Migraine: mimics, borderlands
Dr Heather Angus-Leppan,
Department of Neurology,
Barnet and Royal Free
Hospitals, Pond Street,
London NW32QG, UK;
Published Online First
1 August 2013
To cite: Angus-Leppan H.
Pract Neurol 2013;13:
Diagnostically, headache is the easy part of
migraine. It is the surrounds of migraine—the
aura, prodrome and postdrome—that can be
most challenging, and confused with other
pathologies. This article examines the definition
and variants of migraine; alternative diagnoses
for which migraine may be mistaken (mimics);
conditions that lie between migraine and other
diagnoses (borderlands) and the possible
presentations of migraine posing as other
conditions (chameleons). The focus is on adults,
with only passing reference to children. Migraine
is more often a chameleon than a mimic; and it
is the careful history that usually makes the
distinction. Given migraine’s prevalence of
10–15%, relatively uncommon features of
migraine occur quite often, in comparison with
frequent manifestations of less common
diseases. Thus, even rare or under-recognised
presentations of migraine come into the
differential diagnosis of many presentations.
WHAT IS MIGRAINE? THE HEADACHE,
PREMONITORY SYMPTOMS, THE
AURA AND INTERICTAL
Migraine headache is classified as one of
the primary headache disorders, defined as
recurrent attacks of moderate or severe
intensity lasting 4–72 h; typically with uni-
lateral location, pulsating quality, nausea
and/or photophobia and phonophobia,
worse with physical activity.
For the prac-
tical neurologist, only a minority of
patients with migraine fits entirely into this
International classification of headache dis-
orders (ICHD) definition
Secondary migraine headaches (symptom-
atic migraine) are rare (figure 2), and asso-
ciated features usually make the underlying
cause obvious. Abnormal physical signs
should prompt investigation.
Despite the rarity of secondary
migraine, they create great anxiety: most
of our patients perceive severity of head-
ache as a marker of a sinister pathology.
It can be difficult to distinguish a ‘mimic’
from a primary migraine triggered by an
intercurrent condition—for example, a
migraineur who develops a benign fever
and a primary migraine headache with
photophobia and phonophobia may lead
to investigation for meningitis.
Premonitory symptoms, defined as
non-headache symptoms up to 2 days
before a migraine episode, occur in 33–
87% of patients
and include fatigue,
mood change, poor concentration,
change in bowel and bladder function
and neck stiffness. An electronic diary
study in which entries could not be
altered retrospectively showed that these
‘premonitory’ symptoms occurred before,
during and after migraine attacks, sug-
gesting that these are part of the migraine
Typical migraine aura is defined in the
ICHD as reversible positive and/or nega-
tive sensory, and/or visual and/or speech
focal neurological symptoms that usually
develop gradually, lasting between 5 and
while hemipleg ic migraine is
defined separately and may be of longer
Their gradual onset helps to
differentiate these symptoms from sei-
zures and vascular events, and their
longer duration helps further to distin-
guish them from seizures.
Migraine auras are commonly ‘atyp-
ical’. A recent systematic review of the
usual duration of migraine aura found
that migraine aura lasted longer than 1 h
in a significant proportion of migraineurs
(up to 60% in aphasic aura).
authors’ suggested labelling of these
patients as having probable, rather than
definite, migraine is inappropriate.
Neurologists must untangle the myriad
of sensory, autonomic, motor, perceptual
and cognitive aura and symptoms with
which migraine may present (figure 3).
These are usually positive symptoms,
often with interictal hypersensitivity, and
308 Angus-Leppan H. Pract Neurol 2013;13:308–318. doi:10.1136/practneurol-2012-000502
particularly visual. Most migraineurs develop photo-
phobia, phonophobia and/or osmophobia.
Our patients (and colleagues) may find it hard to
believe that the aura can come before, during, after
the headache, or even without a headache; and an
important part of the management is reassurance and
Research highlights potential pathophysiological
mechanisms for this, and imaging studies show
changes in the brainstem regions suggesting that
migraine involves sensory dysmodulation (upregula-
Electrophysiological studies show increased
amplitude of visual evoked responses in migraine, and
functional studies showing heightened ability of
migraine patients in low-level visual tasks, and heigh-
tened sensitivity to certain visual stimuli. There may
be significantly higher glucose metabolism bilaterally
in the posterior subcortical cerebrum and in the cere-
bellum in those with migraine, during headache-free
periods, compared with controls.
are usually visual and vestibular, but can be olfactory,
gustatory or auditory. They tend to be elementary or
unformed, variable in position and do not conform to
anatomical guidelines, in that they are not necess arily
Figure 1 What is migraine?
Figure 2 Migraine mimics and secondary causes.
Angus-Leppan H. Pract Neurol 2013;13:308–318. doi:10.1136/practneurol-2012-000502 309
contralateral to the headache. Apart from their
importance as a problem to the patient, they tell us a
lot about migraine—and argue against the idea that
migraine is simply a vascular disturbance.
Several migraine variants are common in neurology
clinics. Some authorities classify these as distinct
primary headaches: the debate about their classifica-
tion highlights the difficulties when conditions do not
have clear biological markers, and their diagnosis is
based on a combination of clinical features.
