Amyloid Angiopathy in Brain Hemorrhage: A Postmortem Neuropathological-Magnetic Resonance Imaging Study.

BACKGROUND: Risk factors for intracerebral hemorrhage (ICH) include hypertension and cerebral amyloid angiopathy (CAA). The objective of this study was to determine the autopsy prevalence of CAA and the potential overlap with other risk factors among patients who died from ICH and also the correlation of CAA with cerebral microbleeds. METHODS: We analyzed 81 consecutive autopsy brains from patients with ICH. Staining for CAA detection was performed. We used an age- and sex-matched control group of routine brain autopsies of nonneurological patients to determine the frequencies of CAA and hypertension. Postmortem 3D T2-weighted gradient-echo magnetic resonance imaging (MRI) with a 1.5-T magnet was performed in 11 brains with ICH (5 with CAA and 6 without) and histological correlation was performed when microbleeds were detected. RESULTS: Hypertension and CAA were found in 69.1 and 24.7% of cases respectively. Among patients with CAA, 65.0% also had hypertension. The prevalence of CAA was similar among non-hypertensive cases and controls (33.3 and 23.1%; p = 0.54), whereas a significant difference was found between hypertensive cases vs. controls (28.9% vs. 0; p = 0.01). MRI documented 48 microbleeds and all 5 brains with CAA had ≥1 microbleed, compared to 3/6 brains without CAA. Among 48 microbleeds on MRI, 45 corresponded histologically to microbleeds surrounding microvessels (23 <200 µm in diameter, 19 between 200 µm and 2 mm, 3 were hemosiderin granules). CONCLUSIONS: Both hypertension and CAA frequently coexist in patients with ICH. MRI-detected microbleeds, proven by histological analysis, were twice as common in patients with CAA as in those with hypertensive ICH.

Clinical Significance of Isolated Atypical Transient Symptoms in a Cohort With Transient Ischemic Attack.

BACKGROUND AND PURPOSE: Contrary to typical transient symptoms (TS), atypical TS, such as partial sensory deficit, dysarthria, vertigo/unsteadiness, unusual cortical visual deficit, and diplopia, are not usually classified as symptoms of transient ischemic attack when they occur in isolation, and their clinical relevance is frequently denied. METHODS: Consecutive patients with recent TS admitted in our transient ischemic attack clinic (2003-2008) had systematic brain, arterial, and cardiac investigations. We compared the prevalence of recent infarction on brain imaging, major investigational findings (symptomatic intracranial or extracranial atherosclerotic stenosis ≥50%, cervical arterial dissection, and major source of cardiac embolism), and 1-year risk of major vascular events in patients with isolated typical or atypical TS and nonisolated TS, after exclusion of the main differential diagnoses. RESULTS: Among 1850 patients with possible or definite ischemic diagnoses, 798 (43.1%) had isolated TS: 621 (33.6%) typical and 177 (9.6%) atypical. Acute infarction on brain imaging was similar in patients with isolated atypical and typical TS but less frequent than in patients with nonisolated TS, observed in 10.0%, 11.5%, and 15.3%, respectively (P<0.0001). Major investigational findings were found in 18.1%, 26.4%, and 26.3%, respectively (P=0.06). One-year risk of a major vascular events was not significantly different in the 3 groups. CONCLUSIONS: Transient ischemic attack diagnosis should be considered and investigated in patients with isolated atypical TS.

Impact of diffusion-weighted imaging lesion volume on the success of endovascular reperfusion therapy.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) lesion volume is associated with poor outcome after thrombolysis, and it is unclear whether endovascular therapies are beneficial for large DWI lesion. Our aim was to assess the impact of pretreatment DWI lesion volume on outcomes after endovascular therapy, with a special emphasis on patients with complete recanalization. METHODS: We analyzed data collected between April 2007 and November 2011 in a prospective clinical registry. All acute ischemic stroke patients with complete occlusion of internal carotid artery or middle cerebral artery treated by endovascular therapy were included. DWI lesion volumes were measured by the RAPID software. Favorable outcome was defined by modified Rankin Scale of 0 to 2 at 90 days. RESULTS: A total of 139 acute ischemic stroke patients were included. Median DWI lesion volume was 14 cc (interquartile range, 5-43) after a median onset time to imaging of 110 minutes (interquartile range, 77-178). Higher volume was associated with less favorable outcome (adjusted odds ratio, 0.55; 95% confidence interval, 0.31-0.96). A complete recanalization was achieved in 65 (47%) patients after a median onset time of 238 minutes (interquartile range, 206-285). After adjustment for volume, complete recanalization was associated with more favorable outcome (adjusted odds ratio, 6.32; 95% confidence interval, 2.90-13.78). After stratification of volume by tertiles, complete recanalization was similarly associated with favorable outcome in the upper 2 tertiles (P<0.005). CONCLUSIONS: Our results emphasize the importance of initial DWI volume and recanalization on clinical outcome after endovascular treatment. Large DWI lesions may still benefit from recanalization in selected patients.

