Uncommon causes of ischaemic stroke: how to approach the diagnosis.

Stroke is a common neurological emergency and although most cases are associated with traditional vascular risk factors leading to cerebral ischaemia by well-recognised pathophysiological mechanisms, around 4% of ischaemic strokes are due to rare conditions. These are important to recognise due to their different management, which is often specific and effective, and due to their different prognosis from otherwise cryptogenic ischaemic strokes. We outline a practical approach to identifying uncommon causes of ischaemic stroke by highlighting diagnostic 'red flags' and propose a structured approach to investigating them.

Intracranial arterial stenosis in Caucasian versus Chinese patients with TIA and minor stroke: two contemporaneous cohorts and a systematic review.

BACKGROUND: Intracranial arterial stenosis (ICAS) is an important cause of stroke worldwide. Separate reports in Caucasians and Asians with stroke/transient ischaemic attack (TIA) have suggested lower ICAS prevalence in Caucasians, but there has been no direct comparisons of the two ethnic groups with the same criteria to define ICAS. METHODS: Acute minor stroke or TIA patients in two cohorts respectively recruiting patients in Oxford (2011-2018, predominantly Caucasians) and Hong Kong (2011-2015, predominantly Chinese) were compared. ICAS was defined as ≥50% stenosis/occlusion in any major intracranial artery in MR/CT angiography. Prevalence, distribution and risk factors of ICAS were compared between the two cohorts. We also systematically reviewed literature on ICAS prevalence in stroke/TIA patients in different populations. RESULTS: Among 1287 patients from Oxford and 691 from Hong Kong (mean age 69 vs 66), ICAS prevalence was higher in Chinese than in Caucasians (43.0% vs 20.0%; OR 3.02; 95% CI 2.47 to 3.70; p<0.001), independent of age (age-adjusted OR 3.73; 95% CI 3.00 to 4.63; p<0.001) and vascular risk factors (multivariable-adjusted OR 3.21; 95% CI 2.56 to 4.02; p<0.001). This ethnic difference was greater (p interaction=0.005) at age <70 years (OR 5.33; 95% CI 3.79 to 7.50; p<0.001) than at ≥70 years (OR 2.81; 95% CI 2.11 to 3.74; p<0.001). ICAS prevalence increased with age and with vascular risk factors in both cohorts, with equivalent prevalence in Chinese aged <60 years and Caucasians aged ≥80, and in Chinese with no vascular risk factor and Caucasians with two vascular risk factors. ICAS locations also differed between Chinese and Caucasian patients. CONCLUSIONS: Chinese are more susceptible to ICAS than Caucasians, with an earlier onset age and a higher prevalence, independent of vascular risk factors.

Prevalence, prognosis, and treatment of atherosclerotic intracranial stenosis in Caucasians.

BACKGROUND: Intracranial atherosclerotic stenosis is a highly prevalent cause of stroke worldwide with important ethnic disparities. Widely considered to be a common cause of stroke in Asian and Afro-Caribbean populations, relatively less is known about the burden and significance of intracranial atherosclerotic stenosis in Caucasians. AIMS: We aim to highlight recent insights and advances into the prevalence, prognosis, and treatment of symptomatic and asymptomatic atherosclerotic intracranial atherosclerotic stenosis in Caucasian patients. SUMMARY OF REVIEW: We identified 48 articles studying intracranial atherosclerotic stenosis in Caucasian patients with ischemic stroke or transient ischemic attack. Most studies were on hospital-based cohorts of consecutive patients and half were graded as "fair" quality. There was significant variation between studies in the definition of intracranial atherosclerotic stenosis and in the imaging modalities used to detect intracranial atherosclerotic stenosis. Overall, 12.1% of Caucasian patients were found to have any intracranial atherosclerotic stenosis, 6.4% symptomatic intracranial atherosclerotic stenosis and 11.1% asymptomatic intracranial atherosclerotic stenosis, with higher rates at older ages. In studies reporting prognosis, there were 61 and 10 same-territory ischemic strokes in 1000 person-years in patients with symptomatic and asymptomatic intracranial atherosclerotic stenosis, respectively. Percutaneous stenting and angioplasty have not proven superior to intensive medical management in patients with symptomatic intracranial atherosclerotic stenosis. CONCLUSIONS: Intracranial atherosclerotic stenosis has previously been neglected as a cause of stroke in Caucasians but is highly prevalent at older ages and frequently discovered with the growing use of noninvasive angiography. Intensive medical therapy is the treatment of choice, but there is a need to develop novel treatments or therapeutic approaches to lower the risk of stroke in higher risk patients.

