Hypereosinophilia and acute bilateral facial palsy: an unusual presentation of a common disease.

A 60-year-old man presented with an acute, pruritic, erythematous rash associated with marked hypereosinophilia (2.34×10(9)/l (0.04-0.40)). There was eosinophilic infiltration on hepatic, bone marrow and lymph node biopsies, with multiple lung nodules and mild splenomegaly. However, extensive investigation excluded parasitic or bacterial causes, specific allergens or the Fip1L1 mutation seen in myeloproliferative hypereosinophilia. Six months into the illness, he developed an acute, left, complete lower motor neurone facial palsy over hours, and an acute right lower motor neurone facial palsy 2 weeks later, without recovery. Over the subsequent 3 months, he developed complex partial seizures, a transient 72-h non-epileptic encephalopathy and episodic vertigo with ataxia. Further investigation showed bilateral enhancement of the VII nerves and labyrinthis on gadolinium-enhanced MR brain scan, cerebrospinal fluid lymphocytosis and neurophysiological evidence of polyradicolopathy. His eosinophil count fell with corticosteroids, hydroxycarbamide, imatinib and ultimately mepolezumab, but without symptomatic improvement. Repeat lymph node biopsy showed Kaposi's sarcoma, leading to a diagnosis of HIV-1 infection with a modestly reduced CD4 count of 413×10(6)/l (430-1690). Hypereosinophila and eosinophilic folliculitis are recognised features of advanced HIV infection, and transient bilateral facial palsy occasionally occurs at the time of seroconversion. This is the first report of a chronic bilateral facial palsy likely due to primary HIV infection, not occurring during seroconversion and in association with hypereosinophilia. This case emphasises the protean manifestations of HIV infection and the need for routine testing in atypical clinical presentations.

Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies.

BACKGROUND AND PURPOSE: Cerebral microbleeds (MB) are potential risk factors for intracerebral hemorrhage (ICH), but it is unclear if they are a contraindication to using antithrombotic drugs. Insights could be gained by pooling data on MB frequency stratified by antithrombotic use in cohorts with ICH and ischemic stroke (IS)/transient ischemic attack (TIA). METHODS: We performed a systematic review of published and unpublished data from cohorts with stroke or TIA to compare the presence of MB in: (1) antithrombotic users vs nonantithrombotic users with ICH; (2) antithrombotic users vs nonusers with IS/TIA; and (3) ICH vs ischemic events stratified by antithrombotic use. We also analyzed published and unpublished follow-up data to determine the risk of ICH in antithrombotic users with MB. RESULTS: In a pooled analysis of 1460 ICH and 3817 IS/TIA, MB were more frequent in ICH vs IS/TIA in all treatment groups, but the excess increased from 2.8 (odds ratio; range, 2.3-3.5) in nonantithrombotic users to 5.7 (range, 3.4-9.7) in antiplatelet users and 8.0 (range, 3.5-17.8) in warfarin users (P difference=0.01). There was also an excess of MB in warfarin users vs nonusers with ICH (OR, 2.7; 95% CI, 1.6-4.4; P<0.001) but none in warfarin users with IS/TIA (OR, 1.3; 95% CI, 0.9-1.7; P=0.33; P difference=0.01). There was a smaller excess of MB in antiplatelet users vs nonusers with ICH (OR, 1.7; 95% CI, 1.3-2.3; P<0.001), but findings were similar for antiplatelet users with IS/TIA (OR, 1.4; 95% CI, 1.2-1.7; P<0.001; P difference=0.25). In pooled follow-up data for 768 antithrombotic users, presence of MB at baseline was associated with a substantially increased risk of subsequent ICH (OR, 12.1; 95% CI, 3.4-42.5; P<0.001). CONCLUSIONS: The excess of MB in warfarin users with ICH compared to other groups suggests that MB increase the risk of warfarin-associated ICH. Limited prospective data corroborate these findings, but larger prospective studies are urgently required.

An urgent access neurovascular clinic: audit of timeliness.

This study aimed to evaluate timeliness of an outpatient urgent access neurovascular clinic in a district general hospital setting through an audit of delay from event to completion of evaluation following transient ischaemic attack (TIA) or minor stroke. Participants included those referred for evaluation of suspected TIA or minor stroke. The median delay from event to completion was 16 days, with 45% seen within two weeks of symptom onset, and 15% within one week of symptom onset. A weekly TIA clinic is not capable of achieving the National Clinical Guidelines for Stroke recommendation for evaluation within one week of symptoms. This audit supports the National Stroke Strategy recommendation for immediate evaluation of patients presenting with a recent TIA or minor stroke.