Overlap of diseases underlying ischemic stroke: the ASCOD phenotyping.

BACKGROUND AND PURPOSE: ASCOD phenotyping (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; and D, dissection) assigns a degree of likelihood to every potential cause (1 for potentially causal, 2 for causality is uncertain, 3 for unlikely causal but disease is present, 0 for absence of disease, and 9 for insufficient workup to rule out the disease) commonly encountered in ischemic stroke. We used ASCOD to investigate the overlap of underlying vascular diseases and their prognostic implication. METHODS: A single rater applied ASCOD in 405 patients enrolled in the Asymptomatic Myocardial Ischemia in Stroke and Atherosclerotic Disease study. RESULTS: A was present in 90% of patients (A1=43% and A2=15%), C in 52% (C1=23% and C2=14%), and S in 66% (S1=11% and S2=2%). On the basis of grades 1 and 2, 25% of patients had multiple underlying diseases, and 80% when all 3 grades were considered. The main overlap was found between A and C; among C1 patients, A was present in 92% of cases (A1=28%, A2=20%, and A3=44%). Conversely, among A1 patients, C was present in 47% of cases (C1=15%, C2=15%, and C3=17%). Grades for C were associated with gradual increase in the 3-year risk of vascular events, whereas risks were similar across A grades, meaning that the mere presence of atherosclerotic disease qualifies for high risk, regardless the degree of likelihood for A. CONCLUSIONS: ASCOD phenotyping shows that the large overlap among the 3 main diseases, and the high prevalence of any form of atherosclerotic disease, reinforces the need to systematically control atherosclerotic risk factors in all ischemic strokes.

Spectrum of transient visual symptoms in a transient ischemic attack cohort.

BACKGROUND AND PURPOSE: Transient visual symptoms (TVS) are common complaints. They can be related to transient ischemic attacks, but the nature of the symptoms often remains uncertain, and data on prognosis are scarce. We studied the prevalence, presentation, and effect of different types of TVS, paying particular attention to the association with high-risk pathology of embolism. METHODS: A total of 2398 patients with suspected transient ischemic attack admitted to the SOS-TIA clinic between January 2003 and December 2008 underwent immediate evaluation and treatment. RESULTS: Eight hundred twenty-six (34.5%) patients had TVS, including 422 (17.6%) patients with isolated TVS. Transient monocular blindness was the most frequent TVS (36.3%), followed by diplopia (13.4%), homonymous lateral hemianopia (12.3%), bilateral positive visual phenomena (10.8%), and lone bilateral blindness (4.5%). Positive diffusion-weighted imaging was found in 11.8%, 8.1%, 8.1%, and 5.0% of patients with homonymous lateral hemianopia, diplopia, lone bilateral blindness, and transient monocular blindness, respectively. Among 1850 patients (595 patients with TVS) with definite/possible transient ischemic attack or minor stroke, a major source of embolism of cardiac or arterial origin was found less frequently in patients with isolated or nonisolated TVS than in patients without TVS (19.6%; 19.7% versus 28.1%, respectively; P<0.001). However, we found a higher rate of atrial fibrillation in patients with homonymous lateral hemianopia (23.2%) than in patients with other TVS (4.0%; adjusted odds ratio, 6.71; 95% confidence interval, 2.99-15.06) or nonvisual symptoms (9.1%; adjusted odds ratio, 4.39; 95% confidence interval, 2.26-8.50). CONCLUSIONS: Approximately 20% of patients with TVS had a major source of embolism detected, requiring urgent management. Atrial fibrillation was particularly frequent in patients with transient homonymous lateral hemianopia.

