Transient ischaemic attacks: mimicsand chameleons

V Nadarajan,1 R J Perry,1 J Johnson,1 D J Werring1,2

1Hyperacute Stroke Unit, UCLHospitals NHS Foundation Trust,London, UK2Stroke Research Group, UCLInstitute of Neurology, London,UK

Correspondence toDr David Werring, Reader inClinical Neurology and HonoraryConsultant Neurologist, StrokeResearch Group, UCL Instituteof Neurology, Queen Square,London WC1N 3BG, UK;d.werring@ucl.ac.uk

To cite: Nadarajan V,Perry RJ, Johnson J, et al.Pract Neurol 2014;14:23–31.

ABSTRACTSuspected transient ischaemic attack (TIA) is acommon diagnostic challenge for physicians inneurology, stroke, general medicine and primarycare. It is essential to identify TIAs promptlybecause of the very high early risk of ischaemicstroke, requiring urgent investigation andpreventive treatment. On the other hand, it isalso important to identify TIA ‘mimics’, to avoidunnecessary and expensive investigations,incorrect diagnostic labelling and inappropriatelong-term prevention treatment. Although thepathophysiology of ischaemic stroke and TIA isidentical, and both require rapid and accuratediagnosis, the differential diagnosis differs forTIA owing to the transience of symptoms. ForTIA the diagnostic challenge is greater, and the‘mimic’ rate higher (and more varied), becausethere is no definitive diagnostic test. TIA heraldsa high risk of early ischaemic stroke, and in manycases the stroke can be prevented if the cause isidentified, hence the widespread disseminationof guidelines including rapid assessment and risktools like the ABCD2 score. However, theseguidelines do not emphasise the substantialchallenges in making the correct diagnosis inpatients with transient neurological symptoms.In this article we will mainly consider thecommon TIA mimics, but also briefly mentionthe rather less common situations where TIAscan look like something else (‘chameleons’).

Definition and pathophysiologyTIA is defined as temporary focal neuro-logical symptoms resulting from cerebral,retinal—or, very occasionally, spinal—ischaemia. The concept of TIA emergedin the 1950s, with the observation by CMiller Fisher, and others, that ischaemicstroke often followed transient neuro-logical symptoms in the same arterial ter-ritory. An arbitrary maximum duration of24 h for TIA is now recognised to beunhelpful—and should be abandoned—for the following reasons: up to 50% ofTIAs, including brief attacks (minutes),

can be associated with infarction ondiffusion-weighted MRI; acute ischaemicstroke requires urgent treatment withinminutes, and certainly long before 24 h;and the vast majority of TIAs last wellunder an hour (usually less than 30 min).More recently, the American HeartAssociation recommended a ‘tissue-based’definition of TIA: “a transient episode ofneurological dysfunction caused by afocal brain, spinal cord, or retinal ischae-mia, without acute infarction”.1 This def-inition usefully eliminates the 24-h timelimit, but is highly dependent on timelyaccess to diagnostic tests (mainly MRI),which is hugely variable, even in devel-oped countries like the UK. Thus, for themoment, TIA remains a clinical diagnosisbased around accurate history interpret-ation skills.2 With regard to patient path-ways, the most important distinction isnot between TIA and stroke, but betweenTIA and disabling stroke, or betweennon-disabling stroke (which can bemanaged in an outpatient setting) anddisabling stroke (which is usuallymanaged as an inpatient stay).Like ischaemic strokes, TIAs are due to

locally decreased blood flow to the brain,causing focal neurological symptoms.Decreased blood flow results from eitherembolism into a cerebral supply artery(from the heart, or the great proximalvessels, extracranial or intracranial arter-ies, usually affected by atherosclerosis), orin situ occlusion of small perforatingarteries; resolution of symptoms probablyoccurs by spontaneous lysis or distalpassage of the occluding thrombus orembolus, or by compensation throughcollateral circulation restoring perfusioninto the ischaemic brain area. Rarely,focal hypoperfusion due to critical arter-ial stenosis can cause TIA, often stereo-typed and related to upright posture.Blood pressure and blood oxygenation orviscosity may also impact upon the

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duration and pattern of symptom evolution orresolution.

Specific challenges in diagnosing TIAThe main diagnostic challenge of TIA is that thesymptoms and signs have usually resolved by the timeof assessment.3 There is no test for TIA: the goldstandard remains assessment as soon as possible by aclinical expert. The diagnosis relies heavily on thepatient’s account of their history and on expert inter-pretation of that history. Interobserver agreement forthe diagnosis of TIA between different stroke-trainedphysicians and non-neurologists is poor.4–7 As instroke, in some patients a collateral history may beessential.

