Published online: 14.01.

2020

Vestibular Migraine I: Mechanisms, Diagnosis,

and Clinical Features
Robert W. Baloh, MD1

1 Department of Neurology and Head and Neck Surgery, David Geffen
School of Medicine at UCLA, Ronald Regan Medical Center,
Los Angeles, California
Semin Neurol
Address for correspondence Robert W. Baloh, MD, Professor of
Neurology and Head and Neck Surgery, David Geffen School of
Medicine at UCLA, Ronald Regan Medical Center, 710 Westwood
Plaza, Los Angeles, CA 90095-1769
(e-mail: rbaloh@mednet.ucla.edu).

Abstract Vestibular migraine (VM), also known as migrainous vertigo or migraine-associated vertigo,
is characterized by recurrent vestibular attacks often accompanied by migraine headaches
and other migraine symptoms. It is one of the most common presenting complaints to

Downloaded by: State University of New York at Stony Brook. Copyrighted material.
physicians in primary care, otolaryngology, and neurology. Epidemiologic data suggest that
VM may affect 1 to 3% of the general population and 10 to 30% of patients seeking
treatment for dizziness. Attacks typically last minutes to hours and range from spontaneous
and positional vertigo to extreme sensitivity to self and surround motion. As with
Keywords headaches, nausea, and vomiting, phonophobia and photophobia are common accompa-
► vestibular migraine nying symptoms. The clinical spectrum of VM and its underlying pathophysiological
► vertigo mechanisms are just being identified, with much debate about the causal relationship
► dizziness of vestibular symptoms and headache, no evidence-based guidelines for clinical manage-
► aura ment, limited characterization of its disease burden, and little information about its
► spreading depression negative impact on health-related quality of life.

Migraine is a complex hereditary disorder that renders people
susceptible to electrical and vascular changes in the brain
leading to a variety of symptoms.1 The most commonly
recognized clinical symptom of the disorder is headache, but
migraine is also characterized by dizziness, visual distortions,
hypersensitivity to sensory stimuli, nausea, paresthesias, and
even paralysis in some cases. The British born, American
Neurologist and writer, Oliver Sachs, nicely summarized the
complexity of migraine in his 1970 book Migraine: Evolution of
a Common Disorder. “The cardinal symptoms of common
migraine are headache and nausea. Complementing these
may be a remarkable variety of other major symptoms, in
addition to minor disorders and physiological changes of
which the patient may not be aware. Presiding over the entire
attack, there will be, in du Bois Reymond’s words, “a general
feeling of disorder,” which may be experienced in either
physical or emotional terms, and tax or elude the patient’s
power of description. Great variability of symptoms is charac-
teristic, not only of attacks in different patients, but between
successive attacks in the same patient.”2
Next to headache, dizziness is the most common symp-
tom reported by patients with migraine.3 The dizziness takes
on several forms, from sensitivity to motion sickness to
nonspecific lightheadedness and difficulty concentrating to
frank vertigo. About two-thirds of patients with migraine
have life-long sensitivity to motion sickness and many have
spontaneous bouts of motion sickness without exposure to
motion. About a third of patients with migraine experience
vertigo during their lifetime. Migraine is the great mimicker
of all causes of vertigo as it can closely resemble attacks of
Meniere’s syndrome, benign paroxysmal positional vertigo
(BPPV), and even vestibular neuritis.
The relationship between migraine and dizziness was
recognized as far back as the 19th century when Liveing noted
their connection in his classic book On Megrim: Sick Headaches
and Some Allied Health Disorders.4 Liveing provided detailed
descriptions of 60 patients with migraine from his own
practice and other sources, the first comprehensive look at
the breadth of the “migraine experience.” He emphasized the
diversity of symptoms with migraine including a variety of

Issue Theme Neuro-Otology; Guest Copyright © by Thieme Medical DOI https://doi.org/

Editor, Terry Fife MD, FAAN, FANS. Publishers, Inc., 333 Seventh Avenue, 10.1055/s-0039-3402735.
New York, NY 10001, USA. ISSN 0271-8235.
Tel: +1(212) 584-4662.
