U Schulz

Incidence, outcome, risk factors, and long-term prognosis of cryptogenic transient ischaemic attack and ischaemic stroke: a population-based study

Summary Background A third of transient ischaemic attacks (TIAs) and ischaemic strokes are of undetermined cause (ie, cryptogenic), potentially undermining secondary prevention. If these events are due to occult atheroma, the risk-factor profile and coronary prognosis should resemble that of overt large artery events. If they have a cardioembolic cause, the risk of future cardioembolic events should be increased. We aimed to assess the burden, outcome, risk factors, and long-term prognosis of cryptogenic TIA and stroke. Methods In a population-based study in Oxfordshire, UK, among patients with a first TIA or ischaemic stroke from April 1, 2002, to March 31, 2014, we compared cryptogenic events versus other causative subtypes according to the TOAST classification. We compared markers of atherosclerosis (ie, risk factors, coronary and peripheral arterial disease, asymptomatic carotid stenosis, and 10-year risk of acute coronary events) and of cardioembolism (ie, risk of cardioembolic stroke, systemic emboli, and new atrial fibrillation [AF] during follow-up, and minor-risk echocardiographic abnormalities and subclinical paroxysmal AF at baseline in patients with index events between 2010 and 2014). Findings Among 2555 patients, 812 (32%) had cryptogenic events (incidence of cryptogenic stroke 0·36 per 1000 population per year, 95% CI 0·23–0·49). Death or dependency at 6 months was similar after cryptogenic stroke compared with non-cardioembolic stroke (23% vs 27% for large artery and small vessel subtypes combined; p=0·26) as was the 10-year risk of recurrence (32% vs 27%; p=0·91). However, the cryptogenic group had fewer atherosclerotic risk factors than the large artery disease (p<0·0001), small vessel disease (p=0·001), and cardioembolic (p=0·008) groups. Compared with patients with large artery events, those with cryptogenic events had less hypertension (adjusted odds ratio [OR] 0·41, 95% CI 0·30–0·56; p<0·0001), diabetes (0·62, 0·43–0·90; p=0·01), peripheral vascular disease (0·27, 0·17–0·45; p<0·0001), hypercholesterolaemia (0·53, 0·40–0·70; p<0·0001), and history of smoking (0·68, 0·51–0·92; p=0·01), and compared with small vessel and cardioembolic subtypes, they had no excess risk of asymptomatic carotid disease (adjusted OR 0·64, 95% CI 0·37–1·11; p=0·11) or acute coronary events (adjusted hazard ratio [HR] 0·76, 95% CI 0·49–1·18; p=0·22) during follow-up. Compared with large artery and small vessel subtypes combined, patients with cryptogenic events also had no excess of minor-risk echocardiographic abnormalities (cryptogenic 37% vs 45%; p=0·18) or paroxysmal AF (6% vs 10%; p=0·17) at baseline or of new AF (adjusted HR 1·23, 0·78–1·95; p=0·37) or presumed cardioembolic events (1·16, 0·62–2·17; p=0·64) during follow-up. Interpretation The clinical burden of cryptogenic TIA and stroke is substantial. Although stroke recurrence rates are comparable with other subtypes, cryptogenic events have the fewest atherosclerotic markers and no excess of cardioembolic markers. Funding Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute for Health Research, Medical Research Council, and the NIHR Oxford Biomedical Research Centre.

BIANCA (Brain Intensity AbNormality Classification Algorithm): A new tool for automated segmentation of white matter hyperintensities.

Reliable quantification of white matter hyperintensities of presumed vascular origin (WMHs) is increasingly needed, given the presence of these MRI findings in patients with several neurological and vascular disorders, as well as in elderly healthy subjects. We present BIANCA (Brain Intensity AbNormality Classification Algorithm), a fully automated, supervised method for WMH detection, based on the k-nearest neighbour (k-NN) algorithm. Relative to previous k-NN based segmentation methods, BIANCA offers different options for weighting the spatial information, local spatial intensity averaging, and different options for the choice of the number and location of the training points. BIANCA is multimodal and highly flexible so that the user can adapt the tool to their protocol and specific needs. We optimised and validated BIANCA on two datasets with different MRI protocols and patient populations (a “predominantly neurodegenerative” and a “predominantly vascular” cohort). BIANCA was first optimised on a subset of images for each dataset in terms of overlap and volumetric agreement with a manually segmented WMH mask. The correlation between the volumes extracted with BIANCA (using the optimised set of options), the volumes extracted from the manual masks and visual ratings showed that BIANCA is a valid alternative to manual segmentation. The optimised set of options was then applied to the whole cohorts and the resulting WMH volume estimates showed good correlations with visual ratings and with age. Finally, we performed a reproducibility test, to evaluate the robustness of BIANCA, and compared BIANCA performance against existing methods. Our findings suggest that BIANCA, which will be freely available as part of the FSL package, is a reliable method for automated WMH segmentation in large cross-sectional cohort studies.