Subsequent stroke risk and importance of accuratediagnosisPatients with a diagnosis of TIA have an increased riskof future ischaemic stroke. Fifteen per cent to 30% ofischaemic strokes are preceded by TIA symptoms,often on the same day.8 A meta-analysis found acumulative early risk at 7 days of 5.2%.9 The risk ofstroke is highest within the first 24 h,10 so promptand accurate diagnosis is critical11; misdiagnosis canexpose patients to unnecessary investigation and long-term secondary prevention treatment, as well asanxiety.12

The ABCD2 score (which includes age, blood pres-sure, clinical features, duration and diabetes) is apopular clinical prediction tool used to identify thosepatients with suspected TIA at high risk of developingearly ischaemic stroke,3 but may not always be usedappropriately. It is of limited practical relevance inmodern stroke clinical practice, since the aspiration isto see all patients with suspected TIA within 24 h.The ABCD2 is not designed as—and should not beused as—a diagnostic instrument, although a highABCD2 score may predict subsequent stroke, in partbecause such patients are more likely to have had aTIA rather than a mimic.3 13 14 The ABCD2 scoredoes not include other known predictors of highstroke risk, including carotid disease, recurrent TIAsand evidence of tissue damage on MRI.15 Finally, thevalidity of the ABCD2 score in the hands of generalpractitioners and other non-stroke doctors may belimited and is not extensively studied.

Role of brain imaging in TIAEven transient deficits can be associated with evidenceof persistent tissue ischaemia on diffusion-weightedimaging (DWI). In those cases, positive DWI supportsa clinical diagnosis of TIA. In early series, 35–67% ofpatients with TIAs had restricted diffusion suggestingcerebral ischaemic injury.16 The likelihood of a DWIlesion increases with symptom duration. Recent riskscores incorporating DWI suggest that this imaging

modality can help to identify individuals at highestrisk of early ischaemic stroke.15

CLINICAL FEATURES OF TIAThe key rule here is that symptoms of TIA shouldmimic known stroke syndromes, and so depend onthe arterial territory involved. Distinguishing the terri-tory is important to guide further investigation andsecondary prevention. Some common patterns ofpresentation (eg, hemiparesis) are not very helpful indistinguishing the arterial territory, as they can occurwith both anterior and posterior circulation TIAs.Others can be more localising: for example, aphasiaor transient monocular visual loss suggest carotid ter-ritory ischaemia, while bilateral limb weakness,vertigo, hearing loss, haemianopia or diplopia are fea-tures of vertebrobasilar (brainstem) ischaemia. TIAsdue to perforating artery disease should mimic aknown lacunar syndrome (most often hemisensory orhemimotor symptoms affecting the face, arm and leg);moreover, such ‘lacunar’ TIAs may be recurrent andstereotyped over a short period (days) as in the “cap-sular warning syndrome”. Increased awareness ofsymptoms means that patients can now present withvery restricted transient syndromes, including isolatedvertigo, dysarthria or hemisensory disturbance: insuch cases, clinicians should consider other causesbefore diagnosing TIA.Abrupt onset of maximal symptoms predicts a final

diagnosis of TIA,12 but there is no evidence for a stat-istical difference between duration of symptoms inpatients with TIA and mimics.14 These findings mayof course be rather circular, since sudden symptomsare part of the usual criteria for diagnosis of TIA, andpart of what makes a mimic is its similar time courseto TIA. Nevertheless, other key aspects of the historythat are useful to help identify TIA from mimics areas follows:▸ Age and other demographic data: is there a high a priori

probability of a cerebrovascular event?▸ Nature of the symptoms: ‘positive’ versus ‘negative’?▸ Onset and progression▸ Duration▸ Precipitating factors▸ Associated symptoms, for example, headache, loss of

awareness, during or after the attacks

Age and other demographic dataTIAs are rare in young people without vascular riskfactors (eg, hypertension, ischaemic heart disease, dia-betes mellitus, smoking, haematological disease, etc).In otherwise healthy pregnant women, transientneurological symptoms are a common reason forneurological referral, but are often related tomigraine. Seizures and syncope occur at all ages,although the underlying causes may differ. Syncope ismore common in women, but seizures have no sexpredilection. TIAs are more common in men at

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younger ages, but the sex difference reduces after themenopause.

Nature of the symptoms▸ Positive symptoms indicate an ‘excess’ of central nervous

system neurone electrical discharges and may be visual(eg, flashing lights, zigzag shapes, lines, shapes, objects),somatosensory (eg, pain, paraesthesia) or motor (eg,jerking limb movements).

▸ Negative symptoms indicate a loss or reduction ofcentral nervous system neurone function (eg, loss ofvision, hearing, sensation or limb power).