Vestibular Migraine I: Mechanisms, Diagnosis, and Clinical Features
headache and dizziness symptoms. Liveing concluded that
migraine resulted from a “nerve-storm” analogous to other
similar paroxysmal disorders such as epilepsy. In the case of a
migraine visual aura, Liveing suggested that the nerve-storm
began in the visual thalamus (a key visual relay station deep in
the brain) and then moved from above to downward or from
front to backward. Had Liveing chosen the visual cortex rather
than the visual thalamus for the origin of the “nerve-storm,”
his theory might have had more lasting impact, but it was
largely forgotten by future researchers on the mechanism of
migraine. In Liveing’s defense, little was known about cerebral
cortical localization at that time.
The idea that migraine might have a vascular origin dates
back to Thomas Willis in the 17th century, but it was not until
the 1930s that an American neurologist, Harold Wolff, con-
ducted seminal experiments in patients with migraine at the
Cornell Medical Center in New York reinventing the vascular
theory of migraine. After completing medical school at
Harvard and an internship in New York, Wolff returned to
Harvard from 1926 to 1928 to work as a research fellow with
Stanley Cobb, the pioneer of biological psychiatry who
believed that there was no distinction between functional
and organic disease.5 Wolff chose to study migraine as it
seemed to be the ideal disease to investigate the interaction
between the psyche and biology in producing nervous dis-
orders. At Cornell, Wolff developed methods to measure
intracranial and extracranial blood flow changes during a
migraine attack, and noted that a migraine aura could be
temporarily aborted with a drug that caused dilatation of
blood vessels increasing blood flow to the brain. He gave a
medical student who was experiencing a typical migraine
scintillating scotoma a whiff of amyl nitrate, a vasodilating
drug used to treat cardiac angina, and the scotoma transient-
ly disappeared only to return as the drug wore off. On the
other hand, he could abort the headache phase of migraine
by giving a patient ergotamine tartrate, a drug known to
cause constriction of blood vessels and decrease blood flow.
Based on these observations, Wolff concluded that migraine
aura resulted from vasoconstriction of intracranial blood
vessels causing decreased blood flow to areas of the brain
such as the visual cortex, and migraine headaches were
caused by vasodilation of the extracranial blood vessels
activating pain fibers in the walls of the blood vessels. Wolff’s
vascular theory provided a potential new treatment for
migraine headaches, ergotamine.
At about the same time Wolff was developing his vascular
theory of migraine, a new neuronal theory of migraine was
taking shape based on a combination of clinical and labora-
tory observations. In 1941, Karl Lashley, a well-known
psychologist at the Harvard University, published an article
in Archives of Neurology and Psychiatry in which he reported
a series of sketches of his own scintillating scotoma over
time, and concluded that “a wave of intense excitation is
propagated at a rate of 3 mm/minute across the visual cortex.
This wave is followed by complete inhibition of activity, with
recovery progressing at the same rate.”6 Lashley had studied
the cellular architecture of the cerebral cortex in a variety of
animals including primates, and he had a particular interest
Seminars in Neurology
Baloh
in the visual cortex (occipital cortex) and the study of color
vision. Over several years, Lashley mapped a large number of
his migraine auras that occurred in isolation from headache
or any other symptoms. He wrote, “The scotoma usually
occurs first as a small blind or scintillating spot, subtending
less than 1 degree, in or immediately adjacent to the foveal
field (central vision). This spot rapidly increases in size and
drifts away from the fovea toward the temporal field of one
side. Usually, both quadrants of one side only are involved,
the right and left being affected with about equal frequency.”
To map the developing scotoma in his visual field, Lashley
placed a dot on a white piece of paper and while focusing on
the dot he moved a pencil toward the developing scintillating
scotoma from different directions and marked the position
on the paper where the pencil disappeared. He kept repeat-
ing the process at fixed time intervals to map the changing
size of the scotoma. Lashley estimated the 3 mm/minute rate
Downloaded by: State University of New York at Stony Brook. Copyrighted material.
of spread across the visual cortex assuming that the “distur-
bance” began near the occipital pole and moved toward the
temporal margin (a distance of 67 mm) in approximately
20 minutes (the typical duration of the aura). He speculated
that scintillations on the rim of the scotoma represented a
wave of intense excitation of the visual cortex, followed by a
wave of total inhibition, the blind area.
