Should I stay or should I go? The cerebral bases of street-crossing decision.

An observer willing to cross a street must first estimate if the approaching cars offer enough time to safely complete the task. The brain areas supporting this perception, known as Time-To-Contact (TTC) perception, have been mainly studied through noninvasive correlational approaches. We carried out an experiment in which patients were tested during an awake brain surgery electrostimulation mapping to examine the causal implication of various brain areas in the street-crossing decision process. Forty patients were tested in a gap acceptance task before their surgery to establish a baseline performance. The task was individually adapted upon this baseline level and carried out during their surgery. We acquired and normalized to MNI space the coordinates of the functional areas that influenced task performance. A total of 103 stimulation sites were tested, allowing to establish a large map of the areas involved in the street-crossing decision. Multiple sites were found to impact the gap acceptance decision. A direct implication was however found mostly for sites within the right parietal lobe, while indirect implication was found for sites within the language, motor, or attentional networks. The right parietal lobe can be considered as causally influencing the gap acceptance decision. Other positive sites were all accompanied with dysfunction in other cognitive functions, and therefore should probably not be considered as the site of TTC estimation.

Randomized phase III trial of metabolic imaging-guided dose escalation of radio-chemotherapy in patients with newly diagnosed glioblastoma (SPECTRO GLIO trial).

BACKGROUND: Glioblastoma (GBM) systematically recurs after a standard 60 Gy radio-chemotherapy regimen. Since magnetic resonance spectroscopic imaging (MRSI) has been shown to predict the site of relapse, we analyzed the effect of MRSI-guided dose escalation on overall survival (OS) of patients with newly diagnosed GBM. METHODS: In this multicentric prospective phase III trial, patients who had undergone biopsy or surgery for a GBM were randomly assigned to a standard dose (SD) of 60 Gy or a high dose (HD) of 60 Gy with an additional simultaneous integrated boost totaling 72 Gy to MRSI metabolic abnormalities, the tumor bed and residual contrast enhancements. Temozolomide was administered concomitantly and maintained for 6 months thereafter. RESULTS: One hundred and eighty patients were included in the study between March 2011 and March 2018. After a median follow-up of 43.9 months (95% CI [42.5; 45.5]), median OS was 22.6 months (95% CI [18.9; 25.4]) versus 22.2 months (95% CI [18.3; 27.8]) for HD, and median progression-free survival was 8.6 (95% CI [6.8; 10.8]) versus 7.8 months (95% CI [6.3; 8.6]), in SD versus HD, respectively. No increase in toxicity rate was observed in the study arm. The pseudoprogression rate was similar across the SD (14.4%) and HD (16.7%) groups. For O(6)-methylguanine-DNA methyltransferase (MGMT) methylated patients, the median OS was 38 months (95% CI [23.2; NR]) for HD patients versus 28.5 months (95% CI [21.1; 35.7]) for SD patients. CONCLUSION: The additional MRSI-guided irradiation dose totaling 72 Gy was well tolerated but did not improve OS in newly diagnosed GBM. TRIAL REGISTRATION: NCT01507506; registration date: December 20, 2011. https://clinicaltrials.gov/ct2/show/NCT01507506?cond=NCT01507506&rank=1.

Immunohistologic Features of Cerebral Venous Thrombosis Due to Vaccine-Induced Immune Thrombotic Thrombocytopenia.

OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia (VITT), a recently described entity characterized by thrombosis at unusual locations such as cerebral venous sinus and splanchnic vein, has been rarely described after adenoviral-encoded COVID-19 vaccines. In this study, we report the immunohistological correlates in 3 fatal cases of cerebral venous thrombosis related to VITT analyzed at an academic medical center. METHODS: Detailed neuropathologic studies were performed in 3 cases of cerebral venous thrombosis related to VITT after adenoviral COVID-19 vaccination. RESULTS: Autopsy revealed extensive cerebral vein thrombosis in all 3 cases. Polarized thrombi were observed with a high density of neutrophils in the core and a low density in the tail. Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall. DISCUSSION: Data indicate that neutrophils and complement activation associated with antispike immunity triggered by the vaccine is probably involved in the disease process.

Variability of Intraoperative Electrostimulation Parameters in Conscious Individuals: Language Fasciculi.

