Predictive factors of functional independence after optimal reperfusion in anterior circulation ischaemic stroke with indication for intravenous thrombolysis plus mechanical thrombectomy.

BACKGROUND AND PURPOSE: Intravenous thrombolysis plus mechanical thrombectomy (IVT + MT) is the best current management of acute stroke due to large-vessel occlusion and results in optimal reperfusion for most patients. Nevertheless, some of these patients do not subsequently achieve functional independence. The aim was to identify baseline factors associated with 3-month independence after optimal reperfusion and to validate a prediction model. METHODS: All consecutive patients with intracranial anterior large-vessel occlusion, with indication for IVT + MT and achieving optimal reperfusion (defined as modified Treatment in Cerebral Ischaemia score 2b-3), from the THRACE trial and the ETIS registry, were included in order to identify a prediction model. The primary outcome was 3-month independence [modified Rankin Scale (mRS) score ≤ 2]. Multivariate inferences invoked forward logistic regression, multiple imputation and bootstrap resampling. Predictive performance was assessed by c-statistic. Model validation was conducted on patients from the ASTER trial. RESULTS: Amongst 139 patients (mean age 65.5 years; 54.3% female), predictors of 3-month mRS ≤ 2 (n = 82) were younger age [odds ratio 0.62 per 10-year increase; 95% confidence interval (CI) 0.53-0.72] and higher Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (odds ratio 1.65 per 1-point increase; 95% CI 1.47-1.86) with c-statistic 0.77. Model validation (n = 104/181 patients with 3-month mRS ≤ 2) demonstrated a moderate discrimination (c-statistic 0.74; 95% CI 0.66-0.81) combining age and ASPECTS. The validation model was improved by the adjunction of three candidate variables that were found to be predictors. Addition of baseline National Institutes of Health Stroke Scale (NIHSS) score, history of vascular risk factor and onset-to-reperfusion time significantly improved discrimination (c-statistic 0.85; 95% CI 0.83-0.87). CONCLUSIONS: After optimal reperfusion, younger age, higher ASPECTS, lower NIHSS score, shorter onset-to-reperfusion time and absence of vascular risk factor were predictive of independence and could help to guide patient management.

Laboratory effect on platelet activity within 24 h of the first 300-mg oral dose of aspirin given in hospital during the acute phase of ischemic cerebral events.

BACKGROUND AND PURPOSE: Aspirin is the most commonly used antiplatelet treatment during the acute phase of cerebral ischemic events. It inhibits the production of thromboxane (TX) A(2), a powerful platelet activator. Despite this protection, early ischemic recurrences are frequent and considered clinical failures of this therapy. Only a few trials have focused on the use of antiplatelet therapy during this phase, and none has described the laboratory effect of the first dose of aspirin given after an ischemic cerebral event. However, this study may help clinicians to understand the mechanisms of early recurrences, and to design new therapeutic strategies, in particular for patients already treated with a daily dose of aspirin. METHOD: We studied laboratory parameters of the first 300-mg oral dose of aspirin given within 48 h after an ischemic cerebral event. Two blood samples were taken from all of the patients: the first during the third hour following aspirin intake (T1) and the second during the twenty-fourth hour (T2). For patients already treated with a daily dose of aspirin, a supplementary sample was taken before aspirin intake (T0). Platelet reactivity was studied on the basis of serum TXB(2) levels, a metabolite of TXA(2), and light transmission aggregometry after stimulation of platelet-rich plasma by arachidonic acid and by two concentrations of collagen, i.e. 2 µg/ml (Col2), dependent on the TXA(2) pathway, and 20 µg/ml (Col20), independent of the TXA(2) pathway. Results with Col2 were related to results with Col20 (Col2/20 ratio) to limit the impact of variations induced by the effects of preanalytical conditions. RESULTS: Fifty patients were included. TXB(2) values (p < 0.001) and relative values of the Col2/20 ratio (p = 0.037) were significantly higher at T2 compared to T1. For patients already treated with aspirin, TXB(2) levels (p < 0.001) were significantly lower at T1 compared to T0, and the Col2/20 ratio tended to decrease (p = 0.096). CONCLUSION: Platelet reactivity recovers within 24 h following the first 300-mg oral dose of aspirin during the acute phase of a cerebral ischemic event as demonstrated by an increase in TXB(2) levels, and the Col2/20 ratio, at T2 compared to T1. This would favor early ischemic recurrences. However, for patients already treated with aspirin, this dose is able to decrease TXB(2) levels and to complete the inhibition of the TXA(2) pathway, which shows the utility of this prescription in this case.