Age-specific association of migraine with cryptogenic TIA and stroke: Population-based study

Objective: To determine whether there is an association between previous migraine and cryptogenic TIA or ischemic stroke at older ages. Methods: We determined the age-specific associations of history of migraine and Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtype of TIA and ischemic stroke in a population-based cohort study (Oxford Vascular Study; 2002–2012). Results: Among 1,810 eligible patients with TIA or ischemic stroke, 668 (36.9%) had cryptogenic events, of whom 187 (28.0%) had previous migraine. Migraine was more commonly associated with cryptogenic events than with those of known etiology (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.38–2.16, p < 0.0001; cardioembolic 2.00, 1.50–2.66, p < 0.0001; large artery 1.75, 1.20–2.53, p = 0.003; small vessel 1.32, 0.95–1.83, p = 0.096). The association of migraine with cryptogenic events was independent of age, sex, and all measured vascular risk factors (RFs) (adjusted OR 1.68, 1.33–2.13, p < 0.0001) and was strongest at older ages (<55 years, OR 1.11, 0.55–2.23; 55–64 years, 1.48, 0.83–2.63; ≥65 years, 1.81, 1.39–2.36) and in patients without vascular RFs (0 RFs OR 2.62, 1.33–5.15; 1 RF 2.01, 1.35–3.01; 2 RFs 1.80, 1.21–2.68; 3 RFs 1.21, 0.71–2.07; 4 RFs 0.92, 0.28–2.99). Results were consistent for migraine with or without aura and for analyses excluding TIA or stratified by sex or vascular territory of event. Conclusions: In this population-based study of stroke etiology stratified by age, migraine was most strongly associated with cryptogenic TIA and ischemic stroke, particularly at older ages, suggesting a causal role or a shared etiology.

Total small vessel disease score and risk of recurrent stroke Validation in 2 large cohorts

Objective: In patients with TIA and ischemic stroke, we validated the total small vessel disease (SVD) score by determining its prognostic value for recurrent stroke. Methods: Two independent prospective studies were conducted, one comprising predominantly Caucasian patients with TIA/ischemic stroke (Oxford Vascular Study [OXVASC]) and one predominantly Chinese patients with ischemic stroke (University of Hong Kong [HKU]). Cerebral MRI was performed and assessed for lacunes, microbleeds, white matter hyperintensities (WMH), and perivascular spaces (PVS). Predictive value of total SVD score for risk of recurrent stroke was determined and potential refinements considered. Results: In 2,002 patients with TIA/ischemic stroke (OXVASC n = 1,028, HKU n = 974, 6,924 patient-years follow-up), a higher score was associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio [HR] per unit increase: 1.32, 1.16–1.51, p < 0.0001; c statistic 0.61, 0.56–0.65, p < 0.0001) and intracerebral hemorrhage (ICH) (HR 1.54, 1.11–2.13, p = 0.009; c statistic 0.65, 0.54–0.76, p = 0.006). A higher score predicted recurrent stroke in SVD and non-SVD TIA/ischemic stroke subtypes (c statistic 0.67, 0.59–0.74, p < 0.0001 and 0.60, 0.55–0.65, p < 0.0001). Including burden of microbleeds and WMH and adjusting the cutoff of basal ganglia PVS potentially improved predictive power for ICH (c statistic 0.71, 0.60–0.81, phet = 0.45), but not for recurrent ischemic stroke (c statistic 0.60, 0.56–0.65, phet = 0.76) on internal validation. Conclusions: The total SVD score has predictive value for recurrent stroke after TIA/ischemic stroke. Prediction of recurrence in patients with nonlacunar events highlights the potential role of SVD in wider stroke etiology.

