Usually, diyculty in the diagnosis and management of stroke occurs because of the rarity of

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1 IDENTIFICATION AND MANAGEMENT CEREBROVASCULAR DISEASES OF DIFFICULT STROKE AND TIA SYNDROMES Correspondene to: Professor Martin M Brown, Department of Clinial Neurology, Institute of Neurology, Queen Square, London WC1N 3BG, UK m.brown@ion.ul.a.uk DIFFERENTIAL Martin M Brown Usually, diyulty in the diagnosis and management of stroke ours beause of the rarity of the presentation, ignorane about the ondition, or the lak of sientifi linial trial data to support linial deisions. This artile fouses on a very individual seletion of topis, with muh of the advie onerning management representing a personal view. It is not intended to be omprehensive, and is limited mainly to transient ishaemi attak (TIA) and ishaemi stroke. The importane of retaking a detailed history from the patient and their arers or friends in diffiult ases annot be overemphasised. Radiologial investigations should be reviewed, taking the history into aount, and remembering that minor vasular abnormalities are ommon in the elderly and that optimum sequenes may not have been used, partiular with magneti resonane imaging (MRI). More extensive investigation may be required. DIAGNOSIS OF TRANSIENT SYMPTOMS J Neurol Neurosurg Psyhiatry 2001;70(suppl I):i17 i22 The diyulty of diagnosing TIA is illustrated by the wide variety of diagnoses made in patients referred to vasular linis (table 1). 1 The sudden onset of neurologial symptoms is a useful riterion for the diagnosis of TIA. Most reover within minutes. As a general priniple, the syndromes of TIA will mimi those of stroke, sine the symptoms are a funtion of the vasular territory of the oluded artery or arteriole. Thus isolated dizziness or vertigo, or loss of onsiousness, are unlikely to be TIAs, whereas pure unilateral motor weakness provided it involves at least two of fae, arm or leg an be learly reognised as a launar TIA. The symptoms of most TIAs are loss of funtion, suh as aphasia, weakness or numbness, as opposed to positive symptoms suh as tingling or involuntary movements, whih are more likely to have a non-ishaemi ause. Haemodynami TIAs are an important exeption. These are usually assoiated with very severe internal arotid artery stenosis (> 95%) or olusion. 2 A TIA that ours with ativities assoiated with relative hypotension (for example, orthostasis, a hot bath) is likely to be haemodynami. The symptoms of haemodynami transient monoular blindness (TMB) are harateristially desribed by the patient as a white out or as hekerboard distortion of vision similar to looking through frosted glass, in ontrast to emboli TMB where the loss of vision is desribed as blakness or a urtain oming down over the site of one eye. Haemodynami TMB may be preipitated by going from a dark room into bright sunlight or even by looking at a bright light. In these ases, fundal examination may show poor perfusion pressure on the retinal arterioles whih an be seen to pulsate and ollapse in diastole in response to a slight pressure on the eyeball. In severe ases, fundosopy may also show the features of a low pressure ishaemi retinopathy, with dilated veins, peripheral miroaneurysms, and blot haemorrhages. The symptoms of haemodynami hemisphere TIAs oasionally onsist of jerking of the arm and an easily be onfused with foal seizures from other auses. Haemodynami TIAs are an indiation for angiography to visualise the whole of the arotid artery; often the patient has extensive atheromatous disease with tandem stenoses of the arotid bifuration and distal internal arotid artery (fig 1). Migraine The foal symptoms of migraine with aura preede the headahe in most ases and usually last from minutes; foal symptoms lasting more than an hour are unusual in migraine. The foal symptoms of migraine are fairly harateristi, namely visual fortifiation spetra, hemianopia or less ommonly perioral tingling with tingling in one arm. Isolated dysphasia is the only other transient symptom that I am happy to aept as migraine aura, if followed by otherwise typial headahe and aompanying symptoms; however, it is helpful to hear a history of a marh from typial visual symptoms or tingling in one limb to isolated dysphasia (usually fairly mild), over 15 minutes or so. The diyulty arises when a patient presents with symptoms suggestive of migraine aura without headahe. A prior history of more typial migraine headahe is helpful, but one should be aware of attributing foal symptoms to migraine rather than TIA *i17 J Neurol Neurosurg Psyhiatry: first published as /jnnp.70.suppl_1.i17 on 1 April Downloaded from on 6 June 2018 by guest. Proteted by opyright.

