Stroke is a clinical syndrome.

J Neurol Neurosurg Psyhiatry 2001;70 (suppl I):i7 i11 RADIOLOGY OF STROKE J M Wardlaw *i7 Stroke is a linial syndrome. 1 In the investigation of stroke and transient ishaemi attak (TIA) imaging is used to diverentiate: vasular from non-vasular lesions, suh as tumours or infetions ishaemi from haemorrhagi stroke arterial from venous infartion and to distinguish anterior and posterior irulation strokes to determine whether a tight arotid stenosis is symptomati or not. In the future imaging may be used to show the extent of salvageable tissue in aute stroke before treatment. Imaging should be used to diret management. Investigation should be organised to resolve speifi, preferably artiulated, management dilemmas. This may inlude imaging to larify and guide prognosis. COMPUTED Correspondene to: Dr JM Wardlaw, Department of Clinial Neurosienes, Bramwell Dott Building, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK jmw@skull.dn.ed.a.uk TOMOGRAPHY Computed tomography (CT) will diverentiate infart from haemorrhage up to at least five days after stroke. Reent haemorrhages are high density (white) and usually rounded and spae oupying. Infarts are usually low density (dark) and oupying a vasular territory with some swelling (fig 1). In a patient with a stroke a normal san exludes a haemorrhage and, in the absene of an alternative, infartion is assumed. 2 Intravenous ontrast is not normally required and may ause onfusion. There is some unertainty as to how quikly small haemorrhages lose their harateristi whiteness and beome isodense and then hypodense ompared with normal brain, and so indistinguishable from an infart. Certainly by 10 days, small haemorrhages will be indistinguishable from infarts, and we have seen small haemorrhages disappear by seven days. Large haemorrhages remain visible as suh for 2 3 weeks. There is no optimal time to image stroke patients with CT and expet to show a definite infart. Many infarts do not beome visibly hypodense until hours or even a day after the stroke, if ever. 3 Small infarts are less likely to be visible than large ones about 90% of patients with symptoms of a large ortial infart (total anterior irulation infart TACI) have a visible infart by 48 hours after stroke ompared with about 40% of patients with launar (LACI) or small ortial infarts (partial anterior irulation infart PACI). 3 Many larger infarts are visible within six hours though the appearane is subtle and depends on how losely the san is examined. Observer reliability for speifi signs of early infartion (even among experts) is poor (fig 1). 45 Furthermore, between 10 days and three weeks after stroke, infarts loose their hypodensity and beome isodense with normal brain for several days to two weeks. 2 As the swelling has also gone by this stage, they may be ompletely invisible or their true extent impossible to determine. This phase is termed as fogging. By 2 3 months the infart has usually beome shrunken and is of erebrospinal fluid density, and so is more readily visible. The best time to image stroke routinely with CT is as soon as possible; nothing is gained by waiting, and muh may be lost. In pratie the timing of sanning is influened by what treatments are being onsidered and available resoures. In patients onsidered andidates for reombinant tissue plasminogen ativator (rt-pa), CT sanning is mandatory to exlude intraranial haemorrhage or sizeable infartion before the thrombolyti drug is given. 6 Currently, in view of the potential hazards, there are good arguments for only onsidering the use of thrombolysis in a highly organised linial environment, with appropriate dediated are pathways established and expert CT san review available immediately. In view of the relative lak of harm arising from a few doses of aspirin in patients who turned out to have a haemorrhage in the IST/CAST trials (International stroke trial/chinese aute stroke trial), 78 liniians should onsider starting aspirin pending the san if they onsider that haemorrhage is unlikely on linial grounds, and obtain a CT san the next day. Aspirin may then be stopped if the CT san shows a haemorrhage. Cliniians and radiologists need to have established guidelines on sanning whih reflet the available loal resoures (see below). www.jnnp.om

