Mal de Debarquement Syndrome: a survey on subtypes, misdiagnoses, onset and associated psychological features

Mal de Debarquement Syndrome (MdDS) is a neurological disorder, typically characterized by the perception of self-motion that persists for more than 1 month from an onset, which in most cases occurs after disembarkation from a vehicle (e.g., boat, cruise, train, plane). The phenomenon was first described by Erasmus Darwin in 1796 [1] and anchored by Brown and Baloh in 1987 as Mal de Debarquement [2‐5]. Those cases with a symptomatic remission in 1 month from the onset are considered transient and hence named Mal de Debarquement (MdD) [3, 4]. The main features of MdDS are a constant sensation of rocking, swaying, bobbing and bouncing when walking, as well as continuing when lying down [3, 6]. These sensations are persistent while patients are awake and are independent on body position or movements. They are also accompanied by a myriad of symptoms such as heightened sensory sensitivity (e.g., photophobia), head pressure, nausea, agoraphobia, brain fog, associated migraine and fatigue, as well as depression and anxiety [5]. Interestingly, these symptoms often subside temporarily when patients are re-exposed to passive motion (e.g., driving or being a passenger in a car) [4, 5]. This temporary alleviation of symptoms is unique to MdDS patients and usually used for confirming a diagnosis of the condition [7].

In the past decade, there has been a growing interest in MdDS from the scientific community, as well as from patients. Despite some MdDS information that is available from the MdDS community, many patients still find it difficult to receive a clear diagnosis from a healthcare professional for timely treatment [8]. In general, MdDS is still considered a rare neurological disorder [5], and the prevalence of this condition has only been assessed in one study to date [9], where it was estimated to have an occurrence rate of 1.3% in a neuro-otological clinic. Currently, it is still unclear how many MdDS patients are misdiagnosed or undiagnosed. It is known that on average, MdDS patients undergo around 19 appointments with healthcare professionals before receiving a correct diagnosis [10], and that this diagnostic process can take as long as several years [11]. This is primarily due to unawareness and limited knowledge of MdDS amongst physicians or healthcare professionals, but also due to the lack of clear diagnostic guidelines [7]. There was only one publication by Van Ombergen et al. that set forth preliminary diagnostic guidelines based on a literature review [4]. Due to the lack of understanding of the condition when they developed the guidelines, specific aspects of MdDS such as onset types were not distinguished [2]. MdDS is often unremarkable in peripheral vestibular function [3, 4], and brain imaging studies. This makes the diagnosis even more challenging. According to recent publications, MdDS, regardless of the cause of onset, has been typically misdiagnosed as vestibular migraine [9], ‘atypical’ Ménière’s disease, general space and motion disorder, panic disorders and generalised anxiety disorders [8].

The past few decades has seen rapid growth in interest and knowledge regarding MdDS. As more patients have been evaluated, it has become clear that typical MdDS symptoms can occur from events other than motion or spontaneously. It is apparent that MdDS can be categorized into two subtypes according to the patient’s onset cause. From the literature, a less common and less acknowledged form of MdDS is non-motion or spontaneous/other (SO) onset MdDS. This type of MdDS can occur either in the complete absence of an event or trigger, uncharacterised by a specific motion-related event (spontaneous), or can be associated with stressful events such as surgery, trauma, childbirth and others. Although there might be a better term than spontaneous MdDS or SO MdDS to describe the non-motion triggered nature of MdDS, this term has been accepted differentially from MT MdDS. The literature about spontaneous MdDS is very limited and there is a need to develop clear diagnostic guidelines for this MdDS subtype. Aside from the differences in onset cause, MT and SO MdDS appear to be symptomatically identical [9] and respond similarly to at least one of the proposed treatments for MdDS [12]. However, a clear comparison between the two subtypes has yet to be done, in particular taking into account epidemiology, diagnostic procedures and potential triggers responsible for the onset.

