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1.
Arch Pediatr ; 31(4): 231-237, 2024 May.
Article in English | MEDLINE | ID: mdl-38485568

ABSTRACT

BACKGROUND: Cerebellar mutism syndrome (CMS) occurs in 8-29 % of children undergoing posterior fossa tumor surgery. Its main symptoms are mutism and emotional lability. Although it is always transient, recovery time can be lengthy with long-term cognitive sequelae. There is no approved drug treatment for CMS, but some drugs are used in everyday medical practice. One of these is fluoxetine, which has been used for many years in our institution. The main objective of this study was to establish the safety profile of fluoxetine in this condition. MATERIALS AND METHODS: The records of patients admitted to the pediatric intensive care unit after brain surgery at Angers University Hospital from 2010 to 2020 were reviewed. Children aged 2 years and older who underwent a posterior fossa tumor surgery and were diagnosed with CMS were included. Data on patient characteristics, prescription of fluoxetine treatment, side effects if any, and complete mutism duration were collected. RESULTS: Among 246 patients admitted to the pediatric intensive care unit for brain surgery during the study period, 23 had CMS and eight were prescribed fluoxetine. No serious adverse event related to fluoxetine was reported. Complete mutism duration did not differ significantly between the fluoxetine group and the non-fluoxetine group(p = 0.22). However, the treatment was initiated after recovery from complete mutism in half of the treated patients. CONCLUSION: This study suggests a positive safety profile of fluoxetine used in postoperative CMS. It does not answer the question of whether the treatment is effective for this indication. A randomized controlled trial based on a syndrome severity scale should be conducted to provide a more reliable assessment of the efficacy and safety of fluoxetine.


Subject(s)
Fluoxetine , Mutism , Postoperative Complications , Humans , Fluoxetine/therapeutic use , Fluoxetine/adverse effects , Mutism/drug therapy , Mutism/etiology , Male , Child , Female , Child, Preschool , Postoperative Complications/drug therapy , Retrospective Studies , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/therapeutic use , Infratentorial Neoplasms/surgery , Cerebellar Diseases/surgery , Adolescent , Syndrome , Neurosurgical Procedures/adverse effects , Neurosurgical Procedures/methods
2.
EJNMMI Radiopharm Chem ; 8(1): 30, 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37843660

ABSTRACT

BACKGROUND: c-MET is a transmembrane receptor involved in many biological processes and contributes to cell proliferation and migration during cancer invasion process. Its expression is measured by immunehistochemistry on tissue biopsy in clinic, although this technique has its limitations. PET-CT could allow in vivo mapping of lesions expressing c-MET, providing whole-body detection. A number of radiopharmaceuticals are under development for this purpose but are not yet in routine clinical use. EMP100 is a cyclic oligopeptide bound to a DOTA chelator, with nanomolar affinity for c-MET. The aim of this project was to develop an automated method for radiolabelling the radiopharmaceutical [68Ga]Ga-EMP100. RESULTS: The main results showed an optimal pH range between 3.25 and 3.75 for the complexation reaction and a stabilisation of the temperature at 90 °C, resulting in an almost complete incorporation of gallium-68 after 10 min of heating. In these experiments, 90 µg of EMP-100 peptide were initially used and then lower amounts (30, 50, 75 µg) were explored to determine the minimum required for sufficient synthesis yield. Radiolysis impurities were identified by radio-HPLC and ascorbic acid and ethanol were used to improve the purity of the compound. Three batches of [68Ga]Ga-EMP100 were then prepared according to the optimised parameters and all met the established specifications. Finally, the stability of [68Ga]Ga-EMP100 was assessed at room temperature over 3 h with satisfactory results in terms of appearance, pH, radiochemical purity and sterility. CONCLUSIONS: For the automated synthesis of [68Ga]Ga-EMP100, the parameters of pH, temperature, precursor peptide content and the use of adjuvants for impurity management were efficiently optimised, resulting in the production of three compliant and stable batches according to the principles of good manufacturing practice. [68Ga]Ga-EMP100 was successfully synthesised and is now available for clinical development in PET-CT imaging.

3.
Ann Pathol ; 43(6): 462-474, 2023 Nov.
Article in French | MEDLINE | ID: mdl-37635016

ABSTRACT

INTRODUCTION: Infant-type hemispheric gliomas belong to pediatric-type diffuse high-grade gliomas according to the 2021 WHO classification of central nervous system tumors. They are characterized by tyrosine kinase gene rearrangements (NTRK1/2/3, ALK, ROS1, MET). The aim of the study was to describe the clinical, histopathologic, and molecular characteristics of such tumors, and to provide a review of the literature. PATIENTS AND METHODS: This retrospective series comprises four cases of infant-type hemispheric glioma diagnosed at Angers University Hospital between 2020 and 2022. The diagnosis was suspected based on morphology and immunohistochemistry and was confirmed by molecular biology techniques. RESULTS: The most common clinical sign was raised intracranial pressure. Imaging showed a large cerebral hemispheric tumor with contrast enhancement. Microscopic examination revealed diffuse astrocytoma with high-grade features, sometimes with neuronal or pseudo-ependymal differentiation. Identification of a gene fusion involving a tyrosine kinase gene allowed to make a definitive diagnosis of infant-type hemispheric glioma. DISCUSSION AND CONCLUSION: Infant-type hemispheric gliomas are rare and present as large cerebral hemispheric tumors in very young children. Searching for a tyrosine kinase gene fusion should be systematic when dealing with a high-grade glioma in an infant. Importantly, these gene fusions are therapeutic targets. The impact of targeted therapies on patient survival should be evaluated in future prospective studies.


Subject(s)
Brain Neoplasms , Glioma , Humans , Infant , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Gene Fusion , Glioma/pathology , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Receptor Protein-Tyrosine Kinases/genetics , Retrospective Studies
4.
J Neurooncol ; 160(2): 445-454, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36326944

ABSTRACT

PURPOSE: Neurosurgeons use three main surgical approaches for left-sided glioblastoma (GB) in eloquent areas: biopsy, tumor resection under general anesthesia (GA), and awake craniotomy (AC) with brain mapping for maximal safe resection. We performed a retrospective study of functional and survival outcomes for left-sided eloquent GB, comparing these surgical approaches. METHODS: We included 87 patients with primary left-sided eloquent GB from two centers, one performing AC and the other biopsy or resection under GA. We assessed Karnofsky performance score (KPS), language and motor deficits one month after surgery, progression-free survival (PFS) and overall survival (OS). RESULTS: The 87 patients had a median PFS of 8.6 months [95% CI: 7.3-11.6] and a median OS of 20.2 months [17-3-24.4], with no significant differences between the three surgical approaches. One month after surgery, functional outcomes for language were similar for all approaches, but motor function was poorer in the biopsy group than in other patients. The proportion of patients with a KPS score > 80 was higher in the resection with AC group than in the other patients at this timepoint. CONCLUSION: We detected no real benefit of a resection with AC over resection under GA for left-sided eloquent GB in terms of survival or functional outcomes for language. However, given the poorer motor function of biopsy patients, resection with AC should be proposed, when possible, to patients ineligible for surgical resection under GA, to improve functional outcomes and patient autonomy.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/surgery , Wakefulness , Brain Neoplasms/surgery , Retrospective Studies , Craniotomy , Anesthesia, General , Brain Mapping , Biopsy
5.
J Neurosurg Pediatr ; 30(2): 210-216, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35916100

ABSTRACT

OBJECTIVE: Chiari malformation type I (CM-I) is frequent in children and remains a surgical challenge. Several techniques have been described for posterior fossa decompression. No decision algorithm has been validated, and strategies are highly variable between institutions. The goal of this study was to define therapeutic guidelines that take into consideration patient specificities. METHODS: The authors retrospectively collected data from patients who were < 18 years of age, were diagnosed with CM-I, and were treated surgically between 2008 and 2018 in 8 French pediatric neurosurgical centers. