Betty Jean

Atorvastatin decreases computed tomography and S100-assessed brain ischemia after subarachnoid aneurysmal hemorrhage: a comparative study.

Objective: Statins, which improve the bioavailability of endogenous nitric oxide and upregulate endothelial nitric oxide synthase, have been used to prevent cerebral vasospasm after aneurysmal subarachnoid hemorrhage. The objective of this study was to determine whether statin therapy diminished vasospasm-induced ischemia as assessed using daily measurements of serum S100B, a biomarker for cerebral ischemia, and computed tomography measurement of ischemic lesion volume. Design: Single-center study of cases and historical controls. Setting: Neurointensive care unit in a university hospital. Patients: Consecutive patients with aneurysmal subarachnoid hemorrhage treated with clipping or coiling within 96 hrs of symptom onset (n = 278) were included from April 2004 to October 2007. Intervention: Oral atorvastatin, 40 mg/day for 21 days, was used routinely starting on December 1, 2005, in 142 patients, who were compared with the 136 patients managed earlier. Measurements and Main Results: Ischemic lesion size was measured using computed tomography on the last available scan and serum S100B was assayed daily for 15 days after admission. Angiographic narrowing was semiquantitatively assessed in patients with vasospasm. In the overall population, cerebral vasospasm was significantly less common in the statin-treated group. Severity of vasospasm, as assessed on the most severe angiogram, was lowered with statin. Statins significantly reduced volume of ischemia in patients with vasospasm and an uncomplicated coiling procedure. S100B levels were significantly lower in statin-treated patients, and the decrease was greatest among high-grade patients (World Federation of Neurological Surgeons 3–5). No differences were found between statin-treated and untreated groups regarding rescue therapy intensity or 1-yr clinical outcomes. Conclusions: Atorvastatin reduces the incidence, the severity and the ischemic consequences of vasospasm as assessed on computed tomography. In high-grade World Federation of Neurological Surgeons patients, atorvastatin decreases serum levels of S100B, a biomarker of brain ischemia. Despite these positive effects on biomarkers, no improvement of outcome was seen in the overall population, although there was a tendency for a better clinical outcome in high-grade patients.

Proton MR Spectroscopy for Diagnosis and Evaluation of Treatment Efficacy in Parkinson Disease

PURPOSEnTo assess the neurochemical profile in the putamen of patients with parkinsonian syndromes undergoing L-3,4-dihydroxyphenylalanine (L-DOPA) treatment (drug-on) or after withdrawal of L-DOPA medication (drug-off) compared with healthy volunteers to identify dopaminergic therapy-sensitive biomarkers of Parkinson disease.nnnMATERIALS AND METHODSnThe local institutional review board approved the study, and all participants gave informed consent. A short echo-time (29 msec) single-voxel (1-cm(3)) proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopic approach was used at 3 T to explore the metabolic profile in the putamen of patients with Parkinson disease. Spectra obtained from 20 healthy volunteers were blindly compared with spectra obtained from 20 patients with parkinsonian syndromes in drug-on and drug-off conditions in a randomized permuted block study to assess the accuracy of diagnostic biomarkers for Parkinson disease and efficacy of L-DOPA therapy. The statistical tests were two sided, with a type-I error set at α of .05. Random-effects models were used to compare healthy subjects and patients with parkinsonian syndromes in drug-on or drug-off conditions.nnnRESULTSnMeasured concentrations of putaminal total N-acetylaspartate (tNAA) (8.1 ± 0.2 vs 9.4 ± 0.4; P < .01), total creatine (tCr) (7.5 ± 0.2 vs 8.3 ± 0.3; P < .01), and myo-inositol (m-Ins) (3.8 ± 0.3 vs 5.6 ± 0.4; P < .001) were significantly lower in patients with parkinsonian syndromes in drug-off condition than in healthy volunteers. Moreover, L-DOPA therapy restored tNAA (9.1 ± 0.4 vs 8.1 ± 0.2; P < .01) and tCr (8.1 ± 0.3 vs 7.5 ± 0.2; P < .01) levels, whereas m-Ins levels remained unchanged. The combined glutamate and glutamine and choline showed no changes in drug-off or drug-on condition compared with those in control subjects.nnnCONCLUSIONntNAA, tCr, and m-Ins were identified as putative biomarkers of Parkinson disease in the putamen of patients. tNAA and tCr levels are responsive to L-DOPA therapy.

