Keywords:
Headache - Migraine Disorders
Palavras-chave:
Cefaleia - Transtornos de Enxaqueca
INTRODUCTION
Vestibular migraine (VM) is defined by recurrent vestibular symptoms occurring in
at least 50% of migraine attacks, lasting hours to days. Less than 10% vestibular
migraine patients meet diagnostic criteria for brainstem aura. Vestibular symptoms
can be more limiting than headache. VM remains an underdiagnosed condition. Knowledge
about VM is largely extrapolated from migraine, and studies specifically addressing
VM are scarce.
EPIDEMIOLOGY
Understanding the epidemiology of VM is limited by lack of biological markers, and
by the fact that the diagnosis is established solely on clinical grounds. Using current
criteria, vestibular migraine would be the most common cause of vertigo, with a prevalence
between 1 to 2.7% of the adult population[1]. Age at onset of vestibular migraine (38) is usually later than migraine (23)[2]. Patients may not present headaches for many years, until the onset of vestibular
symptoms[3]. VM is more prevalent in women (4:1)[1] and approximately two thirds of patients will report a family history of migraine[2].
PATHOPHYSIOLOGY
Pathophysiology of vestibular migraine remains poorly understood ([Figure 1]). In addition to trigeminovascular dysfunction, considered the primary migraine
mechanism, vestibular hyperexcitability, calcium voltage channel dysfunction, temporoparietal
structural and functional changes also appear to play a role in VM.
Figure 1 Vestibular migraine mechanisms (adapted from Huang TC - Vestibular migraine: An update
on current understanding and future directions)[3].Possible mechanisms involved in the pathogenesis of vestibular migraine. Abnormal
sensory modulation or integration within the thalamo-cortical network could result
in dizziness and spatial disorientation. Hyperactivity within the trigeninovascular
system and nociceptive brainstem centers could result in headache. Altered activity
in the vestibular system could lead to transient vestibulo-ocular dysfunction or vestibular
hypersensitivity associated with migraine features.
Thalamocortical network disfunction
Thalamocortical network dysfunction is well established in migraine. (Goadsby, 2017).
Thalamic nuclei activation modulates trigeminovascular input and other nociceptive
information. Cortical hyperexcitability lowers migraine attack threshold in some patients[4]. VM patients are more sensitive to motion due to increased sensitivity to stimuli,
and also display a lower threshold for perception of changes in body position, and
more discomfort after oculocephalic reflex maneuvers, as well as more spatial perception
errorsactivation[5]. Ballet dancers, on the other hand, display higher threshold for vestibular output,
and less cerebellar gray matter, suggesting that exercise interferes with vestibular
processing[19].
Vestibular hyperexcitability
Painful trigeminal stimulation in migraine patients elicits new or worsening pre-existing
peripheral nystagmus, suggesting vestibular hyperexcitability and predisposition to
vertigo. Labyrinth dysfunction may be explained by ion calcium channel dysfunction,
vasospasm, or central vestibular system dysfunction through brainstem nuclei activation[5].
Voltage gated calcium channels (VGCC)
Clinical similarity between vestibular migraine and episodic type 2 ataxia, suggests
shared pathophysiological mechanisms, such as voltage-gated calcium channel (CACNA1A)
changes, also found in familial hemiplegic migraine[3].
Structural/functional temporoparietal changes
Temporoparietal structural and functional changes may also play a role in VM. FDG-PET
studies during VM attacks show increased metabolism in these areas, underscoring the
role of the vestibulo-thalamo-cortical pathway in VM[6].
DIAGNOSTIC CRITERIA
VM diagnosis is based on clinical criteria.
Diagnostic criteria of VM[7],[8]:
Vestibular migraine [International Classification of Headache Disorders (ICHD-3) and
International Classification of Vestibular Disorders (ICVD)]
-
At least five episodes fulfilling criteria C and D;
-
Current or past history of migraine with or without aura.
