André Peeters

Usefulness of Magnetic Resonance–Derived Quantitative Measurements of Cerebral Blood Flow and Volume in Prediction of Infarct Growth in Hyperacute Stroke

Background and Purpose The identification of the tissue at risk for infarction remains challenging in stroke patients. In this study, we evaluated the value of quantitative cerebral blood flow (CBF) and cerebral blood volume (CBV) measurements in the prediction of infarct growth in hyperacute stroke. Methods Fluid-attenuated inversion recovery (FLAIR), diffusion-weighted (DW), and gradient-echo echo-planar perfusion-weighted (PW) sequences were obtained in 66 patients within 6 hours of stroke onset; ischemia was confirmed on follow-up FLAIR images. We delineated the following: (1) the initial infarct on DW images, (2) the area of hemodynamic disturbance on mean transit time (MTT) maps, and (3) the final infarct on follow-up FLAIR images. MTT, CBF, and CBV were calculated in the following areas: area of initial infarct (INF), area of infarct growth (IGR, final minus initial infarct), the hemodynamically disturbed area that remained viable (OLI, hemodynamic disturbance minus final infarct), and all contralateral mirror regions. Results Compared with mirror regions, the MTT in abnormal areas was always prolonged. The respective mean±SD CBF and CBV values were as follows: for INF, 28±16 mL/min per 100 g and 6.9±2.7%; for IGR, 36±20 mL/min per 100 g and 8.9±3.1%; for OLI, 50±17 mL/min per 100 g and 11.2±3%; and for mirror regions, 64±23 mL/min per 100 g and 8.7±2.5%. The CBV and CBF values were significantly different between all abnormal areas (except for the CBF between INF and IGR). In the area of DW/PW mismatch, a combined CBF or CBV threshold of 35 or 8.2, respectively, predicted evolution to infarction with a sensitivity of 81% and a specificity of 76%. Conclusions Quantitative measurements of CBF and CBV in hyperacute stroke may help to predict infarct growth and to select the subjects who will benefit from thrombolysis.

Paraquat Poisoning - State-of-the-art

The authors describe the main features of acute paraquat poisoning. The clinical picture together with severity grading is presented. The pathophysiological mechanisms responsible for multiple organ dysfunction are discussed. Despite a better understanding of pathophysiological pathways and numerous experimental data, the treatment of the most severe forms of poisoning remains limited. The efficacy of more recently developed therapeutic approaches is still to be evaluated.

Increased functional connectivity one week after motor learning and tDCS in stroke patients

Recent studies using resting-state functional magnetic resonance imaging (rs-fMRI) demonstrated that changes in functional connectivity (FC) after stroke correlate with recovery. The aim of this study was to explore whether combining motor learning to dual transcranial direct current stimulation (dual-tDCS, applied over both primary motor cortices (M1)) modulated FC in stroke patients. Twenty-two chronic hemiparetic stroke patients participated in a baseline rs-fMRI session. One week later, dual-tDCS/sham was applied during motor skill learning (intervention session); one week later, the retention session started with the acquisition of a run of rs-fMRI imaging. The intervention+retention sessions were performed once with dual-tDCS and once with sham in a randomized, cross-over, placebo-controlled, double-blind design. A whole-brain independent component analysis based analysis of variance (ANOVA) demonstrated no changes between baseline and sham sessions in the somatomotor network, whereas a FC increase was observed one week after dual-tDCS compared to baseline (qFDR <0.05, t63=4.15). A seed-based analysis confirmed specific stimulation-driven changes within a network of motor and premotor regions in both hemispheres. At baseline and one week after sham, the strongest FC was observed between the M1 and dorsal premotor cortex (PMd) of the undamaged hemisphere. In contrast, one week after dual-tDCS, the strongest FC was found between the M1 and PMd of the damaged hemisphere. Thus, a single session of dual-tDCS combined with motor skill learning increases FC in the somatomotor network of chronic stroke patients for one week.

