O. Naggara

Diffusion tensor imaging in early Alzheimer's disease

Our aim was to investigate the extent of white matter tissue damage in patients with early Alzheimer disease (AD) using diffusion tensor magnetic resonance imaging (DTI). Although AD pathology mainly affects cortical grey matter, previous magnetic resonance imaging (MRI) studies showed that changes also exist in the white matter (WM). However, the nature of AD-associated WM damage is still unclear. Conventional and DTI examinations (b=1000 s/mm(2), 25 directions) were obtained from 12 patients with early AD (Mini Mental State Examination [MMSE] score=27, Grober and Buschke test score=33.2, digit span score=5.6) and 12 sex- and age-matched volunteers. The right and left mean diffusivity (MD) and fractional anisotropy (FA) of several WM regions were pooled in each patient and control, and compared between the two groups. Volumes of the whole brain and degree of atrophy of the temporal lobe were compared between the two groups. In AD, MD was increased in the splenium of the corpus callosum and in the WM in the frontal and parietal lobes. FA was bilaterally decreased in the WM of the temporal lobe, the frontal lobe and the splenium compared with corresponding regions in controls. Values in other areas (occipital area, superior temporal area, cingulum, internal capsule, and genu of the corpus callosum) were not different between patients and controls. No correlations were found between the MMSE score and the anisotropy indices. Findings of DTI reveal abnormalities in the frontal and temporal WM in early AD patients. These changes are compatible with early temporal-to-frontal disconnections.

Endovascular Treatment of Intracranial Unruptured Aneurysms: Systematic Review and Meta-Analysis of the Literature on Safety and Efficacy

PURPOSE To report an updated, systematic review of medical literature from January 2003 to July 2008, on endovascular treatment (EVT) of intracranial unruptured aneurysms (UAs) (a) to assess the morbidity and case fatality rate of EVT of UAs, (b) to understand how bias can affect results, and (c) to estimate the efficacy of EVT by using reported digital subtraction angiographic (DSA) results and clinical follow-up events. MATERIALS AND METHODS This article was prepared in accordance with the Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The literature was searched by using PubMed and the EMBASE and Cochrane Library databases. Eligibility criteria were (a) explicit procedural mortality and morbidity rates; (b) at least 10 patients; (c) saccular, intradural, nondissecting UAs; (d) original study published in English or French between January 2003 and July 2008; and (e) a methodological quality score higher than 6, according to Strengthening the Reporting of Observational Studies in Epidemiology criteria. End points included procedural mortality and morbidity, defined as a modified Rankin scale score of 3-6 at 1 month, and efficacy, estimated by using immediate and follow-up digital subtraction angiographic results, as well as delayed hemorrhagic events. RESULTS Seventy-one studies were included. Procedural unfavorable outcome was found in 4.8% (random-effect weighted average; 189 of 5044) of patients (99% confidence interval [CI]: 3.9%, 6.0%). Immediate angiographic results showed satisfactory occlusion in 86.1% (2660 of 3089) of UAs. Recurrences were shown in 321 (24.4%) of 1316 patients followed up for 0.4-3.2 years. Retreatment was performed in 9.1% (random-effect weighted average; 166 of 1699) of patients (99% CI: 6.2%, 13.1%). The annual risk of bleeding after EVT was 0.2% (random-effect weighted average; nine of 1395) of patients (99% CI: 0.1%, 0.3%), but clinical follow-up was short, limited to the first 6 months for 76.7% (n = 1071) of reported patients. CONCLUSION EVT of UAs can be performed with relative safety. The efficacy of treatment as compared with observation has not been rigorously documented.

Safety and occlusion rates of surgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis of the literature from 1990 to 2011

Background and purpose Surgical clipping of unruptured intracranial aneurysms (UIAs) has recently been challenged by the emergence of endovascular treatment. We performed an updated systematic review and meta-analysis on the surgical treatment of UIAs, in an attempt to determine the aneurysm occlusion rates and safety of surgery in the modern era. Methods A detailed protocol was developed prior to conducting the review according to the Cochrane Collaboration guidelines. Electronic databases spanning January 1990–April 2011 were searched, complemented by hand searching. Heterogeneity was assessed using I2, and publication bias with funnel plots. Surgical mortality and morbidity were analysed with weighted random effect models. Results 60 studies with 9845 patients harbouring 10 845 aneurysms were included. Mortality occurred in 157 patients (1.7%; 99% CI 0.9% to 3.0%; I2=82%). Unfavourable outcomes, including death, occurred in 692 patients (6.7%; 99% CI 4.9% to 9.0%; I2=85%). Morbidity rates were significantly greater in higher quality studies, and with large or posterior circulation aneurysms. Reported morbidity rates decreased over time. Studies were generally of poor quality; funnel plots showed heterogeneous results and publication bias, and data on aneurysm occlusion rates were scant. Conclusions In studies published between 1990 and 2011, clipping of UIAs was associated with 1.7% mortality and 6.7% overall morbidity. The reputed durability of clipping has not been rigorously documented. Due to the quality of the included studies, the available literature cannot properly guide clinical decisions.

