Search for Lepton Number and Flavor Violation in K

Searches for the lepton number violating K^{+}→π^{-}µ^{+}e^{+} decay and the lepton flavor violating K^{+}→π^{+}µ^{-}e^{+} and π^{0}→µ^{-}e^{+} decays are reported using data collected by the NA62 experiment at CERN in 2017-2018. No evidence for these decays is found and upper limits of the branching ratios are obtained at 90% confidence level: B(K^{+}→π^{-}µ^{+}e^{+})<4.2×10^{-11}, B(K^{+}→π^{+}µ^{-}e^{+})<6.6×10^{-11} and B(π^{0}→µ^{-}e^{+})<3.2×10^{-10}. These results improve by 1 order of magnitude over previous results for these decay modes.

The Impact of Compressed Femtosecond Laser Pulse Durations on Neuronal Tissue Used for Two-Photon Excitation Through an Endoscope.

Accurate intraoperative tumour margin assessment is a major challenge in neurooncology, where sparse tumours beyond the bulk tumour are left undetected under conventional resection. Non-linear optical imaging can diagnose tissue at the sub-micron level and provide functional label-free histopathology in vivo. For this reason, a non-linear endomicroscope is being developed to characterize brain tissue intraoperatively based on multiple endogenous optical contrasts such as spectrally- and temporally-resolved fluorescence. To produce highly sensitive optical signatures that are specific to a given tissue type, short femtosecond pulsed lasers are required for efficient two-photon excitation. Yet, the potential of causing bio-damage has not been studied on neuronal tissue. Therefore, as a prerequisite to clinically testing the non-linear endomicroscope in vivo, the effect of short laser pulse durations (40-340 fs) on ex vivo brain tissue was investigated by monitoring the intensity, the spectral, and the lifetime properties of endogenous fluorophores under 800 and 890 nm two-photon excitation using a bi-modal non-linear endoscope. These properties were also validated by imaging samples on a benchtop multiphoton microscope. Our results show that under a constant mean laser power, excitation pulses as short as 40 fs do not negatively alter the biochemical/ biophysical properties of tissue even for prolonged irradiation.

Malignant primary diffuse leptomeningeal gliomatosis with histone H3.3 K27M mutation.

INTRODUCTION: Malignant primary diffuse leptomeningeal gliomatosis (MPDLG) are rare central nervous system neoplasms associated with a poor outcome. CASE REPORT: We report the case of a 40-year-old woman who presented with unusual worsening of bilateral sciatica, headaches, diplopia and a left proptosis. MRI of the head and spine showed multiple leptomeningeal lesions with no intra parenchymal involvement. The search for a primary tumor was negative. An open surgical biopsy of the prominent intradural lumbar tumor was performed within a week. Histopathology, immunochemistry and molecular analyses revealed a malignant glioma with histone H3.3 K27M mutation. The patient was referred to the neuro-oncologist for chemotherapy and craniospinal radiotherapy. Despite aggressive therapy, she died of disseminated tumoral progression, 18 weeks after the diagnosis. CONCLUSION: MPLG is a rare tumor which should be considered whenever a patient presents with diffuse or multinodular meningeal contrast-enhancing lesions. Some cases of MLPG share histological and immunophenotypical features with diffuse midline gliomas H3-K27M-mutant, a rapidly fatal disease. The diagnosis remains histopathological and, therefore a biopsy is obligatory without delay. Immunohistochemistry and/or molecular analyses are now currently essential for a formal classification and, to provide a better prediction of clinical outcome, particularly in this heterogeneous group of tumors.

Solitary fibrous tumours and haemangiopericytoma of the meninges. A retrospective study for outcome and prognostic factor assessment.

