Segmental microbleeds: a radiological sign for cranial dural arteriovenous fistula.

A 57-year-old man presented to the emergency department following a road traffic accident, having experienced a sudden ascending 'wave of emotion'. After the event, he developed an intense right-sided temporal headache and was thought to have a complex grief reaction resulting from a recent bereavement. Given persistent symptoms, a computed tomography (CT) scan of head was conducted at an outpatient transient ischaemic attack (TIA) clinic, which showed a possible right occipital infarct. Further magnetic resonance imaging (MRI) scanning revealed instead a segmental area of microbleeds in the posterior right temporal lobe, with occipital extension. Upon discussion at the neuroradiology multidisciplinary team meeting and subsequent digital subtraction angiography (DSA), a cranial dural arteriovenous fistula (DAVF) was confirmed. He underwent a successful embolisation, with his symptoms fully resolving 16 months later.

Utility of white matter disease and atrophy on routinely acquired brain imaging for prediction of long-term delirium risk: population-based cohort study.

BACKGROUND: brain imaging done as part of standard care may have clinical utility beyond its immediate indication. Using delirium as an exemplar, we determined the predictive value of baseline brain imaging variables [white matter changes (WMC) and atrophy] for delirium risk on long-term follow-up after transient ischemic attack (TIA)/stroke in a population-based cohort study. METHODS: surviving TIA/stroke participants in the Oxford Vascular Study (OXVASC) were assessed prospectively for delirium during all hospitalisations over 6 months (2013-14). Using logistic regression, independent associations were determined between baseline OXVASC computed tomography or magnetic resonance brain imaging measures of WMC and cerebral atrophy (none/mild versus moderate/severe) and delirium adjusted for age, sex, baseline stroke severity, depression, illness severity and pre-admission cognition. RESULTS: among 1,565 TIA/stroke survivors with 194 hospital admissions (158 patients, mean/standard deviation age at admission = 79.2/11.5 years), delirium occurred in 59 (37%). WMC and atrophy on baseline imaging were associated with delirium [odds ratio (OR) = 3.41, 1.21-5.85, P = 0.001 and OR = 2.50, 1.23-5.08, P = 0.01 (unadjusted) and OR = 2.67, 1.21-5.85, P = 0.02 and OR = 2.18, 1.00-4.73, P = 0.05 (adjusted age and sex)]. Associations were strengthened when analyses were restricted to patients hospitalised within 5 years of baseline brain imaging [OR = 6.04, 2.39-15.24, P < 0.0001 and OR = 4.64, 1.46-14.82, P = 0.009 (unadjusted)] but only WMC remained significant after adjustment for all covariates including pre-admission cognition (OR = 4.83, 1.29-18.13, P = 0.02 for Mini-Mental State Examination and OR = 5.15, 1.26-21.09, P = 0.02 for Montreal Cognitive Assessment). CONCLUSIONS: WMC and atrophy on brain imaging done up to 5 years earlier predicted delirium and may have clinical utility in risk stratification. Associations with WMC but not atrophy were independent of pre-admission cognitive impairment.

Frequency of New Silent MRI Lesions in Myelin Oligodendrocyte Glycoprotein Antibody Disease and Aquaporin-4 Antibody Neuromyelitis Optica Spectrum Disorder.

Importance: In multiple sclerosis, magnetic resonance imaging (MRI) new silent lesions contribute to the diagnostic criteria, have prognostic value, and are used in treatment monitoring; but in aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD), they are rare between attacks. Their frequency and their association with relapses in adults with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are still unclear. Objective: To examine the frequency and characteristics of MRI new silent lesions in MOGAD and AQP4-NMOSD. Design, Setting, and Participants: This retrospective cohort study analyzed clinical and MRI data of 404 patients with MOGAD or AQP4-NMOSD between February 1, 1994, and April 1, 2021; data were prospectively recorded on the Oxford NMOSD clinical database under follow-up. The study was conducted at the Oxford National Referral Center for NMOSD. Participants included patients with MOGAD and AQP4-NMOSD who were treated within the Oxford National NMO Specialist Service. Exposures: Seropositive MOGAD and AQP4-NMOSD patients who had MRIs during attacks and the remission phase of their disease. Main Outcomes and Measures: Frequency of new silent lesions detected by either attack MRIs (during the acute clinical event) or remission MRIs (performed outside of a relapse and at least 3 months from last attack). Median time to next relapse in the presence of definite (reference MRI performed at least 4 weeks from last attack onset), probable (reference MRI performed during last attack), and no new silent lesions on remission MRIs was also evaluated. Results: One hundred eighty-two MOGAD patients and 222 AQP4-NMOSD patients were included. Of the MOGAD patients, 113 (62%) were female, median age at onset was 28 years (range, 2-72), and median follow-up was 52 months (range, 11-253). Of the AQP4-NMOSD patients, 189 (85%) were female, median age at onset was 43 years (range, 2-82), and median follow-up was 87.5 months (range, 11-260). MOGAD patients had 296 attack MRI sessions and 167 remission MRI sessions. New attack silent lesions were found in 97 of 296 (33%) attack MRI sessions, whereas new remission silent lesions were found in 5 of 167 (3.0%) remission MRI sessions. Median time from remission scan to the next relapse in the presence of definite or probable new remission lesions was 2 months (IQR, 1-6), whereas in the absence of any new remission lesions it was 73 months (IQR, 20-104; hazard ratio, 23.86; 95% CI, 7.51-75.79; P < .001). AQP4-NMOSD patients had 470 attack MRI sessions and 269 remission MRI sessions. New attack silent lesions were detected in 88 of 470 (18.7%) attack MRI sessions, whereas new remission silent lesions were found in 7 of 269 (2.6%) remission MRI sessions. Median time from remission scan to the next relapse in the presence of definite or probable new remission lesions was 5 months (IQR, 2-6), whereas in the absence of any new remission lesions it was 85 months (IQR, 29-167; hazard ratio, 21.23; 95% CI, 8.05-53.65; P < .001). Conclusions and Relevance: In contrast to that reported in multiple sclerosis, results of this cohort study suggest that new remission silent lesions are rare on follow-up scans in MOGAD and AQP4-NMOSD and appear to indicate a high risk of imminent relapse.

