Abstracts Cerebrovasc Dis 2013;36(suppl 2):1–52 DOI: 10.1159/000356197
Published online: November 15, 2013
KL
SP1-1
Blood Pressure Control for Stroke Prevention
Controversies in the Definition of Transient Ischaemic Attack (TIA)
Peter M. Rothwell
Graeme J. Hankey
Department of Clinical Neurology, University of Oxford, Oxford, UK
School of Medicine & Pharmacology, The University of Western Australia, Department of Neurology, Sir Charles Gairdner Hospital, Perth, Western Australia
Hypertension is the most important treatable risk factor stroke, although exactly how raised blood pressure (BP) causes stroke is poorly understood. Yet, one hypothesis has come to dominate research and practice in hypertension – that each of us has an underlying ‘usual’ BP, which is the main determinant of BP-related vascular risk and of benefit from BP lowering drugs. All major guidelines recommend that diagnosis and treatment be based on estimates of this ‘true’ BP. However, recent reports have shown that patients with episodic hypertension also have an increased risk of stroke, that maximum BP may be a better predictor of stroke than mean BP, at least in treated hypertensives, and that residual variability in BP on treatment therefore has a poor prognosis despite good control of mean BP. It has also been shown that benefits of some BP-lowering drugs are due partly to reduced variability in BP and more consistent overall control of BP. Compared to other drugs, variability and peaks in SBP are reduced by calcium channel blockers (CCBs) and non-loop diuretics and increased by ACE-inhibitors angiotensinreceptor blockers and beta-blockers. These findings may explain why beta-blockers are less effective, and CCBs and diuretics are more effective, in preventing stroke than can be accounted for by effects on mean BP. Increased mean BP is undoubtedly still a very important risk factor for stroke and other vascular events, particularly in the primary prevention setting, but there is increasing evidence that variability and instability in BP and peak levels are also important in progression of end-organ damage and particularly in triggering stroke. Consistency of control of BP is therefore vital, particularly in secondary prevention of stroke, including control of nocturnal BP and avoidance of too great a trough in BP in the afternoon. Nevertheless, recent trial evidence suggests that more intensive control of blood pressure is more effective than less intensive control in secondary prevention of stroke.
© 2013 S. Karger AG, Basel 1015–9770/13/0368–0001$38.00/0 Fax 141 61 306 12 34 E-Mail [email protected] www.karger.com
Accessible online at: www.karger.com/ced
The importance of defining a TIA is to identify a clinical entity which, although no longer manifest clinically, heralds an increased risk of disabling or fatal stroke unless the underlying cardiovascular cause and/or its consequences are promptly treated. Hence, the definition of a TIA should distinguish it from other differential diagnoses and contain important prognostic information about the future risk of stroke. Traditionally, the definition of TIA was based on a clinical history of rapid onset symptoms of focal neurological dysfunction thought to be of vascular origin which resolve within 24 hours. The first three features – rapid onset and symptoms of focal brain ischaemia due to a vascular cause – remain relevant. However, the validity of the latter – duration of symptoms up to 24 hours – as a distinguishing clinical feature, coupled with the advent of advances in brain and vascular imaging, has led to a revised, tissue-based, definition of TIA which requires magnetic resonance diffusion-weighted imaging (MR-DWI) to exclude recent brain infarction. The revised definition of TIA is a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. Advocates for the new definition argue that: • The presence of acute brain infarction, as defined by a positive MR-DWI, is associated with an increased risk of stroke. • A tissue-based definition of TIA will harmonize cerebrovascular nosology with other ischemic conditions (e.g. myocardial infarction) and appropriately direct diagnostic attention to whether brain injury occurred and to identify the cause of ischemia. • A 24-hour limit for the duration of symptoms is arbitrary, not reflective of the typical duration (usually 24 hours (clinically definite stroke) in whom the MR DWI is negative.
SP1-2
ACS-ACVS: Similarities and Differences J. Donald Easton University of California, San Francisco, Calif., USA
Acute Coronary Syndrome (ACS) is comprised of unstable angina, non-ST-segment elevation MI (NSTEMI) and ST-segment elevation MI (STEMI). In the first instance there is ischemia without infarction, in NSTEMI there is partial arterial occlusion with infarction, and in STEMI there is total arterial occlusion with infarction. The typical intravascular pathophysiology is recurring thrombosis and thrombolysis evolving over minutes to hours. If the anticoagulant factors in the blood and the arterial wall at the thrombosis site prevail, the process resolves (unstable angina) whereas if procoagulant factors prevail MI occurs. There are chest pain mimics of ACS in which there is no myocardial ischemia. Acute Cerebral Vascular Syndrome (ACVS) is comprised of TIA and brain infarction. As in ACS, it typically is due to atherothrombosis, often with embolism distally, or cardioembolism. This is likely true of most cryptogenic ACVS events too. The occlusive processes in lacunar ischemia are less certain but many lacunes are also caused by thrombosis due to microatheromas. As in ACS, there are mimics of ACVS in which there is no brain ischemia. Patients with ACS are treated promptly with aspirin and a heparin-type anticoagulant. They then commonly proceed to coronary angiography and the culprit lesion is stented. A second antiplatelet drug (typically clopidogrel, prasugrel or ticagrelor) is loaded before or during the procedure. Dual antiplatelet along with anticoagulant treatment and PCI are strongly evidence-based. Patients with ACVS, after hemorrhage is excluded, are treated promptly with aspirin. They are not routinely treated with a second antiplatelet drug or a heparin-type anticoagulant because neither is strongly evidence-based. Nevertheless, based on the discussion above is very likely both would be effective in TIA or minor ischemic stroke where the early risk of recurrent thrombosis in high and the risk of ICH is low due to the small or no infarc-
2
Cerebrovasc Dis 2013;36(suppl 2):1–52 DOI: 10.1159/000356197
tion. TPA is effective for larger ischemic episodes and intravascular intervention also may prove effective but the time factor is challenging. Additional similarities and differences will be discussed.