-
Vestibular symptoms of moderate to severe intensity, lasting between five minutes
and 72 hours;
-
At least 50% of episodes are associated with at least one of the following three migrainous
features:
-
Headache with at least two of the following four characteristics:
-
Photophobia and phonophobia
-
Visual aura
Probable vestibular migraine (ICVD)
-
At least five episodes of vestibular symptoms of moderate to severe intensity, lasting
five minutes to 72 hours;
-
Only one of the B and C criteria for vestibular migraine is fulfilled (migraine history
or migraine features during the episode);
-
Not better accounted for another vestibular or ICHD diagnosis, and presence of vestibular
symptoms defined by Bárány Society’s Classification of Vestibular Symptoms, including[9]:
-
spontaneous vertigo;
-
internal vertigo, a false sensation of self-motion;
-
external vertigo, a false sensation that visual surrounding is spinning or flowing.
-
positional vertigo, occurring after head position changes;
-
visually-induced vertigo, triggered by complex or large moving visual stimulus;
-
head motion-induced vertigo, occurring during head motion;
-
head motion-induced dizziness with nausea; dizziness is characterized by sensation
of disturbed spatial orientation; other forms of dizziness are currently not included
in the classification of vestibular migraine.
An isolated symptom is sufficient to characterize an episode.
Vestibular symptoms are rated as “moderate”, interfering but do not hindering daily
activities, and as “severe” when daily activities must be interrupted[9].
The criteria underscore the importance of a directed clinical history of vertigo to
accurately identify symptoms, leading to diagnosis.
CLINICAL PRESENTATION
Vertigo can antecede or may occur during, after, or even independently of the migraine
attack, occurring in up to 30% of episodes, rendering diagnosis more challenging ([Figure 2]).
Figure 2 Vestibular symptoms during a migraine attack (adapted from Stolte B - Vestibular
Migraine)[9].
Many patients consider vestibular symptoms as the most disabling feature of VM. Most
patients report more than one vestibular symptom during attacks[1], and up to 30% of VM episodes may be unaccompanied by headache.
Episode duration follows the “30% rule”[10].
Auditory symptoms were reported in 40% of VM patients. the most common being sensation
of blocked ear. Since symptoms are nonspecific, they were not included in the diagnostic
criteria[3]. Presence of these symptoms may lead to misdiagnosis, especially of Ménière’s disease.
Other VM symptoms include nausea, vomiting, prostration, imbalance and motion sickness[9]. Triggers do not differ from migraine: sleep deprivation, stress, menstrual cycle,
food, weather changes and light.
Psychiatric comorbidities are very common in VM patients (50% of cases), similar to
migraine; most common symptoms are depression, anxiety and insomnia[1].
Several findings on physical examination, none specific, can confound diagnosis, such
as presence of spontaneous or positional nystagmus consistent with central or peripheral
nystagmus. Nystagmus can be evoked by positional maneuvers, and are slower and more
persistent compared to BPPV nystagmus. [Table 1] depicts the main neurological features, during and between VM attacks. Physical
exam may be normal.
Table 1
Clinical findings in VM patients (Adapted from Sohn JH - Recent Advances in the Understanding
of Vestibular Migraine)[10]
|
Neurological findings
|
|
Between attacks
|
|
Gaze-induced nystagmus (27%) and spontaneous nystagmus (11%)
|
|
Persistent positional nystagmus and positional nystagmus (12-28%)
|
|
Vertical (48%) and/or horizontal (22%) saccadic pursuit
|
|
Subtle saccadic pursuit 20-63% on follow-up study (over 9 years)
|
|
Unilateral canal paresis (8-22%)
|
|
Bilateral vestibular failure (11%)
|
|
Low-frequency, mild cochlear loss (3-12%()
|
|
Mild bilateral sensorineural hearing loss (18%) on follow-up study (over 9 years)
|
|
During Attacks
|
|
Spontaneous nystagmus (19%) and nystagmus elicited by horizontal headshaking (35%)
|
|
Low-velocity, sustained, central positional nystagmus (100%)
|
|
Pathologic nystagmus with spontaneous or positional nystagmus (70%)
|
|
Central vestibular dysfunction (50%)
|
|
Peripheral vestibular dysfuntion (15%)
|
|
Unclear, mixture (35%)
|
DIFFERENTIAL DIAGNOSES
The main differential diagnosis is Ménière's disease. Symptom duration is similar,
ranging from 20 minutes to 12 hours, accompanied by tinnitus and hearing loss. Low
frequency hearing loss seen in more advanced stages of Ménière (inverted U peak in
audiometry) may aid in diagnosis. Brain MRI can be useful to rule out other causes
of vestibular symptoms, and to disclose endolymphatic hydrops, found in, 90% of Ménière's
cases[12]. Migraine prevalence is twice more common in Ménière's disease patients[11].