Neurology in Pratie *i8 Figure 1 CT brain san showing a right hemisphere total anterior irulation infart (A) at four hours, and (B) at five days after symptom onset. Note on (A) the subtle signs of early infartion: loss of the basal ganglia on the right (white arrow ompare with the left where the audate and lentiform nulei are learly visible), loss of the grey/white matter ortial differentiation (blak arrowheads), a little swelling with sulal effaement (blak arrow and ompare left side). On day 5 there is obvious hypodensity and massive infart swelling with midline shift and obstrution of the left lateral ventrile. Uses of CT in stroke To differentiate vasular from non-vasular disorders To differentiate infart from haemorrhage If in doubt, repeat san a few weeks later without ontrast Contrast an be misleading and should only be used in speial irumstanes Caveats on CT in stroke Identifies all parenhymal haemorrhage with near 100% auray only within 5 7 days of stroke thereafter small haemorrhages are indistinguishable from infarts Only about 50% of infarts ever beome visible There is no optimal time for seeing an infart Seeing the infart is not neessary to diagnose ishaemi stroke Routine magneti resonane imaging The magneti resonane (MR) appearane of aute haemorrhage is omplex, but with the appropriate sequene, aute haemorrhage may be identified orretly even within the first six hours of stroke. 2 Routine (spin eho) MR sequenes remain speifi for haemorrhage indefinitely in 90% of patients. 9 In the remaining 10% who have had a definite intraerebral haemorrhage, the diagnosti features (that is, low signal aused by haemosiderin) are not visible on spin eho T2 MR, although erebromalaea may be visible. Other MR sequenes vary in their sensitivity to the presene of haemosiderin. In partiular, the now frequently used fast spin eho T2 and proton density sequenes are relatively insensitive whereas gradient eho sequenes are the most sensitive (fig 2). If the identifiation of former haemorrhage is important, it is imperative that the radiologist is told otherwise an inappropriate sequene may be used. With the right sequene, MR will make this diagnosis in the majority of ases. The same priniples of infart evolution apply to routine MR imaging (T2, proton density and T1) as desribed for CT, inluding the problems of fogging and that a proportion of infarts will never be visible on routine Figure 2 Brain imaging from a 75 year old woman presenting six weeks after a left hemisphere stroke. (A) CT san. (B) Fast spin eho T2 MR san. (C) Gradient eho MR san. Note on the CT san (A) the luent areas onsistent with small vessel disease. The luent area in the left hemisphere would be onsistent with the symptoms and looks like an infart. The MR (B, C) obtained on the same day shows not only more small vessel ishaemi hanges (white spots) but also haemorrhage (dark area arrowed) in the left lentiform nuleus. The haemorrhage is more readily identified on the gradient eho MR (C) than on the fast spin eho T2 (B). On the latter, old haemorrhage may easily be overlooked. There are also several old mirohaemorrhages visible on the gradient eho MR (blak dots) and an inidental small alified lesion in the oipital lobe (arrowhead). www.jnnp.om

Neurology in Pratie Figure 3 Cerebral venous thrombosis and infartion (A) pre- and (B) post-intravenous ontrast. The sans were obtained at six hours after symptom onset. Note that the hypodensity in the left posterior temporal region is muh more developed than for an arterial infart of the same age (fig 1A), with more learly defined edges and entral haemorrhage (white arrow). After ontrast there is entral enhanement (white arrow) and a thrombosed transverse sinus is visible (blak arrow). The affeted territory does not orrespond with either the middle erebral or posterior erebral arteries, providing a further lue to the venous origin. *i9 MR. Examples of the evolution of the appearane of infarts and haemorrhages on MR are also given elsewhere. 2 Advaned magneti resonane tehniques Infarts may be demonstrated on MR with greater sensitivity than CT using ertain sequenes suh as fluid attenuated inversion reovery (FLAIR) or divusion weighted imaging (DWI). Unfortunately FLAIR also shows many more additional inidental white matter lesions that may simply add to onfusion rather than help to identify the new lesion. 2 Of all tehniques divusion imaging has the greatest sensitivity, but is not speifi for infartion. 