Seizures and migraine auras typically start as positivesymptoms, while TIAs typically begin with negativesymptoms (but may develop positive symptoms aswell). Seizures only occasionally cause paresis fromthe outset, but even then close questioning or examin-ation may reveal minor positive motor or sensorysymptoms or signs. Of course, postictal paresis is verycommon after seizures, so an accurate history of thesequence of events is essential.Transient speech disturbance is a challenging

symptom for TIA diagnosis. It is important to try todistinguish between dysphasia and dysarthria, as thismay affect classification of arterial territory and subse-quent management. However, in practice this may beimpossible. A history of ‘slurring’ suggests dysarthria,while altered word content or grammatical structure,with or without impaired reading suggests a languagedisturbance. Asking some of the following questionsmay be helpful. For the patient: did they know exactlywhich words they were trying to say? For the witness:were the words that you heard the right ones, albeitslurred? Were there any nonsense words, or any thatwere clearly the wrong word for the context?Judging the time of onset of speech or language dif-

ficulties can be challenging. Recently descriptionsreport abnormal texting on mobile devices (‘dystex-tia’) as a useful guide to a language disturbance andprecise onset time of neurological deficit. Isolatedcomplete and brief speech arrest, particularly if recur-rent and stereotyped, is probably more commonlyrelated to seizures than TIA.Likewise determining the onset time and nature

(monocular vs binocular) of visual disturbance can bedifficult unless the patient deliberately covers one eyeduring the attack, but is crucial.

Onset and evolution of the symptomsSymptoms of TIA usually start abruptly, followed bygradual offset, usually over minutes. TIA symptomsare usually negative, and if there are multiple symp-toms, they all typically occur more or less togetherfrom onset. By contrast, migraine aura typically pro-gresses slowly over minutes to tens of minutes, andpositive symptoms may be followed by negative onesin the same functional domain or modality. Forexample, paraesthesias may begin in the hand, then

gradually progress up the arm to the shoulder, trunk,and then the face and leg, frequently followed bynumbness. In the visual domain, a visual aura maymigrate across the field and be followed by a visualfield defect. Although at onset only one sensorymodality is usually affected, migraine aura may subse-quently progress to other modalities, as adjacent cor-tical regions are affected; such evolution is not afeature of a single TIA.Seizures usually progress very quickly (seconds) in a

single functional neurological domain. Loss of con-sciousness is common in seizures and syncope.Seizures are usually recurrent stereotyped attacks. Inmost cases TIAs do not cause recurrent stereotypedattacks; exceptions to this are lacunar TIAs (the mostdramatic form of which is the capsular warning syn-drome, see below), TIAs due to distal intracranialstenosis, and occasionally haemodynamic TIAs due tocritical perfusion relating to a large artery stenosis.Loss of consciousness is extremely rare in TIAs (butnot impossible, see ‘Chameleons’).

Duration of the symptomsMigrainous auras usually last 10–30 min, but maypersist for many hours. TIAs nearly always last lessthan 1 h. Seizures last usually up to about 5 min.Syncope usually lasts a few seconds, unless the patientstays upright. Episodes recurring over some years arevery likely due to syncope, seizures or migraine. Bycontrast, TIAs usually occur over a relatively shortspace of time (days to weeks), and may occur as aseries of attacks in a much shorter time (days toweeks; so-called ‘crescendo’ TIAs).

Precipitating factorsSeizure triggers include hyperventilation, intercurrentsepsis, altered alcohol intake or missing antiepilepticmedication. Haemodynamic “jerking” TIAs (see‘Chameleons’) may occur upon sudden standing, aftertaking antihypertensive medication, or following a largemeal or hot bath. Benign paroxysmal positional vertigois triggered by sudden head movements (see case study).Syncope may be precipitated by emotional stimuli (eg,seeing blood) or fluid loss (eg, diarrhoea and vomiting).

Associated symptomsTongue biting (especially if lateral) and muscle painsafter the event are markers of seizure. Vomiting iscommon after migraine and occasionally followssyncope, but is extremely rare in TIA or seizures.Nausea, sweating, pallor and a need to urinate ordefaecate commonly precede or follow syncope.

MIMICSUp to 60% of patients referred to a TIA clinic do nothave a final diagnosis of TIA,12 17–19 but this willdepend on how patients are referred and the methodof diagnosis. Any cause of transient neurological

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symptoms is a potential TIA mimic, giving a hugerange of alternative diagnoses. Of 1532 consecutivepatients attending our TIA service, 1148 (75%) hadeither definite or possible TIA, 46 (3%) had minorstroke and the remaining 338 (22%) had one of 25alternative diagnoses (figure 1).Frequent causes of transient neurological symptoms

that can mimic TIA include:▸ Migraine aura▸ Seizure▸ Syncope▸ Functional or anxiety relatedTable 1 shows some useful clinical distinguishing

features for these common mimics.We will now consider in more detail some of the

key TIA mimics likely to be encountered in clinicalpractice.

