjunct to VOR rehabilitation Both groups improved; no between-group difference — iTBS added no benefit over VOR rehab alone
Scoping review (PMID: 40228811) Review, 7 studies — TMS for chronic vestibular disorders Statistically significant DHI improvement in 3/7; postural control improved in 7/7

Cha et al. concluded: "Our study provides evidence that the dizziness, mood and anxiety symptoms of MdDS can be improved with 10 Hz rTMS over left DLPFC beyond the treatment period in selected individuals" (PMID: 27176615). However, the scoping review found: "Statistically significant improvements were noted on the Dizziness Handicap Inventory (3/7 studies) but clinically significant improvements were not observed" (PMID: 40228811). rTMS response also has a connectivity correlate: improvement correlated with reduced connectivity between left entorhinal cortex and posterior default-mode nodes, and higher baseline DLPFC–entorhinal connectivity predicted response (PMID: 28967282).

7. Treatment — Vestibular-Migraine Prophylaxis (F009)

Given the high migraine comorbidity, migraine-prophylactic pharmacotherapy benefits many patients. Ghavami et al. treated 15 MdDS patients (73% female, mean age 50 ± 13 y) with an institutional vestibular-migraine protocol: "Eleven patients (73%) responded well to management with a vestibular migraine protocol, which included lifestyle changes, as well as pharmacotherapy with verapamil, nortriptyline, topiramate, or a combination thereof" (PMID: 27730651). Nearly all had a personal or family migraine history, and the response rate exceeded that of a retrospective vestibular-rehabilitation control group. Chronic-dizziness management additionally emphasizes serotonergic antidepressants that "modulate sensory gating and reduce anxiety," vestibular rehabilitation, CBT, and trigger avoidance (PMID: 34351113). Benzodiazepines (e.g., clonazepam) are used symptomatically. There is no FDA-approved drug specifically for MdDS.

8. Epidemiology and Demographics (F005, F015)

MdDS shows a strong female predominance (21/24 female in the Dai cohort; 73% female in Ghavami's series) with typical adult onset in the 4th–6th decades (mean ages across cohorts: 44.5 ± 7.0, 50 ± 13, 52.9 ± 12.6 years). A sex-hormone review notes: "In females, gonadal hormones and sex-specific synaptic plasticity may play a significant role in the underlying pathophysiology of peripheral and central vestibular disorders" (PMID: 34864753), consistent with frequent perimenopausal onset.

Migraine comorbidity is high: in a study of rocking dizziness, "both groups had a comparable prevalence of migraine headache (41%: MT; 46%: non-MT)" (PMID: 23674832). True population prevalence and incidence are unknown — MdDS is considered rare and under-recognized, with no registry-based figures. Information derives from disease-level case series and specialty-clinic cohorts rather than population EHR data. No specific ethnic or geographic clustering is established.

Synonyms/nomenclature: Mal de débarquement syndrome; "sickness of disembarkment / disembarkment syndrome"; "debarkment syndrome"; MdDS; historically "landsickness."

9. Diagnosis by Exclusion (F006)

MdDS is diagnosed clinically per Bárány criteria; no confirmatory laboratory test or biomarker exists. Standard vestibular function testing (VNG/ENG, caloric, rotary chair, VEMP), audiometry, and structural brain MRI are characteristically normal: "We found normal inner-ear function, non-related abnormalities and normal brain imaging" (PMID: 32364688). FDG-PET limbic hypermetabolism and resting-state fMRI/EEG connectivity changes are research-only biomarkers. The one described diagnostic physical sign is oscillating vertical nystagmus on head roll in darkness (PMID: 25076935).

Key differential diagnoses include "persistent postural perceptual dizziness, mal de débarquement syndrome, motion sickness and visually induced motion sickness, bilateral vestibulopathy" (PMID: 34351113), plus vestibular migraine, BPPV, and Ménière's disease. The distinguishing feature is transient relief with re-exposure to passive motion.

10. Natural History and Prognosis (F007)

MdDS symptoms characteristically persist for months to years (median 17.5 months in the imaging cohort; 19.1 ± 33 months in the treatment cohort). Ghavami et al. note a key prognostic threshold: "symptoms that persist beyond 6 months have been described as unlikely to remit" (PMID: 27730651). The course is fluctuating/relapsing, exacerbated by psychological stress, fatigue, hormonal changes, and busy visual environments; Cha describes these as "chronic syndromes with fluctuations that are both innate and driven by environmental stressors" (PMID: 34351113). MdDS is not associated with increased mortality; morbidity arises from disability, occupational impairment, anxiety/depression, and reduced quality of life (PMID: 37987715; PMID: 40296474).