Is intracerebral hemorrhage a time-dependent phenomenon after successful combined intravenous and intra-arterial therapy?

BACKGROUND AND PURPOSE: Onset-to-reperfusion time (ORT) has recently emerged as an essential prognostic factor in acute ischemic stroke therapy. Although favorable outcome is associated with reduced ORT, it remains unclear whether intracranial bleeding depends on ORT. We therefore sought to determine whether ORT influenced the risk and volume of intracerebral hemorrhage (ICH) after combined intravenous and intra-arterial therapy. METHODS: Based on our prospective registry, we included 157 consecutive acute ischemic stroke patients successfully recanalized with combined intravenous and intra-arterial therapy between April 2007 and October 2011. Primary outcome was any ICH within 24 hours posttreatment. Secondary outcomes included occurrence of symptomatic ICH (sICH) and ICH volume measured with the ABC/2. RESULTS: Any ICH occurred in 26% of the study sample (n=33). sICH occurred in 5.5% (n=7). Median ICH volume was 0.8 mL. ORT was increased in patients with ICH (median=260 minutes; interquartile range=230-306) compared with patients without ICH (median=226 minutes; interquartile range=200-281; P=0.008). In the setting of sICH, ORT reached a median of 300 minutes (interquartile range=276-401; P=0.004). The difference remained significant after adjustment for potential confounding factors (adjusted P=0.045 for ICH; adjusted P=0.002 for sICH). There was no correlation between ICH volume and ORT (r=0.16; P=0.33). CONCLUSIONS: ORT influences the rate but not the volume of ICH and appears to be a critical predictor of symptomatic hemorrhage after successful combined intravenous and intra-arterial therapy. To minimize the risk of bleeding, revascularization should be achieved within 4.5 hours of stroke onset.

Coronary artery disease and risk of major vascular events after cerebral infarction.

BACKGROUND AND PURPOSE: The impact of asymptomatic coronary artery disease on the risk of major vascular events in patients with cerebral infarction is unknown. METHODS: Four hundred five patients with acute cerebral infarction underwent carotid, femoral artery, thoracic, and abdominal aorta ultrasound examination. Of 342 patients with no known coronary heart disease, 315 underwent coronary angiography. We evaluated the 2-year risk of major vascular events (myocardial infarction, resuscitation after cardiac arrest, hospitalization for unstable angina or heart failure, stroke, or major peripheral arterial disease events) in patients with known coronary heart disease (n=63), and in the no known coronary heart disease group (n=315) as a function of coronary angiographic status (n=315). RESULTS: At 2 years, the estimated risk of major vascular events was 11.0% (95% confidence interval, 8.2-14.7). According to baseline coronary angiography, estimated risk was 3.4% in patients with no coronary artery disease (n=120), 8.0% with asymptomatic coronary artery stenosis <50% (n=113), 16.2% with asymptomatic coronary artery stenosis ≥ 50% (n=81), and 24.1% with known coronary heart disease (P<0.0001). Using no coronary artery disease as the reference, the age- and sex-adjusted hazard ratio (95% confidence interval) of vascular events was 2.10 (0.63-6.96) for asymptomatic coronary stenosis <50%, 4.36 (1.35-14.12) for asymptomatic coronary stenosis ≥ 50%, and 6.86 (2.15-21.31) for known coronary artery disease. CONCLUSIONS: In patients with nonfatal cerebral infarction, presence and extent of asymptomatic stenoses on coronary angiography are strong predictors of major vascular events within 2 years.

Circulating markers of endothelial dysfunction and platelet activation in patients with severe symptomatic cerebral small vessel disease.