Combined DTI Tractography and Functional MRI Study of the Language Connectome in Healthy Volunteers: Extensive Mapping of White Matter Fascicles and Cortical Activations

Despite a better understanding of brain language organization into large-scale cortical networks, the underlying white matter (WM) connectivity is still not mastered. Here we combined diffusion tensor imaging (DTI) fiber tracking (FT) and language functional magnetic resonance imaging (fMRI) in twenty healthy subjects to gain new insights into the macroscopic structural connectivity of language. Eight putative WM fascicles for language were probed using a deterministic DTI-FT technique: the arcuate fascicle (AF), superior longitudinal fascicle (SLF), uncinate fascicle (UF), temporo-occipital fascicle, inferior fronto-occipital fascicle (IFOF), middle longitudinal fascicle (MdLF), frontal aslant fascicle and operculopremotor fascicle. Specific measurements (i.e. volume, length, fractional anisotropy) and precise cortical terminations were derived for each WM fascicle within both hemispheres. Connections between these WM fascicles and fMRI activations were studied to determine which WM fascicles are related to language. WM fascicle volumes showed asymmetries: leftward for the AF, temporoparietal segment of SLF and UF, and rightward for the frontoparietal segment of the SLF. The lateralization of the AF, IFOF and MdLF extended to differences in patterns of anatomical connections, which may relate to specific hemispheric abilities. The leftward asymmetry of the AF was correlated to the leftward asymmetry of fMRI activations, suggesting that the lateralization of the AF is a structural substrate of hemispheric language dominance. We found consistent connections between fMRI activations and terminations of the eight WM fascicles, providing a detailed description of the language connectome. WM fascicle terminations were also observed beyond fMRI-confirmed language areas and reached numerous cortical areas involved in different functional brain networks. These findings suggest that the reported WM fascicles are not exclusively involved in language and might be related to other cognitive functions such as visual recognition, spatial attention, executive functions, memory, and processing of emotional and behavioral aspects.

Using High Spatial Resolution to Improve BOLD fMRI Detection at 3T.

For different functional magnetic resonance imaging experiments using blood oxygenation level-dependent (BOLD) contrast, the acquisition of T 2*-weighted scans at a high spatial resolution may be advantageous in terms of time-course signal-to-noise ratio and of BOLD sensitivity when the regions are prone to susceptibility artifacts. In this study, we explore this solution by examining how spatial resolution influences activations elicited when appetizing food pictures are viewed. Twenty subjects were imaged at 3 T with two different voxel volumes, 3.4 μl and 27 μl. Despite the diminution of brain coverage, we found that high-resolution acquisition led to a better detection of activations. Though known to suffer to different degrees from susceptibility artifacts, the activations detected by high spatial resolution were notably consistent with those reported in published activation likelihood estimation meta-analyses, corresponding to taste-responsive regions. Furthermore, these regions were found activated bilaterally, in contrast with previous findings. Both the reduction of partial volume effect, which improves BOLD contrast, and the mitigation of susceptibility artifact, which boosts the signal to noise ratio in certain regions, explained the better detection noted with high resolution. The present study provides further evidences that high spatial resolution is a valuable solution for human BOLD fMRI, especially for studying food-related stimuli.

Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study

BACKGROUNDnPrediction of neurological outcome after cardiac arrest is a major challenge. The aim of this study was to assess whether quantitative whole-brain white matter fractional anisotropy (WWM-FA) measured by diffusion tensor imaging between day 7 and day 28 after cardiac arrest can predict long-term neurological outcome.nnnMETHODSnThis prospective, observational, cohort study (part of the MRI-COMA study) was done in 14 centres in France, Italy, and Belgium. We enrolled patients aged 18 years or older who had been unconscious for at least 7 days after cardiac arrest into the derivation cohort. The following year, we recruited the validation cohort on the same basis. We also recruited a minimum of five healthy volunteers at each centre for the normalisation procedure. WWM-FA values were compared with standard criteria for unfavourable outcome, conventional MRI sequences (fluid-attenuated inversion recovery and diffusion-weighted imaging), and proton magnetic resonance spectroscopy. The primary outcome was the best achieved Glasgow-Pittsburgh Cerebral Performance Categories (CPC) at 6 months, dichotomised as favourable (CPC 1-2) and unfavourable outcome (CPC 3-5). Prognostication performance was assessed by the area under the receiver operating characteristic (ROC) curves and compared between groups. This study was registered with ClinicalTrials.gov, number NCT00577954.nnnFINDINGSnBetween Oct 1, 2006, and June 30, 2014, 185 patients were enrolled in the derivation cohort, of whom 150 had an interpretable multimodal MRI and were included in the analysis. 33 (22%) patients had a favourable neurological outcome at 6 months. Prognostic accuracy, as quantified by the area under the ROC curve, was significantly higher with the normalised WWM-FA value (area under the ROC curve 0·95, 95% CI 0·91-0·98) than with the standard criteria for unfavourable outcome or other MRI sequences. In a subsequent validation cohort of 50 patients (enrolled between April 1, 2015, and March 31, 2016), a normalised WWM-FA value lower than 0·91, set from the derivation cohort, had a negative predictive value of 71·4% (95% CI 41·9-91·6) and a positive predictive value of 100% (90·0-100), with 89·7% sensitivity (75·8-97·1) and 100% specificity (69·1-100) for the prediction of unfavourable outcome.nnnINTERPRETATIONnIn patients who are unconscious 7 days after cardiac arrest, the normalised WWM-FA value, measured by diffusion tensor imaging, could be used to accurately predict neurological outcome at 6 months. This evidence requires confirmation from future large-scale trials with a strict protocol of withdrawal or limitation-of-care decisions and time window for MRI.nnnFUNDINGnFrench Ministry of Health, French National Agency for Research, Italian Ministry of Health, and Regione Lombardia.