11. Etiology and Environmental Triggers (F011)

The defining environmental cause is prolonged exposure to passive oscillatory motion — classically sea travel, also air and road travel — with onset within 48 hours of disembarking: "Onset occurs within 48 hours after the end of exposure to passive motion" (PMID: 32986636). Occupational exposure is documented in pilots, where "As flight time and age increased, the severity of the symptoms of MdDS increased for all subfactors" (PMID: 40296474), and in military personnel exposed to transport motion (PMID: 37987715). Symptom-exacerbating factors include busy visual environments, fatigue, sleep deprivation, psychological stress, and hormonal fluctuations. No toxin, radiation, pollutant, drug, or infectious agent is implicated. Paradoxically, re-exposure to passive motion transiently relieves symptoms.

12. Phenotype Spectrum (F012)

The core phenotype (100% by definition) is continuous non-spinning oscillatory self-motion (rocking, bobbing, swaying) present most of the day, adult-onset, chronic/fluctuating. Frequently co-occurring symptoms: "Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety" (PMID: 32986636). The symptom burden is variable across patients: even "dizziness, fatigue, and brain fog, were endorsed variably across subjects" (PMID: 42440785). Imbalance is largely subjective, though objective postural sway at ~0.2 Hz and oscillating vertical nystagmus on head roll are described. Quality-of-life impact is significant, including occupational disability.

Suggested HPO terms: Vertigo (HP:0002321), Abnormal vestibular function (HP:0410008), Fatigue (HP:0012378), Anxiety (HP:0000739), Depressivity (HP:0000716), Impaired concentration / cognitive impairment (HP:0100543), Nystagmus (HP:0000639).

13. Genetic/Molecular Basis — Non-Mendelian (F008)

No causal gene, pathogenic variant, chromosomal abnormality, or Mendelian inheritance pattern has been identified. MdDS is not catalogued in OMIM as a gene-associated disorder; it is an acquired, multifactorial functional/central vestibular disorder triggered by environmental motion exposure (PMID: 32986636; PMID: 33746890). Proposed molecular-level contributors are neuromodulatory/hormonal rather than genetic: gonadal (estrogen) influence on vestibular synaptic plasticity (PMID: 34864753) and migraine-related physiology (CGRP, serotonergic/sensory-gating pathways) given high migraine comorbidity. No transcriptomic, proteomic, metabolomic, or epigenetic disease signature has been established. Germline/somatic variants, modifier genes, founder effects, penetrance, and carrier frequencies are not applicable.

14. Prevention, Other Species, and Model Organisms (F013)

Prevention: No vaccine, screening program, or proven primary prevention exists. Practical risk reduction is behavioral — limiting/preparing for prolonged provocative passive motion, and, once symptomatic, avoiding triggers, managing stress/sleep, and initiating early VOR-readaptation therapy (tertiary prevention of chronicity). Persistence >6 months predicts lower remission, arguing for early intervention (PMID: 27730651; PMID: 34351113). Genetic counseling is not applicable.

Other species / natural disease: MdDS is a human-specific clinical entity; no naturally occurring MdDS is documented in companion animals or wildlife (no OMIA entry).

Model organisms: There is no transgenic/knockout genetic model. The mechanistic underpinning — velocity storage and roll-while-rotating VOR adaptation — was characterized experimentally in non-human primates (Macaca; NCBI Taxon 9544) and modeled computationally, informing the human treatment (PMID: 25076935; PMID: 41122084). Rotating optokinetic/roll paradigms in humans serve as the principal experimental system.

15. Integrated Synthesis — A Treatable Maladaptive-Plasticity Network Disorder (F016)

Convergent evidence supports a unified causal model: prolonged passive oscillatory motion entrains the central velocity-storage/VOR mechanism, producing a self-sustaining cortico-limbic network dysrhythmia (left entorhinal/amygdala hypermetabolism; altered default-mode/salience/executive and fronto-parietal coherence), which manifests as chronic internal rocking with fatigue, brain fog, visual-motion intolerance, and anxiety (PMID: 23209584; PMID: 33746890; PMID: 30099627; PMID: 41122084). Treatment targets each node — VOR/optokinetic readaptation (velocity storage; ~70% response) and DLPFC/cerebellar neuromodulation (network). Response is heterogeneous and increasingly personalized: two velocity-storage strategies (correction vs. attenuation) yield differing outcomes, and visual-motion sensitivity predicts poorer response to attenuation approaches (PMID: 42440785; PMID: 41122084).