OBJECTIVE: The authors analyzed the current-intensity thresholds for electrostimulation of language fasciculi and the possible consequences of threshold variability on brain mapping. METHODS: A prospective protocol of subcortical electrostimulation was used in 50 patients undergoing brain mapping, directly stimulating presumed language fasciculi identified by diffusion tensor imaging. RESULTS: The stimulation-intensity thresholds for identification of language fasciculi varied among patients (mean minimum current intensity of 4.4 mA, range = 1.5-10 mA, standard deviation = 1.1 mA), and 23% of fascicular interferences were detected only above 5 mA. Repeated stimulation of the same site with the same intensity led to different types of interferences in 20% of patients, and a higher current intensity led to changes in the type of response in 27%. The mean minimum stimulation intensities did not differ significantly between different fasciculi, between the different types of interference obtained, or with age, sex, or type of tumor. Positive results on cortical mapping were significantly associated with positive results on subcortical mapping (P < 0.001). Subcortical intensity thresholds were slightly lower than cortical ones (mean = 4.43 vs. 5.25 mA, P = 0.034). In 23 of 50 subcortical mappings, fascicular stimulation produced no language interference. CONCLUSIONS: Individual variability of minimum stimulation-intensity thresholds for identification of language fasciculi is frequent. Nevertheless, even when a high current intensity was used, many stimulations on language fasciculi remained negative for various hypothetic reasons. Finding the optimal current intensity for identifying language fasciculi is of paramount importance to refine the clinical results and scientific data derived from brain mapping.

Outcome of glioblastoma resection in patients 80 years of age and older.

OBJECTIVE: To evaluate the role and possible complications of tumor resection in the management of glioblastoma (GBM) in a series of patients 80 years of age and older with review of literature. METHODS: The authors retrospectively analyzed cases involving patients 80 years or older who underwent biopsy or initial resection of GBM at their hospital between 2007 and 2018. A total of 117 patients (mean age 82 years) met the inclusion criteria; 57 had resection (group A) and 60 had biopsy (group B). Functional outcomes and survival at follow-up were analyzed. RESULTS: Group A differed significantly from group B at baseline in having better WHO performance status, better ASA scores, more right-sided tumors, and no basal ganglia or "butterfly" gliomas. Nevertheless, 56% of group A patients had an ASA score of 3. Median survival was 9.5 months (95% CI 8-17 months) in group A, 4 months (95% CI 3.5-6 months) in group B, and 17.5 months (95% CI 12-24 months) in the 56% of group A patients treated with resection and Stupp protocol. Rates of postoperative neurologic and medical complications were almost identical in the 2 groups, but the rate of surgical site complications was substantially greater in group A (12% vs 5%). There was no significant difference in mean preoperative and postoperative KPS scores (group A). CONCLUSIONS: In selected patients 80 years or older, radical removal of GBM was associated with acceptable survival and a low perioperative complication rate which is comparable to that of a biopsy. Although the median survival of the whole group was lower than reported for younger patients, a subgroup amenable to radical surgery and Stupp protocol achieved a median survival of 17.5 months.

The Impact of Surgery on the Survival of Patients with Recurrent Glioblastoma.

OBJECTIVE: The purpose of this study was to investigate the possible benefit of repeat surgery on overall survival for patients with recurrent glioblastoma multiforme (GBM). METHODS: We performed a retrospective analysis of data from patients who presented with recurrent GBM over a 5-year period (n = 157), comparing baseline characteristics and survival for patients who had at least 1 new tumor resection followed by chemotherapy (reoperation group, n = 59) and those who received medical treatment only (no-reoperation group, n = 98) for recurrence. RESULTS: The baseline characteristics of the two groups differed in terms of WHO performance status (better in the reoperation group), mean age (60 years in the reoperation group vs. 65 years in the no-reoperation group), mean interval to recurrence (3 months later in the reoperation group than in the no-reoperation group) and more gross total resections in the reoperation group. Nevertheless, the patients in the reoperation group had a higher rate [32.8%] of sensorimotor deficits than those of the no-reoperation group [14.2]. There was no significant difference in sex; tumor localization, side, or extent; MGMT status; MIB-1 labeling index; or Karnofsky Performance Status [KPS] score. After adjustment for age, the WHO performance status, interval of recurrence, and extent of resection at the first operation, multivariate analysis showed that median survival was significantly better in the reoperation group than in the no-reoperation group (22.9 vs. 14.61 months, P < 0.05). After a total of 69 repeat operations in 59 patients (10 had 2 repeat surgeries), we noted 13 temporary and 20 permanent adverse postoperative events, yielding a permanent complication rate of 28.99% (20/69). There was also a statistically significant (P = 0.029, Student's t-test) decrease in the mean KPS score after reoperation (mean preoperative KPS score of 89.34 vs. mean postoperative score of 84.91). CONCLUSION: Our retrospective study suggests that repeat surgery may be beneficial for patients with GBM recurrence who have good functional status (WHO performance status 0 and 1), although the potential benefits must be weighed against the risk of permanent complications, which occurred in almost 30% of the patients who underwent repeat resection in this series.