Early Functional Connectome Integrity and 1-Year Recovery in Comatose Survivors of Cardiac Arrest

Purpose To assess whether early brain functional connectivity is associated with functional recovery 1 year after cardiac arrest (CA). Materials and Methods Enrolled in this prospective multicenter cohort were 46 patients who were comatose after CA. Principal outcome was cerebral performance category at 12 months, with favorable outcome (FO) defined as cerebral performance category 1 or 2. All participants underwent multiparametric structural and functional magnetic resonance (MR) imaging less than 4 weeks after CA. Within- and between-network connectivity was measured in dorsal attention network (DAN), default-mode network (DMN), salience network (SN), and executive control network (ECN) by using seed-based analysis of resting-state functional MR imaging data. Structural changes identified with fluid-attenuated inversion recovery and diffusion-weighted imaging sequences were analyzed by using validated morphologic scales. The association between connectivity measures, structural changes, and the principal outcome was explored with multivariable modeling. Results Patients underwent MR imaging a mean 12.6 days ± 5.6 (standard deviation) after CA. At 12 months, 11 patients had an FO. Patients with FO had higher within-DMN connectivity and greater anticorrelation between SN and DMN and between SN and ECN compared with patients with unfavorable outcome, an effect that was maintained after multivariable adjustment. Anticorrelation of SN-DMN predicted outcomes with higher accuracy than fluid-attenuated inversion recovery or diffusion-weighted imaging scores (area under the receiver operating characteristic curves, respectively, 0.88, 0.74, and 0.71). Conclusion MR imaging-based measures of cerebral functional network connectivity obtained in the acute phase of CA were independently associated with FO at 1 year, warranting validation as early markers of long-term recovery potential in patients with anoxic-ischemic encephalopathy.

Interest of local intra-arterial fibrinolysis in acute central retinal artery occlusion: Clinical experience in 16 patients

OBJECTIVEnCentral retinal artery occlusion (CRAO) is a rare disease with poor visual prognosis. We evaluated clinical effectiveness of in situ fibrinolysis with original angiographic scores describing the aspect of carotid siphon, proximal ophthalmic artery, and choroid blush.nnnMETHODSnRetrospective study of 16 consecutive cases of CRAO between 2007 and 2013. Fourteen underwent in situ fibrinolysis, two were excluded due to pre-occlusive internal carotid stenosis on pre-procedural diagnostic angio-CT. Fibrinolysis was performed with rt-PA (average injected dose: 35 mg), with an average onset delay of 8hours (4-17h). We reported angiographic scores pre- and post-fibrinolysis, visual acuity (VA) before and after treatment, and VA improvement evaluated by ophthalmologist 6 to 12 months after thrombolysis.nnnRESULTSnSix patients (43%) recovered post-fibrinolysis VA significally improved, superior or equal to 1/10 (1/10 to 8/10). An irregular carotid siphon (2 cases) appeared as a predictive factor of failure. Fibrinolysis procedure led to a significant improvement of angiographic permeability of proximal ophthalmic artery (P=0.0498), but this result was not accompanied by any VA improvement. The aspect of choroid blush showed no correlation with the management of thrombolysis.nnnCONCLUSIONnIn situ fibrinolysis was more effective than medical treatments or natural evolution of CRAO (VA improvement was respectively 40% and 20%). However, the benefit/risk ratio must be discussed, and an angio-CT of supra-aortic trunks could be systematically performed before thrombolysis, to assess the potential VA recovery compared with complications such as ischemic stroke.

