DÄ internationalArchive41/2018The Neurophysiology and Treatment of Motion Sickness

cme

The Neurophysiology and Treatment of Motion Sickness

Dtsch Arztebl Int 2018; 115(41): 687-96; DOI: 10.3238/arztebl.2018.0687

Koch, A; Cascorbi, I; Westhofen, M; Dafotakis, M; Klapa, S; Kuhtz-Buschbeck, J P

Background: Seasickness and travel sickness are classic types of motion illness. Modern simulation systems and virtual reality representations can also induce comparable symptoms. Such manifestations can be alleviated or prevented by various measures.

Methods: This review is based on pertinent publications retrieved by a PubMed search, with special attention to clinical trials and review articles.

Results: Individuals vary in their susceptibility to autonomic symptoms, ranging from fatigue to massive vomiting, induced by passive movement at relatively low frequencies (0.2 to 0.4 Hz) in situations without any visual reference to the horizontal plane. Younger persons and women are considered more susceptible, and twin studies have revealed a genetic component as well. The various types of motion sickness are adequately explained by the intersensory conflict model, incorporating the vestibular, visual, and proprioceptive systems and extended to include consideration of postural instability and asymmetry of the otolith organs. Scopolamine and H1-antihistamines, such as dimenhydrinate and cinnarizine, can be used as pharmacotherapy. The symptoms can also be alleviated by habituation through long exposure or by the diminution of vestibular stimuli.

Conclusion: The various types of motion sickness can be treated with general measures to lessen the intersensory conflict, behavioral changes, and drugs.

LNSLNS

The term “motion sickness” (also called “kinetosis”) describes a set of symptoms that occur in association with motion of a person or his or her surroundings, triggering a stress reaction that results in autonomic symptoms. The onset is often insidious, with drowsiness/yawning and reduced alertness, and symptoms progress through cold sweating and pallor, salivation, and occasionally headache, to nausea and vomiting with incapacitation that can be severe (1).

Once the triggering motion ceases, symptoms generally disappear completely within 24 hours.

Learning goals

After reading this article, the reader should:

  • Be familiar with the wide array of motion types and patterns that can trigger motion sickness.
  • Understand the widely accepted model of the pathogenesis of motion sickness—the sensory conflict model and its extensions.
  • Be able to diagnose motion sickness.
  • Be familiar with drug and non-drug treatments and know when each is appropriate.

Introduction

Motion or travel sickness is as old as the various types of motion that cause it, whether on land, in the air, or at sea; sea sickness is the most notorious and in the extreme case can affect as many as 60% of even an experienced crew (2). In any vehicle or ship, it is generally persons being passively transported who are affected most—a fact well explained by the sensory conflict model presented below.

In days of old, those affected were mainly professional seafarers, a few of whom were unable to adapt adequately. Today, however, we see increasing numbers of temporary “seafarers,” not just on cruise ships, but also, for example, in the offshore wind industry, where it is necessary for “landlubber” engineers and technicians to be transported out to the wind parks in small boats. Modern transportation is also producing an increasing number of other trigger situations that are becoming relevant, from motion sickness in the back seat of a car, in a tilting train or an aircraft, to the “space sickness” experienced by astronauts in conditions of weightlessness.

It would appear that about two thirds of travelers have experienced symptoms of motion sickness at least once in a car, especially when in the back seat; half of them have even vomited, which among other things could have implications for the development of self-driving cars (3). In regard to the risk of becoming seasick on board a ship, and as an aid for shipbuilding design to help mitigate it, an ISO standard (IDO 2631) has even been defined, together with principles for the calculation of “motion sickness incidence” (MSI) that make it easier to estimate the expected percentage of persons who will vomit within 2 hours in given sea conditions (4).

And then there is the new phenomenon of “simulator sickness,” where playing complex video games on large screens or using virtual reality (VR) headsets can lead to symptoms surprisingly similar to those of classic seasickness, even though the persons affected are not physically in motion. As early as 1994, in a study of 146 volunteers, 61% of probands developed symptoms of malaise during a 20-min VR immersion period (5).

Young people, especially children between the ages of 6 and 12 years, and women are believed to be more susceptible to motion sickness (69, e1), meaning that symptoms induced by computer simulations are particularly significant for this group.

Whatever the scenario that leads to motion sickness, it is nevertheless often necessary for the person affected to carry out active control tasks in fast-moving scenarios and/or on screen. Examples are the driver who has to intervene in a self-driving car, the drone pilot in a complex situation, or the operator of a virtual reality operation system. To ensure that such control tasks are carried out safely, critical issues are whether and when any relevant reductions in alertness and competence occur, and whether these are noticed at all before the symptoms of nausea obtrude.

Early symptoms of incipient motion sickness with reduced alertness are also called “sopite syndrome” (from the Latin sopire, “to lull, to put to sleep”). The term describes a condition of withdrawal with increasing apathy and lethargy (e2), which the person affected may not even notice him- or herself. Few scientific publications exist on sopite syndrome. At the present time, PubMed shows only 16 publications on this subject.

Many people habituate well to kinetogenic situations that at first cause them malaise. However, other affected persons can be unable to habituate adequately. For example, twins often react very similarly, as shown by a 2006 study of monozygotic and dizygotic twins, suggesting the existence of a genetic background (10).

What, now, do the various situations from seasickness to “simulator sickness” have in common, such that predisposed persons can develop a complex of symptoms that range from reduced alertness to discomfort to feeling violently ill with severe vomiting?

This article will first present pathophysiological models of the causes of motion sickness. Next, neurophysiological aspects of nausea and vomiting in motion sickness will be discussed. The complexity of the neurophysiology involved explains why there are so many different approaches to treatment, including habituation exercises and more unconventional methods in addition to medication.

For the presentation of the pathophysiology of the various forms of motion sickness, a selective literature search on PubMed was carried out for the purpose of determining the extent of consensus on the dominant conflict theory model on the basis of the number of high-quality publications (human studies, clinical trials, reviews) found, and also on particular aspects that extend or supplement the model (eBox).

Literature search on particular aspects of the pathophysiology of various forms of motion sickness
Literature search on particular aspects of the pathophysiology of various forms of motion sickness
eBox
Literature search on particular aspects of the pathophysiology of various forms of motion sickness

Explanatory models of motion sickness

Vestibular, somatosensory, and visual afferents (eFigure) provide information about body posture and body movements (e3). The three semicircular canals of the vestibular apparatus are stimulated by angular acceleration, while the otolith organs of the vestibular apparatus (saccule and utricle) are stimulated by linear acceleration (including the acceleration of the Earth), because the otolithic membranes are weighed down by a layer of calcium carbonate crystals embedded within them (e3). The position of the head relative to the torso is reported by proprioceptive afferents from the neck muscles and the vertebral column. Visual inputs provide information on the body‘s own motion and/or that of its environment. Proprioceptive afferents from the joints and skeletal musculature transmit the sense of joints movements, joint position, and acceleration. Normally the three sensory channels (vestibular, visual, and proprioceptive) complement each other without contradiction. The afferents are connected to motor centers in the brainstem, which stabilize body position, e.g., through the use of stabilization reactions.

Sensory conflict
Sensory conflict
eFigure
Sensory conflict

Sensory conflicts are the most current explanation of motion sickness (1116). These conflicts arise when information from different sensory channels is contradictory or disagrees with expectations (eFigure). Two categories, each with three conflict types, are described in Table 1 (13, 16). Category A contains conflicts between visual and vestibular information. When both sensory systems report motion, but the reports disagree temporospatially, this is a type A1 conflict. An example would be watching the waves from the deck of a lurching ship. With a type A2 conflict, the visual system is reporting motion but the vestibular system is not. Because in this case the body is actually not in motion, this form is also referred to as “pseudo motion sickness” (13). An example is the already mentioned “simulator sickness” experienced by an observer in a stationary travel simulator watching scenes of traveling around a curve (e4). In type A3 conflict, the vestibular system reports motion but the visual system does not. Examples are reading below deck in a swaying ship, or being a back-seat passenger during a bumpy car ride.