At the time of Lashley’s report, a young Brazilian physiolo-
gist, Aristides Leão, was working on his doctorate at Harvard
Medical School, which he received in 1943. In the following
year, based on his doctoral thesis, Leão published an article in
the Journal of Neurophysiology describing a curious phenome-
non that he had observed in his studies of epilepsy, cortical
spreading depression.7 The article has become one of the most
widely quoted articles in the history of neuroscience and
provides a conceptual basis for understanding the mechanism
of migraine. Leão’s basic observation was that he could trigger
a slowly propagating wave of depression of electrical activity
in the cerebral cortex of a rabbit, pigeon, or cat with a pinpoint
electrical or mechanical stimulus, and that the wave of
depression moved across the cortex at a rate of between
2 and 5 mm/minute. In a second article in the same journal,
he reported that the wave of depression was associated with
dilatation and constriction of the tiny arteries overlying the
cortical area with the depressed electrical activity.8 This
observation suggested a close interrelationship between neu-
ronal activity and cerebral blood flow (now considered the
neurovascular unit) and a potential link between the neural
and vascular theories of migraine.
Mechanism
Many factors contribute to the complex and only partially
understood pathophysiology of migraine (►Fig. 1).
Familial Predilection
Numerous studies over the years have documented familial
aggregation of patients with migraine, and many neurologists,
including myself, consider it a genetic disease.9 In nearly all
studies, the incidence of a positive family history for migraine
headaches is significantly greater than in controls. The
 Vestibular Migraine I: Mechanisms, Diagnosis, and Clinical Features
Fig. 1 Some of the factors contributing to the pathophysiology of migraine. (Used with permission from Terry D. Fife, MD, Barrow Neurological
Institute.)
incidence of a positive family history varies from approximately
40 to 90%, compared with approximately 5 to 20% in controls.
The percentage of positive family histories tends to be greater in
those studies in which family members were individually
interviewed than in studies that relied on questionnaires or
on the recall of the proband. Studies in monozygotic and
dizygotic twins have also supported a strong genetic compo-
nent for migraine, particularly for migraine with aura (MA).
Also, the fact that the prevalence of migraine in African and
Asian populations is lower than in European and North
American populations favors a major genetic component.
Studies of migrainous vertigo show the same familial aggrega-
tion seen in other migraine syndromes.10,11
The situation with migraine is analogous to that of epilepsy.
Some seizure syndromes are inherited, and genetic factors are
important for most types of epilepsy, but anyone can have a
seizure with adequate provocation. Similarly, several inherited
syndromes are associated with migraine headache, and genetic
factors are important in determining the threshold for migraine
headaches, but structural lesions such as vascular malforma-
tions and vasculopathies can trigger migraine headaches in
anyone. Genotype heterogeneity has already been established
for several migraine syndromes. These syndromes are defined
based on the presence of hemiplegic episodes or other aura
symptoms that accompany migraine headaches. Within such
families, however, some members may have only migraine
headaches, indicating that there is also phenotypic
heterogeneity.
Insights from Molecular Genetics
The recent identification of the genes for several rare subtypes
of migraine provides the first true molecular insight into
migraine pathophysiology.12 Familial hemiplegic migraine
(FHM) is an autosomal dominant disease characterized by
headache attacks preceded or accompanied by episodes of
hemiplegia, sometimes lasting days. Within reported families
Baloh
Downloaded by: State University of New York at Stony Brook. Copyrighted material.
with FHM, some affected members have interictal nystagmus,
ataxia, essential tremor, and seizures. MA and episodes of
hemiplegia may alternate within individuals and co-occur
within families. So far, mutations in three genes have been
identified in FHM: CACNA1A, ATP1A2, and SCN1A. These muta-
tions result in defective regulation of glutamatergic neuro-
transmission and alter the excitatory/inhibitory balance in the
brain, which lowers the threshold for cortical spreading
depression, a wave of cortical depolarization thought to be
involved in headache initiation mechanisms.