Clinical long-term consequences of thoraco-lumbar spine fracture and osteosynthesis.

OBJECT: Although traumatic spine fractures can be treated by osteosynthesis, their long-term clinical, social, and familial consequences are less known. The aim of this study was to assess these global consequences to a very long-term (at least more than 12 years after the fracture). METHODS: Two groups, one composed of 30 patients operated for a thoracolumbar fracture by posterior fixation and one with 30 controls (who never had a spinal fracture) matched for age, sex, job and time of follow-up were studied. Patients and control subjects had to answer to 3 questionnaires: one about clinical, familial, and socio-professional changes, and 2 back pain (Dallas and Eifel) scales. RESULTS: The mean patient follow-up was 14.5 years (from 12 to 18 years, sd 2.3) - control subjects, 15 years. The majority (56%) of the fractures occurred at T12/L1 level. At last follow-up, the chronic low back pain concerned 20 (66,7%) patients versus 11 (36.7%) control subjects (p=0.03); more patients (13 patients - 43.3%) consumed analgesics than control (5 persons - 16.6%) subjects (p=0.04). A large majority (13 patients, 57%) had sick leaves that exceeded 6 months. The loss of wage due to traumatism or chronic low back pain was also significant (p=0.002) between patients and matched controls over the period. At follow-up, the mean Eifel score for the whole patients' cohort was significaty superior compared to control group (4.7 [sd 3.75] vs. 2.6 [sd 4.2], p=0.008). Dallas score was superior in the patient's group for the daily, work-leisure activities and sociability aspect (p<0.05). CONCLUSION: Chronic back pain, long sick leaves, changes in professional and familial life, the very long-term postoperative outcome of patients could be more difficult than expected in a majority of patients operated for thoracolumbar fracture. In order to facilitate the back to work and reduce these long-term consequences, we propose that guidelines about job resume in traumatic spinal fractures should be established along with early occupational medicine consultations. LEVEL OF EVIDENCE: III; retrospective case control study.

Time-to-contact perception in the brain.

Time-to-contact (TTC) perception refers to the ability of an observer to estimate the remaining time before an object reaches a point in the environment, and is of crucial importance in daily life. Noninvasive correlational approaches have identified several brain areas sensitive to TTC information. Here we report the results of two studies, including one during an awake brain surgery, that aimed to identify the specific areas causally engaged in the TTC estimation process. In Study 1, we tested 40 patients with brain tumor in a TTC estimation task. The results showed that four of the six patients with impaired performance had tumors in right upper parietal cortex, although this tumoral location represented only six over 40 patients. In Study 2, 15 patients underwent awake brain surgery electrostimulation mapping to examine the implication of various brain areas in the TTC estimation process. We acquired and normalized to MNI space the coordinates of the functional areas that influenced task performance. Our results seem to demonstrate that the early stage of the TTC estimation process involved specific cortical territories in the ventral region of the right intraparietal sulcus. Downstream processing of TTC could also involve the frontal eye field (middle frontal gyrus) related to ocular search. We also found that deactivating language areas in the left hemisphere interfered with the TTC estimation process. These findings demonstrate a fine grained, cortical representation of TTC processing close to the ventral right intraparietal sulcus and complement those described in other human studies.

One-Step Customized PEEK Cranioplasty After 3D Printed Resection Template Assisted Surgery for a Frontal Intraosseous Meningioma: A Case Report.