SP1-3
Intracranial Atheroclerosis and ACVS KS Lawrence Wong Chinese University of Hong Kong, Hong Kong
Intracranial atherosclerosis is the most common vascular lesion found in Asians with ischemic stroke or transient ischemic attack (TIA). In Chinese, Malaysian and South Asians, the frequency of intracranial atherosclerosis was found to be around 33– 50%. Among patients with TIA or minor stroke, the frequency was even higher up to 70%. The mechanisms for TIA/ minor stroke in patients with intracranial atherosclerosis are many. Artery-to-artery embolism, branch atheromatous disease and hemodynamic compromise are all important mechanisms. Sometimes the topography of infarcts on DWI MRI in patients with intracranial atherosclerosis is the same as in patients with small vessel disease. This is the case when isolated infarct is found in the basal ganglion region. However, multiple small infarcts, especially locations in the subcortical and cortical regions along the borderzone areas, point to underlying intracranial atherosclerosis. Vascular work-up for intracranial occlusive disease is strongly indicated with patients with ischemic stroke or TIA when there are multiple small infarcts found on DWI MRI along the borderzone regions.
SP1-4
Activity of Von Willebrand Factor During the Acute Phase of Ischemic Stroke Might Predict Worse Outcome Masahiro Uemura, Yasuhisa Akaiwa, Itaru Ninomiya, Hiroaki Arakawa, Masafumi Toriyabe, Takayoshi Shimohata, Masatoyo Nishizawa Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
State the Purpose: This study aimed to determine the relationship between von Willebrand factor (vWF) activity and clinical profiles during the acute phase of ischemic stroke. Methods: We retrospectively reviewed 137 patients (94 males; mean age, 71.5 years) who were admitted to our department with acute ischemic stroke between November 2010 and December 2012. Patients with severe disability (modified Rankin Scale [mRS] >2) before stroke onset were excluded. vWF activity was measured within one week of symptom onset in all patients. Cause of stroke was determined based on the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Associations between vWF activity and clinical features, including etiology, morbidity,
Abstracts
and mortality, were then investigated. A worse outcome was defined as mRS >2 at the time of discharge. Results: Mean vWF activity associated with cardio-embolic stroke, large artery atherosclerosis, small vessel disease, undetermined and other causes was 162.5 ± 87.3%, 173.5 ± 44.0%, 120.8 ± 50.0%, 171.3 ± 83.7% and 188.0%, respectively. No significant differences were found among causes (p = 0.24); however, vWF activity was significantly higher in patients with worse outcomes than in those with better outcomes (185.5 ± 91.3% vs. 147.3 ± 63.8%, p = 0.018). Conclusion: High vWF activity within one week of acute ischemic stroke onset might predict a worse outcome at the time of discharge. Disclosure of Interest: None Declared.
cerebral microbleeds can be found and imply prognostic significance. Cerebral small vessel disease may be associated with increased risk of death and ischemic stroke and leukoaraiosis is reported to predict poor functional recovery and worse quality of life in patients with stroke or TIA. Also cerebral microbleeds are considered to increase the risk of future intracerebral hemorrhage. Therefore more attention should be paid to small vessel disease and microbleeds for planning preventive and treatment strategies in patients with TIA and AIS.
SP2-3
Short- and Long-Term Risk of Stroke after TIA SP2-1
Risk Stratification in TIA Patients Pierre Amarenco
Tomoyuki Ohara, Toshiyuki Uehara, Kazunori Toyoda, Kazuo Minematsu Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
SOS-TIA Clinic, Bichat Stroke Center, Paris, France
In this lecture I will address risk stratification of patients with a transient ischemic attack using simple clinical scoring system as well as etiological findings based on immediate simple diagnostic tests such as magnetic resonance imaging, arterial imaging and cardiac evaluation. The relative yield of these systems used in practice (i.e., after first call to medical attention, admission to the TIA clinic) or in clinical research (i.e., to characterize an epidemiological cohort, or select patients at higher risk in clincial trial) will be reviewed.