Intravenous thrombolysis after reversal of dabigatran by idarucizumab: a moment to be a pioneer

A 85-year-old, right-handed woman patient with a history of atrial fibrillation, arterial hypertension, dyslipidemia, and a recent transient ischemic attack was admitted to the Emergency Department at 7.15 AM. At 3.00 AM, she had awakened, time we took as ‘last known well’. Her husband noted then she had forgotten to take the evening dose of dabigatran 110 mg, which he immediately gave her. At 5.00 AM, he observed a right facial palsy. As symptoms did not resolve spontaneously, he called the emergency medical service. On admission, blood pressure was 170/100 mmHg, glycemia was 176 mg/dL, and cardiac rate was 98, irregular. Neurological examination showed drowsiness, a right-sided paresis of face, arm, and leg, together with right-sided homonymous hemianopsia and severe aphasia. The total NIHSS score was 17. Brain computed tomography (CT) excluded an intracranial hemorrhage and demonstrated an insular and left frontal acute ischemic area. CT angiography did not show a large vessel occlusion but several distal emboli (Fig. 1a). CT perfusion demonstrated a mismatch between MTT and CBV maps, thereby delineating a salvageable ‘penumbra’ (Fig. 1b). We believe patients with a small infarct core and a significant volume of reversible ischemic injury are likely to benefit from reperfusion strategies. Therefore, we asked for obtained informed consent from the husband to proceed to IV thrombolysis slightly outside the 4.5-h window. As the time of administration of dabigatran was well known, we did not wait for the results of the coagulation assays at admission, but administered immediately the reversal agent idarucizumab at the recommended dose of 5 g intravenously. Five minutes later, samples for clotting tests were taken and immediately thereafter, at 8.05 AM, IVT using rt-PA was initiated at a standard dose of 0.9 mg/kg (bolus 5 mg and 1-h perfusion 44.5 mg). The results of the coagulation assays at admission were as follows: non-diluted thrombin time 112.0 s (normal 10.0–18.0), prothrombin time 15.5 s (normal 9.35–14.30), activated partial thromboplastin time 32.2 s (normal 25.1–36.5), and elevated international normalized ratio (INR) 1.32 (normal 0.8–1.2). The values after & G. Turine andre.peeters@uclouvain.be

High-dose insulin therapy for neurogenic-stunned myocardium after stroke.

A 44-year-old woman with a history of complicated type 2 diabetes mellitus presented with a diagnosis of right-hemispheric ischaemic stroke. She developed acute respiratory distress with radiological evidence of pulmonary oedema. The ECG showed poorly significant ST-segment changes, with a minimal increase of cardiac biomarkers. Echocardiography showed a severely depressed left ventricular function, with also low values of cardiac output at invasive monitoring. The possibility of neurogenic-stunned myocardium was discussed and a metabolic resuscitation with high-dose insulin was proposed. An intravenous bolus of 80 units of insulin (0.72 IU/kg) was followed by a continuous infusion at the rate of 160 IU/h (1.45 IU/kg/h). The treatment led to a rapid and sustained improvement of the haemodynamic condition and was well tolerated. In comparison with dobutamine, insulin had significant inotropic effects without tachycardia. The patient unfortunately died on day 35, from respiratory complications after poor neurological recovery.

EPITHET--where next?

Comment on EPITHET: failed chance or new hope? Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial.

Profil clinique de la dépression post- accident vasculaire cérébral étude transversale descriptive menée au centre de réhabilitation des personnes handicapées de Kinshasa (RD Congo)