Although there is overlap in clinical features, most families
with FHM due to mutations in CACNA1A have progressive ataxia
and interictal nystagmus, while families reported with muta-
tions in ATP1A2 and SCN1A usually have associated epileptic
seizures. All of the mutations in CACNA1A associated with FHM
have been missense mutations.13 Nonsense mutations in the
same gene produce a related disorder, episodic ataxia type 2
(EA-2), which is also associated with migraine headaches.14 In
some families, there can be an overlap between episodes of
hemiplegia and episodes of ataxia.15 Of the many FHM families
with identified mutations in CACNA1A, about half have the
T666M mutation. Most of the patients with the T666M muta-
tion also have symptoms and signs of cerebellar ataxia,
although there is a broad clinical spectrum.16 It is likely that
mutations in several other genes will be identified, particularly
in cases of sporadic hemiplegic migraine. No mutations in
CACNA1A or ATP1A2 were found in patients with sporadic
migraine headaches or families with migraine (with and with-
out aura); so, it does not appear that CACNA1A and ATP1A2 are
important for the common migraine syndromes.17,18
Mutations in NOTCH3, TREX1, and COL4A1 all cause
inherited vasculopathies associated with migraine.12 Inter-
estingly, families with hemiplegic migraine were initially
linked to the same area on chromosome 19p previously
linked to families with cerebral autosomal dominant arterio-
pathy with subcortical infarcts and leukoencephalopathy
Seminars in Neurology
Vestibular Migraine I: Mechanisms, Diagnosis, and Clinical Features
(CADASIL), suggesting that the same gene caused both dis-
orders. But later, more detailed studies found that NOTCH3
and CACNA1A causing CADASIL and hemiplegic migraine,
respectively, are next to each other on chromosome 19p. The
most common migraine syndromes highly prevalent in the
general population are almost certainly polygenic with many
susceptibility genetic variants. Genome-wide association
studies (GWAS) have so far identified nearly 40 loci signifi-
cantly associated with migraine risk.19 Genes in proximity to
these loci are involved in both neuronal and vascular path-
ways, corroborating the neurovascular pathophysiology of
migraine.
Ion Channelopathy Hypothesis
One way to explain the genetic heterogeneity of migraine
syndromes is to postulate defects in groups of genes that
code for families of proteins with similar properties and
functions. The family of genes that code for ion channels is a
good example, because many of the migraine syndromes share
the clinical features of known inherited ion channel disorders. A
defective ion channel could explain the local buildup of extra-
cellular potassium that initiates the spreading wave of depres-
sion in migraine. Since ion channels in the inner ear are critical
for maintaining the potassium-rich endolymph and neuronal
excitability, a defective ion channel shared by the brain and
inner ear could lead to a reversible hair cell depolarization and
auditory and vestibular symptoms. Furthermore, many of the
well-known triggers for migraine symptoms, including stress
and menstruation, could result from hormonal influences on
the defective ion channels. Migraine prophylactic drugs such as
β-blockers, calcium channel blockers, acetazolamide, and
tricyclic amines might work by stabilizing abnormal ion chan-
nels. Acetazolamide appears to work in episodic ataxia type 2
by changing cerebellar pH and stabilizing the calcium channel
CACNA1A.20
Probably the most characteristic of migraine symptoms is
the classic visual aura. It typically begins with a small
scintillating scotoma that gradually enlarges over 10 to
20 minutes. There is convincing evidence that the visual
aura is secondary to a spreading wave of cortical depression
beginning at the occipital pole, which gradually spreads
across the cortex before stopping at the central sulcus.21
Although decreased cerebral perfusion is associated with
the spreading wave of depression, it is probably a secondary
phenomenon rather than a primary process. The spreading
wave of cortical depression is associated with a marked
accumulation of extracellular potassium that must be
cleared before neural activity can return to normal. Although
the mechanism for the spreading wave of depression is not
completely known, most agree that the initial event is local
buildup of potassium in the extracellular space.
Nearby synaptic terminals then depolarize in response to
the high extracellular potassium releasing both excitatory
and inhibitory neurotransmitters. This release in turn leads
to the opening of subsynaptic channels, resulting in further
ionic exchange between the intracellular and extracellular
fluids. During the spreading wave of depression, neurons are
completely silent for approximately 1 minute and they then
Seminars in Neurology
Baloh
slowly recover their predepression level of firing. The rate of
movement of the spreading wave of depression across the
visual cortex nicely correlates with the rate of enlargement of
the scintillating scotoma as proposed by Lashley.22 Animals
with mutations in the calcium channel gene CACNA1A have
decreased thresholds for spreading depression.23
Trigeminovascular Hypersensitization
How does the spreading wave of depression and associated
increase in extracellular potassium lead to a typical migraine
headache?24 Trigeminal nerve fibers surrounding pial arteries
on the ventral surface of the brain could be depolarized by the
high potassium concentration. This in turn would lead to the
release of neurotransmitters such as substance P and calcito-
nin gene–related peptide (CGRP) by both orthodromic and
antidromic conduction. The result is an increase in vascular
permeability, dilatation of cerebral vessels, and a local inflam-
Downloaded by: State University of New York at Stony Brook. Copyrighted material.
