Catherine Oppenheim

Cortex morphology in first-episode psychosis patients with neurological soft signs.

Schizophrenia is a complex brain disorder associated with numerous etiological factors and pathophysiological pathways leading to multiple clinical outcomes. Compelling evidence suggests that deviations in neurodevelopmental processes are a major risk factor of schizophrenia. The identification of patients with high neurodevelopmental deviance is an important issue as it could help to identify homogeneous subgroups of patients with similar pathophysiological pathways, a key step to decipher the etiology of this complex condition. Several clinical arguments suggest that schizophrenia patients with Neurological Soft Signs (NSS)--ie, observable defects in motor coordination, motor integration, and sensory integration--would have high neurodevelopmental deviance. Based on the analysis of magnetic resonance imaging of 44 first-episode psychosis patients, we compared the cortex morphology, a marker of brain development, in patients with NSS vs patients with nonsignificant NSS. The cortex morphology was automatically assessed from three-dimensional global sulcal index (g-SI, the ratio between total sulcal area and outer cortex area) and regional sulcal indexes (r-SI, the ratio between the area of pooled labeled sulci and the total outer cortex area). Patients with NSS were found to have a lower g-SI in both hemispheres and a lower r-SI in left dorsolateral prefrontal and right lateral occipital cortices. Exploratory analyses revealed correlations between NSS dimensions and r-SI in distinct cortical areas, including dorsolateral and medial prefrontal cortices, lateral temporal, occipital, superior parietal, and medial parieto-occipital cortices. These findings provide evidence of distinct neurodevelopmental pathways in patients with NSS as compared with patients with nonsignificant NSS.

Relationships Between Recent Intraplaque Hemorrhage and Stroke Risk Factors in Patients With Carotid Stenosis The HIRISC Study

Objective—Intraplaque hemorrhage (IPH) is an emerging marker of plaque instability. However, little is known about the relationships between IPH and traditional risk factors and whether these relationships differ between symptomatic and asymptomatic disease. Methods and Results—Two hundred thirty-four patients with symptomatic (n=114) or asymptomatic (n=120) carotid stenosis underwent high-resolution plaque magnetic resonance imaging. Seventy-five patients had recent IPH (symptomatic, 33%; asymptomatic, 31%). In symptomatic stenosis, recent IPH was independently associated with degree of stenosis (odds ratio [OR]=4.21, 1.61–10.98 for North American Symptomatic Carotid Endarterectomy Trial >35%; OR=2.92, 1.18–7.24 for European Carotid Surgery Trial >60%), qualifying event (OR=4.13; 1.11–15.32 for stroke or hemispheric transient ischemic attack ≥1 hour versus transient ischemic attack <1 hour or ocular symptoms), time from ischemic event (OR=6.65, 1.56–28.35 for ⩽2 weeks; OR=2.24, 0.87–5.81 for 2–12 weeks versus >12 weeks; P for trend=0.03). In asymptomatic stenosis, IPH was only associated with stenosis severity >70% by ECST (OR=6.65; 1.95–22.73) but not by the NASCET method. Conclusion—Our findings support the potential link between recent IPH and risk of ipsilateral stroke in symptomatic disease but also imply that prognostic studies should adjust for known stroke risk factors in multivariate analyses. In asymptomatic stenosis, the potential predictive value of recent IPH is less likely to be confounded by stroke risk factors.

Mechanical and Structural Characteristics of Carotid Plaques by Combined Analysis With Echotracking System and MR Imaging

