IRecentAdvances

in Pharmacotherapy

Transient ischemic attacksand stroke

Thomas R. Mirsen, MDVladimir C. Hachinski, MD, MSc (DME), FRCPC

Transient ischemic attacks (TIAs) constitute themost specific and powerful warnings of impend-ing stroke. They are defined as brief, focalneurologic events of sudden onset. Their properrecognition and treatment rank second only tothe modification of risk factors in importance forstroke prevention. Carotid endarterectomy, al-though widely used to treat TIAs, remainsunproven; randomized clinical trials are at-tempting to define its role. Anticoagulant ther-apy appears worth while for suspected cardiacembolism and possibly for disabling TIAs.Acetylsalicylic acid is the only agent that hasbeen found to be effective in controlled trials,but questions persist about its dosage, its effica-cy in women and its use after stroke. Anotherplatelet inhibitor, ticlopidine hydrochloride, isbeing investigated and may prove to be aneffective alternative.

Les crises d'ischemie cerebrale transitoire (ICT)sont les signes avant-coureurs les plus impor-tants et les plus specifiques d'un accident cere-brovasculaire imminent. II s'agit de brefs episo-des, a debut soudain, de troubles neurologiquesfocaux. Le diagnostic et le traitement des ICT nele cedent en importance qu'a la modification desfacteurs de risque dans la prevention de cesaccidents. Le traitement des ICT par l'endar-terectomie carotidienne, qui se pratique sur unelarge dchelle, n'a pas encore fait ses preuves; il

From the Department of Clinical Neurological Sciences, Facultyof Medicine, and the John P. Robarts Research Institute,University of Westem Ontario, London

Dr. Hachinski is a career investigator of the Heart and StrokeFoundation of Ontario.

Reprint requests to: Dr. Vladimir C. Hachinski, Department ofClinical Neurological Sciences, University Hospital, PO Box5339, Stn. A, London, Ont. N6A 5A5

est actuellement l'objet d'essais cliniques com-paratifs sur des sujets choisis au hasard. L'anti-coagulotherapie semble utile si on croit etre enpresence d'embolies d'origine cardiaque et peut-etre devant des ICT qui s'accompagnent d'unegene fonctionnelle grave. Seule l'acide acetyl-salicylique a ete reconnu efficace a la suited'essais comparatifs avec des sujets temoins;restent 'a definir sa posologie, son efficacite chezla femme et son emploi une fois survenu l'acci-dent cerebrovasculaire. Un autre antiplaquet-taire, le chlorhydrate de ticlopidine, actuelle-ment a lessai, se montrera peut-etre efficaceaussi.

Mt r ost strokes occur unannounced, but someare heralded by transient ischemic at-tacks (TIAs), which are episodes of sud-

den focal neurologic deficit of presumed vascularorigin that last less than 24 hours.1 The duration ofan attack has been less than an hour in half of thereported cases2,3 and is usually minutes.4 TIAs havebeen found to precede as few as 9% of strokes inpopulation surveys and as many as 35% of thosein hospital-based studies.5 They not only constitutemarkers of stroke risk6 but also direct attention tospecific cerebral vascular areas, unlike other riskfactors such as carotid bruit7 and heart disease.Thus, although they are present in a small propor-tion of stroke cases, TIAs uniquely identify possi-ble sites of cerebral infarction. TIAs are discussedhere with minor strokes, which are strokes thatleave no residual signs, because the two eventshave a similar prognosis.8 Also mentioned arereversible ischemic neurologic deficits (RINDs),which are strokes that resolve fully within 3weeks.

Classification of TIAs

About 80% of the cases of TIAs involve the

CMAJ, VOL. 138, JUNE 15, 1988 1099

internal carotid arteries, the remainder affectingthe vertebrobasilar system.3,4'910 Typical symptomsin approximate order of frequency that are associ-ated with carotid TIAs include ipsilateral weaknessof the face, arm and leg (alone or in combination),ipsilateral paresthesia of the face, arm and leg(alone or in combination), transient blindness inone eye (amaurosis fugax) and difficulties in un-derstanding or speaking (aphasia); the symptomsassociated with vertebrobasilar TIAs include ataxia,vertigo, diplopia, bilateral visual impairment anddysarthria.1'

Differential diagnosis

Migraine and focal seizures may be confusedwith TIAs, but, unlike TIAs, which occur abruptlyand maximally, they tend to display an "anatomicmarch" of symptoms; often the patients' historieswill suggest these disorders. Tumours may producesimilar symptoms, but computed tomography (CT)will identify them. "Cerebral vascular insufficien-cy", a concept borrowed from the heart and legs,has proven an erroneous and misleading term. Forpractical purposes there is no analogy to intermit-tent claudication in the brain.12 Moreover, thisconcept is mistakenly used to explain nonspecificdizziness and memory disturbance, which seldomreflect underlying vascular disease.12

Management of TIAs

Although TIAs have multiple causes, eachdeserving consideration,13 a general approach tomanagement appears in Table I.13

The control of risk factors probably benefitsmost patients, pharmacologic agents many patientsand carotid endarterectomy some patients withTIAs.