2 i18 * Neurology in Pratie Table 1 Final diagnosis in 211 new patients referred to a erebrovasular disease lini. 1 Diagnosis Cerebrovasular disease 71 Cerebral infart 32 TIA 30 Asymptomati arotid disease 6 Vasular dementia 2 Primary intraerebral haemorrhage 1 Non-erebrovasular disease 29 Cardia synope 5 Migraine 5 Vestibular dysfuntion 4 Epilepsy 2 Transient global amnesia 2 Cerebral tumour 1 Tension headahe 1 No diagnosis made 4 Other* 5 Perentage of patients *One eah (0.5%) of the following: multiple slerosis, motor neurone disease, erebellar degeneration, ishaemi retinopathy, radiulopathy, horea, Alzheimer s disease, hypoglyaemia, anxiety. Figure 1 Digital subtration angiogram showing a tight distal arotid stenosis in a diabeti man who presented with attaks of ipsilateral transient monoular white out of vision preipitated by bright light. simply beause the patient is a migraineur. I san patients with foal symptoms without headahe to exlude foal lesions, partiularly arteriovenous malformations, exept when there is a history of typial fortifiation spetra when I usually aept the diagnosis without further investigation. The diagnosis of migraineous infartion is disussed later. Migraine equivalent of middle age or late onset migraine aompaniment These synonymous terms desribe the fairly ommon ourrene in middle aged patients of foal symptoms very similar, or idential, to those of the aura of migraine, without headahe or a history of previous migraine. 3 The patients may have oinidental vasular risk fators, but the ourrene of migraine equivalent does not appear to predit an inreased risk of stroke, and patients an be reassured about the benign nature of the symptoms. Transient global amnesia Transient global amnesia is often onfused with TIA. However, the disorder is distint and does not arry the import of an inreased risk of stroke. 4 The attaks are often longer than TIAs, typially lasting 4 8 hours. Witnesses desribe the patient as being onfused, repeatedly asking the same questions, and being unable to reollet reent events. However, the patient often reognises family and the environment, if it has been familiar to him or her for some time. The patients are not dysphasi, whih is a helpful distinguishing feature from a dominant hemisphere TIA, and they do not have any other foal features other than the amnesia. Bilateral thalami ishaemia may ause an amnesi syndrome similar to transient global amnesia, but there will usually be other midbrain features. Progressive symptoms Classially, the symptoms of stroke are onsidered to be of sudden onset. However, a proportion of patients progress over the first day or two after onset. This is more ommon in patients with large vessel olusion but is also seen in launar infartion. Cerebellar infartion and haemorrhage have a propensity to progress beause of oedema and brain stem ompression. In erebellar, lateral medullary or brain stem infartion, progression may reflet propagation of thrombus in the vertebral artery to involve the basilar artery and its perforators. The patient may initially omplain of vertigo or intermittent diploplia, whih may be misinterpreted as a vestibular disturbane. These symptoms may improve or stabilise for several days or even a week, before the patient deteriorates with the development of progressive brain stem symptoms and signs, inluding oma. The history an be misinterpreted as indiating enephalitis, espeially if the patient has headahe or fever. Computed tomography (CT) may be normal in patients with posterior fossa ishaemia, and it is partiularly important to onsider the diagnosis and perform MRI before doing a lumbar punture. Lumbar punture in patients with signifiant erebellar or brain stem oedema seondary to infartion an be hazardous and ause rapid deterioration. Malignant middle erebral artery oedema An important ause of progressive symptoms in supratentorial infartion is malignant middle erebral artery oedema. Cytotoxi oedema auses swelling of the hemisphere with brain stem ompression in patients with infartion in most or all of the middle erebral artery territory. Clinially, the patient presents with the lassial symptoms of ishaemia in the middle erebral artery territory, but initially remains alert. There is then a delay of hours before the onset of a rapid deline in onsious level leading to unresponsiveness and often death, sometimes within a few hours. The syndrome is usually seen in younger patients, beause erebral atrophy assoiated with aging protets against the rapid rise in intraranial pressure. Malignant erebral oedema should be antiipated in young patients who have early signs of omplete middle erebral artery infartion on CT present within the first few hours of onset. The syndrome has a very poor prognosis when treated medially, but reent ase series suggest that surgial deompressive ranietomy improves outome in seleted patients. 5 The likelihood of severe residual aphasia argues against onsidering ranietomy in patients with dominant hemisphere infartion, unless the dysphasia is mild. J Neurol Neurosurg Psyhiatry: first published as /jnnp.70.suppl_1.i17 on 1 April Downloaded from on 6 June 2018 by guest. Proteted by opyright.