SP2-2
Small Vessel Disease and Microbleeds in TIA and AIS Byung-Woo Yoon Seoul National University Hospital, Seoul, Republic of Korea
Small vessel ischemic disease and microbleeds are pathologic processes affecting small caliber vessels of the brain. These changes are frequently related to age, hypertension and cerebral amyloid angiopathy. They can have no symptoms or present as a stroke, TIA or cognitive impairments. Small vessel disease can easily be found by magnetic resonance imaging (MRI), and susceptibilityweighted image (SWI) and T2* weighted gradient-recalled echo (GRE) MRI are sensitive methods for detecting cerebral microbleeds. Small vessel disease and microbleeds are reported to be common in the general population. MRI-defined silent brain infarcts were detected in 20% of healthy elderly people and up to 50% of patients in selected series. Overall prevalence of cerebral microbleeds was high and increased with age to more than one third in those over 80 years. In patients with TIA or AIS as well as those with intracerebral hemorrhage, small vessel disease and
International TIA/ACVS Conference 2013
Numerous studies have shown that the short-term risk of stroke after transient ischemic attack (TIA) is particularly high, with approximately 5–10% within 7 days and 10–20% within 90 days. However, the reported short-term risks of stroke after TIA were highly heterogeneous, because they depended on various factors as study methods, study population, and treatments. Especially, urgent treatment after TIA has been proved to reduce the shorttime stroke risk. The short-term stroke risk after TIA also differed by its etiology. In most European studies, large artery atherosclerosis was reportedly a stroke subtype with higher subsequent stroke risk. On the other hand, in Japan, limited data suggested that small vessel disease including capsular warning syndrome is the common etiology with early subsequent stroke. In contrast to short-term risk, there are limited reports for longterm risk after TIA. Previous reports demonstrated that TIA patients had the increased long-term risk of both cerebrovascular and cardiovascular events without a decline over time. These findings highlight the importance of continuous secondary prevention in the long term after TIA. In Japan, we are going on a multicenter prospective study to clarify the short-term (90 days) and long-term (1-year) risk of ischemic stroke and other cardiovascular events in patients with TIA. The strength of our TIA registry was the high examination rate of DWI and intracranial and extracranial vascular imaging (more than 90%). We enrolled more than 1,200 TIA patients by September 2013. From the interim analysis in 502 patients who completed 1-year follow up, the 7-day, 90-day, and 1-year stroke risk were 5.2%, 7.4%, and 9.0%, respectively. The leading subtypes of the ischemic strokes were intracranial large artery atherosclerosis and small-vessel disease.
Cerebrovasc Dis 2013;36(suppl 2):1–52 DOI: 10.1159/000356197
3
SP2-4
SP3-1
Stroke Incidence after Onset of Transient Ischemic Attack: A Meta-Analysis
TIA Triage of Stroke Risk Using Neuroimaging
Yoshihiro Kokubo
Gregory W. Albers
Preventive Cardiology, National Cerebral and Cardiovascular Center, Suita, Japan
Stanford University, Stanford, Calif., USA
State the Purpose: Transient ischemic attack (TIA) is a
recognized risk factor for stroke. However, there are few studies on the incidence of TIA and the incidence rates of stroke after onset of TIA. The aim of this study was to conduct a meta-analysis of the incidence of TIA and the incidence of stroke after onset of TIA. Methods: A systematic review and meta-analysis of prospective cohorts with TIA were performed by using PubMed. Prospective cohort studies published between 1987 and March 2013 were included. The search was limited to English language and reports showing the number of subjects according to sex and age. The incidence of stroke after TIA was calculated by population- and hospital-based studies. Results: Among 115 articles of PubMed search, 8 articles met the inclusion criteria for the incidence of TIA and 7 and 9 articles met the incidence of stroke after TIA (population- and hospital-based), respectively. In total, data from 2,963,593 and 8,763 subjects for the incidence of TIA and the incidence of stroke after TIA, respectively, were used. During the follow-ups, the incidence rates of TIA were 1.22, 1.02, and 1.15 per 1,000 person-years in men, women, and both sexes, respectively. The incidence rates of TIA according to the year categories (84 years old) in both sexes were 0.03, 0.08, 0.19, 0.18, 1.04, 2.70, 6.36, and 11.9 per 1,000 person-years, respectively. One article in an Asian population, the Hisayama study has shown that the incidence rates of TIA were 0.78 and 0.38 per 1,000 person-years in men and women, respectively. In population-based studies, the incidence rates of stroke were 1.7%, 4.8%, 6.6%, 8.5%, and 11.4% at 2 days, 1 week, 1, 3, and 6 months after onset of TIA, respectively. In hospital-based studies, the incidence rates of stroke were 13.7% and 12.4% at 1 and 3 months after onset of TIA, respectively. Conclusion: In this meta-analysis, the incidence rates of TIA were 1.2 and 1.0 per 1,000 person-years in men and women, respectively. After one month onset of TIA, one in 15 and 7 people have strokes in population- and hospital-based cohort studies. Disclosure of Interest: None Declared.
4
Cerebrovasc Dis 2013;36(suppl 2):1–52 DOI: 10.1159/000356197
Multimodal MRI is more specific and sensitive than head CT for the detection of acute brain ischemia. DWI reveals an acute infarction in about 30% of patients with a discharge diagnosis of TIA. Symptom characteristics (motor deficit or speech disorder) and the presence of a symptomatic vessel lesion are associated with the presence of an acute ischemic lesion on DWI. Several studies have shown that DWI positivity has prognostic implications. A recent meta-analysis showed that 7% of TIA patients with a positive DWI will suffer a stroke within a week compared to only 0.5% of the DWI negative patients. Interestingly, in DWInegative patients the ABCD2 score did not influence the risk of stroke, suggesting that a proportion of these patients may not have experienced a transient ischemic event. Two types of automatically processed perfusion sequences are available: Dynamic susceptibility contrast (DSC) perfusion imaging (applicable to both MRI and CT perfusion) and Arterial Spin Labeling (ASL) MR imaging. While preliminary data suggest that TIA patients with perfusion lesions may also be at increase stoke risk, further data are required prior to incorporation of perfusion imaging into clinical decision making. In addition to brain imaging, imaging of the craniocervical vessels can help clarify stroke risk in TIA patients. The importance of vessel imaging in the evaluation and management of TIA was recently confirmed in the CATCH study. Positive CTA (occlusion or stenosis ≥50% in the intracranial or extracranial vessels on the clinically relevant side) was an independent predictor of recurrent stroke. Vessel occlusion on MRA is also associated with a 4-fold increased risk of stroke. TIA/minor stroke patients who are identified as being at very high risk of early recurrent stroke should be strongly considered for acute hospitalization for expedited diagnostic evaluation, therapy and observation. If a stroke occurs, thrombolytic therapy can be administrated rapidly if appropriate. Patients assessed to be at low stroke risk can typically be treated with stroke preventative therapies and managed as outpatients. Neuroimaging based TIA triage was safe and cost-effective in the prospective TWO ACES study. Larger studies of imaging based TIA triage in diverse patient populations are warranted.