AIM: To present one-step customized cranioplasty for intraosseous meningiomas. CASE DESCRIPTION: The authors report the case of a 54-year-old woman with a consequent frontal intraosseous meningioma invading the superior sagittal sinus. The patient only suffered from local pain and cosmetic damage. A complete resection was scheduled with a one-step reconstruction of the frontal bone by a polyetheretherketone (PEEK) specific implant. This implant was computer-assisted designed and manufactured and verified by the surgeon before the intervention. During surgery, the resection was guided by a computer designed resection template and by the classic neuronavigation system. Cranioplasty has been considered optimal intraoperatively by surgeons. The patient, a few weeks after surgery, underwent a subcutaneous fluid collection, rapidly resolutive with a circumferential pressure bandage. Six months after surgery, the patient considered the surgery a success with a very good cosmetic result and a total regression of her local pain. CONCLUSION: One-step computer-assisted cranioplasty is a safe and effective procedure for large skull defects. PEEK specific implant for cranioplasty offer advantages compared to other materials that will be discussed under the scope of the one-step reconstruction.

Functional architecture of the motor homunculus detected by electrostimulation.

KEY POINTS: We performed a prospective electrostimulation study of the motor homunculus in 100 patients without motor deficit or brain lesion in the precentral gyrus in order to acquire accurate Montreal Neurological Institute (MNI) coordinates of the functional areas. The analysis of 248 body coordinates in the precentral gyrus showed rare inter-individual variations in the medial-to-lateral somatotopic movement organization with quite similar intensity thresholds. Electrostimulation only induced basic and stereotyped movements. We detected a relative medial-to-lateral somatotopy of the wrist/hand/global/individual fingers, with sometimes different sites for an individual muscle or movement. We found some similarities to, but also substantial differences from, the seminal work of Penfield and colleagues. We propose an updated version of the human motor homunculus and of its correlation with the somatosensory homunculus, previously defined in MNI space with a similar brain mapping technique. ABSTRACT: In this prospective electrostimulation study, based on 100 operated patients without motor deficit or brain lesion in the precentral gyrus, we acquired coordinates of the functional areas of the motor homunculus and normalized them to standard MNI space. Among 608 sites stimulated in the precentral gyrus (and 1937 in gyri nearby), 248 positive points (40%) for motor response were detected - 245 in the precentral gyrus. Positive stimulations were detected through the 'on/off' outbreak effect, and only basic movements were detected. We found no significant difference in mean intensity threshold between the motor representations of the fingers (1.94 mA), tongue and lower limbs (both 2.0 mA), or face (2.25 mA). In the precentral gyrus, the evoked body movements displayed a medial-to-lateral somatotopy in very small (often <10 mm2 ) areas. The hand region displayed multiple areas for a specific movement, with areas inducing either global or single-finger movement (with a relative medial-to-lateral somatotopy). Among these tested patients, the somatotopic organization of the intact motor cortex showed little inter-individual variations. Unlike Penfield and collaborators, we evoked no sensations such as sense of movement or desire to move, and only 2% of motor responses outside the precentral gyrus. We propose a rationalization of the standard drawing of the motor homunculus according to MNI space. We found a somatotopic correlation perpendicular to the central sulcus when matching our motor data to those previously obtained for the somatosensory homunculus.

Glioblastoma survival is better analyzed on preradiotherapy MRI than on postoperative MRI residual volumes: A retrospective observational study.

OBJECTIVES: Establishing an overall survival prognosis for resected glioblastoma during routine postoperative management remains a challenge. The aim of our single-center study was to assess the usefulness of basing survival analyses on preradiotherapy MRI (PRMR) rather than on postoperative MRI (POMR). PATIENTS AND METHODS: A retrospective review was undertaken of 75 patients with glioblastoma treated at our institute. We collected overall survival and MRI volumetric data. We analyzed two types of volumetric data: residual tumor volume and extent of resection. Overall survival rates were compared according to these two types of volumetric data, calculated on either POMR or PRMR and according to the presence or absence of residual enhancement. RESULTS: Analysis of volumetric data revealed progression of some residual tumors between POMR and PRMR. Kaplan-Meier analysis of the correlations between extent of resection, residual tumor volume, and overall survival revealed significant differences between POMR and PRMR data. Both MRI scans indicated a difference between the complete resection subgroup and the incomplete resection subgroup, as median overall survival was longer in patients with complete resection. However, differences were significant for PRMR (25.3 vs. 15.5, p =  0.012), but not for POMR (21.3 vs. 15.8 months, p =  0.145). With a residual tumor volume cut-off value of 3 cm3, Kaplan-Meier survival analysis revealed non-significant differences on POMR (p =  0.323) compared with PRMR (p =  0.007). CONCLUSION: Survival in patients with resected glioblastoma was more accurately predicted by volumetric data acquired with PRMR. Differences in predicted survival between the POMR and PRMR groups can be attributed to changes in tumor behavior before adjuvant therapy.