Migraine auraUp to about 20% of patients with suspected TIA havemigraine aura2; this is the most common mimic in ourexperience (figure 1). The diagnostic challenge arisesparticularly when the aura occurs with minimal or noheadache. This phenomenon, described by MillerFisher as ‘late-life migraine accompaniment’, is nowusually referred to as acephalgic migraine.20 Amigraine aura reflects cortical spreading depression,so classically has a spreading onset corresponding toadjacent cortical regions over minutes, usually resolv-ing within 30 min and only rarely lasting over an

hour. Visual disturbances, sometimes with scintillatingscotomata, geometric (especially zigzag) patterns orother positive symptoms with varied descriptions(‘like looking through a heat haze’; ‘like lookingthrough raindrops moving down a window’; ‘likelooking through a kaleidoscope’, etc), are the mostcommon. It may help to ask the patient to draw theirvisual aura (figure 2). Auras can include sensory,motor or speech disturbances. In migraine, differentmodalities may be involved (eg, visual and somatosen-sory) but they often occur sequentially, with oneresolving as the other begins, rather than all simultan-eously as in TIAs. Although auras are typically experi-enced just before or simultaneously with headache,headache onset can occasionally be delayed for morethan an hour after the end of the aura.Headache may also occur at TIA or stroke onset,

especially in young women with a prior history ofmigraine,21 where it is probably triggered by the stroke(ie, a ‘symptomatic’ rather than “primary” migraine).Thus the presence of typical migrainous aura or head-ache does not exclude TIA (or stroke). The concept ofmigrainous infarction is controversial and the safestinitial policy is to assume that migraine does not causecerebrovascular events, and to investigate all patientsfor alternative causes.

SeizuresGeneralised seizures without partial features shouldnot be difficult to distinguish from TIA, provided

Figure 1 Frequency of transient ischaemic attack (TIA) mimics from 1532 consecutive suspected TIA referrals to the UniversityCollege London comprehensive stroke service.

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there is an adequate witnessed account. In generalisedseizures with partial features, postictal confusion,14

headache, involuntary movements and incontinencemay be helpful pointers against TIA (see table 1).‘Negative’ motor symptoms (eg, haemiparesis) arevery rare as the sole manifestation of seizures, but notunheard of.22 Complete speech arrest may be morelikely in seizures than in TIA. Todd’s paresis—a focalneurological deficit following about 1 in 10 general-ised seizures—can last for hours, or occasionallylonger. Postictal dysphasia can follow seizures involv-ing the dominant hemisphere. The key is a witnessedaccount of seizure activity at onset. While focal sei-zures are often very stereotyped even over multipleevents, recurrent TIAs may be totally different in char-acter. Finally, a previous history of epilepsy is clearlyuseful.

SyncopeSyncope is a transient loss of consciousness with loss ofpostural tone and rapid recovery. It is not usually char-acterised by truly focal symptoms. Presyncopal symp-toms may be a helpful pointer, including a faintfeeling, dimming of vision and muffling of hearing,reflecting global, retinal and cochlear hypoperfusion,respectively. Common causes are reflex (vasovagal)syncope, postural hypotension and carotid sinus hyper-sensitivity. The most important serious causes ofsyncope are cardiac arrhythmias. Vertebrobasilar TIAscan rarely cause loss of consciousness if thalamic

structures are involved (‘top of the basilar’ syndrome)but this is very rarely transient (but see ‘Chameleons’).Upon hearing a clinical history consistent withsyncope, a diagnosis of TIA seems to be more likely tobe considered by a non-neurologist in comparison witha neurologist.19

Peripheral vestibular disturbanceComplaints of acute vertigo or ‘dizziness’ are commonin TIA clinics, primary care and emergency depart-ments. It is important to assess whether the symptomis ‘true vertigo’—a feeling of usually rotatory move-ment with respect to the environment—or is in factunsteadiness without vertigo, or faintness. The words‘dizzy’ or ‘giddy’ may be used by patients to describevertigo or presyncope, and always deserve furtherdetailed exploration. Even with a detailed history itcan be difficult to distinguish clinically between a ver-tebrobasilar TIA and peripheral vestibular disturbance,particularly in older patients with comorbidities. Thischallenge is compounded as often the clinical examin-ation is normal (the head-impulse test and Hallpike’stest are specific but not sensitive). Overall, isolated ‘diz-ziness’ is much more likely to be due to peripheral ves-tibular disturbance than TIA: a population-based studyreported that only 3.2% of patients presenting to theemergency department with ‘dizziness’ have a finaldiagnosis of TIA or stroke.23 Even an expert taking acareful history may remain uncertain, and in thosecases MRI with diffusion-weighted sequences can be