Abstracts
SP3-2
Timing of DWI Positivity after TIA Junichiro Satomi1, Naomi Morita2, Masafumi Harada3, Shinji Nagahiro1 1
The Department of Neurosurgery, Tokushima University Hospital, Tokushima, 2Department of Radiology, National Cerebral and Cardiovascular Center, Suita, 3 The Department of Radiology, Tokushima University Hospital, Tokushima, Japan
According to a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council, TIAs are brief episodes of neurological dysfunction resulting from focal cerebral ischemia not associated with permanent cerebral infarction. In the past, TIAs were defined as any focal cerebral ischemic event with symptoms lasting 50% (p < 0.029) are best suitable to predict a high early stroke risk immediately after index TIA. This presentation will show, how clinical and neuroimaging studies (either by MR or/and in particular noninvasive and easily applicable ultrasound technologies in nearly all patients) can contribute to the identification of these patients within 2 complete remitting and relapsing TIAs within 24 h after onset) and positive MR-DWI findings. The more recently propopsed ABCD3-I score takes into consideration positive DWI findings, dual TIA episodes within 7 days of the index event and relevant
International TIA/ACVS Conference 2013
State the Purpose: The role of anticoagulant therapy for acute cardiogenic cerebral infarction is controversial. Intravenous heparin dosage is often suspected to increase symptomatic hemorrhagic transformation, while the therapy is considered as an essential treatment to avoid secondary cardio-embolic events in acute stage. We investigated the association of hemorrhagic transformation with the clinical features and predisposing factors in acute cardiogenic cerebral infarction. Methods: Subjects were consisted of 398 patients (216 males; age, 76.3 ± 10.5 years), who admitted in our hospitals for acute cardiogenic cerebral infarction in anterior circulation started with intravenous heparin dosage (5,000 or 10,000 unit/day) within 48 hours after onset between January 2010 and December 2012. We retrospectively evaluated the associations between their clinical features, predisposing factors, and hemorrhagic transformation defined on Computed Tomography (CT) or Magnetic Resonance Image (MRI) during heparin dosage.
Cerebrovasc Dis 2013;36(suppl 2):1–52 DOI: 10.1159/000356197
5
Results: Hemorrhagic transformation (n = 83, 20.9%) was associated with the score of ASPECTS-DWI (odds ratio 1.25, 95% CI: 1.12 to 1.40), NIHSS at admission (odds ratio 0.95, 95% CI: 0.92 to 0.99), and the presence of recanalization of occlusion vessels (odds ratio 6.64, 95% CI: 3.50 to 12.9). The score of ASPECTS-DWI and the presence of recanalization were more strongly associated factors than NIHSS at admission. With respect to ASPECTS-DWI, score = 7 was the cut-off value of hemorrhagic transformation, and the hemorrhagic transformation tended to be increasing in score 70% in Japan. In specialty hospitals, diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) should be considered indispensable. If hyperintense signals are identified in the ischemic area, emergency hospitalization is needed. Patients with continuous mild hemiparesis and unusual focal neurological symptoms without any lesions on first imaging are also regarded as showing evolving stroke. Recurrent ischemic stroke often occurs as a combination of atrial fibrillation and occlusive arterial disease, and this condition may carry a high risk of early recurrence of ischemic stroke in TIA patients. To prevent stroke subsequent to TIA/ACVS, ACVS triage and optimal management thereafter is the most effective.