3 Summary 1 The symptoms of haemodynami TIA inlude white out of vision and jerking of one arm Cerebellar infartion and haemorrhage have a partiular tendeny to progress Malignant middle erebral artery oedema is an indiation for onsidering ranietomy Heparin is not benefiial in aute stroke, even in patients with progressive symptoms Additional investigations are warranted in younger patients with stroke, but no ause may be found in as many as 40% Migraine-like headahe aused by stroke or arotid dissetion is more ommon than stroke aused by migraine Although it is tempting to heparinise patients with progressive stroke, two relatively small randomised trials showed no evidene that intravenous heparin in this situation is benefiial 67 ; the large randomised trials of subutaneous heparin in stroke of any type also showed no overall benefit to antioagulation. 8 The young adult with ishaemi stroke In linial pratie most young adults with stroke do not have a rare underlying disorder responsible for their symptoms, and the ause will often be suggested by the previous history or examination for example, hypertension or heart disease. However, it is reasonable to investigate all patients under a ertain age (for example, 50 years old) more extensively (see box right). In as many as 27% of ases of young stroke, no ause is apparent, 9 although many have risk fators for stroke (for example, smoking) of unertain relevane. In patients with no obvious ause, reurrene is unusual and it seems likely that in many an unknown fator or ombination of fators, suh as a reent infetion, has temporarily resulted in hyperoagulability or endothelial injury, whih by hane has tipped the balane of oagulation and thrombolysis over the threshold of thrombosis. Carotid and vertebral artery dissetion Carotid and vertebral artery dissetion aount for a signifiant proportion of ases (5 10%) of young stroke, but is rare above the age of 50 years. A history of minor or major nek trauma, abnormal nek postures, or of joint hypermobility may be obtained. The diagnosis is suggested by pain in the nek before or at the time of stroke onset and finding of a Horner s syndrome with an anterior irulation syndrome. Carotid dissetion may oasionally preipitate migraine-like symptoms, inluding visual aura. Aorti arh dissetion should be onsidered in patients with Marfan s syndrome or pseudoxanthoma elastium. Mitohondrial ytopathy Mitohondrial enephalomyopathy with lati aidosis and stroke-like episodes (MELAS) is often onsidered in the diverential diagnosis of young stroke. It is rare, however, and I do not routinely investigate for this ondition unless the patient has other features to suggest mitohondrial disease for example, myopathy, enephalopathy, prolonged migraine-like headahe with vomiting, seizures, ophthalmoplegia, or the CT or MRI has the harateristi appearanes in the oipital lobes not onfined to the territory of the posterior erebral arteries. 10 Hemiplegi migraine One of the more ommon misdiagnoses in patients with stroke is the attribution of foal symptoms assoiated with throbbing headahe in a teenager or young patient to migraine. For some reason, almost all trainees know of hemiplegi migraine. However, the ondition is extremely rare. Hemiplegi migraine should be regarded as a separate syndrome to migraine with aura. The hemiplegia aompanies or follows the onset of severe headahe, may alternate from side to side within or between attaks, an be assoiated with fever, drowsiness, onfusion or oma, and may last for several days. 11 Imaging may show reversible areas of oedema, mimiking ishaemia, although some patients eventually develop permanent defiits. The diagnosis requires a history of reurrent episodes or a history of similar attaks in other family members (familial hemiplegi migraine). There is an assoiation with MELAS and erebral autosomal dominant arteriopathy with subortial infarts and leukoenephalopathy (CADASIL). In pratie, in almost all patients with hemiplegia assoiated with a migraine-like headahe, the apparent migraine-like headahe is seondary to the ishaemia, rather than the other way round. Headahe of varying severity is surprisingly ommon in aute ishaemi stroke and may be generalised, ipsilateral or ontralateral to the infart. Migraineous infartion should only be aepted as the diagnosis if the patient has a prior history of typial migraine with aura and is left with a persistent foal defiit after otherwise reovering from their usual migraine aura. There is some evidene that a history of migraine with aura is a risk fator for ishaemi stroke, but the mehanism and strength of the assoiation is unertain. 