Enrico Flossmann

A simple score (ABCD) to identify individuals at high early risk of stroke after transient ischaemic attack

BACKGROUND Effective early management of patients with transient ischaemic attacks (TIA) is undermined by an inability to predict who is at highest early risk of stroke. METHODS We derived a score for 7-day risk of stroke in a population-based cohort of patients (n=209) with a probable or definite TIA (Oxfordshire Community Stroke Project; OCSP), and validated the score in a similar population-based cohort (Oxford Vascular Study; OXVASC, n=190). We assessed likely clinical usefulness to front-line health services by using the score to stratify all patients with suspected TIA referred to OXVASC (n=378, outcome: 7-day risk of stroke) and to a hospital-based weekly TIA clinic (n=210; outcome: risk of stroke before appointment). RESULTS A six-point score derived in the OCSP (age [> or =60 years=1], blood pressure [systolic >140 mm Hg and/or diastolic > or =90 mm Hg=1], clinical features [unilateral weakness=2, speech disturbance without weakness=1, other=0], and duration of symptoms in min [> or =60=2, 10-59=1, <10=0]; ABCD) was highly predictive of 7-day risk of stroke in OXVASC patients with probable or definite TIA (p<0.0001), in the OXVASC population-based cohort of all referrals with suspected TIA (p<0.0001), and in the hospital-based weekly TIA clinic-referred cohort (p=0.006). In the OXVASC suspected TIA cohort, 19 of 20 (95%) strokes occurred in 101 (27%) patients with a score of 5 or greater: 7-day risk was 0.4% (95% CI 0-1.1) in 274 (73%) patients with a score less than 5, 12.1% (4.2-20.0) in 66 (18%) with a score of 5, and 31.4% (16.0-46.8) in 35 (9%) with a score of 6. In the hospital-referred clinic cohort, 14 (7.5%) patients had a stroke before their scheduled appointment, all with a score of 4 or greater. CONCLUSIONS Risk of stroke during the 7 days after TIA seems to be highly predictable. Although further validations and refinements are needed, the ABCD score can be used in routine clinical practice to identify high-risk individuals who need emergency investigation and treatment.

Heritability of ischemic stroke in relation to age, vascular risk factors, and subtypes of incident stroke in population-based studies.

Background— Appropriate design of molecular genetic studies of ischemic stroke requires an understanding of the genetic epidemiology of stroke. However, there are no published population-based data on heritability of aetiological subtypes of ischemic stroke, confounding by heritability of other vascular risk factors, or the relationship between heritability and age of onset. Methods— We studied family history of stroke (FHxStroke) and of myocardial infarction (FHxMI) in first-degree relatives in 2 population-based studies (Oxford Vascular Study [OXVASC]; Oxfordshire Community Stroke Project [OCSP]). We related FHxStroke and FHxMI to subtype of ischemic stroke, age, and the presence of vascular risk factors and performed a systematic review of all studies of FHxStroke by stroke subtype. Results— In our population-based studies and in 3 hospital-based studies, FHxStroke was least frequent in cardioembolic stroke (OR=0.74, 95%CI=0.58 to 0.95, P =0.02) but was equally frequent in the other subtypes. In OXVASC and OCSP, FHxStroke (P =0.02), FHxMI (P =0.04), and FHx of either (P =0.006) were associated with stroke at a younger age. Only FHxStroke was associated with previous hypertension (OR=1.59, 95%CI=1.08 to 2.35, P =0.02). FHxMI was more frequent in large-artery stroke (OR=1.63, 95%CI=0.99 to 2.69, P =0.05). Conclusion— Consistent results in our population-based studies and previous hospital-based studies suggest that inclusion bias is not a major problem for studies of the genetic epidemiology of stroke. Molecular genetic studies might be best targeted at non-cardioembolic stroke and younger patients. However, genetic susceptibility to hypertension may account for a significant proportion of the heritability of ischemic stroke.

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.