Endovascular Treatment of Intracranial Unruptured Aneurysms: A Systematic Review of the Literature on Safety with Emphasis on Subgroup Analyses

PURPOSE To report subgroup analyses of an updated systematic review on endovascular treatment of intracranial unruptured aneurysms (UAs); to compare types of embolic agents, adjunct techniques, and newer devices; and to identify potential risk factors for poor outcomes. MATERIALS AND METHODS Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to prepare this article, and the literature was searched with PubMed and with EMBASE and Cochrane databases. Six eligibility criteria (procedural complications rates; at least 10 patients; saccular, nondissecting UAs; original study published in English or French between January 2003 and July 2011; methodological quality score > 6 [modified Strengthening and Reporting of Observational Studies in Epidemiology criteria]; a study published in a peer-reviewed journal) were used. End points included procedural mortality and unfavorable outcomes (death or modified Rankin Scale, Glasgow Outcome Scale, or World Federation of Neurosurgeons Scale at 1 month scores, all > 2). A fixed-effects model (Mantel-Haenszel) was used for pooled estimates of mortality and unfavorable outcomes; a random-effects model (DerSimonian-Laird) was used in case of heterogeneity. RESULTS Ninety-seven studies with 7172 patients (26 studies published July 2008 through July 2011) were included. Sixty-nine (1.8%) of 7034 patients died (fixed-effect weighted average; 99% confidence interval [CI]: 1.4%, 2.4%; Q value, 55.0; I(2) = 0%). Unfavorable outcomes, including death, occurred in 4.7% (242 of 6941) of patients (99% CI: 3.8, 5.7; Q value, 128.3; I(2) = 26.8%). Patients treated after 2004 had better outcomes (unfavorable outcome, 3.1; 99% CI: 2.4, 4.0) than patients treated during 2001-2003 (unfavorable outcome, 4.7%; 99% CI: 3.6%, 6.1%; P = .01) or in 2000 and before (unfavorable outcome, 5.6%; 99% CI: 4.7%, 6.6%; P < .001). Significantly higher risk was associated with liquid embolic agents (8.1%; 99% CI: 4.7%, 13.7%) versus simple coil placement (4.9%; 99% CI: 3.8%, 6.3%; P = .002). Unfavorable outcomes occurred in 11.5% (99% CI: 4.9%, 24.6%) of patients treated with flow diversion. CONCLUSION Procedure-related poor outcomes occurred (4.7% of patients), risks decreased, and liquid embolic agents and flow diversion were associated with higher risks.

Analysis by Categorizing or Dichotomizing Continuous Variables Is Inadvisable: An Example from the Natural History of Unruptured Aneurysms

SUMMARY: In medical research analyses, continuous variables are often converted into categoric variables by grouping values into ≥2 categories. The simplicity achieved by creating ≥2 artificial groups has a cost: Grouping may create rather than avoid problems. In particular, dichotomization leads to a considerable loss of power and incomplete correction for confounding factors. The use of data-derived “optimal” cut-points can lead to serious bias and should at least be tested on independent observations to assess their validity. Both problems are illustrated by the way the results of a registry on unruptured intracranial aneurysms are commonly used. Extreme caution should restrict the application of such results to clinical decision-making. Categorization of continuous data, especially dichotomization, is unnecessary for statistical analysis. Continuous explanatory variables should be left alone in statistical models.

Epidemiology, pathophysiology, diagnosis, and management of intracranial artery dissection

Spontaneous intracranial artery dissection is an uncommon and probably underdiagnosed cause of stroke that is defined by the occurrence of a haematoma in the wall of an intracranial artery. Patients can present with headache, ischaemic stroke, subarachnoid haemorrhage, or symptoms associated with mass effect, mostly on the brainstem. Although intracranial artery dissection is less common than cervical artery dissection in adults of European ethnic origin, intracranial artery dissection is reportedly more common in children and in Asian populations. Risk factors and mechanisms are poorly understood, and diagnosis is challenging because characteristic imaging features can be difficult to detect in view of the small size of intracranial arteries. Therefore, multimodal follow-up imaging is often needed to confirm the diagnosis. Treatment of intracranial artery dissections is empirical in the absence of data from randomised controlled trials. Most patients with subarachnoid haemorrhage undergo surgical or endovascular treatment to prevent rebleeding, whereas patients with intracranial artery dissection and cerebral ischaemia are treated with antithrombotics. Prognosis seems worse in patients with subarachnoid haemorrhage than in those without.

