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ABSTRACT
RESUMO
Descritores: Enxaqueca com aura; Enxaqueca sem aura; Vertigem; Distúrbios
vestibulares; Tontura.
ORIGINAL ARTICLE
Accompanying Symptoms in Vestibular Migraine
Sintomas Acompanhantes na Enxaqueca Vestibular
Aline Turbino Neves Martins da Costa
Daniel Guedes Tomedi
Camila Naegeli Caverni
Larissa Mendonça Agessi
Rosemeire Rocha Fukue
Henrique Ballalai Ferraz
Thais Rodrigues Villa
Universidade Federal de São Paulo
*Correspondence
Aline Turbino Neves Martins da Costa
E-mail: alineturbino@gmail.com
Received: May 6, 2019.
Accepted: May 17, 2019.
Objective: The aim of this study was to classify the patients with vestibular
migraine into the subgroups with and without aura, and to evaluate the occurrence
of the accompanying symptoms of migraine in each subgroup. Methods: A
prospective study performed at a tertiary center of vestibular migraine, with
patients fullling denitive diagnostic criteria for vestibular migraine through
International Classication of Headache Disorders ICHD-3 β. Patients were
stratied in the subtypes with and without aura, and the accompanying symptoms
were veried in each subgroup. Results: A total of 143 patients were included,
124 women and 19 men (86% and 13%, respectively). The mean age of onset of
migraine in the patients ranged from 4 to 71 years (SD: 16.0) with a mean of 23
years, and an average headache frequency of 17 days per month (SD: 19.6), with a
visual analog scale mean of 7.45 (SD: 1.88). Of the 143 patients evaluated, 101 (70%)
had ICHD-3 β criteria for the diagnosis of migraine with aura. In patients with the
migraine subgroup with aura, we found a higher relative risk for nausea 2,78 (CI:
0.15-1.0; p0.04), vomiting, 2.65 (CI: 1.26-5.55; p0.009), phonophobia 3,546 (1,647-
7,637, p0,001), osmophobia 3,016 (1,219-7,462, p0,014), kinesiophobia, 2,391 (1,128-
5,071, p, 021), tinnitus 2,275 (1,062-4,873, 032), aural fullness 3,934 (1,519 - 10,192,
p0,003), motion sickness associated with dizziness 3,924 (1,415 - 10,881, p0,006).
Conclusion: In our center, migraine with aura was the most frequent subtype
of migraine in patients with vestibular migraine. During the head attacks, some
associated symptoms were more likely to occur in the aura subgroup, among them:
nausea, vomiting, phonophobia, osmophobia, kinesiophobia, tinnitus, aural fullness
and motion sickness accompanied by dizziness. In our sample, vestibular migraine
associated with migraine with aura showed a higher risk of associated symptoms,
suggesting that this subgroup is more severe, and with a more disabling disease.
Keywords: Migraine with aura; Migraine without aura; Vertigo; Vestibular
disorders; Dizziness.
Objetivo: O objetivo deste estudo foi classicar os pacientes com enxaqueca
vestibular nos subgrupos com e sem aura e avaliar a ocorrência dos sintomas
associados à enxaqueca em cada subgrupo. Métodos: Estudo prospectivo
realizado em um centro terciário de enxaqueca vestibular, com pacientes
preenchendo critérios diagnósticos denitivos para enxaqueca vestibular por
meio da Classicação Internacional de Distúrbios da Dor de Cabeça ICHD-3 β.
Os pacientes foram estraticados nos subtipos com e sem aura, e os sintomas
associados foram vericados em cada subgrupo. Resultados: Foram incluídos 143
pacientes, 124 mulheres e 19 homens (86% e 13%, respectivamente). A idade média
de início da enxaqueca nos pacientes variou de 4 a 71 anos (DP: 16,0), com média
de 23 anos e frequência média de cefaleia de 17 dias por mês (DP: 19,6), com média
da escala visual analógica de 7,45 (DP: 1,88). Dos 143 pacientes avaliados, 101 (70%)
apresentavam critérios ICHD-3 β para o diagnóstico de enxaqueca com aura. Nos
pacientes com subgrupo de enxaqueca com aura, encontramos maior risco relativo
de náusea 2,78 (IC: 0,15-1,0; p0,04), vômitos 2,65 (IC: 1,26-5,55; p0,009), fonofobia
3.546 ( 1.647-7.637, p0.001), osmofobia 3.016 (1.219-7.462, p0.014), cinesiofobia,
2.391 (1.128-5.071, p, 021), zumbido 2.275 (1.062-4.873, 032), plenitude auricular
3.934 (1.519 - 10.192, p0.003), enjoo de movimento associado a tontura 3.924
(1.415 - 10.881, p0.006). Conclusão: Em nosso centro, a enxaqueca com aura foi
o subtipo mais frequente de enxaqueca em pacientes com enxaqueca vestibular.