Blood Pressure Control and Recurrent Stroke After Intracerebral Hemorrhage in 2002 to 2018 Versus 1981 to 1986: Population-Based Study.

Background and Purpose: The PROGRESS trial (Perindopril Protection Against Recurrent Stroke Study) conducted in the early 1990s showed that blood pressure (BP) lowering therapy reduced the risks of recurrent stroke by about 50% after spontaneous intracerebral hemorrhage (ICH). However, the ICH subgroup was a minority, and trial cohorts are invariably selective. Therefore, it is unclear whether the impact of BP control on risk of recurrent stroke in ICH observed in PROGRESS would be as great in real-world practice. Methods: We compared BP control (mean BP during study follow-up) and risks of recurrent stroke after first-ever primary ICH in 2 colocated population-based studies before and after the PROGRESS trial (1995­2001) in Oxfordshire: Oxfordshire Community Stroke Project (OCSP; 1981­1986) and OXVASC (Oxford Vascular Study; 2002­2018). Results: Two hundred seventy-seven patients (753 patient-years of follow-up) with first-ever primary ICH were ascertained in OXVASC and OCSP. Baseline systolic BP was comparable between the 2 studies (mean/SD=183.8/36.5 in OXVASC versus 178.1/38.2 in OCSP, P=0.30) but among one hundred thirty-seven 90-day survivors, mean BP during follow-up was substantially lower in OXVASC versus OCSP (135.2/16.4 versus 157.3/17.8, P<0.0001). Risks of recurrent stroke (per 100 patient-years) decreased from 10.3 (95% CI, 4.7­19.5) in OCSP to 3.1 (1.8­4.8) in OXVASC (P=0.006), predominantly driven by a reduction at younger ages (5-year risk at age <75 years: 35.4% versus 6.9%, P=0.001; hazard ratio, 0.14 [0.04­0.54]). Conclusions: Risks of recurrent stroke after primary ICH have fallen significantly in Oxfordshire over the past 4 decades, coinciding with substantial improvements in BP control during follow-up.

Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies.

BACKGROUND: Patients with stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) are at risk of recurrent ICH, ischaemic stroke, and other serious vascular events. We aimed to analyse these risks in population-based studies and compare them with the risks in RESTART, which assessed antiplatelet therapy after ICH. METHODS: We pooled individual patient data from two prospective, population-based inception cohort studies of all patients with an incident firs-in-a-lifetime ICH in Oxfordshire, England (Oxford Vascular Study; April 1, 2002, to Sept 28, 2018) and Lothian, Scotland, UK (Lothian Audit of the Treatment of Cerebral Haemorrhage; June 1, 2010, to May 31, 2013). We quantified the absolute and relative risks of recurrent ICH, ischaemic stroke, or any serious vascular event (non-fatal stroke, non-fatal myocardial infarction, or vascular death), stratified by ICH location (lobar vs non-lobar) and comorbid atrial fibrillation (AF). We compared pooled event rates with those after allocation to avoid antiplatelet therapy in RESTART. FINDINGS: Among 674 patients (mean age 74·7 years [SD 12·6], 320 [47%] men) with 1553 person-years of follow-up, 46 recurrent ICHs (event rate 3·2 per 100 patient-years, 95% CI 2·0-5·1) and 25 ischaemic strokes (1·7 per 100 patient-years, 0·8-3·3) were reported. Patients with lobar ICH (n=317) had higher risk of recurrent ICH (5·1 per 100 patient-years, 95% CI 3·6-7·2) than patients with non-lobar ICH (n=355; 1·8 per 100 patient-years, 1·0-3·3; hazard ratio [HR] 3·2, 95% CI 1·6-6·3; p=0·0010), but there was no evidence of a difference in the risk of ischaemic stroke (1·8 per 100 patient-years, 1·0-3·2, vs 1·6 per 100 patient-years, 0·6-4·4; HR 1·1, 95% CI 0·5-2·8). Conversely, there was no evidence of a difference in recurrent ICH rate in patients with AF (n=147; 3·3 per 100 patient-years, 95% CI 1·0-10·7) compared with those without (n=526; 3·2 per 100 patient-years, 2·2-4·7; HR 0·9, 95% CI 0·4-2·1), but the risk of ischaemic stroke was higher with AF (6·3 per 100 patient-years, 3·7-10·9, vs 0·7 per 100 patient-years, 0·1-5·6; HR 8·2, 3·3-20·3; p<0·0001), resulting in patients with AF having a higher risk of all serious vascular events than patients without AF (15·5 per 100 patient-years, 10·0-24·1, vs 6·8 per 100 patient-years, 3·6-12·5; HR 1·78, 95% CI 1·16-2·74; p=0·0090). Only for patients with lobar ICH without comorbid AF was the risk of recurrent ICH greater than the risk of ischaemic stroke (5·2 per 100 patient-years, 95% CI 3·6-7·5, vs 0·9 per 100 patient-years, 0·2-4·8; p=0·00034). Comparing data from the pooled population-based studies with that from patients allocated to not receive antiplatelet therapy in RESTART, there was no evidence of a difference in the rate of recurrent ICH (3·5 per 100 patient-years, 95% CI 1·9-6·0, vs 4·4 per 100 patient-years, 2·6-6·1) or ischaemic stroke (3·4 per 100 patient-years, 1·9-5·9, vs 5·3 per 100 patient-years, 3·3-7·2). INTERPRETATION: The risks of recurrent ICH, ischaemic stroke, and all serious vascular events after ICH differ by ICH location and comorbid AF. These data enable risk stratification of patients in clinical practice and ongoing randomised trials. FUNDING: UK Medical Research Council, Stroke Association, British Heart Foundation, Wellcome Trust, and the National Institute for Health Research Oxford Biomedical Research Centre.