Control of risk factors

The continuing decrease in the incidence ofstroke has probably resulted primarily from thetreatment of hypertension,5 which is the principalrisk factor.14'15 Other prevalent risk factors arediabetes mellitus,15 cigarette smoking16 and possi-bly hypercholesterolemia.15 Treatment of theseconditions has not been proven to reduce theincidence of stroke, although one might expectsuch a favourable result. Various cardiac diseasesalso constitute important risk factors.15 The pres-ence of atrial fibrillation indicates particularly highrisk,17 but the value of anticoagulant therapy re-mains uncertain.

Carotid endarterectomy

The status of carotid endarterectomy has notbeen settled. No single well-designed trial hasshown that it decreases morbidity and mortalityrates. One randomized study was aborted after theentry of 41 patients because of the excessive early

stroke and death rate after surgery.18 However,follow-up at 5 years showed that the medicallytreated group had a higher incidence of late strokeand death and had more TIAs than the surgicallytreated group.

The Joint Study of Extracranial Arterial Occlu-sion19 randomly assigned 316 patients with TIAs tosurgical or medical treatment after angiography.Surgery was claimed to be beneficial, largely be-cause of a decreased incidence of TIAs. If strokeand death alone were considered, no benefit ac-crued, in the entire group or in the specificsubgroups. Warlow20 showed that the study hadseveral flaws, particularly an inadequate number ofsubjects to support any definite conclusions. Otherfactors have changed since the time of that study:surgical results have improved, in some centres atleast,21 and acetylsalicylic acid (ASA) therapy, nowcommon, may influence the outcome in bothmedically and surgically treated groups.

Carotid endarterectomy remains a commonprocedure.22 More research will help to define theproper role of this operation, as it did for extra-cranial-intracranial bypass.23 Two separate studiesin the United States - one conducted by Dr. JamesToole and associates24 and the other the VeteransAdministration Cooperative Study25- will assessthe effect of endarterectomy on stenotic vessels inpatients without previous ischemic symptoms inthe cerebral areas supplied by those vessels. As forsymptomatic patdents a North American study,26

Table I Approach to the management of patientr.with transient ischemic attacks or stroke

Modification of risk factorsSurgical treatment

Carotid endarterectomy*Factors in favour:

Carotid stenosis, as seen by angiography, tharlhemodynamically significant and involves ulcerintraluminal thrombus

Availability of experienced angiographer and sLayge:who have had good reslts with the procedur'

Factors opposed:Patient older than 75 yearsSerious associated diseaseWidespread cervicocerebral vascular disease

Surgery on the vertebrobasilar system',Extracranial-intracranial arterial bypass4

Drug therapyAnticoagulants (in cases of cardiac embolism (r disabliri:.:

attacks)HeparinCoumadin

Platelet inhibitorsAcetylsalicylic acid, 325 mg four times dailv idose in:

be decreased if side effects occur)Ticlopidine hydrochloride (under investigatiorna

*Given the uncertainty about the -dicatioris trc 1arotvendarterectomy, patients should, when possible, be referre(to the North American Symptomatic Carotid Endarterectomy Trial26 through Dr. Mirsen (519-663-57-7 7tHas not been proven effective.4ls no better than drug therapy alone.

1100 CMAJ, VOL. 138, JUNE 15, 1988

directed by Drs. Henry Bamett and Sydney Peer-less, has also begun, as has a European trial. Onlythe North American trial is accessible to Canadianphysicians and patients; 3000 patients will enterthe study over 2 years and then be followed up for5 years.

Anticoagulant therapy

Anticoagulant therapy is sometimes justifiedfor TIAs of cardiac origin1 27 and may controlrecurrent TIAs,1 28'29 although some of the evidenceis poor30 and some negative.3132 Anticoagulationhas not been proven to protect against stroke anddeath in unselected patients with TIAs, as re-viewed by Weksler and Lewin27 and by Brust.33The older randomized trials27-30 included so fewsubjects, with even fewer events, that no conclu-sions could be drawn. More recent reports thatcompared anticoagulants with platelet inhib-itors32'34 had more patients but still failed to showbenefit from anticoagulants.