Six types of kinetogenic sensory conflict, with examples*
Six types of kinetogenic sensory conflict, with examples*
Table 1
Six types of kinetogenic sensory conflict, with examples*

Category B sensory conflicts (eFigure, Table 1) are those caused by incongruent afferent information of the vestibular apparatus. These, then, are sensory conflicts between the five sensors (three semicircular canals, two otolith organs) that are active in the two labyrinths and show some frequency specificity. Slow passive motion, with a period between 0.1 and 0.5 Hz, is more likely to lead to nausea and vomiting than oscillating motion at a higher frequency (11). Studies of probands have shown that linear accelerations in vertical and horizontal directions (raising and lowering or laterally translating a closed cabin) with a varying cycle around 0.2 Hz had a particularly kinetogenic effect (17, e5, e6). The signals from the vestibular apparatus during motion of this periodicity are ambiguous (conflict type B), so that translation is sometimes incorrectly interpreted as tipping over (18, 19, e7). It is possible that visceral receptors registering the movements of the viscera are also involved (20, e8). The frequency specificity explains why the slower motion of ships and car journeys often triggers motion sickness where horse riding and riding a mountain bike, as a general rule, do not (11, 13, 21, e7). Optic flow patterns mimicking cyclical to-and-fro motion at a frequency of 0.2 to 0.4 Hz also triggered pseudo motion sickness (22).

A clear type B1 conflict (Table 1) with motion sickness in the form of a vestibular Coriolis reaction also occurs (1113, 16, 23, 24, e9) when people tilt their head forward and backward while spinning about their own long axis (Lansberg test). With type B2 conflict, the semicircular canals are stimulated but the otolith organs are not. Examples are caloric nystagmus and head movements under conditions of weightlessness—a rare trigger (12, 13). The rare type B3 conflict, in which the otolith organs alone are stimulated under laboratory conditions, e.g., during constant rotation (no stimulation of the semicircular canals) about the long axis of the body when horizontal (so-called “barbecue rotation”) (e10). Sensory conflicts with proprioception are less important (1116).

Apart from the sensory conflict (or mismatch) theory, there is also the concept of postural instability (25, e11). This emphasizes the role of the motor system and postulates that the main element leading to motion sickness is inefficient postural control that has not yet adapted to the situation. According to another hypothesis, asymmetry between the bilateral otolith organs favors the occurrence of “space sickness” in astronauts (e12).

Explanatory hypotheses like these add to the sensory conflict theory without invalidating it. The latter has become widely accepted, with a PubMed literature search identifying a correspondingly large number of reviews and clinical trials devoted to it as the main factor (eBox).

Habituation is an important element in motion sickness (1116). Just as sea sickness often moderates after a few days as the sufferer becomes accustomed to the swaying of the ship, so the converse can happen, although quite rarely: that going ashore after a long voyage can lead to an impaired ability to “switch back” again or “reset,” also known as “mal de débarquement syndrome” or “unsteadiness syndrome.”

Neurophysiologic aspects of nausea and vomiting in motion sickness

Afferents from the vestibular apparatus are involved in all relevant/significant sensory conflicts (Table 1), even those in which it is absence of these signals that leads to the mismatch (type A2 conflict, pseudo motion sickness). Patients with bilateral vestibular failure do not get seasick, neither do they develop pseudo motion sickness (26). The afferents from the labyrinth arrive at the vestibular nuclei of the brainstem, which also receive visual and proprioceptive input and are connected with the vestibulocerebellum (27).

The activity of the vestibular nuclei is influenced by numerous transmitters including acetylcholine, dopamine, γ-aminobutyric acid (GABA), glutamate, glycine, histamine, norepinephrine, and serotonin (24). Efferent projections of these nuclei to the reticular formation, the spinal cord, and the oculomotor nuclei serve the postural motor and the oculomotor systems. Ascending projections from the nuclei reach the temporoparietal cortex areas and insular cortex via the posterolateral thalamus (28). Autonomic reactions can be triggered via connections to the hypothalamus, the nucleus tractus solitarii (NTS), the locus ceruleus, and other nuclei of the reticular formation (including the nucleus parabrachialis).

Recent studies have described brain activity in pseudo motion sickness (29, e13). Probands lying in an MRI scanner were shown a moving pattern of stripes that resulted in the sensation of apparent motion (vection) and in about half the probands led to nausea. The onset of nausea coincided with activity in the amygdala, putamen, and dorsal pons; stronger persistent nausea was accompanied by activity in a variety of cortical areas (insular cortex, cingulate and prefrontal cortex, premotor cortex). Brain areas that react selectively to sensory conflicts alone have not yet been identified, however.

Vomiting due to motion sickness can also take place without involving the higher brain areas, however, as animal studies have shown (15, 30). The core area of interest is a network of brainstem regions often referred to for simplicity as the vomiting center. Various inputs from the vestibular nuclei, the area postrema, the gastrointestinal tract, and other nuclei of the reticular formation all converge at a central “switchboard,” the nucleus tractus solitarii. This means that the NTS can be excited by different stimuli such as toxins in the blood, sensory conflicts, or gastrointestinal symptoms, and this results in activation of adjacent areas of the brainstem and thus finally to vomiting.

The biogenic amine histamine is believed to contribute to the triggering of vomiting in sea sickness (31, e14). Animal studies have shown a direct correlation between sea sickness and histamine metabolism (32, e15). After excessive motion, increased histamine concentrations were shown in the inner ear and brain of the animals studied. This is underscored by experiences with sea sickness, where food with a strong histamine content appears to aggravate symptoms (33).

Diagnosis and treatment strategies in motion sickness

Motion sickness can usually be diagnosed on the basis of the characteristic history of a triggering situation and appropriate differential diagnosis (in accordance with guidelines) to rule out other diseases most of which are otorhinolaryngological or neurological, such as Menière’s disease, certain forms of migraine, or psychological causes (34, e16). In addition to these, however, because of the complex pathophysiology of motion sickness, gastroenterological and infectious diseases and any possible orthopedic causes should also be included in the differential diagnosis. Besides these, visual or cardiovascular disorders such as hypotension or hypoglycemia can also trigger symptoms similar to those of motion sickness (e17). Singh et al. provide an up-to-date overview of the causes of nausea and vomiting (35).

The sensory conflict theory is regarded as the best candidate construct of the pathophysiology of motion sickness, and involves complex neurophysiologic signaling with numerous brain nuclear regions and neurotransmitters participating in the production of the symptoms before the “homestretch” of vomiting is reached. Understandably, therefore, approaches to palliating or treating this “disorder” are similarly varied (Table 2).

Non-drug interventions for motion sickness*1
Non-drug interventions for motion sickness*1
Table 2
Non-drug interventions for motion sickness*1

Looking in a vehicle’s direction of travel or focusing on the horizon are simple measures that are well known to avoid or at least palliate the symptoms of motion sickness, most likely by reducing intersensory conflict (36). Lying down and reducing visual influences can also have a positive effect. One approach to treatment along similar lines which may perhaps also prove useful against sea sickness is the head-mounted display providing an artificial horizon or horizon information (2, e18e20).

Another approach is to try appropriate measures to improve habituation to motion stimuli. Such measures include desensitizing physiotherapy (reactive motion and body positioning exercises [e21, e22]) and practicing actively synchronizing body movements with the motion, including tilting the head into turns (36).

Some centers offer specialized habituation training before the start of a sea voyage for patients who suffer from sea sickness (37). This can include optokinetic desensitization over a period of weeks, plus simulated sea motion (swell) and balance training. As a general principle, habituation training attempts to reproduce the disturbing motion pattern as accurately as possible. Repeated exposure training can induce adequate habituation lasting for months, as described in detail by Zhang et al. (38).

Positive effects seem also to have been achieved by the application of transcutaneous electrical nerve stimulation (TENS) and by general stress-reduction measures such as pleasant music or odors (e23e26).

However, it must be pointed out at this stage that for many of the non-drug interventions in particular, too few prospective controlled clinical studies have yet been carried out for a judgment on their true efficacy to be made; one study dating from 1990 on acupressure bands (“SeaBand”) to prevent sea sickness did not show a positive effect, although P6 point stimulation has been shown to be effective against postoperative vomiting (e27, e28).