Abstracts
SP5-4
SP5-5
Endovascular Therapy for TIA or Minor Ischemic Stroke
Surgical Treatment of TIA in Acute Settings
Hiroshi Yamagami1, Shinichi Yoshimura2, Kenichi Todo3, Nobuyuki Sakai3
Department of Neurosurgery, Nagasaki University, Nagasaki, Japan
Izumi Nagata
1
Department of Neurology, National Cerebral and Cardiovascular Center, Suita, 2Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, 3Stroke Center, Kobe City Medical Center General Hospital, Kobe, Japan
The usefulness of endovascular therapy (EVT) for acute ischemic stroke (AIS) has not been established. Potential limitations of EVT include damage to the arterial wall from devices, fragmentation and distal embolization of the thrombus, and complications of systemic and cerebral hemorrhage. Patients with TIA or minor ischemic stroke are usually excluded from the indication of EVT. However, major artery occlusive disease is associated with early neurological deterioration or recurrent stroke in TIA or minor ischemic stroke. In such case, EVT is performed after the severe deterioration of neurological symptoms, which is refractory to optimal medical therapy. In the Recovery by Endovascular Salvage for Cerebral Ultraacute Embolism (RESCUE)-Japan registry, 1,442 AIS patients with major artery occlusion within 24 hours after the onset were recruited in 84 Japanese stroke centers. Of those, 303 patients with TIA or minor stroke [National Institutes of Health Stroke Scale (NIHSS)
Published online: November 15, 2013
KL
SP1-1
Blood Pressure Control for Stroke Prevention
Controversies in the Definition of Transient Ischaemic Attack (TIA)
Peter M. Rothwell
Graeme J. Hankey
Department of Clinical Neurology, University of Oxford, Oxford, UK
School of Medicine & Pharmacology, The University of Western Australia, Department of Neurology, Sir Charles Gairdner Hospital, Perth, Western Australia
Hypertension is the most important treatable risk factor stroke, although exactly how raised blood pressure (BP) causes stroke is poorly understood. Yet, one hypothesis has come to dominate research and practice in hypertension – that each of us has an underlying ‘usual’ BP, which is the main determinant of BP-related vascular risk and of benefit from BP lowering drugs. All major guidelines recommend that diagnosis and treatment be based on estimates of this ‘true’ BP. However, recent reports have shown that patients with episodic hypertension also have an increased risk of stroke, that maximum BP may be a better predictor of stroke than mean BP, at least in treated hypertensives, and that residual variability in BP on treatment therefore has a poor prognosis despite good control of mean BP. It has also been shown that benefits of some BP-lowering drugs are due partly to reduced variability in BP and more consistent overall control of BP. Compared to other drugs, variability and peaks in SBP are reduced by calcium channel blockers (CCBs) and non-loop diuretics and increased by ACE-inhibitors angiotensinreceptor blockers and beta-blockers. These findings may explain why beta-blockers are less effective, and CCBs and diuretics are more effective, in preventing stroke than can be accounted for by effects on mean BP. Increased mean BP is undoubtedly still a very important risk factor for stroke and other vascular events, particularly in the primary prevention setting, but there is increasing evidence that variability and instability in BP and peak levels are also important in progression of end-organ damage and particularly in triggering stroke. Consistency of control of BP is therefore vital, particularly in secondary prevention of stroke, including control of nocturnal BP and avoidance of too great a trough in BP in the afternoon. Nevertheless, recent trial evidence suggests that more intensive control of blood pressure is more effective than less intensive control in secondary prevention of stroke.
© 2013 S. Karger AG, Basel 1015–9770/13/0368–0001$38.00/0 Fax 141 61 306 12 34 E-Mail [email protected] www.karger.com
Accessible online at: www.karger.com/ced
The importance of defining a TIA is to identify a clinical entity which, although no longer manifest clinically, heralds an increased risk of disabling or fatal stroke unless the underlying cardiovascular cause and/or its consequences are promptly treated. Hence, the definition of a TIA should distinguish it from other differential diagnoses and contain important prognostic information about the future risk of stroke. Traditionally, the definition of TIA was based on a clinical history of rapid onset symptoms of focal neurological dysfunction thought to be of vascular origin which resolve within 24 hours. The first three features – rapid onset and symptoms of focal brain ischaemia due to a vascular cause – remain relevant. However, the validity of the latter – duration of symptoms up to 24 hours – as a distinguishing clinical feature, coupled with the advent of advances in brain and vascular imaging, has led to a revised, tissue-based, definition of TIA which requires magnetic resonance diffusion-weighted imaging (MR-DWI) to exclude recent brain infarction. The revised definition of TIA is a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. Advocates for the new definition argue that: • The presence of acute brain infarction, as defined by a positive MR-DWI, is associated with an increased risk of stroke. • A tissue-based definition of TIA will harmonize cerebrovascular nosology with other ischemic conditions (e.g. myocardial infarction) and appropriately direct diagnostic attention to whether brain injury occurred and to identify the cause of ischemia. • A 24-hour limit for the duration of symptoms is arbitrary, not reflective of the typical duration (usually 24 hours (clinically definite stroke) in whom the MR DWI is negative.
SP1-2
ACS-ACVS: Similarities and Differences J. Donald Easton University of California, San Francisco, Calif., USA
Acute Coronary Syndrome (ACS) is comprised of unstable angina, non-ST-segment elevation MI (NSTEMI) and ST-segment elevation MI (STEMI). In the first instance there is ischemia without infarction, in NSTEMI there is partial arterial occlusion with infarction, and in STEMI there is total arterial occlusion with infarction. The typical intravascular pathophysiology is recurring thrombosis and thrombolysis evolving over minutes to hours. If the anticoagulant factors in the blood and the arterial wall at the thrombosis site prevail, the process resolves (unstable angina) whereas if procoagulant factors prevail MI occurs. There are chest pain mimics of ACS in which there is no myocardial ischemia. Acute Cerebral Vascular Syndrome (ACVS) is comprised of TIA and brain infarction. As in ACS, it typically is due to atherothrombosis, often with embolism distally, or cardioembolism. This is likely true of most cryptogenic ACVS events too. The occlusive processes in lacunar ischemia are less certain but many lacunes are also caused by thrombosis due to microatheromas. As in ACS, there are mimics of ACVS in which there is no brain ischemia. Patients with ACS are treated promptly with aspirin and a heparin-type anticoagulant. They then commonly proceed to coronary angiography and the culprit lesion is stented. A second antiplatelet drug (typically clopidogrel, prasugrel or ticagrelor) is loaded before or during the procedure. Dual antiplatelet along with anticoagulant treatment and PCI are strongly evidence-based. Patients with ACVS, after hemorrhage is excluded, are treated promptly with aspirin. They are not routinely treated with a second antiplatelet drug or a heparin-type anticoagulant because neither is strongly evidence-based. Nevertheless, based on the discussion above is very likely both would be effective in TIA or minor ischemic stroke where the early risk of recurrent thrombosis in high and the risk of ICH is low due to the small or no infarc-
2
Cerebrovasc Dis 2013;36(suppl 2):1–52 DOI: 10.1159/000356197
tion. TPA is effective for larger ischemic episodes and intravascular intervention also may prove effective but the time factor is challenging. Additional similarities and differences will be discussed.