OBJECTIVESnThe purpose of this study was to correlate the arterial mechanics of carotid atherosclerotic plaques assessed from echotracking with their composition by high-resolution magnetic resonance imaging (HR-MRI).nnnBACKGROUNDnAnalysis of the relationship between mechanical parameters and structure of the plaque allows better understanding of the mechanisms leading to mechanical fatigue of plaque material, plaque rupture, and ischemic events. A specific longitudinal gradient of strain (reduced strain, i.e., lower radial strain at the plaque level than at the adjacent segment) has been shown in atherosclerotic plaques on the common carotid artery (CCA) in patients with hypertension, dyslipidemia, or type 2 diabetes mellitus. The structural abnormalities underlying this functional behavior have not been determined.nnnMETHODSnForty-six carotid plaques from 27 patients were evaluated; plaques were present at the site of the carotid bifurcation and extended to the CCA. Among the 27 patients, 9 had previous ischemic stroke ipsilateral to carotid stenosis (symptomatic) and 18 had not (asymptomatic). Mechanical parameters were measured at 128 sites on a 4-cm long CCA segment by noninvasive echotracking system, and strain gradient was calculated. Plaque composition was noninvasively determined by HR-MRI.nnnRESULTSnComplex plaques at HR-MRI (i.e., American Heart Association [AHA] stages IV to VIII) more often displayed a reduced strain than the simple plaques (i.e., AHA stages I to III; p = 0.046). HR-MRI verified complex plaques were associated with an outer remodeling upon echotracking, and had a lower distensibility than adjacent CCA (17.0 ± 5.0 MPa⁻¹ vs. 21.7 ± 7.3 MPa⁻¹; p = 0.007). An outer remodeling was observed in plaques with a lipid core at HR-MRI and was more frequent in symptomatic carotids.nnnCONCLUSIONSnThese findings indicate that the longitudinal mechanics of complex plaques follows a specific pattern of reduced strain. They also suggest that reduced strain, associated with an outer remodeling, may be a feature of high-risk plaques.

Glioma dissemination along the corticospinal tract

Department of Neuroradiology,Centre Hospitalier Sainte-Anne, Paris, FranceKey words: corticospinal tract, descending pathways, dissemination, glioma, white matter fiber tractsA 25-year-old right-handed woman, without anymedical history, was presented with a two-monthhistory of headaches. Neurological examinationwas unremarkable apart from signs of intracranialhypertension. The fundoscopy showed bilateral pap-illedema.The MRI demonstrated a multifocal heterogeneousmass, involving both frontal lobes, corpus callosum andthe basal ganglia on the right-hand side. The mass washypointense on T1-weighted images, contrast enhancedafter gadolinium injection, and hyperintense on T2-weighted and fluid-attenuated inversion recovery(FLAIR) images. The T2-weighted and FLAIR imagesdemonstrated an area of hyperintense signal locatedalong the left corticospinal tract (Figure 1). An incom-plete resection of the left frontal part of the tumor wasperformed. Pathological examination revealed an oli-godendroglioma WHO grade III and Sainte AnneClassification grade B [1]. The postoperative manage-ment consisted in Temozolomide chemotherapy andexternal conformational radiotherapy. Six months aftersurgery, neurological examination revealed a rightpyramidal syndrome without any motor deficit. Thepatient is still under therapy.

Comparison between voxel-based and subtraction methods for measuring diffusion-weighted imaging lesion growth after thrombolysis

Background Infarct growth (IG) is used as surrogate end-point in therapeutic trials. For practical reasons, infarct growth is commonly assessed using simple subtraction of acute from follow-up diffusion-weighted imaging (DWI) lesion volumes. However, the volume subtraction method will underestimate true infarct growth in case of diffusion-weighted imaging lesion reversal. Aim To measure the size of the difference between true infarct growth on voxel-based coregistration and infarct growth approximated with simple volume subtraction. Methods We retrospectively analyzed 322 consecutive stroke patients (median (IQR) age: 70 years (57–80), National Institute of Health Stroke Score at admission 14 (8–19)), who underwent a magnetic resonance imaging before (DWI1) and ≈24u2009h (DWI2) after IV-thrombolysis. IGvoxel-based was defined as the volume of signal changes on DWI2 that did not overlap with that on coregistered DWI1. This was compared with simply subtracting DWI1 from DWI2 lesion volume (IGsubtracted). We also compared these two metrics for the prediction of three-month unfavorable outcome (mRSu2009≥u20092) using c-statistics of multivariable models, adjusted for age, and National Institute of Health Stroke Score. Results Infarct growth volume metrics were strongly correlated (ρu2009=u20090.94), but IGsubtracted substantially underestimated IGvoxel-based (median (IQR): 9.52 (0.23–38.9) vs. 16.98 (4.4–45.4) mL). Of the 75 patients with shrinking or stable diffusion-weighted imaging lesion using volume subtraction, IGvoxel-based was ≥5u2009mL in 20 (27% of the subset, 6.2% of the whole population). Moreover, IGvoxel-based better predicted unfavorable outcome than IGsubtracted (c-statisticsu2009=u20090.86 (95% CI, 0.82–0.90) vs. 0.82 (0.78–0.87), Pu2009=u20090.003). Conclusion At early post-thrombolysis time points, the simple subtraction of lesion volumes masked substantial diffusion-weighted imaging lesion growth in 6.2% of patients. Although more time-consuming, the voxel-based method may impact results of trials that use infarct growth attenuation as an end-point.