Table 1 Clinical features of transient ischaemic attack (TIA) and some common mimics

TIA Migraine Seizure SyncopeFunctional/anxiety

Demographic Older ageVascular risk factorsMore common in men

Younger ageMore common in women

Any age Any age, oftenyoungerMore common inwomen

YoungerMore common inwomen

Neurologicalsymptoms

Negative symptoms, usuallymaximal at onset: for example,numbness, weakness, visualloss. Transient diplopia andmonocular visual loss are oftendue to TIADoes not spread into othersensory modalities.Alteration or loss ofconsciousness almost neveroccur

Positive, spreading symptoms atonset. Visual the mostcommon. May be followed bynegative symptoms in the samedomainSymptoms may evolve intoanother modality (eg, visualfollowed by somatosensory)True alteration or loss ofconsciousness almost neveroccur, though there may be‘confusion’ or muddled thinking

Positive symptomsincluding painful sensorydisturbance, limb jerking,head turning, dystonicposturing, lip smacking.Loss of awareness andamnesia for event unlesssimple partial seizuresPostictal negativesymptoms (eg, Todd’sparesis) may persist fordays

Faint or light headed(presyncopal). Visionmay darken, orhearing becomesmuffled.Loss of awareness

Isolated sensorysymptomscommon

Timing Abrupt onset, gradual offset(minutes). Usually totalduration minutes, nearly always<1 hRecur over days or weeks,usually not months or years.

Usually last 20–30 min, butmay be much longerCan recur over years ordecades.

Usually less than 2 min.Can recur over years

Seconds to less than aminute.Can recur over years

Tend to berecurrent andstereotyped

Associatedsymptoms

Headaches may occur, usuallyduring the attacks

Headache usually afterwardswith migrainous features(nausea, vomiting,photophobia, phonophobia,mechanosensitivity)

Tongue biting (especiallylateral), incontinence,muscle pains, exhaustionor disorientation, headachefollow

Sweating, pallor,nausea, rapid recoveryto full alertness

May be precededby emotional orpsychosocialstressorsAnxiety

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very helpful since it has high sensitivity for posteriorcirculation ischaemic injury.

Transient global amnesiaTransient global amnesia is a rare but striking condi-tion characterised by the temporary loss of antero-grade episodic memory,24 usually in people aged over50 years. Risk factors for vascular disease arecommon. Neurologists are familiar with the typicalattacks, which usually last for several hours afterwhich there is a filling in of old memory and a restor-ation of ability to lay down new ones; a gap for theepisode persists. Procedural memory is intact butrepetitive questions are common. EEG during theattacks has not demonstrated seizure activity, but awitnessed account should be sought to seek clinicalevidence (eg, lip-smacking, dystonic limb posturing,etc). Attacks rarely recur, and patients can be reas-sured that the risk of future stroke does not appear tobe increased. Functional imaging during attacks hasdemonstrated transient hypoperfusion mainly in themesial temporal lobes. Memory loss from TIA onlyoccurs very rarely in posterior circulation TIAs affect-ing bilateral medial temporal structures, so it stronglysuggests a TIA mimic.14

Functional/anxiety disorderThe rate of functional disorder in TIA clinics has beenreported to be as high as 7%.12 Approximately 60%of patients with functional weakness present initiallywith symptoms of sudden onset or on waking.25

Symptoms may be stereotyped and recurrent and maybe accompanied by panic, pain or physical injury atthe time of onset. There may be dissociative or mul-tiple symptoms. Other features of a functional presen-tation include inconsistency between symptoms andexamination, or examination and functional observa-tions, or ‘collapsing’ weakness. Functional symptomsare more common in younger patients without con-ventional vascular risk factors and may affect the non-

dominant side more often than the dominant side.Panic attacks may follow an otherwise typical TIA,which may occasionally cause a diagnostic challenge.

Amyloid ‘spells’ and cerebral convexity subarachnoidhaemorrhageCerebral amyloid angiopathy, a common cause oflobar cerebral haemorrhage in older patients, can alsopresent with transient focal neurological episodes,which are sometimes known as ‘amyloid spells’.26