Icepick headaches (primary stabbing headaches) are
isolated brief stabbing pains, usually in the orbital,
temporal or parietal area, which occur in 40% of
They usually require no treatment
beyond reassurance, though will frequently respond to
Icecream headaches occur in one-third of the popu-
lation, and their link with migraine is less cer tain.
Primary thunderclap headache is a diagnosis of
exclusion. Thunderclap headache of new onset—
defined as headache reaching maximum intensity
within 10 s and including coital and other
exercise-induced headache—requires urgent investiga-
tion. Although nausea, neck stiffness, occipital loca-
tion and impaired consciousness more frequently
accompany subarachnoid headache,
they are not
invariable, and their absence cannot be relied upon
all patients need investigation. There is no consensus
on percentage of thunderclap headaches that are due
to subarachnoid haemorrhage: estimates range from
11% to 70%. Reassuringly, if investigations (at least
CT scan and lumbar puncture) exclude haemorrhage,
stroke or a sinister cause, follow-up for 1–7 years
shows no subarachnoid haemorrhage mortality,
although thunderclap headaches recur in 24%.
supports the entity of benign thunderclap headache as
a migraine variant, and is in keeping with district hos-
pital clinical experience. Studies from tertiary centres,
which lack the long-term follow-up of studies on
primary thunderclap headache, suggest that primary
thunderclap headache is rare, and that most are due to
reversible cerebral vasospastic syndrome,
cussed below. The issue is unresolved, and hinges on
whether angiography is showing pre-existent vaso-
spasm, or whether it triggers vasospasm in patients
with acute migraine.
Chronic daily headache describes a phenotype
occurring 15 or more days per month for at least
3 months, with each attack averaging 4 h or more.
Chronic migraine, with or without a history of epi-
sodic migraine, is a subtype of chronic daily headache,
and may occur with or without analgesia overuse.
This section comprises two distinct groups:
▪ Primary headache conditions classified as separate
entities, such as the trigeminal autonomic cephalgias
which are distinguished by differences in their postulated
pathophysiology and treatment recommendations.
▪ Secondary or symptomatic migraine, much less common
than primary migraine, but important to differentiate
because of their underlying causes.
Trigeminal autonomic cephalgias
The trigeminal autonomic cephalgias are a group of
primary headache disorders characterised by auto-
nomic features in conjunction with unilateral head-
ache. The group includes cluster headaches,
paroxysmal hemicranias, hemicrania continua and
‘short-lasting, unilateral, neuralgiform headache
attacks with conjunctival tearing’ (SUNCT). Cluster
headache is the most common of these, differing from
migraine in the boring quality of pain, often nocturnal
and usually orbital, lasting 45–90 min, with
Figure 3 The migraine icecream.
310 Angus-Leppan H. Pract Neurol 2013;13:308–318. doi:10.1136/practneurol-2012-000502
prominent autonomic features, and a desire to walk
around rather than sit still. The clinical features and
treatments of trigeminal autonomic cephalgias are
There are distinct pathophysi-
ology and treatment paradigms postulated for trigem-
inal autonomic cephalgias. Although these entities are
presented as distinct syndromes, in clinical practice,
many patients with cluster headache have migrainous
Some patients have attacks with the car-
dinal features of cluster headache, but also have a few
migrainous symptoms, especially a visual aura.
recent study found 24.5% of patients with cluster
headache had at least one migrainous feature.
term ‘cluster migraine’ is used to denote syndromes
when there is significant overlap between cluster
headache and migraine.
see changing patterns occurring in some patients, who
may have migraine with aura, migraine without aura,
cluster headache and cluster migraine at different
times in their lives.
Response to treatment is also
not exclusive: for example, migraine and other
primary headache may respond to high-flow oxygen
therapy as cluster headache does,
headaches may respond to medications used for
migraine, such as pizotifen and propranolol.
While striving for diagnostic clarity and avoiding
unfocussed thinking, it is sensible to keep an open
mind to the rich permeations encountered in presen-
tations and responses to treatment of primary head-
ache. Some patients have headaches that move from
one phenotype to another (in the current headache
classification). In the future, other biological markers
may help with better understanding of the overlap-
ping or changing phenotypes of primary headache in
individual patients, and to mod ifications in our
It may be difficult to know whether headaches occur-
ring with newly recognised hypertension are solely
due to the hypertension, or represent a triggering of a
tendency to migraine. Either way, new migraine or
worsening migraine should always prompt checking
of blood pressure.
Severe headache, with pain centred on one eye (some-
times with tenderness and hardness of the eye), with
blurred vision or visual loss, with haloes around
objects, or with redness of the eye, may each indicate
acute closed-angle glaucoma, and is an emergency.
Carotid artery dissection
The headache of carotid artery dissection is variable.
Most commonly it is distinguishable from migraine by
being dull and without throbbing; however, it may be
more migrainous, and even with a reported classical
visual aura. As headache may precede ischaemic
manifestations, it is important to consider the diagno-
sis, and look for ipsilateral neck pain, along with
Horner’s syndrome (40% of cases). Although
Horner’s syndrome is non-specific, it should prompt
investigation of possible carotid artery dissection at its
Structural intracranial lesions with or without raised
Raised intracranial pressure or mass lesions may
present with headache alone. This may be either
chronic daily or subacute daily headache, and may
have migrainous features; characteristically, however,
there is an early morning preponderance, vomiting
without nausea, visual obscurations, and later, clinical
signs of reduced alertness, cranial nerves palsies—
including sixth nerve palsy—and papilloedema.