Durante os ataques na cabeça, alguns sintomas associados apresentaram maior
probabilidade de ocorrer no subgrupo aura, entre eles: náusea, vômito, fonofobia,
osmofobia, cinesiofobia, zumbido, plenitude aural e enjoo acompanhados de
tontura. Em nossa amostra, a enxaqueca vestibular associada à enxaqueca com
aura apresentou maior risco de sintomas associados, sugerindo que esse subgrupo
é mais grave e com uma doença mais incapacitante.
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INTRODUCTION
Vestibular migraine (VM) is one of the variants of
migraine, with vestibular symptoms (VS) beyond the
typical disease model, with a lifetime prevalence of 1%.
1
It is the most common cause of episodic vertigo and the
second most frequent cause of vertigo in general.
2
Studies on vertigo and dizziness showed a
prevalence of 4% to 51.7% among patients with migraine.
3
A tertiary neuro-otology center studied the epidemiology
of vestibular disorders and their clinical form and found
28.2% of patients with VM.
4
Many authors have already demonstrated the
association between migraine and vestibular symptoms,
which are three times more common in the migraine
population.
2
The International Headache Society (IHS) has
included in an appendix, in 2013, the third edition of the
International Classication of Headache Disorders a rst
step towards the identication of new entities.
5,6
(Table 1)
The accompanying symptoms are part of the
diagnostic criteria for both migraine and vestibular
migraine and may be responsible together with
vestibular symptoms for the signicant impact on
patients’ quality of life.
7
METHODS
A prospective study carried out in a tertiary VM
outpatient clinic at the Federal University of São
Paulo, from Jan 2014 to July 2016, by a neurologist
specialized in headache, where demographic data
was collected, as diagnosis of the migraine subtypes
and accompanying symptoms.
We evaluated 198 patients with vestibular symptoms
and headache, and 55 patients were excluded. All
patients included had diagnostic criteria for denitive VM
by ICHD-3β, and the neurological and otoneurological
examination of these patients was normal.
We excluded 55 patients, where dizziness could
be attributed to systemic causes, or to patients with
neurological diseases (epilepsy, stroke) and vestibular,
as well as those who used ototoxic medications, chronic
alcoholics, patients with a history of drug addiction,
previous history of otologic diseases (antecedent of
repeated ear infections, ear trauma) and cranial injuries.
Audiometric examination and computerized cranial
tomography were performed, before inclusion of the
patients. Patients with low-frequency sensorineural
hearing loss were excluded, as well as patients with
ischemic lesions in neuroimaging
Regarding statistics, we rst characterized the
sample collected by calculating frequencies and
percentages or means and standard deviations. Patients
were then divided into migraine without aura and
migraine with aura and the rates and the percentages
were obtained for each group.
The groups were compared with respect to the
follow-up symptoms, using the chi-square test
7
and,
if necessary, the Fisher’s exact test.
8
. Odds ratios (OR)
and respective 95% condence intervals (95% CI) were
also calculated.
8
The statistical package used was Minitab, version 18.
This research was approved by the Ethics
Committee of the University and the patients completed
the Informed Consent Term.
RESULTS
Of the 198 patients evaluated, 55 were excluded with
a denitive diagnosis of VM. Thus, the group consisted of
124 women and 19 men (86% and 13%, respectively). The
mean age of onset of migraine in patients ranged from 4
to 71 years, with a mean of 23 years (SD16), with a mean
frequency of 17 days of headache per month (SD10.8). Of
the 143 patients with VM, 101 (70%) had ICHD-3 β criteria
for migraine with aura (MA) and 29% (42) for migraine
without aura (MWO) (Table 2).
As for the type of aura, 87 (86%) patients presented
visual aura, 31 (30%), sensory aura and 3 (2.9%), motor
aura (Table 3).
Concerning pain intensity assessed by visual analog
scale (VAS), a mean of 7.45 (SD1.88) was obtained.
During VM crises, we evaluated some accompanying
symptoms in the subgroups of migraine with and without
aura. The symptoms were more frequent in VM with aura.
Definite V
1.
At least ve episodes with vestibular symptoms of a
moderate or severe intensity, lasting 5 minutes to 72
hours.
2.
Current or previous history of migraine with or without
aura according to the International Classication of
Headache Disorders (ICHD).
3.
One or more migraine features with at least 50% of the
vestibular episodes:
- Headache with at least two of the following
characteristics: one-sided location, pulsating quality,
moderate or severe pain intensity, aggravation by
routine physical activity;
- Photophobia and phonophobia;
- Visual aura.
4.
Not better accounted for by another vestibular or ICHD
diagnosis.