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.

Diagnosis and management of acute ischaemic stroke.

Acute ischaemic stroke is a major public health priority and will become increasingly relevant to neurologists of the future. The cornerstone of effective stroke care continues to be timely reperfusion treatment. This requires early recognition of symptoms by the public and first responders, triage to an appropriate stroke centre and efficient assessment and investigation by the attending stroke team. The aim of treatment is to achieve recanalisation and reperfusion of the ischaemic penumbra with intravenous thrombolysis and/or endovascular thrombectomy in appropriately selected patients. All patients should be admitted directly to an acute stroke unit for close monitoring for early neurological deterioration and prevention of secondary complications. Prompt investigation of the mechanism of stroke allows patients to start appropriate secondary preventative treatment. Future objectives include improving accessibility to endovascular thrombectomy, using advanced imaging to extend therapeutic windows and developing neuroprotective agents to prevent secondary neuronal damage.

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.

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.

Oedema extension distance in intracerebral haemorrhage: Association with baseline characteristics and long-term outcome.

INTRODUCTION: Oedema extension distance is a derived parameter that may reduce sample size requirements to demonstrate reduction in perihaematomal oedema in early phase acute intracerebral haemorrhage trials. We aimed to identify baseline predictors of oedema extension distance and its association with clinical outcomes. PATIENTS AND METHODS: Using Virtual International Stroke Trials Archive-Intracerebral Haemorrhage, first Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial, and Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation II datasets, we calculated oedema extension distance at baseline and at 72 h measured using computed tomography. Using linear regression, we tested for associations between baseline characteristics and oedema extension distance at 72 h. Ordinal regression (underlying assumptions validated) was used to test for associations between oedema extension distance at baseline and 72 h and oedema extension distance change between baseline and 72 h, and modified Rankin scale scores at 90 days, adjusted for baseline and 72 h prognostic factors. RESULTS: There were 1028 intracerebral haemorrhage cases with outcome data for analyses. Mean (standard deviation, SD) oedema extension distance at 72 h was 0.54 (0.26) cm, and mean oedema extension distance difference from baseline (EED72-0) was 0.24 (0.18) cm. Oedema extension distance at 72 h was greater with increasing baseline haematoma volume and baseline oedema extension distance. Increasing age, lobar haemorrhage, and intraventricular haemorrhage were independently associated with EED72-0. In multifactorial ordinal regression analysis, EED72-0 was associated with worse modified Rankin scale scores at 90 days (odds ratio 1.96, 95% confidence interval 1.00-3.82). DISCUSSION: Increase in oedema extension distance over 72 h is independently associated with decreasing functional outcome at 90 days. Oedema extension distance may be a useful surrogate outcome measure in early phase trials of anti-oedema or anti-inflammatory treatments in intracerebral haemorrhage.

Is Unexplained Early Neurological Deterioration After Intravenous Thrombolysis Associated With Thrombus Extension?

BACKGROUND AND PURPOSE: Early neurological deterioration (END) after anterior circulation stroke is strongly associated with poor outcome. Apart from straightforward causes, such as intracerebral hemorrhage and malignant edema, the mechanism of END occurring after intravenous thrombolysis remains unclear in most instances. We tested the hypothesis that unexplained END is associated with thrombus extension. METHODS: From our database of consecutively thrombolysed patients, we identified anterior circulation stroke patients who had both admission and 24-hour T2* magnetic resonance imaging, visible occlusion on admission magnetic resonance angiography and no recanalization on 24-hour magnetic resonance angiography. END was defined as ≥4 National Institutes of Health Stroke Scale-point deterioration on 24-hour clinical assessment and unexplained END as END without clear cause. The incidence of susceptibility vessel sign extension on T2* imaging, defined as any new occurrence or extension of susceptibility vessel sign from admission to 24-hour follow-up magnetic resonance, was compared between patients with unexplained END and those without END. RESULTS: Of 120 eligible patients for the present study, 22 experienced unexplained END. Susceptibility vessel sign extension was present in 41 (34%) patients and was significantly more frequent in the unexplained END than in the no-END group (59% versus 29%, respectively; adjusted odds ratio=3.96; 95% confidence interval, 1.25-12.53; P=0.02). CONCLUSIONS: In this study, unexplained END occurring after thrombolysis was independently associated with susceptibility vessel sign extension, suggesting in situ thrombus extension or re-embolization. These findings strengthen the need to further investigate early post-thrombolysis administration of antithrombotics to reduce the risk of this ominous clinical event.

