EPIDEMIOLOGY
Despite vestibular migraine is one of the most common diagnoses in dizziness units
(the second most common cause of recurrent vertigo after benign paroxysmal positional
vertigo (BPPV)) accounting for 6-9% of all diagnoses, it is still underdiagnosed[2]
,
[9]. In a study conducted by a specialized clinic in Switzerland, dizziness was diagnosed
as vestibular migraine in 20.2% of patients, although VM was previously suspected
by the requesting physicians in only 1.8%. The diagnosis of “uncertain dizziness”
accounted for almost 60% of patients[11]. In another study in Germany, with 33 patients, two-thirds of patients diagnosed
with VM had consulted a doctor because of vertigo, but only 20% were diagnosed with
VM. The remaining patients were diagnosed with other diseases such as anemia, diabetes,
hypovolemia[12]. Vestibular migraine has a year prevalence of 0.89% and represents about 10% of
patients treated for either migraine and dizziness[13]. Hsu and colleagues reported a year prevalence of vestibular migraine in women aged
40-54 years of 5%[14]. Forty percent of patients with vestibular migraine reported missing work because
of their symptoms, showing the impact of the disease on daily life[12]. Vestibular migraine can occur at any age, but the average age of onset of dizziness
in migraine is about 40, and a first attack late age in 72 years has been reported.
It has a female predominance, the female and male ratio of 5: 1[2]
,
[12]
,
[15]. In older patients, particularly post-menopausal women, typical migraine attacks
are sometimes replaced by isolated episodes of vertigo, dizziness or transient feeling
of imbalance[16]. In a population-based study, the prevalence of recurrent vertigo probably related
to migraine was estimated at 2.8% in children with 6-12 years[17]. Vestibular migraine is diagnosed more often in children than adults (35% vs 6%)[8]. The most common cause of vertigo in children is benign paroxysmal vertigo, which
has a strong association with a family history of migraine and may predict the development
of typical migraine[18].
Pathophysiology
The exact neural mechanisms of vestibular migraine are still unclear. The variability
of symptoms and clinical findings both during and between attacks suggests that migraine
interacts with the vestibular system at various levels[19].
The vestibular nuclei receive noradrenergic inputs from the locus ceruleus and serotoninergic
inputs from the dorsal raphe nucleus[20]
,
[21]. Therefore, activation of these nuclei during migraine attacks may give rise to
vestibular symptoms. Since the caudalis trigeminal nucleus also has reciprocal connections
with the vestibular nuclei, and neurogenic inflammation of the trigeminal system is
believed to be a mechanism of migraine, trigeminal activation may provoke vestibular
symptoms during migraine attacks. Trigeminal activation by painful electrical stimulation
of the forehead produced spontaneous nystagmus in migraine patients, but not in controls,
indicating that those with migraine have a lowered threshold for crosstalk between
these neighboring brainstem structures[22]. Shin and colleagues studied 2 patients with vestibular migraine who underwent FDG-PET
images. During attacks of vestibular migraine, the increased metabolism of the temporo-parieto-insular
areas and bilateral thalami indicated activation of the vestibulothalamo-vestibulocortical
pathway, and the decreased metabolism in the occipital cortex may represent reciprocal
inhibition between the visual and vestibular systems[23]. Another image study comparing vestibular migraine patients with migraine without
aura (MwoA) and healthy controls (HC) showed that patients with VM showed a significantly
increased left mediodorsal thalamic activation in response to an ipsilateral vestibular
stimulation, relative to both HC and patients with MwoA. Furthermore, the magnitude
of left thalamic activation was uniquely correlated with frequency of migraine attacks
in patients with VM[24]. The role of mediodorsal thalamus in VM pathophysiology could reflect the involvement
of a dysfunctional vestibulo-thalamocortical network, which overlaps with the migraine
circuit[19].
Cortical spreading depression (CSD) in both multisensory vestibular areas of the cortex
and brainstem was used as an explanation for ‘aura’-like dizziness/vertigo attacks
with consecutive headache. However, an isolated CSD, which is limited to the brain
stem without causing any other symptoms, is not very likely[25].