These are stereotyped, recurrent, transient neuro-logical episodes of paraesthesias, numbness or weak-ness of spreading onset over seconds to minutes,resolving over a similar period. The events are pre-sumed to be secondary to focal seizures or corticalspreading depression. Recent data suggest that symp-toms are equally likely to be predominantly positive(spreading paraesthesias, positive visual phenomena,or limb jerking) or negative symptoms (weakness, lan-guage impairment or visual loss).27 Blood-sensitiveMRI (gradient echo T2*-weighted or susceptibility-weighted sequences) are critical in investigatingattacks of this sort, since superficial cortical siderosisor acute sulcal haemorrhage is commonly found, sug-gesting a causative role in generating these symptoms.The key clinical point here is that the future risk ofsymptomatic intracerebral haemorrhage after suchtransient neurological events seems to be very high(figure 3). It is currently difficult to estimate howoften in clinical practice focal transient symptoms arerelated to small areas of haemorrhage because so fewcentres routinely acquire the necessary MRIsequences; this is an important topic for futureresearch. If imaging findings suggest cerebral amyloidangiopathy—especially with lobar cerebral haemor-rhage and superficial siderosis—we suggest thatantithrombotic drugs should generally be avoided due

Figure 2 Drawing of a visual migraine aura by a patientshowing a characteristic zigzag pattern.

Figure 3 (A) MR scan of brain from an 82-year-old womanwho presented with recurrent episodes of sudden onset needlesaffecting the face, gum and hand, with facial drooping, lastingabout 20 min. The patient was treated with clopidogrel. (B) CTscan of head following admission 1 month later with suddenleft haemiparesis. Note large right frontal intracerebralhaematoma.

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to the high risk of further cerebral haemorrhage(figure 3).

Structural brain lesionsOccasionally structural intracranial lesions, particu-larly meningiomas, can cause TIA-like symptoms.These symptoms are thought to arise due to masseffect resulting in a partial impairment of cerebralblood flow.28 A diagnostic difficulty can also arisebecause of associated seizures with prominent negativesymptoms. For example arteriovenous malformationsmay undergo dynamic changes in flow due to haemor-rhage or thrombosis, or may disturb local cerebralblood flow. Tumours may undergo haemorrhage orinfarction or can cause partial seizures. Clues to astructural TIA mimic include a gradual or stutteringonset over a longer period (eg, weeks), or associatedsymptoms of raised intracranial pressure.

Paroxysmal symptoms due to demyelinationTwo types of paroxysmal symptoms that can mimicTIA are seen in multiple sclerosis. They are rare, buthighly characteristic of mutliple sclerosis. The first isparoxysmal dysarthria, where there are recurrentstereotyped episodes of slurred speech; the second is‘tonic spasms’, manifesting as painful brief posturingoften affecting the upper limb on one side. These areusually recurrent and stereotyped and occur typicallyin younger people with few vascular risk factors.Usually these can be recognised, particularly in thecontext of established multiple sclerosis, but occasion-ally can be the first manifestation.

CHAMELEONSLimb-shaking TIAsRhythmic, involuntary jerky limb movements canoccur in haemodynamic TIAs, which may thus be mis-taken for focal motor seizures.29 30 The presence oflimb shaking is a well-established sign of hemispherehypoperfusion, due to severe carotid or middle cere-bral artery disease.29–32 The episodes tend to be brief(<5 min), recurrent and avoid the face. They can beprecipitated by activities that may reduce cerebralblood flow (such as postural change, coughing andexercise).32 Previously reported cases do not exhibitthe Jacksonian march typical of focal motor sei-zures,29–31 the other main differential for this presen-tation. MRI, including DWI sequences, can help inshowing a classical ‘borderzone’ pattern of establishedor recent ischaemia, especially if symptoms are pro-longed or recurrent (figure 4).

TIAs with altered conscious level or other brainstemsymptomsLoss of consciousness is not characteristic of a TIA.33

However, transient ischaemia of the thalami or brain-stem can very rarely cause such symptoms. We havevery occasionally seen patients who give a classical

history of transient quadriparesis with intact cognitionsuggesting a ‘locked-in’ TIA due to brainstemischaemia.

Spontaneous limb movements or posturing due tobrainstem ischaemiaOccasionally, rhythmic movements of the limbs canaccompany acute brainstem ischaemia. These move-ments may be seizure-like rhythmic jerking, sometimeswith prolonged tonic muscle contractions. The move-ments may be intermittent, and easily confused with aseizure. It is vitally important clinically to recognisethe possibility of brainstem ischaemia in such cases, asthey may be a warning of impending brainstem infarc-tion from basilar thrombosis.34 The pathophysiologyof these movements is not well understood: they mayrepresent a ‘release phenomenon’ resembling ‘decere-brate’ posturing, or disturbance of function of thereticular formation.

Capsular warning syndromeThe capsular warning syndrome is one of the mostdramatic presentations in stroke medicine. In thisstriking phenomenon, in situ disease of a single pene-trating artery is thought to cause fluctuating ischaemiaand neuronal dysfunction limited to the internalcapsule. The early stroke risk is high.35 Many attackscan occur in a short period of time (eg, 24–48 h)leading to suspicions of seizures or functional disorderin some patients. A similar phenomenon relating topontine perforating artery ischaemia (“pontinewarning syndrome”) is also described.