The brain signature of paracetamol in healthy volunteers: a double-blind randomized trial

Background Paracetamol’s (APAP) mechanism of action suggests the implication of supraspinal structures but no neuroimaging study has been performed in humans. Methods and results This randomized, double-blind, crossover, placebo-controlled trial in 17 healthy volunteers (NCT01562704) aimed to evaluate how APAP modulates pain-evoked functional magnetic resonance imaging signals. We used behavioral measures and functional magnetic resonance imaging to investigate the response to experimental thermal stimuli with APAP or placebo administration. Region-of-interest analysis revealed that activity in response to noxious stimulation diminished with APAP compared to placebo in prefrontal cortices, insula, thalami, anterior cingulate cortex, and periaqueductal gray matter. Conclusion These findings suggest an inhibitory effect of APAP on spinothalamic tracts leading to a decreased activation of higher structures, and a top-down influence on descending inhibition. Further binding and connectivity studies are needed to evaluate how APAP modulates pain, especially in the context of repeated administration to patients with pain.

Personalized mapping of the deep brain with a white matter attenuated inversion recovery (WAIR) sequence at 1.5-tesla: Experience based on a series of 156 patients.

OBJECTIVEnDeep brain mapping has been proposed for direct targeting in stereotactic functional surgery, aiming to personalize electrode implantation according to individual MRI anatomy without atlas or statistical template. We report our clinical experience of direct targeting in a series of 156xa0patients operated on using a dedicated Inversion Recovery Turbo Spin Echo sequence at 1.5-tesla, called White Matter Attenuated Inversion Recovery (WAIR).nnnMETHODSnAfter manual contouring of all pertinent structures and 3D planning of trajectories, 312xa0DBS electrodes were implanted. Detailed anatomy of close neighbouring structures, whether gray nuclei or white matter regions, was identified during each planning procedure. We gathered the experience of these 312xa0deep brain mappings and elaborated consistent procedures of anatomical MRI mapping for pallidal, subthalamic and ventral thalamic regions. We studied the number of times the central track anatomically optimized was selected for implantation of definitive electrodes.nnnRESULTSnWAIR sequence provided high-quality images of most common functional targets, successfully used for pure direct stereotactic targeting: the central track corresponding to the optimized primary anatomical trajectory was chosen for implantation of definitive electrodes in 90.38%.nnnCONCLUSIONnWAIR sequence is anatomically reliable, enabling precise deep brain mapping and direct stereotactic targeting under routine clinical conditions.

Use of a prototype radioprotection cabin in vascular neuroradiology: Dosimetry and ergonomics.

OBJECTIVESnThe aim of this work was to compare the performance of a prototype radioprotection cabin in interventional neuroradiology, and to assess its suitability for routine use.nnnMATERIALS AND METHODSnThe radioprotection cabin was a prototype derived from the CATHPAX AF(®) model. Three operators carried out 21 procedures (19 brain arteriographies and 2 embolizations) using the radioprotection cabin and not wearing the usual lead individual protection equipment (IPE), and 17 procedures (16 brain arteriographies and 1 embolization) wearing the standard lead IPE (vest, skirt, thyroid shield and goggles), and not using the radioprotection cabin. In all cases, thermoluminescent dosimeters (TLDs) were positioned at head, trunk, pelvic region, and upper and lower limbs to measure the dose equivalent for Hp(0.07) or Hp(3) that they received, attenuated by either the cabin or the lead IPE. Parallel to these dosimetric measurements, the ergonomics of the protection cabin were appraised by each radiologist after each procedure.nnnRESULTS AND CONCLUSIONnThe cabin procured an overall reduction of 74% of the dose received on the whole body with Hp(0.07)=0.04 mSv ± 0.01 (CL=95%) against Hp(0.07)=0.12 mSv ± 0.04 (CL=95%) for the IPE. Body protection with the cabin was near complete, and close to 100% for the regions not protected by the usual IPE (e.g. the head). We also showed that design weaknesses noted by the operators that hampered procedures (light reflections, reduced hand mobility, awkward access to radioscopy pedal) could be remedied by makers improvements to the prototype and minor changes in work habits.