10 Enephalitis, multiple slerosis plaques, and tumours may all appear of inreased signal and be mistaken for an infart by the unwary. On DWI, larger infarts are visible more often than small ones, and a proportion of patients with a definite stroke never have a visible infart; some patients who turn out to have a TIA have a relevant visible lesion on DWI when 10 11 imaged within 24 hours of symptom onset. Although there is onsiderable interest in the use of DWI and perfusion MR imaging to identify patients with salvageable tissue, this is still experimental. MR takes longer than CT (so may expose the patient to greater risk of aspiration while supine in the sanner), and may delay the start of treatment as most entres do not have the immediate MR availability required. DWI may be most useful linially to identify positively the lesion site in patients with minor ortial or launar strokes, or to determine whether a patient with a previous infart and worsening signs has developed a new infart or not; DWI is likely to be positive up to a week at least after the stroke. 12 Perfusion imaging with MR is not in routine use. The most readily available method provides only relative, not absolute, perfusion measurements. Further work is required to improve the interpretation of this tehnique. MR spetrosopy provides information on metabolites, notably latate, holine reatine, and N aetyl aspartate (NAA found in normal funtioning neurones). Improved spetrosopi imaging and faster image aquisition times may bring it into wider use, but urrently its main appliation is in stroke researh. The exeptions where it may oasionally be useful linially are to distinguish tumours from infarts where other imaging is ambiguous (a high holine ontent is found in tumours, whereas infarts typially have redued NAA and normal or redued holine); or in rare metaboli onditions assoiated with stroke like MELAS (mitohondrial enephalomyopathy with lati aidosis and stroke see below). Uses of MR in stroke To distinguish haemorrhage from infart in patients presenting late after stroke but only if the appropriate sequenes are used More often shows an ishaemi lesion than CT so may be more useful in diffiult young patients with suspeted stroke In diffiult strokes suh as suspeted venous infartion or arotid or vertebral dissetions, as it may show the vasular anatomy also Speial linial irumstanes Venous infarts are probably underdiagnosed as a ause of stroke (fig 3). Inreasing awareness leads to better reognition. 213 Venous infarts beome hypodense and www.jnnp.om

Neurology in Pratie i10 * swollen muh more rapidly than arterial infarts and more often ontain entral areas of haemorrhage. Additional features suh as thrombosed venous sinuses (hyperdense sinus pre-ontrast, or filling defet in the sinus post-ontrast), or opaified paranasal sinuses or mastoids indiating probable infetion as the ause of thrombosis, should be sought. MR shows these features more learly, though they may be visible on CT. Distinguishing tumours from infarts on CT (or MR) is not usually a problem, but oasionally slow growing tumours suh as gliomas an mimi a small ortial infart by appearing wedge shaped, involving ortex and adjaent white matter, being slightly hypodense, and not enhaning with ontrast. Oasionally tumours may also present as a haemorrhage and the bleeding may be extensive enough to obliterate temporarily the underlying neoplasm on the san. Time is a useful diagnosti tool; repeating the imaging will larify diagnosis, as infarts and haemorrhages generally get smaller whereas tumours stay the same or get bigger. Furthermore, patients who initially present with what seems like a straightforward stroke, but who do not behave subsequently as a typial stroke, should have a repeat san to identify the oasional tumour or other non-vasular lesion. Enephalitis an oasionally mimi stroke, partiularly in patients found unwell with diminished onsiousness, foal neurology, and no available history of the onset. Imaging, either CT, MR or advaned MR tehniques, does not always reliably distinguish between these linial entities. Diagnosis depends on other assessment. Dissetion of the arotid or vertebral artery should be suspeted in patients with nek pain and a stroke. MR is best as it may show the vasular and the parenhymal lesion. A typial feature is narrowing