It has been reported that MdDS patients have a high level of depression, poor quality of life and high illness intrusiveness [8], regardless of their onset type. Illness intrusiveness is considered an underlying determinant of the psychosocial impact of chronic diseases and illness, and it has been found to be correlated with poor quality of life [8]. Psychological and mood disorders (e.g., anxiety, depression) secondary to MdDS have been previously described in patients [6, 12]. It has been proposed that secondary mood disorders develop as a consequence of the continuous perception of motion, which may lead to mental strain [9, 13], as well as the frustration with the endless search for a correct diagnosis and the changes in lifestyle required to cope with the condition. MdDS is believed to be extremely debilitating, both physically and mentally [2, 3, 8‐10]. The lack of awareness and recognition of MdDS from healthcare professionals further aggravates patient predisposition to the development of psychological disorders (e.g., anxiety and/or depression) [7]. Despite psychological symptoms being common, and considered part of the MdDS pathophysiology, it remains unclear if they are a pure consequence of MdDS inducement; or rather exist as vulnerability factors for developing the condition. Similarly, stress has also been known for negatively impacting MdDS patients [7]. It has long been known that stress has many physiological effects on the body [14] and it may be involved in influencing central vestibular and automatic functions in healthy individuals as well as in patients [15]. However, despite the potential role of stress in MdDS [7], the relevance of stress has never been closely evaluated. As a result, it remains unclear if it is a key trigger during MdDS onset, or if stress responses are triggered once the condition is established.

Observing the commonality of specific triggers across MdDS patients could help researchers understand why MdDS develops at a specific time. For example, it is possible that MT patients might have been exposed to similar passive motion before but yet they did not develop MdDS. As a result, the current study aimed to examine such factors as stress, depression and emotional status that may be equally important for eliciting MdDS. We also assess the prevalence of psychological comorbidities before and after MdDS onset. Based on previous studies [3, 9], it is reasonable to believe that psychological symptoms originate from MdDS. However, in this study, we also investigated if psychological disorders (e.g., being previously diagnosed with depression/being previously diagnosed with anxiety) were pre-existing conditions in MdDS patients. If true, this may help us to understand why there is a particular group of the population who seem more susceptible to MdDS.

To assess differences and similarities between MT and SO MdDS, specifically regarding diagnosis, onset and the major associated symptoms, two online surveys were made available to MT and SO MdDS patients. To date, some surveys have been popularized: the first by Gordon on transient MdD [16], followed by Hain et al. in 1999 [17] on MdDS. Epidemiological questionnaires and surveys on MdDS pathophysiology were also performed more recently [7, 10]. In this study, we aimed to provide a broad overview of MdDS and comprehensive diagnostic guidelines for both MdDS subtypes. The current study analysed diagnostic procedures, onset, and additional features associated with MdDS such as depression, anxiety and the role of stress.

In light of the difficulties involved in recruitment for a study concerning a rare condition, a multi-institutional collaboration was setup to collect data from MdDS respondents around the world. In total, 370 respondents completed either the MT or SO questionnaire. The current study is the largest in terms of MdDS respondents recruited to date, and is the only survey comparing MT versus SO subtypes. Furthermore, this study is the first to assess MdDS patients in a multicentred design and international setting. When considering the two onset subtypes, we have ascertained that the two categories clearly meet the clinical features of MT and SO MdDS. In line with published research [6], most MT respondents reported that their MdDS symptoms developed after a cruise, despite being on a cruise may be less frequent than being in a car, train or on a plane, time normally spent on a cruise is longer and during such type of travel, passengers are exposed to complex oscillation frequencies capable of disrupting the vestibular system and potentially the vestibular ocular reflex, following Dai’s theory [6]. Specifically, cruise ships normally rock from side to side at ≈ 0.2 Hz [12], which is known to induce motion sickness. We hypothesize that the exposure to such a strong stimulation and longer exposure times (typically), may be the reason why more people develop MdDS after disembarking a cruise ship. While 32% of the SO respondents developed MdDS after a period of psychological or physical stress or strong emotional experience, without the involvement of a motion event. It is possible that SO patients associate the onset of their disorder with a biographical event, and may appear ambiguous, nevertheless for this early stage of investigation, we believe it is important to collect as much information as possible about patients’ onset to identify any correlations between individuals within the subtype and to better objectify the differences between MT and SO subtypes.

We are aware that terms such as ‘psychological stress’ and ‘emotional experience’ are subjective terms with potentially broad interpretations. However, as these are the only events that these subsets of patients associate with their onset, they are of likely significance. A more extensive number of SO respondents is needed, as the SO survey was completed by a smaller number than the MT. A larger sample group could allow us to further define the psychological related aspects that SO patients attribute to MdDS onset.