Family History of Stroke in Patients With Transient Ischemic Attack in Relation to Hypertension and Other Intermediate Phenotypes

Background and Purpose— Family history of stroke (FHxstroke) is a risk factor for ischemic stroke, but there are insufficient data on the relationship with stroke subtypes and intermediate phenotypes (IPs), such as hypertension. Specifically, there are no reliable data on the associations of FHxstroke in patients with transient ischemic attack (TIA) in whom relationships with IPs are likely to be determined most reliably. Methods— We studied FHxstroke and FHx of myocardial infarction (FHxMI) in TIA patients from 2 population-based incidence studies and 2 prospective consecutive hospital-referred series. We related the presence of FHx to baseline characteristics, clinical subtype, and IPs. Results— Results were similar in the 4 cohorts, and so data on all 783 patients were pooled. FHxstroke was less common than FHxMI (189 versus 254; P=0.0003). FHxstroke and FHxMI were strongly related to history of hypertension in the proband (odds ratio [OR], 1.78; 95% CI, 1.28 to 2.48; P=0.0008; and OR, 2.10, 95% CI, 1.55 to 2.85; P<0.0001, respectively). Highest recorded premorbid systolic and diastolic blood pressures (mm Hg) were significantly higher in cases with FHxstroke than those without and increased with the number of affected first-degree relatives (0 181/100; 1 185/104; ≥2 198/109; P=0.03). There was no association between FHxstroke and age, diabetes, smoking, plasma glucose, cholesterol, or territory of TIA, but FHxstroke was less common in patients with ocular TIA than in cases with cerebral TIA (OR, 0.53; 95% CI, 0.34 to 0.82; P=0.004), although the association was no longer significant after adjustment for hypertension. Conclusions— The strong association between hypertension and FHxstroke suggests that familial susceptibility to cerebral ischemia is attributable, at least partly, to familial predisposition to hypertension. This should be taken into account in studies of the genetics of ischemic stroke.

Potential Confounding by Intermediate Phenotypes in Studies of the Genetics of Ischaemic Stroke

Background: Family history (FHx) of stroke is perceived to be an important risk factor for ischaemic stroke. However, there are several intermediate phenotypes that are often involved in the aetiology of ischaemic stroke and that have a substantial genetic component themselves. We studied FHx of ischaemic heart disease (IHD), hypertension (HTN) and diabetes mellitus (DM) as risk factors for ischaemic stroke. Methods: We performed a systematic review of case-control and cohort studies reporting on FHxIHD, FHxHTN or FHxDM as risk factors for stroke using bibliographic databases, and by hand searching reference lists and journals. Odds ratios of FHx as a risk factor for stroke were calculated within individual studies. We included unpublished data from two Oxfordshire population-based studies to assess effects on subtypes of ischaemic stroke. Results: We identified 54 studies that investigated the odds of stroke conferred by a positive FHx, 24 of which reported data on FHx of one or more intermediate phenotypes in addition to FHx of stroke. Most studies reported an increased frequency of FHxIHD and FHxHTN in stroke patients versus controls. The association was significant in 6 out of 14 studies for FHxIHD and 4 out of 11 studies for FHxHTN. In contrast, FHxDM was not associated with stroke. FHxIHD was particularly associated with large vessel strokes (OR 1.72, CI 1.3–2.2, p = 0.00004). Conclusions: FHxIHD and FHxHTN are both risk factors for stroke. It is likely that the apparent heritability of stroke is partly accounted for by heritability of HTN and large vessel atherosclerosis. Analyses of heritability of stroke and candidate gene studies should be adjusted accordingly.

Genetics of ischaemic stroke; single gene disorders

Examples of single gene disorders have been described for all major subtypes of ischaemic stroke: accelerated atherosclerosis and subsequent thrombo-embolism (e.g. homocysteinuria), weakening of connective tissue resulting in arterial dissections (e.g. Ehler–Danlos type IV), disorders of cerebral small vessels (e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and the collagen COL4A1 mutation), disorders increasing the thrombogenic potential of the heart through affecting the myocardium or the heart valves or through disturbance of the heart rhythm (e.g. hypertrophic cardiomyopathy), mitochondrial cytopathies increasing cerebral tissue susceptibility to insults (e.g. mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), and finally disorders of coagulation that can either directly cause stroke or act synergistically with the aforementioned abnormalities (e.g. sickle cell disease). Most of these disorders are rare but they are important to consider particularly in young patients with stroke, those with a family history or those who have other characteristics of a particular syndrome.

