Current Pain and Headache Reports (2018) 22:77

https://doi.org/10.1007/s11916-018-0725-1

UNCOMMON AND/OR UNUSUAL HEADACHES AND SYNDROMES (J AILANI, SECTION EDITOR)

Current Aura Without Headache

Divya R. Shah 1 & Sonam Dilwali 2,3 & Deborah I. Friedman 1,4

# Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract
Purpose of Review This review evaluates and explains our current understanding of a rare subtype of migraine, typical aura
without headache, also known as migraine aura without headache or acephalgic migraine.
Recent Findings Typical aura without headache is a known entity within the spectrum of migraine. Its pathophysiology is
suggested to be similar to classic migraines, with cortical spreading depression leading to aura formation but without an
associated headache. No clinical trials have been performed to evaluate treatment options, but case reports suggest that most
patients will respond to the traditional treatments for migraine with aura. Bilateral greater occipital nerve blocks may be helpful in
aborting migraine with prolonged aura. Transcranial magnetic stimulation has shown efficacy in aborting attacks of migraine
with aura but has not been specifically tested in isolated aura.
Summary Typical aura without headache occurs exclusively in 4% patients with migraine, and may take place at some point in
38% of patients with migraine with aura. Typical aura without headache commonly presents with visual aura without headache,
brainstem aura without headache, and can also develop later in life, known as late-onset migraine accompaniment.

Keywords Typical aura without headache . Acephalgic migraine . Migraine aura

Introduction and Epidemiology attacks of reversible focal neurological symptoms that usually
develop gradually over 5-20 minutes and last for less than 60
According to the International Headache Society (IHS), mi- minutes” (Table 1) [1••]. The American Migraine Prevalence
graine aura is defined as a “recurrent disorder manifesting in and Prevention Study estimates that migraine affects 12% of
the population. Based on current census figures, approximate-
ly 39 million people in the USA are affected [2, 3•]. A mi-
This article is part of the Topical Collection on Uncommon and/or
graine aura can occur with or without headache; importantly,
Unusual Headaches and Syndromes typical aura without headache (TAH), previously also known
as acephalgic headache, migraine equivalent, or migraine ac-
* Deborah I. Friedman companiment, is neither accompanied nor followed by head-
Deborah.Friedman@utsouthwestern.edu ache of any sort [1••]. Isolated TAH occurs in 4% of patients
Divya R. Shah with diagnosis of migraine and can occur at some point in
Divya.Shah@phhs.org 38% of patients with migraine headaches [4]. In another study,
the incidence of TAH was higher in females (3%) compared to
Sonam Dilwali
sdilwaliutsw@gmail.com 1% in men with migraine [4, 5••]. TAHs also tend to occur
later in life and are more common in elderly patients [5••, 6•,
1
Department of Neurology and Neurotherapeutics, University of 7•]. However, a prevalence study by Aiba et al. showed that it
Texas Southwestern Medical Center, 5323 Harry Hines Blvd, MC may follow a biphasic distribution between ages 20 to 39 years
9322, Dallas, TX 75390-9322, USA
and 60 to 69 years [8].
2
University of Texas Southwestern, Dallas, TX, USA TAH commonly presents with visual aura without head-
3
Massachusetts General Hospital, Boston, MA, USA ache, although brainstem aura without headache and can also
4
Department of Ophthalmology, University of Texas Southwestern develop later in life, known as late-onset migraine accompa-
Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA niment (LOMA) [7•].