BACKGROUND: Small deep infarcts (SDI), also called lacunar infarcts, resulting from the occlusion of deep branch arteries, account for 25% of ischemic strokes. The physiopathology of the disease remains largely unknown. However, evidence about the role of endothelial dysfunction has emerged. Whereas chronic platelet activation is of major importance in acute thrombosis of large atherosclerotic arteries, its role in SDI remains unclear. Frequently associated risk factors are hypertension and diabetes mellitus. The aim of this study was to determine platelet and endothelial activation in patients with recent SDI in comparison to population-based control subjects matched for age, sex and vascular risk factors. METHODS: Platelet activation markers (activated glycoprotein IIb/IIIa, P-selectin and platelet microparticles), shear-induced platelet aggregation (SIPA) studied in the SIPAgreg device at 4,000 s(-1), endothelial activation markers [including von Willebrand factor (vWF) antigen and homocysteine] and high-sensitivity C-reactive protein (hsCRP) were measured in 74 consecutive patients with recent SDI, in whom detectable large artery atherosclerosis or cardiac embolism had been ruled out. Blood samples were collected 1 and 3 months after symptom onset. These factors were also measured in 74 population-based controls with no stroke history and matched for age, sex, hypertension and diabetes. RESULTS: One month after symptom onset, the patients had similar levels of platelet activation to matched controls (p > 0.40 for all comparisons). In contrast, endothelial activation parameters were increased in patients in comparison to controls (vWF: p = 0.002 and homocysteinemia/creatinemia: p = 0.025). The level of hsCRP was slightly increased in patients compared to controls (p = 0.059). At 3 months, we observed a significant decrease in vWF and hsCRP levels in patients (median change in vWF = 10%, p = 0.004; median change in hsCRP = 0.4 mg/l, p = 0.02). Homocysteine levels and all platelet parameters remained unchanged at this time compared to at 1 month. CONCLUSIONS: Our results confirm that chronic platelet activation, when compared to controls matched for age, sex and vascular risk factors, did not seem to play a central role in the pathophysiology of lacunar stroke. In contrast, we found markers of endothelial dysfunction, the role of which in the occurrence of lacunar infarction has still to be clarified in further studies.

Dramatic recovery in acute ischemic stroke is associated with arterial recanalization grade and speed.

BACKGROUND AND PURPOSE: Dramatic recovery (DR) is a predictor of stroke outcome among others. However, after successful recanalization, systematic favorable outcome is not the rule. We sought to analyze the impact of recanalization on DR in patients with acute ischemic stroke eligible for any revascularization strategies (either intravenous or endovascular). METHODS: We analyzed data collected between April 2007 and May 2011 in our prospective clinical registry. All patients with acute ischemic stroke with National Institutes of Health Stroke Scale≥10 at admission and an identification of arterial status before treatment were included. DR was defined as National Institutes of Health Stroke Scale≤3 at 24 hours or a decrease of ≥10 points within 24 hours. RESULTS: DR occurred in 75 of 255 patients with acute ischemic stroke (29.4%). Patients with persistent occlusion had a low DR rate (11.1%) than those with no documented occlusion (36.5%) and those with occlusion followed by recanalization (35.3%; both P<0.001). Among patients with recanalization monitored by angiography, DR was higher among patients with complete recanalization than among those with partial recanalization (46.8% versus 14.3%; P<0.001) and increased with tertiles of time to recanalization (Ptrend=0.002). In multivariable logistic regression analysis, grade and time to recanalization appeared independently associated with DR; the adjusted ORs were 4.17 (95% CI, 1.61-10.77) for complete recanalization and 1.24 (95% CI, 1.04-1.48) for each 30-minute time decrease. Patients with versus without DR more frequently had modified Rankin Scale≤1 (67.6% versus 9.0%; P<0.001) and less frequently had hemorrhage (17.3% versus 33.9%; P=0.024). CONCLUSIONS: DR is strongly associated with favorable clinical outcome and is dependent on complete recanalization and time to recanalization.

Atherogenic dyslipidemia in patients with transient ischemic attack.

BACKGROUND AND PURPOSE: There is mounting evidence that atherogenic dyslipidemia (ie, low high-density lipoprotein cholesterol combined with high triglyceride concentrations) is an independent predictor of high cardiovascular risk and possibly of stroke. METHODS: All patients included in the SOS-TIA cohort underwent an initial standardized evaluation, including medical history, physical examination, routine blood biochemistry, and diagnostic testing, and were followed for 1 year. Lipid profile was evaluated under fasting conditions. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol blood concentration ≤ 40 mg/dL and triglycerides ≥ 150 mg/dL. RESULTS: Among 1471 consecutive patients with transient ischemic attack (TIA) or minor stroke, overall prevalence of atherogenic dyslipidemia was 5.8%, but varied from 4.6% to 11.1%, depending on final diagnosis (possible TIA or TIA with a cerebral ischemic lesion, respectively). Prevalence of atherogenic dyslipidemia was independently associated with male sex, diabetes, and body mass index, but not with ABCD2 score. Atherogenic dyslipidemia also strongly associated with symptomatic intracranial stenosis ≥ 50% (adjusted odds ratio, 2.77; 95% CI, 1.38-5.55), but not with symptomatic extracranial stenosis ≥ 50% (adjusted odds ratio, 1.20; 95% CI, 0.64-2.26). Despite appropriate secondary prevention treatment, 90-day stroke risk was greater in patients with versus without atherogenic dyslipidemia (4.8% versus 1.7%; P=0.04). CONCLUSIONS: The atherogenic dyslipidemia phenotype in patients with TIA may be associated with intracranial artery stenosis and higher risk of early recurrent stroke. Additional data are needed to confirm these findings and to assess the best way to reduce important residual risk in such patients.