Sex Differences in the Neural Correlates of Specific and General Autobiographical Memory

Autobiographical memory (AM) underlies the formation and temporal continuity over time of personal identity. The few studies on sex-related differences in AM suggest that men and women adopt different cognitive or emotional strategies when retrieving AMs. However, none of the previous works has taken into account the distinction between episodic autobiographical memory (EAM), consisting in the retrieval of specific events by means of mental time travel, and semantic autobiographical memory (SAM), which stores general personal events. Thus, it remains unclear whether differences in these strategies depend on the nature of the memory content to be retrieved. In the present study we employed functional MRI to examine brain activity underlying potential sex differences in EAM and SAM retrieval focusing on the differences in strategies related to the emotional aspects of memories while controlling for basic cognitive strategies. On the behavioral level, there was no significant sex difference in memory performances or subjective feature ratings of either type of AM. Activations common to men and women during AM retrieval were observed in a typical bilateral network comprising medial and lateral temporal regions, precuneus, occipital cortex as well as prefrontal cortex. Contrast analyses revealed that there was no difference between men and women in the EAM condition. In the SAM condition, women showed an increased activity, compared to men, in the dorsal anterior cingulate cortex, inferior parietal and precentral gyrus. Overall, these findings suggest that differential neural activations reflect sex-specific strategies related to emotional aspects of AMs, particularly regarding SAM. We propose that this pattern of activation during SAM retrieval reflects the cognitive cost linked to emotion regulation strategies recruited by women compared to men. These sex-related differences have interesting implications for understanding psychiatric disorders with differential sex prevalence and in which one of key features is overgenerality in AM.

Extent of resection and Carmustine wafer implantation safely improve survival in patients with a newly diagnosed glioblastoma: a single center experience of the current practice

For newly diagnosed glioblastomas treated with resection in association with the standard combined chemoradiotherapy, the impact of Carmustine wafer implantation remains debated regarding postoperative infections, quality of life, and feasibility of adjuvant oncological treatments. To assess together safety, tolerance and efficacy of Carmustine wafer implantation and of extent of resection for glioblastoma patients in real-life experience. Observational retrospective monocentric study including 340 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent surgical resection with (nu2009=u2009123) or without (nu2009=u2009217) Carmustine wafer implantation as first-line oncological treatment. Carmustine wafer implantation and extent of resection did not significantly increase postoperative complications, including postoperative infections (pu2009=u20090.269, and pu2009=u20090.446, respectively). Carmustine wafer implantation and extent of resection did not significantly increase adverse events during adjuvant oncological therapies (pu2009=u20090.968, and pu2009=u20090.571, respectively). Carmustine wafer implantation did not significantly alter the early postoperative Karnofsky performance status (pu2009=u20090.402) or the Karnofsky performance status after oncological treatment (pu2009=u20090.636) but a subtotal or total surgical resection significantly improved those scores (pu2009<u20090.001, and pu2009<u20090.001, respectively). Carmustine wafer implantation, subtotal and total resection, and standard combined chemoradiotherapy were independently associated with longer event-free survival (adjusted Hazard Ratio (aHR), 0.74 [95% CI 0.55–0.99], pu2009=u20090.043; aHR, 0.70 [95% CI 0.54–0.91], pu2009=u20090.009; aHR, 0.40 [95% CI 0.29–0.55], pu2009<u20090.001, respectively) and with longer overall survival (aHR, 0.69 [95% CI 0.49–0.96], pu2009=u20090.029; aHR, 0.52 [95% CI 0.38–0.70], pu2009<u20090.001; aHR, 0.58 [95% CI 0.42–0.81], pu2009=u20090.002, respectively). Carmustine wafer implantation in combination with maximal resection, followed by standard combined chemoradiotherapy is safe, efficient, and well-tolerated in newly diagnosed supratentorial glioblastomas in adults.