Aneurysms of the communicating segment of the internal carotid artery with posterior communicating artery agenesis are associated with perforator infarction after embolization.

BACKGROUND: While anatomic features associated with the risk of posterior communicating artery (PcoA) occlusion after embolization of aneurysms of the PcoA segment of the internal carotid artery (ICA) are well known, the link between perforator origin and perforator infarction has only been reported following neurosurgical clipping. The aim of this study was to determine the origin of anterior thalamic perforators and correlate it with risk of perforator infarction after embolization of PcoA segment aneurysms. METHODS: One-hundred-and-ninety consecutive patients treated for PcoA segment aneurysms between 2017 and 2019 were included. PcoA and anterior thalamic perforator origin anatomy was assessed with computed tomography (CT) angiography, digital subtracted angiography, and high-resolution three-dimensional rotational cone-beam CT angiography (CBCT-A) by two independent interventional neuroradiologists. The presence of perforator infarction after embolization was ascertained from the patient's notes and follow-up imaging. RESULTS: CBCT-A was superior in demonstrating the origin of perforators (P<0.001). The prevalence of perforator origin was estimated at 86% (95% CI 81%-92%) for PcoA, 8% (95% CI 4%-13%) for aneurysm wall, and 5% (95% CI 2%-9%) for ICA. The aneurysm wall origin was exclusively associated with PcoA agenesis, as well as higher risk of perforator infarction after aneurysm coiling compared with other variants (OR=14, 95% CI 2-88, P=0.006). CONCLUSIONS: Our study suggests that anterior thalamic perforators may arise from aneurysm wall when there is no PcoA. Anatomic association between PcoA agenesis and perforator arising from ICA could underlie such findings, and careful consideration is essential before aneurysm repair to anticipate the risk of thalamic infarction in such cases.

Prevalence, predictors and prognosis of incidental intracranial aneurysms in patients with suspected TIA and minor stroke: a population-based study and systematic review.

INTRODUCTION: Unruptured intracranial aneurysms (UIAs) are common incidental imaging findings, but there are few data in patients with transient ischaemic attack (TIA)/stroke. The frequency of UIA might be higher due to shared risk factors, but rupture risk might be reduced by intensive secondary prevention. We determined the prevalence and prognosis of UIA in patients with suspected TIA/minor stroke. METHODS: All patients referred to the population-based Oxford Vascular Study (2011-2020) with suspected TIA/minor stroke and non-invasive angiography were included. We determined the prevalence of incidental asymptomatic UIA and the risk of subsequent subarachnoid haemorrhage (SAH) by follow-up on intensive medical treatment, with guideline-based monitoring/management. We also did a systematic review of UIA prevalence/prognosis in cohorts with TIA/stroke. FINDINGS: Among 2013 eligible patients, 95 (4.7%) had 103 previously unknown asymptomatic UIA. Female sex (OR 2.3, 95% CI 1.5 to 3.7), smoking (2.1, 1.2 to 3.6) and hypertension (1.6, 1.0 to 2.5) were independently predictive of UIA, with a prevalence of 11.1% in those with all three risk factors. During mean follow-up of 4.5 years, only one SAH occurred: 2.3 (95% CI 0.3 to 16.6) per 1000 person-years. We identified 19 studies of UIA in TIA/stroke cohorts (n=12 781), all with either symptomatic carotid stenosis or major acute stroke. The pooled mean UIA prevalence in patients with TIA/stroke was 5.1% (95% CI 4.8 to 5.5) and the incidence of SAH was 4.6 (95% CI 1.9 to 11.0) per 1000 person-years. INTERPRETATION: The 5% prevalence of UIA in patients with confirmed TIA/minor stroke is likely higher than that in the general population. However, the risk of SAH on intensive medical treatment and guideline-based management/monitoring is low.

Prognosis of Asymptomatic Intracranial Stenosis in Patients With Transient Ischemic Attack and Minor Stroke.

