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1.
JAMA Surg ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598199

RESUMO

This article discusses the implementation of surgical activity regulation methodology in the operating room to reduce organizational dysfunction, improve quality of work life of the surgical staff, and decrease staff overtime.

2.
Epilepsia ; 65(5): 1333-1345, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38400789

RESUMO

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.


Assuntos
Benchmarking , Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/cirurgia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Criança , Pré-Escolar , Lactente , Complicações Pós-Operatórias/epidemiologia , Procedimentos Neurocirúrgicos/normas , Procedimentos Neurocirúrgicos/métodos , Epilepsia Resistente a Medicamentos/cirurgia , Lobectomia Temporal Anterior/métodos
3.
J Neurointerv Surg ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307722

RESUMO

BACKGROUND: Middle meningeal artery (MMA) embolization has been proposed as a treatment of chronic subdural hematoma (CSDH). The benefit of the procedure has yet to be demonstrated in a randomized controlled trial. We aim to assess the efficacy of MMA embolization in reducing the risk of CSDH recurrence 6 months after burr-hole surgery compared with standard medical treatment in patients at high risk of postoperative recurrence. METHODS: The EMPROTECT trial is a multicenter open label randomized controlled trial (RCT) involving 12 French centers. Adult patients (≥18 years) operated for CSDH recurrence or for a first episode with a predefined recurrence risk factor are randomized 1:1 to receive either MMA embolization within 7 days of the burr-hole surgery (experimental group) or standard medical care (control group). The number of patients to be included is 342. RESULTS: The primary outcome is the rate of CSDH recurrence at 6 months. Secondary outcomes include the rate of repeated surgery for a homolateral CSDH recurrence during the 6-month follow-up period, the rate of disability and dependency at 1 and 6 months, defined by a modified Rankin Scale (mRS) score ≥4, mortality at 1 and 6 months, total cumulative duration of hospital stay during the 6-month follow-up period, directly or indirectly related to the CSDH and embolization procedure-related complication rates. CONCLUSIONS: The EMPROTECT trial is the first RCT evaluating the benefit of MMA embolization as a surgical adjunct for the prevention of CSDH recurrence. If positive, this trial will have a significant impact on patient care. TRIAL REGISTRATION NUMBER: NCT04372147.

4.
Nat Commun ; 15(1): 1650, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396134

RESUMO

Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. After surgery, activation to disrupt the BBB was performed every four weeks either before or after carboplatin infusion. The primary objective of the Phase 1 was to evaluate the safety of escalating numbers of ultrasound emitters using a standard 3 + 3 dose escalation. The primary objective of the Phase 2 was to evaluate the efficacy of BBB opening using magnetic resonance imaging (MRI). The secondary objectives included safety and clinical efficacy. Thirty-three patients received a total of 90 monthly sonications with carboplatin administration and up to nine emitters activated without observed DLT. Grade 3 procedure-related adverse events consisted of pre syncope (n = 3), fatigue (n = 1), wound infection (n = 2), and pain at time of device connection (n = 7). BBB opening endpoint was met with 90% of emitters showing BBB disruption on MRI after sonication. In the 12 patients who received carboplatin just prior to sonication, the progression-free survival was 3.1 months, the 1-year overall survival rate was 58% and median overall survival was 14.0 months from surgery.


Assuntos
Barreira Hematoencefálica , Glioblastoma , Humanos , Carboplatina/efeitos adversos , Barreira Hematoencefálica/patologia , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Ultrassonografia , Transporte Biológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
Cancer Cell ; 42(3): 358-377.e8, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38215747

RESUMO

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Proteogenômica , Animais , Humanos , Glioblastoma/genética , Proteínas Proto-Oncogênicas B-raf , Proteômica , Linhagem Celular Tumoral , Recidiva Local de Neoplasia , Modelos Animais de Doenças , Neoplasias Encefálicas/genética , Resistencia a Medicamentos Antineoplásicos , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Eur J Surg Oncol ; 50(2): 107935, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199005