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.

Reliability of clinical diagnosis of the symptomatic vascular territory in patients with recent transient ischemic attack or minor stroke.

BACKGROUND AND PURPOSE: Knowledge of the vascular territory of a recent transient ischemic attack or minor stroke determines appropriate investigations and the need for territory-specific interventions such as endarterectomy and stenting. However, there are few published data on the accuracy of clinical assessment of the vascular territory. METHODS: We studied agreement of clinical diagnosis of vascular territory in consecutive patients with transient ischemic attack or minor stroke with diffusion-weighted MRI who had an acute ischemic lesion(s) in a single vascular territory (determined by a neuroradiologist). Three independent neurologists (one had seen the patients, the others had a clinical summary) diagnosed the most likely vascular territory (carotid or vertebrobasilar) for each patient blind to brain imaging. RESULTS: One hundred thirty-three (28.0%) of 476 patients had a high signal lesion on diffusion-weighted imaging of whom 115 (86.5%) had a minor stroke and 18 (13.5%) a transient ischemic attack. Interobserver agreement (kappa statistic) on the territory ranged from 0.46 to 0.60. The agreement with diffusion-weighted imaging was only moderate (observer 1: kappa=0.54, 95% CI=0.36 to 0.72; observer 2: 0.48, 0.31 to 0.64; observer 3: 0.48, 0.28 to 0.67). Only the presence of visual symptoms improved the accuracy of the vascular territory diagnosis (range of kappa: 0.63 to 0.77) but not the presence of motor, speech, or sensory symptoms. Sensitivity and specificity for the diagnosis of vertebrobasilar territory ranged between 54.2% and 70.8% and 84.4% to 91.7%, respectively. CONCLUSIONS: The reliability of clinical diagnosis of the vascular territory is only moderate, highlighting the importance of sensitive brain imaging after transient ischemic attack or minor stroke. Further imaging-based research is required to determine the optimal clinical diagnostic criteria for classification of the vascular territory.

Systematic review of associations between the presence of acute ischemic lesions on diffusion-weighted imaging and clinical predictors of early stroke risk after transient ischemic attack.

BACKGROUND AND PURPOSE: Early risk of stroke after a transient ischemic attack can be reliably predicted with risk scores based on clinical features of the patient and of the ischemic event, but it is unclear how these features correlate with findings on brain imaging. METHODS: We performed a systematic review of the literature and identified all previous studies which reported patient characteristics and the nature of transient ischemic attack symptoms in relation to appearances on diffusion-weighted imaging (DWI). We then performed a meta-analysis of the associations between the components of the risk scores and positive DWI. Authors were contacted for additional unpublished data. RESULTS: Nineteen studies were identified by the systematic review, and additional unpublished data were obtained from 11 of these studies. On meta-analysis, several components of the risk scores were associated with positive DWI, including symptom duration > or =60 minutes (13 studies, odds ratio [OR], 1.50; 95% CI, 1.16 to 1.96; P=0.004), dysphasia (9 studies, OR, 2.25; 95% CI, 1.57 to 3.22; P<0.001), dysarthria (8 studies, OR, 1.73; 95% CI, 1.11 to 2.68; P=0.03) and motor weakness (9 studies, OR, 2.20; 95% CI, 1.56 to 3.10; P<0.001). However patient age, sex, hypertension and diabetes were not associated with the presence of DWI lesions. From an etiologic perspective, atrial fibrillation (9 studies, OR, 2.75; 95% CI, 1.78 to 4.25; P<0.001) and ipsilateral > or =50% carotid stenosis (10 studies, OR, 1.93; 95% CI, 1.34 to 2.76; P=0.001) were associated with positive DWI. CONCLUSIONS: Presence of acute ischemic lesions on DWI correlates with several clinical features known to predict stroke risk after transient ischemic attack. Large studies (sample size >1000) will therefore be required to determine the independent prognostic value of DWI and its interactions with these clinical characteristics.

Diffusion-weighted MRI in 300 patients presenting late with subacute transient ischemic attack or minor stroke.