77 Page 2 of 8
Table 1 Diagnostic criteria of typical aura without headache and
migraine with typical aura [1••]
1.2.1 Migraine with typical aura
Description:
Migraine with aura in which aura consists of visual and/or sensory and/or
speech/language symptoms, but no motor weakness, and is
characterized by gradual development, duration of each symptom no
longer than 1 h, a mix of positive and negative features, and complete
reversibility
Diagnostic criteria:
A. At least 2 attacks fulfilling criteria B and C
B. Aura consisting of visual, sensory and/or speech/language symptoms,
each fully reversible, but no motor, brainstem, or retinal symptoms
C. At least 2 of the following four characteristics:
• At least 1 aura symptom spreads gradually over ≥ 5 min, and/or 2 or
more symptoms occur in succession
• Each individual aura symptom lasts 5–60 min
• At least 1 aura symptom is unilateral
• The aura is accompanied, or followed within 60 min, by headache
D. Not better accounted for by another ICHD-3 diagnosis, and transient
ischemic attack has been excluded
1.2.1.2 Typical aura without headache
Description:
Migraine with typical aura in which aura is neither accompanied nor
followed by headache of any sort
Diagnostic criteria:
A. Fulfils criteria for migraine with typical aura
B. No headache accompanies or follows the aura within 60 min
1.2.2 Migraine with brainstem aura
Description:
Migraine with aura symptoms clearly originating from the brainstem, but
no motor weakness
Diagnostic criteria:
A. At least 2 attacks fulfilling criteria B–D
B. Aura consisting of visual, sensory and/or speech/language symptoms,
each fully reversible, but no motor or retinal symptoms
C. At least 2 of the following brainstem symptoms:
• 1. Dysarthria
• 2. Vertigo
• 3. Tinnitus
• 4. Hypacusis
• 5. Diplopia
• 6. Ataxia
• 7. Decreased level of consciousness
D. At least 2 of the following four characteristics:
• 1. At least 1 aura symptom spreads gradually over ≥ 5 min, and/or 2
or more symptoms occur in succession
• 2. Each individual aura symptom lasts 5–60 min
• 3. At least 1 aura symptom is unilateral
• 4. The aura is accompanied, or followed within 60 min, by headache
E. Not better accounted for by another ICHD-3 diagnosis, and transient
ischemic attack has been excluded
Subtypes and Clinical Characteristics
Typical auras without headache can have diverse presenta-
tions, the most common being a visual aura without headache
and brainstem aura without headache (Table 2). The features
of aura are similar in children and adults [10]. In the context of
Curr Pain Headache Rep (2018) 22:77
Table 2 Clinical characteristics of reported cases of typical aura without
headache [5••, 6•, 9••]
Visual Neurological/brainstem
Photopsia Paresthesias
Scotoma Aphasia
Scintillating scotoma Dysarthria
Hemianopia Vertigo
Diplopia Amnesia
Blindness Confusion or stupor
Metamorphopsia Loss of consciousness
Transient monocular blindness Alteration of mood
Hemiparesis
Hearing loss
Hiccups
Mydriasis
Horner syndrome
Diplopia
epidemiology, TAH can also be subcategorized into LOMA
[9••, 11, 12].
Many previous cases reported in the literature show a se-
quence of early migraine with aura followed by aura alone
later in life, sometimes with an intermediate period in which
headache gradually becomes a less prominent feature [12].
Others report visual aura in patients who have never experi-
enced headache [13, 14]. The prognosis of typical aura with
headache remains the same as other forms of migraine for
morbidity and mortality independent of this evolution in head-
ache characteristics [12]. Similar to classic migraine, the neu-
rological deficits do not persist between attacks [12].
Visual Aura Without Headache
Case 1 A 41-year-old woman first experienced recurrent visual
disturbances at age 33 during pregnancy. She described seeing
gray waves in the superior visual field of both eyes lasting 5–
30 min. It sometimes occurred multiple times in the same day,
and happened during each of her pregnancies, as well as at
other times. There was no associated headache. A year prior to
her consultation, she had a different type of episode while
driving. There was a small geometric shape in her vision that
spiralled and enlarged to the point that she was unable to see
well. It was mostly silver in color, lasted 20 min, and dissipat-
ed gradually. She developed a mild headache 30–60 min later,
with photophobia and possibly phonophobia but no nausea.
She lied down and took ibuprofen and it resolved in about an
hour. There was no history of debilitating headaches.
Visual aura alone is the most common presentation, occur-
ring in approximately 23% of individuals with TAH [9••]. The
presence of both positive and negative features is the hallmark
Curr Pain Headache Rep (2018) 22:77
of visual aura. The aura most often begins centrally, mono- or
binocularly, and gradually progresses toward the periphery,
usually lasting 15 to 30 min. Positive visual symptoms, occur-
ring in to up to 90% of patients, include bright images (e.g.,
bright lines, small bright dots, flashes of light, white spots,
disco lights), colored lights (zigzag rainbow colors), and
movement of images in the field (wavy lines, dancing,
jumping) [9••, 13–15]. Negative visual symptoms include sco-
tomas, blind spots, transient monocular visual loss or partial
loss of sight, blurred vision, homonymous hemianopia, bin-
ocular tunnel vision, cortical blindness, and black spots, and
occur in up to 50% of patients. The most commonly reported
of these visual symptoms are scintillating scotomas, with an
area of scotoma with bright and shimmering zigzag lines at the
temporal margin [14]. These may enlarge and travel across the
visual field or appear without a change in size, in which case
they are often crescent-shaped. Importantly, visual aura can
also occur in concert with other accompaniments such as sen-
sory changes, with aura symptoms generally progressing from
one to another over time [7•, 9••].
