Chapter 7

Motion sickness and vestibular hypersensitivity

Mallinson AI, Longridge NS.

J. Otolaryngol 2002 Dec;31(6):381-385.


ABSTRACT

Objective: Motion sickness is poorly understood, although it has been recognized for years as debilitating. Vestibular function is required for motion sickness to occur, but motion sickness can also be brought on without body motion. The aim of this study was to see if there was a correlation between caloric response and motion sickness susceptibility.

Design: One experiment was a prospective study carried out on 200 patients. A second prospective study was carried out on 121 patients.

Setting: Patients referred to our tertiary/quaternary care dizziness clinic.

Methods: In experiment 1, caloric scores in patients were correlated with symptoms of motion sickness as established by responses to a simple question. In experiment 2, caloric scores were correlated with symptomatic responses to caloric testing itself.

Main Outcome Measures: Caloric responses of the best ear were measured according to standardized caloric evaluation methods.

Results: There was no correlation between motion sickness and caloric scores. There was a significant difference in caloric scores between patients made symptomatic by calorics and those who were not.

Conclusions: The autonomic response seen in some patients is not triggered by a specific level of semicircular canal response (as measured by caloric testing). We hypothesize that (similar to space motion sickness) the trigger is a signal differential that arises between semicircular canals and otoliths and that some patients are unable to suppress this response. These patients often suffer motion sickness on a long-term basis.

KEYWORDS: calorics, electronystagmography, motion sickness, nausea, otoliths


The set of unpleasant symptoms referred to as motion sickness has been recognized as a significant problem for hundreds of years, and yet the problem remains an enigma. Maitland, in 1931, commented that the “eminently seafaring British nation is conspicuous for its neglect of the study of seasickness.” (1) Different aspects of motion sickness, such as seasickness, train sickness, or carsickness, are not abnormal and are all related. However, the de novo development or worsening of motion sickness, either as carsickness or as a symptomatic response to visual vestibular mismatch (VVM), is strongly suggestive of the development of vestibular pathology.(2) Space sickness is also a motion sickness, although, interestingly, when ranking subjects susceptible to space sickness and those susceptible to motion sickness, the least and most sensitive subjects switch positions.(3)

Motion sickness is related to vestibular function; individuals with total bilateral vestibular loss do not suffer from motion sickness. (4) However, the vestibular system influences autonomic function in several ways that have clinical implications. The control mechanisms of this influence are poorly understood, and the huge variation in individual susceptibility remains unresolved.(5) Today's understanding of motion sickness is as poor as it was at the end of the Second World War.(6)

Unfortunately, the lack of understanding is closely paralleled by the lack of effective treatment of the symptoms. Some medications, largely based on antihistamines, can suppress the symptoms of nausea, but their mode of action is not well understood.

Flack, in 1931, stated that seasickness was predominantly of vestibular origin. He observed that certain individuals were “unduly sensitive” to symptoms of nausea and vomiting, and, with these symptoms, these individuals also had a related rise in pulse and blood pressure. (7) He attributed these changes to reflex vagal stimulation and ocular muscle imbalance. Pappas et al., in 1986, also correlated autonomic sensitivity with dizziness; in a group of dizzy patients with “no demonstrable reason for dizziness,” he found a high percentage of autonomic dysfunction on Valsalva and postural tests.(8) It is now presumed that the purpose of the autonomic response influence is to help restore homeostasis.(5) This is supported by animal studies that show direct vestibular input to important centres of autoregulation (6). The clinical importance of the generalized autonomic malaise is that, in some patients, it can dominate or even override the acute vestibular disturbance and can persist long after the traditional vestibular symptoms have resolved.

Various theories have emerged over the years to try to explain the enormous variability in individual susceptibility and the widely differing symptom intensity between people. The reader is referred to reviews such as that by Oman (9) to follow the developmental progression of these theories. The contemporary view is the sensorimotor conflict theory, which states that a conflict of signals, rather than excessive vestibular stimulation, is the symptom generator. The main purpose of the conflict is to invoke either a short-term response, in the form of a postural adjustment, or a long-term adaptive process in the form of “sea legs.” Although these conflicts serve a physiologic purpose, they can still be triggered inappropriately. For instance, excessive vestibular stimulation (e.g., dancing, twirling, etc.) does not ordinarily generate symptoms, but passive exposure to real motion or even to apparent, perceived motion (e.g., in a giant-screen theatre) can generate motion sickness. (3) It has been suggested that the conflict between motor outflow and sensory return triggers conflict neurons,(9) perhaps in the vestibular system (primary vestibular afferents?), and the result is abnormal stimulation of the autonomic response, which, in some individuals, is inappropriately strong.