Prevalence of coronary atherosclerosis in patients with cerebral infarction.

BACKGROUND AND PURPOSE: there is an overlap between stroke and coronary heart disease, but the exact prevalence of coronary artery disease in patients with nonfatal cerebral infarction is unclear, particularly when there is no known history of coronary heart disease. METHODS: we consecutively enrolled 405 patients presenting with acute cerebral infarction documented by neuroimaging who underwent carotid and femoral artery, thoracic, and abdominal aorta ultrasound examinations. Of the 342 patients with no known coronary heart disease, 315 underwent coronary angiography a median of 8 days (interquartile range, 6-11) after stroke onset. RESULTS: coronary plaques on angiography, regardless of stenosis severity, were present in 61.9% of patients (95% confidence interval [CI], 56.5-67.3) and coronary stenoses ≥ 50% were found in 25.7% (95% CI, 20.9-30.5). The overall prevalence of coronary plaque increased with the number of arterial territories (carotid or femoral arteries) involved, with an adjusted odds ratio of coronary artery disease of 1.25 (95% CI, 0.58-2.71) for presence of plaque in 1 territory, and 4.31 (95% CI, 1.92-9.68) for presence of plaque in both territories, compared with no plaque in either territory. The presence of plaque in both femoral and carotid arteries had an age- and sex-adjusted positive predictive value of 84% for presence of coronary plaque and a negative predictive value of 44%. CONCLUSIONS: there is a high burden of silent coronary artery disease in patients with nonfatal cerebral infarction and no known coronary heart disease, even in the absence of systemic atherosclerosis. The prevalence is even higher in patients with evidence of carotid and/or femoral plaque.

Outcomes of mechanical endovascular therapy for acute ischemic stroke: a clinical registry study and systematic review.

BACKGROUND AND PURPOSE: Recanalization is a powerful predictor of stroke outcome in patients with arterial occlusion. Intravenous recombinant tissue plasminogen activator is limited by its recanalization rate, which may be improved with mechanical endovascular therapy (MET). However, the benefit and safety of MET remain to be determined. The aim of this study was to give reliable estimates of efficacy and safety outcomes of MET. METHODS: We analyzed data from our prospective clinical registry and conducted a systematic review of all previous studies using MET published between January 1966 and November 2009. RESULTS: From April 2007 to November 2009, 47 patients with acute stroke were treated with MET at Bichat Hospital. The literature search identified 31 previous studies involving a total of 1066 subjects. In the meta-analysis, including our registry data, the overall recanalization rate was 79% (95% CI, 73-84). Meta-analysis of clinical outcomes showed a pooled estimate of 40% (95% CI, 34-46; 27 studies) for favorable outcome, 28% (95% CI, 23-33; 28 studies) for mortality, and 8% (95% CI, 6-10; 27 studies) for symptomatic intracranial hemorrhage. The likelihood of a favorable outcome increased with the use of thrombolysis (OR, 1.99; 95% CI, 1.23-3.22) and with proportion of patients with isolated middle cerebral artery occlusion (OR per 10% increase, 1.14; 95% CI, 1.04-1.25). CONCLUSIONS: MET is associated with acceptable safety and efficacy in stroke patients, and it may be a therapeutic option in those presenting with isolated middle cerebral artery occlusion.

Yield of systematic transcranial Doppler in patients with transient ischemic attack.