of the flow void in the symptomati arotid or vertebral artery due to a ring or uv of high signal aused by fresh haemorrhage in the artery wall. Unfortunately this appearane an also be mimiked (more ommonly in the arotid than the vertebral artery) by slow flow in the artery above a tight (atheromatous) stenosis, or proximal to a major intraranial arterial olusion, so some aution is required not to overdiagnose dissetion. In view of possible therapeuti impliations, intra-arterial angiography should be onsidered if there is any doubt as to the diagnosis of dissetion. CADASIL (erebral autosomal dominant arteriopathy with subortial infarts and leuoenephalopathy) auses prominent subortial white matter abnormalities whih may mimi multiple launar infarts and atrophy, often in a relatively young patient. Imaging is supportive of the diagnosis. MR shows more detail than CT. MELAS (mitohondrial enephalopathy, lati aidosis, and stroke) presents with stroke in younger patients. On CT or MR ortial infart-like lesions are visible usually in the posterior temporal or oipito-temporal regions, often bilaterally and not stritly oupying a typial vasular territory. Who should read the san? MR is ompliated and should be left to neuroradiologists or oasionally general radiologists who have a partiular interest in neuroimaging. Neurologists and stroke physiians are more used to reading CT sans as the tehnology has been available for longer, and they should be able to diverentiate an infart from a haemorrhage and to know when a lesion looks non-vasular. Gaining this experiene takes time and requires looking losely at as many films as possible. Cliniians should be aware, however, that the signs of early infartion and small haemorrhages an be subtle and overlooked, and alifiation may be mistaken for haemorrhage. Therefore liniians may not be onfident to base management deisions on their interpretation of the san where the identifiation of early infartion or of subtle haemorrhage is partiularly important (for example, before thrombolysis). This is partiularly true in the ase of trainees in neurology and stroke mediine who simply may not have had the opportunity to see enough sans to gain the requisite experiene. What about the nek arteries? Carotid Doppler ultrasound is the simplest, safest, quikest, and best way of assessing the arotid and vertebral arteries to identify atheromatous stenosis or dissetion. However, although it looks deeptively easy in experiened hands and when the patient is normal, it is very operator dependent and there are numerous pitfalls for the unwary. Thus it should only be done by properly trained operators with a reasonable throughput of patients to maintain their expertise and where evorts are made to audit the results. Patients with launar strokes are less likely than those with ortial infarts to have a stenosis; about 8% of launar stroke patients will have a tight stenosis in the symptomati artery. 14 In some entres ultrasound is the only imaging of the nek done before endarteretomy, while others still rely on intra-arterial angiography for the definitive measurement of stenosis, or use MR or CT angiography. Intra-arterial angiography is risky in patients with symptomati ishaemi erebrovasular disease (4% permanent stroke, 1% death) and delays endarteretomy, and MR and CT angiography are no better than Doppler ultrasound in ompetent hands (though they may be alternatives where ultrasound expertise is laking). Whatever is used, it is important that the imaging is reported by radiologists with an interest in arotid disease. Use of guidelines and organising loal investigations Stroke is suh a ommon ondition that an average general hospital will admit one or two ases per day. Thus the investigation of stroke must be well organised, otherwise a baklog develops resulting in delayed, ineyient, and suboptimal patient management. Imaging resoures (either money or sanner time) are not infinite. Inappropriate resoure use also displaes patients with other (possibly more needy) diagnoses, and reates onflit and frition between diverent linial departments and radiologial servie providers. These diyulties may be partiularly true in hospitals where there is a large mixed general body sanning workload. Imaging resoures in most parts of the ountry are still well below those required by the loal populations. Various bodies have issued guidelines for the investigation of stroke. 