The definitive trial of anticoagulant therapywill likely never occur now that ASA is thepreferred treatment. Anticoagulants are still usedempirically when TIAs recur despite ASA therapy,but whether they truly decrease the incidence ofTIAs or prevent stroke in such cases remainsunknown. In any event, multiple TIAs have notbeen established as indicators of an increased riskof stroke.35-38

The duration of anticoagulation also bearsmention. The results of a retrospective study sug-gested that anticoagulants prevented stroke onlyduring the first 2 months after a TIA.39 An analysisof the hemorrhagic complications of long-termanticoagulant therapy for cerebral vascular diseaseimplied that the risks far exceed the benefits.40However, the information in these two articleslargely predates the era of CT scanning. Conse-quently, at least some of the morbidity and mortal-ity reflects undetected cerebral hemorrhages andhemorrhagic infarctions in patients who receivedanticoagulants.

Anticoagulants should be used after TIAs onlyif clearly indicated, as in cases of suspected cardiacembolism or disabling TIAs, and then carefully.The duration of therapy should depend on theindividual situation, which deserves re-evaluationafter 3 to 6 months.

Antiplatelet therapy

The literature contains hundreds of papers onthe use of platelet inhibitors in cases of cerebrovas-cular disease, but few approach clinical credibilityby the criteria outlined by Sackett.41 These studiesincluded patients with TIAs and those with minorstroke.

The Canadian Cooperative Study Group38compared ASA (325 mg four times daily), sulfin-pyrazone (200 mg four times daily), the combina-tion of these agents and placebo in the prevention

of cerebral ischemia and death. A total of 585patients who had had TIAs within the preceding 3months were divided into four groups and werefollowed up for a mean of 26 months. ASA wasfound to decrease the incidence of stroke anddeath by 48% in men as a group and by 62% inmen with no history of myocardial infarction.Women did not appear to benefit. The overallstroke and death rates decreased by 30%. Sulfin-pyrazone did not prove valuable. Pain in the upperabdomen and heartburn occurred more often inthose who took ASA than in those who did not;the incidence of symptomatic gastrointestinalhemorrhage was, however, equal in the twogroups. The authors included patients who died ofcauses other than vascular disease in their analysis.Their comparison of the combined results in theASA and ASA-sulfinpyrazone treatment groupswith the combined results in the placebo andsulfinpyrazone treatment groups has been criti-cized by Kurtzke,42 who also questioned whetherthe effect ascribed to ASA was due in part to asynergy between ASA and sulfinpyrazone.

This synergy is unlikely;43 Candelise and col-leagues44 found that sulfinpyrazone was no betterand was possibly worse than ASA in preventingstroke, myocardial infarction or death after TIA.They included relatively few subjects - 124, divid-ed in two groups - who were followed up for amean of only 11 months. Consequently, few vas-cular events occurred. Nevertheless, no strikingeffect of sulfinpyrazone emerged.

Bousser and collaborators36 randomly assigned604 patients who had suffered a stroke or TIA notmore than 1 year earlier to receive placebo, ASAalone (1 g/d) or ASA and dipyridamole (1 g/d and225 mg/d respectively); follow-up lasted an aver-age of 3 years. The cumulative stroke rate was 18%among the control subjects but only 10.5% (42%less) in the ASA-treated groups. Dipyridamole didnot add protection. Women derived less benefitthan did men. Of the patients 23% had ex-perienced a stroke or TIA between 3 months and 1year before entry into the study. Because the riskof stroke appears to be greatest in the first 3months after TIAs,45 the detection of a beneficialeffect of ASA is more difficult if so many subjectsare included long after their symptoms have oc-curred. This bias actually bolsters the results of thestudy. The patients who used ASA had a signifi-cantly elevated incidence of peptic ulcer diseaseand gastrointestinal hemorrhage, although nodeaths occurred.