RESUMO

BACKGROUND: Metastatic epidural spinal cord compression (MESCC) and pathological vertebral compression fractures (pVCF) are the most serious debilitating morbidities of spine metastases (SpMs) causing devastating neurological damages. The respective impact of these two metastasis-spreading entities on survival and on neurological damage is debated. METHODS: A French prospective cohort study collected 279 consecutive patients presenting with SpMs between January 2017 and 2021. We compared 174 patients with MESCC and 105 patients with pVCF. RESULTS: The median Overall Survival (OS) for the MESCC group was 13.4 months (SD 1.5) vs 19.2 months (SD 2.3) for pVCF patients (p = 0.085). Sixty-five patients (23.3 %) were operated on: 49/65 (75.4 %) in the MESCC group and 16/65 (15.2 %) in the pVCF group, p < 0.0001. At 6 months FU, in the MESCC group, 21/44 (45.4 %) of non-ambulatory patients at onset improved to ambulatory status (Frankel D-E) vs 10/13 (76.9 %) in the pVCF group (p = 0.007). In multivariable analysis with the Cox proportional hazard model, good ECOG-PS and SINS Score 7-12 [HR: 6.755, 95 % CI 2.40-19.00; p = 0.001] were good prognostic factors for preserved ambulatory neurological status. However, SpMs diagnosed synchronously with the primary tumor [HR: 0.397, 95 % CI 0.185-0.853; p = 0.018] and MESCC [HR: 0.058, 95 % CI 0.107-0.456; p = 0.007] were independent risk factors for impaired neurological function. CONCLUSION: Contrary to pVCF, MESCC causes neurological damage. Nevertheless, neurological recovery remains possible. MESCC and pVCF have no impact on survival. The management of MESCC remains to be clarified and optimized to reduce neurological damage.


Assuntos
Fraturas por Compressão , Fraturas Espontâneas , Compressão da Medula Espinal , Fraturas da Coluna Vertebral , Neoplasias da Coluna Vertebral , Humanos , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Fraturas por Compressão/complicações , Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/secundário , Descompressão Cirúrgica/efeitos adversos , Prognóstico , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/cirurgia
7.
Eur J Neurol ; 31(1): e16093, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37823694

RESUMO

BACKGROUND: Dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) positron emission tomography (PET) is a valuable tool for managing high-grade gliomas (HGGs), but there is a lack of literature on its relationship with glioma subtypes since the 2021 reclassification of brain tumors. There is also debate surrounding the mechanism of 18F-FDOPA uptake, particularly after chemoradiation therapy. This study aimed to investigate the correlation between 18F-FDOPA uptake and histomolecular characteristics, particularly L-amino acid transporter 1 (LAT1) expression, in recurrent gliomas, and examine their impact on survival in HGGs. METHODS: Thirty-nine patients with recurrent HGGs (14 isocitrate dehydrogenase [IDH]-mutant, 25 IDH-wildtype) who underwent a brain 18F-FDOPA PET/computed tomography (CT) or PET/magnetic resonance imaging (MRI) followed by surgical resection of the 18F-FDOPA-avid lesion within 6 months, were retrospectively reviewed. PET results were compared with histological examination and for SCL7A5/LAT1 immunostaining. The study also examined the relationship between PET parameters, LAT1 expression, and survival outcomes. RESULTS: Astrocytoma IDH-mutant G4 had higher 18F-FDOPA uptake than glioblastoma IDH-wildtype G4 (maximum tumor-to-normal brain ratio [TBRmax] 5 [3.4-9] vs. 3.8 [2.8-5.9], p = 0.02). IDH-mutant gliomas had higher LAT1 expression than IDH-wildtype gliomas (100 [14-273] vs. 15.5 [0-137], p < 0.05) as well as higher TBRmax (5 [2.4-9] vs. 3.8 [2.8-6], p < 0.05). In survival analysis, LAT1 score >100 was a predictor for longer progression-free survival in IDH-mutant HGGs. CONCLUSIONS: To our knowledge, our study is the first to suggest a link between LAT1 expression and IDH mutation status. We showed that higher TBRmax was associated with higher LAT1 expression and IDH mutation status. Further studies are needed to better understand the mechanisms underlying amino acid PET tracers uptake, especially in the post-radiation and chemotherapy settings.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Estudos Retrospectivos , Glioma/diagnóstico por imagem , Glioma/genética , Di-Hidroxifenilalanina , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia
8.
Epilepsy Res ; 198: 107260, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38007914