Do the lingering complaints seen in certain patients represent vestibular hypersensitivity or autonomic hypersensitivity? The minimal circuitry responsible for the emetic response is present in the brainstem (decorticate humans can get emesis), but we wondered why this response is triggered so violently by vestibular stimulation in some individuals and not at all in others. One of the earliest attempts to address this question was by Preber, who, in 1958, using the new technique of electronystagmographic recordings of caloric irrigation responses, found that motion sick individuals had both greater maximum eyespeed and also significantly different changes in skin resistance.(10) Lidvall, in 1962, using measurement of the slow-phase velocity of calorically induced nystagmus, concluded that the tendency to motion sickness is in direct proportion to the sensitivity of the balance organs.(11)

We wondered if motion sick patients did, in fact, have higher caloric responses than their non-motion sick counterparts or if they just had a higher “autonomic sensitivity.” The purpose of the described experiments was to address this issue.

METHODS

In a prospective study, we examined the results of 200 patients referred sequentially to our tertiary/quaternary care dizzy clinic. The caloric results of these patients were scored according to the method delineated by Barber and Stockwell.(12) Although these patients were referred for complaints of dizziness, patients with true vertigo are, by definition, suffering from unilateral pathology, and we felt justified in using the caloric score of their better ear (i.e., the nonpathologic ear) as a valid measure of “maximum caloric response.” We excluded any patient with possible bilateral disease using the exclusion criteria as set out in Table 1.

Table 1. Patient Exclusion Criteria

Any patient meeting any of the following factors, which may have influenced maximum caloric response, were excluded from the study:

  • Any history of aminoglycoside exposure
  • History suspicious of vestibular pathology affecting both sides. (A typical history that might suggest this would be two sequential attacks of acute vertigo and persistent imbalance following the second one, coupled with calorics that were bilaterally hypoactive.)
  • Any sedative medication in the previous 48 hours
  • Previous electronystagmography (as caloric scores can habituate)
  • Any spontaneous nystagmus with eyes closed (making calculation of one caloric response less accurate)

Table 2. Groupings of Patients According to Motion Sickness Susceptibility

Group 0
no complaints of motion sickness in a moving car
Group 2
extreme motion sickness (many patients actually said they were unable to read in a car for more than one or two minutes before becoming sick, so we accepted two minutes as the upper time limit for this group)
Group 1
“a little motion sick”. This group included all other patients not in the first two groups

Table 3. Groupings of Patients According to Subjective Caloric Response

Calorics 0
either denied sensation from calorics or found them pleasurable
Calorics 1
calorics tolerable, but not pleasant, but they denied nausea. (a typical sensation in this group would be the sensation of true vertigo, classically induced by caloric testing)
Calorics 2
nausea and extreme discomfort from calorics

Patients were divided into three groups based on their answer to a simple standardized question always asked by the same investigator during history taking: “How long can you read in a moving car?” The groups were delineated as outlined in Table 2. We delineated three groups: a group who was not bothered by reading in a car at all (0), a group who could not tolerate even looking at a map in a car (2), and a group in between who could read for a period of time (1). (We accepted up to 2 minutes.) Patients who could not understand our very simple question owing to a language barrier or dementia were excluded. Rare patients who had no experience as a passenger in any moving vehicle were also excluded. We compared the caloric scores of the three groups.

In our second experiment, also a prospective study, we gathered sequential data on a further 122 patients. These patients were subjected to the same inclusion/exclusion criteria, but this time we asked them after caloric testing what subjective sensation they experienced from calorics. Again, there was a wide range of subjective sensation, ranging from no feeling at all to excessive nausea and vomiting. We once again delineated three groups of patients based on their answers (Table 3). A group we called “calorics 0” either denied sensation from calorics or found them pleasurable. A group called “calorics 1” found them to be tolerable but not pleasant, but they denied nausea. (A typical sensation in this group would be the sensation of true vertigo classically induced by caloric testing.) A group called “calorics 2” reported nausea and extreme discomfort from calorics. We compared average caloric scores between groups.

RESULTS

Our first study was of 200 patients. Table 4 compares the average caloric score in each of the three groups of motion sensitivity. Caloric scores were not significantly different between the three groups of patients, although there was a suggestion of a subtle relationship between motion sickness and caloric score, with slightly higher caloric scores in more sensitive groups.

