Jean-François Meder

Risk of stroke and recurrent dissection after a cervical artery dissection: A multicenter study

Objective: To assess the risk of stroke, TIA, or dissection recurrence after a first event of cervical artery dissection (CAD). Methods: The authors undertook a historical cohort study of consecutive patients with a first event of CAD who were admitted in 24 departments of neurology within a period of at least 1 year. Patients were retrospectively selected from a stroke data bank or from the local administrative data bank using the 10th revision of the International Statistical Classification of Diseases. A neurologist and a radiologist reviewed all charts to validate diagnosis and collect data. In 2002, patients were interviewed by phone or during a visit by the local investigators. Results: Four hundred fifty-nine patients (mean age 44.0 ± 9.7 years) were included in the study. Among the 457 survivors, 25 (5.5%) could not be contacted in 2002 because they had moved. After a mean follow-up of 31 months, four (0.9%) patients presented a recurrent ischemic stroke attributable to either not yet completely recovered initial CAD (n = 2) or a recurrent CAD (n = 2). Eight (1.8%) patients had a TIA without CAD recurrence. Two TIA occurred at the acute stage of CAD. Of the six remaining TIA, only one was associated with chronic arterial stenosis. In addition, two patients had recurrent CAD without stroke, giving a total of four (0.9%) CAD recurrences. Conclusions: Patients with a first event of CAD have a very low risk of ischemic events or dissection recurrences. Ischemic events seem rarely to be in relation with chronic arterial lesions.

Intraspinal meningiomas: review of 54 cases with discussion of poor prognosis factors and modern therapeutic management.

INTRODUCTION Intraspinal meningiomas account for 25%-46% of primary spinal cord tumors. Technical advances in magnetic resonance imaging (MRI) and surgical procedures (ultrasonic cavitation aspirators [CUSA], lasers) have brought about better clinical results. In spite of these new techniques, a small percentage of patients still present with poor postoperative results and/or a recurrence. The authors tried to determine which data could influence clinical outcome and what therapeutic modalities could limit recurrence rate. MATERIALS AND METHODS We reviewed 54 patients who from 1963 to 1994, each had surgery for an intraspinal meningioma. There were 43 females and 11 males, aged 8 to 85 years old. Thirty-six (66.6%) patients were ambulatory on admission; only 2 presented with a paraplegia. Tumor location was cervical in 10 cases, thoracic in 43 cases, lumbar in 1 case. Forty-seven tumors were intradural, 5 epidural, 2 epidural and intradural. Thirty patients underwent a myelography, 10 a computed tomography (CT) scan, and 14 an MRI. Twenty-three spinal angiographies were performed before surgery. Complete removal was achieved in 50 patients (92.6%). Ultrasonic cavitation was used 10 times for debulking the tumor, and laser was used in 12 surgical procedures to perform hemostasis of the meningioma and to coagulate the dural attachment. RESULTS The majority of the neoplasms were meningothelial (N = 24) or psammomatous (N = 11). No mortality was noted. Morbidity concerned five patients: two pulmonary embolisms, one definitive paraplegia, one transient deficit, and one epidural suppuration, which necessitated a second operation. Mean follow-up was 28 months. Final functional results were very good in 85% and good in 13%; one patient (2%) worsened. Two recurrences were noted: one with clinical signs and the other with only CT-scan modifications. Both patients underwent complementary radiotherapy. DISCUSSION AND CONCLUSION The authors discuss factors influencing functional results. Sex, pregnancy, pathologic diagnosis, and recurrence do not seem to have any influence. Calcification of the meningioma, as well as an anterior dural attachment, are pejorative factors. They insist on preoperative angiography and point out the advantage of using a CUSA and/or a laser to debulk and coagulate the tumor itself and its dural attachment. They propose radiation therapy as an adjuvant treatment or an alternative to reoperation, which could be hazardous for some patients when, for instance, a recurrence is located in a critical area or when the patients general status is fragile.