RESUMO

PURPOSE: Patients with severe drug-resistant epilepsy (DRE) experience psychomotor disorders. Our study aimed to assess the psychomotor outcomes after vagus nerve stimulation (VNS) in this population. METHODS: We prospectively evaluated psychomotor function in 17 adult patients with severe DRE who were referred for VNS. Psychomotor functions were examined, in the preoperative period and at 18 months post-surgery, by a psychomotor therapist using a full set of the following specific tests: the Rey-Osterrieth complex figure (ROCF) test, the Zazzo's cancelation task (ZCT), the Piaget-Head test and the paired images test. RESULTS: At 18 months post-VNS surgery, the Piaget-head scores increased by 3 points (p = 0.008) compared to baseline. Performances were also improved for ROCF test both in copy (+2.4 points, p = 0.001) and recall (+2.0 points, p = 0.008) tasks and for the paired images test (accuracy index: +28.6 %, p = 0.03). Regarding the ZCT findings, the efficiency index increased in both single (+16 %, p = 0.005) and dual (+17.1 %, p < 0.001) tasks. QoL improved in 88.2 % of patients. CONCLUSIONS: Patients with severe DRE treated with VNS experienced improved performance in terms of global psychomotor functions. Perceptual organization, visuospatial memory, laterality awareness, sustained attention, concentration, visual scanning, and inhibition were significantly improved.


Assuntos
Epilepsia Resistente a Medicamentos , Estimulação do Nervo Vago , Adulto , Humanos , Estimulação do Nervo Vago/métodos , Qualidade de Vida , Epilepsia Resistente a Medicamentos/terapia , Rememoração Mental , Desempenho Psicomotor , Resultado do Tratamento , Nervo Vago
10.
Neuropathol Appl Neurobiol ; 49(5): e12937, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37740653

RESUMO

OBJECTIVE: Mesial Temporal Lobe Epilepsy-associated Hippocampal Sclerosis (MTLE-HS) is a syndrome associated with various aetiologies. We previously identified CD34-positive extravascular stellate cells (CD34+ cells) possibly related to BRAFV600E oncogenic variant in a subset of MTLE-HS. We aimed to identify the BRAFV600E oncogenic variants and characterise the CD34+ cells. METHODS: We analysed BRAFV600E oncogenic variant by digital droplet Polymerase Chain Reaction in 53 MTLE-HS samples (25 with CD34+ cells) and nine non-expansive neocortical lesions resected during epilepsy surgery (five with CD34+ cells). Ex vivo multi-electrode array recording, immunolabelling, methylation microarray and single nuclei RNAseq were performed on BRAFwildtype MTLE-HS and BRAFV600E mutant non-expansive lesion of hippocampus and/or neocortex. RESULTS: We identified a BRAFV600E oncogenic variant in five MTLE-HS samples with CD34+ cells (19%) and in five neocortical samples with CD34+ cells (100%). Single nuclei RNAseq of resected samples revealed two unique clusters of abnormal cells (including CD34+ cells) associated with senescence and oligodendrocyte development in both hippocampal and neocortical BRAFV600E mutant samples. The co-expression of the oncogene-induced senescence marker p16INK4A and the outer subventricular zone radial glia progenitor marker HOPX in CD34+ cells was confirmed by multiplex immunostaining. Pseudotime analysis showed that abnormal cells share a common lineage from progenitors to myelinating oligodendrocytes. Epilepsy surgery led to seizure freedom in eight of the 10 patients with BRAF mutant lesions. INTERPRETATION: BRAFV600E underlies a subset of MTLE-HS and epileptogenic non-expansive neocortical focal lesions. Detection of the oncogenic variant may help diagnosis and open perspectives for targeted therapies.