While visual disturbances are common in migraine, total
visual field loss (cortical blindness) occurs in a limited number
of patients. In a study done by Yener et al., total field deficit
occurred only in 6% of individuals with migraine [16].
Another study found that such losses increased with age as
well as duration of disease [17].
Case 2 A 50-year-old construction manager had a 1-year his-
tory of episodic visual blurring, usually noticed while driving.
He experienced blurred vision in the left eye lasting between
30 s and 5–10 min, affecting his distance and near vision
equally. There was no subjective scotoma, pain, positive visu-
al phenomena, or symptoms of dry eye. The episodes occurred
at least 10–15 times daily. He had no personal history of mi-
graine but his sister had migraine. He took no medications and
was healthy. Prior evaluation including magnetic resonance
imaging (MRI) of the brain and orbits with contrast, carotid
Doppler were normal. The neuro-ophthalmic examination
was normal.
Retinal migraine is an extremely rare condition that gener-
ally affects young women in the second and third decades of
life, often with a history of migraine with aura [18, 19•]. The
ICHD-3 defines retinal migraine as repeated attacks of fully
reversible, unilateral vision disturbance or complete loss, last-
ing less than 60 min, associated with a headache [1••].
However, some cases of vision loss without a headache have
been reported, as have cases with a residual visual deficit
[19•]. A study of 46 patients with retinal migraine found that
54% experienced monocular visual symptoms only while
46% experienced permanent visual loss with otherwise typical
attacks of migraine [19•]. All 46 patients had a previous his-
tory of migraine, both with (50%, including sensory and
speech disturbance in two patients) and without (26%) aura
Page 3 of 8 77
and probable migraine (24%). Attacks occurred exclusively in
one eye in 82% of patients. Most patients (65%) experienced
only negative symptoms, 31% had both positive and negative
symptoms and 4% had positive symptoms only. In another
observational study of monocular symptoms in an Indian pop-
ulation, 3 out of 12 patients studied had episodes of transient
monocular vision loss without associated headache [20].
It can, therefore, be extremely difficult to differentiate ret-
inal migraine from other causes of transient monocular vision
loss such as ischemic optic neuropathy, central retinal artery
occlusion, TIA or emboli, or retinal vein occlusion [21, 22]. It
may also be difficult to distinguish monocular vision loss of
retinal migraine from migraine aura, particularly when there is
absence of headaches in the former, given that patients often
have trouble distinguishing vision loss in one eye from vision
loss in the same hemifield of both eyes [23].
Brainstem Aura Without Headache
Case 3 A 34-year-old woman first experienced brief episodes
of vertigo in 2008 while running. She described “everything
spinning around me” lasting seconds to minutes, possibly as-
sociated with diplopia. The episodes occurred every 1 to
2 weeks over a 4–5-week period and resolved after she
discontinued drinking diet soda. They resumed in 2015, still
provoked by running. When lifting weights in 2015, she de-
veloped a more severe episode accompanied by nausea.
Subsequent episodes occurred up to three times weekly and
could be triggered by a Valsalva maneuver or occur while
sitting quietly. A typical episode began with binocular, vertical
diplopia lasting 2 min followed by vertigo and nausea for 5–
10 min. There was a pressure-like sensation at the onset of
each episode that was not painful.
There was no personal or family history of migraine. She
experienced tension-type headaches in high school and there
was a history of motion sickness in childhood. Triggers for her
recent symptoms included exercise, alcohol, caffeine, aspar-
tame, stress, menses, ovulation, and some forms of chocolate.
Magnetic resonance imaging including angiography and ve-
nography were normal with no signs of intracranial hypoten-
sion or hypertension. Her neuro-ophthalmologic and neuro-
logical examinations were normal. Verapamil 20 mg BID was
prescribed for migraine prevention but she did not take it
because she became pregnant. She made lifestyle changes
and discontinued caffeine with improvement in her symptoms
beginning in her second trimester. After delivery, her episodes
occurred about twice weekly and lasted less than 5 s with
minimal vertigo.