Mechanistic Model / Interpretation

   TRIGGER (upstream)            CENTRAL MALADAPTATION            NETWORK STATE (downstream)         CLINICAL PHENOTYPE
 +--------------------+      +---------------------------+    +---------------------------+    +-----------------------+
 | Prolonged passive  |      | Velocity-storage / VOR    |    | Cortico-limbic dysrhythmia|    | Continuous rocking/    |
 | oscillatory motion | ---> | maladaptation:            |--> | - L entorhinal cortex +   |--> | bobbing/swaying        |
 | (cruise, flight,   |      | roll-while-rotating       |    |   amygdala HYPERmetabolism|    | + fatigue, brain fog,  |
 | car); onset <48 h  |      | cross-axis coupling       |    | - altered DMN/salience/   |    | visual-motion          |
 | after motion ends  |      | (3x3 dynamical system)    |    |   fronto-parietal coherence|   | intolerance, anxiety   |
 +--------------------+      +---------------------------+    +---------------------------+    +-----------------------+
|                              ^                                  ^                               |
|  re-exposure to motion       |  VOR / optokinetic               |  rTMS / tDCS over DLPFC        |  migraine prophylaxis,
+--- transiently RELIEVES -----+  READAPTATION (~70%)             +- neuromodulation (adjunct)     +- CBT, symptomatic Rx

Modifiers/amplifiers: female sex and gonadal hormones (perimenopausal onset), migraine physiology (CGRP, serotonergic sensory gating), psychological stress, fatigue, sleep deprivation, and busy visual environments. The paradoxical relief on re-exposure to motion is a defining clue that the disorder reflects a learned/entrained internal model that is transiently "matched" when real motion resumes.

Ontology term suggestions: - UBERON / anatomy: vestibular system, semicircular canal (UBERON:0001840), brainstem vestibular nuclei, entorhinal cortex (UBERON:0002728), amygdala (UBERON:0001876), dorsolateral prefrontal cortex, cerebellum (UBERON:0002037), insula. - CL / cell types: central vestibular neurons; no specific pathological cell population is identified (no cell death or lesion). - GO / biological process: vestibulo-ocular reflex (GO:0060013), regulation of neuronal synaptic plasticity (GO:0048168), adaptation of signaling pathway, sensory perception of balance. - CHEBI / chemicals (therapeutic): verapamil, nortriptyline, topiramate, clonazepam; estradiol/estrogen (modifier). - NCIT / interventions: vestibular rehabilitation therapy, transcranial magnetic stimulation, transcranial direct current stimulation, cognitive behavioral therapy. - HPO: see Finding 12.

Evidence Base

PMID Focus Contribution
32986636 Bárány Society diagnostic criteria Authoritative case definition, temporal qualifiers, triggers, ICVD classification
25076935 VOR readaptation relieves MdDS Core mechanism (VOR maladaptation) + landmark ~70%-response treatment; NHP + human data
41122084 Model-based treatment-effect heterogeneity Velocity-storage 3x3 dynamical model; personalization rationale
42440785 Toward personalized medicine for MdDS Maladaptive-plasticity framing; variable symptom burden; correction vs. attenuation strategies
23209584 Metabolic/connectivity changes Primary FDG-PET/fMRI evidence of limbic hypermetabolism
33746890 Neuroimaging markers review Synthesis of limbic focus + connectivity/VBM changes
30099627 EEG signatures of rTMS treatment Entrainment brain-state framing; EEG coherence biomarker; midlife-female demographics
28967282 RSFC signature of rTMS Connectivity predictor/biomarker of rTMS response
27176615 Double-blind sham rTMS crossover Controlled evidence rTMS improves dizziness/mood/anxiety
27117283 Home tDCS after rTMS RCT tDCS extends benefit; home safety (0/556 burns)
38345630 iTBS + VOR rehab RCT Negative: iTBS adds no benefit over VOR rehab
40228811 TMS scoping review Modest / statistically-but-not-clinically-significant benefit
30410464 Sham-controlled optokinetic stimuli Controlled support for optokinetic treatment
36323329 Roll Readaptation case (audiology) Translation of readaptation to clinic; functional recovery
27730651 MdDS as vestibular migraine 73% response to migraine prophylaxis; >6-month prognosis threshold
23674832 Rocking dizziness & headache Quantifies migraine comorbidity (41–46%)
34864753 Sex hormones & vestibular disorders Hormonal/plasticity basis; female predominance
34351113 Chronic Dizziness Differential diagnosis; fluctuating course; management principles
32364688 "Sickness of disembarkment" review Normal testing -> exclusion diagnosis
31580016 The MdDS (review) Phenotype, female predominance, QoL, normal work-up
40296474 MdDS in pilots by flight time Occupational exposure-response relationship
37987715 MdDS in military operations Occupational burden; disability/morbidity

Convergence vs. challenge: The mechanistic (VOR/velocity-storage), imaging (limbic/network), and electrophysiological (entrainment) lines of evidence are mutually reinforcing. The main challenge within the treatment literature is the negative iTBS RCT (PMID: 38345630) and the scoping-review conclusion that TMS benefits are statistically but not clinically significant (PMID: 40228811) — tempering enthusiasm for neuromodulation as a stand-alone therapy and reinforcing VOR readaptation as the primary disease-specific intervention.