A US study of ASA in the prevention of strokeincluded 178 patients with carotid TIAs that haddeveloped within the previous 3 months; thepatients were treated with either ASA (650 mgtwice daily) or placebo.46 The investigators foundthat ASA decreased the risk of cerebral or retinalinfarction by 30% and the risk of infarction ordeath by 28% after 2 years. Because of the smallnumbers the results were not statistically signifi-cant. The authors also suggested, but did not

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establish, that ASA decreased the incidence ofTIAs. ASA reduced the risk of death, stroke orretinal infarction after 2 years by 55% in thepatients who had ulceration or stenosis of morethan 50% of the carotid artery on the same side astheir TIAs. ASA did not prevent such eventsamong those who presented with a single TIA butdid decrease the risk by 48% among those withmultiple TIAs. The authors did not evaluatewhether the single-TIA and multiple-TIA groupsdiffered in any other way to explain the contrastingresponses to therapy. The ASA and placebo groupshad comparable incidence rates of occult blood inthe stool; however, four patients in the ASA grouphad severe hemorrhage (gastrointestinal in threecases and cerebral in one), whereas only oneperson in the placebo group had a duodenal ulcer.

In the UK-TIA Aspirin Trial47 2436 patientswith TIAs or minor stroke received either ASA(600 mg twice daily or 300 mg once daily) orplacebo starting between 1979 and 1985; thefollow-up averaged 4 years. The interim resultsindicated that ASA decreased the risk of myocardi-al infarction, major stroke or death by 18%. Thechance of suffering disabling stroke or vasculardeath decreased by 7%, which was not a statisti-cally significant change. There was no clear-cutdifference in the results between the two ASAgroups. The demonstrable benefits of ASA wererestricted to the men, as seen in the Canadian,38French36 and Italian44 trials; perhaps this is becausefew women were entered in any of these trials.Remarkably, ASA seemed to decrease the mortali-ty rate of cancer in the treated subjects. This mayindicate another beneficial effect of ASA or anundetected bias in the study. Interestingly, thestrokes that did occur were fatal slightly moreoften in the treated group than in the controlgroup. This likely reflects the worse outcome ofintracranial hemorrhage in the treated group. Nodoubt an increased availability of CT scanning, asin North America, would have improved thedetection of this condition and prevented its in-appropriate treatment with ASA. Hemorrhage andother disorders of the upper gastrointestinal tractoften developed with ASA use and were dosedependent. Admission to hospital because of gas-trointestinal hemorrhage followed the same pat-tern; however, the number of deaths from thiscause was too low to disclose any differencesbetween the various groups.

A Danish multicentre study examined theefficacy of ASA (1000 mg/d) in preventing strokein people who within the preceding month hadsuffered reversible cerebral ischemic attacks,48 de-fined as episodes that lasted not more than 72hours and included both classic TIAs (lasting lessthan 24 hours) and some RINDs or minor strokes.Of the 203 subjects, who were observed for anaverage of 25 months, 13% in each group died orhad disabling cerebral infarction. The frequency ofnondisabling strokes, RINDs and TIAs likewise didnot differ. Dyken,49 in an accompanying editorial,

showed that the numbers involved in the studywere insufficient to prove that ASA does notprevent stroke. Remarkably, gastrointestinal sideeffects bore no relation to ASA use. The incidenceof myocardial infarction was more than twice asgreat in the placebo group (13.7%) as in the treatedgroup (5.9%), but the difference fell short ofstatistical significance.

The observation that ASA may decrease theincidence of myocardial infarction in patients withTIAs merits attention, because this condition ac-counts for a large proportion of the deaths in sucha population.9Y045'50'51 Some of the decrease inmortality rates may have been due to this effectand not to a decrease in the incidence of stroke. Infact, Bousser and collaborators36 noted a statistical-ly significant decrease in the incidence of myocar-dial infarction among their patients. Others38'48described similar trends, but the Swedish Coopera-tive Study Group52 found no such effect.

Dipyridamole, a vasodilator and platelet an-tiaggregant, is widely prescribed as an adjunct toor instead of ASA. It was initially tested at dailydoses of 400 or 800 mg over 11 months and wasfound not to influence the development of cerebralischemia, whether as TIA or stroke.53 Bousser andcollaborators36 did not find an improved outcomewith the addition of dipyridamole, 225 mg/d, toASA therapy. In addition, dipyridamole was con-vincingly shown to be of no benefit by theAmerican-Canadian Co-operative Study Group,54which randomly assigned 890 patients who hadhad TIAs not more than 3 months before enteringthe study to receive either ASA (325 mg four timesdaily) or dipyridamole and ASA (75 and 325 mgrespectively four times daily). The mean follow-upperiod was more than 25 months. The incidence ofstroke, death and retinal infarction did not differbetween the two groups, nor did the incidence ofstroke and retinal infarction alone.