Incidence and predicting factors of perioperative complications during monitored anesthesia care for awake craniotomy.

STUDY OBJECTIVE: To assess incidence and predicting factors of awake craniotomy complications. DESIGN: Retrospective cohort study. SETTING: Operating room and Post Anesthesia Care unit. PATIENTS: 162 patients who underwent 188 awake craniotomy procedures for brain tumor, ASA I to III, with monitored anesthesia care. MEASUREMENTS: We classified procedures in 3 groups: major event group, minor event group, and no event group. Major events were defined as respiratory failure requiring face mask or invasive ventilation; hemodynamic instability treated by vasoactive drugs, or bradycardia treated by atropine, bleeding >500 ml, transfusion, gaseous embolism, cardiac arrest; seizure, cerebral edema, or any events leading to stopping of the cerebral mapping. Minor event was defined as any complication not classified as major. Multivariate logistic regression was used to determine predicting factors of major complication, adjusted for age and ASA score. MAIN RESULTS: 45 procedures (24%) were classified in major event group, 126 (67%) in minor event group, and 17 (9%) in no event group. Seizure was the main complication (n = 13). Asthma (odds ratio: 10.85 [1.34; 235.6]), Remifentanil infusion (odds ratio: 2.97 [1.08; 9.85]) and length of the operation after the brain mapping (odds ratio per supplementary minute: 1.01 [1.01; 1.03]) were associated with major events. CONCLUSIONS: Previous medical history of asthma, remifentanil infusion and a long duration of neurosurgery after cortical mapping appear to be risk factors for major complications during AC.

Awake Craniotomy and Memory Induction Through Electrical Stimulation: Why Are Penfield's Findings Not Replicated in the Modern Era?

From the 1930s through the early 1960s, Wilder Penfield12 collected a large number of memories induced by electrical brain stimulation (EBS) during awake craniotomy. As a result, he was a major contributor to several neuroscientific and neuropsychological concepts of long-term memory. His 1963 paper, which recorded all the cases of memories he induced in his operating room, remains a substantial point of reference in neuroscience in 2019, although some of his interpretations are now debatable. However, it is highly surprising that, since Penfield's12 reports, there has been no other surgical publication on memories induced during awake surgery. In this review, we explore this phenomenon and analyze some of the reasons that might explain it. We hypothesize that the main reasons for lack of subsequent reports are related to changes in operative procedures (ie, use of anesthetics, time constraints, and insufficient debriefings) and changes in EBS parameters, rather than to the sites that are stimulated, the pathology treated, or the tasks used. If reminiscences are still induced, they should be reported in detail to add valuable contributions to the understanding of long-term memory networks, especially memories that are difficult to reproduce in the laboratory, such as autobiographical memories.

Intraoperative electrostimulation for awake brain mapping: how many positive interference responses are required for reliability?

OBJECTIVE: The purpose of this study was to characterize the reproducibility of language trials within and between brain mapping sessions. METHODS: Brain mapping and baseline testing data from 200 adult patients who underwent resection of left-hemisphere tumors were evaluated. Data from 11 additional patients who underwent a second resection for recurrence were analyzed separately to investigate reproducibility over time. In all cases, a specific protocol of electrostimulation brain mapping with a controlled naming task was used to detect language areas, and the results were statistically compared with preoperative and intraoperative baseline naming error rates. All patients had normal preoperative error rates, controlled for educational level and age (mean 8.92%, range 0%-16.25%). Intraoperative baseline error rates within the normal range were highly correlated with preoperative ones (r = 0.74, p < 10-10), although intraoperative rates were usually higher (mean 13.30%, range 0%-26.67%). Initially, 3 electrostimulation trials were performed in each cortical area. If 2 of 3 trials showed language interference, 1 or 2 additional trials were performed (depending on results). RESULTS: In the main group of 200 patients, there were 82 single interferences (i.e., positive results in 1 of 3 trials), 227 double interferences (2/3), and 312 full interferences (3/3). Binomial statistics revealed that full interferences were statistically significant (vs intraoperative baseline) in 92.7% of patients, while double interferences were significant only in 38.5% of patients, those with the lowest error rates. On further testing, one-third of the 2/3 trials became 2/4 trials, which was significant in only one-quarter of patients. Double interference could be considered significant for most patients (> 90%) when confirmed by 2 subsequent positive trials (4/5). In the 11 patients who were operated on twice, only 26% of areas that tested positive in the initial operation tested positive in the second and showed the same type of interference and the same current threshold (i.e., met all 3 criteria). CONCLUSIONS: Electrostimulation trials in awake brain mapping produced graded patterns of positive reproducibility levels, and their significance varied with the baseline error rates. The results suggest that caution is warranted when 2 of 3 trials are positive, although the need for additional trials depends on the individual patients' baseline error rates. Reproducibility issues should be considered in the interpretation of data from awake brain mapping.