A brainstem aura without headache, previously known as
basilar artery or basilar-type migraine, involves symptoms that
originate from the brainstem such as vertigo, dysarthria, tinni-
tus, hyperacusis, diplopia ataxia, or reduced level of
77 Page 4 of 8
awareness or level of consciousness [1••]. Other symptoms
include unilateral ptosis and hiccups [24]. This type of aura
requires at least two aura symptoms, which are referable to the
vertebro-basilar territory and last between 5 and 60 min [1••].
A typical aura symptom (visual, sensory, speech/language)
must also be present. Brainstem aura without headache makes
up a minority of the patients with aura without headache [25].
A separate diagnosis of vestibular migraine was proposed
in the appendix (A.1.6.5) of the ICHD-3 classification, but has
not yet been accepted and incorporated into the main docu-
ment [1••]. Nonetheless, the diagnosis is frequently used in
clinical practice to distinguish it from migraine with brainstem
aura. The proposed diagnostic criteria for vestibular migraine
are vestibular symptoms of moderate to severe intensity last-
ing between 5 min and 72 h with at least 50% of the episodes
associated with either a migraine headache or visual aura. If
headache is not present, patients may remain undiagnosed or
incorrectly diagnosed for years, precluding appropriate treat-
ment [1••].
Late Onset Migraine Accompaniments
(LOMA)
Case An 80-year-old man started having migraines at age 10.
The episodes began with shimmering in his peripheral vision
or a flashbulb effect followed by severe pain, “like a nail was
coming out of either eye,” associated with profuse vomiting
(he would lose 4–5 pounds during an attack) and worsening
with activity. His last migraine headache was at age 70.
Although the headaches resolved, he continued to experience
the same visual aura symptoms about once or twice monthly,
lasting 8–15 min and he sometimes had more than one episode
in a day. He took ibuprofen 400 mg at the onset of aura. His
previous migraine headaches were so severe that he experi-
enced significant anticipatory anxiety that one of the auras
would be followed by a headache.
C. Miller Fisher (1913–2012), one of the leading clinical
neurologists of the twentieth century, described amaurosis
fugax cause by migraine in 1952, later publishing two articles
describing 205 patients with late-life migrainous accompani-
ments in the 1980s [6•, 7•, 26]. He recounted various neuro-
logical symptoms, occurring both with and without an associ-
ated headache, in individuals over age 40 to distinguish them
from transient ischemic attacks [6•, 7•]. LOMA is another
subtype of TAH, with onset after the age of 40 [11]. It is
characterized by the evolution of migraine aura symptoms in
mid or late-life, often without headache. LOMA may occur for
the first time in 33–77% of patients with migraine with aura.
Unlike migraine in general, migrainous visual aura symptoms
do not necessarily decrease in advanced age [9••].
LOMA patients can present with various types of auras.
Visual symptoms are the most common presentation in 92–
Curr Pain Headache Rep (2018) 22:77
100% of LOMA patients, followed by sensory auras (e.g.,
paresthesias) in 28–31%, speech disturbances (such as aphasic
auras) in 18–33%, and motor auras (such as weakness or pa-
ralysis) in 2–6%, respectively [9••]. Other visual, sensory,
motor, and brainstem aura symptoms may occur (Table 2).
Of these, visual aura often occurs in isolation whereas the
others almost always occur along with visual aura [2, 4].
Hallmarks of LOMAs that help distinguish them from tran-
sient ischemic attacks include the “flurry” of similar episodes,
a march of progression from one manifestation to another
(rather than sudden onset of all symptoms simultaneously)
and a buildup in intensity. [6•, 7•]. Occurrences are character-
ized by recurrent, stereotyped episodes with sequential symp-
toms and evolution across different sensory modalities [9••].
LOMAs can also present as an aura increasing in intensity or
has chronological progression such as movement of visual
symptoms across the visual field or migrating sensory symp-
toms [11, 26].
Pathophysiology
The pathophysiology of migraine has transitioned from a
purely vascular hypothesis to a neurovascular hypothesis, in-
volving the trigeminovascular system and projections within
central nervous system itself [3]. The site of initial activation
generating the migraine process is uncertain but likely in-
volves the hypothalamus and midbrain tegmentum.