SP1-3
Intracranial Atheroclerosis and ACVS KS Lawrence Wong Chinese University of Hong Kong, Hong Kong
Intracranial atherosclerosis is the most common vascular lesion found in Asians with ischemic stroke or transient ischemic attack (TIA). In Chinese, Malaysian and South Asians, the frequency of intracranial atherosclerosis was found to be around 33– 50%. Among patients with TIA or minor stroke, the frequency was even higher up to 70%. The mechanisms for TIA/ minor stroke in patients with intracranial atherosclerosis are many. Artery-to-artery embolism, branch atheromatous disease and hemodynamic compromise are all important mechanisms. Sometimes the topography of infarcts on DWI MRI in patients with intracranial atherosclerosis is the same as in patients with small vessel disease. This is the case when isolated infarct is found in the basal ganglion region. However, multiple small infarcts, especially locations in the subcortical and cortical regions along the borderzone areas, point to underlying intracranial atherosclerosis. Vascular work-up for intracranial occlusive disease is strongly indicated with patients with ischemic stroke or TIA when there are multiple small infarcts found on DWI MRI along the borderzone regions.
SP1-4
Activity of Von Willebrand Factor During the Acute Phase of Ischemic Stroke Might Predict Worse Outcome Masahiro Uemura, Yasuhisa Akaiwa, Itaru Ninomiya, Hiroaki Arakawa, Masafumi Toriyabe, Takayoshi Shimohata, Masatoyo Nishizawa Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
State the Purpose: This study aimed to determine the relationship between von Willebrand factor (vWF) activity and clinical profiles during the acute phase of ischemic stroke. Methods: We retrospectively reviewed 137 patients (94 males; mean age, 71.5 years) who were admitted to our department with acute ischemic stroke between November 2010 and December 2012. Patients with severe disability (modified Rankin Scale [mRS] >2) before stroke onset were excluded. vWF activity was measured within one week of symptom onset in all patients. Cause of stroke was determined based on the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Associations between vWF activity and clinical features, including etiology, morbidity,
Abstracts
and mortality, were then investigated. A worse outcome was defined as mRS >2 at the time of discharge. Results: Mean vWF activity associated with cardio-embolic stroke, large artery atherosclerosis, small vessel disease, undetermined and other causes was 162.5 ± 87.3%, 173.5 ± 44.0%, 120.8 ± 50.0%, 171.3 ± 83.7% and 188.0%, respectively. No significant differences were found among causes (p = 0.24); however, vWF activity was significantly higher in patients with worse outcomes than in those with better outcomes (185.5 ± 91.3% vs. 147.3 ± 63.8%, p = 0.018). Conclusion: High vWF activity within one week of acute ischemic stroke onset might predict a worse outcome at the time of discharge. Disclosure of Interest: None Declared.
cerebral microbleeds can be found and imply prognostic significance. Cerebral small vessel disease may be associated with increased risk of death and ischemic stroke and leukoaraiosis is reported to predict poor functional recovery and worse quality of life in patients with stroke or TIA. Also cerebral microbleeds are considered to increase the risk of future intracerebral hemorrhage. Therefore more attention should be paid to small vessel disease and microbleeds for planning preventive and treatment strategies in patients with TIA and AIS.
SP2-3
Short- and Long-Term Risk of Stroke after TIA SP2-1
Risk Stratification in TIA Patients Pierre Amarenco
Tomoyuki Ohara, Toshiyuki Uehara, Kazunori Toyoda, Kazuo Minematsu Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
SOS-TIA Clinic, Bichat Stroke Center, Paris, France
In this lecture I will address risk stratification of patients with a transient ischemic attack using simple clinical scoring system as well as etiological findings based on immediate simple diagnostic tests such as magnetic resonance imaging, arterial imaging and cardiac evaluation. The relative yield of these systems used in practice (i.e., after first call to medical attention, admission to the TIA clinic) or in clinical research (i.e., to characterize an epidemiological cohort, or select patients at higher risk in clincial trial) will be reviewed.