Ischaemic stroke and essential thrombocythemia: a series of 14 cases.

BACKGROUND: Essential thrombocythemia (ET) is considered as a rare cause of stroke, partially because of difficulties to identify it when platelet count is not greatly elevated. However, early detection of ET is important because, without adapted treatment, recurrent thromboses are frequent. METHOD: We collected, retrospectively, data from 14 cases of stroke patients with ET. Clinical characteristics, ischaemic stroke, laboratory data (platelet and leucocyte count, haemoglobin, JAK2 V617F mutation, culture of haematopoietic progenitors) and treatment were reviewed. Every patient has been interviewed by phone to evaluate outcome. RESULTS: The population consisted of nine women and five men with ages ranging from 40 to 87 years. Most of the patients (12) had atherosclerotic risk factors and two presented a thrombus in the internal carotid. ET was diagnosed early after the onset of stroke except in two patients. The platelet count was under 600*10(9) /L for five patients. Mutation JAK2 V617F was found for eight patients. Thirteen patients were treated with an association between antiplatelet and cytoreductive treatment and did not present further thrombosis. Median follow-up is 2.8 years. CONCLUSION: These cases emphasize the problems of diagnosing ET at the onset of the stroke. Complete blood count has to be carefully read and ET can be suspected even if platelet count is not greatly increased. Diagnosis must be confirmed by haematologist to initiate appropriate treatment.

Cerebral venous thrombosis caused by spontaneous intracranial hypotension: two cases.

The association of spontaneous intracranial hypotension (SIH) with cerebral venous thrombosis (CVT) is rare. We are reporting two new cases. In one case, CVT is extensive concerning three sinuses and bilateral parietal cortical veins and, in the other case, only a cortical vein is involved. Both the patients presented had no thrombosis risk factors. There is certainly a link between these two pathologies. SIH should be considered as a risk factor of CVT. Modification of symptoms of SIH leading to CVT must be known to start early treatment.

Comparison of intravenous and intra-arterial urokinase thrombolysis for acute ischaemic stroke.

Intravenous fibrinolysis (IVF) with rt-PA (alteplase) provides significant benefits in acute ischaemic stroke when it is given within the first three hours following stroke onset. Intra-arterial fibrinolysis (IAF) with pro-urokinase in PROACT II study provides quite the same benefit in the first 6 hours. IVF and IAF have never been compared. To compare the efficacy and safety of IVF and IAF with urokinase given within the first 6 hours of acute ischaemic stroke. Patients fulfilling the selection criteria were randomly assigned to receive urokinase 900,000 units via intravenous or intra-arterial routes. This randomised monocentre study was done between December 1995 and August 1997. The primary outcome was defined as the number of patients with a modified Rankin score of 2 or less. Secondary outcomes included mortality, frequency of symptomatic intracranial haemorrhage (SIH), neurological and functional scores. Fourteen patients were given IVF and 13 IAF. The study was terminated by the National Health Authorities when 27 patients had been included because of the mortality rate. Seven patients (26%) died, 4 in the IV group (oedematous infarct in 3 and recurrence in 1), 3 in the IA group (SIH in 2, and oedematous infarct in 1). Patients given IVF were treated significantly earlier (4:16 h vs 5:24 h; p=.007). Although IA patients showed greater and earlier improvement there was no significant difference in primary and secondary outcomes. Because of premature termination, the trial was too small to provide any reliable and conclusive results. Intra-arterial fibrinolysis began significantly later than IV fibrinolysis but it gave non-significantly better results in this prematurely terminated study.

[Thrombus of the left lateral sinus spreading to the internal jugular vein]. / Thrombose du sinus latéral gauche étendue à la veine jugulaire interne.

Cerebral venous thrombosis is an uncommon event which presents a wide spectrum of sometimes extraneurological signs different from the classical clinical presentation. We report the cases of two middle-aged women who developed thrombosis of the left lateral sinus spread-ing to the internal jugular vein from the sigmoid sinus. The time course of the symptoms suggested that intracranial thrombosis occurred first. No infectious or neoplastic local disease could be found but both women were taking oral contraceptives. Medical treatment led to good reperfusion of the intracranial sinuses but occlusion of the jugular vein persisted despite prolonged oral anticoagulants. Long-term outcome was favorable with residual benign epilepsy in one patient, and occurrence of an arteriovenous fistula in the other.