Assuntos
Epilepsias Parciais , Epilepsia do Lobo Temporal , Epilepsia , Neocórtex , Humanos , Epilepsia do Lobo Temporal/patologia , Neocórtex/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Hipocampo/patologia , Epilepsias Parciais/genética , Epilepsias Parciais/complicações , Epilepsias Parciais/patologia , Epilepsia/patologia , Esclerose/patologia , Imageamento por Ressonância Magnética
11.
Int J Mol Sci ; 24(15)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37569786

RESUMO

Alzheimer's disease (AD) is the leading cause of dementia. No treatments have led to clinically meaningful impacts. A major obstacle for peripherally administered therapeutics targeting the central nervous system is related to the blood-brain barrier (BBB). Ultrasounds associated with microbubbles have been shown to transiently and safely open the BBB. In AD mouse models, the sole BBB opening with no adjunct drugs may be sufficient to reduce lesions and mitigate cognitive decline. However, these therapeutic effects are for now mainly assessed in preclinical mouse models of amyloidosis and remain less documented in tau lesions. The aim of the present study was therefore to evaluate the effects of repeated BBB opening using low-intensity pulsed ultrasounds (LIPU) in tau transgenic P301S mice with two main readouts: tau-positive lesions and microglial cells. Our results show that LIPU-induced BBB opening does not decrease tau pathology and may even potentiate the accumulation of pathological tau in selected brain regions. In addition, LIPU-BBB opening in P301S mice strongly reduced microglia densities in brain parenchyma, suggesting an anti-inflammatory action. These results provide a baseline for future studies using LIPU-BBB opening, such as adjunct drug therapies, in animal models and in AD patients.


Assuntos
Doença de Alzheimer , Tauopatias , Camundongos , Animais , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Doença de Alzheimer/patologia , Barreira Hematoencefálica/patologia , Tauopatias/terapia , Tauopatias/patologia , Camundongos Transgênicos , Ondas Ultrassônicas
12.
Magn Reson Imaging ; 103: 119-123, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37481093

RESUMO

Areas of marked T2-FLAIR hyperintensity around perivascular spaces can be misdiagnosed as tumor, especially in case of lesion evolution. In this report, we show and describe increased T2-FLAIR signal intensity around anterior temporal perivascular spaces in three patients and shortly review this poorly known entity. In addition, we discuss for the first time the added value of fluid suppressed APTw imaging, an emerging noninvasive molecular technique, in the characterization of this "do not touch" abnormality.


Assuntos
Imageamento por Ressonância Magnética , Prótons , Humanos , Imageamento por Ressonância Magnética/métodos
13.
World Neurosurg ; 176: e680-e685, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37295466

RESUMO

OBJECTIVE: Multiple myeloma (MM) is too often wrongly categorized as a spinal metastasis (SpM), although it is distinguishable from SpM in many aspects, such as its earlier natural history at the time of diagnosis, its increased overall survival (OS), and its response to therapeutic modalities. The characterization of these 2 different spine lesions remains a main challenge. METHODS: This study compares 2 consecutive prospective oncologic populations of patients with spine lesions: 361 patients treated for MM spine lesions and 660 patients treated for SpM between January 2014 and 2017. RESULTS: The mean time between the tumor/MM diagnosis and spine lesions was respectively 0.3 (standard deviation [SD] 4.1) and 35.1 months (SD 21.2) for the MM and SpM groups. The median OS for the MM group was 59.6 months (SD 6.0) versus 13.5 months (SD 1.3) for the SpM group (P < 0.0001). Regardless of Eastern Cooperative Oncology Group (ECOG) performance status, patients with MM always have a significantly better median OS than do patients with SpM: ECOG 0, 75.3 versus 38.7 months; ECOG 1, 74.3 versus 24.7 months; ECOG 2, 34.6 versus 8.1 months; ECOG 3, 13.5 versus 3.2 months and ECOG 4, 7.3 versus 1.3 months (P < 0.0001). The patients with MM had more diffuse spinal involvement (mean, 7.8 lesions; SD 4.7) than did patients with SpM (mean, 3.9; SD 3.5) (P < 0.0001). CONCLUSIONS: MM must be considered as a primary bone tumor, not as SpM. The strategic position of the spine in the natural course of cancer (i.e., nurturing cradle of birth for MM vs. systemic metastases spreading for SpM) explains the differences in OS and outcome.