15 Individual hospitals will need to determine how best to apply these guidelines in light of their own resoures. Good ommuniation between linial and radiologial departments is absolutely fundamental to this proess. Referenes 1 Hatano S. Experiene from a multientre stroke register: a preliminary report. Bull WHO 1976;54:541 53. 2 Wardlaw JM. What pathologial type of stroke is it? In: Warlow CP, et al, eds. Stroke, a pratial guide to management, 2nd ed. Oxford: Blakwell Siene (in press). In depth and omprehensive overage of brain imaging in stroke set out in a pratial and logial order with lots of examples. There are important additions to the seond edition so read that in preferene to the first, as there has been an explosion of information on neuroimaging sine the first edition appeared. www.jnnp.om

Neurology in Pratie 3 Wardlaw JM, Lewis SC, Dennis MS, et al. Is visible infartion on omputed tomography assoiated with an adverse prognosis in aute ishaemi stroke? Stroke 1998;29:1315 19. 4 Wardlaw JM, Dorman PJ, Lewis SC, et al. Can stroke physiians and neuroradiologists identify signs of early erebral infartion on CT? J Neurol Neurosurg Psyhiatry 1999;67:651 3. 5 von Kummer R, Bozzao L, Manelfe C. Early CT diagnosis of hemispheri brain infartion. Berlin: Springer, 1995. A very useful guide to early infart signs on CT with lots of exellent examples and follow up sans so that the reader an see how the infart developed. 6 Wardlaw JM, del Zoppo G, Yamaguhi T. Thrombolyti therapy in aute ishaemi stroke. Part 1. Thrombolysis versus ontrol. In: Warlow C, Van Gijn J, Sanderok P, eds. Stroke module of the Cohrane Database of Systemati Reviews, [updated 10 Otober 1999]. Available in The Cohrane Library [database on disk and CD-ROM]. The Cohrane Collaboration; Issue 4. Oxford: Update Software; 1999. Updated quarterly third substantive revision. Full details of all the available evidene on thrombolysis in aute ishaemi stroke. A must for anyone onsidering either partiipating in a new trial or implementing a routine thrombolysis servie. 7 The International Stroke Trial Collaborative Group. The international stroke trial (IST): a randomised trial of aspirin, subutaneous heparin, both or neither among 19435 patients with aute ishaemi stroke. Lanet 1997;349:1569 81. 8 Chen ZM, Sanderok PAG, Pan HC, et al, on behalf of the CAST and IST ollaborative groups. Indiations for early aspirin use in aute ishaemi stroke. A ombined analysis of 40,000 randomised patients from the Chinese aute stroke trial and the international stroke trial. Stroke 2000;31:1240 9. A must for all dotors treating aute stroke the full details on the risks and benefits of aspirin. 9 Wardlaw JM, Statham PFX. How often is haemosiderin not visible on routine MRI following traumati intraerebral haemorrhage. Neuroradiology 2000;42:81 4. 10 Powers WJ. Testing a test. A report ard for DWI in aute stroke. Neurology 2000;54:1549 51. A very well balaned ritique of the enthusiasti literature on diffusion MR imaging, pointing out some problems. 11 Keir SL, Wardlaw JM. A systemati review of diffusion and perfusion MR imaging. Stroke 2000;31:2723 31. The detailed data to bak up the omments in referene 10! Both 10 and 11 are essential for anyone interested in either routine use of advaned MR in stroke, or its use in researh. 12 Wardlaw JM, Armitage P, Dennis MS, et al. The use of diffusion-weighted magneti resonane imaging to identify infartions in patients with minor strokes. J Stroke Cerebrovas Dis 2000;9:70 5. 13 Bakaç G, Wardlaw JM. Problems in the diagnosis of intraranial venous infartion. Neuroradiology 1997;39:566 70. 14 Mead GM, Wardlaw JM, Lewis SC, et al. Can simple linial features be used to identify patients with severe arotid stenosis on Doppler ultrasound? J Neurol Neurosurg Psyhiatry 1999;66:16 19. 15 Sottish Interollegiate Guidelines Network (SIGN). Management of patients with stroke. 1. Assessment, investigation, immediate management and seondary prevention. Edinburgh: SIGN, 1997. *i11 Want to know more? Data supplements Limited spae in printed journals means that interesting data and other material are often edited out of artiles; however, limitless yberspae means that we an inlude this information online. Look out for additional tables, referenes, illustrations. www.jnnp.om www.jnnp.om