The 2021 WHO classification distinguishes adult-type diffuse gliomas as astrocytoma, oligodendroglioma, and glioblastoma. Recently, a new epigenetic subtype-high-grade glioma IDH-wildtype, subtype F (HGG-F)-has been described, characterized by gliomatosis-like infiltration, low proliferative index, and unexpectedly prolonged survival despite a grade 4 methylation profile. We report the first HGG-F evaluated with 18 F-DOPA PET. Despite extensive FLAIR-hyperintense lesions, tracer distribution was entirely normal. This "amino acid PET silence," contrasting with the typically intense uptake in high-grade gliomas, together with the gliomatosis-like MRI appearance, should raise suspicion for this emerging subtype.
Chronic subdural hematoma (CSDH) is a common neurosurgical condition in the elderly population, with an increasing incidence attributed to longer life expectancy, widespread use of anticoagulant or antiplatelet agents, and a higher risk of falls. Its diagnosis remains challenging due to its nonspecific and often subtle clinical presentation, typically including confusion, cognitive decline, gait disturbances, or somnolence, which may mimic other geriatric syndromes. Neuroimaging is essential, with non-contrast CT as the first-line modality, complemented by MRI in selected cases to better characterize complex or atypical lesions. Surgical evacuation via burr-hole trepanation remains the cornerstone of management in symptomatic patients, particularly when associated with significant mass effect. The addition of subdural drainage and intraoperative irrigation with warm saline (37 °C) has been shown to reduce postoperative recurrence. Recently, middle meningeal artery (MMA) embolization has emerged as a promising minimally invasive technique aimed at occluding the vascular supply of the neomembrane responsible for persistent microbleeding. Recent randomized controlled trials have demonstrated the efficacy and safety of MMA embolization in reducing recurrence rates, either as a primary or adjunctive therapy, particularly in high-risk or inoperable patients. Beyond the procedure itself, patient outcomes largely depend on a multidisciplinary approach encompassing neurosurgery, interventional neuroradiology, anesthesiology, geriatrics, and rehabilitation. Optimal perioperative management includes correction of coagulation disorders, monitoring of fluid balance, and individualized postoperative surveillance. The integration of novel endovascular strategies with traditional surgical treatment opens new avenues for personalized care and improved prognosis in this vulnerable population. Further research is warranted to refine patient selection criteria for embolization, evaluate long-term outcomes, and determine its place in treatment algorithms.
Frame-based stereotactic biopsy has long been the gold standard for diagnostic brain biopsy, whereas robot-assisted stereotactic techniques have emerged as promising alternatives. However, rigorous methodological comparisons between these approaches remain scarce. To compare the diagnostic yield and complication rates of frame-and robot-assisted stereotactic brain biopsy using a rigorously matched cohort methodology. This retrospective, bicentric, comparative analysis included adult patients who underwent stereotactic brain biopsy between January 2011 and December 2019. Each patient who underwent robot-assisted biopsy (n = 230) was matched in a 2:1 ratio with patients who underwent frame-based biopsy (n = 460). Matching was performed based on clinically relevant criteria including lesion location, size, contrast enhancement, histopathology, and patient age. The primary outcomes were diagnostic yield and complication rates. The diagnostic yield was identical for both techniques 97.4
Background Epstein-Barr virus (EBV)-associated primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma closely linked to immunodeficiency. Imaging characteristics of EBV-associated are reported to differ from those of typical EBV-negative PCNSL. This study aims to describe the radiological and nuclear medicine imaging features in a large cohort of patients with EBV-associated PCNSL.Methods We conducted a multicenter retrospective descriptive study between 2008 and 2025 on patients with a diagnosis of EBV-associated PCNSL. MRI variables and FDG-PET/CT uptake were assessed.Results Fifty-eight cases of EBV-associated PCNSL were included. All but 1 patient were immunosuppressed. Multiple lesions were present in 71% of cases (41/58). Supratentorial involvement was observed in 90% of cases (52/58). Heterogeneous contrast enhancement was noted in 90% (52/58), with ring-like enhancement in 41% (24/58). Leptomeningeal enhancement occurred in 31% of cases (18/58), and within this group, 50% showed perivascular space enhancement. Lesions showed hypercellularity in 83% (48/58) and intralesional hemorrhage in 81% (47/58). An "eccentric target" sign was present in 26% of cases (15/58), while a "concentric target" sign in 14% (5/35). On FDG-PET, 25/30 patients had hypermetabolic lesions (25/30, 83%).Conclusion Diagnosing EBV-associated PCNSL is challenging due to its rarity and the broad differential diagnosis. Multiple necrotic and hemorrhagic lesions are the most suggestive MRI feature of EBV-associated PCNSL. "Eccentric" and "concentric" target signs, typically associated with CNS toxoplasmosis, can be observed. FDG-PET often reveals hypermetabolic lesions that support a neoplastic diagnosis. Histological confirmation remains essential for confidently treating this tumor entity.