Table 4. Maximum Caloric Responses of Differing Car-sickness Groups

  No. Patients (n = 200) Maximum Caloric Score (Slow Phase Vel. in deg/sec)
Group 1 (not carsick) 123 39.5
Group 2 (a little carsick) 18 42.0
Group 3 (very carsick) 59 44.0

Table 5. Maximum Caloric Responses of Differing Caloric Sensitivities

  No. Patients (n = 122) Maximum Caloric Score (Slow Phase Vel. in deg/sec)
Calorics 0 (avg. age 53.1) 25 32.5*
Calorics 1 (avg. age 44.7) 51 41.7
Calorics 2 (avg. age 42.3) 46 46.1

* Significant at .05

Our second study was of 122 patients. Table 5 compares the average caloric score in each of these three groups. These results did show significant differences. Caloric scores in the group reporting little or no sensation from calorics were significantly lower (p <.05) than in the other two groups. We looked for age-related effects but found none as there was no significant difference in age among the three groups.

DISCUSSION

It has been postulated by Oman(9) that the symptoms of motion sickness, which can be referred to as the vestibuloautonomic response, have appeared only very recently on the evolutionary scale, since the advent and use of moving vehicles, and may represent a flaw in the developing vestibuloautonomic network. Symptoms of motion sickness can also be generated without any direct stimulus to the vestibular system, for instance, from many “old-fashioned” pursuits, such as watching clouds in the sky, water flowing in a stream, or leaves fluttering on a windy day. Today we have modern-day activities such as video games and cinemas.

In some people, motion sickness and the clinical symptom set known as VVM(2) seem to be an abnormal hypersensitivity invoked by a stimulus that is perceived as potentially destabilizing from the postural point of view. Motion sickness results predominantly from otolithic stimulation. The crucial otolithic role in the production of motion sickness was originally outlined by Preber.(10) More recently, it has been suggested that the otolith organs may be responsible for the vestibulosympathetic response,(13) and space motion sickness seems to be partly attributable to otolith asymmetry(14) or to a canal/otolith conflict.(15,16) Our data showed no correlation between caloric scores (i.e., semicircular canal [SCC] response) and motion sensitivity.

In both experiments, we took the liberty of delineating three groups of patients based on their subjective sensations to a given stimulus. We realize that we were probably dividing up a “continuum of response” rather than identifying specific groups. However, our clinical practice for some time has been to ask about motion sickness, and we have formed the impression that there is a group of patients with no complaints whatsoever from reading in a car for prolonged periods of time. Other patients state voluntarily that consulting a map or even looking down at their car radio is impossible when the car is moving. Time estimation in a patient suffering from the malaise of motion sickness seems to be extremely distorted, just as it is when a patient estimates the length of dizzy spells. As a result, when dividing our groups, we decided to divide them into “motion sick” and “not motion sick” and not to press patients to estimate how long they could read in a moving car. The only time estimate we did use was to delineate a “very sensitive group.” Many patients reported being able to “read for a minute or two,” as discussed earlier, and this was the only time quantification used. In a similar fashion, our three groups of caloric sensitivities also likely represent three segments of a continuum.

We also looked at any relationship between motion sensitivity (i.e., in everyday life) and caloric experience (i.e., vestibular sensitivity in our clinic).

We postulate that sensitivity to motion sickness (or to caloric stimulation) is a result of a signal differential at the conflict neuron level and that a vestibular counterbalance mechanism exists. Its task is to “balance” vestibular activity between vestibular structures, otolithic and SCCs. For example, a caloric (SCC) stimulus generates a corollary signal to the otoliths under ideal circumstances so that similar signals are seen from both structures at the conflict neuron level.

Many patients seem not to be sensitive to the autonomic symptoms generated by either type (calorics or motion) of vestibular stimulation. Twenty-five of the 122 patients were not bothered at all by the calorics. This group of patients had significantly lower caloric scores. Twenty of these 25 (80%) were also not carsick.

Forty-six of the 122 patients were extremely nauseated by the calorics. But of these 46 patients, 19 (41%) were not motion sick. We postulate that in this group of 19, only one arm of the counterbalance system may be functioning properly; these patients can successfully suppress the stimulus invoked by automobile rides, but stimulation of the SCC with calorics does not invoke the postulated mechanism.

The opposite limb of the pathway could potentially also be abnormal, but only 1 of our 25 patients (4%) who was not bothered by calorics was a motion sick patient.