Table 1. VM diagnostic criteria - ICHD-B β diagnosis
Photophobia, phonophobia, nausea, and vomiting
are present in the diagnostic criteria of VM and should
accompany at least 50% of the episodes of dizziness.
5-6
The association of VM with subtypes of migraine,
migraine with and without aura, and its association with
accompanying symptoms has not been consistently
analyzed in the literature.
OBJECTIVE
To classify the patients with denitive diagnosis of
VM in the subtypes of migraine with and without aura
and to evaluate the accompanying symptoms of each
subgroup.
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In the MA subgroup we found a higher relative risk
for: nausea 2,788 (1,020 - 7,623, p0,040); vomiting 2,655
(1,269-5,557, p0.009); phonophobia 3,546 (1,647 - 7,637,
p = 0.001), osmophobia 3,016 (1,219 - 7,462, p = 0,014),
kinesiophobia 2,391 (1,128 - 5,071, p = 0,021), tinnitus
4,273 (1,215 - 15,049, p = 3,934 (1,519-10,192, p = 0.003),
motion sickness associated with dizziness 3,924 (1,415-
10,881, p = 0.006) (Table 4).
Table 3. Frequency distribution of the variable Type of
aura
Type of aura
Yes No
n % n %
Visual aura 87 86,14 14 13,86
Sensory Aura 31 30,69 70 69,31
Motor aura 3 2,97 98 97,03
Others 2 1,98 99 98,02
n: number of patients.
Variable N Mean SD
Age (years) 143 37.83 17.66
Age at headache onset
(years)
143 23.13 16.08
Pain duration (hours) 143 15.43 9.92
Pain frequency (days/
month)
143 17.52 10.82
Daily headache (months) 143 13.53 19.68
Pain intensity (VAS) 143 7.45 1.88
Sex
Female Male
86.71% 13.29%
Aura
with aura without aura
70.63% 29.37%
Table 2. Demographic and clinical characteristics of
patients with migraine
SD: standard deviation, VAS: visual analog scale.
Table 4. Joint frequency distribution between patient characteristics and VM and migraine groups with aura and
without aura, p-value of the chi-square test, odds ratio and respective 95% condence interval.
Variables
Without aura With aura
P Value Odds ratio
Confidenc
interval
n % n %
Nausea 33 78,57 92 91,02 0,040 2,788 1,020 7,623
Vomiting 17 40,48 65 64,36 0,009 2,655 1,269 5,557
Phonophobia 13 30,95 101 61,39 0,001 3,546 1,647 7,637
Photophobia 14 33,33 51 50,50 0,060 2,040 0,963 4,322
Osmophobia 7 16,67 38 37,62 0,014 3,016 1,219 7,462
Kinesiophobia 14 33,33 55 54,46 0,021 2,391 1,128 5,071
Tinnitus 3 7,14 25 24,75 0,016 4,273 1,215 15,049
Headache 25 59,52 75 74,26 0,080 1,962 0,917 4,197
Aural fullness 6 14,29 40 39,60 0,003 3,934 1,519 10,192
Hearing loss 5 11,90 18 17,82 0,380 1,605 0,554 4,650
Motion sickness + headache 6 14,29 30 29,70 0,053 2,535 0,967 6,647
Motion sickness + dizziness 5 11,90 35 34,65 0,006 3,924 1,415 10,881
Motion sickness 6 14,29 29 28,71 0,068 2,417 0,920 6,348
Source: the author
DISCUSSION
The migraine association with aura and MV remains
controversial. In the study by Calhoun et al.
9
, which
aimed to determine and characterize the prevalence
of dizziness in migraine, 425 patients were evaluated,
of which 28% had MA. The prevalence of dizziness was
twice as high (24.5% vs 12.1%) in migraine with aura
compared to migraine without aura (P <0.01). Prevalence
also increased with age (P <0.05).
Another study
10
evaluated the prevalence of vertigo,
dizziness, and VM over the years in patients diagnosed
with migraine, comparing them with a control group.
Both groups were assessed for symptoms of dizziness
and vertigo.
The study included 327 patients diagnosed with
migraine with and without aura and 324 controls with no
history of a frequent headache. 199 (60.9%) patients had
migraine with aura (MA), 128 (39.1%) migraine without
aura (MWA).
Patients of the MA subgroup had, more frequently,
vertigo symptoms/dizziness than those with MWA. Of
the 199 patients in the MA subgroup, 19 (14.84%) always
reported vertigo symptoms/dizziness associated with
headache, than those of the MWA 19 subgroup (9.55%)
reported. Patients in the MA subgroup had a higher
association with dizziness and vertigo (P <0001).
In Neuhauser’s study
11
, 4869 patients were evaluated
on the epidemiology of MV in the general population. In
this sample 33 patients had VM, being 36% MA and 64%
MWA, and after regression analysis of migraine with aura,
it was not a risk factor for VM.