Superficial siderosis following spontaneous intracranial hypotension

A 33-year-old man presented in 2002 with an acute, severe, occipital headache associated with nausea and photophobia, causing him to collapse to the pavement; there was no persisting neurological impairment. He had mild hypertension, hypercholesterolaemia and asthma, but took no regular medication. His initial neurological examination was normal. A CT scan of head was normal but cerebrospinal fluid (CSF) showed xanthochromia, but was otherwise normal. A four-vessel digital subtraction cerebral angiogram was normal. He took nimodipine for 3 weeks and was discharged. He subsequently developed recurrent left-sided headaches, each lasting hours to days, with backache and dizziness, nausea and photophobia. These varied in frequency and severity but progressed over time, eventually having more days with headache than without. Following a more severe episode, he required hospital admission, with a diagnosis of migraine. In 2008, he developed neck pain with tingling in his left middle finger. An MR scan of cervical spine showed a posterior osteophytic bar with root impingement at C5/6 and C6/7. He obtained temporary relief from a nerve root blockade at both levels but eventually underwent a C5/6/7 anterior cervical decompression and fusion. In 2014, he became progressively unsteady and developed a subtle right-hand tremor. One day he woke with severe headache with nausea, vomiting and photophobia, with worsened unsteadiness. On examination there was mild ataxia on tandem gait with scanning dysarthria. CT scan of …

Asymptomatic Recurrent Cerebral Ischaemic Lesions on Diffusion-Weighted Imaging in the Subacute and Chronic Phase after Transient Ischaemic Attack or Minor Ischaemic Stroke

Introduction The risk of recurrent stroke can be as high as 10% in the first 7 days after transient ischaemic attack (TIA) or minor stroke [1] and is highest in patients with large artery atherosclerosis (LAA) compared to the other aetiological stroke subtypes [2] . However, trials of secondary stroke prevention often recruit patients after the high early risk period has passed [1, 3] and the rate of symptomatic vascular events is low. Diffusion-weighted MR brain imaging (DWI) is a highly sensitive and specific technique in the diagnosis of acute ischaemia [4] . Asymptomatic cerebral ischaemic lesions on DWI in the acute phase after TIA or minor stroke are more frequent than recurrent symptomatic stroke [5] and are associated with poor outcome [6] . Consequently, DWI lesions may be a useful surrogate marker of stroke risk. Indeed, trials of antiplatelet therapy in which recurrent lesions on DWI performed at 3 months after TIA or minor stroke will form part of a composite end-point are already being planned [7, 8] . DWI studies in the acute phase after TIA or minor stroke have suggested that lesion recurrence is positively associated with LAA 5, 9]. Furthermore, patients with multiple infarcts on baseline DWI and patients with early recurrent asymptomatic lesions are more likely to have further recurrent lesions on DWI at 3 months. [10] However, there are no data on the clinical predictors of recurrent DWI lesions in the chronic phase after TIA or minor stroke. Therefore, we performed serial DWI 1–9 months after a TIA or minor stroke in patients with risk factors for LAA who were not undergoing carotid endarterectomy (CEA). We compared lesion recurrence on DWI in patients with 1 50% versus ̂ 50% carotid stenosis.

Primary angiitis of the CNS mimicking a spinal cord tumour.

JO N 2 85 3 on the right. Deep tendon reflexes were depressed in the legs, and the plantar responses were absent. There was a sensory level to light touch and pin-prick corresponding to spinal segment T12. Vibration sense was absent up to the iliac crest. No abnormality was detected in the arms and cranial nerves. A general medical examination was unremarkable. Magnetic resonance imaging (MRI) of the spinal cord, with and without contrast, showed T2 signal change within the cord from T3 to the conus (Fig. 1). There was mild cord expansion in the lower thoracic region with irregular uptake of contrast. An MRI of the brain was normal. Laboratory investigations for routine biochemistry, full blood count, ESR, C-reactive protein, antinuclear antibodies, ANCA, rheumatoid factor, cryoglobulins, complement, antineuronal antibodies, Hepatitis B and C, syphilis serology and urinalysis were normal or negative. Cerebrospinal fluid showed a mononuclear Dirk Baumer Enrico Flossmann Simon Cudlip Geradine Quaghebeur Alexander Jeans Kevin Talbot

A 'broken heart' artifact in cardiovascular MR.

This 33-year-old man volunteered for a research study wearing a pair of shorts for the MR scan. The MR investigation was performed on a 1.5 T MR system (Siemens Medical Solutions, Erlangen, Germany). The TrueFISP localizers (TR/TE 254.3/1.1 ms, FoV 234 · 340 mm, Matrix 134 · 256, bandwidth 975 Hz, transverse plane, breath-hold, ECG-triggering) showed a remarkable ‘broken heart’ artifact (Figure 1a), and the ‘restitutio ad integrum’ after taking away the pair of shorts (Figure 1b). The shorts had a small metal ring in the waistband, which was responsible for this remarkable metal artifact.