Limitations and Knowledge Gaps

  1. No population-based epidemiology. True prevalence and incidence are unknown; all demographic estimates derive from small specialty-clinic case series (often N < 25), risking referral and sex-ascertainment bias.
  2. Small treatment trials. The pivotal readaptation and neuromodulation studies enroll tens of patients; several are single-arm, crossover, or case reports. There are no large multicenter RCTs and no head-to-head comparisons of readaptation vs. neuromodulation vs. pharmacotherapy.
  3. No validated clinical biomarker. FDG-PET, fMRI, and EEG signatures are research-only; diagnosis remains purely clinical and by exclusion, contributing to under-recognition and diagnostic delay.
  4. Mechanism is inferential. The velocity-storage model is well-motivated by NHP physiology and computational modelling but not directly confirmed in human MdDS tissue or with causal manipulation; the relationship between the peripheral VOR account and the cortico-limbic imaging findings is correlational.
  5. No animal disease model. Absence of a naturalistic or genetic model limits mechanistic dissection and therapeutic screening.
  6. Heterogeneous outcome measures. Studies use DHI, MdDS Balance Rating Scale, HADS, and postural sway inconsistently, hindering meta-analysis.
  7. Non-motion-triggered variant is poorly delineated from PPPD, blurring case boundaries.
  8. Molecular biology is essentially unexplored — no transcriptomic, proteomic, metabolomic, or epigenetic studies; the hormonal/migraine hypotheses remain associative.

Proposed Follow-up Experiments / Actions

  1. Multicenter registry and prevalence study. Establish a standardized MdDS registry (with the non-motion-triggered variant flagged) to derive population prevalence/incidence, sex ratio, and natural-history remission curves, formally testing the ">6-month = unlikely to remit" threshold.
  2. Definitive RCT of VOR/optokinetic readaptation with sham control, standardized DHI/MdDS-BRS endpoints, and 12-month follow-up; pre-register correction vs. attenuation strategy arms stratified by baseline visual-motion sensitivity (the predictor identified in PMID: 42440785).
  3. Biomarker validation. Prospectively test whether baseline DLPFC–entorhinal RSFC (PMID: 28967282) or EEG alpha/beta coherence (PMID: 30099627) predicts response, moving toward a treatment-selection tool.
  4. Hormonal mechanism study. Characterize onset/severity relative to menstrual cycle, menopause, and hormone therapy to test the gonadal-hormone hypothesis (PMID: 34864753); consider a pilot of hormonal modulation.
  5. Migraine-overlap trial. Head-to-head RCT of vestibular-migraine prophylaxis (verapamil/nortriptyline/topiramate) vs. readaptation vs. combination, given the 73% response signal (PMID: 27730651) and CGRP biology; explore anti-CGRP agents as a mechanistically motivated experimental therapy.
  6. Computational/personalized modelling. Extend the velocity-storage dynamical model (PMID: 41122084) into a patient-specific readaptation-protocol optimizer, validated prospectively.
  7. Molecular pilot. Exploratory plasma metabolomic/proteomic and, where feasible, blood transcriptomic profiling to seek any peripheral signature, acknowledging the low prior probability given the functional nature of the disorder.

Conclusion

Mal de Débarquement Syndrome is an acquired, non-genetic, chronic central/functional vestibular disorder in which prolonged passive oscillatory motion inappropriately conditions the brain's velocity-storage/VOR machinery, producing a self-sustaining cortico-limbic network state that is experienced as continuous internal rocking, bobbing, or swaying — accompanied by fatigue, brain fog, visual-motion intolerance, and anxiety. It predominates in midlife women, is highly comorbid with migraine, and is diagnosed clinically by exclusion in the presence of normal vestibular testing and MRI. The maladaptive-plasticity model is directly actionable: VOR readaptation / optokinetic therapy achieves ~70% substantial improvement, with adjunctive DLPFC neuromodulation and migraine-prophylaxis pharmacotherapy for selected patients. It is not life-threatening but is often chronic and disabling, and early intervention is favored because symptoms persisting beyond six months are less likely to remit spontaneously.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.2.1.

Outcome Count
References checked 22
Resolved 22
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 22
On topic 18
Off topic 0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 13
Resolved 13
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 0
Terms whose name was checked 2
Terms named correctly 0
Terms named as a different term 1
Terms whose name is worth a second look 1

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • GO:0060013 (1 mention) - the report calls it "GO / biological process: vestibulo-ocular reflex"; GO calls it righting reflex**

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

  • UBERON:0001840 (1 mention) - the report calls it "UBERON / anatomy: vestibular system, semicircular canal"; UBERON calls it semicircular canal**