Motion Sickness

Etiology

Motion sickness is typically triggered by low-frequency lateral and vertical motion (example: air, sea, road transportation) or by virtual simulator motion (video games, virtual simulators).[4]  The sensory conflict and neural mismatch theory is the most widely accepted theory for explaining motion sickness.[1]  It describes the conflict that occurs between the visual, vestibular and somatosensory systems resulting from real or virtual motion. Afferents from the vestibular apparatus arrive at the vestibular nuclei of the brainstem, which also receives inputs from the visual and proprioceptive systems.[5] Efferent projections then reach the temporoparietal cortex via the posterolateral thalamus, triggering autonomic reactions and the vomiting center. When there is a discrepancy between actual versus expected patterns of vestibular, visual, and kinesthetic inputs, it initiates the cascade of motion sickness symptoms.[3]

Epidemiology

Motion sickness is inducible in almost all people with a functioning vestibular apparatus and a sufficient provocative stimulus.[3]  Patients with a total loss of labyrinthine function are immune to motion sickness.[6]  

Individual susceptibility varies.  Certain characteristics associated with motion sickness include[3][5][2]:

• Sex – women are more susceptible than men 
• Age – motion sickness begins around age 6 and peaks at age 9 - there is a subsequent decline during teen years due to habituation
• Elderly people are the least susceptible to motion sickness
• Fitness level – cross-sectional studies show increased susceptibility in persons with high levels of aerobic fitness; there have been suggestions that this is due to a more reactive autonomic system
• Medical conditions – patients with vertigo, vestibular pathology, Meniere’s disease, and migraines are at elevated risk
• Hormones – fluctuations during pregnancy and the menstrual cycle increase susceptibility

Pathophysiology

Motion sickness tends to occur when the input from the proprioceptive, vestibular and visual are mixed or in conflict.

History and Physical

The symptoms of motion sickness can be diverse, ranging from the most common, nausea and vomiting, too cold sweating, pallor, headache, drowsiness, yawning, loss of appetite and increased salivation.[2][6]  Typically, an inciting event or exposure to an unfamiliar motion precedes symptoms of motion sickness.  The constellation of symptoms known as “sopite syndrome” refers to profound drowsiness and fatigue that can persist for hours to days following exposure. It may appear to untrained observers as apathy, boredom, irritability and personality changes.

Less commonly, severe symptoms may occur.  These include the inability to walk, incapacitation, postural instability, intractable retching, and social isolation.  The failure to diagnose the early and more mild symptoms of motion sickness may delay treatment.[7]

Evaluation

Motion sickness is a clinical diagnosis made with a thorough history and physical.  Generally, further workup through laboratory or radiographic testing is not necessary if a patient has a typical presentation or a previous history of motion sickness. 

In a patient with an abrupt onset of motion sickness symptoms, workup for migraine headaches may be indicated, as they have shown to be closely associated.  The prophylactic treatment of migraines may not only decrease headaches but can improve associated dizziness and motion sickness symptoms.[8]

It is crucial to identify the life-threatening causes for motion sickness like basilar artery occlusion. Sometimes the initial presenting symptom for basilar artery occlusion is dizziness and motion sickness. Usually, these patients have other associated symptoms which are sudden in onset like diplopia, dysarthria, dysphagia and drop attacks. When suspecting basilar artery occlusion, it is vital to do CT angiography to rule out basilar artery occlusion. Once it is ruled out, then one can look for benign paroxysmal positional vertigo, vestibular migraine, vestibular neuritis, etc. 

Treatment / Management

Behavioral Management

Behavioral countermeasures against motion sickness are among the most effective treatments.[2]

Short-term maneuvers include[2][9][10][11]:(A1)

• Body postural changes: reducing head movements, restraining movement of the head, shoulders, hips, and knees 
• Avoiding reading in moving vehicles
• Sitting in a forward facing seat, a front seat, or actively steering the vehicle 
• Focusing on a stable horizon 
• Controlled, mindful breathing
• Avoiding nicotine (if the patient is a smoker)
• Listening to pleasant music 
• Avoiding travel in turbulent conditions or with poor visibility

Habituation is the most effective long-term countermeasure. It lacks the adverse effects of pharmacotherapy, such as drowsiness and blurred vision.  Unfortunately, this time-consuming approach may last many weeks, as evidenced by the military-run motion sickness desensitization programs created to treat pilots in which anti-motion sickness medications are contraindicated. These programs are designed for long-term success, with rates exceeding 85%. In the general population, with continuous exposure, the symptoms of motion sickness generally resolve within 24 to 72 hours.  However, if the intervals between exposure are greater than one week, long-term habituation may not be achieved.[2]

Alternative treatments include the use of ginger, which acts as an antagonist at the 5-HT3 receptor that plays a role in vomiting.[5][12]  Acupressure bands at the P6 or Neiguan point on the anterior wrist have shown benefit in the treatment of nausea and vomiting in a limited number of trials. However, more data is needed.[13][14](A1)

Pharmacologic Therapy

Medications for the treatment of motion sickness are only partially effective and may have unwanted side effects.  They are most effective when used prophylactically or at the early onset of symptoms. Patients should be encouraged to first trial the medications first in a safe environment before using during work or travel. Medications can subdivide into categories: anticholinergic, antihistamine and sympathomimetic.[2]

Anticholinergic

• Scopolamine – the most effective agent presently, acting as a nonselective antimuscarinic by inhibiting input to the vestibular nuclei.[14]  It has less sedation than antihistamines.  It is available by prescription in the USA as a transdermal patch. The patch should be applied to the mastoid at least 4 hours before travel, with effects lasting for 72 hours.  Common side effects include dry eyes/mouth, photosensitivity, blurred vision, dizziness, headache, and sedation.  This drug is not recommended for children under 12 years old and used with caution in the elderly.  Rare side effects include acute angle glaucoma, confusion, contact dermatitis, and urinary retention.
  • Intranasal scopolamine has been of particular interest in recent studies conducted by NASA and the Naval Aerospace Medical Research Laboratory, to address the significant discomfort of space motion sickness in astronauts.  The nasal gel formulation of scopolamine has been found to have a more rapid absorption and the onset of action than its transdermal or oral counterparts, with a more predictable efficacy and favorable side effect profile.[15][16]  Studies have reported no significant cognitive or sedative effects, which may offer a promising solution to both astronauts operating in highly technical environments and also the general public. 
(A1)

Antihistamines

H1 receptor antagonists decrease the firing of afferent nerves of the semicircular canals that are triggered by the histaminergic system in the hypothalamus.[14] Unfortunately, H1 antagonists are highly sedating. Studies have determined the less sedating second-generation antihistamines to be ineffective in treating motion sickness, likely due to mediation via peripheral versus central receptors.[17](A1)

• Diphenhydramine– First generation antihistamine that also possesses anticholinergic properties.  It is available in oral (over the counter) and injectable preparations.  Sedation is common.  Other common side effects include dry mouth/eyes, blurred vision, and photosensitivity.  Confusion and urinary retention occur rarely. 
• Cyclizine – First generation antihistamine available orally over the counter.  It has shown similar efficacy to diphenhydramine, but with slightly less sedation and more direct action on the stomach in treating gastrointestinal symptoms.[18]  It is FDA approved for adults and children over 6 years old. 
• Meclizine – First-generation antihistamines are available orally over the counter.  They are approved for patients 12 years and older but are highly sedating.
• Cinnarizine – A first-generation antihistamine with higher efficacy in treating motion sickness symptoms with the least amount of drowsiness.  This drug is not available in the USA or Canada due to its calcium channel blocking properties but is still widely used in Mexico and Europe. 
• Promethazine – First generation antihistamine with anticholinergic properties.  It is prescription-only, available in oral, rectal, and intramuscular preparations.  Promethazine has also been studied in space motion sickness, where intramuscular injections are commonly used.  Studies suggest, however, its side effects may impair operational performance.[19] Combination therapy with caffeine has proven effective in counteracting some side effects of promethazine.[20]
(A1)

Sympathomimetic

• Dextroamphetamine has been shown to act synergistically with anticholinergics and antihistamines by stimulating the dopaminergic and noradrenergic pathways.[14] Studies have demonstrated dextroamphetamine and scopolamine to be the most effective anti-motion sickness combination as they act through different pathways and their respective side effects cancel each other out.[2] However, the risk of drug dependence has to be a consideration.  The use of sympathomimetic drugs for motion sickness is mainly during space flights.[14]
(B3)

Therapies Not Recommended

• Dopamine antagonists such as metoclopramide have not consistently demonstrated efficacy in the treatment of motion sickness.  Although metoclopramide is an effective antiemetic and promotes gastric emptying, studies have not demonstrated efficacy in the treatment of motion sickness.[20]
• Serotonin (5-HT3) receptor antagonists like ondansetron are potent antiemetics and inhibit gastric tachyarrhythmia but are not effective in preventing motion sickness symptoms.[20]

Medications For Pregnant Patients

Pregnant women may have increased susceptibility to motion sickness. Medications used for morning sickness are felt to be safe for use in motion sickness, including meclizine and dimenhydrinate.  The FDA classifies these as category B in pregnancy.  Scopolamine and promethazine are Class C in pregnancy.

Differential Diagnosis

Vestibulopathy

• Vestibular conditions (including, but not limited to, benign paroxysmal positional vertigo, vestibular migraine, vestibular neuritis, ototoxic medication exposure) may present with similar symptoms of motion sickness as they can increase visual-vestibular conflict.  This etiology should be a consideration in a patient with new-onset motion sickness without explanation.  These patients may require referral to a neurologist or vestibular specialist.

Cerebrovascular Event

• Patients with risk factors for a cerebrovascular accident should have a high index for suspicion, especially in new-onset, severe symptoms with no history of motion sickness in the past.

Prognosis

Individuals with a history of motion sickness will have a high likelihood of recurrence in the presence of a provocative stimulus unless able to achieve habituation. Due to the wide variation of symptom severity, patients and providers should weigh the risks and benefits of pharmacotherapy on an individual basis. 

Complications

The majority of individuals with motion sickness have mild to moderate symptoms that are self-limited.  Once the triggering motion ceases, symptoms often resolve entirely within 24 hours.[5]  The minority of patients whose condition progresses to extreme nausea and vomiting may result in dehydration, electrolyte disturbances or esophageal tears.