Assuntos
Mieloma Múltiplo , Osteossarcoma , Neoplasias da Coluna Vertebral , Humanos , Mieloma Múltiplo/terapia , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico , Estudos Prospectivos , Prognóstico , Coluna Vertebral/cirurgia
14.
JCO Precis Oncol ; 7: e2200525, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37262394

RESUMO

PURPOSE: The Lynch syndrome (LS)-glioma association is poorly documented. As for mismatch repair deficiency (MMRd) in glioma, a hallmark of LS-associated tumors, there are only limited data available. We determined MMRd and LS prevalence in a large series of unselected gliomas, and explored the associated characteristics. Both have major implications in terms of treatment, screening, and prevention. METHODS: Somatic next-generation sequencing was performed on 1,225 treatment-naive adult gliomas referred between 2017 and June 2022. For gliomas with ≥1 MMR pathogenic variant (PV), MMR immunohistochemistry (IHC) was done. Gliomas with ≥1 PV and protein expression loss were considered MMRd. Eligible patients had germline testing. To further explore MMRd specifically in glioblastomas, isocitrate dehydrogenase (IDH)-wild type (wt), we performed IHC, and complementary sequencing when indicated, in a series of tumors diagnosed over the 2007-2021 period. RESULTS: Nine gliomas were MMRd (9/1,225; 0.73%). Age at glioma diagnosis was <50 years for all but one case. Eight were glioblastomas, IDH-wt, and one was an astrocytoma, IDH-mutant. ATRX (n = 5) and TP53 (n = 8) PV were common. There was no TERT promoter PV or EGFR amplification. LS prevalence was 5/1,225 (0.41%). One 77-year-old patient was a known LS case. Four cases had a novel LS diagnosis, with germline PV in MSH2 (n = 3) and MLH1 (n = 1). One additional patient had PMS2-associated constitutional mismatch repair deficiency. Germline testing was negative in three MSH6-deficient tumors. In the second series of glioblastomas, IDH-wt, MMRd prevalence was 12.5% in the <40-year age group, 2.6% in the 40-49 year age group, and 1.6% the ≥50 year age group. CONCLUSION: Screening for MMRd and LS should be systematic in glioblastomas, IDH-wt, diagnosed under age 50 years.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Glioblastoma , Glioma , Síndromes Neoplásicas Hereditárias , Humanos , Adulto , Pessoa de Meia-Idade , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Síndromes Neoplásicas Hereditárias/epidemiologia , Síndromes Neoplásicas Hereditárias/genética , Glioma/epidemiologia , Glioma/genética
16.
Ultrasound Med Biol ; 49(5): 1327-1336, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36878831

RESUMO

OBJECTIVE: It is unknown whether ultrasound-induced blood-brain barrier (BBB) disruption can promote epileptogenesis and how BBB integrity changes over time after sonication. METHODS: To gain more insight into the safety profile of ultrasound (US)-induced BBB opening, we determined BBB permeability as well as histological modifications in C57BL/6 adult control mice and in the kainate (KA) model for mesial temporal lobe epilepsy in mice after sonication with low-intensity pulsed ultrasound (LIPU). Microglial and astroglial changes in ipsilateral hippocampus were examined at different time points following BBB disruption by respectively analyzing Iba1 and glial fibrillary acidic protein immunoreactivity. Using intracerebral EEG recordings, we further studied the possible electrophysiological repercussions of a repeated disrupted BBB for seizure generation in nine non-epileptic mice. RESULTS: LIPU-induced BBB opening led to transient albumin extravasation and reversible mild astrogliosis, but not to microglial activation in the hippocampus of non-epileptic mice. In KA mice, the transient albumin extravasation into the hippocampus mediated by LIPU-induced BBB opening did not aggravate inflammatory processes and histologic changes that characterize the hippocampal sclerosis. Three LIPU-induced BBB opening did not induce epileptogenicity in non-epileptic mice implanted with depth EEG electrodes. CONCLUSION: Our experiments in mice provide persuasive evidence of the safety of LIPU-induced BBB opening as a therapeutic modality for neurological diseases.