Importance: Asymptomatic intracranial stenosis (ICS) is a frequent finding on imaging results, particularly in the assessment of acute stroke. Although the management of symptomatic ICS is informed by randomized trials, to our knowledge there are few data on the prevalence and prognosis of asymptomatic ICS in patients with stroke and transient ischemic attack (TIA). Objective: To study the age-specific prevalence and prognosis of asymptomatic ICS in a population-based cohort of patients with TIA and minor stroke. Design, Setting, and Participants: All patients (predominantly white) recruited to the Oxford Vascular Study (Oxfordshire, England) between March 1, 2011, and March 1, 2018, with TIA and minor ischemic stroke (National Institutes of Health Stroke Scale score, ≤3), irrespective of age, were included (n = 1579). We determined the age-specific prevalence of 50% or more asymptomatic ICS and the associated stroke risk by face-to-face follow-up to 2018 on standard medical treatment without stenting. Exposures: Patients underwent magnetic resonance angiography of the intracranial and cervicocranial arteries, computed tomography angiography if magnetic resonance angiography was contraindicated, or carotid/transcranial Doppler ultrasonography if computed tomography angiography was contraindicated. Main Outcomes and Measures: The primary outcomes were the prevalence and prognosis of asymptomatic ICS. Results: Of 1368 eligible patients (mean [SD] age, 69.2 [13.9] years; 700 men [51.2%]) with intracranial vascular imaging, 426 ICS were identified in 260 patients (19.0%): 58 (4.2%) with only symptomatic ICS, 155 (11.3%) with only asymptomatic ICS, and 47 (3.4%) with both. The prevalence of any asymptomatic ICS increased from 4.8% for patients younger than 70 years to 34.6% for patients 90 years or older (P for trend < .001; odds ratio per decade, 1.96; 95% CI, 1.69-2.27) and was greater than that of 50% or more asymptomatic carotid bifurcation stenosis (202 [14.8%] vs 105 patients [7.2%]; relative risk, 2.04; 95% CI, 1.63-2.55, P < .001). However, the 155 patients with only asymptomatic ICS had no increase in risk of ischemic stroke compared with those with no ICS (unadjusted HR, 1.03, 95% CI, 0.49-2.17), with 8 first recurrent events (5.2%) during 506 patient-years of follow-up and 3 in the territory of the ICS (annualized risk, 0.59%; 95% CI, 0.12-1.73). Conclusions and Relevance: The prevalence of asymptomatic ICS increases with age in white patients with TIA and minor stroke and is greater than that of asymptomatic carotid stenosis, but asymptomatic ICS does not increase the short- or medium-term risk of distal recurrent ischemic stroke for patients receiving standard medical treatment.

Prevalence, predictors, and prognosis of symptomatic intracranial stenosis in patients with transient ischaemic attack or minor stroke: a population-based cohort study.

BACKGROUND: Symptomatic intracranial stenosis was perceived to convey a high risk of recurrent stroke, but two previous trials (SAMMPRIS and VISSIT) did not show superiority of intracranial stenosis stenting over intensive medical management alone. These findings were partly due to a lower than expected risk of recurrent stroke without stenting, possibly reflecting the young age of recruits (median age <60 years), and raise questions about generalisability to routine clinical practice. We therefore studied the age-specific prevalence, predictors, and prognosis of symptomatic intracranial stenosis in a population-based cohort of patients with transient ischaemic attack and minor stroke on intensive medical management. METHODS: The Oxford Vascular Study (OXVASC) is a prospective incidence cohort study of all vascular events in a population of 92 728 people residing in Oxfordshire, UK. All patients, irrespective of age, with transient ischaemic attack and minor ischaemic stroke occurring between March 1, 2011, and March 1, 2018 (follow-up to Sept 28, 2018), were ascertained with multiple methods, including assessment in a dedicated daily emergency clinic and daily review of all hospital admissions. Imaging was by MR angiography of the intracranial and cervicocranial arteries, by CT angiography if MR angiography was contraindicated, and by transcranial Doppler and carotid ultrasound if CT angiography was contraindicated. All patients received intensive medical treatment without stenting, and those with intracranial vascular imaging were analysed in our study, which assessed the age-specific prevalence of 50-99% intracranial stenosis and the associated stroke risk of 50-99% and 70-99% stenosis (adjusted for age and vascular risk factors) during follow-up to Sept 28, 2018. FINDINGS: Of 1368 eligible patients with intracranial vascular imaging, 241 (17·6%) had 385 50-99% symptomatic or asymptomatic intracranial stenosis. The prevalence of symptomatic 50-99% intracranial stenosis increased from 29 (4·9%) of 596 at younger than 70 years to 10 (19·6%) of 51 at 90 years or older (ptrend<0·0001). Of 94 patients with 50-99% symptomatic intracranial stenosis, 14 (14·9%) had recurrent strokes (12 ischaemic and two haemorrhagic) during a median follow-up of 2·8 years (IQR 1·5-4·6). Although symptomatic intracranial stenosis conveyed an increased risk of ischaemic stroke compared with no intracranial stenosis (adjusted hazard ratio 1·43, 95% CI 1·04-1·96), the risk of same-territory ischaemic stroke in patients with 70-99% symptomatic intracranial stenosis tended to be less than those reported in the non-stenting groups of the previous trials (1-year risk 5·6% [95% CI 0·0-13·0] vs 9·4% [3·1-20·7] in VISSIT; 2-year risk 5·6% [0·0-13·0] vs 14·1% [10·1-19·4] in SAMMPRIS). INTERPRETATION: The prevalence of 50-99% symptomatic intracranial stenosis increases steeply with age in predominantly Caucasian patients with transient ischaemic attack and minor ischaemic stroke. However, the risk of recurrent stroke on intensive medical treatment of symptomatic intracranial stenosis is consistent with the two previous randomised controlled trials in younger cohorts, supporting the generalisability of the trial results to routine practice. FUNDING: Wellcome Trust, Wolfson Foundation, British Heart Foundation, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, Association of British Neurologists.

Ten-year risks of recurrent stroke, disability, dementia and cost in relation to site of primary intracerebral haemorrhage: population-based study.