Diffusion tensor imaging in early Alzheimer's disease

Our aim was to investigate the extent of white matter tissue damage in patients with early Alzheimer disease (AD) using diffusion tensor magnetic resonance imaging (DTI). Although AD pathology mainly affects cortical grey matter, previous magnetic resonance imaging (MRI) studies showed that changes also exist in the white matter (WM). However, the nature of AD-associated WM damage is still unclear. Conventional and DTI examinations (b=1000 s/mm(2), 25 directions) were obtained from 12 patients with early AD (Mini Mental State Examination [MMSE] score=27, Grober and Buschke test score=33.2, digit span score=5.6) and 12 sex- and age-matched volunteers. The right and left mean diffusivity (MD) and fractional anisotropy (FA) of several WM regions were pooled in each patient and control, and compared between the two groups. Volumes of the whole brain and degree of atrophy of the temporal lobe were compared between the two groups. In AD, MD was increased in the splenium of the corpus callosum and in the WM in the frontal and parietal lobes. FA was bilaterally decreased in the WM of the temporal lobe, the frontal lobe and the splenium compared with corresponding regions in controls. Values in other areas (occipital area, superior temporal area, cingulum, internal capsule, and genu of the corpus callosum) were not different between patients and controls. No correlations were found between the MMSE score and the anisotropy indices. Findings of DTI reveal abnormalities in the frontal and temporal WM in early AD patients. These changes are compatible with early temporal-to-frontal disconnections.

Linac radiosurgery for cerebral arteriovenous malformations: results in 169 patients

PURPOSE To present the SALT group results using Linac radiosurgery (RS) for AVM in 169 evaluable patients treated from January 1990 thru December 1993. METHODS AND MATERIALS Median age was 33 years (range 6-68 years). Irradiation was the only treatment in 55% patients. Other treatment modalities had been used prior to RS in 45%: one or more embolizations in 36%, surgery in 6%, and embolization and surgery in 3% patients. Nidus were supratentorial in 94% patients, infratentorial in 6% patients. Circular 15 MV x-ray minibeams (6-20 mm) were delivered in coronal arcs by a GE-CGR Saturne 43 Linac. Patient set-up included a Betti arm-chair, a Talairach frame. Prescribed peripheral dose was 25 Gy on the 60%-70% isodose (max dose 100%). Arteriographic results were reassessed in December 1997 at 48 to 96 months follow-up. RESULTS The overall obliteration rate (OR) was 64% (108/169). AVM volumes ranged from 280 to 19,920 mm(3), median 2460 mm(3). OR was 70% for AVM </= 4200 mm(3) 4200 mm(3) (p 25 mm (p = 0.04). OR was 71%, in the absence of embolization, vs. 54% for previously embolized nidus (p = 0.03). OR was 71% for monocentric RS vs. 54% for multi-isocenters (p 28 Gy vs. 55% for values </= 28 Gy (p 79% vs. 57% for lower values (p 17 Gy, vs. 59% for mLd </= 16 Gy (p 40%, vs. 54% for mLi </= 40% (p 85% vs. 60% for CR </= 84% (NS). For patients treated according to our protocol, i.e., 24-26 Gy on the 60%-70% isodoses, OR was higher (68%) than for other patients (47%) (p = 0.02). After multivariate analysis, absence of previous embolization and mono isocentric-irradiation were independent factors predicting obliteration. Complications were: recurrent hemorrhage, 4 patients (1 patient died); brain necrosis on MRI, 2 patients; subsequent epilepsy, 4 patients; other subsequent neurologic deficits, 3 patients. CONCLUSION Overall OR was 64% (48-96 months follow-up). After monovariate analysis higher ORs were associated with smaller volumes </= 4200 mm(3), smaller nidus size </= 25 mm, absence of prior embolization, monoisocentric RS, higher values for mean and minimum lesion doses and compliance to our protocol. Higher values for the peripheral dose and isodose tended to give better results. Multivariate analysis showed that the absence of prior embolization and monoisocentric irradiation were independent factors predicting successful irradiation.

Brain networks of spatial awareness: evidence from diffusion tensor imaging tractography.

Left unilateral neglect, a dramatic condition which impairs awareness of left-sided events, has been classically reported after right hemisphere cortical lesions involving the inferior parietal region. More recently, the involvement of long range white matter tracts has been highlighted, consistent with the idea that awareness of events occurring in space depends on the coordinated activity of anatomically distributed brain regions. Damage to the superior longitudinal fasciculus (SLF), linking parietal to frontal cortical regions, or to the inferior longitudinal fasciculus (ILF), connecting occipital and temporal lobes, has been described in neglect patients. In this study, four right-handed patients with right hemisphere strokes underwent a high definition anatomical MRI with diffusion tensor imaging (DTI) sequences and a pencil and paper neglect battery of tests. We used DTI tractography to visualise the SLF, ILF and the inferior fronto-occipital fasciculus (IFOF), a pathway running the depth of the temporal lobe, not hitherto associated with neglect. Two patients with cortical involvement of the inferior parietal and superior temporal regions, but intact and symmetrical fasciculi, showed no signs of neglect. The other two patients with signs of left neglect had superficial damage to the inferior parietal cortex and white matter damage involving the IFOF. These findings suggest that superficial damage to the inferior parietal cortex per se may not be sufficient to produce visual neglect. In some cases, a lesion to the direct connections between ventral occipital and frontal regions (ie, IFOF) may contribute to the manifestation of neglect by impairing the top down modulation of visual areas from the frontal cortex.