matory response further activating pain-provoking fibers of
the trigeminal vascular system. Thus, the headache of migraine
could be a secondary phenomenon, the end result of a local
increase in extracellular potassium concentration. Further-
more, the inner ear receives innervation from the trigeminal
nerve through the basilar artery and the anterior inferior
cerebellar artery, and chemical and electrical stimulations of
the trigeminal nerve cause a significant increase in inner ear
blood flow, changing intravascular permeability with plasma
protein extravasation into the inner ear.25 Many of the drugs
used for prophylactic treatment of migraine have been shown
to suppress the cortical spreading wave of depression in an
animal model of migraine. Drugs that block CGRP, such as
monoclonal antibodies against CGRP (e.g., erenumab, frema-
nezumab, and galcanezumab), are promising new treatments
for migraine headaches, but so far none of these drugs have
been tested for treating vestibular migraine (VM).
Vasodilatation of extracranial vessels accompanies the typi-
cal migraine headache. As suggested earlier, vasospasm occurs
in some intracranial vessels with migraine, although there is
controversy regarding its role in the production of symptoms.
Although vasospasm is associated with the classical migraine
visual aura, the vasospasm is probably secondary to hypome-
tabolism associated with the spreading wave of depression
moving across the cerebral cortex. Vasospasm is more likely
involved in the pathophysiology of retinal migraine. Some
patients experience episodes of monocular blindness, and
when examined during these episodes there is vasospasm of
retinal arteries. Furthermore, such patients respond to anti-
spasmodic agents such as the calcium channel blocker verapa-
mil.26 Sudden episodes of hearing loss and/or vertigo associated
with migraine could be explained by vasospasm of the cochlear
and/or vestibular branches of internal auditory artery. The T2/
FLAIR hyperintensities in the deep periventricular white matter
commonly seen on MRI in patients with migraine may be
caused by microvascular vasospasm in the brain.
Diagnosis
Based on a joint committee of the International Headache
Society (IHS) and the Barany Society, consensus criteria for the
 Vestibular Migraine I: Mechanisms, Diagnosis, and Clinical Features
Table 1 Diagnostic criteria for definite vestibular migraine
(ICHD-III)26
A At least 5 episodes of vestibular symptomsa of
moderate or severe intensity,b lasting 5 min to 72 h
B Current or previous history of migraine with or
without aura according to the ICHD
C One or more migraine features with at least 50%
of the vestibular episodesc
D Not better accounted for by another vestibular
or ICHD diagnosis
Abbreviation: ICHD, International Classification of Headache Disorders.
a
Vestibular symptoms qualifying for a diagnosis of vestibular migraine
include (1) spontaneous vertigo—false sensation of self-motion or that
the visual surround is spinning or flowing; (2) positional vertigo,
occurring after a change in head position; (3) visually induced vertigo,
triggered by a complex or large moving visual stimulus; (4) head-
motion–induced vertigo, occurring during head motion; (5) head-
motion–induced dizziness with nausea, characterized by a sensation of
disturbed spatial orientation.
b
Moderate, interferes with but does not prohibit daily activities; severe,
prevents daily activities.
c
Associate migraine features: (1) headache with at least two of the
following: unilateral location, pulsating quality, moderate or severe
intensity, and aggravation by routine physical activity; (2) photophobia
and phonophobia; and (3) visual aura.
diagnosis of VM were developed and included in the appendix
of the β-version of the IHS (International Classification of
Headache Disorders III [ICHD-III] β-version; ►Table 1).27
These criteria define the types of vestibular symptoms; mini-
mum number, severity, and duration of attacks; association of
vestibular and migrainous symptoms; requirement for a
migraine diagnosis; and absence of other causes of symptoms.
The diagnosis of probable VM is made if either criteria B or
C is identified. The ICHD-III also included four episodic
syndromes associated with migraine in infancy and child-
hood, the so-called migraine equivalents: benign paroxysmal
vertigo, benign paroxysmal torticollis, cyclical vomiting, and
episodic abdominal pain. Follow-up studies in children with
these syndromes show a large percentage of children go on to
develop typical migraine later in life. As suggested earlier,
susceptibility to motion sickness in childhood is also consid-
ered a precursor for development of migraine, particularly
where there are multiple family members with migraine.