11 If the foal defiit is anatomially loated outside the territory of the patient s usual aura, I am relutant to aept the diagnosis of migraineous infartion and searh hard for alternative explanations. Migraine status may ause onfusion. In this ondition, the patient experienes a prolonged migraine aura, usually hemianopi, with or without other features of migraine. The foal defiit harateristially flutuates in severity, oming and going over the ourse of a week or two, before full reovery. Foal defiits may also flutuate in patients with spasm seondary to subarahnoid haemorrhage and ause diagnosti diyulty in patients in whom the headahe of subarahnoid haemorrhage is unusually mild or not eliited beause of onfusion or dysphasia. Moyamoya Moyamoya was originally thought to be onfined to the Asian population, but is oasionally seen in other raes. 12 It an also develop in hildren with sikle ell disease. The diagnosis is based on the finding of severe stenosis or olusion of the terminal arotid artery and origins of the branhes of the irle of Willis. The term refers to the Additional investigations performed in young or reurrent stroke (routine investigations are listed by Bamford, page i3) Magneti resonane imaging (MRI) Autoantibody sreen Antiardiolipin antibodies Thrombophilia sreen Sikle sreen Serum homoysteine Serum latate Syphilis serology Drug sreen 24 hour eletroardiogram (ECG) reording Transthorai ehoardiography Transoesophageal ehoardiography Cerebral angiography Neurology in Pratie *i19 J Neurol Neurosurg Psyhiatry: first published as /jnnp.70.suppl_1.i17 on 1 April Downloaded from on 6 June 2018 by guest. Proteted by opyright.

4 i20 * Neurology in Pratie appearanes of fine ollaterals on angiography, whih appear during dynami angiography like a hazy puv of smoke (moyamoya in Japanese). The diagnosis an be suspeted from ross setional MRI, whih may show the dilated ollaterals as flow voids in the basal ganglia and onfirmed by vasular imaging (magneti resonane angiography (MRA) or angiography). Management is diyult beause of the desire to prevent both infartion and haemorrhage. I presribe antihypertensive treatment to maintain as low a blood pressure as an be tolerated by the patient, and avoid antioagulation and antiplatelet treatment. Extraranial to intraranial bypass surgery may have a role in patients with progressive ishaemia. Vasulitis Most patients presenting with stroke seondary to vasulitis have symptoms of systemi disease. Headahe is a harateristi feature. Isolated erebral vasulitis without other systemi features of vasulitis (primary angiitis of the entral nervous system) is very rare, but should be suspeted in the patient with reurrent stroke-like events and deteriorating intelletual funtion. 13 Radiology is usually unhelpful in the diagnosis of vasulitis, but CT or MRI may show progressive deep white matter ishaemia and angiography oasionally shows beading. Cerebral biopsy is neessary to make the diagnosis and exlude other auses. Intensive immunosuppression with ylophosphamide is often required to ontrol vasulitis. A trial of steroids before erebral biopsy may only partially ontrol the vasulitis, while suppressing diagnosti features on biopsy, so is to be avoided. Takayasu s arteritis Takayasu s arteritis is an idiopathi granulomatous aortitis whih leads to olusion of the origins of the great vessels, most ommonly the arotid arteries. 14 The disease is usually seen in young women born in Asia, who present with TIA or stroke, but an our in whites. There is often malaise and fever, and the erythroyte sedimentation rate is raised without evidene of autoantibodies. Redued amplitude or absene of one or both brahial pulses, with pronouned asymmetry of blood pressure readings between the upper and lower limbs, should suggest the diagnosis. Ultrasound may show thikening of the walls of the ommon arotid artery. Angiography is required to make the diagnosis. Prednisolone is usually suyient to ontrol the malaise and prevent progression of the disease. In some ases, bypass graft surgery may be neessary. Systemi lupus erythematosus Less than 5% of ases with erebral lupus present with stroke as their first manifestation of systemi lupus erythematosus (SLE); in most of these ases there are systemi features to suggest the diagnosis for example, alopeia, skin rash, nail fold or retinal infarts. 