Software output from semi-automated planimetry can underestimate intracerebral haemorrhage and peri-haematomal oedema volumes by up to 41.

INTRODUCTION: Haematoma and oedema size determines outcome after intracerebral haemorrhage (ICH), with each added 10 % volume increasing mortality by 5 %. We assessed the reliability of semi-automated computed tomography planimetry using Analyze and Osirix softwares. METHODS: We randomly selected 100 scans from 1329 ICH patients from two centres. We used Hounsfield Unit thresholds of 5-33 for oedema and 44-100 for ICH. Three raters segmented all scans using both softwares and 20 scans repeated for intra-rater reliability and segmentation timing. Volumes reported by Analyze and Osirix were compared to volume estimates calculated using the best practice method, taking effective individual slice thickness, i.e. voxel depth, into account. RESULTS: There was excellent overall inter-rater, intra-rater and inter-software reliability, all intraclass correlation coefficients >0.918. Analyze and Osirix produced similar haematoma (mean difference: Analyze - Osirix = 1.5 ± 5.2 mL, 6 %, p ≤ 0.001) and oedema volumes (-0.6 ± 12.6 mL, -3 %, p = 0.377). Compared to a best practice approach to volume calculation, the automated haematoma volume output was 2.6 mL (-11 %) too small with Analyze and 4.0 mL (-18 %) too small with Osirix, whilst the oedema volumes were 2.5 mL (-12 %) and 5.5 mL (-25 %) too small, correspondingly. In scans with variable slice thickness, the volume underestimations were larger, -29%/-36 % for ICH and -29 %/-41 % for oedema. Mean segmentation times were 6:53 ± 4:02 min with Analyze and 9:06 ± 5:24 min with Osirix (p < 0.001). CONCLUSION: Our results demonstrate that the method used to determine voxel depth can influence the final volume output markedly. Results of clinical and collaborative studies need to be considered in the context of these methodological differences.

Oxidative phosphorylation and lacunar stroke: Genome-wide enrichment analysis of common variants.

OBJECTIVE: We investigated whether oxidative phosphorylation (OXPHOS) abnormalities were associated with lacunar stroke, hypothesizing that these would be more strongly associated in patients with multiple lacunar infarcts and leukoaraiosis (LA). METHODS: In 1,012 MRI-confirmed lacunar stroke cases and 964 age-matched controls recruited from general practice surgeries, we investigated associations between common genetic variants within the OXPHOS pathway and lacunar stroke using a permutation-based enrichment approach. Cases were phenotyped using MRI into those with multiple infarcts or LA (MLI/LA) and those with isolated lacunar infarcts (ILI) based on the number of subcortical infarcts and degree of LA, using the Fazekas grading. Using gene-level association statistics, we tested for enrichment of genes in the OXPHOS pathway with all lacunar stroke and the 2 subtypes. RESULTS: There was a specific association with strong evidence of enrichment in the top 1% of genes in the MLI/LA (subtype p = 0.0017) but not in the ILI subtype (p = 1). Genes in the top percentile for the all lacunar stroke analysis were not significantly enriched (p = 0.07). CONCLUSIONS: Our results implicate the OXPHOS pathway in the pathogenesis of lacunar stroke, and show the association is specific to patients with the MLI/LA subtype. They show that MRI-based subtyping of lacunar stroke can provide insights into disease pathophysiology, and imply that different radiologic subtypes of lacunar stroke subtypes have distinct underlying pathophysiologic processes.

Cerebral venous thrombosis-a primer for the haematologist.

Cerebral venous thrombosis (CVT) is a condition that can affect all age groups and can often be difficult to diagnose and treat. The difficulties in diagnosis are mainly due to the non-specific presenting features of CVT, which can range from isolated headache and visual or auditory problems, to serious symptoms such as hemiparesis and coma. Therefore, it can present to various specialists including general physicians, obstetricians and neurologists. In recent years, more widespread use of cerebral imaging has led to the diagnosis being made more often. Since thrombosis is the key component, haematologists are consulted in the management of these patients including for identification of a causative factor for CVT. In this regard, the pivotal International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) has shed more light on its epidemiology and management options. This review aims to provide guidance to haematologists when faced with a patient with CVT, based on the currently available evidence.