Management of stroke

The reports cited have dealt primarily with theprevention of stroke after TIA and minor stroke.Others have investigated the prevention of strokeafter completed infarction. In one study suloctidil,a calcium-channel blocker and platelet antiaggre-gant, or placebo was administered to 438 peoplewho had suffered thromboembolic stroke 2 weeksto 4 months before entry into the study.55 Thesubjects were observed for the development ofstroke, myocardial infarction or death from eithercause over a mean follow-up period of 20 months.Although suloctidil therapy reduced the incidenceof these events by 24%, this benefit resulted solelyfrom a decrease in the number of cardiac-relateddeaths. Constipation, vertigo and hepatitis accom-panied suloctidil therapy.

Swedish researchers52 compared the efficacy ofASA (1500 mg/d) with that of placebo in prevent-ing another stroke in 505 people who had had aminor or major stroke; patients having TIAs at the

1102 CMAJ, VOL. 138, JUNE 15, 1988

time of potential entry into the study were exclud-ed. The follow-up period averaged 2 years. Majorstroke - stroke associated with persistent impair-ment in activities of daily living and communica-tion after 3 weeks - had occurred in 56% of thepatients. Most of the patients (93%) underwentcranial CT scanning. ASA did not affect the rate ofdeath, regardless of the cause, or the incidence ofstroke, myocardial infarction or TIAs. No sexdifferences emerged. Subjects with known is-chemic heart disease upon entry into the studyshowed a statistically significant decrease, from34% to 26%, in the stroke and death rate afterASA therapy. When examined separately, neitherrate fell significantly. Gent56 criticized the study forincluding too few patients to definitively rule outbenefits from ASA and added that 26% of thedeaths stemmed from the initial stroke; thus, thedetection of any decrease in the mortality rate dueto ASA would be difficult.

Of all the studies whose results support ben-efit from ASA, only the French one36 resembles theSwedish trial,52 in that many (29%) of the patientsin the former had presented with moderate se-quelae of stroke. If, indeed, ASA does not protectpeople with stroke as well as it does those withTIAs against further stroke, the different patientpopulations in the two studies may account for thediscordant results.

The French and Swedish trials also handledthe patients with severe carotid disease very differ-ently: in the French study these patients wereexcluded and underwent endarterectomy, but inthe Swedish study they were included becauseangiography was not used to identify that condi-tion. If one assumes that patients with severestenoses have a relatively poor prognosis, theirexclusion from a study will render the detection ofdifferences in outcome more difficult, especially ifASA protects those with advanced carotid diseasein particular, as suggested by Fields and cowork-ers.46 Thus, the findings in the French study are allthe more impressive. Conversely, the inclusion ofpresumed surgical candidates in the Swedish studysupports its negative results.

The efficacy of combination therapy with ASAand dipyridamole (325 and 75 mg respectivelythree times daily) in preventing stroke and deathwas studied in 1861 patients with TIA, RINDs orstroke.57 The rate of stroke decreased by half, butthe overall death rate was not influenced. Thecombined rates of stroke and death fell by 35%.The importance of these results lies in the compo-sition of the patient group. The number of menwas only slightly higher than the number ofwomen, the male:female ratio being 55:45; 60% ofthe subjects presented with stroke, 33% with TIAsand 6% with RINDs.58 So far these results haveappeared only in abstract form. If found to be validwhen published-in full they will provide strongevidence that ASA prevents stroke after cerebralinfarction and that it works as well in women as itdoes in men. Because of its track record it is

unlikely that dipyridamole accounted for thesefindings.

Unanswered questions about ASA

ASA evidently prevents stroke and death fromvascular disease after TIA. Various reports havesuggested that its efficacy is highest in certainsubgroups; however, the only observation verifiedby a second study was that its benefit is restrictedto men, especially those over 60 years of age.59 Asimilar finding emerged from a study of theprophylaxis of venous thrombosis after total hipreplacement.60 This disagreement between thesexes may reflect a low incidence of stroke or afavourable prognosis among women,59 or it may bea statistical fluke - the so-called type II error. Itcould be that ASA protects women against strokebut that there are too few women in the variousstudies to prove the point. The European study,57with its large numbers, may accomplish this, justas it may settle the issue of ASA's usefulness afterstroke.