Acute and chronic meningitis
Acute meningitis is usually apparent from the accom-
panying fever, neck stiffness and other neurological
features. Chronic meningeal infection, inflammation
and malignant meningitis usually have other symp-
toms and signs.
Giant cell (temporal) arteritis
The characteristic headache of giant cell arteritis is
throbbing, and the headache may be migrainou s; but
the associated features of scalp tenderness, jaw claudi-
cation, weight loss, fatigue and myalgia, in a person
over 60 years of age, are important indicators of the
diagnosis; any clinical suspicion should prompt urgent
Reversible cerebral vasospastic syndrome
This entity is now defined as severe headache—with
or without additional neurological symptoms—asso-
ciated with vasospasm on cerebral angiography. The
headaches are usually thunderclap.
There is an
underlying cause in about two-thirds of cases (post
partum, hypertension, drugs), with the remainder
having no known cause. Early descriptions empha-
sised its link with migraine, with headache indistin-
guishable from migraine and a good prognosis.
Vasospasm in migraine does occur,
can trigger migrainous infarction. However, in one
series persistent focal cerebral events occurred at
similar rates in patients with migraine compared to
non-age-matched patients having angiography for
other reasons (2.6% compared to 2.8%), although
migraineurs had a 5% rate of transient deficits.
angiography is not usually carried out for acute
uncomplicated migraine, the incidence of vasospasm
THE BORDERLAND OF MIGRAINE
Some entities are difficult to categorise, such as symp-
tomatic migraine and migrainous stroke.
Angus-Leppan H. Pract Neurol 2013;13:308–318. doi:10.1136/practneurol-2012-000502 311
Recent genetic advances have added a range of very
rare causes of secondary migraine, usually with other
specific features: such as mitochondrial cytopathies
and cerebral autosomal-dominant arteriopathy with
subcortical infarctions and leukoencephalopathy
(CADASIL). Familial hemiplegic migraine, and its
association with channelopathies—most commonly
voltage-gated calcium channel genes—is rare, but a
subject of much research.
These familial hemiplegic
migraines may be associated with epileptic seizures,
and sometimes with ataxia. Severe recurrent migraine
encephalopathy is usually secondary, for example, to a
mitochondrial encephalomyelopathy, but migraine
may be its only manifestation at onset. This may give
motor, visual and speech deficits, but can also result
in deafness, persistent vestibular, auditory or retinal
disturbance (chronic vertigo or tinnitus). It is essential
to investigate for other causes of stroke in patients
Migralepsy is defined as an epileptic seizure follow-
ing at a maximum of an hour after a migraine aura.
These have been covered in a previous article.
Rarely, migraine is less benign, with migrainous
infarction, leaving the patient with a fixed deficit.
The syndrome of transient global amnesia is
common, may be associated with migraine or vascular
disease, and must be distinguished from transient epi-
In some patients, there is no specific
aetiology; investigations are normal or non-
contributory and prognosis is good.
leptic amnesia is clearly distinguishable from transient
global amnesia by having much shorter and recurrent
episodes, together with characteristic progressive
interictal memory problems, particularly autobio-
graphical amnesia. Differentiating vascular from
migrainous causes of transient global amnesia is more
difficult, but table 1 outlines some helpful features,
for example, absence of vascular risk factors, low
recurrence rate and normal investigations, in migrain-
ous causes. The difference is important for prognosis
(excellent for migrainous transient global amnesia),
and for management, including advice on driving.
Clinical studies show a clear temporal link between
migrainous headache and transient global amnesia,
in some cases the amnesic episode being triggered
only by migraine.
Such a temporal link is similar to
that of other accepted migraine accompaniments, such
as visual aura, hemiplegia, or limb pain; all of which
are considered to be due to, or part of, a migraine
episode. Normal ictal and inter-ictal EEG, MRI and
Doppler studies support transient global amnesia
having a migrainous aetiology, but diffusion-weighted
MRI changes in transient global amnesia are contra-
dictory: diffusion-weighted imaging changes in
patients with migraine do not imply generalised vascu-
lar disease. Patients with migraine have a significantly
higher rates of non-specific diffusion-weighted
imaging abnormalities and other imaging changes
than controls, even when the MRI is normal.
This section covers situations when migraine is the
correct diagnosis—although it looks like something
else. Migraine is most commonly confused with other
paroxysmal disorders, particularly epilepsy or stroke.
Table 2 summarises some common differentials, with
key distinguishing features.
Transient ischaemic attacks
Visual loss may present as part of vertebro–basilar
migraine, although lone transient bilateral blindness is
an unusual migrainous phenomenon. It is more likely
that this is a transient ischaemic event—generally pos-
terior circulation if bilateral, carotid if unilateral.