Some authors suggested a genetic inheritance. A linkage analysis in a four-generation
family with 10 affected individuals mapped the locus for vestibular migraine to chromosome
5q35[26]. In a larger study, familial vestibular migraine was found to be genetically heterogeneous
with a subgroup linking to chromosome 22q12[27].
The most current pathophysiologic model of vestibular migraine is summarized in [Figure].
Figure Summary of patophysiologic model of vestibular migraine.
Diagnostic criteria
The International Headache Society (IHS) and the Bárány-Society (International Society
for Neuro-Otology) created a consensus document with diagnostic criteria for vestibular
migraine, which was added in the appendix of the new ICHD-3 beta version of the International
Headache Classification[28] ([Table 1]).
Table 1
Vestibular migraine: diagnostic criteria.
|
A. At least five episodes fulfilling criteria C and D.
|
|
B. A current or past history of 1.1 Migraine without aura or 1.2 Migraine with aura.
|
|
C. Vestibular symptoms of moderate or severe intensity, lasting between 5 minutes
and 72 hours.
|
|
D. At least 50% of episodes are associated with at least one of the following three
migrainous features:
|
|
1. headache with at least two of the following four characteristics:
|
|
a) unilateral location;
|
|
b) pulsating quality;
|
|
c) moderate or severe intensity;
|
|
d) aggravation by routine physical activity.
|
|
2. photophobia and phonophobia;
|
|
3. visual aura.
|
|
E. Not better accounted for by another ICHD-3 diagnosis or by another vestibular disorder.
|
ICHD-3: International Classification of Headach Disorders 3rd edition (beta version).
Clinical presentation
Vestibular migraine often begins several years after typical migraine[2]
,
[15]. In a previous study, migraine manifested before VM in 74% of participants and in
more than half of these (52%) migraine was preceded by VM by more than 5 years, and
in 26% even by more than 10 years. The vast majority of patients (85%) had experienced
both VM and migraine during the last 12 months[12]. Vestibular migraine is more common in patients without aura than in patients with
aura[29]. The most frequent vestibular symptoms associated with migraine are spontaneous
vertigo in 67% followed by positional vertigo in 24% of these patients[12]. Other commonly described symptoms are: imbalance, head motion intolerance, visual
vertigo and non-vertiginous dizziness such as lightheadness or “boat like” rocking[13]
,
[30].
The duration of attacks can vary from a few seconds (10% of patients) to some minutes
(30% of patients), some hours (30% of patients) and even up to a few days (30% of
patients)[25]. Only 10-30% of patients described a typical vestibular aura. Vestibular symptoms
can occur before, during or after the migraine attack and in 30% of the patients the
two symptoms never occurred together[2]
,
[31]. Some patients reported vertigo as the most disabling symptom and only report a
slight felling of pressure in the head replacing a typical migraine headache[32]
,
[33].
Auditory symptoms, including hearing loss, tinnitus, and aural pressure have been
reported in up to 38% patients with vestibular migraine. Hearing loss is usually mild
and transient, without or with only minor progression in the course of the disease[2]
,
[34]
,
[35].
Radtke et al. reassessed 61 patients with definitive VM according to validated diagnostic
criteria after a follow-up time of 9 years and their findings are shown on [Table 2]
[36].
Table 2
Clinical characteristics of vertigo and concomitant symptoms in 61 patients with definite
vestibular migraine.36
|
Initial presentation (%)
|
Follow up (%)
|
|
Type of vertigo
|
|
Spontaneous
|
85
|
95
|
|
Spinning
|
75
|
82
|
|
Positional
|
39
|
80
|
|
Head-Motion-Induced
|
61
|
84
|
|
Unsteadiness
|
66
|
90
|
|
Duration of vertigo attacks
|
|
|
|
< 1 min
|
31
|
75
|
|
1-5 min
|
30
|
56
|
|
5-60 min
|
34
|
64
|
|
< 24h
|
49
|
74
|
|
> 24h
|
52
|
69
|
|
Cochlear symptoms during vertigo spells
|
|
Tinnitus
|
10
|
33
|
|
Aural fullness
|
13
|
26
|
|
Hearing loss
|
12
|
26
|
|
Migraine symptoms during vertigo attacks
|
|
Headache
|
75
|
90
|
|
Photophobia
|
59
|
80
|
|
Phonophobia
|
54
|
77
|
|
Aura
|
18
|
44
|
Episodes of vestibular migraine can be brought about by the same triggers as those
for migraine headache, including menstruation, irregular sleep, stress, physical exertion,
dehydration, food and drinks, and intense sensory stimulation, mostly movement [29].