BACKGROUND: To report on the outcome of patients diagnosed with central nervous system haemangiopericytoma (HPC) or solitary fibrous tumours (SFT) and identify factors that may influence recurrence and survival. MATERIAL AND METHODS: Between January 1977 and December 2016, a retrospective search identified 22 HPCs/SFTs. The patients underwent a total of 40 surgical resections and 63.6% received radiotherapy. Median follow-up was 7.8 years. RESULTS: Six patients (27.3%) were re-operated for tumour recurrence. At the end of the study, 15 patients (68.2%) had no residual tumour on the last imaging. Surgical recurrence-free survival at 5 years was 77.4%, [95% CI: 60.1-99.8]. None of the investigated variables was associated with recurrence. At the end of the study, 5 patients were deceased (22.7%) and only 10 patients (45.5%) had no residual tumour on the last imaging and were alive. Overall survival at 5 years was 95%, [95% CI: 85.9-100]. None of the investigated variables was associated with overall survival. Patients who received radiotherapy demonstrated neither a reduced risk of surgical recurrence (P=0.378) nor a longer overall survival (P=0.405). CONCLUSION: SFTs/HPCs are associated with a significant risk of recurrence that may reduce the survival. Even if we could not demonstrate their benefit in this limited series, we believe that tailored maximal tumour resection on initial surgery is beneficial and that adjuvant RT is useful for tumours displaying grade II or III, even in case of complete removal.

Optical properties, spectral, and lifetime measurements of central nervous system tumors in humans.

A key challenge of central nervous system tumor surgery is to discriminate between brain regions infiltrated by tumor cells and surrounding healthy tissue. Although monitoring of autofluorescence could potentially be an efficient way to provide reliable information for these regions, we found little information on this subject, and thus we conducted studies of brain tissue optical properties. This particular study focuses on the different optical quantitative responses of human central nervous system tumors and their corresponding controls. Measurements were performed on different fixed human tumoral and healthy brain samples. Four groups of central nervous system tumors (glioblastoma, diffuse glioma, meningioma and metastasis) were discriminated from healthy brain and meninx control tissues. A threshold value was found for the scattering and absorption coefficient between tumoral and healthy groups. Emission Spectra of healthy tissue had a significant higher intensity than tumoral groups. The redox and optical index ratio were thenn calculated and these also showed significant discrimination. Two fluorescent molecules, NADH and porphyrins, showed distinct lifetim values among the different groups of samples. This study defines several optical indexes that can act as combinated indicators to discriminate healthy from tumoral tissues.

Surgery for dysembryoplastic neuroepithelial tumors and gangliogliomas in eloquent areas. Functional results and seizure control.

INTRODUCTION: Dysembryoplastic neuroepithelial tumors and gangliogliomas are developmental glioneuronal tumors usually revealed by partial epilepsy. High epileptogenicity, childhood epilepsy onset, drug-resistance, temporal location, and seizure freedom after complete resection are common characteristics of both tumors. We report the specificity of surgical management, functional results and seizure outcome in cases of a tumor location in eloquent areas. METHODS: Among 150 patients (88 males, 3-55 years) operated on for refractory epilepsy due to a glioneuronal tumor (1990-2015), 30 (20%, dysembryoplastic neuroepithelial tumors=21; gangliogliomas=9) had a tumor located in an eloquent cortex (sensory-motor, insular or language areas). Surgery was performed after a preoperative work-up, including stereo-electroencephalography in 48 patients (26%) and functional MRI in 100 (67%). MRI-guided lesionectomy was mainly performed in extra-temporal location, whereas an additional corticectomy was performed in a temporal location. Tumor microsurgical resections were guided using neuronavigation and cortical/subcortical electrical stimulations. Multiple stereotactic thermocoagulations were performed in two insular tumors. RESULTS: New motor/language deficits related to eloquent areas occurred postoperatively in 6/30 patients (20%) without any major permanent disability. Minor sensorimotor (n=2) and moderate language disturbance (n=1) persisted in three of them. Postoperative seizure-free outcome (mean follow-up>5 years) was obtained in 81% of the entire series, but significantly decreased to 60% in eloquent areas. Incomplete tumor resection was the main cause of surgical failure. However, unfavorable seizure outcome was also observed despite complete tumor resection. Malignant transformation occurred in one ganglioglioma. CONCLUSION: Epilepsy surgery for benign glioneuronal tumors in eloquent areas provides acceptable results regarding the functional risks. Complete tumor resection is crucial for long-term favorable outcome.

Spectral and fluorescence lifetime endoscopic system using a double-clad photonic crystal fiber.