Cortical spreading depression (CSD) is a wave of neuronal
and glial depolarization and then suppression, resulting in al-
tered local blood flow and metabolism in the brainstem and
cortex. CSD is thought to be the physiological mechanism of
migraine aura, especially a migraine visual aura. For example,
prior to a visual aura, there may be an initial neuronal depo-
larization followed by hyperpolarization (making it a state of
relative neuronal suppression) that spreads from the occipital
lobe anteriorly [3, 5]. This is accompanied by a rise in extra-
cellular potassium, release of glutamate, and a brief decline in
cerebral blood flow [27••]. Based on animal studies, this
spreading wave of neuronal depression travels at 3 to 5 mm
per minute, similar to the propagation of the scintillating sco-
toma in the visual field described by Lashley in the 1940s and
corroborated by functional imaging studies [28, 29], and
seems to antecede the development of a typical visual aura
[30]. Additionally, prior work studying pattern reversal visual
evoked potentials in patients experiencing visual aura with
and without headache appears supports the theory that mi-
graine aura is related to CSD [31]. High-field blood-oxygen-
ation level-dependent (BOLD) functional MRI studies per-
formed during visual aura found an increase response in pa-
tients with positive symptoms and bi-hemispheric changes in
those with symptoms in both hemifields, suggesting that
Curr Pain Headache Rep (2018) 22:77
different types of cerebral dysfunction occur with different
aura manifestations [32].
The difference between a brainstem aura and a typical vi-
sual aura is most likely that the location of the aura symptoms.
Brainstem aura primarily involves the brainstem or the bilat-
eral occipital hemispheres, whereas a visual aura is mainly
restricted to a unilateral hemisphere and occipital lobe pro-
cess. A study of patients with spontaneous attacks of vestibu-
lar migraine using 18FDG-PET showed activation of the
vestibular-thalamo-cortical pathway and decreased metabo-
lism in the visual cortex [33]. Although changes in brainstem
activation are well documented in migraine with aura, specific
studies investigating isolated brainstem aura are lacking [34].
CSD most likely triggers the migraine aura but it may not
always be a sufficient trigger to develop a headache [4]. This
is indirectly supported by the observation that migraine aura
tends to be more severe and of longer duration if followed by a
headache [4]. The understanding of migraine pathophysiology
thus far could explain the existence of typical auras without
headache or the progression of migraine headaches with aura
to typical auras without headache as people age, as in the case
of LOMA. Further work is needed to confidently elucidate the
underlying mechanisms of TAH and of migraines.
Differential Diagnosis
The lack of headache and presence of transient focal neuro-
logical symptoms makes diagnosis of TAH challenging.
Although a benign condition, it can mimic more serious dis-
eases and usually requires careful medical history and appro-
priate investigations before it can be diagnosed [1, 5, 9••]. The
differential diagnosis is broad and includes transient ischemic
attacks [35, 36], seizures [37–39], subarachnoid hemorrhage
[40, 41], and brain tumors. Other possible diagnoses include
but are not limited to reversible cerebral vasoconstriction syn-
drome, cerebral amyloid angiopathy, arteriovenous
malformations, internal carotid artery or vertebral artery dis-
section, and cerebral vasculitis [9••].
Distinguishing TAH from TIA relies heavily on patient
history and description of the symptoms. TIAs are most fre-
quently associated with cardiovascular comorbidities such as
hypertension and diabetes mellitus. Visual symptoms in mi-
graine most commonly include teichopsia and photopsia with
gradual buildup and slow evolution whereas patients with TIA
often present with homonymous hemianopsia or other nega-
tive visual symptoms of sudden onset; however, homonymous
hemianopia most often begins suddenly in migraine. Other
neurologic symptoms and signs occurring in TIA usually start
simultaneously compared to a gradual onset and progression
in migraine. The duration of TIA symptoms is short, lasting 5
to 10 min, while aura symptoms can last up to 60 min [5, 9••].