In most patients, the neurologic and otologic examination is normal during the interictal
phase[32]. About 10 to 30% of patients with vestibular migraine have unilateral hypoexcitability
to caloric stimulation and 10% have directional preponderance of nystagmus responses.
Such findings, however, are not specific for vestibular migraine, because they can
be found also in migraine patients without vestibular symptoms and in many other vestibular
syndromes[37]. In one study, patients with vestibular migraine became nauseous after caloric testing
four times more often than migraine patients and patients with other vestibular disorders[38]. A neuro-otologic study of 20 patients during the acute phase of vestibular migraine
showed pathological nystagmus in 14 patients, mostly central spontaneous or positional
nystagmus. Three patients had a peripheral spontaneous nystagmus and a unilateral
deficit of the horizontal vestibulo-ocular reflex. Imbalance was observed in all patients
except one[39]. Since there are no specific abnormalities in vestibular migraine, in general practice
the diagnosis will be based in the patient clinical history.
Differential diagnosis
The main differential diagnosis of VM is Ménière’s disease (MD). An association between
MD and migraine was already suggested by Prosper Ménière himself in 1861[40]. Some studies have ratified a higher prevalence of migraine in patients with MD[41]
,
[42], almost 30% of patients with Ménière syndrome may also have VM[41]. The overlap or coexistence of both diseases may make the patient’s diagnosis difficult
and the most reliable distinguishing feature is the low-frequency hearing loss in
MD[42]. In general, MD distinguished from vestibular migraine by symptoms of ear fullness
or pain preceding the attack or at attack onset, and accompanying tinnitus and/or
hearing loss during the episode. These symptoms are not very prominent in vestibular
migraine[41]
,
[42].
Endolymphatic hydrops is the primary pathological entity seen in Ménière’s disease[43]. Recent progress has made it possible to reliably visualize endolymphatic hydrops
in living humans by employing a Locally Enhanced Inner ear MRI technique. Gurkov et
al. investigated the occurrence of endolymphatic hydrops (EH) in patients with VM
and auditory symptoms. Nineteen patients with definite or probable VM and auditory
symptoms were examined by locally enhanced inner ear MR imaging. Of the 19 included
patients, four patients (21 %) demonstrated evidence of cochlear and vestibular endolymphatic
hydrops[44]. In contrast, Nakada et al. investigated endolymphatic hydrops in seven patients
with definitive VM and 7 patients with MD. EH was not found in VM patients but all
patients with MD showed significant EH[45].
BPPV is the most common cause of recurrent vertigo[46]. Episodic vertigo related to migraine occurs several times per year or month with
a duration of some hours up to few days, whereas BPPV leads to episodes of short lasting
vertigo typically lasting weeks to months without therapy[47]. During acute attacks of vertigo, the analysis of the positional nystagmus usually
permits differentiation of positional VM from BPPV[47].
Transient ischemia within the vertebrobasilar system is a common cause of episodic
vertigo in older people. It is abrupt in onset, usually lasts several minutes, and
is frequently associated with nausea
and vomiting[48]. Baloh studied 42 patients with vertigo in a neurotology service with the diagnosis
of vertebrobasilar insufficiency and found that 62% had at least one episode of isolated
vertigo and in 19% the transient ischemic attack began with an isolated episode of
vertigo[49]. Therefore, it is reasonable to investigate older patients with sudden onset of
unilateral deafness and vertigo, particularly if there is a prior history of TIA,
stroke, or known atherosclerotic vascular disease.
