Motion sickness in migraine and vestibular disorders

Motion sickness is a syndrome provoked by sensory conflict that involves the vestibular system with symptoms resembling those of common neuro-otological disorders including vestibular neuritis (VN) and vestibular migraine (VM). By contrast, it is generally believed that bilateral vestibular failure (BVF) causes reduced motion sickness susceptibility. We investigate differences between these conditions with a single protocol using validated objective experimental (off-vertical axis rotation, OVAR1) and validated patient-centred measures of motion sickness susceptibility.2 

Five groups were studied:

1. Normal healthy controls ( n=12; mean age 51, SD 17.2; 4/12 women).

2. VN (history of acute vertigo without neurological features or hearing loss; none treated with steroids acutely; positive head thrust test; spontaneous unidirectional horizontal nystagmus; acute caloric canal paresis >30%, mean canal paresis repeated in chronic phase after 6 weeks was 38% (SD 31); n=12; disease duration range 10–33 months; mean age 45, SD 15.3; 5/12 women).

3. BVF (absent caloric or rotational responses; confirmed in chronic phase; n=8; mean age 51, SD 11.5; 3/8 women).

4. VM (recurrent episodic vestibular symptoms in association with migraine according to published criteria with no vestibular test abnormalities3; n=12; mean age 45, SD 15.3; 11/12 women).

5. Migraine without vestibular symptoms ( M ; recurrent headaches meeting International Headache Society (IHS) 2004 criteria; with/without aura but with no significant vestibular symptoms3; n=12; mean age 41, SD 13.6; 8/12 women.



Two groups of patient with migraine were studied (one with vestibular symptoms, VM, and one without vestibular symptoms, M) to determine whether the presence of vestibular symptoms in the setting of migraine influences motion sickness susceptibility. The normal controls and the migraine group were screened for vestibular symptoms but did not undergo formal vestibular testing.

Participants were …

requirements for dissemination in time and space, while retaining high specificity. [1][2][3] Among patients with CIS in this study who ultimately developed CDMS, the mean time to diagnosis of MS halved from 12 months with the 2001 criteria to 6.2 months with the 2010 criteria, a time gain of 16.9 months compared with mean time to CDMS. The time gain using the McDonald criteria was significantly greater in this study than in a previous hospital-based series. 4 However, in that study spinal imaging was not performed and not all patients had postcontrast T1-weighted scans or follow-up MRI, both important for demonstrating dissemination in time.
The McDonald criteria identify a significant number of patients with CIS with MRI evidence of dissemination of time and space in the absence of further clinical events, 5 and the number has increased as the criteria have been revised. These patients probably have a form of MS that remains largely subclinical. Given the relatively high frequency of MRI-only MS (almost a third of those diagnosed using the 2010 criteria), the possibility arises that the new diagnostic criteria are identifying a milder form of MS than in the past when the diagnosis was based on clinical course alone. There is the potential for the natural history of relapse-onset MS to be being favourably modified by changes to the diagnostic criteria, independent of any effect of diseasemodifying treatments. 7 These issues are important when counselling patients with CIS about prognosis and in deciding whether to initiate treatment.
One potential limitation of our study is an over-representation of patients with optic neuritis, which may have a more benign prognosis that other CIS types. 8 However, almost 80% of patients with optic neuritis had baseline MRI abnormalities, indicating a group at high-risk for developing MS.
In conclusion, the McDonald criteria allow MS to be diagnosed sooner and more often in patients with CIS. While the McDonald criteria facilitate an earlier diagnosis of MS, up to a third of patients with CIS who satisfy the 2010 criteria do not have further clinical events, at least in the medium-term.

