Gérald Devuyst

Stroke patterns, etiology, and prognosis in patients with diabetes mellitus

Background: Although diabetes mellitus (DM) is a risk factor for stroke, it is unclear whether stroke features are different in diabetic vs nondiabetic individuals. Objective: To assess the role of DM in stroke patients. Methods: Risk factors, etiology, lesion topography, clinical features, and outcome were assessed in 611 diabetic individuals (history of DM or fasting plasma glucose level of ≥7.0 mmol/L) among 4,064 consecutive patients of the Lausanne Stroke Registry. Results: Patients with DM were 5.3 years older than non-DM patients. After multivariate analysis, DM was associated with lower relative prevalence of intracerebral hemorrhage (ICH; odds ratio [95% CI]: 0.63 (0.45 to 0.9); p = 0.022), higher relative prevalence of subcortical infarction (SCI; 1.34 [1.11 to 1.62]; p = 0.009), and higher relative frequency of small-vessel (SVD; 1.78 [1.31 to 3.82]; p = 0.012) and large-artery (LAD; 2.02 [1.31 to 2.02]; p = 0.002) disease. In the cohort of diabetic stroke patients, there was no interaction of DM with either hypertension or age for the outcomes of ICH, SCI, SVD, and LAD. Moderate to severe deficit on admission (31.1 vs 31.6%; p = 0.4) and poor functional outcome at 1 month (14.1 vs 15.3%; p = 0.24) did not differ in patients with DM compared with non-DM patients. In multivariate analysis, neither DM (0.86 [0.63 to 1.11]; p = 0.15) nor hypertension (1.09 [0.91 to 1.39]; p = 0.32) was associated with poor functional outcome. Conclusions: Diabetic stroke patients are associated with specific patterns of stroke type, etiology, and topography but not with poor functional outcome. There was no interaction between DM and hypertension or age.

Prognosis after stroke followed by surgical closure of patent foramen ovale A prospective follow-up study with brain MRI and simultaneous transesophageal and transcranial Doppler ultrasound

Background: The risk of stroke and the long-term prognosis of recurrent strokes in young patients with patent foramen ovale (PFO) are not well known. For this reason, the treatment of these patients remains empirical. An alternative treatment to prolonged antithrombotic therapy may be surgical closure of the PFO. Methods: Thirty patients (20 men and 10 women) with stroke and PFO were prospectively selected among 138 patients with stroke and PFO for a study of surgical closure of PFO at our center. Eligible patients were <60 years old, had negative results of a systematic search for another cause of stroke (first criterion), and met two of the four following criteria: (1) recurrent clinical cerebrovascular events or multiple ischemic lesions on brain MR, (2) PFO associated with an atrial septal aneurysm, (3) >50 microbubbles counted in the left atrium on contrast transesophageal echocardiography (TEE), and (4) Valsalva maneuver or cough preceding the stroke. Patients selected in this manner for surgery were considered to be a subgroup with a higher risk of stroke recurrence. Results: All patients had a direct suture of PFO while under cardiopulmonary bypass without recorded early or delayed significant complication. All patients underwent a new brain MRI and TEE simultaneous with transcranial Doppler ultrasonography after contrast injection at 8 +/- 3 months after surgery. After a mean follow-up of 2 years without antithrombotic treatment, no recurrent cerebrovascular event (stroke or transient ischemic attack [TIA]) and no new lesion on MRI had developed. Postoperative contrast TEE and transcranial Doppler ultrasonography showed that two patients had residual interatrial right-to-left shunting, although much smaller than before surgery, associated with single versus double continuous suture. Conclusions: Our study of 30 selected stroke patients with surgical suture of PFO showed a stroke recurrence rate of 0% and no significant complication. Residual right-to-left shunting may be avoided by double continuous suture of the PFO. In the absence of controlled studies to guide individual therapeutic decisions, our findings show that PFO closure can be done safely and may be considered to avoid recurrence in selected patients with long life expectancy and presumed paradoxic embolism. NEUROLOGY 1996;47: 1162-1166

Better outcome after stroke with higher serum cholesterol levels.