Transient lone visual loss in young people can be
benign, as documented in follow-up of 14 patients
over 4–13 years
; it is probably migrainous but can
present as part of a benign occipital epilepsy (see
below). In this series, investigations were normal, with
no deficits developing over the subsequent years. At
presentation, it is difficult to make this diagnosis: the
clinician must consider other causes and investigate
accordingly. Their brief duration (seconds), sudden
Table 1 Transient global amnesia: usual characteristics
Transient global amnesia
Transient epileptic amnesia
(temporal lobe epilepsy)
Transient global amnesia
(vascular) Psychogenic amnesia
Middle-aged women Middle-aged men Vasculopaths Young
Anterograde amnesia Anterograde amnesia Anterograde amnesia Variable amnesia
2–24 h <1 h <24 h Variable duration
Recurrence uncommon Recurrence common Recurrence and new events Variable
Cannot learn new information Cannot learn new information Cannot learn new information May learn new information
Retained identity Retained identity Retained identity Personal identity lost
Any time of day Frequently from sleep Any time of day After acute stress/trigger
Headache/nausea/dizziness Variable headache Variable headache Variable headache
Normal investigations EEG temporal abnormalities EEG normal or non-specific EEG normal or non-specific
Memory normal Accelerated forgetting
Remote memory impairment
Related to vascular disease Variable
312 Angus-Leppan H. Pract Neurol 2013;13:308–318. doi:10.1136/practneurol-2012-000502
onset, and negative symptom of visual loss would
each be unusual for migraine aura.
The most frequent migraine auras are elementary
visual symptoms (40%).
Visual ‘blurring’ is
common, but non-specific, and further questioning is
needed to distinguish an ill-defined difficulty in focus-
sing, unformed hallucinations (‘frosted glass’),
reduced acuity, complex perceptual disturbances,
mental clouding or poor concentration.
Strokes rarely cause positive visual symptoms; but it
is important to remember the Charles Bonnet syn-
drome (visual hallucinations in the presence of severe
visual impairment) which may follow an occipital
stroke with visual field disturbance. This syndrome is
more common in older people, who may discuss
hallucinations reluctantly, fearing a psychiatric label.
Auras of gradual onset often include motor symp-
toms—a gradual onset of heaviness or ‘numbness’—
easily distinguished from sudden onset ischaemic
Dysphasia as an apparent migraine aura requires
investigation. It can often be distinguished clinically
from an ischaemic event by a stuttering onset, other
symptoms relating to more than one vascular territory,
past episodes and other features of migraine.
Misperceptions, such as prosopagnosia may occur
in migraine as an aura, sometimes with object agnosias
with hemianopia or memory disturbance.
usually recover if the diagnosis is migraine, but stroke
should obviously be the first consideration.
Visual aura may be confused with the much rarer
occipital epilepsy, particularly in childhood.
Occipital epilepsy auras are well characterised through
their short duration (seconds) is the
most robust distinguishing feature (figure 4).
Autonomic symptoms of vomiting, pallor and sweat-
ing are very common, especially in children. It may be
difficult to differentiate migraine from childhood
occipital epilepsies, particularly as the pathognomonic
visual symptoms may be brief and overlooked, or may
not even occur.
Transient lone blindness can rarely
occur in occipital epilepsy; as well as in stroke and
Olfactory and gustatory hallucinations are usually
attributed to temporal lobe seizures, and may be
under-recognised in migraine. The context and long
duration—between 5 min and 24 h—suggest a
As with other sensory migrainous
phenomena, there may be altered olfaction between
attacks. In one study, atypically for migraine, there
was reduced (rather than heightened) olfaction in
18% of migraineurs versus 1% of controls.
small series, seven patients reported olfactory and/or
gustatory hallucinations with most migraine attacks.
They reported distortions or body image as well as
abnormal perceptual experiences and mood change:
unsurprising, given that this is a temporal–limbic
Motor seizures are usually much briefer, lasting
only seconds or very few minutes, with a positive
element—sudden shaking, progressive shaking, dys-
tonia or hypermotor—whereas, this is exceedingly
rare in ischaemic or migrainous events.
It is crucial to distinguish migrainous dysphasia
from dysphasia due to a postictal (Todd’s) phenom-
enon, or intermittent dysphasia from a fixed lesion
such as tumour.
Somatosensory auras, usually tingling or numbness,
comprise about one-third of all migraine auras, and
are the second most common after visual ones.
patients aged over 40 years, upper and lower limb
sensory symptoms occur in 24% of the 70% of
patients with somatosensory migrainous aura; they
have variable distribution, sometimes circumscribed
A sensory migrainous aura may have
a pseudo-peripheral distribution.
upper and lower limb paraesthesia, entering the differ-
ential diagnosis of peripheral neuropathy
in migraineurs as an aura of varying duration, without
headache, including basilar migraine. I have seen
several patients with such recurrent migraine auras of
who have been investigated for per-
ipheral neuropathy, usually when headaches are absent
or inconspicuous, at initial presentation.