BACKGROUND: Patients with primary intracerebral haemorrhage (ICH) are at increased long-term risks of recurrent stroke and other comorbidities. However, available estimates come predominantly from hospital-based studies with relatively short follow-up. Moreover, there are also uncertainties about the influence of ICH location on risks of recurrent stroke, disability, dementia and quality of life. METHODS: In a population-based study (Oxford Vascular Study/2002-2018) of patients with a first ICH with follow-up to 10 years, we determined the long-term risks of recurrent stroke, disability, quality of life, dementia and hospital care costs stratified by haematoma location. RESULTS: Of 255 cases with primary ICH (mean/SD age 75.5/13.1), 109 (42.7%) had lobar ICH, 144 (56.5%) non-lobar ICH and 2 (0.8%) had uncertain location. Annual rates of recurrent ICH were higher after lobar versus non-lobar ICH (lobar=4.0%, 2.7-7.2 vs 1.1%, 0.3-2.8; p=0.02). Moreover, cumulative rate of dementia was also higher for lobar versus non-lobar ICH (n/% lobar=20/36.4% vs 16/20.8%, p=0.047), and there was a higher proportion of disability at 5 years in survivors (15/60.0% vs 9/31.0%, p=0.03). The 10-year quality-adjusted life years (QALYs) were also lower after lobar versus non-lobar ICH (2.9 vs 3.8 for non-lobar, p=0.04). Overall, the mean 10-year censor-adjusted costs were £19 292, with over 80% of costs due to inpatient hospital admission costs, which did not vary by haematoma location (p=0.90). CONCLUSION: Compared with non-lobar ICH, the substantially higher 10-year risks of recurrent stroke, dementia and lower QALYs after lobar ICH highlight the need for more effective prevention for this patient group.

Prodromal headache in MOG-antibody positive optic neuritis.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody (MOG-Ab) disease is an inflammatory autoimmune condition of the central nervous system, defined by antibodies (Abs) against MOG. Of the various clinical phenotypes optic neuritis (ON) is the commonest. We have observed that some patients with MOG-Ab ON present with a severe associated headache. OBJECTIVE: To highlight the importance of headache in MOG-Ab related optic neuritis. METHODS: Clinical and MRI data from MOG-Ab patients with ON (n = 129) were obtained from observational cohort studies and clinical notes at the NeuroCure Clinical Research Center, Charité Berlin and at the Diagnostic and Advisory Service for Neuromyelitis Optica, John Radcliffe Hospital, Oxford. RESULTS: Sixty-four of 129 MOG-Ab patients (49.6%) reported ≥1 headache-related ON. Headache usually started a few days prior to visual loss and extended from the ocular region to the periorbital and fronto-temporal area, sometimes mimicking migraine. Of those, thirty-two patients (50%) reported severe headache. Two patients did not have headache. No headache history was recorded for 63 patients. MRIs performed acutely during headache-related MOG-Ab ON (n = 15) showed anterior ON with extensive swelling and edema of the optic nerve/s in all patients, either unilaterally (n = 5) or bilaterally (n = 10). Peri-optic cerebro-spinal fluid (CSF) was undetectable due to the inflammatory extension in 12 out of 15 patients. CONCLUSION: Our findings indicate that acute MOG-Ab ON shows florid intra-orbital and peri­optic inflammation, likely to involve meninges and nociceptive fibers around the optic nerve. This may explain the frequent and often severe headache that precedes the visual deficit, sometimes misdiagnosed as migraine.

Comparison of Clinical Outcomes of Transverse Myelitis Among Adults With Myelin Oligodendrocyte Glycoprotein Antibody vs Aquaporin-4 Antibody Disease.

Importance: Recognizing the differences between transverse myelitis (TM) associated with myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) disease vs aquaporin-4 (AQP4)-Ab disease and prognosticating patients within each group may be an important factor for better clinical treatment for these respective patients. Objectives: To compare the clinical and radiological findings of the first TM episode in patients with MOG-Ab disease vs patients with AQP4-Ab disease and to assess factors associated with worse outcomes and relapse risk. Design, Setting, and Participants: This retrospective cross-sectional study used data collected from the Oxford Neuromyelitis Optica Service database, a national service that serves the south of England, including detailed clinical data, and high-quality imaging from within 4 weeks of the first TM episode from patients with MOG-Ab disease or AQP4-Ab disease and a confirmed history of TM from April 2018 to January 2019. Data analyses were conducted from February 2019 to April 2019. Main Outcomes and Measures: Onset features of each condition measured using the Expanded Disability Status Scale (EDSS) score, time to an EDSS score of 6, time to relapse, and residual sphincter dysfunction at least 6 months after the first TM episode and at last follow-up. Results: The total cohort included 115 adult patients, including 46 patients with MOG-Ab disease and 69 patients with AQP4-Ab disease. Patients with AQP4-Ab disease, compared with patients with MOG-Ab disease, tended to be older at onset of disease (mean [SD] age, 48.5 [14.9] years vs 33.7 [1.2] years) and female (57 [83%] women vs 24 [52%] women). Transverse myelitis occurred at onset of disease for 32 patients (70%) with MOG-Ab disease and 57 patients (78%) with AQP4-Ab disease. Onset severity did not differ between groups. An acute disseminated encephalomyelitis-like presentation occurred at the time of the TM in 4 patients (9%) with MOG-Ab disease but no patients with AQP4-Ab disease. Compared with patients with AQP4-Ab disease, patients with MOG-Ab disease were more likely to have short cord lesions (22 patients [48%] vs 10 patients [15%]; P < .001) and multiple cord lesions (18 patients [39%] vs 7 patients [10%]; P < .001). Approximately 50% of patients with MOG-Ab disease had only short cord lesions when the TM occurred as a relapse. Median (range) recovery EDSS score was lower in patients with MOG-Ab disease than patients with AQP4-Ab disease (1.8 [1.0-8.0] vs 3.0 [1.0-8.0]). Persistent bladder dysfunction associated with an increased prevalence of conus lesions occurred more frequently in patients with MOG-Ab disease than in patients with AQP4-Ab disease (27 patients [59%] vs 33 patients [48%]). Long-term catheter requirement was roughly equal between groups (9 patients [20%] vs 16 patients [23%]). Relapses after TM occurred in 17 patients with MOG-Ab disease (37%) and 36 patients with AQP4-Ab disease (52%). Concomitant brainstem lesions in patients with MOG-Ab disease were associated with a higher mean (SD) EDSS score at recovery (3.5 [2.3] vs 1.4 [0.9]; P < .001). In patients with AQP4-Ab disease, those younger than 50 years were more likely to relapse (27 of 36 patients aged <50 years [75%] vs 9 of 33 patients aged ≥50 years [27%]; P < .001) and those 50 years and older were more likely to reach an EDSS score of 6 (19 of 33 patients aged ≥50 years [58%] vs 11 of 36 patients aged <50 years [31%]; P = .03). Conclusions and Relevance: This study found that in patients who experienced a TM episode, short and multiple lesions at onset were more common in those with MOG-Ab disease than among those with AQP4-Ab disease. The presence of a brainstem lesion at the time of a TM episode in patients with MOG-Ab disease was associated with a worse recovery. In patients with AQP4-Ab disease, those 50 years and older at disease onset had more disability, and those younger than 50 years at disease onset had more relapses.