Individual longitudinal changes in PET MTV and FLAIR volumes during treatment. For each patient, changes in PET-derived MTV (red line) and FLAIR lesion volume (blue line) are plotted over time, with treatment initiation marked as day 0. Numeric values indicate the change in volume at each time point, referenced either to baseline or to the lowest value observed (best response) in cases with multiple follow-ups. Each panel represents the data for a single patient.
PURPOSE:Cystathionine (Cth) has emerged as a promising biomarker for identifying 1p/19q codeleted gliomas. However, little is known about the T2 relaxation time constant of Cth in gliomas. The aim of this study was to measure the T2 of Cth in vivo in glioma and compare it to the T2s of other metabolites at 3 T. METHODS:Ten participants with glioma were scanned at 3 T. Single-voxel proton PRESS spectra were acquired at four echo-times to determine the T2 relaxation time constants of Cth, N-acetylaspartate, scyllo-inositol, total creatine, and total choline. Processed spectra were analyzed using LCModel, and the results were fitted using a mono-exponential function to estimate the T2 relaxation time constants. T2 of Cth was also measured using high-resolution NMR. RESULTS:The T2 of Cth varied across participants (42-128 ms, with a mean and standard deviation of 75 ± 24 ms). Additionally, T2 relaxation time constants of Cth were shorter than those of singlets measured in glioma in the same participants. Distinct differences in T2 between the CH and CH2 proton groups in Cth were also observed both in vitro and in vivo. CONCLUSION:Knowledge of the T2 of Cth should improve its quantification and may help increase understanding of the intracellular environment in glioma cells, potentially providing insights into tumor metabolism in future studies.
Percutaneous biopsy of petrous apex lesions is technically challenging due to deep skull base anatomy and proximity to critical neurovascular structures.1-5 In this technical video 1, we present a cone beam CT-guided biopsy using a contralateral subzygomatic transclival approach, initially described under CT guidance.6 The minimally invasive route provides a safe, direct trajectory to the petrous apex while preserving the internal carotid artery. The step-by-step workflow includes cone beam CT-based trajectory planning, fluoroscopic guidance, and coaxial bone sampling using an 11-gauge biopsy needle. Two clinical cases are demonstrated: one revealing metastatic breast cancer and another confirming Erdheim-Chester disease. Both procedures were completed without complications and allowed definitive histopathological diagnosis. This approach expands the interventional neuroradiologist's toolkit for skull base access and represents a valuable alternative to open surgical biopsy in selected patients, combining precision, safety, and diagnostic efficacy. neurintsurg;18/3/893/V1F1V1Video 1Cases presentation.
Non-traumatic infratentorial cerebellar haematomas can occur spontaneously or secondarily to a vascular malformation, leading to life-threatening conditions that can necessitate surgical or radiological interventions and admission to the Neurological Intensive Care Unit (NICU). We conducted a retrospective, single-centre observational study over a 17-year period (2005-2022) involving all adult patients admitted to the NICU of a French tertiary centre with a diagnosis of non-traumatic infratentorial cerebellar brain haematoma. Among the 88 patients (median age 58 (interquartile range (IQR) 48-67) years) included in the study, a vascular malformation was found in 36 patients (41%). Surgical evacuation of the haematoma or a radio-embolisation procedure was performed in 53 patients (60%) and 18 patients (20%) respectively. Median length of NICU stay was 26 (IQR 12-45) days, and prolonged ventilatory support (>21 days) was necessary in 35 patients (40%). In NICU survivors, awareness recovery occurred at a median of 3 (IQR 1-6) days after discontinuation of sedation. NICU mortality was 19% (n = 17), and 97% (n = 62) of the NICU survivors who were included in the three-month follow-up were alive, while 56% (n = 36) had a favourable neurological outcome (modified Rankin Scale (mRS) ⩽ 3). We found a significant association between an unfavourable neurological outcome (three-month mRS score > 3) and advanced age (P = 0.004), pre-existing antithrombotic therapy (P = 0.04), low Glasgow Coma Scale score on admission (P < 0.001), presence of a ventricular haemorrhage (P = 0.04), presence of brainstem compression (P < 0.001) and delay in awareness recovery (P = 0.005). Among patients with a cerebellar haematoma and impaired alertness, half will have a favourable outcome at three months. Further studies are needed to explore these results over time and at other centres.