SUMMARYSuspected TIA remains a common and importantdiagnostic challenge for physicians in primary and sec-ondary care, including neurologists. The transience ofsymptoms makes historical features paramount in

Figure 4 Imaging from a patient who presented withrecurrent attacks of rhythmic jerking of the left arm, related tochanging from a sitting to standing position. (A) MR angiogramshowing critical right middle cerebral artery stenosis. (B) Fluid-attenuated inversion recovery (FLAIR) MRI showing high signalsin the right hemisphere white matter in a ‘borderzone’distribution.

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establishing the diagnosis among the many ‘mimics’.The pathophysiological differences between TIA andthe most common mimics (including migraine, sei-zures and syncope) mean that careful consideration ofclinical features can be very helpful in establishing thediagnosis. However, the clinical history does notallow complete certainty. Indeed, recent studies showthat haemorrhagic cerebrovascular disease can mimicTIA (especially cortical superficial siderosis in associ-ation with cerebral amyloid angiopathy), with some-times devastating consequences if antithromboticdrugs are started or continued; the proportion ofpatients with transient symptoms who may be harmedby incorrect diagnosis requires formal study. It never-theless seems reasonable to recommend MRI (includ-ing optimum sequences to detect ischaemia andhaemorrhage) as the imaging modality of choice inassessing TIA, since it may provide positive evidenceof ischaemic injury and can exclude significant haem-orrhage. Together with careful clinical evaluation thisshould allow the most effective distinction of TIAfrom the myriad of ‘mimics’.

Contributors DJW: idea for the review, drafting and editing themanuscript. VN: drafting and editing the paper. RJP: draftingand editing the paper. JJ: editing the paper and criticalrevisions.

Competing interests None.

Provenance and peer review Commissioned; externally peerreviewed. This paper was reviewed by William Whiteley,Edinburgh, UK.

Open Access This is an Open Access article distributed inaccordance with the Creative Commons Attribution NonCommercial (CC BY-NC 3.0) license, which permits others todistribute, remix, adapt, build upon this work non-commercially, and license their derivative works on differentterms, provided the original work is properly cited and the useis non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

REFERENCES1 Easton JD, Saver JL, Albers GW, et al. Definition and

evaluation of transient ischemic attack: a scientific statementfor healthcare professionals from the American HeartAssociation/American Stroke Association Stroke Council;Council on Cardiovascular Surgery and Anesthesia; Council onCardiovascular Radiology and Intervention; Council onCardiovascular Nursing; and the Interdisciplinary Council onPeripheral Vascular Disease. The American Academy ofNeurology affirms the value of this statement as an educationaltool for neurologists. Stroke 2009;40:2276–93.

2 Schrock JW, Glasenapp M, Victor A, et al. Variables associatedwith discordance between Emergency Physician andNeurologist Diagnoses of transient ischaemic attacks in theemergency department. Ann Emerg Med 2012;59:19–26.

3 Sheehan OC, Merwick A, Kelly LA, et al. Diagnostic usefulnessof the ABCD2 score to distinguish transient ischemic attackand minor ischemic stroke from noncerebrovascular events: theNorth Dublin TIA Study. Stroke 2009;40:3449–54.

4 Castle J, Mlynash M, Lee K, et al. Agreement regardingdiagnosis of transient ischemic attack fairly low amongstroke-trained neurologists. Stroke 2010;41:1367–70.

5 Tomasello F, Mariani F, Fieschi C, et al. Assessment ofinter-observer differences in the Italian multicenter study onreversible cerebral ischemia. Stroke 1982;13:32–5.

6 Kraaijeveld CL, van Gijn J, Schouten HJ, et al. Interobserveragreement for the diagnosis of transient ischemic attacks.Stroke 1984;15:723–5.

7 Koudstaal PJ, Gerritsma JG, van Gijn J. Clinical disagreementon the diagnosis of transient ischemic attack: is the patient orthe doctor to blame? Stroke 1989;20:300–1.

8 Rothwell PM, Warlow CP. Timing of TIAs preceding stroke:time window for prevention is very short. Neurology2005;64:817–20.

9 Giles MF, Rothwell PM. Risk of stroke early after transientischaemic attack: a systematic review and meta-analysis. LancetNeurol 2007;6:1063–72.

10 Chandratheva A, Mehta Z, Geraghty OC, et al. Populationbased study of risk and predictors of stroke in the first fewhours after a TIA. Neurology 2009;72:1941–7.

11 Rothwell PM, Giles MF, Chandratheva A, et al. Effect ofurgent treatment of transient ischaemic attack and minor strokeon early recurrent stroke (EXPRESS Study): a prospectivepopulation-based sequential comparison. Lancet2007;370:1432–42.