OBJECTIVE: Urgent evaluation and treatment of transient ischemic attack (TIA) patients in a dedicated TIA clinic may reduce the 90-day stroke risk by 80%. ABCD2 (Age, Blood pressure, Clinical features, Duration, Diabetes) score and magnetic resonance imaging abnormalities help to identify patients at high risk of stroke. Our aim was to determine whether the use of transcranial Doppler (TCD) examination on arrival at the TIA clinic yields additional information that facilitates the identification of patients at high risk of stroke recurrence. METHODS: Between January 2003 and December 2007, 1,881 patients were admitted to SOS-TIA clinic (a TIA clinic with around-the-clock access). Clinical and vascular assessment included TCD performed by a neurologist immediately after admission. Stroke prevention measures were initiated on arrival, in accordance with guidelines. All patients were followed for 1 year after presentation to the SOS-TIA clinic. RESULTS: A total of 1,823 TCD examinations were performed within 4 hours of admission. Intracranial narrowing or occlusion was found in 8.8% of patients, and was independently associated with age, hypertension, and diabetes. After 1-year follow-up on best preventive therapy, the incidence of recurrent vascular events (intracranial revascularization for TIA recurrence, stroke, myocardial infarction, and vascular death combined) was 7.0% in patients with intracranial narrowing or occlusion and 2.4% in those without (log-rank, p = 0.007). The hazard ratio of combined outcome for the presence of intracranial narrowing or occlusion was 2.29 (95% confidence interval [CI], 1.15-4.56; p = 0.02) in multivariate analysis including age, gender, hypertension, and diabetes, and was 2.50 (95%CI, 1.24-5.05; p = 0.01) in multivariate analysis including ABCD2 score > or =4. INTERPRETATION: Immediate TCD examination on arrival at the TIA clinic is feasible and could help to identify patients at high risk of vascular events recurrence. This study supports a systematic intracranial vascular examination in the initial management of TIA.

Impact of a combined intravenous/intra-arterial approach in octogenarians.

BACKGROUND: Intravenous (IV) alteplase is not currently recommended in octogenarian patients, and the benefit/risk ratio of endovascular (intra-arterial, IA) therapy remains to be determined. The aim of this study was to determine the impact of a combined IV-IA approach in octogenarians. METHODS: From a single-centre interventional study, we report age-specific outcomes of patients treated by a combined IV-IA thrombolytic approach. Patients ≥80 years with documented arterial occlusion treated by conventional IV thrombolysis constituted the control group. RESULTS: Among 84 patients treated by the IV-IA approach, those ≥80 years (n = 25) had a similar rate of early neurological improvement to that of patients <80 years, whereas the 90-day favourable outcome rate was lower in octogenarians (adjusted odds ratio, OR, 0.21; 95% confidence interval, CI, 0.06-0.75). No difference in symptomatic intracranial haemorrhage was observed whereas a higher rate of 90-day mortality (adjusted OR, 3.27; 95% CI, 0.76-14.14) and asymptomatic intracranial haemorrhage (adjusted OR, 6.39; 95% CI, 1.54-26.63) were found in patients ≥80 years old. Among octogenarians, and compared to IV-thrombolysis-treated patients (n = 24), patients treated by the IV-IA approach had a higher rate of recanalization (76 vs. 33%, p = 0.003) associated with increased early neurological improvement (32 vs. 8%, p = 0.07). Although there was a higher rate of asymptomatic intracranial haemorrhage (44 vs. 8%, p = 0.005) observed in the IV-IA group, no difference existed in symptomatic intracranial haemorrhage rates and 90-day favourable outcome. CONCLUSION: The IV-IA approach in octogenarians was associated with lower efficacy at 3 months and higher mortality and asymptomatic haemorrhagic complications than in patients <80 years old. Definite recommendations cannot be given, but an endovascular approach may cause more harm than positive effects in patients over 80 years and should not be considered outside an approved protocol.

Basilar artery atherosclerotic plaques in paramedian and lacunar pontine infarctions: a high-resolution MRI study.