15 These should be looked for in all patients with stroke of unertain ause, espeially as SLE an also avet the elderly and the diagnosis an be overlooked. Serologial tests for DNA binding are usually positive, but the titres may not math the severity of the disease and stroke an our with normal values. A number of diverent mehanisms an be responsible for stroke in SLE, inluding oagulopathy assoiated with the lupus antioagulant, small vessel vasulitis, ardia embolism from Libman-Saks endoarditis, and hypertension from renal involvement. Antiphospholipid antibody syndrome In the full syndrome, antiphospholipid antibodies are assoiated with reurrent venous and arterial thrombosis, thromboytopenia, and reurrent misarriages in younger women. 16 There is a lose assoiation with SLE, but not all patients with the antiphospholipid antibody syndrome have serologial or linial features of SLE and these patients are said to have primary antiphospholipid antibody syndrome. The lupus antioagulant is itself an antiphospholipid antibody. Antiardiolipin antibody is the most ommon antiphospholipid antibody measured in the laboratory. The signifiane of antiardiolipin antibodies as a single indiator of stroke risk in the absene of features of the full syndrome is unertain. In patients with stroke and features of the full syndrome, espeially if there is evidene of SLE, the diagnosis an be aepted as likely to be relevant to the ause of the stroke, although whether antiardiolipin antibodies have a pathogeni role or are markers of an autoimmune hyperoagulable state remains unertain. In the majority of ases of stroke in whom antiardiolipin antibodies are deteted without evidene of any other autoimmune disorder, the impliations are unlear. Current evidene suggests that the finding of antiardiolipin antibodies does not neessarily onfer a greater risk of reurrene than in patients without the antibody, other risk fators being similar. My urrent pratie is therefore to treat patients with isolated antiardiolipin antibodies and stroke with antiplatelet treatment in the first instane. I only onsider antioagulation in patients with the full syndrome, ative SLE, evidene of a major disturbane of oagulation in the laboratory indiated by a positive lupus antioagulant test, or reurrent thromboti events. Sneddon s syndrome Sneddon desribed the assoiation of stroke with florid livedo retiularis in the absene of any other systemi disease. 17 The ondition is mainly seen in young women. Livedo retiularis is assoiated with a number of onnetive tissue disorders, inluding primary antiphospholipid antibody syndrome, but to make a diagnosis of Sneddon s syndrome the livedo retiularis should be florid and generalised and there should be no evidene of any other relevant disorder. Skin biopsy shows a non-vasuliti arteriopathy with thikening of the blood vessel walls. Some patients experiene reurrent stroke, progressing to vasular dementia. Treatment appears inevetive, but a trial of antioagulation would seem justified in patients with reurrent events, although erebral haemorrhage has been desribed. Susa s syndrome (retinoohleoerebral vasulopathy) This rare ondition is an idiopathi small vessel vasulopathy with a prediletion for the retina, ohlea, and brain stem. 18 Patients develop reurrent vasular episodes over a period of several years with foal visual loss, seondary to disrete small retinal infarts, sudden unilateral deafness, tinnitus, and brain stem stroke. Cortial involvement is less ommon, but an lead to dementia. The ombination of sudden visual loss, asymmetrial segmental visual field defets, and deafness should suggest the diagnosis. No treatment appears to be evetive. Thrombophilia The term thrombophilia is used to desribe an inreased tendeny to linial thrombosis assoiated with laboratory evidene of an abnormality in the oagulation pathway, partiularly defiieny of one of the natural antioagulant fators (antithrombin III, protein C, protein S, heparin ofator 2, and the fator V Leiden mutation). Inherited thrombophilia, partiularly the fator V Leiden mutation, aounts for at least 20% of ases of venous thromboembolism J Neurol Neurosurg Psyhiatry: first published as /jnnp.70.suppl_1.i17 on 1 April Downloaded from on 6 June 2018 by guest. Proteted by opyright.

5 in patients under the age of 45 years, and there is a lear assoiation with erebral venous thrombosis. 19 However, most reent ase ontrol studies found no assoiation between thrombophilia and arterial stroke in the young. It is important to reognise that inherited heterozygote defiieny in one of the antioagulant fators is found in a signifiant proportion of the normal population, often without any history of thrombosis, and may therefore be a oinidental finding in a patient with stroke. In addition, onentrations of protein C, protein S, and antithrombin III are depressed after stroke. Blood tests should therefore be repeated at least three months after the aute event before onluding that inherited defiieny is present. If the patient has been antioagulated, interpretation of the result may be diyult beause warfarin lowers the onentration of protein C and S. In general, it seems reasonable to ignore the assoiation if other strong risk fators for stroke are found, but in patients in whom no obvious other ause is established life long antioagulation should be onsidered. In some patients, partiularly those with the fator V Leiden mutation, it may be more appropriate to antioagulate only patients with reurrent thrombosis. Patent foramen ovale The relevane and optimum management of a patent foramen ovale in a patient with otherwise unexplained stroke is unertain. Patent foramen ovale ours in as many as 20 40% of adults and therefore is likely to be a oinidental finding in many patients with stroke. 20 For paradoxial embolism to our, three oinidental onditions are required. Firstly, there must be a blood lot in the deep veins of the legs or pelvis whih embolises to the right side of the heart. Seondly, there must be a ommuniation of suyient size to allow the blood lot through the atria. Thirdly, the pressure in the right atrium must be higher than in the left atrium. Normally the pressure is higher on the left side than on the right side, so even with patent foramen ovale the flow of blood is from left to right. However, the pressure may be inreased on the right side of the heart to ause reversed flow from right to left if the patient also has right ventriular hypertrophy. Reversed flow an also our transiently in patients with otherwise normal hearts by manoeuvres that raise intrathorai pressure, suh as straining at stool. Beause all these features have to oinide, paradoxial embolism is probably a rare ause of stroke and I only aept the diagnosis as likely if the stroke ours in assoiation with prior deep vein thrombosis, pulmonary embolism or pulmonary hypertension. Given the doubts about the mehanism of stroke in most ases, I usually treat the patient with aspirin and only onsider warfarin or perutaneous losure of the septal defet in patients with reurrent symptoms despite antiplatelet treatment. Combination of haemorrhage and infartion Haemorrhagi transformation A number of disorders are assoiated with the ombination of haemorrhage and infartion. The most ommon enountered in aute stroke is haemorrhagi transformation of an initially ishaemi infart. Frank haemorrhage in this situation is often the result of spontaneous reperfusion of the infart or therapeuti thrombolysis, and therefore is more likely to our within the first day after onset of ishaemi stroke. The CT and MR appearanes an be indistinguishable from a primary intraerebral haemorrhage, and it is only the existene of a previous san that allows the diagnosis of seondary haemorrhage to be established. At a Neurology in Pratie week after stroke onset, petehial haemorrhage into the infart is very ommon and is visible on MRI in as many as 80% of patients with large middle erebral artery territory infarts, partiularly in the putamen. My own pratie is to stop or delay starting antiplatelet treatment or antioagulation for 2 4 weeks in those with haemorrhagi transformation, unless the bleeding is only petehial, but thereafter I ignore the haemorrhage in making deisions about appropriate prevention of reurrene. Cerebral venous thrombosis ommonly auses both infartion and haemorrhage. This is disussed elsewhere in this supplement. Mirohaemorrhage The reent introdution of T2* MR sequenes as a routine investigation in our unit for stroke and TIA has led to the new dilemma of how we should manage patients with mirohaemorrhages, whih may be deteted on MR sequenes in the basal ganglia of patients presenting with apparent launar infartion. Usually the patient has lear evidene of ishaemi small vessel disease in addition to the mirohaemorrhages, and it is unlear whether the symptoms have resulted from the haemorrhages or from launar infartion. In patients with florid hanges, I have taken the view that antioagulation and aspirin are both ontraindiated. Intravasular lymphoma Intravasular lymphoma (malignant angioendotheliosis) is an important diverential diagnosis of the ombination of haemorrhage and infartion in separate loations. This is a rare malignany in whih neoplasti lymphoid ells proliferate within apillaries, small veins, and arteries with little or no adjaent parenhymal involvement. 