BACKGROUND AND PURPOSE: Many patients with transient ischemic attack (TIA) or minor stroke present to medical attention after a delay of several days or weeks, at which time it may be more difficult to obtain a clear history and clinical signs may have resolved. Because ischemic lesions on diffusion-weighted MRI (DWI) often persist for several weeks, we hypothesized that adding DWI to a standard protocol with T2-weighted imaging might be useful in the management of patients presenting late. METHODS: We studied consecutive patients with TIA or minor stroke presenting > or =3 days after the event. Two independent observers recorded the presence or absence of recent ischemic lesions on 2 different occasions, first with the T2 scan only, and second with T2 and DWI. Each time, with the aid of a written clinical summary, the observers recorded their diagnosis and proposed management. RESULTS: 300 patients (159 men) were scanned at a median of 17 (interquartile range=10 to 23) days after symptom onset. DWI showed a high signal lesion in 114/164 (70%) minor strokes versus 17/136 (13%) TIAs (P<0.0001). The presence of high-signal lesions on DWI decreased nonlinearly with time since symptom onset (P<0.0001) and increased with National Institutes of Health Stroke Score (P=0.038) and with age (P=0.01). In 90/206 (43.7%) patients with 1 or multiple lesions on T2, DWI helped to clarify whether these were related to a recent ischemic event (79 [48%] strokes; 11 [31%] TIAs). Compared with T2 alone, DWI provided additional information in 108 (36%) patients (91 [56%] strokes and 17 [13%] TIAs), such as clarification of clinical diagnosis (18 patients, 6%) or vascular territory (28 patients, 9.3%), which was considered likely to influence management in 42 (14%) patients (32 [19%] strokes; 10 [7.4%] TIAs). CONCLUSIONS: The clinically useful information available from DWI provides a further justification for an MRI-based imaging protocol in patients with subacute TIA or minor stroke.

Leukoaraiosis and increased cerebral susceptibility to ischemia: lack of confounding by carotid disease.

BACKGROUND: Leukoaraiosis is associated with an increased risk of stroke, but the underlying mechanism remains uncertain, as do the associations with other risk factors, such as carotid disease. We aimed to determine the role of carotid disease and of other clinical variables in the development of leukoaraiosis and to define their contributions to the associated increased risk of stroke. METHODS AND RESULTS: We prospectively studied a large cohort of consecutive patients with transient ischemic attack (TIA) and minor stroke who attended a TIA clinic between 2002 and 2009. Detailed clinical data were obtained, and patients underwent magnetic resonance brain and vascular imaging. We assessed the severity of leukoaraiosis with use of the ARWMC (Age Related White Matter Changes) score: 671 patients (374 [56%] men; mean [SD] age 71 [11] years) were studied, of whom 415 (62%) had leukoaraiosis. In a multivariate analysis, leukoaraiosis was associated with increasing age (P<0.0001) and hypertension (P=0.01), as well as the presence of acute (P<0.0001) and chronic (P=0.014) infarction on magnetic resonance imaging. In the univariate analysis, a current and past diagnosis of stroke versus TIA also showed a strong association. Carotid disease was not associated with leukoaraiosis, even in the presence of a flow-limiting (>70%) stenosis or occlusion, and the risk factor profiles for leukoaraiosis and carotid disease differed. CONCLUSIONS: The association with more severe ischemic events (stroke versus TIA) and infarction on imaging is consistent with leukoaraiosis being a marker of increased cerebral susceptibility to ischemia. In contrast, the presence, severity of, and risk factors for atheromatous disease showed no association with leukoaraiosis, suggesting that these are two unrelated disease processes.

Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis.

Patients with cerebral small vessel disease (SVD) can present as isolated lacunar infarction or with diffuse white matter changes, with the imaging appearance of leukoaraiosis. Endothelial dysfunction, which can lead to breakdown of the blood-brain barrier, impaired cerebral autoregulation and prothrombotic changes, is believed to be important in mediating disease. Circulating levels of intercellular adhesion molecule 1 (ICAM1), thrombomodulin (TM), tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are markers of endothelial activation and damage, and may provide insights into disease pathogenesis or differences between phenotypes. We therefore measured these markers in a prospective series of patients with lacunar stroke. One hundred and ten white Caucasian patients with previous lacunar stroke and 50 community control subjects were studied. Markers of endothelial function were measured on venous blood samples. Patients were classified on brain imaging into two groups: isolated lacunar infarction (n = 47) and ischaemic leukoaraiosis, defined as a clinical lacunar stroke and leukoaraiosis on brain imaging (n = 63). The number of lacunes and severity of leukoaraiosis were also scored on MRI. ICAM1, TM and TFPI were elevated in cerebral SVD subjects compared with controls (P