It is also important to mention that several recent clinical studies have shown considerable positive placebo effects of drug and non-drug interventions on symptoms of motion sickness (e29e31). On the one hand this makes it harder to assess the true efficacy of individual treatments, but on the other hand it can also be employed to beneficial effect.

Finally, especially at sea, avoiding foods with a high histamine content, such as tuna, some kinds of cheese, salami, sauerkraut, and red wine (foods/drinks altered by microorganisms) is one of the non-drug interventions or preventive measures (33).

The various forms of drug therapy (Table 3) are based primarily on the role of histamine, referred to above, in the pathophysiology of sea sickness, and on the importance of muscarinic receptors in the vestibular apparatus and vomiting center. Preparations containing antihistamines and anticholinergic drugs are both important here. An example of a monodrug is dimenhydrinate, which dissociates in the blood to diphenhydramine and 8-chlorotheophylline. Dimenhydrinate is often prescribed in combination with cinnarizine for short-term acute therapy. This H1-antagonist acts additionally as a dopamine, serotonin, and bradykinin receptor antagonist and as a calcium inhibitor. This is believed to result in synergistic effects in the vestibular apparatus. Typical adverse effects of the antihistaminergic properties of dimenhydrinate alone or in combination with cinnarizine are fatigue, slowed reactions, and impaired coordination and concentration. The incidence of adverse effects varies greatly in prospective studies and has been estimated at about 5% (e32e35); the duration of action when taken orally is 4–8 hours.

Drug therapy for motion sickness
Drug therapy for motion sickness
Table 3
Drug therapy for motion sickness

In a prospective study of patients with vestibular disorders, the response rate to a combination of dimenhydrinate and cinnarizine was 78%, whereas when these drugs taken separately the rates were only 45% and 55% respectively (e33). Anticholinergics in the form of transdermal scopolamine patches (TTS-S, transdermal therapeutic system—scopolamine) are also often used (38). The patches have a duration of action of up to 3 days and are used both preventively and for long-term therapy.

There are no prospective randomized studies on the effect of this treatment on motion sickness, nor any valid comparative studies with other drugs. However, the authors of a Cochrane review conclude that the effect of scopolamine is not superior to that of antihistamines or combination drugs, but it does have fewer adverse effects (39). The adverse effects derive from its anticholinergic properties and include, especially, mucosal dryness and mydriasis, palpitations, urinary retention, and, very rarely, hallucinogenic effects (e36). All of these substances have in common that they do not totally prevent or suppress sea sickness, for example, but they can greatly ameliorate symptoms. This comes at a cost, however, of adverse effects that can impair alertness and thus represent a safety risk for many tasks, e.g., on board a ship (19, 23).

Apart from these drug therapies, natural remedies are also used to suppress sea sickness. There are indications, even including a prospective, placebo-controlled study of sea cadets, showing that ginger can be used as an antiemetic with few adverse effects (40, e37, e38). The substances it contains are believed to act as antagonists at the 5-HT3 receptor, which has an important role in the vomiting center.

High-dose vitamin C, another remedy which has been credited with some antihistaminergic effect, was shown in a prospective, double-blind, placebo-controlled study to reduce the symptoms of sea sickness without identifiable adverse effects (31).

The dopamine antagonist metoclopramide is not indicated for the treatment of motion sickness. Metoclopramide can cause extrapyramidal symptoms in children and adolescents and/or when given at high doses, and if given over long periods, especially in older patients, can trigger tardive dyskinesia that can sometimes be irreversible. For this reason, metoclopramide may be used only for the prevention of delayed nausea and vomiting after chemo- and radiotherapy or for symptomatic treatment of nausea and vomiting due to acute migraine (and not in children or adolescents). Particularly effective antiemetics such as the 5-HT3 antagonist ondansetron or the neurokinin-1 antagonist aprepitant are also contraindicated for the treatment of motion sickness. Ondansetron can very often cause headache and sometimes seizures, extrapyramidal symptoms, and constipation, among other effects. Aprepitant often causes headache, constipation, and other adverse effects which may appear acceptable in the context of weighing risks against benefits during a highly emetogenic form of chemotherapy, but are unacceptable in the context of preventing motion sickness.

Conclusion

The explanatory model of sensory conflicts involving primarily the visual, vestibular, and proprioceptive systems describes how motion sickness arises in a range of forms, from classic sea sickness to “simulator sickness” in modern virtual reality systems. The symptoms can vary greatly, ranging from reduced alertness (sopite syndrome) to full-blown severe vomiting. The importance of sopite syndrome and how to measure it objectively is the subject of ongoing research.

Reflecting the complexity of the central nucleus areas and neurotransmitters involved in the development of the symptoms of motion sickness, options for treatment include a number of approaches that differ greatly from each other but may nevertheless achieve success. They range from drug treatment, tried and tested and based mainly on H1-antihistamines and anticholinergics, to symptom relief with vitamin C and ginger, to a multiplicity of behavioral measures aimed at desensitizing or improving habituation by means of physiotherapeutic exercises or habituation to stimuli that trigger motion sickness.

Given the increasing relevance of sensory conflicts, not just in faster moving vehicles, but in digitally processed environments, in some of which full alertness is still absolutely essential, it would seem that continued development of drug options with fewer adverse effects is required.

Definition
The term “motion sickness” describes a set of autonomic symptoms caused by incongruent sensory impressions under conditions of motion. Cold sweats, pallor, nausea, and vomiting are caused by a stress reaction to the motion.

Prevalence
Young people, especially children between the ages of 6 and 12 years, and women are believed to be more susceptible to motion sickness.

Genetic component
Twins often react very similarly, as shown by a 2006 study of monozygotic and dizygotic twins, suggesting the existence of a genetic background.

Explanatory model
The sensory conflict model is widely accepted as explaining the pathogenesis of motion sickness. Incongruent sensory information results in conflict between the vestibular, optic, and proprioceptive systems.

Type A conflict
Type A sensory conflicts are caused by incongruent afferent information from the vestibular and visual sensory organs.

Type B conflict
Incongruence between information from the semicircular canals and the otolith organs produces type B conflict.

Neurophysiologic aspects
Development of symptoms involves complex central brain structures and nuclear regions with many neurotransmitters participating, including histamine.

Diagnosis
Motion sickness is diagnosed on the basis of a history of a triggering situation and exclusion of neurologic, otorhinolaryngologic, gastroenterologic, and infectious diseases and orthopedic causes.

Non-drug treatment
Various non-drug interventions relieve the symptoms of motion sickness, by, for instance, reducing sensory conflict.

Preventive medication
Anticholinergics are used for prevention, e.g., transdermal scopolamine. Administration should be 6 to 8 h before travel starts or before the expected onset of motion sickness.

Drug treatment
Apart from a number of non-drug interventions, H1-antihistamines with the lowest possible potential for sedation are the main treatment of choice for vertigo, nausea, and vomiting due to motion sickness.

Contraindicated drugs
Because of severe adverse effects, the use of metoclopramide, ondansetron, or aprepitant to prevent or treat motion sickness is contraindicated.

Conclusion
The development of vehicles without constant outside view, and of virtual reality environments, requires drug options with fewer adverse effects.

Conflict of interest statement
The authors declare that no conflict of interest exists.