Objective: To examine whether serum cholesterol levels have any prognostic value in the first month following acute ischemic stroke. Background: Although the association between serum cholesterol levels and cerebrovascular disorders has been extensively studied, the relationship between cholesterol levels and outcome following ischemic stroke has not been investigated. Methods: Using data from 3,273 consecutive patients with first-ever ischemic stroke, the authors compared poor functional outcome (severe disability or death) at 1 month in patients with high cholesterol (total serum cholesterol greater than 6.5 mmol/L or 250 mg/dL) and normal cholesterol (level equal to or less than 6.5 mmol/L or 250 mg/dL). Data were analyzed by univariate and multivariate analysis. Results: In comparison with patients with normal cholesterol levels, patients with high cholesterol levels had a 2.2-fold lower risk of death (p = 0.002) and a 2.1-fold lower risk of poor functional outcome at 1 month (p < 0.001). After adjustment for known confounding variables, multivariate analysis showed that higher cholesterol levels remained an independent predictor of better functional outcome (OR 0.48, CI 0.34 to 0.69, p < 0.001). Conclusions: The authors’ findings suggest that higher levels of cholesterol are associated with a better outcome in the early phase after ischemic stroke.

Continuous assessment of electrical epileptic activity in acute stroke

Objective: To determine the incidence and risk factors of electrical seizures and other electrical epileptic activity using continuous EEG (cEEG) in patients with acute stroke. Methods: One hundred consecutive patients with acute stroke admitted to our stroke unit underwent cEEG using 10 electrodes. In addition to electrical seizures, repetitive focal sharp waves (RSHWs), repetitive focal spikes (RSPs), and periodic lateralized epileptic discharges (PLEDs) were recorded. Results: In the 100 patients, cEEG was recorded for a mean duration of 17 hours 34 minutes (range 1 hour 12 minutes to 37 hours 10 minutes). Epileptic activity occurred in 17 patients and consisted of RSHWs in seven, RSPs in seven, and PLEDs in three. Electrical seizures occurred in two patients. On univariate Cox regression analysis, predictors for electrical epileptic activity were stroke severity (high score on the National Institutes of Health Stroke Scale) (hazard ratio [HR] 1.12; p = 0.002), cortical involvement (HR 5.71; p = 0.021), and thrombolysis (HR 3.27; p = 0.040). Age, sex, stroke type, use of EEG-modifying medication, and cardiovascular risk factors were not predictors of electrical epileptic activity. On multivariate analysis, stroke severity was the only independent predictor (HR 1.09; p = 0.016). Conclusion: In patients with acute stroke, electrical epileptic activity occurs more frequently than previously suspected.

Trends in Risk Factors, Patterns and Causes in Hospitalized Strokes over 25 Years: The Lausanne Stroke Registry

Background and Objective: The Lausanne Stroke Registry includes, from 1979, all patients admitted to the department of Neurology of the Lausanne University Hospital with the diagnosis of first clinical stroke. Using the Lausanne Stroke Registry, we aimed to determine trends in risk factors, causes, localization and inhospital mortality over 25 years in hospitalized stroke patients. Methods: We assessed temporal trends in stroke patients characteristics through the following consecutive periods: 1979–1987, 1988–1995 and 1996–2003. Age-adjusted cardiovascular risk factors, etiologies, stroke localizations and mortality were compared between the three periods. Results: Overall, 5,759 patients were included. Age was significantly different among the analyzed periods (p < 0.001), showing an increment in older patients throughout time. After adjustment for age, hypercholesterolemia increased (p < 0.001), as opposed to cigarette smoking (p < 0.001), hypertension (p < 0.001) and diabetes and hyperglycemia (p < 0.001). In patients with ischemic strokes, there were significant changes in the distribution of causes with an increase in cardioembolic strokes (p < 0.001), and in the localization of strokes with an increase in entire middle cerebral artery (MCA) and posterior circulation strokes together with a decrease in superficial middle cerebral artery stroke (p < 0.001). In patients with hemorrhagic strokes, the thalamic localizations increased, whereas the proportion of striatocapsular hemorrhage decreased (p = 0.022). Except in the older patient group, the mortality rate decreased. Conclusions: This study shows major trends in the characteristics of stroke patients admitted to a department of neurology over a 25-year time span, which may result from referral biases, development of acute stroke management and possibly from the evolution of cerebrovascular risk factors.