Vasospasm after subarachnoid hemorrhage: interest in diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Vasospasm secondary to subarachnoid hemorrhage (SAH) is responsible for severe ischemic complications. Although effective, angioplasty must be performed at a very early stage to produce any clinical recovery. Diagnostic investigations to assess arterial narrowing (transcranial Doppler, angiography) or cerebral perfusion (xenon CT, single-photon emission CT) do not provide evidence of the extent of parenchymal ischemia. In stroke, diffusion-weighted MR imaging (DWI) appears to be the most sensitive procedure to detect cerebral ischemia. We studied asymptomatic vasospasm in patients with aneurysmal SAH to assess whether DWI provides predictive markers of silent ischemic lesions and/or progression toward symptomatic ischemia. METHODS: Seven asymptomatic vasospasm patients (average blood velocity rates >120 cm/s), 3 patients with symptomatic vasospasm, and 4 patients with SAH but without vasospasm were studied at regular intervals by DWI, and their apparent diffusion coefficients (ADCs) were calculated. RESULTS: All patients with vasospasm including those without symptoms presented abnormalities on DWI with a reduction of the ADC prevalently in the white matter. No such abnormalities were observed in patients without vasospasm. The abnormalities on DWI resolved completely in 4 of the 7 patients, with no parenchymal lesion. Resolution was partial in 3 patients whose white matter still presented residual round, focal ischemic lesions. CONCLUSIONS: Being able to correlate abnormalities on DWI with parenchymal involvement in asymptomatic patients would be of considerable clinical significance. It is hoped that larger studies will be undertaken to determine whether the ADC has a reversibility threshold, because this would facilitate patient management.

[Thrombosis of deep cerebral veins in form adults: clinical features and diagnostic approach]. / Les thromboses veineuses profondes de l'encéphale de l'adulte: aspects cliniques et approche diagnostique.

Thrombosis of deep cerebral veins is a rare condition, and is associated with a poor prognosis. We report four new cases observed between 1994 and 1997. All four cases were women, aged less than 45 years. Initial symptoms associated alteration of consciousness, change in mental status, progressive headache and vomiting. We observed also uni or bilateral signs of long tract injury. In three cases, diagnosis initially suspected by CT scan was confirmed with encephalic MRI. For the last patient, conventional angiography was needed. Thrombosis affected straight sinus, vein of Galien and internal cerebral veins in all patients. Basilar veins were also affected in one patient, without dural sinuses extension. Lateral sinus was involved in two others cases, and superior sagittal in the last patient. Etiology remains undetermined in one patient, associated with post-partum, use of oral contraceptive pill, and familial protein S deficiency, one case each. Outcome was favorable in all four cases with anticoagulation therapy. Precocity of diagnosis is determinant and MRI is usefull in this issue. These observations show that evolution of deep veins thrombosis can be favorable, without needing fibrinolytic therapy.

[Ethical approach to informed consent for participation in clinical studies in acute cerebral infarct]. / Approche éthique du recueil du consentement pour la participation à des études cliniques à la phase aiguë de l'infarctus cérébral.