Radiculopathy, thoracic outlet syndrome and
Migraine limb pain syndrome is intermittent pain
occurring in upper or lower limbs, temporally related
Table 2 Migraine chameleons
Feature Onset Offset Duration Quality (usual modality) Loss of function
Acute migraine Gradual Gradual 5 min to several hours Positive (special sensory) Usually none, or temporary
Chronic migraine Gradual Ongoing Ongoing Positive (special sensory) Usually none, or temporary
Transient ischaemic attacks Sudden Sudden Minutes to 24 h Negative (loss of function) Temporary
Stroke Sudden Ongoing Long-term Negative Permanent, incomplete recovery
Epileptic seizures Sudden Sudden 1–120 s Positive Nil, occasional temporary (Todd’s paresis)
Angus-Leppan H. Pract Neurol 2013;13:308–318. doi:10.1136/practneurol-2012-000502 313
either to a migraine episode, cluster headache or
cluster migraine; it may be mistaken for cervical or
lumbar radiculopathy. Limb pain is usually ipsilateral
to the headache, but can alternate sides and may
spread with a migrainous march over 20 min or
Limb pain and headache may alternate in
severity in different attacks. It is often unrecognised,
as limb pain may not coincide with headache at pres-
entation; other initially suspected diagnoses may
include cervical radiculopathy, thoracic outlet syn-
drome, arthritis or nerve entrapment. The diagnosis
may become apparent only later, when both limb pai n
and headache are reported or discovered on direct
questioning. Sporadic reports go back to 1873,
the first series suggesting an incidence of 1–2%;
subsequent prospective series suggested that 4.4% of
245 migraineurs had limb pain.
Limb pain, by either day or night, may be the only
or the first manifestation of migraine in childhood;
once again, a careful elucidation of other features may
give the clue. The child may be pale and photophobic.
Migraine limb pain in children may be mistaken for
joint or bone pathology, ‘growing pains’ or psycho-
logical disturbance. Limb pain may vary in posi tion,
excluding local joint pathology. Limb pain accompan-
ies migraine in children with an incidence of 2.6%.
One family had limb pain in childhood followed by
migraine in adulthood.
The physiological basis for migraine limb pain syn-
drome may be the convergence of nociceptive input
from meningeal vessels in the cervical spinal cord,
brainstem, thalamus and cortex.
Vestibular and auditory disorders
Migrainous vertigo is extremely common, usually giving
a sense of disequilibrium rather than true rotation. It is
often missed, it may be labelled as an acute vestibular
neuritis. It may be triggered by a change in position, and
may be difficult to distinguish from benign paroxysmal
positional vertigo. The longer duration of migrainous
vertigo—between 5 min and 72 h,—and a negative
Hallpike’s manoeuvre, are important distinguishing fea-
tures. The International Headache Society will acknow-
ledge migrainous vertigo in the next classification,
hopefully increasing its recognition.
The incidence of auditory hallucinations in migraine
is uncertain, but they do occur in both children and
Simple auditory hallucinations, such as bilat-
eral or unilateral tinnitus, are probably frequent and
may be misdiagnosed as idiopathic. It is always worth
enquiring about migraine in patients with tinnitus, given
its potential for treatment. The context, associations,
hearing and examination help to distinguish migrainous
vertigo from the effects of vestibular toxins, and struc-
tural or inflammatory causes, particularly if unilateral.
In some patients with migraine, intermittent tinnitus
may become a chronic fixed deficit, just as a few patients
with motor migraine are left with a persistent hemipar-
esis due to migrainous infarction. This diagnosis can
only be made with a clear history of migraine with epi-
sodic tinnitus, and exclusion of other causes.
Cyclical vomiting is a curious entity, which is some-
times a form of migraine. The International Headache
Figure 4 Elementary visual auras–differentiation.
314 Angus-Leppan H. Pract Neurol 2013;13:308–318. doi:10.1136/practneurol-2012-000502
Society includes it as a childhood syndrome that com-
monly precedes migraine,
but do not recognise it as
adult syndrome. However, it can be migrainous in
adults; sometimes ascribed to idiopathic gastroparesis.
It must be distinguished from gastric stasis due to
autonomic neuropathy, particularly from diabetes
Abdominal migraine in children may be mistaken
for local pathologies, particularly appendicitis and
gastroenteritis; or with psychological disturbance or
school refusal. Children with abdominal migraine are
often pale and quiet, and withdraw briefly from pleas-
ant activities. They may have associated headache,
photophobia and dizziness, and it is important to ask
specifically about this. The symptoms are often much
briefer than in adults, so that some diagnostic features
could be overlooked.
In adults, jaw, neck, shoulder and chest pain—some-
times with limb pain (see above)—may occur with or
without headache, and be confused with ischaemic
heart disease: the painful areas are often allodynic.
There is a significant association between migraine
with atypical chest pain (Prinzmetal’s angina) and
with Raynaud’s disease, hypothesised to form part of
a generalised vasospastic disorder. This issue has not
Syncope in vertebro–basilar migraine occurs, but with
an unknown incidence. It may be mistaken for
syncope due to other causes, or with epileptic drop
attacks, but the initial symptoms indicating involve-
ment of territories within vertebro–basilar distribu-
tion, and sometimes long duration of the syncope
should help to distinguish it.
Intermittent ‘tingling’ without objective sensory
change is the most common somatosensory symptom
in migraine. Paraesthesia may involve the limbs, face
or tongue. Particularly in young women, in whom
migraine and demyelination are each common, the
symptoms may be mistaken for multiple sclerosis
(table 3). In young people worried about multiple
sclerosis, other migraine symptoms may be less con-
spicuous and their identification requires direct
Allodynia (pain from non-noxious stimuli) in the
face occurs in up to 70% of people with migraine.
Allodynia in the limbs may be ipsilateral, bilateral or
contralateral to the headache, and is thus not simply a
cortical ischaemic phenomenon.
When the allodynia
varies in position and intensity, and occurs with other
migrainous features, the diagnosis is straightforward.