Manuscript received on 28 March 2018, revised version accepted on
9 August 2018

Translated from the original German by Kersti Wagstaff, MA

Corresponding author:
Prof. Dr. med. Andreas Koch
Schifffahrtmedizinisches Institut der Marine,
24119 Kronshagen, Germany
Sektion Maritime Medizin am Institut für Experimentelle Medizin
der Christian-Albrechts-Universität zu Kiel
a.koch@iem.uni-kiel.de

Supplementary material
For eReferences please refer to:
www.aerzteblatt-international.de/ref4118

eBox and eFigure:
www.aerzteblatt-international.de/18m0687

1.
Jelinek T: Kursbuch Reisemedizin: Beratung, Prophylaxe, Reisen mit Erkrankungen. Stuttgart, New York: Georg Thieme Verlag 2012; 68–71.
2.
Krueger WWO: Controlling motion sickness and spatial disorientation and enhancing vestibular rehabilitation with a user-worn see-through display. Laryngoscope 2011; 121(Suppl. 2): 17–35 CrossRef MEDLINE PubMed Central
3.
Diels C, Bos JE: Self-driving carsickness. Appl Ergon 2016; 53 Pt B: 374–82.
4.
Riola JM, Pérez R: The seasickness phenomenom. J Marit Res 2012; 9: 67–72.
5.
Regan EC, Price KR: The frequency of occurrence and severity of side-effects of immersion virtual reality. Aviat Space Environ Med 1994; 65: 527–30 MEDLINE
6.
Paillard AC, Quarck G, Paolino F, et al.: Motion sickness susceptibility in healthy subjects and vestibular patients: effects of gender, age and trait-anxiety. J Vestib Res Equilib Orientat 2013; 23: 203–9.
7.
Klosterhalfen S, Kellermann S, Pan F, Stockhorst U, Hall G, Enck P: Effects of ethnicity and gender on motion sickness susceptibility. Aviat Space Environ Med 2005; 76: 1051–7 MEDLINE
8.
Bos JE, Damala D, Lewis C, Ganguly A, Turan O: Susceptibility to seasickness. Ergonomics 2007; 50: 890–901 CrossRef MEDLINE
9.
Zhou W, Wang J, Pan L, et al.: Sex and age differences in motion sickness in rats: The correlation with blood hormone responses and neuronal activation in the vestibular and autonomic nuclei. Front Aging Neurosci 2017; 9: 29 CrossRef MEDLINE PubMed Central
10.
Reavley CM, Golding JF, Cherkas LF, Spector TD, MacGregor AJ: Genetic influences on motion sickness susceptibility in adult women: a classical twin study. Aviat Space Environ Med 2006; 77: 1148–52 MEDLINE
11.
Bertolini G, Straumann D: Moving in a moving world: A review on vestibular motion sickness. Front Neurol 2016; 7: 14 CrossRef MEDLINE PubMed Central
12.
Lackner JR: Motion sickness: more than nausea and vomiting. Exp Brain Res 2014; 232: 2493–510 CrossRef MEDLINE PubMed Central
13.
Schmäl F: Neuronal mechanisms and the treatment of motion sickness. Pharmacology 2013; 91: 229–41 CrossRef MEDLINE
14.
Tal D, Hershkovitz D,Kaminski-Graif, Wiener G, Samuel O, Shupak A: Vestibular evoked myogenic potentials and habituation to seasickness. Clin Neurophys 2013; 124: 2445–49 CrossRef MEDLINE
15.
Yates BJ, Miller AD, Lucot JB: Physiological basis and pharmacology of motion sickness: an update. Brain Res Bull 1998; 47: 395–406 CrossRef
16.
Reason JT: Motion sickness adaptation: a neural mismatch model. J R Soc Med 1978; 71: 819–29 CrossRef
17.
Golding JF, Mueller AG, Gresty MA: A motion sickness maximum around the 0.2 Hz frequency range of horizontal translational oscillation. Aviat Space Environ Med 2001; 72: 188–92 MEDLINE
18.
Bronstein AM, Golding JF, Gresty MA: Vertigo and dizziness from environmental motion: visual vertigo, motion sickness, and drivers’ disorientation. Semin Neurol 2013; 33: 219–30 CrossRef MEDLINE
19.
Golding JF, Gresty MA: Pathophysiology and treatment of motion sickness. Curr Opin Neurol 2015; 28: 83–88 CrossRef MEDLINE
20.
von Gierke HE, Parker DE: Differences in otolith and abdominal viscera graviceptor dynamics: implications for motion sickness and perceived body position. Aviat Space Environ Med 1994; 65: 747–51 MEDLINE
21.
Golding JF, Gresty MA: Motion sickness. Curr Opin Neurol 2005; 18: 29–34 CrossRef
22.
Diels C, Howarth PA: Frequency characteristics of visually induced motion sickness. Hum Factors 2013; 55: 595–604 CrossRef MEDLINE
23.
Shupak A, Gordon CR: Motion sickness: advances in pathogenesis, prediction, prevention, and treatment. Aviat Space Environ Med 2006; 77: 1213–23.
24.
Takeda N, Morita M, Horii A, Nishiike S, Kitahara T, Uno A: Neural mechanisms of motion sickness. J Med Invest 2001; 48: 44–59.
25.
Riccio GE, Stoffregen TA: An ecological theory of motion sickness and postural instability. Ecol Psychol 1991; 3: 195–240 CrossRef
26.
Money KE: Motion sickness. Physiol Rev 1970; 50: 1–39 CrossRef MEDLINE
27.
Barmack NH: Central vestibular system: vestibular nuclei and posterior cerebellum. Brain Res Bull 2003; 60: 511–41 CrossRef
28.
Dieterich M, Brandt T: Functional brain imaging of peripheral and central vestibular disorders. Brain 2008; 131: 2538–52 CrossRef MEDLINE
29.
Sclocco R, Kim J, Garcia RG, et al.: Brain circuitry supporting multi-organ autonomic outflow in response to nausea. Cereb Cortex 2016; 26: 485–97.
30.
Yates BJ, Catanzaro MF, Miller DJ, McCall AA: Integration of vestibular and emetic gastrointestinal signals that produce nausea and vomiting: potential contributions to motion sickness. Exp Brain Res 2014; 232: 2455–69 CrossRef MEDLINE PubMed Central
31.
Jarisch R, Weyer D, Ehlert E, et al.: Impact of oral vitamin C on histamine levels and seasickness. J Vestib Res Equilib Orientat 2014; 24: 281–8.
32.
Takeda N, Morita M, Hasegawa S, Horii A, Kubo T, Matsunaga T: Neuropharmacology of motion sickness and emesis. A review. Acta Oto-Laryngol Suppl 1993; 501: 10–5 CrossRef
33.
Jarisch R: Histaminintoleranz – Histamin und Seekrankheit. Stuttgart, New York: Georg Thieme 2013; 26–39.
34.
van Esch BF, van Wensen E, van der Zaag-Loonen HJ, Benthem PPG van, van Leeuwen RB: Clinical characteristics of benign recurrent vestibulopathy: clearly distinctive from vestibular migraine and menière’s disease? Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 2017; 38: 357–63.
35.
Singh P, Yoon SS, Kuo B: Nausea: a review of pathophysiology and therapeutics. Ther Adv Gastroenterol 2016; 9: 98–112 CrossRefMEDLINE PubMed Central
36.
Brainard A, Gresham C: Prevention and treatment of motion sickness. Am Fam Physician 2014; 90: 41–6.
37.
Ressiot E, Dolz M, Bonne L, Marianowski R: Prospective study on the efficacy of optokinetic training in the treatment of seasickness. Eur Ann Otorhinolaryngol Head Neck Dis 2013; 130: 263–8 CrossRef MEDLINE
38.
Zhang LL, Wang JQ, Qi RR, Pan LL, Li M, Cai YL: Motion sickness: current knowledge and recent advance. CNS Neurosci Ther 2016; 22: 15–24 CrossRef MEDLINE
39.
Spinks A, Wasiak J: Scopolamine (hyoscine) for preventing and treating motion sickness. Cochrane Database Syst Rev 2011; 6: CD002851.
40.
White B: Ginger: an overview. Am Fam Physician 2007; 75: 1689–91.
e1.
Li J, Zhu L, Yuan W, Jin G, Sun J: [Habituation of seasickness in adult during a long voyage]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2012; 47: 642–5 MEDLINE
e2.