BACKGROUND AND PURPOSE: Pontine infarction is most often related to basilar artery atherosclerosis when the lesion abuts on the basal surface (paramedian pontine infarction), whereas small medial pontine lesion is usually attributed to small vessel lipohyalinosis. A previous study has found that high-resolution MRI can detect basilar atherosclerotic plaques in up to 70% of patient with paramedian pontine infarction, even in patients with normal angiograms, but none has evaluated the presence of basilar artery plaque by high-resolution MRI in patients with small medial pontine lesion in the medial part of the pons. METHODS: Consecutive patients with pontine infarction underwent basilar angiography using time-of-flight and contrast-enhanced 3-dimensional MR angiography to assess the presence of basilar artery stenosis and high-resolution MRI to assess the presence of atherosclerotic plaque. Basilar artery angiogram was scored as "normal," "irregular," or "stenosed" >or=30%" and basilar artery by high-resolution MRI was scored as "normal" or "presence of plaque." Medial pontine infarcts were divided into paramedian pontine infarction and small medial pontine lesion groups. RESULTS: Forty-one patients with pontine infarction were included, 26 with paramedian pontine infarction and 15 with small medial pontine lesion. High-resolution MRI detected basilar artery atherosclerosis in 42% of patients with a pontine infarction and normal basilar angiograms. Among patients with paramedian pontine infarction, 65% had normal basilar angiograms but 77% had basilar artery atherosclerosis detected on high-resolution MRI. Among patients with small medial pontine lesion, 46% had normal basilar angiograms but 73% had basilar artery plaques detected on by high-resolution MRI. CONCLUSIONS: This study suggests that medial pontine lacunes may be due to a penetrating artery disease secondary to basilar artery atherosclerosis. High-resolution MRI could help precise stroke subtyping.

Update on investigation and management of postinfectious encephalitis.

PURPOSE OF REVIEW: Encephalitis is a complex syndrome associated with significant morbidity and mortality. Despite biological and neuroimaging investigations, the cause of encephalitis remains undetermined in more than half of the cases. The aim of this review was to describe available data concerning diagnosis and treatment of postinfectious encephalitis, focusing on acute disseminated encephalomyelitis (ADEM) and acute hemorrhagic leukoencephalitis (AHLE). RECENT FINDINGS: The increasing availability of brain MRI studies has allowed a better delineation of diagnosis and prognosis of postinfectious central nervous system disorders. Beneficial effects of steroids and plasma exchange have been described in the most severe forms of postinfectious encephalitis, including ADEM and AHLE, but randomized controlled studies are lacking. Intravenous immunoglobulins may be of value in ADEM with peripheral nerve involvement and for patients in whom corticosteroid therapy is contraindicated. SUMMARY: Postinfectious encephalitis needs to be identified early in the management of patients with unexplained encephalitis as it represents a treatable disease. Randomized studies are needed in order to assess the potential benefit of early combined immunotherapy in ADEM.

Is moderate atherosclerotic stenosis in the middle cerebral artery a cause of or a coincidental finding in ischemic stroke?

BACKGROUND: Few pathological data have focused on the causal link between intracranial atherosclerotic disease and parent artery stroke. The objective of this study was to investigate the cause of middle cerebral artery (MCA) atherosclerotic disease in patients with fatal stroke. METHODS AND RESULTS: In 123 patients with unilateral MCA territory infarction we performed a case-control autopsy study evaluating the frequency of atherosclerotic plaque and moderate (<70%) or severe (>or=70%) stenosis in the ipsilateral and contralateral MCA. Clinical history, risk factors, imaging data and general autopsy reports were available. The entire cerebral arterial tree was studied pathologically. MCA atherosclerosis (either moderate or severe stenosis) was more frequent in the ipsilateral (21.1%, n = 26) than the contralateral MCA (8.1%, n = 10). The corresponding odds ratio (OR) for the presence of atherosclerosis in the ipsilateral MCA relative to the contralateral MCA was 6.33 [95% confidence interval (CI) = 1.87-21.40]. This difference was found with both moderate (OR = 5.75, 95% CI = 1.45-22.76) and severe (OR = 7.18, 95% CI = 1.58-32.73) stenosis. CONCLUSIONS: Moderate MCA atherosclerotic stenosis may be responsible for parent territorial stroke. Novel arterial wall magnetic resonance imaging techniques should now be used to investigate in vivo the hypothesis that moderate MCA stenosis is a possible explanation in patients with nonfatal stroke of unknown cause.

Placebo-controlled trial of high-dose atorvastatin in patients with severe cerebral small vessel disease.