Anatomical and Technical Factors Associated With Stroke or Death During Carotid Angioplasty and Stenting Results From the Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S) Trial and Systematic Review

Background and Purpose— The purposes of this study were to assess the relationships between anatomic and technical factors and the 30-day risk of stroke or death after carotid angioplasty and stenting in the Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial and to perform a systematic review of the literature. Methods— We included patients from EVA-3S in whom carotid stenting was attempted irrespective of allocated treatment. Two radiologists blinded to clinical data independently assessed the aortic arch and carotid arteries on procedural angiograms. In addition, we performed a systematic review of studies that reported 30-day risk of stroke or death in relation with arterial anatomy and technique. Outcomes were stroke or death and stroke occurring within 30 days of the carotid angioplasty and stenting procedure. Results— Two hundred sixty-two patients from EVA-3S fulfilled the inclusion criteria (including 1 initially allocated to surgery and 13 in whom stent insertion failed).Within 30 days after the procedure, 25 (9.5%) patients had a stroke or had died. The risk of stroke or death was higher in patients with internal carotid artery-common carotid artery angulation ≥60° (relative risk, 4.96; 2.29 to 10.74) and lower in those treated with cerebral protection devices (relative risk [RR], 0.38; 0.17 to 0.85). In the systematic review (56 studies; 34 398 patients), the risk of stroke or death was higher in patients with left-sided carotid angioplasty and stenting (RR, 1.29; 1.05 to 1.58), increased internal carotid artery-common carotid artery angulation (RR, 3.41; 1.52 to 7.63), and when the target internal carotid artery stenosis was >10 mm (RR, 2.36; 1.28 to 3.38). There was no significant increase in risk of stroke or death in patients with Type III aortic arch, aortic arch calcification, or with ostial involvement, calcification, ulceration or degree of stenosis of the target internal carotid artery stenosis. The use of a cerebral protection device was associated with a lower risk of stroke or death (RR, 0.55; 0.41 to 0.73). Risk was not related with stent or cerebral protection device type. Conclusions— Our results strongly suggest that some technical and anatomic factors, especially extreme angulation of the carotid artery, have an impact on the risks of carotid angioplasty and stenting.

Does Aneurysmal Wall Enhancement on Vessel Wall MRI Help to Distinguish Stable From Unstable Intracranial Aneurysms

Background and Purpose— Arterial wall enhancement on vessel wall MRI was described in intracranial inflammatory arterial disease. We hypothesized that circumferential aneurysmal wall enhancement (CAWE) could be an indirect marker of aneurysmal wall inflammation and, therefore, would be more frequent in unstable (ruptured, symptomatic, or undergoing morphological modification) than in stable (incidental and nonevolving) intracranial aneurysms. Methods— We prospectively performed vessel wall MRI in patients with stable or unstable intracranial aneurysms. Two readers independently had to determine whether a CAWE was present. Results— We included 87 patients harboring 108 aneurysms. Interreader and intrareader agreement for CAWE was excellent (&kgr;=0.85; 95% confidence interval, 0.75–0.95 and &kgr;=0.90; 95% confidence interval, 0.83–0.98, respectively). A CAWE was significantly more frequently seen in unstable than in stable aneurysms (27/31, 87% versus 22/77, 28.5%, respectively; P<0.0001). Multivariate logistic regression, including CAWE, size, location, multiplicity of aneurysms, and daily aspirin intake, revealed that CAWE was the only independent factor associated with unstable status (odds ratio, 9.20; 95% confidence interval, 2.92–29.0; P=0.0002). Conclusions— CAWE was more frequently observed in unstable intracranial aneurysms and may be used as a surrogate of inflammatory activity in the aneurysmal wall.

Primary angiitis of the central nervous system: description of the first fifty-two adults enrolled in the French cohort of patients with primary vasculitis of the central nervous system.

To describe characteristics and outcomes of a multicenter cohort of patients diagnosed as having primary angiitis of the central nervous system (PACNS).

Clinical Scales Do Not Reliably Identify Acute Ischemic Stroke Patients With Large-Artery Occlusion

Background and Purpose— It remains debated whether clinical scores can help identify acute ischemic stroke patients with large-artery occlusion and hence improve triage in the era of thrombectomy. We aimed to determine the accuracy of published clinical scores to predict large-artery occlusion. Methods— We assessed the performance of 13 clinical scores to predict large-artery occlusion in consecutive patients with acute ischemic stroke undergoing clinical examination and magnetic resonance or computed tomographic angiography ⩽6 hours of symptom onset. When no cutoff was published, we used the cutoff maximizing the sum of sensitivity and specificity in our cohort. We also determined, for each score, the cutoff associated with a false-negative rate ⩽10%. Results— Of 1004 patients (median National Institute of Health Stroke Scale score, 7; range, 0–40), 328 (32.7%) had an occlusion of the internal carotid artery, M1 segment of the middle cerebral artery, or basilar artery. The highest accuracy (79%; 95% confidence interval, 77–82) was observed for National Institute of Health Stroke Scale score ≥11 and Rapid Arterial Occlusion Evaluation Scale score ≥5. However, these cutoffs were associated with false-negative rates >25%. Cutoffs associated with an false-negative rate ⩽10% were 5, 1, and 0 for National Institute of Health Stroke Scale, Rapid Arterial Occlusion Evaluation Scale, and Cincinnati Prehospital Stroke Severity Scale, respectively. Conclusions— Using published cutoffs for triage would result in a loss of opportunity for ≥20% of patients with large-artery occlusion who would be inappropriately sent to a center lacking neurointerventional facilities. Conversely, using cutoffs reducing the false-negative rate to 10% would result in sending almost every patient to a comprehensive stroke center. Our findings, therefore, suggest that intracranial arterial imaging should be performed in all patients with acute ischemic stroke presenting within 6 hours of symptom onset.