Pure superficial posterior cerebral artery territory infarction in The Lausanne Stroke Registry

Abstract.Objective: To determine the patterns of clinical presentation, lesion topography, and etiology in patients with ischemic stroke limited to the superficial territory of the posterior cerebral artery (s-PCA). Methods: In the Lausanne Stroke Registry (LSR, 1983–1998), we determined the patterns of clinical presentation, lesion topography and mechanisms of stroke, among 117 patients with s-PCA infarction (s-PCAI) on brain imaging. Results: s-PCAIs accounted for 30.5 % of all PCA territory ischemic strokes. The presumed etiology was embolism in 64 (54.5 %) patients [cardiac in 51 (43.5 %) and arterial in 13 (11 %)], indeterminate in 38 (32 %), PCA atherothrombosis in 4 (3.4 %), migraine in 4 (3.4 %), other rare causes in 4 (3.4 %), and multiple potential sources of embolism in 3 (2.5 %). The clinical findings were hemianopsia in 78 (67 %), quadrantanopsia in 26 (22 %), and bilateral visual field defects in 8 (7 %). Motor, sensory, or sensorimotor deficits were detected in 14 (12 %), 8 (6.8 %), or 8 (6.8 %) patients, respectively. Neuropsychological dysfunction included memory impairment in 20 (17.5 %; with left [L], right [R], or bilateral [B] lesions in 15, 2, or 3 patients, respectively), dysphasia in 17 (14.5 %; L/B: 14/3), dyslexia with dysgraphia in 5 (4 %; L/B: 4/1), dyslexia without dysgraphia in 10 (8.5 %; L/B: 8/2), hallucinations in 12 (10 %; L/R/B: 5/5/2), visual neglect in 11 (9.5 %; L/R: 2/9), visual agnosia in 10 (8.5 %; L/B: 7/3), prosopagnosia in 7 (6 %; R/B: 4/3), and color dysnomia in 6 (5 %; L: 6). Conclusions: s-PCAIs are uncommon, representing less than a third of all PCA infarctions. Although embolism is the main cause in 60 % of patients, identification of the emboli source is often not possible. In 1/3 of cases, the stroke mechanism cannot be determined. Neuropsychological deficits are frequent if systematically searched for.

Controlled Contrast Transcranial Doppler and Arterial Blood Gas Analysis to Quantify Shunt Through Patent Foramen Ovale

Background and Purpose— A right-to-left shunt can be identified by contrast transcranial Doppler ultrasonography (c-TCD) at rest and/or after a Valsalva maneuver (VM) or by arterial blood gas (ABG) measurement. We assessed the influence of controlled strain pressures and durations during VM on the right-to-left passage of microbubbles, on which depends the shunt classification by c-TCD, and correlated it with the right-to-left shunt evaluation by ABG measurements in stroke patients with patent foramen ovale (PFO). Methods— We evaluated 40 stroke patients with transesophageal echocardiography–documented PFO. The microbubbles were recorded with TCD at rest and after 4 different VM conditions with controlled duration and target strain pressures (duration in seconds and pressure in cm H2O, respectively): V5-20, V10-20, V5-40, and V10-40. The ABG analysis was performed after pure oxygen breathing in 34 patients, and the shunt was calculated as percentage of cardiac output. Results— Among all VM conditions, V5-40 and V10-40 yielded the greatest median number of microbubbles (84 and 95, respectively; P <0.01). A significantly larger number of microbubbles were detected in V5-40 than in V5-20 (P <0.001) and in V10-40 than in V10-20 (P <0.01). ABG was not sensitive enough to detect a shunt in 31 patients. Conclusions— The increase of VM expiratory pressure magnifies the number of microbubbles irrespective of the strain duration. Because the right-to-left shunt classification in PFO is based on the number of microbubbles, a controlled VM pressure is advised for a reproducible shunt assessment. The ABG measurement is not sensitive enough for shunt assessment in stroke patients with PFO.