Impact on survival of early tumor growth between surgery and radiotherapy in patients with de novo glioblastoma.

PURPOSE: Systematic pre-radiotherapy MRI in patients with newly resected glioblastoma (OMS 2016) sometimes reveals tumor growth in the period between surgery and radiotherapy. We evaluated the relation between early tumor growth and overall survival (OS) with the aim of finding predictors of regrowth. METHODS: Seventy-five patients from 25 to 84 years old (Median age 62 years) with preoperative, immediate postoperative, and preradiotherapy MRI were included. Volumetric measurements were made on each of the three MRI scans and clinical and molecular parameters were collected for each case. RESULTS: Fifty-four patients (72%) had an early regrowth with a median contrast enhancement volume of 3.61 cm3-range 0.12-71.93 cm3. The median OS was 24 months in patients with no early tumor growth and 17.1 months in those with early tumor regrowth (p = 0.0024). In the population with initial complete resection (27 patients), the median OS was 25.3 months (19 patients) in those with no early tumor growth between surgery and radiotherapy compared to 16.3 months (8 patients) in those with tumor regrowth. In multivariate analysis, the initial extent of resection (p < 0.001) and the delay between postoperative MRI and preradiotherapy MRI (p < 0.001) were significant independent prognostic factors of regrowth and of poorer outcome. CONCLUSIONS: We demonstrated that, in addition to the well known issue of incomplete resection, longer delays between surgery and adjuvant treatment is an independent factors of tumor regrowth and a risk factor of poorer outcomes for the patients. To overcome the delay factor, we suggest shortening the usual time between surgery and radiotherapy.

EWSR1-PATZ1 gene fusion may define a new glioneuronal tumor entity.

We investigated the challenging diagnostic case of a ventricular cystic glioneuronal tumor with papillary features, by RNA sequencing using the Illumina TruSight RNA Fusion panel. We did not retrieve the SLC44A1-PRKCA fusion gene specific for papillary glioneuronal tumor, but an EWSR1-PATZ1 fusion transcript. RT-PCR followed by Sanger sequencing confirmed the EWSR1-PATZ1 fusion. It matched with canonic EWSR1 fusion oncogene, juxtaposing the entire N-terminal transcriptional activation domain of EWSR1 gene and the C-terminal DNA binding domain of a transcription factor gene, PATZ1. PATZ1 protein belongs to the BTB-ZF (broad-complex, tramtrack and bric-à-brac -zinc finger) family. It directly regulates Pou5f1 and Nanog and is essential to maintaining stemness by inhibiting neural differentiation. EWSR1-PATZ1 fusion is a rare event in tumors: it was only reported in six round cell sarcomas and in three gliomas of three exclusively molecular studies. The first reported glioma was a BRAFV600E negative ganglioglioma, the second a BRAFV600E negative glioneuronal tumor, not otherwise specified and the third, very recently reported, a high grade glioma, not otherwise specified. In our study, forty BRAFV600E negative gangliogliomas were screened by FISH using EWSR1 break-apart probes. We performed methylation profiling for the index case and for seven out of the ten FISH positive cases. The index case clustered apart from other pediatric low grade glioneuronal entities, and specifically from the well-defined ganglioglioma methylation group. An additional pediatric intraventricular ganglioglioma clustered slightly more closely with ganglioglioma, but showed differences from the main ganglioglioma group and similarities with the index case. Both cases harbored copy number variations at the PATZ1 locus. EWSR1-PATZ1 gene fusion might define a new type of glioneuronal tumors, distinct from gangliogliomas.

Frontoethmoidal meningoencephalocele: appraisal of a craniofacial surgical teaching program in Cambodia.