Neurotologic conditions such as Meniere’s disease and BPPV
share symptoms in common with VM.28 Recurrent vertigo
without ear symptoms can be the first presentation of Meniere’s
disease; however, with Meniere’s disease, tinnitus and hearing
loss invariably occur within a year of onset. Vertigo attacks in
BPPV are positional and last no more than a minute. Although
vertigo attacks with VM typically have a positional element,
symptoms persist even when patients are still and typically last
longer than a minute. Migrainous positional vertigo can be
differentiated from BPPV by (1) longer-duration symptomatic
episodes, (2) migrainous symptoms during episodes, and (3)
atypical positional nystagmus. Finally, VM may coexist with
Meniere’s disease, BPPV, anxiety, and depression. Coexisting
conditions may alter its clinical presentation and morbidity.
Baloh
Clinical Feature
Vestibular migraine, previously known as migrainous vertigo
and migraine-associated vertigo, affects approximately 1 to 3%
of the general population and 10 to 30% of patients seen in
dizziness and headache clinics.29,30 When vestibular symp-
toms were assessed in patients with migraine using the
Dizziness Handicap Inventory Questionnaire, more than
two-thirds reported vestibular symptoms, compared with
12% in controls.31 Patients with MA and chronic migraine
were significantly more likely to have vestibular symptoms
than patients with migraine without aura (MoA). Vestibular
symptoms can occur during headaches, but often occur during
headache-free intervals. Only about one-quarter of patients
reliably experience headaches during vestibular attacks.
Vestibular attacks in patients with VM typically last minutes
to days.32 If examined during an attack, patients with VM may
show spontaneous or positional nystagmus that can have
Downloaded by: State University of New York at Stony Brook. Copyrighted material.
central or peripheral features, raising concerns about other
neurotologic illnesses.33 Conventional migraine and VM share
numerous features. Both have a marked female preponderance
(2–4:1). Attacks of both can be precipitated by alcohol, lack of
sleep, fasting, certain foods, and emotional stress. Patients
with VM have past or present histories of migraine and often
have family histories of both migraine and vestibular
symptoms.
We reviewed the clinical features of 208 patients who
presented to the neurotology clinic over a 2-year period with
idiopathic recurrent spontaneous attacks of vertigo without
associated auditory symptoms (benign recurrent vertigo
[BRV]).34 Of these 208 patients, 180 (87%) met ICHD criteria
for migraine (112 with aura and 68 without aura). Among the
patients with recurrent vertigo and ICHD migraine, 70% expe-
rienced headache, aura, photophobia, or phonophobia with
some or all of their vestibular attacks, meeting the consensus
criteria for VM for ICHD-III.26 The age of onset of migraine
headaches preceded the onset of vestibular attacks by an
average of 14 years, and aura preceded vestibular attacks by
8 years. The most frequent duration of vestibular attacks
was minutes to hours, with a small percentage lasting days.
These numbers are very similar to those seen in a more recent
cross-sectional study of 252 patients with VM in Europe.32
The designation of BRV as a migraine equivalent remains an
unresolved issue in headache research, but the majority of
patients with BRV in our study met criteria for migraine,
indicating that the association is not by chance. In some cases,
the acceptance of the vertigo attack as a migraine symptom is
clear because of the temporal correlation of vestibular symp-
toms with migraine headaches. In many cases, however, the
temporal correlation does not exist, but other features such as
duration, associated features, and age of onset suggest that
vertigo is indeed a migraine equivalent. Supporting this desig-
nation is that the largest group of patients with migraine and
BRV in our series reported having some vertigo attacks along
with other migraine symptoms, and some attacks without. A
corollary to this situation is the phenomenon of visual auras,
which are usually associated with migraine headaches but are
well recognized to occur in isolation, and are accepted as a
migraine equivalent.