Vertebral artery stenting to prevent recurrent stroke in symptomatic vertebral artery stenosis: the VIST RCT.

BACKGROUND: Symptomatic vertebral artery (VA) stenosis has been associated with a markedly increased early risk of recurrent stroke. VA stenosis can be treated with stenting; however, there are few data from randomised controlled trials evaluating the efficacy of this treatment, and recent studies in intracranial stenosis have suggested that stenting may be associated with increased risk. OBJECTIVE: The Vertebral artery Ischaemia Stenting Trial (VIST) was established to compare the risks and benefits of vertebral angioplasty and stenting with best medical treatment (BMT) alone for recently symptomatic VA stenosis. DESIGN: VIST was a prospective, randomised, open, parallel, blinded end-point clinical trial. SETTING: The trial was performed in 14 hospitals in the UK. PARTICIPANTS: Recruitment began on 23 October 2008 and follow-up ended on 1 March 2016, by which time every patient had been followed up for at least 1 year. Participants had to have symptomatic vertebral stenosis of at least 50% resulting from presumed atheromatous disease. Both patients and clinicians were aware of treatment allocation; however, an independent adjudication committee, masked to treatment allocation, assessed all primary and secondary end points. INTERVENTIONS: Participants were randomly assigned (1 : 1) to either vertebral angioplasty/stenting plus BMT (n = 91) or BMT alone (n = 88). A total of 182 patients were initially enrolled; however, three patients (two who withdrew after randomisation and one who did not attend after the initial randomisation visit) did not contribute any follow-up data and were excluded. None of these three patients had outcome events. MAIN OUTCOMES AND MEASURES: The primary end point was the occurrence of fatal or non-fatal stroke in any arterial territory during follow-up. RESULTS: The median follow-up was 3.5 (interquartile range 2.1-4.7) years. Of the 61 patients who were stented, 48 (78.7%) had extracranial stenosis and 13 (21.3%) had intracranial stenosis. No perioperative complications occurred with extracranial stenting; two strokes occurred during intracranial stenting. The primary end point occurred in five patients (including one fatal stroke) in the stent group and in 12 patients (including two fatal strokes) in the medical group (giving a hazard ratio of 0.40, 95% confidence interval 0.14 to 1.13; p = 0.08), with an absolute risk reduction of 25 strokes per 1000 person-years. LIMITATIONS: The study was underpowered because it failed to reach target recruitment. The high rate of non-confirmation of stenosis in the stented group of the trial was a second limitation. CONCLUSIONS: The trial found no difference in risk of the primary end point between the two groups. FUTURE: Post hoc analysis suggested that stenting could be associated with a reduced recurrent stroke risk in symptomatic VA and further studies are now required to confirm these findings, particularly in extracranial VA stenosis where complication rates with stenting were confirmed to be very low. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95212240. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 41. See the NIHR Journals Library website for further project information. In addition, funding for the pilot phase was provided by the Stroke Association.

About one-quarter of all strokes occur in the back of the brain, which is supplied by the vertebral and basilar arteries. An important cause of stroke is a narrowing, or stenosis, of these arteries. It is known that patients who have a minor stroke due to narrowing of a vertebral artery (VA) have a high risk of a further stroke: as much as 30% in the next year. Stenosis of the VA can be treated with stenting, in which a wire mesh is put into the narrowed artery and opens it up. Many operations to insert a vertebral stent have been carried out worldwide with good technical results; however, it is not known whether it is better to treat vertebral stenosis with stenting or only tablets. The Vertebral artery Ischaemia Stenting Trial was a randomised controlled trial comparing vertebral stenting and best medical treatment (BMT) with BMT alone in patients who had suffered a minor stroke due to vertebral stenosis. Ninety-one patients had stenting and 88 had BMT alone. Patients were followed for an average of 3.5 years. It was planned to enrol 540 patients to the trial, but recruitment was slower than expected and funding for the study was halted; therefore, recruitment was stopped at 181 patients. There was no difference in the rate of recurrent stroke between patients who had stenting and those who had BMT alone. There was some evidence that stenting might be associated with a reduced risk of recurrent stroke, but the difference was not significant. The trial was limited by the failure to recruit the anticipated sample size. The results tell us that stenting is a possible treatment for vertebral stenosis; however, further trials are required to determine whether or not it is more effective at preventing recurrent stroke than BMT alone.

Stenting for symptomatic vertebral artery stenosis: a preplanned pooled individual patient data analysis.