Exploratory comparison of baseline 18F-DOPA-PET values in progressors (n=6) vs non-progressors (n=14) on IDH inhibitor treatment. Parameters include metabolic tumor volume (MTV), total lesion glycolysis (TLG), tumor-to-background maximum ratio (TBRmax), and mean ratio (TBRmean). P-values were calculated using the Mann-Whitney U test.
Contexte et objectif L’imagerie pondérée par transfert de proton amide APTw permet de visualiser la concentration en protéines des gliomes, contribuant ainsi la caractérisation et à l’évaluation pronostique des gliomes1. Cependant, des artefacts peuvent réduire la spécificité de cette technique, incluant la saturation directe de l’eau, le transfert de magnétisation semi-solide (ssMT) et la relaxation T12. Cette étude vise à évaluer si les corrections successives des métriques APTw (spillover, ssMT, T1) améliorent la detection de la mutation IDH et de la co-déléction 1p/19q, deux marqueurs moléculaires clés pour le diagnostic des gliomes. Méthodologie Quarante-six patients présentant un gliome diffus présumé éligible à la chirurgie ont été inclus prospectivement. Les acquisitions ont été réalisées à l’aide d’une séquence 3D snapshot-GRE CEST à 3 Tesla (B1 = 2 µT, T₁sat = 2 s), complétée par une cartographie B₀/B₁ (WASABI) et T₁ (Saturation Recovery, B₁ = 5 µT, 14 points de récupération). Les métriques analysées étaient :• MTRasym (standard, non corrigé)3,• MTRRex (corrigé pour la saturation directe de l’eau et le ssMT)4,• AREX (corrigé pour la saturation, le ssMT et T1)4.Les comparaisons statistiques ont utilisé des tests U de Mann-Whitney (correction de Benjamini-Hochberg) et des tests t de Welch sur les médianes, avec un seuil de significativité fixé à p corrigé < 0,05. Résultats Les métriques corrigées (MTRRex et AREX) séparaient significativement mieux les gliomes IDH-mutés (p ≤ 1,4×10⁻⁶) des gliomes IDH normal que la métrique standard MTRasym (p = 0,008) (Figure 1, A).Au sein des gliomes IDH-mutés, l’AREX distinguait les oligodendrogliomes (codélétés 1p/19q) des astrocytomes (non codélétés, p = 0,010), avec des valeurs plus élevées pour les oligodendrogliomes (Figure 1, B).La séquence de correction (MTRasym → MTRRex → AREX, Figure 2) améliorait la cohérence intra-groupe et la séparabilité des sous-types moléculaires. Conclusion La correction des artefacts liés au contenu liquide des lésions optimise la précision diagnostique de l’imagerie APT. Cette approche offre une méthode robuste, précise et biologiquement fondée pour la stratification moléculaire non invasive des gliomes.
BACKGROUND:Chlorhexidine is the preferred antiseptic for skin preparation owing to its superior antimicrobial efficacy compared with povidone-iodine. However, its supposed neurotoxicity-particularly in combination with alcohol-can cause catastrophic damage if inadvertently introduced into the neuraxial space during epidural or spinal anesthesia. CASE PRESENTATION:We describe a fatal case of arachnoiditis following unintentional intradural injection of alcohol-based chlorhexidine during epidural catheter placement for labor analgesia and report a literature review. Among 114 records, five case reports met the inclusion criteria. All patients were women receiving epidural or spinal anesthesia for obstetric or surgical procedures. Exposure involved either direct injection or contamination of anesthetic solutions with chlorhexidine. Onset ranged from immediate lumbar pain to delayed neurological deterioration. Reported outcomes included paraplegia, tetraplegia, hydrocephalus, syringomyelia, and profound functional loss. Therapeutic interventions-corticosteroids, neurosurgery, cerebrospinal fluid shunting, and analgesia-were ineffective in reversing deficits. Error prevention is essential and relies on the use of colored solutions, strict physical separation between chlorhexidine and other solutions used during procedures, the use of pre-impregnated applicators, or alternatively the use of naturally colored povidone-iodine, which may be less neurotoxic. CONCLUSIONS:Accidental intradural or epidural administration of chlorhexidine is a rare but devastating event most often associated with poor outcomes. Prevention requires mandating colored antiseptics or enforcing strict handling protocols.