Seminars in Neurology
Vestibular Migraine I: Mechanisms, Diagnosis, and Clinical Features
The 62% prevalence of aura seen in our 180 BRV patients
with migraine was higher than the rate of aura in unselected
migraine patients, which is reported to be approximately 27 to
28%. Debate exists as to whether MA is a different clinical entity
from MoA. Anatomical differences in visual motion-processing
areas have been seen in both MoA and MA patients.35 Cortical
spreading depression emanating from the occipital lobe, which
is typically attributed to the aura phase of migraine, has also
been seen in a patient in the midst of a migraine attack but with
no visual aura.36 Furthermore, migraine-preventative medi-
cations are helpful in both MA and MoA, and may all work by
raising the threshold for cortical spreading depression,37 indi-
cating that the mechanism underlying both MoA and MA may
be similar. Nevertheless, the rate of heritability of MA seems to
be higher than that of MoA,38 and comorbidity with vascular
events appears to segregate with MA to a greater degree than
MoA, including the risk of small-vessel ischemic changes in the
brain.39 This higher association of MA with vascular disease,
particularly in the posterior circulation, may be relevant to why
MA patients are more highly represented in our BRV popula-
tion. Indeed, as suggested earlier, vasospasm in the posterior
circulation has been proposed as a mechanism for migraine-
associated damage to the inner ear and may underlie some
forms of migrainous vertigo.
Conclusions
Vestibular migraine presents with recurrent vestibular attacks
lasting minutes to hours and commonly associated with
migraine headaches, nausea, motion sensitivity, photophobia,
and visual vertigo. The clinical spectrum of VM and its under-
lying pathophysiological mechanisms are the subject of ongo-
ing investigations. Published diagnostic criteria may spur
further research into the mechanistic causes and best treat-
ment of VM.
Conflict of Interest
None declared.
References
1 Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin
C, Akerman S. Pathophysiology of migraine: a disorder of sensory
processing. Physiol Rev 2017;97(02):553–622
2 Sacks OW. Migraine: Evolution of a Common Disorder. London:
Farber and Farber; 1970:35
3 Baloh RW, Kerber K. Baloh and Honrubia’s Clinical Neurophysiol-
ogy of the Vestibular System. 4th ed. New York: Oxford University
Press; 2011:287–301
4 Liveing E. On Megrim, Sick-Headache, and Some Allied Disorders.
A Contribution to the Pathology of Nerve Storms. London: J & A
Churchill; 1873
5 Akkermans R. Harold G Wolff. Lancet Neurol 2015;14(10):
982–983
6 Lashley KS. Patterns of cerebral integration indicated by the
scotomas of migraine. Arch Neurol Psychiatry 1941;46:339
7 Leão AAP. Spreading depression of activity in the cerebral cortex.
J Neurophysiol 1944;7:359–390
8 Leão AAP. Pial circulation and spreading depression of activity in
the cerebral cortex. Neurophysiology 1944;7:391–396
Seminars in Neurology
Baloh
9 Baloh RW. Genes and migraine. Drugs Today (Barc) 2004;40(07):
577–588
10 Eggers SD. Migraine-related vertigo: diagnosis and treatment.
Curr Pain Headache Rep 2007;11(03):217–226
11 Lee H, Jen JC, Cha YH, Nelson SF, Baloh RW. Phenotypic and genetic
analysis of a large family with migraine-associated vertigo. Head-
ache 2008;48(10):1460–1467
12 Sutherland HG, Griffiths LR. Genetics of migraine: insights into
the molecular basis of migraine disorders. Headache 2017;57
(04):537–569
13 Ducros A, Denier C, Joutel A, et al. The clinical spectrum of familial
hemiplegic migraine associated with mutations in a neuronal
calcium channel. N Engl J Med 2001;345(01):17–24
14 Jen J, Yue Q, Nelson SF, et al. A novel nonsense mutation in
CACNA1A causes episodic ataxia and hemiplegia. Neurology
1999;53(01):34–37
15 Jen JC, Graves TD, Hess EJ, Hanna MG, Griggs RC, Baloh RW; CINCH
Investigators. Primary episodic ataxias: diagnosis, pathogenesis
and treatment. Brain 2007;130(Pt 10):2484–2493
Downloaded by: State University of New York at Stony Brook. Copyrighted material.
16 Kors EE, Haan J, Giffin NJ, et al. Expanding the phenotypic
spectrum of the CACNA1A gene T666M mutation: a description
of 5 families with familial hemiplegic migraine. Arch Neurol
2003;60(05):684–688
17 Terwindt G, Kors E, Haan J, et al. Mutation analysis of the
CACNA1A calcium channel subunit gene in 27 patients with
sporadic hemiplegic migraine. Arch Neurol 2002;59:1016–1018
18 Jen JC, Kim GW, Dudding KA, Baloh RW. No mutations in CAC-
NA1A and ATP1A2 in probands with common types of migraine.