Altered cortical processing of motor inhibition in schizophrenia

Inhibition is considered a key mechanism in schizophrenia. Short-latency intracortical inhibition (SICI) in the motor cortex is reduced in schizophrenia and is considered to reflect locally deficient γ-aminobutyric acid (GABA)-ergic modulation. However, it remains unclear how SICI is modulated during motor inhibition and how it relates to neural processing in other cortical areas. Here we studied motor inhibition Stop signal task (SST) in stabilized patients with schizophrenia (Nxa0=xa028), healthy siblings (Nxa0=xa021) and healthy controls (nxa0=xa031) matched in general cognitive status and educational level. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were used to investigate neural correlates of motor inhibition. SST performance was similar in patients and controls. SICI was modulated by the task as expected in healthy controls and siblings but was reduced in patients with schizophrenia during inhibition despite equivalent motor inhibition performance. fMRI showed greater prefrontal and premotor activation during motor inhibition in schizophrenia. Task-related modulation of SICI was higher in subjects who showed less inhibition-related activity in pre-supplementary motor area (SMA) and cingulate motor area. An exploratory genetic analysis of selected markers of inhibition (GABRB2, GAD1, GRM1, and GRM3) did not explain task-related differences in SICI or cortical activation. In conclusion, this multimodal study provides direct evidence of a task-related deficiency in SICI modulation in schizophrenia likely reflecting deficient GABA-A related processing in motor cortex. Compensatory activation of premotor areas may explain similar motor inhibition in patients despite local deficits in intracortical processing. Task-related modulation of SICI may serve as a useful non-invasive GABAergic marker in development of therapeutic strategies in schizophrenia.

Fast 4D Flow MRI Re-Emerges as a Potential Clinical Tool for Neuroradiology

Shortly after the introduction of clinical MR imaging, Moran[1][1] demonstrated that velocity and flow could be measured noninvasively by using flow-encoding gradients integrated into conventional MR imaging techniques. This innovation was quickly implemented, resulting in 2D and 3D phase-contrast

Individual Variability of the Human Cerebral Cortex Identified Using Intraoperative Mapping

BACKGROUNDnIntraoperative functional cortical mapping using direct electrical stimulation may show a wider individual variability than suggested by noninvasive imaging data of healthy subjects.nnnMETHODSnWe assessed intraoperative variability of the frontal eye fields and the speech arrest sites in adult patients who underwent awake craniotomy with direct electrostimulation for treatment of diffuse gliomas located within eloquent regions, and we compared findings with human cortical parcellation of the Human Connectome Project.nnnRESULTSnThe frontal eye fields were defined by intraoperative direct electrostimulations (14.3% of patients) projected on the superior subdivision of the premotor cortex covering the areas defined as frontal eye fields (parcel index 10), area 55b (parcel index 12), and premotor eye field (parcel index 11) and in the posterior part of the dorsolateral prefrontal cortex covering the areas defined as inferior 6-8 transitional area (parcel index 97), area 8Av (parcel index 67), and area 8C (parcel index 73). The speech arrest sites were defined by intraoperative direct electrostimulations (100% of patients) projected predominantly posteriorly to the inferior frontal gyrus in the inferior subdivision of the premotor cortex, that is, rostral area 6 (parcel index 78), ventral area 6 (parcel index 54), and area 43 (parcel index 99).nnnCONCLUSIONSnIntraoperative functional cortical mapping using direct electrostimulation highlights that actual individual variability is wider than suggested by analyses of healthy subjects and results in atypical patterns of functional organization and structural and functional changes of the human cerebral cortex under pathologic conditions.