Occipito-temporal white matter involvement in
migraine fits the clinical preponderance of visual
symptoms. The hypersensitivity may be confused with
psychiatric or functional illness or chronic fatigue syn-
drome. Vague or fluctuant sensory symptoms, disequi-
librium and fatigue, without neurological signs, may
be described as ‘functional’ disorders, or ascribed to
chronic fatigue syndrome, especially if other migrain-
ous symptoms are not carefully sought. The absence
of sensory signs with central problems (including
migraine) may falsely reinforce a functional diagnosis.
Children with migraine, especially abdominal
migraine, may be mislabelled as having school refusal
or a psychological disturbance, as it may be charac-
terised by withdrawal from, and disinterest in, usual
Psychiatric illness, organic psychoses and confusional
Hallucinations accompany many neurodegenerative
conditions—classically, in Parkinson’s disease, with
preserved insight—and acute organic psychoses,
including drug-induced and drug-withdrawal states.
Complex visual hallucinations rarely occur in
migraine; the clinician must consider other causes
first. They have been the subject of considerable
speculation. Macropsia is most famously represented
by Lewis Carroll’s description of Alice ’s adventures in
Wonderland, reputedly inspired by Carroll’sown
Table 3 Sensory symptoms
Diagnosis* Prevalence Usual symptom duration Key features Comments
Migraine 150/1000 >5 min to hours Variable intensity and topography No signs, ±headache
Neuropathy 60/1000 Fixed Distal sensory loss and arreflexia May be painful
Stroke 15/1000 Ongoing Focal deficits Fixed deficits (50%)?
Transient ischaemic attack 3/1000 Minutes–24 hours Numbness May have deficits
Sensory seizures 1/1000 Seconds Positive (eg, tingling) Structural cause common
Multiple sclerosis 1/1000 Variable Upper motor neuron signs Interpret MRI with care
Chronic fatigue syndrome 0.3/1000? Frequent, intermittent Hypersensitivity May have ‘migraine plus’
Functional ? Frequent, intermittent Variable, diffuse, no signs May have ‘migraine plus ’
*Variable percentages of these patients will have sensory symptoms.
Angus-Leppan H. Pract Neurol 2013;13:308–318. doi:10.1136/practneurol-2012-000502 315
Complex visual hallucinations are described in chil-
dren as well as adults with recurrent attacks of impair-
ment of time sense, body image and visual analysis of
The same differential diagnosis
applies as for elementary visual hallucinations, includ-
ing psychiatric illness, neurodegeneration, encephal-
itis, and in withdrawal states, such as delirium
tremens. The patient may be fearful and reluctant to
discuss them, owing to concerns about having a psy-
Minor degrees of transient or intermittent cognitive
clouding commonly accompany migraine; in the
setting of other symptoms, they are usually readily
recognised. Patients often report difficulty in concen-
trating and in performing tasks (executive dysfunc-
tion) during times of frequent migraine headaches.
These changes are important to the patient and little
researched. One small series suggested that abnormal
perceptual experiences occur in 15% of migrai-
Blau gave an account of the ‘free interval’—
the gap between the end of the visual aura and
headache onset in migraine with aura. In 22/25
migraineurs with migraine with visual aura, the ‘free
interval’ of about 1 h was marked by altered mood
and perception—detachment from the environment
or other people, fears, disturbances of speech or
thought, or somatic symptoms.
ences, including autoscopy and duplicate or paraso-
may be ascribed to acute
psychosis or to intoxication. Recurrent psychosis after
migraine may occur and leads to consideration of an
organic psychosis or mitochondrial cytopathy. Fuller
describe a 69-year-old man with longstanding
migraine with aura who had four psychotic episodes
lasting 7–28 days during a 17-year period. During
attacks, he developed formed visual hallucination and
Fully blown forms of migrainous encephalopathy or
coma are rare, but mild forms are common. Acute
occurs in children, adoles-
cents, as well as adults. Between 0.45% and 7.8% of
children with migraine present with acute confusional
migraine, but the disorder is probably underdiag-
nosed. In adults, the incidence is harder to estimate,
and the diagnosis requires exclusion of some life-
threatening causes of confusion, such as non-
convulsive status epilepticus, ischaemia, haemorrhage,
neoplasm, intoxication and encephalitis.
Migraine headaches are generally easy to diagnose,
but the aura may be misleading. Migraine aura is
usually a positive phenomenon. Most hallucinations
are elementary rather than complex, with unformed
visual aura being the most common, and usually very
characteristic. Migraine is a ‘functional’ disorder, in
the broadest sense of the term. Investigations in
patients migraine are usually normal: even when
abnormalities are found, they are often incidental. It
is helpful to be aware of the uncommon aura, as well
as migraine variants, such as icepick headache. Once
the diagnosis is ma de, a large part of our role is to
educate and to reassure, as well as to treat.
Migraine is differentiated from autonomic cephal-
gias, but overlap syndromes, such as cluster migraine,
may also occur. Other important mimics must not be
missed—such as headache from hypertension, carotid
artery disease, acute glaucoma, intracranial mass
lesions, raised intracranial pressure, meningitis, giant
cell arteritis and reversible cerebral vasospastic syn-
drome. Borderland conditions include mitochondrial
cytopathies, migralepsy, and migrain ous stroke.