Incidence, predictors and clinical characteristics of orolingual angio-oedema complicating thrombolysis with tissue plasminogen activator for ischaemic stroke.

BACKGROUND: Orolingual angio-oedema is a recognised complication of tissue plasminogen activator (tPA) for ischaemic stroke. We investigated its incidence, clinical characteristics and relationship with other factors in patients receiving tPA at a UK centre. METHODS: 530 consecutive patients (median age 70 years) receiving tPA treatment for confirmed ischaemic stroke were included. Cases were defined as those developing angio-oedema within 24 h of initiation of tPA. Angio-oedema was retrospectively classified as mild, moderate or severe using predefined criteria. The primary analysis was the association between prior ACE inhibitor (ACE-I) treatment and angio-oedema. RESULTS: Orolingual angio-oedema was observed in 42 patients (7.9%; 95% CI 5.5% to 10.6%), ranging from 5 to 189 min after initiation of tPA (median 65 min). 12% of the angio-oedema cases were severe (1% of all patients treated with tPA), requiring urgent advanced airway management. 172 patients (33%) were taking ACE-I. In multifactorial analyses, only prior ACE-I treatment remained a significant independent predictor of angio-oedema (odds ratio (OR) 2.3; 95% CI 1.1 to 4.7). CONCLUSIONS: Angio-oedema occurs more frequently than previously reported and is associated with preceding ACE-I treatment. Angio-oedema may be delayed and progress to life-threatening airway compromise, which has implications for the assessment and delivery of thrombolysis.

MRI-visible perivascular spaces: relationship to cognition and small vessel disease MRI markers in ischaemic stroke and TIA.

BACKGROUND: MRI-visible perivascular spaces (PVS) are potential neuroimaging markers of cerebral small vessel disease, but their functional significance and mechanisms remain uncertain. We investigated the association between PVS and cognitive impairment, and other MRI markers of small vessel disease, in a patient cohort of ischaemic stroke/transient ischaemic attack (TIA) referrals. METHODS: Data were collected from a prospective observational database. Standardised detailed neuropsychological testing was performed. A validated visual rating scale on T2-weighted MRI was used to categorise PVS severity; validated scales were used to assess white matter hyperintensities (WMH), cerebral microbleeds (CMB) and lacunes. RESULTS: We included 246 patients (45.1% female, mean age 62 years). No significant association between PVS severity grade in any brain region and impairment in any cognitive domain was identified. In multivariable analysis, WMH and hypertension (but not age) were independently associated with basal ganglia PVS severity (OR: 1.27; p<0.0001 and OR: 4.89; p=0.013, respectively). Increasing PVS severity in the basal ganglia was associated with lacunar stroke subtype (p<0.0001). Age and hypertension (but not WMH or lacunar stroke subtype) were independently associated with centrum semiovale PVS severity (OR: 1.19; p=0.013 and OR: 3.71; p=0.007, respectively). CONCLUSIONS: PVS do not have an independent association with cognitive impairment in patients with ischaemic stroke or TIA. The associations with clinical-radiological factors are consistent with the hypothesis that PVS reflect cerebral small vessel disease; the different associations for basal ganglia and centrum semiovale PVS might indicate different underlying small vessel arteriopathies according to PVS anatomical distribution, but this requires further study.

Symptomatic lobar intracerebral haemorrhage preceded by transient focal neurological episodes.

We report the case of a symptomatic intracerebral haemorrhage (ICH) in an elderly woman, secondary to cerebral amyloid angiopathy (CAA), and present the relevant imaging. A few months before, our patient experienced multiple, stereotyped, brief episodes of spreading paraesthesias, which were considered to be transient ischaemic attacks (TIAs) and treated with antithrombotic agents. In this case report, we explore CAA, a highly prevalent but under-recognised form of small vessel cerebrovascular disease and common cause of ICH. We then briefly discuss the clinical significance of transient focal neurological episodes in the context of CAA, as potential warning signs of future ICH. An important clinical message is that misdiagnosis of CAA-related focal neurological symptoms as TIAs (and prescribing antithrombotic drugs) could lead to potentially avoidable ICH. We also provide the current evidence base for the acute and secondary prevention treatment of patients with lobar ICH attributed to CAA, and discuss the prognosis.