Objectifs : Decrire l’evolution du profil clinique de la DPAVC sur une periode d’un an et determiner les facteurs associes a l’evolution de la DPAVC sur une periode d’un an. Methodes : Il s’agit d’une etude longitudinale portant sur 30 patients suivis pour hemiplegie post-accident vasculaire cerebral au Centre de rehabilitation pour personnes handicapees de Kinshasa (CRPHK). La severite de la depression a ete evaluee avec le « Patient Health Questionnaire » en abrege PHQ9. Le protocole de l’etude a ete administre a chaque patient a deux reprises avec une annee d’intervalle. Resultats : L’âge moyen des patients etait de 55,87±12,67ans. Soixante-dix pour cent des patients etaient des hommes. Il n’a pas ete note de difference statistiquement significative entre les deux evaluations pour l’etat neurologique, l’etat de sante percu et les resultats du test de l’attention. Le pourcentage des patients presentant un syndrome depressif etait de 26,67 % en 2011 et de 20 % en 2012. Les scores aux echelles de l’invalidite et de l’apathie ont ete ameliores de maniere significative. La moyenne observee pour l’invalidite est passee de 2,77±1,19 a 2,46±2,19 (p=0,002). De 66,7 % en 2011, la proportion des patients capables de marcher sans aide est passee a 93,3 % en 2012 (p=0,03). Par ailleurs, la proportion des patients apathiques est passee de 43,3 % a 13,3 % (p=0,01). L’âge superieur ou egal a 65ans, le sexe feminin, les troubles de sommeil post-AVC et l’apathie sont restes associes a la DPAVC entre les deux evaluations, avec une augmentation de la force de l’association pour l’apathie. Conclusions : La frequence de la DPAVC chez les patients de Kinshasa est elevee et reste stable dans le temps. L’invalidite est la caracteristique clinique qui a evolue le plus favorablement. L’association avec l’apathie, presente au debut de l’etude s’est renforcee dans le temps.

'De novo' Col4A2 mutation in a patient with migraine, leukoencephalopathy, and small carotid aneurysms

Collagen IV-related diseases affect the basement membrane and can be caused by COL4A1 or COL4A2 gene mutations. The phenotypic expression seems to be similar in both and encompass porencephaly, small-vessel disease, ocular involvement, peripheral myopathy, and kidney disease. A 17-year-old boy presented with migraine headaches for 5 years. A brain MRI showed diffuse white matter hyperintensities on FLAIR sequence, while MRA revealed small aneurysms of both carotid siphons (Fig. 1). He had a completely normal physical exam. He never complained of muscular cramps, but a severe transient increase in CK level (970 the normal range) was recurrently measured 24–72 h after mild exercise (football). Myoglobinuria was ruled out at rest. Abdominal MRI and ophthalmologic examination with fluorescein angiography were normal. Sequencing of COL4A1 did not identify any mutation. COL4A2 gene sequencing identified the c.2105 G[A mutation in exon 28, at protein level resulting in a glycine substitution: p.(Gly702Asp). This mutation has been found in a large family showing dominant porencephaly with reduced penetrance [1, 2]. The present report adds a distinct patient of Caucasian origin with the same mutation: this allows to confirm its pathogenicity (after molecular evidence—nucleotide and protein changes as impact on the triple helix formation—and cellular involvement). His healthy parents did not carry the mutation (‘de novo’). After 1-year follow-up, brain MRI and MRA remained unchanged. Type IV collagens are a major component of all basement membranes. Six genes arranged by pairs encode for six alpha polypeptide chains. The COL4A2 gene encodes the alpha 2 polypeptide chain which forms heterotrimers with two alpha 1 chains. Each polypeptide chain contains a triple helical domain, a short 7S domain and a globular non-collagenous (NC1) domain. The collagenous domain consists of Gly-Xaa-Yaa repeats with interruptions. Putative COL4A2 gene mutations were found on X location of the repeats and in the NC1 domain in patients suffering from intra-cerebral haemorrhage (ICH) [3]. Significant differences in phenotypic expression of an individual mutation also suggest a role for environmental influences or genetic modifiers with a focus on the secretion’s regulation of mutant COL4A2 from the endoplasmic reticulum [1]. Phenotypic variability (ICH, myopathy, etc.) seems to depend on different pathogenic mechanisms, and their respective severity may be correlated to the different locations of the mutation [4]. Increase CK level without cramps is well known in patients with HANAC syndrome [5]. A link between CK elevation and exertion has never been reported in patients with COL4A2 gene mutation but was reported in mice with COL4A1 gene mutations [6]. De novo mutations were found in two other patients [7, 8]. Our patient is up to now asymptomatic similar to adult carriers & Paul Kollmann paul.kollmann@chirec.be