We present a customized small-core double-clad photonic crystal fiber for spectral and fluorescence lifetime measurements of human samples. In this Letter, the new fiber has been characterized on different fluorophores and samples of human brain tumor; a comparison to a bi-fiber homemade system and a commercial fiber probe was made.

Role of gap junctions on synchronization in human neocortical networks.

Gap junctions (GJ) have been implicated in the synchronization of epileptiform activities induced by 4-aminopyrine (4AP) in slices from human epileptogenic cortex. Previous evidence implicated glial GJ to govern the frequency of these epileptiform events. The synchrony of these events (evaluated by the phase unlocking index, PUI) in adjacent areas however was attributed to neuronal GJ. In the present study, we have investigated the effects of GAP-134, a recently developed specific activator of glial GJ, on both the PUI and the frequency of the 4AP-induced epileptiform activities in human neocortical slices of temporal lobe epilepsy tissue. To delineate the impact of GJ on spatial spread of synchronous activity we evaluated the effects of carbenoxolone (CBX, a non-selective GJ blocker) on the spread in three axes 1. vertically in a given cortical column, 2. laterally within the deep cortical layers and 3. laterally within the upper cortical layers. GAP-134 slightly increased the frequency of the 4AP-induced spontaneous epileptiform activities while leaving the PUI unaffected. CBX had no effect on the PUI within a cortical column or on the PUI in the deep cortical layers. CBX increased the PUI for long interelectrodes distances in the upper cortical layers. In conclusion we provide new arguments toward the role played by glial GJ to maintain the frequency of spontaneous activities. We show that neuronal GJ control the PUI only in upper cortical layers.

Optimizing MR imaging detection of type 2 focal cortical dysplasia: best criteria for clinical practice.

BACKGROUND AND PURPOSE: Type 2 FCD is one of the main causes of drug-resistant partial epilepsy. Its detection by MR imaging has greatly improved surgical outcomes, but it often remains overlooked. Our objective was to determine the prevalence of typical MR imaging criteria for type 2 FCD, to provide a precise MR imaging pattern, and to optimize its detection. MATERIALS AND METHODS: We retrospectively reviewed 1.5T MR imaging of 71 consecutive patients with histologically proved type 2 FCD. The protocol included millimetric 3D T1-weighted, 2D coronal and axial T2-weighted, and 2D or 3D FLAIR images. Two experienced neuroradiologists looked for 6 criteria: cortex thickening, cortical and subcortical signal changes, blurring of the GWM interface, the "transmantle" sign, and gyral abnormalities. The frequency of each sign and their combination were assessed. We compared the delay between epilepsy onset and surgery, taking into account the time of type 2 FCD detection by MR imaging. RESULTS: Only 42 patients (59%) had positive MR imaging findings. In this group, a combination of at least 3 criteria was always found. Subcortical signal changes were constant. Three characteristic signs (cortical thickening, GWM blurring, and transmantle sign) were combined in 64% of patients, indicating that MR imaging can be highly suggestive. However, typical features of type 2 FCD were overlooked on initial imaging in 40% of patients, contributing to a delay in referral for surgical consideration (17 versus 11.5 years when initial MR imaging findings were positive). CONCLUSIONS: A combination of 3 major MR imaging signs allows type 2 FCD to be recognized in clinical practice, thereby enabling early identification of candidates for surgery.

Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy.

Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive-compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1-8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative-limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.

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.

Diffuse low-grade oligodendrogliomas extend beyond MRI-defined abnormalities.