Gliomas with mutant isocitrate dehydrogenase (IDH) are malignant brain tumours that typically arise in early to mid-adulthood and nearly always recur following treatment1,2. However, the genetic and cellular-state changes that drive IDH-mutant glioma progression under treatment remain incompletely understood. Here we integrated single-nucleus transcriptomic profiles, chromatin accessibility profiles and bulk DNA and RNA sequencing from 75 temporally separated gliomas across 35 patients comprising both the oligodendroglioma and astrocytoma IDH-mutant glioma tumour types. We show that malignant cell states transcriptionally resemble stages of normal glial-neuronal lineage development or a reactive mesenchymal-like state, mirroring states previously described in IDH wild-type glioblastoma3,4. Malignant cell states displayed distinct chromatin accessibility profiles that were comparable between both IDH-mutant glioma types. The abundance of less differentiated malignant cells increased with grade and with genetic alterations such as PDGFRA amplification. Longitudinal analysis highlighted two major malignant cell-state transition patterns. First, reduced lineage differentiation and increased proliferative malignant cells at recurrence were enriched in gliomas that acquired recurrence-associated genetic events. These included treatment-associated hypermutation, increased copy number changes and cell cycle alterations. Second, increased mesenchymal-like-state abundance occurred independently of acquired genetic alterations and instead coincided with elevated macrophage expression. Overall, our findings provide an integrative model that traces the cell intrinsic and extrinsic factors that shape cellular states during IDH-mutant glioma disease progression.
PURPOSE:Small-molecule inhibitors targeting isocitrate dehydrogenase (IDH) 1/2-mutant proteins have demonstrated benefit in IDH1/2-mutant gliomas. However, responses assessed by conventional MRI measurements are infrequent, delayed, and difficult to interpret, highlighting the need for early biomarkers of treatment benefit. In this study, we investigated 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine positron emission tomography (18F-DOPA-PET) and MRI responses in patients with IDH1/2-mutant glioma receiving IDH inhibitors (IDHi). EXPERIMENTAL DESIGN:Patients with IDH1/2-mutant glioma receiving IDHi as part of trials or expanded access programs with pre- and posttreatment MRI and 18F-DOPA-PET were included. Evaluations included 2D/3D measurements on T2-weighted fluid-attenuated inversion recovery images; T1-post-contrast, perfusion, and diffusion imaging for MRI; and metabolic tumor volume (MTV), total lesion glycolysis, and tumor-to-background ratios (TBR) for 18F-DOPA-PET. Disease response evaluation using volumetric assessments, RANO 2.0, and PET RANO 1.0 criteria were compared and correlated with outcomes. RESULTS:From 2021 to 2025, 20 patients with IDH1/2-mutant glioma (8 with astrocytoma and 12 with oligodendroglioma) receiving IDHi (4 receiving ivosidenib and 16 receiving vorasidenib) were analyzed. Significant reductions in 18F-DOPA-PET parameters including TBRmean, TBRmax, and MTV were observed in 10 of 20 patients, aligning with observed changes in perfusion and diffusion imaging. Nine partial responses and one complete response were identified using 18F-DOPA-PET, whereas both volumetric and standard 2D morphologic MRI assessments indicated stable disease as best response. PET response on MTV was correlated with prolonged tumor control. CONCLUSIONS:These results highlight the potential of 18F-DOPA-PET and advanced MRI sequences as valuable complements to standard RANO 2.0 MRI evaluations for assessing treatment response in patients with glioma undergoing IDHi therapy.
Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE/HS) is the most common cause of drug-resistant focal seizures and surgical resection is the primary treatment option, with seizure-free rates ranging from 60 to 80
This single-center pilot study evaluated the feasibility, safety, and patient acceptability of fully ambulatory, home-to-home supratentorial craniotomy for intracerebral lesion resection in a European academic setting. All consecutive adults scheduled between January 2024 and July 2025 for outpatient non-emergent supratentorial craniotomy under general anesthesia for brain lesion resection were retrospectively analyzed. Patients were selected preoperatively according to predefined clinical, anesthetic, and social criteria and managed within a standardized Enhanced Recovery After Surgery–oriented pathway including morning scheduling, systematic early postoperative imaging, and structured telemedicine follow-up. Primary endpoints were failure of same-day discharge, surgery-related complications within 30 days, and unplanned hospital admission or consultation. Patient-reported satisfaction with ambulatory management was assessed by questionnaire. Among 606 supratentorial brain lesion resections performed during the study period, 40 (6.6
Epileptic seizures and interictal epileptiform discharges are strongly influenced by sleep and circadian rhythms. However, human data on the effect of sleep on neuronal behaviour during interictal activity have been lacking. We analysed EEG from eight epileptic patients implanted with macro and micro electrodes in mesial temporal structures. Sleep staging was performed on polysomnography and video-EEG. Automated detection identified thousands of interictal epileptiform discharges per patient. Both their rate and amplitude increased with deeper stages of non-rapid eye movement sleep. Single- and multi-unit firing rates were often temporally coupled with local field potentials, exhibiting increased firing during the spike and decreased activity during the following slow wave. These time-locked firing rate modulations were shown to increase during deeper stages of non-rapid eye movement sleep. Furthermore, neuronal background activity showed a decrease in firing rate, bursting and regularity with deeper stages of non-rapid eye movement sleep.