Ultrasound Measurement of the Fibrous Cap in Symptomatic and Asymptomatic Atheromatous Carotid Plaques

Background—Fibrous cap thickness (FCT) is an important determinant of atheroma stability. We evaluated the feasibility and potential clinical implications of measuring the FCT of internal carotid artery plaques with a new ultrasound system based on boundary detection by dynamic programming. Methods and Results—We assessed agreement between ultrasound-obtained FCT values and those measured histologically in 20 patients (symptomatic [S]=9, asymptomatic [AS]=11) who underwent carotid endarterectomy for stenosing (>70%) carotid atheromas. We subsequently measured in vivo the FCT of 58 stenosing internal carotid artery plaques (S=22, AS=36) in 54 patients. The accuracy in discriminating symptomatic from asymptomatic plaques was assessed by receiver operating characteristic curves for the minimal, mean, and maximal FCT. Decision FCT thresholds that provided the best correct classification rates were identified. Agreement between ultrasound and histology was excellent, and interobserver variability was small. Ultrasound showed that symptomatic atheromas had thinner fibrous caps (S versus AS, median [95% CI]: minimal FCT=0.42 [0.34 to 0.48] versus 0.50 [0.44 to 0.53] mm, P=0.024; mean FCT=0.58 [0.52 to 0.63] versus 0.79 [0.69 to 0.85] mm, P<0.0001; maximal FCT=0.73 [0.66 to 0.92] versus 1.04 [0.94 to 1.20] mm, P<0.0001). Mean FCT measurement demonstrated the best discriminatory accuracy (area under the curve [95% CI]: minimal 0.74 [0.61 to 0.87]; mean 0.88 [0.79 to 0.97]; maximal 0.82 [0.71 to 0.93]). The decision threshold of 0.65 mm (mean FTC) demonstrated the best correct classification rate (82.8%; positive predictive value 75%, negative predictive value 88.2%). Conclusions—FCT measurement of carotid atheroma with ultrasound is feasible. Discrimination of symptomatic from asymptomatic plaques with mean FCT values is good. Prospective studies should determine whether this ultrasound marker is reliable.

Giant Cell Arteritis as a Cause of First-Ever Stroke

The aims of this study were to assess how frequently giant cell arteritis (GCA) was a cause of first-ever stroke in 4,086 patients in the Lausanne Stroke Registry and to determine the risk factors, patterns, latency and current therapy at onset in patients with GCA plus stroke. GCA was recognized using the criteria of the American College of Rheumatology. We report on 6 patients (0.15%) with a histologically proven diagnosis of temporal arteritis and clinical and neuroradiological evidence of cerebral ischemia. The CT and MRI scans showed lacunar infarction in 3 patients, territorial infarction in 2 and were normal in 1. Stroke latency ranged from 0 to 2 months. All patients suffered from headache. We conclude that stroke is a rare, but dangerous, complication of GCA and that a combination of antiplatelet drugs and corticosteroids may be advisable for preventing stroke occurrence.

Clinical trial update: neuroprotection against acute ischaemic stroke.

One of the most recent advances and hopes in stroke therapy concerns neuroprotection, which has recently been investigated in several clinical trials. Furthermore, some new neuroprotective drugs, which are based on newly identified cellular and molecular mechanisms that underlie the development of focal ischaemic injury, will be tested in stroke patients in the future. It must be emphasized, however, that the concept and application of neuroprotection must remain within the frame of the global network and organization of acute stroke care, because neuroprotection at best may become only a link among many other management strategies for acute stroke.