BACKGROUND AND PURPOSE: Uncontrolled studies have shown that statins can improve cerebral vasoreactivity (CVR) in patients with mild small vessel disease. We sought to determine whether high-dose atorvastatin increases CVR compared with placebo in patients with severe small vessel disease. METHODS: Ninety-four adults with recent lacunar stroke were randomly allocated in a double-blind manner to 80 mg of atorvastatin daily or matching placebo after stratification for hypertensive and diabetic status. The primary end point was change in CVR after 3 months of treatment. Secondary outcomes were changes in brachial and carotid artery endothelial-dependent vasodilations. RESULTS: At baseline, all patients had a severely impaired CVR (mean, 12.1%; 95% CI, 9.5-14.7) and carotid (mean, -0.25%; 95% CI, -1.17-0.67) and brachial artery (mean, 2.72%; 95% CI, 1.39-4.05) endothelial function. Despite reductions of 55% in low-density lipoprotein cholesterol and of 30% in high-sensitivity C-reactive protein in the active arm compared to placebo, atorvastatin 80 mg per day did not improve CVR or endothelial dysfunction of carotid and brachial arteries. CONCLUSIONS: We found no positive effect of 3-month treatment with atorvastatin on severe cerebral microvasculature endothelial dysfunction in patients with lacunar stroke.

Does ABCD2 score below 4 allow more time to evaluate patients with a transient ischemic attack?

BACKGROUND AND PURPOSE: The National Institute for Clinical Excellence (NICE) recommends that patients with a transient ischemic attack and ABCD(2) score > or =4 and those with >2 transient ischemic attacks within 1 week be admitted for urgent complete etiologic evaluation within 24 hours and that those with an ABCD(2) score <4 be evaluated less urgently within 1 week. METHODS: Using data from 1176 patients with a definite or possible transient ischemic attack or minor stroke included in the SOS-TIA registry (January 2003 to June 2007), we studied the usefulness of the conventional ABCD(2) score cutoff as well as the NICE criteria for urgent admission to a stroke unit defined as presence of symptomatic internal carotid artery stenosis > or =50%, symptomatic intracranial artery stenosis > or =50%, or major cardiac source of embolism. RESULTS: Among 697 patients with an ABCD(2) score <4, 20% required immediate consideration for emergency treatment (eg, symptomatic internal carotid stenosis > or =50% in 9.1% of patients, symptomatic intracranial stenosis in 5.0%, atrial fibrillation in 5.9%, other major cardiac source of embolism in 2.1%) in comparison to 31.6% of 497 patients with an ABCD(2) score > or =4. The sensitivity and specificity of ABCD(2) score > or =4 or NICE criteria for discriminating between patients requiring admission or not were <62% with low positive predictive values (<30%) and high negative predictive values (> or =80%). CONCLUSIONS: One in 5 patients with an ABCD(2) score <4 had high-risk disease requiring urgent treatment decision-making. When triaging on an ABCD(2) score, we recommend adding systematic carotid ultrasound (or a default angiographic CT scan) and electrocardiography within 24 hours before postponing complete transient ischemic attack evaluation.

Outcomes of intravenous recombinant tissue plasminogen activator therapy according to gender: a clinical registry study and systematic review.

BACKGROUND AND PURPOSE: The natural history of stroke is worse in women than in men. Controversial data have been published on the efficacy of thrombolysis with recombinant tissue plasminogen activator (rtPA) according to gender. We evaluated gender differences in the efficacy and safety outcomes of intravenous rtPA using a clinical registry and systematic review. METHODS: Since January 2002, we collected baseline characteristics and efficacy and safety outcomes for patients who received intravenous rtPA in our center. We performed a systematic PubMed literature search for previous observational studies that examined gender effects on outcomes after intravenous rtPA treatment. RESULTS: No gender difference in good outcome at 3 months (adjusted OR for women, 1.41; 95% CI, 0.76 to 2.60) and in 90-day mortality (adjusted OR, 1.38; 95% CI, 0.59 to 3.19) was found in our registry. We identified 16 studies that evaluated the gender effect among intravenous rtPA-treated patients. None of these studies supported a gender difference in favorable outcome, and one suggested an increased risk of mortality in men. In unadjusted partial meta-analysis in 4074 women and 5840 men including our registry data, we found a trend toward a lower risk of symptomatic intracranial hemorrhage in women (crude OR, 0.87; 95% CI, 0.68 to 1.10). CONCLUSIONS: These results suggest no gender difference in outcome among patients treated with intravenous rtPA.