Motion sickness in migraine and vestibular disorders
Motion sickness is a syndrome provoked by sensory conflict that involves the vestibular system with symptoms resembling those of common neuro-otological disorders including vestibular neuritis (VN) and vestibular migraine (VM). By contrast, it is generally believed that bilateral vestibular failure (BVF) causes reduced motion sickness susceptibility. We investigate differences between these conditions with a single protocol using validated objective experimental (off-vertical axis rotation, OVAR 1 ) and validated patient-centred measures of motion sickness susceptibility. 2 Five groups were studied: Two groups of patient with migraine were studied (one with vestibular symptoms, VM, and one without vestibular symptoms, M) to determine whether the presence of vestibular symptoms in the setting of migraine influences motion sickness susceptibility. The normal controls and the migraine group were screened for vestibular symptoms but did not undergo formal vestibular testing.
Participants were seated in a motorised chair (Neurokinetics Inc, Pittsburgh, USA). The torso, legs, feet and head were restrained. The chair took 60 s to reach a constant velocity of 72°/s (0.2 Hz) on a vertical axis in the light, then tilted over 20 s to an angle of 18°from earth vertical. Velocity and tilt remained constant until the chair was stopped, when it was brought back to rest and earth vertical over 30 s.
At every minute during rotation, participants rated nausea on a scale from: 1=no symptoms, 2=initial symptoms but no nausea, 3=mild nausea, 4=moderate nausea. Rotation continued until participants Sickness Rating (SR) of 4 or to a maximum of 20 min. To quantify recovery, SRs were also obtained at 1, 2, 3, 4, 5, 10, 15, 20 and 30 min after motion end point.
Individual motion sickness susceptibility was reported before rotation using the Motion Sickness Susceptibility Questionnaire, short form (MSSQ-Short). 2 Briefly, participants were asked to report retrospectively the frequency of experiencing nausea on various forms of transport/ motion. Those in the VN, BVF and VM groups also scored themselves after the onset of vestibular disease. Figure 1A shows the mean Sickness Rating scores against time during rotation for all five groups ( p<0.001, analysis of variance). Participants who did not reach SR 4 were allocated values of 20 min for analysis. All patients with BVF tolerated motion to 20 min with no scores of SR 4 reported, and 38% patients with BVF remained at SR 1 (no nausea) for the whole test duration with no participant in any other group demonstrating this effect.
Comparing the time to recovery (no nausea) after rotation ceased, there is a significant difference between groups (p<0.001), attributable to the difference between VM/M and the other groups. There was no relationship between side of lesion in the VN group and time to SR 4 (p=0.21, Kruskal-Wallis), and no correlation between MSSQ and canal paresis (p=0.31).
Our study, using validated experimental and questionnaire paradigms, confirms that individuals with BVF report and demonstrate low levels of motion sickness susceptibility that were not present prior to disease acquisition. Although all BVF individuals could withstand the 20 min rotation, some were not completely immune, perhaps because of residual vestibular function. Some degree of otolith function could still be present since caloric and rotational tests primarily assess horizontal semicircular canal function. It is also known that visual stimuli can provoke symptoms, 4 and since the experiment took place in the light, this may be an alternative explanation.
Seasickness commonly has a negative impact on leisure and tourism activities such as sailing and cruise travel. Ability to identify positive aspects of a condition can predict outcome in chronic conditions. We therefore recommend that patients with BVF be advised of this beneficial aspect of their condition. Those with VN, a unilateral lesion, do not share this beneficial effect.
There is an overall increase in motion sickness susceptibility of patients with VM but this is not different from migraine. This contrasts with findings of previous studies that have shown higher susceptibility scores in questionnaires in VM than migraine in general. 5 Unlike any previous study, the questionnaire data from our study are supported by the experimental data. Some individuals with VM reported reductions in susceptibility, suggesting some heterogeneity in the underlying pathomechanism, which could also explain some observed differences between ours and previous studies.
In conclusion, BVF reduces motion sickness susceptibility, and this can be regarded as a beneficial effect of this disorder, but a unilateral lesion is insufficient to trigger such a reduction. VM and migraine similarly enhance motion sickness susceptibility profiles.
Contributors LM was involved in design and conceptualisation of the study; analysis and interpretation of the data; drafting and revising the manuscript for intellectual content. FC, SC, JFG and AB were involved in design and conceptualisation of the study; analysis and interpretation of the data; revising the manuscript for intellectual content. QA was involved in design and conceptualisation and revising the manuscript. MAG was involved in design and conceptualisation of the study; revising the manuscript for intellectual content.

Patient consent Obtained.
Ethics approval Imperial College Healthcare.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Original data are available on request.
Open Access This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use,

INTRODUCTION
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system that is usually diagnosed in a patient's 20s or 30s and is more common in women than in men. 1 Given this typical patient profile, many patients with MS are women in their reproductive years. None of the currently approved disease-modifying therapies (DMTs) for patients with MS are recommended for use during pregnancy. Furthermore, all of these medications have been given a pregnancy category B, C, D or X by the US Food and Drug Administration, indicating that in the best case (category B), animal studies have failed to identify potential harmful effects of the medication but long-term safety data in humans are not available or, in the worst case (category X), studies in human patients or animals have identified risks of negative birth outcomes associated with exposure during pregnancy and the medication should not be used by patients who are or may become pregnant. 1 Patients should be informed of the potential hazards of medication use during pregnancy, and discontinuation should be considered if patients become pregnant during treatment. However there are few recommendations about when to stop medication before becoming pregnant. Thus, some patients may be taking a DMT when they become pregnant, thereby leading to fetal exposure. In addition, unplanned pregnancies can occur during treatment with DMTs, increasing the chance of accidental exposure to the fetus. Given these potential challenges, counselling patients about the possible risks of DMT use during pregnancy is an important part of disease management for patients with MS.
Reliable data on the effects of DMTs on pregnancy outcomes are difficult to obtain. Randomised, controlled trials of the potential teratogenic effects of DMT exposure during pregnancy are unlikely to be conducted given the ethical concerns of such a trial. In addition, prospective observational studies or registries require many years to reach a sample size that affords the statistical power to detect a difference in the relevant risk compared with the general population or untreated patients. Consequently, an analysis of prospective cases from existing pharmacovigilance databases may be an appropriate alternative to help guide decision-making in this population.

METHODS
The objective of the present analysis was to review pregnancy outcomes in patients who were exposed to interferon beta-1b (Betaferon/Betaseron; Bayer HealthCare Pharmaceuticals) during pregnancy. Worldwide pregnancy cases reported to Open Access Scan to access more free content