Stenting for symptomatic vertebral artery stenosis: The Vertebral Artery Ischaemia Stenting Trial

Objective: To compare in the Vertebral Artery Ischaemia Stenting Trial (VIST) the risks and benefits of vertebral angioplasty and stenting with best medical treatment (BMT) alone for symptomatic vertebral artery stenosis. Methods: VIST was a prospective, randomized, open-blinded endpoint clinical trial performed in 14 hospitals in the United Kingdom. Participants with symptomatic vertebral stenosis ≥50% were randomly assigned (1:1) to vertebral angioplasty/stenting plus BMT or to BMT alone with randomization stratified by site of stenosis (extracranial vs intracranial). Because of slow recruitment and cessation of funding, recruitment was stopped after 182 participants. Follow-up was a minimum of ≥1 year for each participant. Results: Three patients did not contribute any follow-up data and were excluded, leaving 91 patients in the stent group and 88 in the medical group. Mean follow-up was 3.5 (interquartile range 2.1–4.7) years. Of 61 patients who were stented, stenosis was extracranial in 48 (78.7%) and intracranial in 13 (21.3%). No periprocedural complications occurred with extracranial stenting; 2 strokes occurred during intracranial stenting. The primary endpoint of fatal or nonfatal stroke occurred in 5 patients in the stent group vs 12 in the medical group (hazard ratio 0.40, 95% confidence interval 0.14–1.13, p = 0.08), with an absolute risk reduction of 25 strokes per 1,000 person-years. The hazard ratio for stroke or TIA was 0.50 (p = 0.05). Conclusions: Stenting in extracranial stenosis appears safe with low complication rates. Large phase 3 trials are required to determine whether stenting reduces stroke risk. ISRCTN.com identifier: ISRCTN95212240. Classification of evidence: This study provides Class I evidence that for patients with symptomatic vertebral stenosis, angioplasty with stenting does not reduce the risk of stroke. However, the study lacked the precision to exclude a benefit from stenting.

Anti-MOG antibodies with longitudinally extensive transverse myelitis preceded by CLIPPERS

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory brainstem syndrome of uncertain etiology, with distinct radiologic features.1 Autoimmunity has been postulated, although specific CNS antibodies have not been reported. Our patient initially presented with classical clinicoradiologic features of CLIPPERS. Five months later, she developed a longitudinally extensive spinal cord inflammatory lesion affecting mainly the conus, and had antibodies to myelin-oligodendrocyte glycoprotein (MOG). Although neuromyelitis optica spectrum disorders (NMOSD) with brainstem involvement may feature in the broad differential diagnosis of CLIPPERS, this is the first report describing an overlap with the anti-MOG phenotype of NMOSD, and highlights that CLIPPERS may not be a distinct nosologic entity.

Posterior circulation cerebrovascular syndromes: diagnosis and management

One in five strokes affects the posterior circulation. Diagnosing posterior circulation stroke can be challenging, as the vascular anatomy can be variable, and because presenting symptoms are often non-specific and fluctuating. Nevertheless, making the correct diagnosis is important, as these strokes have a high chance of recurrence, can be life threatening, and can lead to equally life-threatening complications. Investigation and management largely follow those for stroke in general, although some specific differences exist. These include the preferred use of MRI for diagnosing posterior fossa lesions, the management of basilar artery thrombosis, which may have a longer time window for recanalisation therapy, and the use of endovascular therapies for secondary prevention, which, so far, have not shown any benefit in the treatment of vertebral or basilar artery stenosis. In this review, we summarise the anatomy, aetiology and presentation of posterior circulation stroke, and discuss current approaches to management.

Quantification of Serial Cerebral Blood Flow in Acute Stroke Using Arterial Spin Labeling

Background and Purpose— Perfusion-weighted imaging is used to select patients with acute ischemic stroke for intervention, but knowledge of cerebral perfusion can also inform the understanding of ischemic injury. Arterial spin labeling allows repeated measurement of absolute cerebral blood flow (CBF) without the need for exogenous contrast. The aim of this study was to explore the relationship between dynamic CBF and tissue outcome in the month after stroke onset. Methods— Patients with nonlacunar ischemic stroke underwent ⩽5 repeated magnetic resonance imaging scans at presentation, 2 hours, 1 day, 1 week, and 1 month. Imaging included vessel-encoded pseudocontinuous arterial spin labeling using multiple postlabeling delays to quantify CBF in gray matter regions of interest. Receiver–operator characteristic curves were used to predict tissue outcome using CBF. Repeatability was assessed in 6 healthy volunteers and compared with contralateral regions of patients. Diffusion-weighted and T2-weighted fluid attenuated inversion recovery imaging were used to define tissue outcome. Results— Forty patients were included. In contralateral regions of patients, there was significant variation of CBF between individuals, but not between scan times (mean±SD: 53±42 mL/100 g/min). Within ischemic regions, mean CBF was lowest in ischemic core (17±23 mL/100 g/min), followed by regions of early (21±26 mL/100 g/min) and late infarct growth (25±35 mL/100 g/min; ANOVA P<0.0001). Between patients, there was marked overlap in presenting and serial CBF values. Conclusions— Knowledge of perfusion dynamics partially explained tissue fate. Factors such as metabolism and tissue susceptibility are also likely to influence tissue outcome.