ASA at low doses irreversibly blocks theproduction of thromboxane, a vasoconstrictor andinducer of platelet aggregation. Higher concentra-tions temporarily stop the generation of prostacy-clin in the vessel wall and result in opposite andundesirable effects. At low doses thromboxanealone may be inhibited, vasodilation and decreasedplatelet aggregation being promoted. Apart fromthis theoretical consideration low doses causefewer side effects than do high ones.61 The resultsof in-vitro studies have suggested that as little as40 mg/d is sufficient,62 but such doses have notbeen found to be effective in vivo. The UK-TIAAspirin Trial47 supports the idea that 325 mg/d isas effective as 1300 mg/d and that the lower doseis associated with fewer complications. Until thefinal results of this trial are published patientsshould be treated with the full dose, which may bedecreased if side effects develop.

The future

What have we to look forward to? The inci-dence rates of TIA and stroke will likely continueto decrease. The proper indications for carotidendarterectomy will be delineated. Anticoagulanttherapy for nonvalvular atrial fibrillation will beassessed. Low-dose anticoagulant therapy, proveneffective in cases of venous thrombosis,63 may finda place in the treatment of cerebral vasculardisease. Most promising is another platelet inhibi-tor, ticlopidine hydrochloride, which is currentlybeing compared with ASA in the prevention ofcerebral infarction after TIA or minor stroke (in theTiclopidine-Aspirin Stroke [TASS] Study) and withplacebo in the secondary prevention of stroke (inthe Canadian-American Ticlopidine [CATS]Study).

Certain areas of treatment remain doubtful.The exact role of anticoagulants is still obscure.

CMAJ, VOL. 138, JUNE 15, 1988 1103

Nevertheless, recent years have witnessed the riseof ASA, the first effective agent for stroke preven-tion. It is only the first.

We thank Dr. Henry Bamett for his helpful discussionand review of the manuscript.

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Additional comments on transientischemic attacks and stroke

This review is an excellent survey of a veryextensive, controversial and often contradictoryliterature on the management and therapy of TIAsand ischemic stroke. The discussion is accuratefrom the scientific viewpoint, yet it does nothesitate to confront the practical realities of every-day management. The authors deal primarily withpharmacotherapy, but their inclusion of surgicalconsiderations is entirely appropriate and providesthe comprehensive and balanced viewpoint neces-sary in clinical practice.

A couple of specific clinical comments arepertinent. In general, the accurate diagnosis ofvertebrobasilar TIAs is more difficult than that ofcarotid TIAs. With respect to vertebrobasilar TIAs,single symptoms, such as vertigo, diplopia anddysarthria, are generally insufficient for accuratediagnosis; instead, various combinations of brain-stem, cerebellar and occipital lobe manifestationsare usually necessary for diagnostic certainty. Fur-thermore, bilateral (or crossed) sensorimotor symp-toms in the face and extremities are generally ahallmark of vertebrobasilar ischemic events.

With respect to differential diagnosis, TIAmimics, such as migraine, focal seizures, peripheralvestibulopathy and a miscellany of other condi-tions, are a common occurrence. Although relative-ly uncommon, an underlying brain tumour mustalso be considered a possibility - one of theprincipal reasons why CT scanning should be donein virtually all patients with TIAs. Tumours usuallypresent with slowly progressive symptoms butoccasionally may be intermittent in their manifes-tations and thus masquerade as TIAs. Unfortunate-ly, many of these neoplasms turn out to bemalignant, but an occasional and highly gratifyingexception is a benign and resectable tumour, suchas a meningioma.

Apart from these clinical points, this article istimely and excellent and should enjoy the widereadership it deserves. Certainly I will recommendit to my colleagues and house staff as a succinctand up-to-date review of a difficult topic.

C. William McCormick, MD, FRCPCAssociate professor of medicine(neurology)

Dalhousie UniversityHalifax, NS

The perfect treatment for patients with TIAs re-mains elusive. Appropriate investigations may oc-casionally identify conditions such as coagulopa-thy, vasculopathy and cardiac embolism that canbe treated specifically. In most of the cases theunderlying vascular disease is atherosclerosis, andtreatment alternatives include platelet inhibitors,anticoagulants and surgery. The only therapy thathas proven beneficial is ASA treatment.

Carotid endarterectomy has become widelyused in recent years for selected patients withcervical carotid disease. Although appealing, thisform of treatment has never been evaluated in aproperly designed clinical trial, which is imperativebecause of the recent concerns about its efficacyand safety. The current North American study ofcarotid endarterectomy in symptomatic patientsthus offers an important opportunity and shouldbe strongly supported by all interested physicians.

Joseph G. D'Alton, MD, FRCPCDivision of NeurologyOttawa Civic HospitalOttawa, Ont.

CMAJ, VOL. 138, JUNE 15, 1988 1105