SP2-2
Small Vessel Disease and Microbleeds in TIA and AIS Byung-Woo Yoon Seoul National University Hospital, Seoul, Republic of Korea
Small vessel ischemic disease and microbleeds are pathologic processes affecting small caliber vessels of the brain. These changes are frequently related to age, hypertension and cerebral amyloid angiopathy. They can have no symptoms or present as a stroke, TIA or cognitive impairments. Small vessel disease can easily be found by magnetic resonance imaging (MRI), and susceptibilityweighted image (SWI) and T2* weighted gradient-recalled echo (GRE) MRI are sensitive methods for detecting cerebral microbleeds. Small vessel disease and microbleeds are reported to be common in the general population. MRI-defined silent brain infarcts were detected in 20% of healthy elderly people and up to 50% of patients in selected series. Overall prevalence of cerebral microbleeds was high and increased with age to more than one third in those over 80 years. In patients with TIA or AIS as well as those with intracerebral hemorrhage, small vessel disease and
International TIA/ACVS Conference 2013
Numerous studies have shown that the short-term risk of stroke after transient ischemic attack (TIA) is particularly high, with approximately 5–10% within 7 days and 10–20% within 90 days. However, the reported short-term risks of stroke after TIA were highly heterogeneous, because they depended on various factors as study methods, study population, and treatments. Especially, urgent treatment after TIA has been proved to reduce the shorttime stroke risk. The short-term stroke risk after TIA also differed by its etiology. In most European studies, large artery atherosclerosis was reportedly a stroke subtype with higher subsequent stroke risk. On the other hand, in Japan, limited data suggested that small vessel disease including capsular warning syndrome is the common etiology with early subsequent stroke. In contrast to short-term risk, there are limited reports for longterm risk after TIA. Previous reports demonstrated that TIA patients had the increased long-term risk of both cerebrovascular and cardiovascular events without a decline over time. These findings highlight the importance of continuous secondary prevention in the long term after TIA. In Japan, we are going on a multicenter prospective study to clarify the short-term (90 days) and long-term (1-year) risk of ischemic stroke and other cardiovascular events in patients with TIA. The strength of our TIA registry was the high examination rate of DWI and intracranial and extracranial vascular imaging (more than 90%). We enrolled more than 1,200 TIA patients by September 2013. From the interim analysis in 502 patients who completed 1-year follow up, the 7-day, 90-day, and 1-year stroke risk were 5.2%, 7.4%, and 9.0%, respectively. The leading subtypes of the ischemic strokes were intracranial large artery atherosclerosis and small-vessel disease.
Cerebrovasc Dis 2013;36(suppl 2):1–52 DOI: 10.1159/000356197
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SP3-1
Stroke Incidence after Onset of Transient Ischemic Attack: A Meta-Analysis
TIA Triage of Stroke Risk Using Neuroimaging
Yoshihiro Kokubo
Gregory W. Albers
Preventive Cardiology, National Cerebral and Cardiovascular Center, Suita, Japan
Stanford University, Stanford, Calif., USA
State the Purpose: Transient ischemic attack (TIA) is a
recognized risk factor for stroke. However, there are few studies on the incidence of TIA and the incidence rates of stroke after onset of TIA. The aim of this study was to conduct a meta-analysis of the incidence of TIA and the incidence of stroke after onset of TIA. Methods: A systematic review and meta-analysis of prospective cohorts with TIA were performed by using PubMed. Prospective cohort studies published between 1987 and March 2013 were included. The search was limited to English language and reports showing the number of subjects according to sex and age. The incidence of stroke after TIA was calculated by population- and hospital-based studies. Results: Among 115 articles of PubMed search, 8 articles met the inclusion criteria for the incidence of TIA and 7 and 9 articles met the incidence of stroke after TIA (population- and hospital-based), respectively. In total, data from 2,963,593 and 8,763 subjects for the incidence of TIA and the incidence of stroke after TIA, respectively, were used. During the follow-ups, the incidence rates of TIA were 1.22, 1.02, and 1.15 per 1,000 person-years in men, women, and both sexes, respectively. The incidence rates of TIA according to the year categories (84 years old) in both sexes were 0.03, 0.08, 0.19, 0.18, 1.04, 2.70, 6.36, and 11.9 per 1,000 person-years, respectively. One article in an Asian population, the Hisayama study has shown that the incidence rates of TIA were 0.78 and 0.38 per 1,000 person-years in men and women, respectively. In population-based studies, the incidence rates of stroke were 1.7%, 4.8%, 6.6%, 8.5%, and 11.4% at 2 days, 1 week, 1, 3, and 6 months after onset of TIA, respectively. In hospital-based studies, the incidence rates of stroke were 13.7% and 12.4% at 1 and 3 months after onset of TIA, respectively. Conclusion: In this meta-analysis, the incidence rates of TIA were 1.2 and 1.0 per 1,000 person-years in men and women, respectively. After one month onset of TIA, one in 15 and 7 people have strokes in population- and hospital-based cohort studies. Disclosure of Interest: None Declared.
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Cerebrovasc Dis 2013;36(suppl 2):1–52 DOI: 10.1159/000356197
Multimodal MRI is more specific and sensitive than head CT for the detection of acute brain ischemia. DWI reveals an acute infarction in about 30% of patients with a discharge diagnosis of TIA. Symptom characteristics (motor deficit or speech disorder) and the presence of a symptomatic vessel lesion are associated with the presence of an acute ischemic lesion on DWI. Several studies have shown that DWI positivity has prognostic implications. A recent meta-analysis showed that 7% of TIA patients with a positive DWI will suffer a stroke within a week compared to only 0.5% of the DWI negative patients. Interestingly, in DWInegative patients the ABCD2 score did not influence the risk of stroke, suggesting that a proportion of these patients may not have experienced a transient ischemic event. Two types of automatically processed perfusion sequences are available: Dynamic susceptibility contrast (DSC) perfusion imaging (applicable to both MRI and CT perfusion) and Arterial Spin Labeling (ASL) MR imaging. While preliminary data suggest that TIA patients with perfusion lesions may also be at increase stoke risk, further data are required prior to incorporation of perfusion imaging into clinical decision making. In addition to brain imaging, imaging of the craniocervical vessels can help clarify stroke risk in TIA patients. The importance of vessel imaging in the evaluation and management of TIA was recently confirmed in the CATCH study. Positive CTA (occlusion or stenosis ≥50% in the intracranial or extracranial vessels on the clinically relevant side) was an independent predictor of recurrent stroke. Vessel occlusion on MRA is also associated with a 4-fold increased risk of stroke. TIA/minor stroke patients who are identified as being at very high risk of early recurrent stroke should be strongly considered for acute hospitalization for expedited diagnostic evaluation, therapy and observation. If a stroke occurs, thrombolytic therapy can be administrated rapidly if appropriate. Patients assessed to be at low stroke risk can typically be treated with stroke preventative therapies and managed as outpatients. Neuroimaging based TIA triage was safe and cost-effective in the prospective TWO ACES study. Larger studies of imaging based TIA triage in diverse patient populations are warranted.