BACKGROUND: Symptomatic vertebral artery stenosis is associated with a high risk of recurrent stroke, with higher risks for intracranial than for extracranial stenosis. Vertebral artery stenosis can be treated with stenting with good technical results, but whether it results in improved clinical outcome is uncertain. We aimed to compare vertebral stenting with medical treatment for symptomatic vertebral stenosis. METHODS: We did a preplanned pooled individual patient data analysis of three completed randomised controlled trials comparing stenting with medical treatment in patients with symptomatic vertebral stenosis. The primary outcome was any fatal or non-fatal stroke. Analyses were performed for vertebral stenosis at any location and separately for extracranial and intracranial stenoses. Data from the intention-to-treat analysis were used for all studies. We estimated hazard ratios (HRs) with 95% CIs using Cox proportional-hazards regression models stratified by trial. FINDINGS: Data were from 354 individuals from three trials, including 179 patients from VIST (148 with extracranial stenosis and 31 with intracranial stenosis), 115 patients from VAST (96 with extracranial stenosis and 19 with intracranial stenosis), and 60 patients with intracranial stenosis from SAMMPRIS (no patients had extracranial stenosis). Across all trials, 168 participants (46 with intracranial stenosis and 122 with extracranial stenosis) were randomly assigned to medical treatment and 186 to stenting (64 with intracranial stenosis and 122 with extracranial stenosis). In the stenting group, the frequency of periprocedural stroke or death was higher for intracranial stenosis than for extracranial stenosis (ten (16%) of 64 patients vs one (1%) of 121 patients; p<0·0001). During 1036 person-years of follow-up, the hazard ratio (HR) for any stroke in the stenting group compared with the medical treatment group was 0·81% CI 0·45-1·44; p=0·47). For extracranial stenosis alone the HR was 0·63 (95% CI 0·27-1·46) and for intracranial stenosis alone it was 1·06 (0·46-2·42; pinteraction=0·395). INTERPRETATION: Stenting for vertebral stenosis has a much higher risk for intracranial, compared with extracranial, stenosis. This pooled analysis did not show evidence of a benefit for stroke prevention for either treatment. There was no evidence of benefit of stenting for intracranial stenosis. Stenting for extracranial stenosis might be beneficial, but further larger trials are required to determine the treatment effect in this subgroup. FUNDING: None.

Prognostic value of "tissue-based" definitions of TIA and minor stroke: Population-based study.

OBJECTIVE: Since use of diffusion-weighted imaging (DWI) positivity in the "tissue-based" definition of stroke in patients with a clinical TIA is supported by the high associated 90-day risk of recurrent stroke, we aimed to determine long-term prognostic significance, stratified by etiologic subtype, and whether the same tissue-based distinction is predictive in minor strokes. METHODS: Consecutive eligible patients with TIA or minor stroke (NIH Stroke Scale [NIHSS] ≤3) in the population-based Oxford Vascular Study underwent brain MRI at baseline. Stroke risk on 10-year follow-up was stratified by NIHSS (0/1 vs 2/3) and Trial of Org 10172 in Acute Stroke Treatment classification of the initial event. RESULTS: Among 1,033 patients (633 TIA; 400 minor stroke), 248 (24.0%) had acute lesions on DWI (13.9% of TIAs; 40.0% of minor strokes). A positive DWI was associated with an increased 10-year risk of recurrent ischemic stroke after an index TIA (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.28-5.54, p = 0.009) or a stroke with NIHSS 0-1 (3.03, 1.29-7.08, p = 0.011), but not after a stroke with NIHSS 2-3 (0.70, 0.24-2.10, p = 0.53). Ischemic stroke risk after DWI-positive TIA was at least equivalent to that after DWI-negative stroke (1.81, 0.82-4.00, p = 0.14). Among all patients, DWI positivity was most predictive of 10-year risk after cryptogenic events (4.68, 1.70-12.92, p = 0.003). CONCLUSION: DWI positivity is associated with an increased long-term risk of recurrent stroke after TIA and minor stroke, supporting a tissue-based definition of minor stroke as well as TIA. Prognostic value is greatest after cryptogenic events.

Treatment of broad-based intracranial aneurysms with low profile braided stents: a single center analysis of 101 patients.

BACKGROUND AND PURPOSE: Low profile braided stents have facilitated the endovascular treatment of broad-based intracranial aneurysms. METHODS: Between 2013 and June 2018, we attempted 104 Leo baby stent placements in 101 patients. Locations were the anterior communicating artery (AcomA) (37 aneurysms, 35.6%), middle cerebral artery (MCA) bifurcation (29 aneurysms, 27.9%) and basilar artery (23aneurysms, 22.1%). Mean neck size was 4.9 mm (2.2-8.2). 60 aneurysms were incidental, 31 of 37 recurrent aneurysms had ruptured before. RESULTS: Stent deployment was successful in 89.4% of cases. Common reasons for failure were inability to access the parent artery (n=5) or to deploy the stent across the aneurysm neck (n=4). Two patients had poor outcomes within 24 hours. One patient developed a brain hemorrhage caused by guide wire perforation (MRS 5), the other an early thrombotic stent occlusion (MRS 4). No patient died. Nine (8.7%) patients experienced transient neurological deficits with ischemic lesions on diffusion weighted imaging (DWI). Initially Raymond-Roy class 1 occlusion was achieved in 23 aneurysms (24.7%), class 2 occlusion in 40 (43%), class 3a occlusion in 14 (15.0%), and 3b occlusion in 16 aneurysms (17.2%). Follow-up imaging in 87 patients showed stable or improved occlusion grades in 76%. Six patients required retreatment while the rest were managed conservatively. Four delayed stent occlusions occurred in three patients, with severe morbidity in one patient (MRS 5). There were no aneurysm ruptures or deaths. CONCLUSION: Stent assisted treatment of broad-based aneurysms with the Leo baby stent is safe and effective. The frequency of delayed thrombotic complications is low and similar to other stents.

Endovascular treatment of patients with high-risk symptomatic intracranial vertebrobasilar stenoses: long - term outcomes.