Mesial (a.k.a., medial) temporal lobe epilepsy (MTLE) is the most common focal epilepsy1,2 and, in drug-resistant cases, is treated by surgical removal of the anterior temporal lobe, which often shows neuronal loss and gliosis consistent with hippocampal sclerosis (HS)2. MTLE with HS has minimal contribution from germline genetic variation3, and is associated with prior precipitating insults such as prolonged childhood seizures and head trauma4-6. Somatic variants in Ras-MAPK pathway genes were recently reported in a few MTLE surgical specimens7,8, but their prevalence, clinical relevance, and underlying biological mechanisms remain unknown. Targeted duplex sequencing of hippocampal DNA from 462 surgical resections revealed significant enrichment of deleterious somatic variants in MTLE versus controls, with >40% of MTLE specimens harboring activating Ras-MAPK variants in PTPN11, NF1, BRAF, KRAS, and twelve genes not previously associated with focal epilepsy. Eight Ras-MAPK genes showed positive clonal selection in MTLE. Increased somatic variant burden predicted worse surgical outcome. Somatic Ras-MAPK variants at ultra-low (<0.5%) variant allele fractions were associated with older seizure onset and HS pathology, supporting a late prenatal or postnatal origin. Ras-MAPK variants in MTLE were enriched in cells derived from hippocampal progenitors-neurons, astrocytes, oligodendrocytes-in line with the known neuronal hyperexcitability and seizures induced by Ras-MAPK overactivation9,10; in contrast, Alzheimer disease hippocampi exhibited microglial enrichment of Ras-MAPK variants, consistent with prior reports11. Single-nucleus RNA sequencing showed increased expression of Ras-MAPK genes in neurons and upregulation of pathways mediating neurogenesis and neural development in MTLE. Functional validation of novel, recurrent PTPN11 variants confirmed gain-of-function, while cellular modeling in induced pluripotent stem cells demonstrated proliferative/survival advantages for mutant cells in mosaic culture. Overall, our data suggest that somatic Ras-MAPK variants and acquired risk factors may converge on clonal competition in the hippocampus to modulate epilepsy risk.
PURPOSE:Surgery is the treatment of choice for drug-resistant temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS). We assessed whether interictal epileptiform discharges (IEDs) on early postoperative EEG predicted seizure outcome after surgery. METHODS:We retrospectively included consecutive patients aged >16 years who underwent surgery for drug-resistant TLE with pathologically confirmed HS at Pitié-Salpêtrière Hospital, Paris, between 2003 and 2023. Eligible patients had at least 1 year of follow-up and an early postoperative EEG performed within 1 month after surgery. IED frequency was classified as high frequency (≥1/min) or low frequency (<1/min). Favourable 1-year outcome was defined as ILAE class 1. Long-term worsening was defined as any increase in ILAE class after the 1-year visit. RESULTS:Among 168 patients, 131 (78.0%) were ILAE class 1 at 1 year. EEG was performed a median of 7 days after surgery. IEDs were present in 81 patients (48.2%), including 48 with low-frequency and 33 with high-frequency IEDs. EEG features, including IED presence and frequency, did not differ between patients with and without ILAE class 1 outcome at 1 year. During longer follow-up, high-frequency IEDs were associated with worsening compared with no IEDs in the whole cohort (HR 2.25, 95% CI 1.01-4.98; p=0.046) and among patients seizure-free at 1 year (HR 2.59, 95% CI 1.10-6.11; p=0.03). Low-frequency IEDs were not associated with worsening. CONCLUSION:High-frequency IEDs on early postoperative EEG may identify patients at increased risk of long-term deterioration after surgery for HS-related TLE. Prospective studies are needed before modifying routine follow-up strategies.
To evaluate the long-term efficacy and safety of stereo-electroencephalography (sEEG)-guided surgical resection in patients with MRI-negative, drug-resistant focal epilepsy and to identify predictors of favorable seizure outcomes. We conducted a retrospective cohort study of 107 patients who underwent sEEG-guided resective epilepsy surgery at a tertiary neurosurgical center. The inclusion criteria were normal brain MRI (MRI-negative), drug-resistant focal epilepsy, and a minimum postoperative follow-up of one year. The temporal lobe was the most commonly resected site (66.2