BACKGROUND: Imaging determinations of the spatial extent of diffuse low-grade gliomas (DLGGs) are of paramount importance in evaluating the risk-to-benefit ratio of surgical resection. However, it is not clear how accurately preoperative conventional MRI can delineate DLGGs. METHODS: We report a retrospective histologic and imaging correlation study in 16 adult patients who underwent serial stereotactic biopsies for the diagnosis of untreated supratentorial well-defined and non-contrast-enhanced DLGG, in whom biopsy samples were taken within and beyond (OutBSs) MRI-defined abnormalities. RESULTS: Thirty-seven OutBSs that extended from 10 to 26 mm beyond MRI-defined abnormalities were studied. Immunostaining revealed MIB-1-positive cells (i.e., cycling cells) in all but 2 of the OutBSs. None of the MIB-1-positive cells coexpressed glial fibrillary acidic protein, and all of them coexpressed OLIG2. MIB-1-positive cells were cycling isolated tumor cells, because 1) their morphologic characteristics reflected those of tumor cells, 2) the number of MIB-1-positive cells per square centimeter was significantly higher than that of controls, 3) the number of MIB-1-positive cells per square centimeter was positively correlated with the tumor growth fraction (p = 0.012), and 4) the number of MIB-1-positive cells per square centimeter in OutBSs decreased with distance from the tumor (p = 0.003). CONCLUSIONS: This study demonstrates, using a multiscale correlative approach, that conventional MRI underestimates the actual spatial extent of diffuse low-grade gliomas (DLGGs), even when they are well delineated. These results suggest that an extended resection of a margin beyond MRI-defined abnormalities, whenever feasible in noneloquent brain areas, might improve the outcome of DLGGs.

Transient symptomatic vasospasm following antero-mesial temporal lobectomy for refractory epilepsy.

RATIONALE: Arterial vasospasm has rarely been reported following temporal lobectomy for intractable epilepsy. CASE PRESENTATION: A 31-year-old patient presented with a global aphasia 2 days after a left dominant anteromesial temporal lobectomy for intractable epilepsy. Magnetic resonance imaging on 5th post-operative day revealed severe narrowing of M1 segment of the left middle cerebral artery (MCA) and Transcranial Doppler (TCD) ultrasonography an increased velocity of the MCA that suggested a severe vasospasm. The patient received continuous intravenous hyperhydratation and nimodipine; aphasia improved within 24 h and resolved completely within 6 weeks, associated with velocity reduction on control TCD. CONCLUSION: Transient vasospasm is a likely underestimated cause of focal deficit following temporomesial resection that deserves appropriate treatment.

[Cranial nerve functional neurosurgery: evaluation of surgical practice]. / La neurochirurgie fonctionnelle des nerfs crâniens Evaluation de l'activité

We report the results of an investigation carried out on the activity of functional neurosurgery of the cranial nerves in the French-speaking countries, based on the analysis of a questionnaire addressed to all the members of the SNCLF. Eighteen centers responded to this questionnaire, which showed that activities and indications varied greatly from one unit to another. The results appear homogeneous and comparable with those reported in the literature. The questionnaire sought to provide a global perspective, open to the comments and questions of all responders on the various techniques raised, with the objective of establishing a common decisional tree for these pathologies and providing if possible to a consensus for better dissemination of these therapies.

[Takotsubo syndrome: a young woman case]. / Un syndrome de Takotsubo chez une patiente jeune.

After induction of anaesthesia for lumbar disc herniation surgery, an ASA-1, 39-year-old woman presented an acute heart failure. A persistent hypotension with tachycardia was observed after a brief hypertension peak during orotracheal intubation. After electrocardiogram, echocardiogram and biologic dosages, the diagnosis seems to be coronary ischemia. Coronarography was normal; takotsubo syndrome diagnosis was made with typical ventriculographic aspect. Evolution at two days and one month was favorable.

[On the best strategies on the best results for surgery of frontal epilepsy]. / Quelles stratégies pour quels résultats dans la chirurgie des épilepsies partielles frontales?

Frontal lobe epilepsy surgery is the second most common surgery performed for drug-resistant partial epilepsy. We investigated the longitudinal outcome in a cohort of patients investigated since 1990 with SEEG and modern diagnostic techniques. We reviewed 105 patients who underwent surgery between 1990 and 2005 (mean follow-up, six years; range: one to 17 years) and analyzed the year-per-year follow-up according to Engel's classification. Favorable outcome (Class I) was observed for 70% and this result was stable at least five years after surgery. More than 90% of patients with lesion-related epilepsies (focal cortical dysplasia and dysembryoplastic neuroepithelial tumors) became seizure-free. Less than 50% of patients classified as having cryptogenic epilepsy (defined as normal imaging and neuropathology on surgical specimen) had a favorable outcome. Permanent neurological sequelae were subtle and rare, especially after surgery for dysplasia in eloquent cortex (primary motor cortex). Our data indicate that frontal surgery is a successful treatment in patients when electrophysiological and morphological investigations demonstrate a well-defined epileptogenic zone or lesion to be surgically resected. Progress in electrophysiological and brain-imaging techniques will further improve the selection of frontal lobe epilepsy surgery candidates.