Nonetheless, there is considerable overlap in the duration of
Page 5 of 8 77
the two conditions. Evidence of ischemic disease is also found
in 30% of patients with TIA using diffusion-weighted imaging
[5, 9••, 35]. Despite these differences, diagnosing TAH in
clinical practice is difficult as evidenced by a case report in
which a patient was previously repeatedly misdiagnosed with
TIAs due to his description of “blurry vision” as well as nor-
mal neuroimaging [5]. Blurred vision is nonspecific com-
plaint. It does not arise from the visual cortex and is much
more likely to represent migraine; patients with incomplete
diplopia may experience “blurred vision” which clears with
monocular viewing and is the exception to this premise [42].
The etiology of amaurosis fugax (“fleeting darkness”), or
brief episodes of transient monocular visual loss is particularly
vexing to diagnose, requiring an evaluation for cardiac, retinal
artery or vein, carotid, inflammatory, medication-induced, and
embolic disorders. However, recurrent episodes of otherwise
typical amaurosis fugax may occur as a manifestation of either
retinal migraine or “vasospasm.” In some patients, attacks may
occur multiple times daily, usually lasting less than 15 min
each [43]. Rare cases have been examined during the attacks,
revealing constriction of retinal vessels, optic disc pallor, and
rouleaux formation [43, 44, 45•]. Retinal spreading depression
has been demonstrated in chick, frog, and rat models, and is
another potential mechanism for retinal migraine. The
calcitonin-like receptor (CLR), a key component of the calci-
tonin gene-related peptide (CGRP) receptor, is expressed in
chick retina [46]. CGRP immunoreactivity was found in
Műller cells of rats, and CLR and receptor activity-modifying
receptor 1 (RAMP1) are located in the rat retinal nerve fiber
layer [47]. Calcium channel blockers (e.g., nifedipine, verapa-
mil) are generally effective in preventing attacks. Retrospective
case series suggest that transient monocular visual loss occur-
ring in patients under age 40 is likely to be benign [48].
Nonconvulsive epilepsy, particularly arising from occipital
lobe, and migraine have a number of overlapping features
such as triggers, recurrent attacks, visual symptoms, positive
sensory symptoms such as paresthesias, motor weakness, and
language disturbances [37, 49]. The localization and patterns
of visual symptoms can differ between the two entities. A
study of 54 patients found that positive visual phenomena
were centrally located in the visual field of epileptic patients
in contrast to a peripheral location in migraine patients, where-
as negative visual phenomena tended to be diffuse in the for-
mer and peripheral in the latter [38]. The duration of symp-
toms in epilepsy tends to be extremely short lasting a few
seconds whereas migraine lasts at least 5 min per ICHD
criteria. Migraine visual phenomena tend to be angulated or
geometric. The presence or absence of color does not distin-
guish the two conditions [50]. Eliciting a detailed description
of each attack and EEG may be helpful in determining the
diagnosis in such cases [9••, 38, 39].
Other worrisome diagnoses, including SAH and brain tu-
mors, must also be considered. SAH usually presents with
77 Page 6 of 8
sudden onset of excruciating headache (“thunderclap head-
ache”) while brain tumors often have insidious onset headache
with or without focal neurological deficits. Attacks of TAH
are usually recurrent with possible remote history of head-
aches when younger. Neuroimaging in such cases can help
establish the diagnosis.
Treatment
Evidence for specific treatment of TAH is limited. Aura symp-
toms tend to resolve spontaneously without acute treatment;
however, prolonged or persistent aura may require
intervention.
Various medications for abortive treatment of prolonged
aura have been reported as single case reports or small case
series [2, 9••, 51]. These include isoproterenol inhalation [51],
calcium channel blockers such as sublingual nifedipine [52],
divalproex sodium [53], intranasal ketamine [54, 55], intrave-
nous furosemide [56], oral acetazolamide [57], and
lamotrigine [58]. A double-blind, randomized, controlled trial
to investigate the effect of intranasal ketamine vs intranasal
midazolam in patients with prolonged aura found that keta-
mine reduced the severity of aura (p = 0.032) but not its dura-
tion, while midazolam had no effect [55]. A prospective open
study in 59 patients with migraine with aura who were treated
with lamotrigine showed that it significantly reduced both
frequency and duration of attacks (p = 0.001) [58].
The role of N-methyl-D-aspartate (NMDA) activity for
propagation of cortical spreading depression is supported by
the fact that NMDA antagonists such as ketamine, as noted
above, may be effective in acute treatment of aura. Similarly,
the efficacy of the ginkgolide B, a herbal constituent extract
from Ginkgo biloba tree leaves, was studied [59]. Ginkgolide
B is a natural modulator of neurotransmitter glutamate via the
NMDA receptors. Use of this remedy was associated with a
shortened duration of aura in 60% of cases (p < 0.001).