Graybiel A, Knepton J: Sopite syndrome: a sometimes sole manifestation of motion sickness. Aviat Space Environ Med 1976; 47: 873–82 MEDLINE
e3.
Geiger J: Gleichgewichts-, Lage- und Bewegungssinn. In: Pape HC, Kurtz A, Silbernagl S, (eds.): Physiologie (7th edition). Stuttgart: Georg Thieme 2014; 756–68.
e4.
Kennedy RS, Drexler J, Kennedy RC: Research in visually induced motion sickness. Appl Ergon 2010; 41: 494–503 CrossRef MEDLINE
e5.
O’Hanlon JF, McCauley ME: Motion sickness incidence as a function of the frequency and acceleration of vertical sinusoidal motion. Aerosp Med 1974; 45: 366–9 MEDLINE
e6.
Griffin MJ, Mills KL: Effect of frequency and direction of horizontal oscillation on motion sickness. Aviat Space Environ Med 2002; 73: 537–43 MEDLINE
e7.
Golding JF. Motion sickness. Handb Clin Neurol 2016; 137: 371–90 CrossRef MEDLINE
e8.
von Gierke HE, Parker DE: Differences in otolith and abdominal viscera graviceptor dynamics: implications for motion sickness and perceived body position. Aviat Space Environ Med 1994; 65: 747–51 MEDLINE
e9.
Dai M, Kunin M, Raphan T, Cohen B: The relation of motion sickness to the spatial-temporal properties of velocity storage. Exp Brain Res 2003; 151: 173–89 CrossRef MEDLINE
e10.
Leger A, Money KE, Landolt JP, Cheung BS, Rodden BE: Motion sickness caused by rotations about earth-horizontal and earth-vertical axes. J Appl Physiol 1981; 50: 469–77 CrossRef MEDLINE
e11.
Riccio GE, Stoffregen TA: An ecological theory of motion sickness and postural instability. Ecol Psychol 1991; 3: 195–240 CrossRef
e12.
Nooij SA, Vanspauwen R, Bos JE, Wuyts FL: A re-investigation of the role of utricular asymmetries in Space Motion Sickness. J Vestib Res Equilib Orientat 2011; 21: 141–51.
e13.
Napadow V, Sheehan JD, Kim J et al.: The brain circuitry underlying the temporal evolution of nausea in humans. Cereb Cortex 2013; 23: 806–13 CrossRef MEDLINE PubMed Central
e14.
Watanabe T, Yamatodani A, Maeyama K, Wada H: Pharmacology of alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase. Trends Pharmacol Sci 1990; 11: 363–7 CrossRef
e15.
Lucot JB, Takeda N: Alpha-fluoromethylhistidine but not diphenhydramine prevents motion-induced emesis in the cat. Am J Otolaryngol 1992; 13: 176–80 CrossRef
e16.
Neuhauser H, Lempert T: Vertigo and dizziness related to migraine: a diagnostic challenge. Cephalalgia Int J Headache 2004; 24: 83–91 CrossRef MEDLINE
e17.
Aust G: [Equilibrium disorders and their diagnosis in childhood]. Laryngorhinootologie 1991; 70: 532–7 MEDLINE
e18.
Buker TJ, Vincenzi DA, Deaton JE: The effect of apparent latency on simulator sickness while using a see-through helmet-mounted display: reducing apparent latency with predictive compensation. Hum Factors 2012; 54: 235–49 CrossRef MEDLINE
e19.
Bonato F, Bubka A, Krueger WWO: A wearable device providing a visual fixation point for the alleviation of motion sickness symptoms. Mil Med 2015; 180: 1268–72 CrossRef MEDLINE
e20.
Tal D, Gonen A, Wiener G, et al.: Artificial horizon effects on motion sickness and performance. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 2012; 33: 878–85 CrossRef MEDLINE
e21.
Wada Y, Nishiike S, Kitahara T, et al.: Effects of repeated snowboard exercise in virtual reality with time lags of visual scene behind body rotation on head stability and subjective slalom run performance in healthy young subjects. Acta Otolaryngol 2016; 136: 1121–4 CrossRef MEDLINE
e22.
Robinson KD: Die Wirkung eines reaktiven Trainings auf die Kinetosesymptomatik. Masterarbeit Sportwissenschaft; Christian-Albrechts-Universität zu Kiel 2017.
e23.
Keshavarz B, Hecht H: Pleasant music as a countermeasure against visually induced motion sickness. Appl Ergon 2014; 45: 521–7 CrossRef MEDLINE
e24.
Keshavarz B, Stelzmann D, Paillard A, Hecht H: Visually induced motion sickness can be alleviated by pleasant odors. Exp Brain Res 2015; 233: 1353–64 CrossRef MEDLINE
e25.
Chu H, Li MH, Juan SH, Chiou WY: Effects of transcutaneous electrical nerve stimulation on motion sickness induced by rotary chair: a crossover study. J Altern Complement Med 2012; 18: 494–500 CrossRef MEDLINE
e26.
Chu H, Li MH, Huang YC, Lee SY: Simultaneous transcutaneous electrical nerve stimulation mitigates simulator sickness symptoms in healthy adults: a crossover study. BMC Complement Altern Med 2013; 13: 84 CrossRef MEDLINE PubMed Central
e27.
Bruce DG, Golding JF, Hockenhull N, Pethybridge RJ: Acupressure and motion sickness. Aviat Space Environ Med 1990; 61: 361–5 MEDLINE
e28.
Lee A, Fan LT: Stimulation of the wrist acupuncture point P6 for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev 2009 CD003281 MEDLINE PubMed Central
e29.
Müller V, Remus K, Hoffmann V, Tschöp MH, Meissner K: Effectiveness of a placebo intervention on visually induced nausea in women—a randomized controlled pilot study. J Psychosom Res 2016; 91: 9–11 CrossRef MEDLINE
e30.
Weimer K, Horing B, Muth ER, Scisco JL, Klosterhalfen S, Enck P: Different disclosed probabilities to receive an antiemetic equally decrease subjective symptoms in an experimental placebo study: to be or not to be sure. Clin Ther 2017; 39: 487–501 CrossRef MEDLINE
e31.
Horing B, Weimer K, Schrade D, et al.: Reduction of motion sickness with an enhanced placebo instruction: an experimental study with healthy participants. Psychosom Med 2013; 75: 497–504 CrossRef MEDLINE
e32.
Hahn A, Sejna I, Stefflova B, Schwarz M, Baumann W: A fixed combination of cinnarizine/dimenhydrinate for the treatment of patients with acute vertigo due to vestibular disorders : a randomized, reference-controlled clinical study. Clin Drug Investig 2008; 28: 89–99 CrossRef
e33.
Hahn A, Novotný M, Shotekov PM, Cirek Z, Bognar-Steinberg I, Baumann W: Comparison of cinnarizine/dimenhydrinate fixed combination with the respective monotherapies for vertigo of various origins. Clin Drug Investig 2011; 31: 371–83 CrossRef MEDLINE
e34.
Novotný M, Kostrica R: Fixed combination of cinnarizine and dimenhydrinate versus betahistine dimesylate in the treatment of Ménière’s disease: a randomized, double-blind, parallel group clinical study. Int Tinnitus J 2002; 8: 115–23 MEDLINE
e35.
Scholtz AW, Schwarz M, Baumann W, Kleinfeldt D, Scholtz HJ: Treatment of vertigo due to acute unilateral vestibular loss with a fixed combination of cinnarizine and dimenhydrinate: a double-blind, randomized, parallel-group clinical study. Clin Ther 2004; 26: 866–77 CrossRef
e36.
Rubner O, Kummerhoff PW, Haase H: [An unusual case of psychosis caused by long-term administration of a scopolamine membrane patch. Paranoid hallucinogenic and delusional symptoms]. Nervenarzt 1997; 68: 77–9 CrossRef MEDLINE
e37.
Hoffman T: Ginger: an ancient remedy and modern miracle drug. Hawaii Med J 2007; 66: 326–7 MEDLINE
e38.
Grøntved A, Brask T, Kambskard J, Hentzer E: Ginger root against seasickness. A controlled trial on the open sea. Acta Otolaryngol 1988; 105: 45–9 CrossRef MEDLINE
e39.