Arch Neurol 2004;61(06):926–928
19 Kowalska M, Prendecki M, Kozubski W, Lianeri M, Dorszewska J.
Molecular factors in migraine. Oncotarget 2016;7(31):50708–50718
20 Bain PG, O’Brien MD, Keevil SF, Porter DA. Familial periodic
cerebellar ataxia: a problem of cerebellar intracellular pH homeo-
stasis. Ann Neurol 1992;31(02):147–154
21 Lauritzen M. Pathophysiology of the migraine aura. The spreading
depression theory. Brain 1994;117(Pt 1):199–210
22 Chong CD, Schwedt TJ, Dodick DW. Migraine: what imaging
reveals. Curr Neurol Neurosci Rep 2016;16(07):64
23 van den Maagdenberg AM, Pizzorusso T, Kaja S, et al. High cortical
spreading depression susceptibility and migraine-associated symp-
toms in Ca(v)2.1 S218L mice. Ann Neurol 2010;67(01):85–98
24 Moskowitz MA, Bolay H, Dalkara T. Deciphering migraine mech-
anisms: clues from familial hemiplegic migraine genotypes. Ann
Neurol 2004;55(02):276–280
25 Espinosa-Sanchez JM, Lopez-Escamez JA. New insights into
pathophysiology of vestibular migraine. Front Neurol 2015;6:12
26 Winterkorn JM, Kupersmith MJ, Wirtschafter JD, Forman S. Brief
report: treatment of vasospastic amaurosis fugax with calcium-
channel blockers. N Engl J Med 1993;329(06):396–398
27 Headache Classification Committee of the International Head-
ache Society (IHS). The international classification of headache
disorders, 3rd edition (beta version). Cephalalgia 2013;
33:629–808
28 Colombo B, Teggi R; NIVE Project. Vestibular migraine: who is the
patient? Neurol Sci 2017;38(Suppl 1):107–110
29 Neuhauser HK, Radtke A, von Brevern M, et al. Migrainous vertigo:
prevalence and impact on quality of life. Neurology 2006;67(06):
1028–1033
30 Formeister EJ, Rizk HG, Kohn MA, Sharon JD. The epidemiology of
vestibular migraine: a population-based survey study. Otol Neu-
rotol 2018;39(08):1037–1044
31 Carvalho GF, Vianna-Bell FH, Florencio LL, et al. Presence of
vestibular symptoms and related disability in migraine with
and without aura and chronic migraine. Cephalalgia 2019;39
(01):29–37
32 Teggi R, Colombo B, Albera R, et al. Clinical features, familial
history, and migraine precursors in patients with definite
 Vestibular Migraine I: Mechanisms, Diagnosis, and Clinical Features
vestibular migraine: the VM-phenotype projects. Headache 2018;
58(04):534–544
33 von Brevern M, Zeise D, Neuhauser H, Clarke AH, Lempert T. Acute
migrainous vertigo: clinical and oculographic findings. Brain 2005;
128(Pt 2):365–374
34 Cha YH, Lee H, Santell LS, Baloh RW. Association of benign
recurrent vertigo and migraine in 208 patients. Cephalalgia
2009;29(05):550–555
35 Granziera C, DaSilva AF, Snyder J, Tuch DS, Hadjikhani N. Anatom-
ical alterations of the visual motion processing network in
migraine with and without aura. PLoS Med 2006;3(10):e402
Baloh
36 Woods RP, Iacoboni M, Mazziotta JC. Brief report: bilateral
spreading cerebral hypoperfusion during spontaneous migraine
headache. N Engl J Med 1994;331(25):1689–1692
37 Ayata C, Jin H, Kudo C, Dalkara T, Moskowitz MA. Suppression of
cortical spreading depression in migraine prophylaxis. Ann Neu-
rol 2006;59(04):652–661
38 Russell MB, Olesen J. Increased familial risk and evidence of
genetic factor in migraine. BMJ 1995;311(7004):541–544
39 Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener H-C, Buring JE.
Migraine and risk of cardiovascular disease in women. JAMA
2006;296(03):283–291
Downloaded by: State University of New York at Stony Brook. Copyrighted material.
Seminars in Neurology