In the study by Cohen et al,(12), they identied
predictive factors of the VM of the 147 individuals, 100
(68%) were women and 47 (32%) men aged 15 to 92
years (mean age 45 years). Of the 147 evaluated, 57
(39%) had migraine with aura and 90 (61%) had no aura;
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of the subgroup with aura 21 (37%) were male and 36
(63%) female. A signicant difference was observed
in the subgroups of migraine patients with vestibular
symptoms: sensitivity to bright lights occurred in 74% of
the subgroup with aura and 43% in the subgroup without
aura (p <0001), motion sickness (51% with aura and 39%
without aura) and climate changes (54% with aura and
31% without aura), the differences approached but did
not reach signicance (P = 0.08 and .07, respectively).
To investigate the clinical features of multiple
diseases that involved vertigo/dizziness, Esch et al.
13
investigated 122 patients, and only 16 were diagnosed
with VM, where the accompanying symptoms were
evaluated. Of the patients, 7 (44%) had aura, 16 (100%)
reported nausea, 7 (44%) vomiting, 11 (69%) photophobia
and 11 (69%) phonophobia, as well as asymmetric hearing
loss in 12 (75%) and tinnitus in 2 (13%).
A study published in the Neurology Journal
14
on
VM, its clinical evolution and cochlear dysfunctions in a
9-year follow-up, followed 61 patients with the diagnosis.
The accompanying symptoms were assessed at baseline
and followed-up after nine years.
The most frequent accompanying symptoms at the
initial evaluation were photophobia in 59% of the patients
and phonophobia in 54%, during the 9-year follow-up,
these symptoms were 80% and 77%, respectively.
During VM crises, cochlear symptoms appeared
in 49% of the patients, tinnitus in 33%, auditory
symptoms (tinnitus symmetrical, aural fullness) in
26% and hearing difculty in 26%. Initially, 18% of the
patients reported aura and, during follow-up, 44% of
the patients reported symptoms.
This study followed patients with a denitive
diagnosis of VM for nine years, their accompanying and
cochlear symptoms both at admission and during follow-
up, showed worsening of symptoms also in the interictal
period. It was possible to observe the appearance of aura
during the patients’ follow-up of the patients. The author
of the publication suggests that the worsening of the
evolution of symptoms, including in the interictal period,
may be associated with a progressive deterioration of
the vestibular system caused by the disease.
In our sample, patients with VM diagnosis of the
aura subgroup had a higher chance of presenting nausea,
vomiting, phonophobia, osmophobia, kinesiophobia,
tinnitus, auricular fullness and motion sickness associated
with dizziness. Photophobia, headache, hearing loss,
headache-associated kinesis, and isolated kinesis were
not associated with the MA subgroup.
There are, to date, no other studies correlating the
odds ratio of the accompanying symptoms between the
VM and the subgroups of migraine.
We must emphasize the signicant size of this
sample, and that this is a tertiary research center of VM.
All patients were diagnosed by a neurologist specialized
in headache and vestibular symptoms and met the
criteria of VM according to ICHD-3 β.
Although there was no statistical difference
between the groups (migraine with or without aura
regarding vestibular symptoms), they appeared three
times more in the subgroup with aura. However, because
of the size of our sample, it may not be possible to state
that having aura is a risk factor for developing vestibular
symptoms. Thus, studies with larger populations should
be carried out.
It is still relevant to note that, in the aura subgroup,
the accompanying symptoms had a higher relative
risk ratio for several accompanying symptoms, which
demonstrates the greater severity and a more debilitating
condition for this association of diagnoses.
Leão’s cortical spreading depression
15
in migraine
with aura and neuronal hyperexcitability exacerbate the
trigeminal activation process, thus causing neurogenic
inammation. This could contribute to the activation and
sustained sensitization of this process, as well as cause
reversible vasospasm of the internal auditory artery,
responsible for vestibular symptoms, both during VM
crises, and could also be responsible for damages in this
pathway, which could justify vestibular symptoms, even
during the interictal period.
16,17
CONCLUSION
Patients with vestibular migraine and migraine
with aura, when compared to patients with VM and
migraine without aura, present a higher relative risk
of having accompanying symptoms such as nausea,
vomiting, phonophobia, osmophobia, kinesiophobia,
tinnitus, auricular fullness, and motion sickness
associated with dizziness.
Detailed anamnesis and the active search for the
presence of aura, during the initial assessment and
also during the evolution of the patient with VM, are
necessary, in order to diagnose vestibular symptoms.
Diagnosing this subgroup with aura, where the
accompanying symptoms are more frequent, makes
them a group of patients with a more severe disease
and with a worse prognosis.
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