Basilar migraine requires at least two aura symptoms, which are assignable to the
vertebrobasilar territory, lasting between 5 and 60 minutes and followed by a typical
migraine headache[25]. Less than 10% of the patients with VM meet the criteria for basilar type migraine[2].
Treatment
Current VM treatment recommendations are most based on expert opinions rather than
on solid data from randomized controlled trials. Most therapeutic approaches are based
on case reports, retrospective cohort studies and open labels trials. In general,
the scientific literature suggests that drugs efficacious for prophylaxis of migraine
are also appropriate for prophylaxis of vestibular migraine[49].
Neuhauser and colleagues suggested a benefit of zolmitriptan 2.5 mg in 38% of patients
with vestibular migraine whereas in the placebo group a positive effect was seen in
22%. Unfortunately, the study had some limitations such as the large interval of confidence
and the small number of patients recruited with only 17 reported attacks[50].
In another study, 48 patients with VM diagnose received flunarizine 10 mg daily along
with betahistine and paracetamol during the migraine episodes and compared to the
control group who received only the symptomatic treatment during the episodes. The
frequency of vertiginous episodes showed a significant difference between the two
groups, although the headache frequency and intensity did not improve in a significant
degree[51].
One retrospective single center open label investigation compared the effect of cinnarizine
on VM and migraine with brainstem aura patients. Cinnarizine reduced the headache
variables (frequency, duration and intensity) in both types of migraine with greater
outcomes in the vestibular migraine group. Vertigo was also decreased in both groups
with significant reduction in the VM group in the first month[52].
One retrospective, open-label study investigated the efficacy of 100 mg lamotrigine
in 19 patients (6 male, 13 female) with vestibular migraine over 3–4months. The average
vertigo frequency per month was reduced from 18.1 to 5.4, headache frequency dropped
from 8.7 to 4.4, but did not reach statistical significance. Therefore, lamotrigine
appears to mainly act on vestibular symptoms and only to a lesser extent on headaches[53].
A large retrospective cohort compared 100 VM patients with and without prophylactic
migraine treatment. All patients on prophylactic treatment showed a decrease of duration,
intensity, and frequency of episodic vertigo as well as its associated features (p
< 0.01). Medications used were beta-blocker, 49 patients, metoprolol (median dose
150 mg) or propranolol (median dose 160 mg), valproic acid, 6 patients (median dose
600 mg), topiramate, 6 patients (median dose 50 mg), butterbur extract, 4 patients
(median dose 50 mg), lamotrigine, 3 patients (median dose 75 mg), amitriptyline 2
patients (75 to 100 mg), flunarizine, 1 patient (5 mg), and magnesium 3 patients (median
dose 400 mg). The group without prophylactic therapy showed a reduction of vertigo
intensity only[54]. An ongoing trial will test the efficacy of metoprolol in vestibular migraine (Prophylactic
treatment of vestibular migraine with metoprolol - PROVEMIG trial)[55].
Behavioral modifications can be tried. One retrospective study showed that 14% of
38 patients enrolled reported an improvement in symptoms after caffeine cessation[56].
Vestibular rehabilitation exercises were described to be beneficial in patients with
vestibular migraine in addition to medical treatment or as stand-alone treatment option[57]. Improvement in physical performance measures and self-perceived abilities after
a 4-month vestibular physical therapy was observed in 14 patients with the diagnosis
of migraine related vertigo[58]. In another cohort study, patients with vestibular disorders with or without a history
of migraine demonstrated improvements after nine weeks in both subjective and objective
measures of balance after 15 minutes daily physical therapy[59].
Clinical implications
Vestibular migraine is quite prevalent but still underdiagnosed, and the impact on
daily life activities and well-being is considerable. Treatment is not well established
and therapeutic recommendations are based on migraine guidelin. The need of specific
treatment is urgent. The migraine patient should be asked about vestibular symptoms
by routine and controlled studies on the efficacy of pharmacologic interventions in
the treatment of vestibular migraine should be performed.