Assuntos
Barreira Hematoencefálica , Epilepsia do Lobo Temporal , Camundongos , Animais , Barreira Hematoencefálica/metabolismo , Epilepsia do Lobo Temporal/terapia , Epilepsia do Lobo Temporal/induzido quimicamente , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Albuminas , Hipocampo
17.
J Neurooncol ; 162(2): 373-382, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36991306

RESUMO

BACKGROUND AND OBJECTIVES: Spinal cord metastasis arising from an intracranial glioblastoma is a rare and late event during the natural course of the disease. These pathological entities remain poorly characterized. This study aimed to identify and investigate the timeline, clinical and imaging findings, and prognostic factors of spinal cord metastasis from a glioblastoma. METHODS: Consecutive histopathological cases of spinal cord metastasis from glioblastomas in adults entered in the French nationwide database between January 2004 and 2016 were screened. RESULTS: Overall, 14 adult patients with a brain glioblastoma (median age 55.2 years) and harboring a spinal cord metastasis were included. The median overall survival as 16.0 months (range, 9.8-22.2). The median spinal cord Metastasis Free Survival (time interval between the glioblastoma diagnosis and the spinal cord metastasis diagnosis) was 13.6 months (range, 0.0-27.9). The occurrence of a spinal cord metastasis diagnosis greatly impacted neurological status: 57.2% of patients were not ambulatory, which contributed to dramatically decreased Karnofsky Performance Status (KPS) scores (12/14, 85.7% with a KPS score ≤ 70). The median overall survival following spinal cord metastasis was 3.3 months (range, 1.3-5.3). Patients with a cerebral ventricle effraction during the initial brain surgery had a shorter spinal cord Metastasis Free Survival (6.6 vs 18.3 months, p = 0.023). Out of the 14 patients, eleven (78.6%) had a brain IDH-wildtype glioblastoma. CONCLUSIONS: Spinal cord metastasis from a brain IDH-wildtype glioblastoma has a poor prognosis. Spinal MRI can be proposed during the follow-up of glioblastoma patients especially those who have benefited from cerebral surgical resection with opening of the cerebral ventricles.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias da Medula Espinal , Adulto , Humanos , Pessoa de Meia-Idade , Glioblastoma/patologia , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgia , Encéfalo/patologia , Prognóstico , Estudos Retrospectivos
18.
Acta Neurochir (Wien) ; 165(3): 717-725, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36808006

RESUMO

INTRODUCTION: Refractory intracranial hypertension (rICH) is a severe complication among patients with severe traumatic brain injury (sTBI). Medical treatment may be insufficient, and in some cases, the only viable treatment option is decompressive hemicraniectomy. The assessment of a corticosteroid therapy against vasogenic edema secondary to severe brain injuries seems interesting to prevent this surgery in sTBI patients with rICH caused by contusional areas. METHODS: This is a monocentric retrospective observational study including all consecutive sTBI patients with contusion injuries and a rICH requiring cerebrospinal fluid drainage with external ventricular drainage between November 2013 and January 2018. Patient inclusion criterium was a therapeutic index load (TIL; an indirect measure of TBI severity) > 7. Intracranial pressure (ICP) and TIL were assessed before and 48 h after corticosteroid therapy (CTC). Then, we divided the population into two groups according to the evolution of the TIL: responders and non-responders to corticosteroid therapy. RESULTS: During the study period, 512 patients were hospitalized for sTBI, and among them, 44 (8.6%) with rICH were included. They received 240 mg per day [120 mg, 240 mg] of Solu-Medrol for 2 days [1; 3], 3 days after the sTBI. The average ICP in patients with rICH before the CTC bolus was 21 mmHg [19; 23]. After the CTC bolus, the ICP fell significantly to less than 15 mmHg (p < 0.0001) for at least 7 days. The TIL decreased significantly the day after the CTC bolus and until day 2. Among these 44 patients, 68% were included in the responder group (n = 30). DISCUSSION: Short and systemic corticosteroid therapy in patients with refractory intracranial hypertension secondary to severe traumatic brain injury seems to be a potentially useful and efficient treatment for lowering intracranial pressure and decreasing the need for more invasive surgeries.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Contusões , Hipertensão Intracraniana , Humanos , Retroalimentação , Lesões Encefálicas Traumáticas/complicações , Hipertensão Intracraniana/etiologia , Lesões Encefálicas/complicações , Contusões/complicações , Pressão Intracraniana
19.
Spine (Phila Pa 1976) ; 48(7): 476-483, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36728778