OBJECTIVE: We sought to evaluate the application of the French law for the protection of persons participating in research studies in biology and medicine. Specifically, we examined comprehension and consequences of informed consent procedures in the field of stroke, characterized by an emergency setting, cognitive impairment and poor prognosis. PATIENTS AND METHODS: Patients (or proxies) included in recent years in clinical studies conducted in our Neurology Department for evaluating treatment of acute phase cerebral ischemia were interviewed to determine their knowledge of the disease, its treatment, the study protocol and the legal regulations, and the affective and psychological consequences of the informed consent procedure. RESULTS: Among 72 patients included in 7 studies ([fibrinolytic agent: 3 (n = 43), anticoagulant agent: 1 (n = 4), neuroprotective drugs (n = 25)], [7 randomized studies, 6 double-blind versus placebo, 5 with a 6-hour inclusion time interval]), 15 died during the acute phase, 5 were lost to follow-up, 4 refused to participate and 7 gave very partial answers. Consent was signed by the patient in 15% of cases, the spouse in 50%, a descendant in 23%. These persons were aware of the spontaneous risk of death (85%) or definitive functional impairment (95%). Half of them thought a specific treatment existed, 11% had some idea of the mechanism of action of the proposed treatment while 67% learned about this mechanism from the information provided. Although they had received information, only 25% of the patients had knowledge of placebo and 7% of therapeutic risk. 37% expected complete recovery from the treatment, 44% partial recovery, and 13% were very disappointed by the outcome. 81% felt they were free to make their own decision. Although 86% did not know there was a law protecting them, 82% were in agreement with the requirement for their consent while 17% would have preferred to delay consent. Most wished to be given the opportunity to discuss the study again, after the acute phase, and to receive the results of the study. CONCLUSION: This study shows that most French stroke victims and their closest relatives are unaware of the law protecting persons in biomedical research and have poor knowledge of medical data after being given appropriate information. Even so, the quality of information increases the quality of the patient-physician relationship. Patients want to be free to make their own decision to consent to biomedical research, but their desire was more for good information than for the power to make their decision alone. Being asked to give informed consent in order to participate in a clinical study accentuates the affective and psychological consequences of stroke, a factor which should be taken into consideration during follow-up.

[Isolated dissection of the basilar artery]. / Dissection isolée de l'artère basilaire.

Two cases of isolated dissection of the basilar artery responsible for ischemic stroke are reported. This rare condition is still associated with a poor outcome. Most patients were male and the clinical presentation consisted of ischemic symptoms or subarachnoid hemorrhage in posterior circulation. Angiography and Magnetic Resonance Imaging are usefull for the diagnostic, showing parietal hematoma, or as for our first case, double lumens. Optimal therapeutic is unknown.

Acute reversible cerebral arteritis associated with parenteral ephedrine use.

Cerebrovascular disorders in association with licit or illicit drugs have rarely been reported. We report a first case of stroke associated with the parenteral use of ephedrine. A 44-year-old woman underwent spinal anaesthesia for varicose vein surgery. She was usually treated with propranolol and occasionally with phenoxazoline. During anaesthesia, ephedrine was administered by the venous route because of arterial hypotension. She developed intracranial hypertension and focal cerebral deficits related to multiple haemorrhagic cerebral infarcts associated with a reversible beading appearance on angiography consistent with the diagnosis of acute cerebral arteritis. The role of ephedrine in this case is discussed beside other causes of acute cerebral arteritis.

[Cerebral ischemic accidents in young subjects. A prospective study of 296 patients aged 16 to 45 years]. / Accidents vasculaires cérébraux ischémiques du sujet jeune. Etude prospective de 296 patients âgés de 16 à 45 ans.

From 1990 to 1997, June, 296 patients (156 males and 140 females), aged 16 to 45 years, admitted in the Neurology Department of the University Hospital of Nancy (F) for ischemic stroke, were prospectively evaluated according to a standardized analysis of anamnestic and clinical data, angiography (90 p. 100 of cases), TEE (78 p. 100), hemostasis. Women were younger (mean age = 34.82 y) than men (36.87 y; p = 0.003), with a peak in the 4th decade. Clinical event was a TIA in 14.2 p. 100, a stroke in 51.7 p. 100; it concerned the anterior circulation in 64.5 p. 100, posterior circulation in 25 p. 100, multiple territories in 10.5 p. 100. History of TIA, cervical-cranial pain or Horner syndrome suggestive of dissection, pregnancy or post-partum were found respectively in 60 (20.3 p. 100), 34 (11.1 p. 100) and 13 (9.3 p. 100) cases. Risk factors concerned 87.2 p. 100 of patients, mainly smoking (55.1 p. 100), oral contraceptive (53 p. 100), hyperlipemia (35 p. 100), and were more frequent in case of atheroma and lacunar stroke (p < 0.0000). Etiology, according to TOAST classification, was: atheroma (8.4 p. 100), cardioembolism (8.7 p. 100), small-artery disease (7.1 p. 100), dissection (15.5 p. 100), other determined causes (11.1 p. 100), multiple causes (5.7 p. 100), undetermined cause (34.8 p. 100). Septal pathology was found 34 times. Patients whose stroke remained unexplained were younger (33.7 y vs 37.7, p = 0.002), had less risk factors (p < 0.0000), had more TIA (p = 0.005), more often in the carotid territory (p = 0.008), had a better prognosis (p = 0.01), and showed more often emboli at angiography (p = 0.001). During a mean follow-up of 33 months (median = 19), 21 recurrent strokes occurred and 6 patients died. 134 (46 p. 100) patients had no sequelae, 101 (34.7 p. 100) minor disability, 42 (14.4 p. 100) major sequelae. These results, compared to the main studies of the literature, suggest the interest of common definition criteria and classification of etiologies. In practice, hierarchisation of investigations may be proposed, and vascular risk factors should be tracked in young patients. In patients whose stroke remains unexplained, further studies, as atrial vulnerability, are needed.