Respondents from the MT and SO groups showed similar epidemiological results. The average age was 49 years old for both groups, with a strong female predominance. These results are comparable to a mean age of 45 years reported by other studies [3, 4, 7, 12, 17]. MdDS is a poorly understood disorder, and the lack of recognition and poor symptom management ultimately impact upon the patient’s mental state and lifestyle [9].

Patients learn to coexist with the syndrome. As reported by respondents from both groups, significant lifestyle changes were necessary, which in some cases had affected their employability, social life and ability to live, and what they consider a normal life. A large number of MT patients reported to have made significant adjustments to their lifestyle to avoid major triggers (such as exposure to bright, flickering light, excessive noise, going to the supermarket, etc.). The percentage of SO respondents implementing significant lifestyle changes was high (69.2%), similar to the MT group (63.1%). However, the number of total respondents in the SO group that responded to this question was much less than the MT group. Indeed, the open-ended comments received from both patients reveal the devastation that many MdDS experience after their onset. The majority of comments made by respondents in both groups referred to their high level of frustration and helplessness due to the great impairment that this condition has on their lives.

The lack of awareness among healthcare professionals contributes severely to misdiagnoses, and as a result some MdDS patients are unable to receive the correct diagnosis for long periods of time. In this survey, as previously stated, a high number of MT (47%) and SO (35.9%) respondents were self-diagnosed, meaning that they did not receive the MdDS diagnosis from any healthcare professional, despite their symptoms coinciding with the criteria for MdDS. Despite the potential risk of inclusion of non-MdDS sufferers, this category was maintained, based on previous research indicating that patients living with undiagnosed or highly debilitating conditions often resort to self-education through internet literature searches [9] and support group discussions [18]. As a result, the self-diagnosed MdDS patients in this study were patients who are still hoping to receive a confirmation of diagnosis but believed themselves to be suffering from MdDS. Results of this study found self-diagnosed SO respondents attended a higher number of medical appointments than the MT self-diagnosed group, indicating perhaps that the SO respondents have been continually seeking answers as they have not yet been officially diagnosed. On average, the SO respondents received a higher number of misdiagnoses, 3 different diagnoses, compared to 2.1 for the MT respondents. Similarly, both groups reported the same most prevalent misdiagnoses, which were vertigo and anxiety. Though these are not diagnostic terms, but rather symptoms, preliminary discussions with multiple patients revealed that many healthcare professionals often reported these terms as diagnoses, as a result we decided to include them in the questionnaire as diagnoses. The high number of patients misdiagnosed with vertigo and anxiety indicates that a great majority of healthcare professionals are not aware of vestibular disorders and more specifically MdDS, and are diagnosing patients with broad terms which focus on symptoms rather than an actual condition, and are using other diagnostic guidelines that do not include MdDS [19]. Following vertigo and anxiety, the most common misdiagnoses reported in the MT group was vestibular dysfunction, labyrinthitis, inner ear infection and BPPV. While the SO group reported diagnoses of vestibular dysfunction, VM, BPPV, labyrinthitis, inner ear infection, and lastly with depression. Related to the numerous misdiagnoses, more than 50% from both groups reported to have had negative experiences with health care providers. Most of the MT respondents were diagnosed by ENT doctors, followed by neurologists, whilst the opposite was true for SO respondents. This difference in diagnostic predominance between the ENT doctors and neurologists is probably due to the peculiarity of the SO group. The atypical onset is likely to have led to incorrect diagnoses. In addition, the MT respondents were found to have received the correct diagnosis earlier than the SO group. This data is understandable given the absence of clear diagnostic criteria for SO MdDS.

Thus, from the data obtained it is clear that diagnostic guidelines are needed to reduce misdiagnoses and improve patient’s management, and which also include the spontaneous or other forms of MdDS.

Hereto, we propose in Tables 6 and 7, new diagnostic guidelines for MT MdDS and SO MdDS, respectively. To be diagnosed with MT or SO MdDS, a patient should fulfil all the below mentioned criteria.

Symptomatic relief during passive motion was similarly reported for the MT and SO groups as presented in the results. This specific feature can clearly help distinguish MdDS patients from persistent postural perceptual dizziness (PPPD) (previously described as chronic subjective dizziness) [9, 20], visually induced dizziness (VID), phobic postural vertigo and motion sickness.

We are aware of the recent updates of the PPPD classification, which includes the previously named, chronic subjective dizziness, visual vertigo as well as phobic postural vertigo. Hereto, the most recent PPPD classification [20].