It seems that motion sickness is closely related to caloric sensitivity, as might be expected. Twenty-two of the 122 patients were very motion sensitive, and 21 of these (95%) were also bothered by calorics. These patients seem to be unable to suppress autonomic symptoms, perhaps owing to a lack of an effective counter-balancing mechanism. Therefore, vestibular stimulation of any kind will result in a net signal at the conflict neuron level, thus invoking resultant autonomic symptoms.

Our hypothesis supports Oman's (9) theory that the “inappropriate” autonomic response seen in some patients represents a flaw in evolutionary development. In the same way, newly developed symptoms in our patients may also have the potential to create such a flaw.

CONCLUSIONS

The “functionally appropriate” autonomic response to vestibular stimulation known as motion sickness can sometimes be excessive in man. Our two experiments suggest that the autonomic trigger for these symptoms may lie in a signal differential at the conflict neuron level. We postulate the existence of a mechanism that controls this differential and hence suppresses excessive symptomatology under ideal circumstances, with the result that many patients are not bothered by motion sickness. However, in some patients, the mechanism we propose to exist may be less efficient or even absent. We describe these patients clinically as “vestibular hypersensitives,” and their vestibuloautonomic responses can sometimes be debilitating.

From an evolutionary point of view, it has been suggested that the vestibular system is vital to survival in even a tired animal as sedative medications causing drowsiness do not affect performance on posturography.(17) An animal, even though drowsy, needs a functioning balance system to find a safe refuge. Perhaps this conflict mechanism may be helpful for the animal to “phase lock” vestibulo-ocular reflex and vestibulospinal reflex responses to maintain equilibrium when hunting, swimming, foraging, or escaping capture.

REFERENCES

  1. Maitland TG. General observations on sea-sickness and the labyrinthine theory. BMJ 1931;1:171-176.
  2. Longridge NS, Mallinson AI. Visual vestibular mismatch in whiplash and Ménière's disease. In: Claussen C-F, Haid C-T, Hofferberth B, eds. Equilibrium research, clinical equilibriometry and modern treatment. Amsterdam: Elsevier Science BV, 2000:397-402.
  3. Oman CM, Lichtenberg BK, Money KE, et al. M.I.T./Canadian vestibular experiments on the Spacelab-1 mission. 4. Space motion sickness: symptoms, stimuli and predictability. Exp Br Res 1986;64:316-334.
  4. Yates BJ, Miller AD, Lucot JB. Physiological basis and pharmacology of motion sickness: an update. Br Res Bull 1998;47:395-406.
  5. Furman JM, Jacob RM, Redfern MS. Clinical evidence that the vestibular system participates in autonomic control. J Vestib Res 1998; 8:27-34.
  6. de Graaf B, Gresty MA. Foreword. Br Res Bull 1998; 47:393.
  7. Flack M. Note on seasickness. Br Med J 1931; 1:176-177.
  8. Pappas DG, Crawford W, Coghlan C. Dizziness and the autonomic disfunction syndrome. Otolaryngol Head Neck Surg 1986; 94:186-194.
  9. Oman CM. Sensory conflict theory and space sickness: our changing perspective. J Vestib Res 1998; 8:51-56.
  10. Preber L. Vegetative reactions in caloric and rotatory tests. A clinical study with special reference to motion sickness. Acta Otolaryngol Suppl (Stockh) 1958; 144:1-119.
  11. Lidvall H. Mechanisms of motion sickness as reflected in the vertigo and nystagmus responses to repeated caloric stimuli. Acta Otolaryngol (Stockh) 1962; 55:527-536.
  12. Barber HO, Stockwell CW. Manual of electro-nystagmography. 2nd Ed. St. Louis: CV Mosby and Co, 1980.
  13. Longridge NS, Mallinson AI, Denton A. Visual vestibular mismatch in patients treated with intratympanic gentamicin for Ménière's disease. J Otolaryngol 2002; 31:5-8.
  14. Yates BJ, Miller AD. Physiological evidence that the vestibular system participates in autonomic and respiratory control. J Vestib Res 1998; 8:17-25.
  15. Coats AC, Norfleet WT. Immersed false vertical room. A new motion sickness model. J Vestib Res 1998; 8:135-149.
  16. Thornton WE, Biggers WP, Pool SL, et al. Electronystagmography and audio potentials in space flight. Laryngoscope 1985; 95:924-932.
  17. Gill C, Mallinson AI, Longridge NS. Effects of dimenhydrinate on computerized dynamic posturography. J Otolaryngol 2000; 29:337- 339.