Benign paroxysmal positional vertigo (BPPV) is another common cause of recurrent acute
vertigo. Differentiation of BPPV and VM is difficult, and may only be possible by
the finding of specific findings in neurological examination compatible with BPPV.
Symptom duration may allow differentiating these conditions. In BPPV, symptoms last
for weeks to months, and recur only after months or years. In VM, on the other hand,
symptoms last hours to days, and recur several times a month or year[10]. Positional maneuvers are key to differentiate both conditions. Additionally, BPPV
and migraine can coexist[12].
Migraine with brainstem aura is commonly confused with VM, but has different diagnostic
criteria. Although different, both can coexist. Migraine with aura must present two
or more brainstem symptoms and/or signs (vertigo, hearing loss, dysarthria, tinnitus,
diplopia, gait imbalance and decreased level of consciousness). Symptoms must be reversible,
lasting from five to 60 minutes. Less than 10% of VM patients meet criteria for brainstem
aura. Diagnostic criteria for brainstem aura according to ICHD-3 are the following:
-
Attacks fulfilling criteria forMigraine with auraand criterion below
-
Aura with both of the following:
Notes:
aDysarthria must be distinguished from aphasia.
bVertigo does not include and should be distinguished from dizziness.
cThis criterion is not fulfilled by sensation of a blocked ear.
dDiplopia does not include (or exclude) blurred vision.
eGlasgow Coma Scale (GCS) score assessed during admission; alternatively, deficits
described by the patient allow GCS estimation.
fWhen motor symptoms are present, code as 1.2.3Hemiplegic migraine.
Former phobic vertigo and current PPPV (persistent perceptual postural vertigo) should
also be included in the differential diagnosis. Symptoms in these cases are nonspecific,
such as empty headedness and malaise[13]. Episodes are recurrent, but tend to be more situational, leading to avoidance behavior.
PPPV is commonly associated with psychiatric diagnoses, such as phobic anxiety disorder
or depression and catastrophic thinking.
Transient ischemic attack should be included in the differential diagnosis, especially
if the initial episode is of sudden onset and if there is associated imbalance, and
in older patients with cardiovascular comorbidities[9].
Type 2 episodic ataxia, although rare, should be included in the differential diagnosis.
Type 2 episodic ataxia is a genetically inherited disease, associated CACNA1A channel
changes, and is characterized by recurrent and disabling episodes of imbalance, vertigo
and ataxia, that are induced by physical exertion or emotional stress. Episodes can
be accompanied by headache in up to half of the cases. Outside attacks patients may
display downbeat nystagmus. Head MRI may show mild anterior cerebellar vermis atrophy.
Acetazolamide is the usual treatment[14]. Genetic testing confirms diagnosis.
[Table 2]displays differential diagnoses for vestibular migraine.[9]
Table 2
Differential diagnosis of vestibular migraine (adapted from Stolte B - Vestibular
Migraine)
|
1. Ménière’s disease
|
|
2. Somatoform vertigo (primary or secondary that develops after vestibular vertigo
|
|
3. Benign paroxysmal positional vertigo (BPPV)
|
|
4. Posterior circulation transient ischemia (TIA)
|
|
5. Syncope or orthostatic hypotension
|
|
6. Vestibular paroxysmia
|
|
7. Episodic ataxia type 2
|
Diagnosis of vestibular migraine is based on clinical findings. In specific situations
where clinical overlap between diagnoses is suspected, additional tests may be requested.