Despite the fact that MdDS shares similar features with these conditions now included and named as PPPD, (i.e., being triggered by visual stimuli, psychological stress and the development of anxiety and depression) [21], MdDS patients, regardless of their onset, are the only category of patients who experience an alleviation of symptoms when exposed to passive motion. Normally, PPPD patient’s symptoms are worse in motion [9], while VID patients are more prone to dizziness when observing their surroundings whilst moving (e.g., being in a car) due to busy or complex visual fields [22]. Finally, sufferers of phobic postural vertigo do not report any improvement of symptoms when exposed to passive motion. Yet, they do experience a reduction of symptoms once the mechanism of their complaints is explained to them and the patient feels reassured [23]. A potential theory regarding why MdDS patients report a reduction of symptoms when exposed to passive motion, may rely in the theory of adaptation to previous stimuli. As previously observed from functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) studies [9], MdDS patients have been shown to have increased functional connectivity between multiple areas involved in spatial awareness (e.g., posterior sensory processing areas and the left entorhinal cortex (EC) [24], as well as within the amygdala). We hypothesize, as previously stated by Cha [24], that the exposure to passive motion generates vestibular and somatosensory signals, which produce frequencies of various amplitudes that are able to override or momentarily suspend any underlying oscillating rhythm perceived by the patients. It is apparent that more research is needed to understand the exact mechanism of this paradoxical relief of symptoms during re-exposure to motion. Novel neuroimaging research should be performed to address the phantom perception of motion experienced by all MdDS patients.

It was identified for most of the SO respondents that psychological stress, or physical or emotional trauma, was present at the time of their believed MdDS onset. The relation of the emotional event to the symptomatic onset is also observed in phobic postural vertigo patients [23]. To distinguish those two entities, we suggest using the criterion point number 3 (relief by passive motion).

In general, more attention should be given to stress and its impact on MdDS development and symptomatology. The MT group reported to be significantly affected by moderate and severe stress, resulting in an aggravation of symptoms. In addition, the SO group is reported to be under severe stress during the period when the potential onset occurred. This strongly indicates that stress can be involved in aggravating symptoms and therefore be considered as a trigger, or it may be involved during onset in MT or SO group. Stress remains an extremely challenging factor in patients with vestibular disorders due to its physiological component and individuality aspect (e.g., age, gender, genetic factors, and early life experiences), as well as the variability of an individual’s perception over time [15]. Recently, the effects of stress on vestibular function and compensation have proven significant and are being increasingly recognised [15]. Several studies have observed stress in vestibular disorders such as chronic subjective dizziness (currently named PPPD) [24, 25], Ménière’s disease [26, 27] and vestibular migraine [26]. Other studies have reported that a chronic stress response was present in patients with a persistent vestibular dysfunction [27]. The vestibular system has been shown to have connections to the hypothalamic–pituitary–adrenal axis (HPA axis), the central stress response responsible for neuroendocrine adaptation to stressors [15, 28]. Balaban and Thayer in 2001 described the pathophysiologic mechanism of this problem [29]. The interaction between vestibular disorders and the psychiatric sphere is mediated through neurological pathways that are common to the control of the vestibular and autonomic systems, as well as emotional responses and anxiety [30].

As presented in Fig. 3, the connections from the vestibular nuclei to the parabrachial nucleus [31] are a direct link between the vestibular system and neural networks involved in expressing anxiety and emotion [32]. Stress may not only be affecting the patient’s symptoms, but also their physiological vestibular compensation mechanisms [14, 33]. In the study of Tschan and colleagues, stress, resilience and anxiety were considered among different vestibular patients as potential factors preventing vestibular compensation and rehabilitation [34]. Chronic stress is able to inhibit normal brain plasticity, leading to detrimental changes in the brain (e.g., hippocampus and prefrontal cortex) [33]. Potentially, chronic stress, as a result of MdDS, may be implicated in the pathophysiology of the disorder per se. Future studies should focus on assessing if MdDS patients report aberrant stress responses and consequently abnormal autonomic responses, ideally before and after a successful intervention. A disrupted HPA axis and autonomic response to stress could potentially be responsible for affecting an individual’s central compensation. Specifically, it could be responsible for the prolongation of MdD symptoms as well as having stress influencing symptoms and being involved in its onset.