12 Prabhakaran S, Silver AJ, Warrior L, et al. Misdiagnosis oftransient ischemic attacks in the emergency room. CerebrovascDis 2008;26:630–5.

13 Josephson SA, Sidney S, Pham TN, et al. Higher ABCD2 scorepredicts patients most likely to have true transient ischaemicattack. Stroke 2008;39:3096–98.

14 Amort M, Fluri F, Schafer J, et al. Transient ischaemic attackversus transient ischaemic attack mimics: frequency, clinicalcharacteristics and outcome. Cerebrovasc Dis 2011;32:57–64.

15 Merwick A, Albers GW, Amarenco P, et al. Addition of brain andcarotid imaging to the ABCD2 score to identify patients at earlyrisk of stroke after transient ischaemic attack: a multicentreobservational study. Lancet Neurol 2010;9:1060–9.

16 Warach S, Kidwell CS. The redefinition of TIA: the uses andlimitations of DWI in acute ischaemic cerebrovascularsyndromes. Neurology 2004;62:359–60.

17 Ferro JM, Falcao I, Rodrigues G, et al. Diagnosis of transientischemic attack by the nonneurologist. A validation study.Stroke 1996;27:2225–9.

18 Martin PJ, Young G, Enevoldson TP, et al. Over diagnosis ofTIA and minor stroke: experience at a regional neurovascularclinic. QJM 1997;90:759–63.

19 Calanchini PR, Swanson PD, Gotshall RA, et al. Cooperativestudy of hospital frequency and character of transientischaemic attacks. IV. The reliability of diagnosis. JAMA1977;238:2029–33.

20 Fisher CM. Late-life migrainous accompaniments—furtherexperience. Stroke 1986;17:1033–42.

21 Tentschert S, Wimmer R, Greisenegger S, et al. Headache atstroke onset in 2196 patients with ischemic stroke or transientischemic attack. Stroke 2005;36:e1–3.

22 Kaplan PW. Focal seizures resembling transient ischaemicattacks due to subclinical ischaemia. Cerebrovascular Dis1993;3:241–3.

23 Kerber KA, Brown DL, Lisabeth LD, et al. Stroke amongpatients with dizziness, vertigo, and imbalance in the emergencydepartment: a population-based study. Stroke 2006;37:2484–7.

24 Harrison M, Williams M. The diagnosis and management oftransient global amnesia in the emergency department. EmergMed J 2007;24:444–5.

REVIEW

30 Nadarajan V, et al. Pract Neurol 2014;14:23–31. doi:10.1136/practneurol-2013-000782

25 Stone J, Warlow C, Sharpe M. Functional weakness: clues tomechanism from the nature of onset. J Neurol NeurosurgPsychiatry 2012;83:67–9.

26 Charidimou A, Law R, Werring DJ. Amyloid “spells” trouble.Lancet 2012;380:1620.

27 Charidimou A, Peeters A, Fox Z, et al. Spectrum of transientfocal neurological episodes in cerebral amyloid angiopathy:multicentre magnetic resonance imaging cohort study andmeta-analysis. Stroke 2012;43:2324–30.

28 Ueno Y, Tanaka A, Nakayama Y. Transient neurological deficitssimulating transient ischemic attacks in a patient withmeningioma--case report. Neurol Med Chir (Tokyo)1998;38:661–5.

29 Schulz UG, Rothwell PM. Transient ischaemic attacksmimicking focal motor seizures. Postgrad Med J 2002;78:246–7.

30 Baquis GD, Pessin MS, Scott RM. Limb shaking--a carotid TIA.Stroke 1985;16:444–8.

31 Tatemichi TK, Young WL, Prohovnik I, et al. Perfusioninsufficiency in limb-shaking transient ischemic attacks. Stroke1990;21:341–7.

32 Persoon S, Kappelle LJ, Klijn CJ. Limb-shaking transientischaemic attacks in patients with internal carotid arteryocclusion: a case-control study. Brain 2010;133(Pt3):915–22.

33 Special report from the National Institute of NeurologicalDisorders and Stroke. Classification of cerebrovascular diseasesIII. Stroke 1990;21:637–76.

34 Wilson LK, Benavente OR, Woolfenden AR, et al. Sponaneouslimb movements and posturing secondary to acute basilarartery occlusion: a potentially devastating seizure mimic. PractNeurol 2014;14:42–4.

35 Donnan GA, O’Malley HM, Quang L, et al. The capsularwarning syndrome: pathogenesis and clinical features.Neurology 1993;24:957–62.

REVIEW

Nadarajan V, et al. Pract Neurol 2014;14:23–31. doi:10.1136/practneurol-2013-000782 31