21 The history is usually of reurrent stroke-like episodes, with either or both haemorrhage and infartion on imaging. Dementia, a spinal ord syndrome, and peripheral or ranial neuropathies have been desribed. It an produe an idential piture to primary angiitis of the entral nervous system and distintion may only be possible on brain biopsy or postmortem. This disorder should be suspeted if a patient has reurrent stroke-like episodes assoiated with white matter disease on the MRI. Often there is a haemorrhagi omponent to the stroke. Other auses of small vessel vasulitis may also oasionally ause both haemorrhage and infartion. Reurrent ishaemi stroke There is nothing more disappointing than the ourrene of reurrent stroke in patients who have taken every preaution to redue their vasular risk and who have been reeiving antiplatelet treatment. Unfortunately, aspirin on average only redues the relative risk of stroke by about 13% and the addition of dipyridamole only approximately doubles the benefit, while at best lopidogrel onfers an additional 8% benefit. 22 Hene, reurrene is not unexpeted, given that at least two thirds of patients do not appear to benefit from even ombination antiplatelet treatment. What further should be done in patients with reurrent stroke or TIA, who have had optimum antiplatelet treatment, other than reiterating advie about vasular risk fators? Firstly, one should review the investigations and onsider extending the range of investigations to inlude those normally performed only routinely in young stroke. Carotid or vertebral angiography should be onsidered to exlude high ervial or intraranial lesions, inluding atheromatous stenosis, and bifuration stenoses missed by ultrasound in patients with arotid territory ishaemia. In this ontext, it should be *i21 J Neurol Neurosurg Psyhiatry: first published as /jnnp.70.suppl_1.i17 on 1 April Downloaded from on 6 June 2018 by guest. Proteted by opyright.

6 i22 * Neurology in Pratie Summary 2 Cerebral biopsy is neessary to make the diagnosis of isolated erebral vasulitis The signifiane of isolated antiardiolipin antibodies is unertain Thrombophilia is strongly assoiated with erebral venous thrombosis, but not arterial stroke Patent foramen ovale may be a oinidental finding in many patients with stroke Antioagulation for ishaemi stroke prevention may be harmful unless a lear ardia ause has been established In patients with hypertension, a target blood pressure of 140/85 mm Hg or less should be set remembered that one posterior erebral artery is supplied by the internal arotid artery via a dominant posterior ommuniating artery in about 5% of the population. Thus, oipital infartion may sometimes result from arotid stenosis. Until reently, I onsidered onventional atheter angiography to be justified in patients with reurrent symptoms, but it is beoming lear that good quality extraranial and intraranial MRA, espeially if ontrast is used, an obviate the need for atheter angiography in many ases. The advantages of adequate angiography is that logial deisions an be made about treatment; in some ases of reurrent symptoms resistant to medial treatment, stenting of arotid or vertebral stenosis may be appropriate, even if the lesion is not amenable to surgery. The only situation where antioagulation has been shown to be benefiial in preventing reurrent stroke is in patients with atrial fibrillation. 23 In ontrast, the only large randomised trial of warfarin treatment for stroke prevention after presumed atherothromboti stroke or TIA was stopped early beause of an exess of erebral haemorrhage in the warfarin group. 