Background and purpose: We present the long-term outcome after endovascular treatment of symptomatic intracranial posterior circulation stenoses. Methods: 30 patients with symptomatic intracranial posterior circulation stenoses exceeding 70% underwent endovascular treatment between 2006 and 2012. Data regarding presentation, follow-up, procedure details, complications and imaging follow-up were reviewed. All surviving patients underwent a phone interview to establish their current Modified Ranking Scales (MRS). Results: Stenoses of the intracranial vertebral artery (24 patients) and basilar artery (6 patients) were treated with stents (10 patients), angioplasty alone (13 patients) or both (5 patients). Two procedures failed. One patient (3.3%) died after the procedure, two had stroke (6.6%) and one a subarachnoid haemorrhage without ensuing deficit. Two patients (6.7%) had asymptomatic complications (dissection and pseudoaneurysm). The median clinical follow-up time was 7 years. Of the 29 patients who survived the procedure, 6 died due to unrelated causes. Three patients (10%) had recurrent strokes and two (6.7%) a transient ischaemic attack in the posterior circulation. Two patients had subsequent middle cerebral artery strokes. Five (16.7%) patients had recurrent stenoses and three (10%) occlusions of the treated artery. Retreatment was performed in six patients, three (10%) with PTA and three (10%) with stenting. Current MRS scores were as follows: nine MRS 0, eight MRS 1, four MRS 2 and one MRS 4. Conclusions: Long-term follow-up after endovascular treatment of high-risk symptomatic intracranial posterior circulation stenoses shows few stroke recurrences. Treatment of intracranial vertebral artery stenosis may be beneficial in appropriately selected patients.

Long-Term Premorbid Blood Pressure and Cerebral Small Vessel Disease Burden on Imaging in Transient Ischemic Attack and Ischemic Stroke.

Background and Purpose- Studies of causes of cerebral small vessel disease (SVD) should fully adjust for blood pressure (BP), but most etiological studies use a single BP measurement or history of hypertension, which might underestimate the role of hypertension. In patients with transient ischemic attack and ischemic stroke, we therefore compared the associations of baseline and long-term premorbid BP with measures of SVD on magnetic resonance imaging brain. Methods- We studied 1009 transient ischemic attack/ischemic stroke patients who had a brain magnetic resonance imaging, in the population-based OXVASC (Oxford Vascular Study), and related baseline and 20-year premorbid BP (median: 15 readings/patient) to the total SVD score on imaging. Results- SVD score was associated with increasing mean baseline systolic BP (SBP; odds ratio of top versus bottom BP quartile: 2.28; [95% CI, 1.62-3.21]; P<0.0001) and with prior hypertension (2.53; [95% CI, 2.01-3.20]; P<0.0001), but the association was much stronger with mean premorbid SBP (6.09; [95% CI, 4.34-8.55]; P<0.0001). Mean diastolic BP at baseline was negatively associated with SVD score (0.71; [95% CI, 0.51-1.00]; P=0.050), and a positive association was only evident for diastolic BP 10 to 20 years previously (3.35; [95% CI, 2.33-4.84]; both P<0.0001). Relationships between overall mean premorbid BP and SVD burden were strongest in patients age <70 (SBP: 6.99; 4.11-11.86; diastolic BP: 3.13; 1.95-5.07; both P<0.0001) versus ≥70 years (2.37; 1.42-3.94; P=0.001; and 1.16; 0.74-1.84; P=0.52). Conclusions- Mean premorbid SBP is more strongly associated with SVD burden than baseline SBP or history of hypertension, and baseline diastolic BP yields a misleading estimate of the likely etiological importance of midlife hypertension for the subsequent development of SVD. Studies of novel potential etiological factors for SVD should aim to adjust for long-term prior BP, and trials of BP lowering with only a few years of follow-up may underestimate the overall impact on SVD.

Age and sex-specific associations of carotid pulsatility with small vessel disease burden in transient ischemic attack and ischemic stroke.

Background Although large artery stiffness has been implicated in the pathogenesis of cerebral small vessel disease, whether carotid pulsatility, a convenient surrogate marker of arterial stiffness, is similarly associated with global burden of small vessel disease is unknown. Aims To determine the age and sex-specific associations of carotid pulsatility with global burden of small vessel disease. Methods We studied consecutive patients with transient ischemic attack or non-disabling ischemic stroke from the Oxford Vascular Study who had a brain MRI and carotid duplex ultrasound during 2002-2014. We determined clinical correlates of common carotid artery (CCA) and internal carotid artery (ICA) pulsatility index (PI) and their associations with the total small vessel disease score on MRI, stratified by age (median = 72). Results In 587 patients, correlates of CCA and ICA-PI were both independently associated with age, diabetes, and premorbid mean pulse pressure after adjustment for age, sex, and cardiovascular risk factors (all p < 0.05). ICA-PI was strongly associated with small vessel disease markers and burden, particularly lacunes, in patients aged<70 (age and sex-adjusted odds ratio of top vs. bottom pulsatility index quartile: 5.35, 1.95-14.70, p = 0.001; increasing small vessel disease score: 2.30, 1.01-5.25, p = 0.048), but not in patients aged ≥ 70 ( p > 0.05). No associations between CCA-PI with small vessel disease score were noted at any age. In 94 consecutive patients who also received transcranial Doppler ultrasound, strong associations between middle cerebral artery (MCA)-PI and an increasing small vessel disease score were noted (unadjusted OR-MCA: 4.26, 1.45-12.55, p = 0.009; ICA: 2.37, 0.81-6.87, p = 0.11; CCA: 1.33, 0.45-3.96, p=0.61). Conclusions ICA and MCA-PI are associated with global small vessel disease burden, especially in individuals aged<70 and may be causally related.