RESUMO

STUDY DESIGN: This study used a French prospective national multi-center database of patients with spine metastasis (SpM). OBJECTIVE: The main challenge was to clarify if SpM patients presenting poor ECOG-PS could benefit from a surgical intervention. BACKGROUND: Spine metastases (SpM) are debilitating lesions commonly found in the evolution of cancer. At present, patients with poor ECOG-PS do not benefit from surgical care. MATERIALS AND METHODS: Between 2014 and 2017, 176 SpM patients with poor initial ECOG-PS (3 or 4) were identified. RESULTS: The median overall survival of patients was 2.1 months (SD 0.2). Seventy-one patients (40.3%) underwent surgery: for 49 patients (27.8%) the intervention consisted of a simple decompression and for 22 patients (12.5%) the previous was associated with an osteosynthesis. Patients who underwent surgery demonstrated significantly longer median overall survival than those who did not: 3.5 months (SD 0.4) versus 1.6 (SD 0.2) ( P <0.0001). No significant differences between operated/nonoperated patients were noted concerning median age (66.4 vs. 64.2 y, P =0.897), the median number of SpM (4.1 vs. 4.2, P =0.374), ECOG-PS 4 ratio (41.6 vs. 39.3%, P =0.616), or for primary tumors ( P =0.103). Patients who underwent surgery statistically improved their neurological impairment according to the Frankel score: 5/11 (45.4%) from A to C, 5/17 (29.4%) from B to C or D, 6/11 (54.5%) from C to D and 2/4 (50%). Twelve patients (16.9%) presented a postoperative complication. CONCLUSION: Patients with poor ECOG-PS could benefit from surgery. Even though survival gain is small, it permits the preservation of their neurological function. By making ambulation possible, pain is decreased during the last months of their lives.


Assuntos
Neoplasias , Humanos , Estudos Prospectivos , Cuidados Paliativos , Caminhada , Estudos Retrospectivos , Prognóstico
20.
Neurology ; 100(14): e1497-e1509, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36690453

RESUMO

BACKGROUND AND OBJECTIVES: Primary spinal glioblastoma (PsGBM) is extremely rare. The dramatic neurologic deterioration and unresectability of PsGBM makes it a particularly disabling malignant neoplasm. Because it is a rare and heterogeneous disease, the assessment of prognostic factors remains limited. METHODS: PsGBMs were identified from the French Brain Tumor Database and the Club de Neuro-Oncologie of the Société Française de Neurochirurgie retrospectively. Inclusion criteria were age 18 years or older at diagnosis, spinal location, histopathologic diagnosis of newly glioblastoma according to the 2016 World Health Organization classification, and surgical management between 2004 and 2016. Diagnosis was confirmed by a centralized neuropathologic review. The primary outcome was overall survival (OS). Therapeutic interventions and neurologic outcomes were also collected. RESULTS: Thirty-three patients with a histopathologically confirmed PsGBM (median age 50.9 years) were included (27 centers). The median OS was 13.1 months (range 2.5-23.7), and the median progression-free survival was 5.9 months (range 1.6-10.2). In multivariable analyses using Cox model, Eastern Cooperative Oncology Group (ECOG) performance status at 0-1 was the only independent predictor of longer OS (hazard ratio [HR] 0.13, 95% CI 0.02-0.801; p = 0.02), whereas a Karnofsky performance status (KPS) score <60 (HR 2.89, 95% CI 1.05-7.92; p = 0.03) and a cervical anatomical location (HR 4.14, 95% CI 1.32-12.98; p = 0.01) were independent predictors of shorter OS. The ambulatory status (Frankel D-E) (HR 0.38, 95% CI 0.07-1.985; p = 0.250) was not an independent prognostic factor, while the concomitant standard radiochemotherapy with temozolomide (Stupp protocol) (HR 0.35, 95% CI 0.118-1.05; p = 0.06) was at the limit of significance. DISCUSSION: Preoperative ECOG performance status, KPS score, and the location are independent predictors of OS of PsGBMs in adults. Further analyses are required to capture the survival benefit of concomitant standard radiochemotherapy with temozolomide.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Adulto , Humanos , Pessoa de Meia-Idade , Adolescente , Temozolomida , Glioblastoma/tratamento farmacológico , Estudos Retrospectivos , Prognóstico , Quimiorradioterapia , Neoplasias Encefálicas/patologia
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