Importantly, migraine is often diagnosed as something
else (a chameleon), being particularly mistaken for
other paroxysmal events, such as cerebrovascular
disease and epilepsy; but also peripheral nervous
system disorders, vestibular disorders, gastrointestinal
and cardiac disease, syncope, multiple sclerosis, and
functional and psychiatric illness.
Acknowledgements Thanks to Professor Jim Lance and
Dr Geoff Lambert who inspired my interest in clinical and
physiological aspects of migraine; and to Professor Roberto
Guiloff for helpful comments on the manuscript. I thank all the
patients who have shared their stories.
Competing interests None.
Provenance and peer review Commissioned; externally peer
reviewed. This paper was reviewed by Peter Goadsby,
San Francisco, USA; and by Richard Stark, Melbourne,
1 International Headache Society classification subcommittee.
International classification of headache disorders, 2nd edition.
Cephalalgia 2004;24(Suppl 1):1–60.
2 Becker WJ. The premonitory phase of migraine and migraine
management. Cephalalgia 2013;53:1191–6.
3 Giffin NJ, Ruggiero L, Lipton RB, et al. Premonitory
symptoms in migraine: an electronic diary study. Neurology
4 Viana M, Sprenger T, Andelova M, et al. The typical duration
of migraine aura: a systematic review. Cephalalgia
5 Goadsby PJ. Recent advances in understanding migraine
mechanisms, molecules and therapeutics. Trends Mol Med
6 Kassab M, Bakhtar O, Wack D, et al. Resting brain glucose
uptake in headache-free migraineurs. Headache 2009;49:90–7.
7 Drummond PD, Lance JW. Neurovascular disturbances in
headache patients. Clin Exp Neurol 1984;20:93–9.
8 Bird N, MacGregor A, Wilkinson MIR. Ice cream headache—
site, duration, and relationship to migraine. Headache
9 Landtblom A-M, Fridriksson S, Boivie J, et al. Sudden onset
headache: a prospective study of features, incidence and causes.
10 Yeh YC, Fuh JL, Chen SP, et al. Clinical features, imaging
findings and outcomes of headache associated with sexual
activity. Cephalalgia 2010;30:1329–35..
316 Angus-Leppan H. Pract Neurol 2013;13:308–318. doi:10.1136/practneurol-2012-000502
11 Linn FH, Rinkel GJ, Algra A, et al. Headache characteristics in
subarachnoid haemorrhage and benign thunderclap headache.
J Neurol Neurosurg Psychiatry 1998;65:791–3.
12 Wijdicks EF, Kerkhoff H, Van Gjin L. Long-term follow up of
71 patients with thunderclap headache mimicking
subarachnoid haemorraghe. Lancet 1988;2:68–70.
13 Ducros A, Bousser M-G. Thunderclap headache. BMJ
14 Lipton RB. Chronic migraine, classification, differential
diagnosis, and epidemiology. Headache 2011;51(Suppl 2):77–83.
15 Matharu MS, Goadsby PJ. Trigeminal autonomic cephalgias.
J Neurol Neurosurg Psychiatry 2002;72:ii19–26.
16 Gaul C, Christmann N, Schröder D, et al. Differences in
clinical characteristics and frequency of accompanying migraine
features in episodic and chronic cluster headache. Cephalalgia
17 Peatfield R. Migrainous features in cluster headache. Curr Pain
Headache Rep 2001;5:67–70.
18 Zidverc-Trajkovic J, Podgorac A, Radojicic A, et al.
Migraine-Like Accompanying Features in Patients With Cluster
Headache. How Important Are They? Headache 2013;27.
19 Solomon S, Karfunkel P, Guglielmo KM. Migraine-cluster
headache syndrome. Headache 1985;25:236–9. 71.
20 Solomon S. Variants of cluster headache. Chapter 17. In:
Vinken PJ, Bruyn GW, Klawans HL, Rose C, eds. Handbook of
Clinical neurology. Vol 4(48), Headache. New York: Elsevier,
21 Guiloff RJ, Fruns M. Limb pain in migraine and cluster
headache. J Neurol Neurosurg Psychiatry 1988;51:1022–31.
22 Ozkurt B, Cinar O, Cevik E, et al. Efficacy of high-flow
oxygen therapy in all types of headache: a prospective,
randomized, placebo- controlled trial. Am J Emerg Med
23 Jürgens TP, Schulte LH, May A. Oxygen treatment is effective
in migraine with autonomic symptoms. Cephalalgia
24 Ducros A, Boukobza M, Porcher R, et al. The clinical and
radiological spectrum of reversible cerebral vasoconstriction
syndrome. A prospective series of 67 patients. Brain
25 Call GK, Fleming MC, Sealfon S, et al. Reversible cerebral
segmental vasoconstriction. Stroke 1988;19:1159–70.
26 Fisher CM. Late-life migraine accompaniments. Stroke
27 Shuaib A, Hachinski VC. Migraine and the risks from
angiography. Arch Neurol 1988;45:911–2.
28 Goadsby PJ, Kullmann DM. Another migraine gene. The
Lancet 2005;366:345–6. study.
29 Smith PEM. Epilepsy: Mimics, Borderland and Chameleons.
Pract Neurol 2012;12:299–307.