Suspected cerebral foreign body granuloma following endovascular treatment of intracranial aneurysm: imaging features

Dear Sir, Coil occlusion of aneurysms has emerged as the mainstay of treatment following the ISAT trial [1]. Advances in technology have facilitated the endovascular treatment of complex and broad necked aneurysms. These procedures often require the simultaneous placement of several pieces of equipment within the intracranial vessels for a prolonged period of time. Usually, complications after these procedures are more frequent but otherwise do not differ from simple coiling. We wish to report a rare complication in a patient after a complex procedure in tortuous anatomy. A 51-year-old woman had previously been treated at our institution after a subarachnoid haemorrhage.While the site of rupture was unknown, a proximal right A1 aneurysm and a left paraophthalmic aneurysm were both secured with bare platinum coils in one sitting. A recurrence of the A1 aneurysm was observed after 6 months and following multidisciplinary discussion, the patient consented to retreatment with stent assisted coiling using Leo + Baby low profile nitinol braided self expanding stent (Balt, Montmorency, France). The patient was pretreated with dual antiplatelets for 7 days (aspirin 75 mg OD and Clopidogrel 75 mg OD). The procedure was performed under general anaesthetic, and the patient was anticoagulated during the procedure with heparin, maintaining the activated clotting time (ACT) twice above baseline. A Fargo (Balt, Montmorency, France) distal access catheter was placed into the right internal carotid artery, and an Echelon-10 (ev3 Endovascular, Plymouth, MN, USA) was advanced into the distal right A1 over a Traxess guidewire (Microvention, Tustin, CA, USA). The placement of this equipment was difficult due to severe tortuosity of the aortic arch and supra-aortic vessels. The Leo + Baby stent was placed across the aneurysm neck in a good position. However, despite multiple attempts, the aneurysm could not be cannulated with a guidewire through the struts of the stent, and therefore, no coiling was performed. The patient was well following the procedure and was discharged 2 days later without complication. Two weeks later, the patient presented to her local hospital with two generalised seizures preceded by a prodrome of malaise, headache, and mild right sided weakness. A CT revealed several areas of cortical and white matter low attenuation within the right cerebral hemisphere. Magnetic resonance imaging of the brain demonstrated several areas of cortical and white matter T2 hyperintensity surrounding multiple lesions that exhibited nodular and peripheral rim enhancement (Fig. 1). Many of these lesions contained a central area of susceptibility artefact on gradient echo (Fig. 1b), which persisted after the resolution of oedema and contrast enhancement (Fig. 1d). The lesions were restricted to the territory of the right internal carotid artery. The patient received empirical treatment with broad spectrum antibiotics on the assumption that these lesions were infective abscesses. However, the blood inflammatory markers were not increased and blood cultures did not reveal an organism. Embolic infarcts were thought to be an unlikely cause due to the delay in the patient’s presentation and the lack of restricted diffusion on MRI. Due to the delay in the presentation and the appearance of multiple enhancing lesions, we concluded that this may be due D. Minks :W. Küker (*) Department of Neuroradiology, West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK e-mail: Wilhelm.Kuker@ndcn.ox.ac.uk

Validation of automated segmentation of white matter hyperintensities on MRI: Correlation with cognitive function after TIA and stroke

BACKGROUNDnControversy exists regarding the question of whether weight change decreases or increases the risk of mortality.nnnAIMnThe aim of this study was to evaluate the prognostic importance of weight change on short-term outcomes in acute ischemic stroke patients.nnnMETHODSnA total of 654 patients with acute ischemic stroke were enrolled in this study from March 2010 to May 2013. We assessed the weight change of each participant between admission and discharge from the Department of Neurology. Weight change was defined as change ≥0·05u2009kg/baseline body mass index unit. We evaluated the short-term outcomes using a modified Rankin Scale at three-months after the onset of a stroke.nnnRESULTSnAmong the 654 patients, 35·2% were included in the weight-change group. Weight loss occurred in 24·6% of the participants during the hospital stay following the stroke, which lasted an average of nine-days. Compared with the weight-stable group, the pronounced weight-loss group had a higher risk of unfavorable outcomes (odds ratio 2·43; 95% confidence interval 1·12-5·25).nnnCONCLUSIONSnShort-term weight loss after stroke appears to be more common than we expected, and our results suggest that it is associated with unfavorable functional outcomes. Therefore, clinical nutrition should be considered as a component of medical treatment and weight loss should be monitored as an indicator of malnutrition.