[Surgical resections in functional areas: report of 89 cases]. / Résections en région fonctionnelle: étude d'une série de 89 cas.

Surgical resections for intractable epilepsy are generally associated with a high risk of permanent neurological deficit and a poor rate of seizure control. We present a series of 89 patients operated on from 1992 through 2007 for drug-resistant partial epilepsy, in whom surgery was performed in a functional area of the brain: the central (sensorimotor and supplementary motor areas) region in 48 cases, posterior regions (parietal and occipital) in 27, the insula in eight, and the language areas in six. Epilepsy was cryptogenic in 12 patients, and lesion-related in 77: malformation of cortical development in 43, tumor in 17, perinatal cicatrix in 13, vascular lesion in three, and another prenatal lesion in one. Seventy patients underwent stereoelectroencephalographic (SEEG) exploration. The surgical procedure was resective (lesionectomy or SEEG-guided corticectomy) in 83 patients and multiple stereotactic thermocoagulations in six. Ten patients were reoperated because of early seizure recurrence. A postoperative complication was observed in 12 patients. Postoperative deficits were observed in 54 patients (61%) and resolved completely in 29. In 25, a permanent deficit persisted, minor in 19 and moderate to severe in six, which did not correlate with localization or etiology. With a one-year follow-up in 74 patients (mean, 3.6 years), 53 (72%) were in Engel's class I, including 38 (51%) in class IA. Seizure outcome was significantly associated with etiology: 93% of Taylor-type focal cortical dysplasia, whereas only 40% of cryptogenic epilepsies were in class I (p<0.05). This suggests that resective or disconnective surgery for intractable partial epilepsy in functional areas of the brain may be followed by excellent results on seizures and a moderate risk of permanent neurological sequelae.

[Epilepsy surgery in France]. / La chirurgie de l'épilepsie en France Evaluation de l'activité

We report here the results of the first survey on epilepsy surgery activity in France. Data from a questionnaire sent to 17 centers practicing epilepsy surgery were analyzed. All centers responded; however, all items were not completely documented. Over 50 years, more than 5000 patients have been operated on for drug-resistant epilepsy and more than 3000 patients underwent some invasive monitoring, most often SEEG. Currently, nearly 400 patients (including more than 100 children) are operated on yearly for epilepsy in France. Over a study period varying among centers (from two to 20 years; mean, 9.5 years), results from more than 2000 patients including one-third children were analyzed. Important differences between adults and children, respectively, were observed in terms of location (temporal: 72% versus 4.3%; frontal: 12% versus 28%; central: 2% versus 11%), etiology (hippocampal sclerosis: 41% versus 2%; tumors 20% versus 61%); and procedures (cortectomy: 50% versus 23%; lesionectomy: 8% versus 59%), although overall results were identical (seizure-free rates following temporal lobe surgery: 80.6% versus 79%; following extratemporal surgery: 65.9% versus 65%). In adults, the best results were observed following temporomesial (TM) resection associated with hippocampal sclerosis or other lesions (class I: 83% and 79%, respectively), temporal neocortical (TNC) lesional (82%), while resections for cryptogenic temporal resections were followed by 69% (TM) and 63% (TNC) class I outcome. Extratemporal lesional resections were associated with 71% class I outcome and cryptogenic 43%. In children, the best results were obtained in tumor-associated epilepsy regardless of location (class I: 80%). A surgical complication occurred in 8% after resective surgery - with only 2.5% permanent morbidity - and 4.3% after invasive monitoring (mostly hemorrhagic). Overall results obtained by epilepsy surgery centers were in the higher range of those reported in the literature, along with a low rate of major surgical complications. Growing interest for epilepsy surgery is clearly demonstrated in this survey and supports further development to better satisfy the population's needs, particularly children. Activity should be further evaluated, while existing epilepsy surgery centers as well as healthcare networks should be expanded.