24 The latter was more ommon in patients over the age of 75 years, in patients with severe leukoaraiosis on CT, and in those with higher international normalised ratio (INR) values. Therefore, I do not reommend antioagulation in patients with reurrent symptoms despite optimum antiplatelet treatment, unless investigations have shown a lear ardia soure of embolism, or onfirmed severe (> 70%) atheromatous disease not amenable to surgery or stenting, and there are no ontraindiations to antioagulation. Instead, I onentrate on optimising medial treatment in addition to antiplatelet treatment. Control of hypertension an often be improved and a target blood pressure of 140/85 mm Hg or less should be set, informing both the patient and his or her general pratitioner about the desirable target. Similarly, I enourage as good as possible ontrol of hyperglyaemia in diabetis. There is good evidene that statins redue both myoardial infartion and stroke in patients with ishaemi heart disease, 25 and it is very likely that similar benefits will be shown in the ongoing trials of statin treatment in stroke. I therefore reommend statin treatment to most patients with reurrent symptoms unless their holesterol is below 5 mmol/l. Referenes 1 Blight A, Pereira AC, Brown MM. A single onsultation erebrovasular lini is ost effetive in the management of transient ishaemi attak and minor stroke. J R Coll Physiians Lond 2000;34: Russell RW, Page NG. Critial perfusion of brain and retina. Brain 1983;106: Fisher CM. Late-life migraine aompaniments further experiene. Stroke 1986;17: Hodges JR, Warlow CP. Syndromes of transient amnesia: towards a lassifiation. A study of 153 ases. J Neurol Neurosurg Psyhiatry 1990;53: Shwab S, Steiner T, Ashoff A, et al. Early hemiranietomy in patients with omplete middle erebral artery infartion. Stroke 1998;29: Duke RJ, Bloh RF, Turpie AG, et al. Intravenous heparin for the prevention of stroke progression in aute partial stable stroke. Ann Intern Med 1986;105: Haley Jr EC, Kassell NF, Torner JC. Failure of heparin to prevent progression in progressing ishaemi infartion. Stroke 1988;19: Pereira AC, Brown MM. Aspirin or heparin in aute stroke. Br Med Bull 2000;56: Antioagulation treatment for aute ishaemi stroke is reviewed in this volume of the British Medial Bulletin, whih ontains many other up to date reviews on stroke treatment and is highly reommended. 9 Carolei A, Marini C, Ferranti E, et al. A prospetive study of erebral ishaemia in the young. Analysis of pathogeni determinants. The National Researh Counil study group. Stroke 1993;24: Ciafaloni E, Rii E, Shanske S, et al. MELAS: linial features, biohemistry, and moleular genetis. Ann Neurol 1992;31: Welh KMA, Tatemihi TK, Mohr JP. Migraine and stroke. In: Barnett HJM, Mohr JP, Stein BM, et al, eds. Stroke: pathophysiology, diagnosis and management, 3rd ed. Philadelphia: Churhill Livingstone, 1998: A omprehensive review of the whole problem of migraine and stroke in one of the major textbooks of stroke. 12 Suzuki J, Kodama N. Moyamoya disease a review. Stroke 1983;14: Ferro JM. Vasulitis of the entral nervous system. J Neurol 1998;245: Hall S, Buhbinder R. Takayasu s arteritis. Rheum Dis Clin North Am 1990;16: Brown MM, Swash M. Systemi lupus erythematosus. In: Vinken PJ, Bruyn GW, Klawans HL, eds. Handbook of linial neurology, revised series, vasular diseases part III, vol 55. Amsterdam: Elsevier Siene Publishers, 1989: Montalban J, Codina A, Ordi J, et al. Antiphospholipid antibodies in erebral ishemia. Stroke 1991;22: Tourbah A, Piette JC, Iba-Zizen MT, et al. The natural ourse of erebral lesions in Sneddon syndrome. Arh Neurol 1997;54: Susa JO. Susa s syndrome: the triad of miroangiopathy of the brain and retina with hearing loss in young women. Neurology 1994;44: Martinelli I, Landi G, Merati G, et al. Fator V gene mutation is a risk fator for erebral venous thrombosis. Thromb Haemost 1996;75: Autore C, Cartoni D, Piininno M. Multiplane transesophageal ehoardiography and stroke Am J Cardiol 1998;81:79G 81G. 21 Glass J, Hohberg FH, Miller DC. Intravasular lymphomatosis. A systemi disease with neurologi manifestations. Caner 1993;71: MCabe DJH, Brown MM. Prevention of ishaemi stroke antiplatelets. Br Med Bull 2000;56: EAFT (European Atrial Fibrillation Trial) Study Group. Seondary prevention in non-rheumati atrial fibrillation after transient ishaemi attak or minor stroke. Lanet 1993;342: This study onviningly established the benefits of antioagulation after stroke and TIA in patients with atrial fibrillation. 24 The Stroke Prevention in Reversible Ishaemia Trial (SPIRIT) Study Group. A randomised trial of antioagulants versus aspirin after erebral ishaemia of presumed arterial origin. Ann Neurol 1997;42: Hess DC, Demhuk AM, Brass LM, et al. HMG-CoA redutase inhibitors (statins): a promising approah to stroke prevention. Neurology 2000:54: J Neurol Neurosurg Psyhiatry: first published as /jnnp.70.suppl_1.i17 on 1 April Downloaded from on 6 June 2018 by guest. Proteted by opyright.