OBJECTIVE The treatment of frontoethmoidal meningoencephaloceles (fMECs) in Cambodia was not possible before the development of a program that taught some Khmer surgeons (working at the Children's Surgical Centre in Phnom Penh) how to surgically correct these deformities without any foreign help. The results of that teaching program are discussed in this paper. METHODS Between 2004 and 2009, both local and visiting foreign neurosurgical and craniofacial surgeons (the visitors coming twice a year) worked together to operate on 200 patients, and a report on those cases was published in 2010. In subsequent years (2010-2016), the Khmer surgeons operated on 100 patients without the presence of the visiting surgeons. In this study, the authors compare the second case series with the previously published series and the literature in terms of results and complications. The operations were performed with limited surgical materials and equipment, using a combined bicoronal and transfacial approach in most cases. Most of the patients came from very poor families. RESULTS Organizing the postoperative follow-up of these low-income patients (mean age 12 years) was probably the most challenging part of this teaching program. Nine of the patients were lost to surgical follow-up. In the other cases, cosmetic results were judged by the surgeons as worse than the patient's preoperative appearance in 1 case, poor in 12 cases, average in 27, and good in 51-data that are significantly less encouraging than the results reported by the joint local/visiting teams in 2010 (p = 0.0001). Nevertheless, patients and parents tended to have a better overall opinion about the surgical results (rating the results as good in 84% of the 80 cases in which parent or patient ratings were available). Twenty postoperative complications were observed (the most common being temporary CSF leaks). The rate of immediate postoperative complications directly related to fMEC surgery was less than that in the previous series, but the difference was not statistically significant (20% vs 28.5%, p = 0.58). No death was noted in this case series (in contrast to the previous series). Social questionnaire results confirmed that fMEC correction partially improved the adverse social and educational consequences of fMEC in affected children. CONCLUSIONS In the current state of this program, the local surgeons are able to correct fMECs in their own country, without foreign assistance, with good results in a majority of patients. Such humanitarian teaching programs generally take years to achieve the initial aims.

Functional architecture of the somatosensory homunculus detected by electrostimulation.

KEY POINTS: We performed a prospective electrostimulation study, based on 50 operated intact patients, to acquire accurate MNI coordinates of the functional areas of the somatosensory homunculus. In the contralateral BA1, the hand representation displayed not only medial-to-lateral, little-finger-to-thumb, but also rostral-to-caudal discrete somatotopy, with the tip of each finger located more caudally than the proximal phalanx. The analysis of the MNI body coordinates showed rare inter-individual variations in the medial-to-lateral somatotopic organization in these patients with rather different intensity thresholds needed to elicit sensations in different body parts. We found some similarities but also substantial differences with the previous, seminal works of Penfield and his colleagues. We propose a new drawing of the human somatosensory homunculus according to MNI space. ABSTRACT: In this prospective electrostimulation study, based on 50 operated patients with no sensory deficit and no brain lesion in the postcentral gyrus, we acquired coordinates in the standard MNI space of the functional areas of the somatosensory homunculus. The 3D brain volume of each patient was normalized to that space to obtain the MNI coordinates of the stimulation site locations. For 647 sites stimulated on Brodmann Area 1 (and 1025 in gyri nearby), 258 positive points for somatosensory response (40%) were found in the postcentral gyrus. In the contralateral BA1, the hand representation displayed not only medial-to-lateral and little-finger-to-thumb somatotopy, but also rostral-to-caudal discrete somatotopy, with the tip of each finger located more caudally than the proximal phalanx. We detected a medial-to-lateral, tip-to-base tongue organization but no rostral-to-caudal functional organization. The analysis of the MNI body coordinates showed rare inter-individual variations in the medial-to-lateral somatotopic organization in these patients with intact somatosensory cortex. Positive stimulations were detected through the 'on/off' outbreak effect and discriminative touch sensations were the sensations reported almost exclusively by all patients during stimulation. Mean hand (2.39 mA) and tongue (2.60 mA) positive intensity thresholds were lower (P < 0.05) than the intensities required to elicit sensations in the other parts of the body. Unlike the previous, seminal works of Penfield and colleagues, we detected no sensations such as sense of movement or desire to move, no somatosensory responses outside the postcentral gyrus, and no bilateral responses for face/tongue stimulations. We propose a rationalization of the standard drawing of the somatosensory homunculus according to MNI space.