Abstracts
SP3-2
Timing of DWI Positivity after TIA Junichiro Satomi1, Naomi Morita2, Masafumi Harada3, Shinji Nagahiro1 1
The Department of Neurosurgery, Tokushima University Hospital, Tokushima, 2Department of Radiology, National Cerebral and Cardiovascular Center, Suita, 3 The Department of Radiology, Tokushima University Hospital, Tokushima, Japan
According to a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council, TIAs are brief episodes of neurological dysfunction resulting from focal cerebral ischemia not associated with permanent cerebral infarction. In the past, TIAs were defined as any focal cerebral ischemic event with symptoms lasting 50% (p < 0.029) are best suitable to predict a high early stroke risk immediately after index TIA. This presentation will show, how clinical and neuroimaging studies (either by MR or/and in particular noninvasive and easily applicable ultrasound technologies in nearly all patients) can contribute to the identification of these patients within 2 complete remitting and relapsing TIAs within 24 h after onset) and positive MR-DWI findings. The more recently propopsed ABCD3-I score takes into consideration positive DWI findings, dual TIA episodes within 7 days of the index event and relevant
International TIA/ACVS Conference 2013
State the Purpose: The role of anticoagulant therapy for acute cardiogenic cerebral infarction is controversial. Intravenous heparin dosage is often suspected to increase symptomatic hemorrhagic transformation, while the therapy is considered as an essential treatment to avoid secondary cardio-embolic events in acute stage. We investigated the association of hemorrhagic transformation with the clinical features and predisposing factors in acute cardiogenic cerebral infarction. Methods: Subjects were consisted of 398 patients (216 males; age, 76.3 ± 10.5 years), who admitted in our hospitals for acute cardiogenic cerebral infarction in anterior circulation started with intravenous heparin dosage (5,000 or 10,000 unit/day) within 48 hours after onset between January 2010 and December 2012. We retrospectively evaluated the associations between their clinical features, predisposing factors, and hemorrhagic transformation defined on Computed Tomography (CT) or Magnetic Resonance Image (MRI) during heparin dosage.
Cerebrovasc Dis 2013;36(suppl 2):1–52 DOI: 10.1159/000356197
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Results: Hemorrhagic transformation (n = 83, 20.9%) was associated with the score of ASPECTS-DWI (odds ratio 1.25, 95% CI: 1.12 to 1.40), NIHSS at admission (odds ratio 0.95, 95% CI: 0.92 to 0.99), and the presence of recanalization of occlusion vessels (odds ratio 6.64, 95% CI: 3.50 to 12.9). The score of ASPECTS-DWI and the presence of recanalization were more strongly associated factors than NIHSS at admission. With respect to ASPECTS-DWI, score = 7 was the cut-off value of hemorrhagic transformation, and the hemorrhagic transformation tended to be increasing in score 70% in Japan. In specialty hospitals, diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) should be considered indispensable. If hyperintense signals are identified in the ischemic area, emergency hospitalization is needed. Patients with continuous mild hemiparesis and unusual focal neurological symptoms without any lesions on first imaging are also regarded as showing evolving stroke. Recurrent ischemic stroke often occurs as a combination of atrial fibrillation and occlusive arterial disease, and this condition may carry a high risk of early recurrence of ischemic stroke in TIA patients. To prevent stroke subsequent to TIA/ACVS, ACVS triage and optimal management thereafter is the most effective.
Abstracts
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Endovascular Therapy for TIA or Minor Ischemic Stroke
Surgical Treatment of TIA in Acute Settings
Hiroshi Yamagami1, Shinichi Yoshimura2, Kenichi Todo3, Nobuyuki Sakai3
Department of Neurosurgery, Nagasaki University, Nagasaki, Japan
Izumi Nagata
1
Department of Neurology, National Cerebral and Cardiovascular Center, Suita, 2Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, 3Stroke Center, Kobe City Medical Center General Hospital, Kobe, Japan
The usefulness of endovascular therapy (EVT) for acute ischemic stroke (AIS) has not been established. Potential limitations of EVT include damage to the arterial wall from devices, fragmentation and distal embolization of the thrombus, and complications of systemic and cerebral hemorrhage. Patients with TIA or minor ischemic stroke are usually excluded from the indication of EVT. However, major artery occlusive disease is associated with early neurological deterioration or recurrent stroke in TIA or minor ischemic stroke. In such case, EVT is performed after the severe deterioration of neurological symptoms, which is refractory to optimal medical therapy. In the Recovery by Endovascular Salvage for Cerebral Ultraacute Embolism (RESCUE)-Japan registry, 1,442 AIS patients with major artery occlusion within 24 hours after the onset were recruited in 84 Japanese stroke centers. Of those, 303 patients with TIA or minor stroke [National Institutes of Health Stroke Scale (NIHSS)