The novel drug tonabersat is a neuronal gap junction inhib-
itor that was developed based on its ability to inhibit cortical
spreading depression. Its efficacy was studied in two clinical
trials for the treatment of migraine headaches with mixed re-
sults [60, 61]. The effect on aura was analyzed in one of the
two clinical trials, showing benefit in participants with mi-
graine with aura but not in those without aura, supporting
the concept of CSD in the generation of migraine aura [61].
Bilateral greater occipital nerve blocks with bupivacaine
0.5% have also been investigated for the treatment of aura.
In a prospective, open-label study of 22 aura episodes in 18
patients, 85% of prolonged auras (> 2 h) improved with the
nerve blocks, with up to 60% having complete resolution
[62•]. Response was complete and sustained in 50% of the
episodes, with no recurrence of symptoms during the first
24 h. Two patients had complete resolution with recurrence
Curr Pain Headache Rep (2018) 22:77
in < 24 h and 6 patients had at least 50% improvement.
Complete response was more likely when the aura duration
was less than 1 week. The mechanism of the greater occipital
nerve block has yet to be determined [62•].
Altered primary visual cortex excitability is postulated to
predispose to spontaneous CSD in migraine aura. Low fre-
quency, single pulse transcranial magnetic stimulation
(sTMS) delivers a brief magnetic pulse to the scalp and un-
derlying cortex, changing neuronal firing. Its use in migraine
was pursued after discovering that TMS inhibits CSF in ani-
mal models [63•]. The handheld, rechargeable device
(SpringTMS™) delivering a single pulse of magnetic stimu-
lation to the back of the head was tested in a randomized,
double-blind, sham controlled trial of patients (n = 201) with
episodic migraine with aura [63•]. Participants were required
to have aura in at least 30% of their migraine episodes.
Treatment with sTMS as soon as aura began (and no later than
1 h after aura onset) resulted in pain freedom in 2 h in 39% of
participants compared to 22% who treated with the sham de-
vice (p = 0.179). The benefit persisted at 24 and 48 h. The
effect of the device on aura was not analyzed. The device is
approved by the Food and Drug Administration for the acute
and preventive treatment of migraine with our without aura.
Conclusions
TAH is a subtype of migraine with aura. Many cases have
been described in the literature, with increasing recognition
of this as a separate clinical entity in the recent years.
Typical auras without headache have diverse presentations,
with the most common manifestations being a visual aura
without headache and brainstem aura without headache.
Either of these syndromes can evolve later in life in migraine
patients as LOMA. Chronological progression such as move-
ment of visual symptoms across the visual field or migrating
sensory symptoms are characteristic of TAH. It is important to
distinguish TAH from TIAs, nonconvulsive epilepsy, SAH,
and brain tumors, depending on the history and clinical pre-
sentation. Our understanding of TAH provides insight into
pathophysiology of migraine, as the aura is attributed to corti-
cal spreading depression that does not trigger a neurovascular
response robust enough to lead to an accompanying headache.
Treatment for this type of migraine has not been well-studied,
but most patients respond well to traditional treatments for
migraine with aura, occipital nerve blocks, and possibly
TMS. Further studies are needed to elucidate the most effective
treatments for this headache subtype.
Compliance with Ethical Standards
Conflict of Interest Divya Shah and Sonam Dilwali declare no conflict
of interest. Deborah Friedman, MD, MPH, has no relevant conflicts of
Curr Pain Headache Rep (2018) 22:77
interest to disclose. She has served on advisory boards for Allergan, Alder
Biopharmaceuticals, Avanir, Amgen, Biohaven Pharmaceuticals,
electroCore, Eli Lilly, Supernus, Teva and Zosano. She speaks on behalf
of Allergan, Amgen, Autonomic Technologies, Inc, electroCore,
Supernus and Teva and has received research support through UT
Southwestern from Autonomic Technologies, Inc, Eli Lilly, Merck and
Zosano. She has received compensation for being on the editorial board
for Neurology Reviews and as a contributing author to MedLink
Neurology.
Human and Animal Rights and Informed Consent This article does not
contain any studies with human or animal subjects performed by any of
the authors.
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