[Diffusion imaging in asymptomatic focal vasospasm. Apropos of a case]. / Imagerie de diffusion dans le vasospasme focalise asymptomatique. A propos d'un cas.

We report a case of an asymptomatic vasospasm with a focal, reversible apparent diffusion coefficient (ADC) decrease after a middle cerebral artery aneurysm rupture. This isolated decrease of ADC has not yet been reported in this pathological situation. It could be interesting to predict the risk of ischemic delayed complications of vasospasm.

[MRI aspects of spinal cord abscesses. Report of 5 cases and review of the literature]. / Les abcès médullaires, aspects en IRM. A propos de 5 cas et revue de la littérature.

The spinal canal is an uncommon site for abscess formation resulting from bloodstream disseminated infection. Prognosis is often unfavorable. Rapid treatment is essential for satisfactory neurological recovery. Abscesses within the spinal canal are thus diagnostic and therapeutic emergencies. The neuro-infectious and inflammatory manifestations and laboratory findings vary considerably and are insufficient for diagnosis. MRI plays a decisive role. The most commonly reported signs are the presence of an intramedullary collection giving a low-intensity signal on T1-weighted images and a high-intensity signal on T2-weighted images with peripheral contrast uptake and generally extended adjacent medullary edema. We report here five cases of spinal canal abscesses diagnoses with MRI at different stages of development (pre-suppurative myelitis in two cases, constituted abscess in three cases). For each case we reviewed the clinical course and describe the details of the imaging findings. In our series, the collected abscesses presented as round lesions within the canal with contrast uptake. It is noteworthy that the periependymal gray matter adjacent to the lesion also took up the contrast agent in all patients with a collected abscess. This sign has not been described previously and appears to be a going argument orienting the diagnosis towards an infectious rather than tumoral formation.

[Atrial electrophysiological study of unexplained ischemic cerebrovascular disorders]. / Exploration électrophysiologique auriculaire des accidents vasculaires ischémiques cérébraux inexpliqués.

The aim of this study was to search for the presence of atrial vulnerability by programmed atrial stimulation in patients with unexplained ischaemic cerebrovascular strokes and to evaluate the effects of intravenous flecainide acetate on the electrophysiological parameters and on the induction of atrial arrhythmias. Thirty-eight patients (20 men, 18 women) with a mean age of 38.4 +/- 11 years were investigated. Programmed atrial pacing triggered a sustained (> 1 min) atrial arrhythmia with 1 or 2 extrastimuli in 23 of the 38 patients (61%), in these patients, there was a significant shortening of the effective refractory periods (ERP: 193 +/- 23 vs 218 +/- 30 ms; p < 0.02) and of the functional refractory periods (FRP: 228 +/- 25 vs 253 +/- 27 ms; p < 0.01) with lengthening of the A2 auriculogramme (99.7 +/- 22 vs 76.1 +/- 16 ms; p < 0.05). A combined study of the refractory periods and conduction defects provides a means of calculating an index of latent vulnerability which is greatly shortened when an atrial arrhythmia is induced (2 +/- 0.5 cm vs 3 +/- 0.6 cm; p < 0.001). Atrial arrhythmias could not be initiated after intravenous 3 mg/kg of flecainide acetate in 4 subjects (17%) with initially positive atrial stimulation tests. This study confirms the high frequency of atrial vulnerability in patients with unexplained ischaemic cerebrovascular strokes. In their population, the authors observed a low efficacy of flecainide acetate in the prevention of reinduction of atrial arrhythmias. The indication of long-term antiarrhythmic drugs in these patients are questionnable and should be assessed by a prospective long-term multicentre trial.