Domeyer JE, Cassavaugh ND, Backs RW: The use of adaptation to reduce simulator sickness in driving assessment and research. Accid Anal Prev 2013; 53: 127–32 CrossRef MEDLINE
e40.
Micarelli A, Viziano A, Augimeri I, Micarelli D, Alessandrini M: Three-dimensional head-mounted gaming task procedure maximizes effects of vestibular rehabilitation in unilateral vestibular hypofunction: a randomized controlled pilot trial. Int J Rehabil Res Int Z Rehabil Rev Int Rech Readaptation 2017; 40: 325–32.
e41.
Buker TJ, Vincenzi DA, Deaton JE: The effect of apparent latency on simulator sickness while using a see-through helmet-mounted display: reducing apparent latency with predictive compensation. Hum Factors 2012; 54: 235–49 CrossRef MEDLINE
e42.
Russell MEB, Hoffman B, Stromberg S, Carlson CR: Use of controlled diaphragmatic breathing for the management of motion sickness in a virtual reality environment. Appl Psychophysiol Biofeedback 2014; 39: 269–77 CrossRef MEDLINE
e43.
Stromberg SE, Russell ME, Carlson CR: Diaphragmatic breathing and its effectiveness for the management of motion sickness. Aerosp Med Hum Perform 2015; 86: 452–7 CrossRef MEDLINE
e44.
Cha YH, Urbano D, Pariseau N: Randomized single blind sham controlled trial of adjunctive home-based tDCS after rTMS for mal de debarquement syndrome: safety, efficacy, and participant satisfaction assessment. Brain Stimulat 2016; 9: 537–44 CrossRef MEDLINE
e45.
Cha YH, Deblieck C, Wu AD: Double-blind sham-controlled crossover trial of repetitive transcranial magnetic stimulation for mal de debarquement syndrome. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 2016; 37: 805–12 CrossRef MEDLINE PubMed Central
e46.
Golding JF: Motion sickness susceptibility. Auton Neurosci 2006; 129: 67–76 CrossRef MEDLINE
e47.
Gil A, Nachum Z, Tal D, Shupak A: A comparison of cinnarizine and transdermal scopolamine for the prevention of seasickness in naval crew: a double-blind, randomized, crossover study. Clin Neuropharmacol 2012; 35: 37–9 CrossRef MEDLINE
e48.
Sherman CR: Motion sickness: review of causes and preventive strategies. J Travel Med 2002; 9: 251–6 MEDLINE
e49.
Zajonc TP, Roland PS: Vertigo and motion sickness. Part II: pharmacologic treatment. Ear Nose Throat J 2006; 85: 25–35 MEDLINE
e50.
Nachum Z, Shupak A, Gordon CR: Transdermal scopolamine for prevention of motion sickness: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet 2006; 45: 543–66 MEDLINE
e51.
Estrada A, LeDuc PA, Curry IP, Phelps SE, Fuller DR: Airsickness prevention in helicopter passengers. Aviat Space Environ Med 2007; 78: 408–13 MEDLINE
e52.
Brand JJ, Colquhoun WP, Gould AH, Perry WL: (—)-Hyoscine and cyclizine as motion sickness remedies. Br J Pharmacol Chemother 1967; 30: 463–9 CrossRef
e53.
Paul MA, MacLellan M, Gray G: Motion-sickness medications for aircrew: impact on psychomotor performance. Aviat Space Environ Med 2005; 76: 560–5 MEDLINE
e54.
Gordon CR, Shupak A: Prevention and treatment of motion sickness in children. CNS Drugs 1999; 12: 369–81 CrossRef
e55.
Cheung BS, Heskin R, Hofer KD: Failure of cetirizine and fexofenadine to prevent motion sickness. Ann Pharmacother 2003; 37: 173–7.
Naval Institute of Maritime Medicine, Kronshagen,
Institute of Experimental Medicine, Section Maritime Medicine Christian-Albrechts-Universität, Kiel: Prof. Dr. med. Andreas Koch, Dr. med. Sebastian Klapa
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel: Prof. Dr. med. Dr. rer. nat. Ingolf Cascorbi
Clinic for Otorhinolaryngology and Plastic Surgery of the Head and Throat, RWTH Aachen: Prof. Dr. med. Martin Westhofen
Department of Neurology, RWTH Aachen: PD Dr. med. Manuel Dafotakis
Institute of Physiology Christian-Albrechts-University, Kiel:
Prof. Dr. med. Johann Peter Kuhtz-Buschbeck
Six types of kinetogenic sensory conflict, with examples*
Six types of kinetogenic sensory conflict, with examples*
Table 1
Six types of kinetogenic sensory conflict, with examples*
Non-drug interventions for motion sickness*1
Non-drug interventions for motion sickness*1
Table 2
Non-drug interventions for motion sickness*1
Drug therapy for motion sickness
Drug therapy for motion sickness
Table 3
Drug therapy for motion sickness
Literature search on particular aspects of the pathophysiology of various forms of motion sickness
Literature search on particular aspects of the pathophysiology of various forms of motion sickness
eBox
Literature search on particular aspects of the pathophysiology of various forms of motion sickness
Sensory conflict
Sensory conflict
eFigure
Sensory conflict
1.Jelinek T: Kursbuch Reisemedizin: Beratung, Prophylaxe, Reisen mit Erkrankungen. Stuttgart, New York: Georg Thieme Verlag 2012; 68–71.
2.Krueger WWO: Controlling motion sickness and spatial disorientation and enhancing vestibular rehabilitation with a user-worn see-through display. Laryngoscope 2011; 121(Suppl. 2): 17–35 CrossRef MEDLINE PubMed Central
3. Diels C, Bos JE: Self-driving carsickness. Appl Ergon 2016; 53 Pt B: 374–82.
4. Riola JM, Pérez R: The seasickness phenomenom. J Marit Res 2012; 9: 67–72.
5. Regan EC, Price KR: The frequency of occurrence and severity of side-effects of immersion virtual reality. Aviat Space Environ Med 1994; 65: 527–30 MEDLINE
6.Paillard AC, Quarck G, Paolino F, et al.: Motion sickness susceptibility in healthy subjects and vestibular patients: effects of gender, age and trait-anxiety. J Vestib Res Equilib Orientat 2013; 23: 203–9.
7. Klosterhalfen S, Kellermann S, Pan F, Stockhorst U, Hall G, Enck P: Effects of ethnicity and gender on motion sickness susceptibility. Aviat Space Environ Med 2005; 76: 1051–7 MEDLINE
8. Bos JE, Damala D, Lewis C, Ganguly A, Turan O: Susceptibility to seasickness. Ergonomics 2007; 50: 890–901 CrossRef MEDLINE
9.Zhou W, Wang J, Pan L, et al.: Sex and age differences in motion sickness in rats: The correlation with blood hormone responses and neuronal activation in the vestibular and autonomic nuclei. Front Aging Neurosci 2017; 9: 29 CrossRef MEDLINE PubMed Central
10. Reavley CM, Golding JF, Cherkas LF, Spector TD, MacGregor AJ: Genetic influences on motion sickness susceptibility in adult women: a classical twin study. Aviat Space Environ Med 2006; 77: 1148–52 MEDLINE
11. Bertolini G, Straumann D: Moving in a moving world: A review on vestibular motion sickness. Front Neurol 2016; 7: 14 CrossRef MEDLINE PubMed Central
12. Lackner JR: Motion sickness: more than nausea and vomiting. Exp Brain Res 2014; 232: 2493–510 CrossRef MEDLINE PubMed Central
13. Schmäl F: Neuronal mechanisms and the treatment of motion sickness. Pharmacology 2013; 91: 229–41 CrossRef MEDLINE
14. Tal D, Hershkovitz D,Kaminski-Graif, Wiener G, Samuel O, Shupak A: Vestibular evoked myogenic potentials and habituation to seasickness. Clin Neurophys 2013; 124: 2445–49 CrossRef MEDLINE
15. Yates BJ, Miller AD, Lucot JB: Physiological basis and pharmacology of motion sickness: an update. Brain Res Bull 1998; 47: 395–406 CrossRef
16.Reason JT: Motion sickness adaptation: a neural mismatch model. J R Soc Med 1978; 71: 819–29 CrossRef