FDG-PET improves surgical outcome in negative MRI Taylor-type focal cortical dysplasias

Objective: To determine the diagnostic accuracy and prognostic value of 18FDG-PET in a recent series of patients operated for intractable partial epilepsy associated with histologically proven Taylor-type focal cortical dysplasia (TTFCD) and negative MRI. Methods: Of 23 consecutive patients (12 male, 7–38 years old) with negative 1.5-Tesla MRI, 10 exhibited subtle nonspecific abnormalities (e.g., unusual sulcus depth or gyral pattern) and the 13 others had strictly normal MRI. FDG-PET was analyzed both visually after coregistration on MRI and using SPM5 software. Metabolic data were compared with the epileptogenic zone (EZ) determined by stereo-EEG (SEEG) and surgical outcome. Results: Visual PET analysis disclosed a focal or regional hypometabolism in 18 cases (78%) corresponding to a single gyrus (n = 9) or a larger cortical region (n = 9). PET/MRI coregistration detected a partially hypometabolic gyrus in 4 additional cases. SPM5 PET analysis (n = 18) was concordant with visual analysis in 13 cases. Location of PET abnormalities was extratemporal in all cases, involving eloquent cortex in 15 (65%). Correlations between SEEG, PET/MRI, and histologic findings (n = 20) demonstrated that single hypometabolic gyri (n = 11) corresponded to EZ and TTFCD, which was localized at the bottom of the sulcus. Larger hypometabolic areas (n = 9) also included the EZ and the dysplastic cortex but were more extensive. Following limited cortical resection (mean follow-up 4 years), seizure freedom without permanent motor deficit was obtained in 20/23 patients (87%). Conclusions: 18FDG-PET coregistered with MRI is highly sensitive to detect TTFCD and greatly improves diagnosis and surgical prognosis of patients with negative MRI.

Endovascular Treatment of Intracranial Unruptured Aneurysms: A Systematic Review of the Literature on Safety with Emphasis on Subgroup Analyses

PURPOSE To report subgroup analyses of an updated systematic review on endovascular treatment of intracranial unruptured aneurysms (UAs); to compare types of embolic agents, adjunct techniques, and newer devices; and to identify potential risk factors for poor outcomes. MATERIALS AND METHODS Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to prepare this article, and the literature was searched with PubMed and with EMBASE and Cochrane databases. Six eligibility criteria (procedural complications rates; at least 10 patients; saccular, nondissecting UAs; original study published in English or French between January 2003 and July 2011; methodological quality score > 6 [modified Strengthening and Reporting of Observational Studies in Epidemiology criteria]; a study published in a peer-reviewed journal) were used. End points included procedural mortality and unfavorable outcomes (death or modified Rankin Scale, Glasgow Outcome Scale, or World Federation of Neurosurgeons Scale at 1 month scores, all > 2). A fixed-effects model (Mantel-Haenszel) was used for pooled estimates of mortality and unfavorable outcomes; a random-effects model (DerSimonian-Laird) was used in case of heterogeneity. RESULTS Ninety-seven studies with 7172 patients (26 studies published July 2008 through July 2011) were included. Sixty-nine (1.8%) of 7034 patients died (fixed-effect weighted average; 99% confidence interval [CI]: 1.4%, 2.4%; Q value, 55.0; I(2) = 0%). Unfavorable outcomes, including death, occurred in 4.7% (242 of 6941) of patients (99% CI: 3.8, 5.7; Q value, 128.3; I(2) = 26.8%). Patients treated after 2004 had better outcomes (unfavorable outcome, 3.1; 99% CI: 2.4, 4.0) than patients treated during 2001-2003 (unfavorable outcome, 4.7%; 99% CI: 3.6%, 6.1%; P = .01) or in 2000 and before (unfavorable outcome, 5.6%; 99% CI: 4.7%, 6.6%; P < .001). Significantly higher risk was associated with liquid embolic agents (8.1%; 99% CI: 4.7%, 13.7%) versus simple coil placement (4.9%; 99% CI: 3.8%, 6.3%; P = .002). Unfavorable outcomes occurred in 11.5% (99% CI: 4.9%, 24.6%) of patients treated with flow diversion. CONCLUSION Procedure-related poor outcomes occurred (4.7% of patients), risks decreased, and liquid embolic agents and flow diversion were associated with higher risks.