Anxiety and/or depression are recognised as the most common psychological symptoms associated with MdDS [4, 10]. MdDS patients have been previously described as being prone to developing psychological symptoms and disorders such as anxiety and/or depression due to the impact the condition has on a patient’s quality of life and lifestyle [10]. However, our study aimed not only to evaluate the prevalence of psychological disorders (specifically depression and anxiety) in MdDS patients, but also to evaluate whether predisposition factors were present before the syndrome onset. From our results, a smaller group of the SO respondents (3 respondents) reported to have been diagnosed with anxiety before MdDS compared to the MT group (53 respondents).

The development of anxiety after MdDS onset was relatively high in the SO respondents (37.5%). This reinforces our previous diagnostic argument, where the SO group’s levels of anxiety may be the consequences of a poorly understood and managed disorder as reported in previous research [3, 4]. However, given the limited number of responses, more data is required. For the MT group, on the other hand, anxiety for certain individuals can also be considered as a predisposing factor for developing MdDS. However, this should be further evaluated. Theoretically, generalised anxiety may contribute to develop an aberrant stress response [35], directly linked to changes in the sympathetic nervous system.

Depression was equally present in the MT and SO respondents prior to MdDS onset. Although the number of SO responses was limited, further studies with larger sample sizes are necessary to ascertain the relationship between depression and MdDS for this subtype.

Some anecdotal studies have previously asserted that depression was a predicting factor in vestibular disorders, but this was never proved [36]. However, if not considered as a predisposing factor, it is well-known that depression is associated in many patients affected by central vertigo/vestibular disorders (e.g., migrainous vertigo) [37]. A great number of MT respondents were diagnosed with depression after MdDS, confirming previous research [9]. Depression in MdDS patients may also be particularly important if considering its effect on cognitive functions [38]. Cognitive problems such as brain fog, and difficulties in focusing and concentrating, have been previously observed in MdDS [39], however, there has not been an established link between depression and the psychological component of MdDS with cognitive dysfunctions. We encourage future studies to examine closely the association between the two.

It is also very likely that the presence of psychological disorders may contribute to altering sensory information and interpretations in the brain regions (amygdala, insular cortex, cingulate cortex and prefrontal cortex) [40].

Previous studies focussing on brain functions in MdDS patients have reported hypometabolism in the left prefrontal cortex, left temporal cortex, right amygdala, and right insula [24]. The severity of MdDS bodily sensations and of vestibular dysfunction suggests that there may be a critical dependence of the brain and body upon vestibular input. It is known that there is a higher presence of depersonalization and derealisation symptoms in patients with vestibular dysfunctions, suggesting that the vestibular inputs are greatly contributing to the definition of self, in terms of the sense of where the body is in relation to the external environment [41]. The association of psychological disorders with MdDS may contribute to the neuroimaging differences previously observed.

Finally, our study suggests that MdDS is the cause for developing psychological disorders in both its subtypes, which is supported by the fact that antidepressants as well as sedative medications (e.g., benzodiazepines) are found to be helpful in MdDS patients and therefore often prescribed by healthcare professionals [39]. The use of such medication may also have an impact on stress levels, which from our study seems to be responsible for aggravating MdDS symptoms. A further and more detailed examination of the psychological component, psychological symptoms associated to MdDS and effect of stress on MdDS patients should be undertaken.

This was the first online survey comparing two subtypes of MdDS. No major significant epidemiological differences were reported between MT and SO groups; both reported a female prevalence and the same mean age. MT patients are easier to diagnose than SO patients in terms of diagnostic procedures. Almost all the MT and SO respondents equally reported to have a reduction or absence of symptoms when re-exposed to passive motion. We encourage further EEG or fMRI studies to address this paradoxical perception of motion in MdDS patients. With this taken into account, we propose an updated version of the diagnostic criteria previously proposed by Van Ombergen and colleagues [4], to which we include symptom alleviation when exposed to motion, and also including the SO subtype.

Finally, these surveys allowed us to gain valuable information about other potential triggers and psychological features associated with MdDS. Stress was identified as a result of MdDS, a symptom aggravation factor, as well as a trigger for the onset especially in SO patients. Further studies should focus on measuring stress responses and autonomic reactions in MdDS. Depression and anxiety were identified as a clear consequence of MdDS and as a result, they should be taken into account for treatment options and patient management.

Overall, this study showed to be clinically relevant, providing more accurate diagnostic guidelines that can help establish an earlier and more accurate diagnosis in MdDS patients and provide more information about MT and SO MdDS subtypes.