17. Golding JF, Mueller AG, Gresty MA: A motion sickness maximum around the 0.2 Hz frequency range of horizontal translational oscillation. Aviat Space Environ Med 2001; 72: 188–92 MEDLINE
18.Bronstein AM, Golding JF, Gresty MA: Vertigo and dizziness from environmental motion: visual vertigo, motion sickness, and drivers’ disorientation. Semin Neurol 2013; 33: 219–30 CrossRef MEDLINE
19.Golding JF, Gresty MA: Pathophysiology and treatment of motion sickness. Curr Opin Neurol 2015; 28: 83–88 CrossRef MEDLINE
20. von Gierke HE, Parker DE: Differences in otolith and abdominal viscera graviceptor dynamics: implications for motion sickness and perceived body position. Aviat Space Environ Med 1994; 65: 747–51 MEDLINE
21.Golding JF, Gresty MA: Motion sickness. Curr Opin Neurol 2005; 18: 29–34 CrossRef
22.Diels C, Howarth PA: Frequency characteristics of visually induced motion sickness. Hum Factors 2013; 55: 595–604 CrossRef MEDLINE
23. Shupak A, Gordon CR: Motion sickness: advances in pathogenesis, prediction, prevention, and treatment. Aviat Space Environ Med 2006; 77: 1213–23.
24. Takeda N, Morita M, Horii A, Nishiike S, Kitahara T, Uno A: Neural mechanisms of motion sickness. J Med Invest 2001; 48: 44–59.
25.Riccio GE, Stoffregen TA: An ecological theory of motion sickness and postural instability. Ecol Psychol 1991; 3: 195–240 CrossRef
26.Money KE: Motion sickness. Physiol Rev 1970; 50: 1–39 CrossRef MEDLINE
27.Barmack NH: Central vestibular system: vestibular nuclei and posterior cerebellum. Brain Res Bull 2003; 60: 511–41 CrossRef
28.Dieterich M, Brandt T: Functional brain imaging of peripheral and central vestibular disorders. Brain 2008; 131: 2538–52 CrossRef MEDLINE
29.Sclocco R, Kim J, Garcia RG, et al.: Brain circuitry supporting multi-organ autonomic outflow in response to nausea. Cereb Cortex 2016; 26: 485–97.
30.Yates BJ, Catanzaro MF, Miller DJ, McCall AA: Integration of vestibular and emetic gastrointestinal signals that produce nausea and vomiting: potential contributions to motion sickness. Exp Brain Res 2014; 232: 2455–69 CrossRef MEDLINE PubMed Central
31.Jarisch R, Weyer D, Ehlert E, et al.: Impact of oral vitamin C on histamine levels and seasickness. J Vestib Res Equilib Orientat 2014; 24: 281–8.
32.Takeda N, Morita M, Hasegawa S, Horii A, Kubo T, Matsunaga T: Neuropharmacology of motion sickness and emesis. A review. Acta Oto-Laryngol Suppl 1993; 501: 10–5 CrossRef
33. Jarisch R: Histaminintoleranz – Histamin und Seekrankheit. Stuttgart, New York: Georg Thieme 2013; 26–39.
34. van Esch BF, van Wensen E, van der Zaag-Loonen HJ, Benthem PPG van, van Leeuwen RB: Clinical characteristics of benign recurrent vestibulopathy: clearly distinctive from vestibular migraine and menière’s disease? Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 2017; 38: 357–63.
35. Singh P, Yoon SS, Kuo B: Nausea: a review of pathophysiology and therapeutics. Ther Adv Gastroenterol 2016; 9: 98–112 CrossRefMEDLINE PubMed Central
36.Brainard A, Gresham C: Prevention and treatment of motion sickness. Am Fam Physician 2014; 90: 41–6.
37.Ressiot E, Dolz M, Bonne L, Marianowski R: Prospective study on the efficacy of optokinetic training in the treatment of seasickness. Eur Ann Otorhinolaryngol Head Neck Dis 2013; 130: 263–8 CrossRef MEDLINE
38.Zhang LL, Wang JQ, Qi RR, Pan LL, Li M, Cai YL: Motion sickness: current knowledge and recent advance. CNS Neurosci Ther 2016; 22: 15–24 CrossRef MEDLINE
39. Spinks A, Wasiak J: Scopolamine (hyoscine) for preventing and treating motion sickness. Cochrane Database Syst Rev 2011; 6: CD002851.
40. White B: Ginger: an overview. Am Fam Physician 2007; 75: 1689–91.
e1.Li J, Zhu L, Yuan W, Jin G, Sun J: [Habituation of seasickness in adult during a long voyage]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2012; 47: 642–5 MEDLINE
e2.Graybiel A, Knepton J: Sopite syndrome: a sometimes sole manifestation of motion sickness. Aviat Space Environ Med 1976; 47: 873–82 MEDLINE
e3. Geiger J: Gleichgewichts-, Lage- und Bewegungssinn. In: Pape HC, Kurtz A, Silbernagl S, (eds.): Physiologie (7th edition). Stuttgart: Georg Thieme 2014; 756–68.
e4. Kennedy RS, Drexler J, Kennedy RC: Research in visually induced motion sickness. Appl Ergon 2010; 41: 494–503 CrossRef MEDLINE
e5. O’Hanlon JF, McCauley ME: Motion sickness incidence as a function of the frequency and acceleration of vertical sinusoidal motion. Aerosp Med 1974; 45: 366–9 MEDLINE
e6.Griffin MJ, Mills KL: Effect of frequency and direction of horizontal oscillation on motion sickness. Aviat Space Environ Med 2002; 73: 537–43 MEDLINE
e7.Golding JF. Motion sickness. Handb Clin Neurol 2016; 137: 371–90 CrossRef MEDLINE
e8.von Gierke HE, Parker DE: Differences in otolith and abdominal viscera graviceptor dynamics: implications for motion sickness and perceived body position. Aviat Space Environ Med 1994; 65: 747–51 MEDLINE
e9.Dai M, Kunin M, Raphan T, Cohen B: The relation of motion sickness to the spatial-temporal properties of velocity storage. Exp Brain Res 2003; 151: 173–89 CrossRef MEDLINE
e10.Leger A, Money KE, Landolt JP, Cheung BS, Rodden BE: Motion sickness caused by rotations about earth-horizontal and earth-vertical axes. J Appl Physiol 1981; 50: 469–77 CrossRef MEDLINE
e11. Riccio GE, Stoffregen TA: An ecological theory of motion sickness and postural instability. Ecol Psychol 1991; 3: 195–240 CrossRef
e12.Nooij SA, Vanspauwen R, Bos JE, Wuyts FL: A re-investigation of the role of utricular asymmetries in Space Motion Sickness. J Vestib Res Equilib Orientat 2011; 21: 141–51.
e13. Napadow V, Sheehan JD, Kim J et al.: The brain circuitry underlying the temporal evolution of nausea in humans. Cereb Cortex 2013; 23: 806–13 CrossRef MEDLINE PubMed Central
e14.Watanabe T, Yamatodani A, Maeyama K, Wada H: Pharmacology of alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase. Trends Pharmacol Sci 1990; 11: 363–7 CrossRef
e15.Lucot JB, Takeda N: Alpha-fluoromethylhistidine but not diphenhydramine prevents motion-induced emesis in the cat. Am J Otolaryngol 1992; 13: 176–80 CrossRef
e16.Neuhauser H, Lempert T: Vertigo and dizziness related to migraine: a diagnostic challenge. Cephalalgia Int J Headache 2004; 24: 83–91 CrossRef MEDLINE
e17.Aust G: [Equilibrium disorders and their diagnosis in childhood]. Laryngorhinootologie 1991; 70: 532–7 MEDLINE
e18.Buker TJ, Vincenzi DA, Deaton JE: The effect of apparent latency on simulator sickness while using a see-through helmet-mounted display: reducing apparent latency with predictive compensation. Hum Factors 2012; 54: 235–49 CrossRef MEDLINE
e19. Bonato F, Bubka A, Krueger WWO: A wearable device providing a visual fixation point for the alleviation of motion sickness symptoms. Mil Med 2015; 180: 1268–72 CrossRef MEDLINE
e20. Tal D, Gonen A, Wiener G, et al.: Artificial horizon effects on motion sickness and performance. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 2012; 33: 878–85 CrossRef MEDLINE