New variants of malignant glioneuronal tumors: a clinicopathological study of 40 cases.

OBJECTIVE:To demonstrate that malignant glioneuronal tumors comprise a large spectrum of neoplasms, without mature ganglion-like cells, that may histologically resemble any malignant glioma (World Health Organization Grade III or IV) but have a distinct biological behavior. METHODS:This series includes all tumors diagnosed as malignant glioneuronal tumors (MGNTs) in our routine practice during a 2-year period during which neurofilament protein (NFP) immunostaining was performed in any case of suspected malignant glioma with unusual clinical, radiographic, and/or histological features. Immunostaining using neuronal markers (NFP, NeuN, synaptophysin, and chromogranin) and glial fibrillary acidic protein was done on paraffin sections after antigen retrieval. The presence of NFP-positive tumor cells, including those in mitosis, was used as a hallmark diagnostic criterion of MGNT. RESULTS:All tumors coexpressed glial fibrillary acidic protein and NFP. Other neuronal markers tested were inconstantly expressed. No recurrence was observed at the primary site in 36.4% of patients who underwent gross total resection. Twelve patients (33.3%) developed intra-axial and/or systemic metastases, and 4 were free of disease at 39 to 184 months. Univariate analysis revealed that gross total surgical resection was the most important prognostic factor predicting survival (44 versus 15 mo; P < 0.0001), followed by a long duration of symptoms (>1 yr; P = 0.005), young age at symptom onset (children versus adults; P = 0.045), and absence of necrosis (P = 0.02). Gross total surgical resection (P = 0.001) and a long duration of symptoms (symptoms > 1 yr; P = 0.013) proved to be independent and statistically significant prognostic factors in the multivariate analysis. CONCLUSION:NFP immunostaining is required to identify MGNTs accurately. Their distinction from malignant gliomas is of paramount clinical importance, particularly for neurosurgeons, because gross total surgical resection may be curative in some cases. Finally, MGNTs may account for the long-term survival and/or occurrence of metastases demonstrated in a subset of malignant gliomas.

DTI-MR tractography of white matter damage in stroke patients with neglect

Left visual neglect is a dramatic neurological condition that impairs awareness of left-sided events. Neglect has been classically reported after strokes in the territory of the right middle cerebral artery. However, the precise lesional correlates of neglect within this territory remain discussed. Recent evidence strongly suggests an implication of dysfunction of large-scale perisylvian networks in chronic neglect, but the quantitative relationships between neglect signs and damage to white matter (WM) tracts have never been explored. In this prospective study, we used diffusion tensor imaging (DTI) tractography in twelve patients with a vascular stroke in the right hemisphere. Six of these patients showed signs of neglect. Nonparametric voxel-based comparisons between neglect and controls on fractional anisotropy maps revealed clusters in the perisylvian WM and in the external capsule. Individual DTI tractography identified specific disconnections of the fronto-parietal and fronto-occipital pathways in the neglect group. Voxel-based correlation statistics highlighted correlations between patients’ performance on two visual search tasks and damage to WM clusters. These clusters were located in the anterior limb of the internal capsule and in the WM underlying the inferior frontal gyrus, along the trajectory of the anterior segment of the arcuate fasciculus (asAF). These results indicate that chronic visual neglect can result from, and correlate with, damage to fronto-parietal connections in the right hemisphere, within large-scale cortical networks important for orienting of spatial attention, arousal and spatial working memory.

Uncinate fasciculus fiber tracking in mesial temporal lobe epilepsy. Initial findings

In temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), ictal discharge spread to the frontal and insulo-perisylvian cortex is commonly observed. The implication of white matter pathways in this propagation has not been investigated. We compared diffusion tensor imaging (DTI) measurements along the uncinate fasciculus (UF), a major tract connecting the frontal and temporal lobes, in patients and controls. Ten right-handed patients referred for intractable TLE due to a right HS were investigated on a 1.5-T MR scanner including a DTI sequence. All patients had interictal fluorodeoxyglucose PET showing an ipsilateral temporal hypometabolism associated with insular and frontal or perisylvian hypometabolism. The controls consisted of ten right-handed healthy subjects. UF fiber tracking was performed, and its fractional anisotropy (FA) values were compared between patients and controls, separately for the right and left UF. The left-minus-right FA UF asymmetry index was computed to test for intergroup differences. Asymmetries were found in the control group with right-greater-than-left FA. This asymmetrical pattern was lost in the patient group. Right FA values were lower in patients with right HS versus controls. Although preliminary, these findings may be related to the preferential pathway of seizure spread from the mesial temporal lobe to frontal and insulo-perisylvian areas.