30 Zeman A, Butler C, Muhlert N, et al. Novel forms of
forgetting in temporal lobe epilepsy. Epilepsy Behav
31 Bartsch T, Deuschl G. Transient global amnesia: functional
anatomy and clinical implications. Lancet Neurol
32 Hodges JR, Warlow CP. The aetiology of transient global
amnesia. Brain 1990;113:639–57.
33 Owen D, Paranandi B, Sivakumar R, et al. Classical diseases
revisited: transient global amnesia. Postgrad Med J
34 Caplan L, Chedru F, Lhermitte F, et al. Transient global
amnesia and migraine. Neurology 1981;31:1167.
35 Maggioni F, Mainardi F, Bellamio M, et al. Transient global
amnesia triggered by migraine in monozygotic twins. Headache
36 Beckmann YY, Gelal F, Eren S, et al. Diagnostics to Look
beyond the Normal Appearing Brain Tissue (NABT)? A
Neuroimaging Study of Patients with Primary Headache and
NABT Using Magnetization Transfer Imaging and Diffusion
Magnetic Resonance. Clin Neuroradiol 2013. [Epub ahead of
37 Bower S, Dennis M, Warlow C, et al. Long-term prognosis of
transient lone bilateral blindness in adolescents and young
adults. J Neurol Neurosurg Psychiatry 1994;57:734–6.
38 Rasmussen BK, Olesen J. Migraine with aura and migraine
without aura: an epidemiological study. Cephalalgia
39 Sándor PS, Morath GP, Hess K, et al. Prosopagnosia as
symptom of migraine with aura: a case report. Cephalalgia
40 Koutroumanidis M, Ferrie CD, Valeta T, et al. Syncope-like
epileptic seizures in Panayiotopoulos syndrome. Neurology
41 Schott GD. Exploring the visual hallucinations of migraine
aura: The tacit contribution of illustration. Brain
42 Fuller GN, Guiloff RJ. Migrainous olfactory hallucinations.
J Neurol Neurosurg Psychiatry 1987;50:1688–90.
43 Demarquay G, Ryvlin P, Royet JP. Olfaction and neurological
diseases: a review of the literature. Rev Neurol (Paris)
44 Morrison DP. Abnormal perceptual experiences in migraine.
45 Russell MB, Olesen J. A nosographic analysis of the migraine
aura in a general population. Brain 1996;119:355–61.
46 Alonso –Navarro H, Jimenez-Jimenez FJ. Sensory
pseudoperipheral migraine aura. J Neurol 2009;256:1349–50.
47 Mumenthaler M. Neurologic differential diagnosis. New York:
Thieme Medical publishers, 1992;137.
48 Guiloff RJ, Fruns M. Migrainous Limb Pain. A Historical
Note. Headache 1990;30:138–41.
49 Raudino F. Limb pain and headache. Headache
50 Abu-Arafeh I, Russell G. Recurrent limb pain in schoolchildren.
Arch Dis Child 1996;74:336–9.
51 Saito Y, Fusayasu E, Iitsuka T, et al. Familial limb pain in
childhood: Unusual manifestation of migraine. Brain Dev
52 Angus-Leppan H, Olausson B, Boers P, et al. Convergence of
afferents from superior sagittal sinus and tooth pulp on cells in
the upper cervical spinal cord of the cat. Neurosci Lett
53 Angus-Leppan H, Lambert GA, Michalicek J. Convergence of
occipital nerve and superior sagittal sinus input in the cervical
spinal cord of the cat. Cephalalgia 1997;17:625–30; discussion
54 Lempert T, Olesen J, Furman J, et al. Vestibular migraine:
Diagnostic criteria. J Vestib Res 2012;22:167–72.
55 Rubin D, McAbee G, Feldman-Winter F. Auditory hallucinations
associated with migraine. Headache 2002;42:646–8.
56 Cuadrado ML, Young WB, Fernández-de-las-Peñas C, et al.
Migrainous corpalgia: body pain and allodynia associated with
migraine attacks. Cephalalgia 2008;28:87–91.
57 Guiloff RJ, Rajakulendran S, Angus-Leppan H. Syncope and
Raynaud’s disease. Arch Neurol 2012;69:608–13.
Angus-Leppan H. Pract Neurol 2013;13:308–318. doi:10.1136/practneurol-2012-000502 317
58 Selby G, Lance JW. Observations on 500 cases of migraine and
allied vascular headache. J Neurol Neurosurg Psychiatry
59 Podoll K, Robinson D. Lewis Carroll’s migraine experiences.
60 Golden GS. The Alice in Wonderland syndrome in juvenile
migraine. Pediatrics 1979;63:517–9.
61 Blau JN. Classical migraine: symptoms between visual aura and
headache onset. Lancet 1992;340:355–6.
62 Podoll K, Robinson D. Out-of-body experiences and
related phenomena in migraine art. Cephalalgia 1999;
63 Fuller GN, Marshall A, Flint J, et al. Migraine madness:
recurrent psychosis after migraine. J Neurol Neurosurg
64 Schipper S, Riederer F, Sándor PS, et al. Acute confusional
migraine: our knowledge to date. Expert Rev Neurother
318 Angus-Leppan H. Pract Neurol 2013;13:308–318. doi:10.1136/practneurol-2012-000502