e21.Wada Y, Nishiike S, Kitahara T, et al.: Effects of repeated snowboard exercise in virtual reality with time lags of visual scene behind body rotation on head stability and subjective slalom run performance in healthy young subjects. Acta Otolaryngol 2016; 136: 1121–4 CrossRef MEDLINE
e22. Robinson KD: Die Wirkung eines reaktiven Trainings auf die Kinetosesymptomatik. Masterarbeit Sportwissenschaft; Christian-Albrechts-Universität zu Kiel 2017.
e23. Keshavarz B, Hecht H: Pleasant music as a countermeasure against visually induced motion sickness. Appl Ergon 2014; 45: 521–7 CrossRef MEDLINE
e24.Keshavarz B, Stelzmann D, Paillard A, Hecht H: Visually induced motion sickness can be alleviated by pleasant odors. Exp Brain Res 2015; 233: 1353–64 CrossRef MEDLINE
e25.Chu H, Li MH, Juan SH, Chiou WY: Effects of transcutaneous electrical nerve stimulation on motion sickness induced by rotary chair: a crossover study. J Altern Complement Med 2012; 18: 494–500 CrossRef MEDLINE
e26. Chu H, Li MH, Huang YC, Lee SY: Simultaneous transcutaneous electrical nerve stimulation mitigates simulator sickness symptoms in healthy adults: a crossover study. BMC Complement Altern Med 2013; 13: 84 CrossRef MEDLINE PubMed Central
e27. Bruce DG, Golding JF, Hockenhull N, Pethybridge RJ: Acupressure and motion sickness. Aviat Space Environ Med 1990; 61: 361–5 MEDLINE
e28.Lee A, Fan LT: Stimulation of the wrist acupuncture point P6 for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev 2009 CD003281 MEDLINE PubMed Central
e29.Müller V, Remus K, Hoffmann V, Tschöp MH, Meissner K: Effectiveness of a placebo intervention on visually induced nausea in women—a randomized controlled pilot study. J Psychosom Res 2016; 91: 9–11 CrossRef MEDLINE
e30.Weimer K, Horing B, Muth ER, Scisco JL, Klosterhalfen S, Enck P: Different disclosed probabilities to receive an antiemetic equally decrease subjective symptoms in an experimental placebo study: to be or not to be sure. Clin Ther 2017; 39: 487–501 CrossRef MEDLINE
e31.Horing B, Weimer K, Schrade D, et al.: Reduction of motion sickness with an enhanced placebo instruction: an experimental study with healthy participants. Psychosom Med 2013; 75: 497–504 CrossRef MEDLINE
e32.Hahn A, Sejna I, Stefflova B, Schwarz M, Baumann W: A fixed combination of cinnarizine/dimenhydrinate for the treatment of patients with acute vertigo due to vestibular disorders : a randomized, reference-controlled clinical study. Clin Drug Investig 2008; 28: 89–99 CrossRef
e33.Hahn A, Novotný M, Shotekov PM, Cirek Z, Bognar-Steinberg I, Baumann W: Comparison of cinnarizine/dimenhydrinate fixed combination with the respective monotherapies for vertigo of various origins. Clin Drug Investig 2011; 31: 371–83 CrossRef MEDLINE
e34.Novotný M, Kostrica R: Fixed combination of cinnarizine and dimenhydrinate versus betahistine dimesylate in the treatment of Ménière’s disease: a randomized, double-blind, parallel group clinical study. Int Tinnitus J 2002; 8: 115–23 MEDLINE
e35.Scholtz AW, Schwarz M, Baumann W, Kleinfeldt D, Scholtz HJ: Treatment of vertigo due to acute unilateral vestibular loss with a fixed combination of cinnarizine and dimenhydrinate: a double-blind, randomized, parallel-group clinical study. Clin Ther 2004; 26: 866–77 CrossRef
e36.Rubner O, Kummerhoff PW, Haase H: [An unusual case of psychosis caused by long-term administration of a scopolamine membrane patch. Paranoid hallucinogenic and delusional symptoms]. Nervenarzt 1997; 68: 77–9 CrossRef MEDLINE
e37.Hoffman T: Ginger: an ancient remedy and modern miracle drug. Hawaii Med J 2007; 66: 326–7 MEDLINE
e38.Grøntved A, Brask T, Kambskard J, Hentzer E: Ginger root against seasickness. A controlled trial on the open sea. Acta Otolaryngol 1988; 105: 45–9 CrossRef MEDLINE
e39. Domeyer JE, Cassavaugh ND, Backs RW: The use of adaptation to reduce simulator sickness in driving assessment and research. Accid Anal Prev 2013; 53: 127–32 CrossRef MEDLINE
e40. Micarelli A, Viziano A, Augimeri I, Micarelli D, Alessandrini M: Three-dimensional head-mounted gaming task procedure maximizes effects of vestibular rehabilitation in unilateral vestibular hypofunction: a randomized controlled pilot trial. Int J Rehabil Res Int Z Rehabil Rev Int Rech Readaptation 2017; 40: 325–32.
e41. Buker TJ, Vincenzi DA, Deaton JE: The effect of apparent latency on simulator sickness while using a see-through helmet-mounted display: reducing apparent latency with predictive compensation. Hum Factors 2012; 54: 235–49 CrossRef MEDLINE
e42. Russell MEB, Hoffman B, Stromberg S, Carlson CR: Use of controlled diaphragmatic breathing for the management of motion sickness in a virtual reality environment. Appl Psychophysiol Biofeedback 2014; 39: 269–77 CrossRef MEDLINE
e43. Stromberg SE, Russell ME, Carlson CR: Diaphragmatic breathing and its effectiveness for the management of motion sickness. Aerosp Med Hum Perform 2015; 86: 452–7 CrossRef MEDLINE
e44. Cha YH, Urbano D, Pariseau N: Randomized single blind sham controlled trial of adjunctive home-based tDCS after rTMS for mal de debarquement syndrome: safety, efficacy, and participant satisfaction assessment. Brain Stimulat 2016; 9: 537–44 CrossRef MEDLINE
e45.Cha YH, Deblieck C, Wu AD: Double-blind sham-controlled crossover trial of repetitive transcranial magnetic stimulation for mal de debarquement syndrome. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 2016; 37: 805–12 CrossRef MEDLINE PubMed Central
e46. Golding JF: Motion sickness susceptibility. Auton Neurosci 2006; 129: 67–76 CrossRef MEDLINE
e47. Gil A, Nachum Z, Tal D, Shupak A: A comparison of cinnarizine and transdermal scopolamine for the prevention of seasickness in naval crew: a double-blind, randomized, crossover study. Clin Neuropharmacol 2012; 35: 37–9 CrossRef MEDLINE
e48.Sherman CR: Motion sickness: review of causes and preventive strategies. J Travel Med 2002; 9: 251–6 MEDLINE
e49.Zajonc TP, Roland PS: Vertigo and motion sickness. Part II: pharmacologic treatment. Ear Nose Throat J 2006; 85: 25–35 MEDLINE
e50. Nachum Z, Shupak A, Gordon CR: Transdermal scopolamine for prevention of motion sickness: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet 2006; 45: 543–66 MEDLINE
e51. Estrada A, LeDuc PA, Curry IP, Phelps SE, Fuller DR: Airsickness prevention in helicopter passengers. Aviat Space Environ Med 2007; 78: 408–13 MEDLINE
e52.Brand JJ, Colquhoun WP, Gould AH, Perry WL: (—)-Hyoscine and cyclizine as motion sickness remedies. Br J Pharmacol Chemother 1967; 30: 463–9 CrossRef
e53.Paul MA, MacLellan M, Gray G: Motion-sickness medications for aircrew: impact on psychomotor performance. Aviat Space Environ Med 2005; 76: 560–5 MEDLINE
e54.Gordon CR, Shupak A: Prevention and treatment of motion sickness in children. CNS Drugs 1999; 12: 369–81 CrossRef
e55. Cheung BS, Heskin R, Hofer KD: Failure of cetirizine and fexofenadine to prevent motion sickness. Ann Pharmacother 2003; 37: 173–7.