Audiometry, electrocochleography and caloric testing are normal in most VM patients,
when performed outside attacks[15]. In Ménière's disease , caloric testing, is usually abnormal and audiometry shows
an inverted U peak in more advanced stages.
TREATMENT
Few studies report specific treatment recommendations for vestibular migraine. A search
of clinical trials in February 2022 showed 18 clinical trials, six of which were stiil
in the recruitment phase, five were completed and two were interrupted. From a practical
standpoint, experts recommend the same treatment as for migraine. Antiemetics may
be beneficial during attacks
A randomized clinical trial showed a possible superiority of zolmitriptan[16] in reducing vertigo intensity from severe/moderate to mild or absent two hours after
medication intake. Design limitations and limited study power do not allow a definite
conclusion, and further studies are needed.
A rizatriptan trial for vestibular migraine was initiated in UCLA in late 2021. The
trial is still underway and results are not yet available.[17] A 2010 clinical trial using rizatriptan showed reduction in motion-induced sickness
in patients with migraine, but this trial was not specifically designed for patients
with vestibular migraine. A retrospective chart review suggested that nortriptyline
and topiramate were effective in preventing VM[18]. Confirmatory clinical trials are lacking.
Non-pharmacological treatment - vestibular rehabilitation - is usually recommended,
and is probably effective, since there seems to be a protective effect of ballet training
on modulation of the vestibular system in dancers, rendering them less sensitive to
movement induced vertigo, as previously mentioned[5],[19].
Although avoiding exposure triggers and caffeine cessation are often recommended,
these measures display low efficacy on VM and may negatively impact on quality of
life, and, therefore, should not be recommended.
[Table 3]shows a summary of the main abortive and preventive medications used in vestibular
migraine, in addition to non-pharmacological treatment.
Table 3
Treatment options for Vestibular Migraine (adapted from Sohn JH. Recent Advances in
the Understanding of Vestibular Migraine)[10].
|
Acute medications
|
|
Zolmitriptan
|
2.5mg oral
|
Randomized controlled trial
|
|
Rizatriptan
|
10mg oral
|
Randomized controlled trial, motion sickness
|
|
Prophylatic medications
|
|
Propranolol
|
160mg, 40-60mg
|
Retrospective cohort analysis
|
|
Propranolol/venlafaxine
|
40-160mg/27.5-150mg
|
Prospective, randomized, controlled clinical trial
|
|
Metoprolol
|
150mg, 100-200mg
|
Retrospective cohort analysis
|
|
Amitryptiline
|
100mg, 10mg
|
Retrospective cohort analysis
|
|
Nortriptyline
|
27-75mg
|
Open-label, chart review
|
|
Valproic acid
|
600mg, 600mg
|
Retrospective cohort analysis, cohort study, vestibulo-ocular reflex
|
|
Topiramate
|
50mg, 50-100mg
|
Retrospective cohort analysis, open-label chart review
|
|
Lamotrigine
|
75mg
|
Retrospective cohort analysis
|
|
Flunarizine
|
5mg, 5-10mg, 5-10mg
|
Retrospective cohort analysis, retrospective
|
|
Cinarizine
|
37.5-75mg
|
Retrospective, open-label
|
|
Cinarizine + dimenhydrate
|
20mg and 40mg
|
Observational trial
|
|
Acetazolamide
|
500mg
|
Retrospective cohort study
|
|
Magnesium
|
400mg
|
Retrospective cohort analysis
|
|
Clonazepam
|
0.25-1mg
|
Retrospective cohort analysis
|
|
Non-medical treatments
|
|
Vestibular rehabilitation
|
5 therapy sessions over nine weeks
|
Uncontrolled observational trial
|
|
Caffeine cessation
|
4 to 6 weeks
|
Retrospective, observational trial
|
Vestibular migraine is a common and often underdiagnosed condition. Recognizing VM
is key to adequately managing this disorder. Some VM episodes present with isolated
vestibular symptoms, without headache. Careful history taking should disclose a history
of associated migraine headaches..
Therapeutic measures are currently based in usual migraine treatment options. Future
studies should provide more information regarding management of VM symptoms.
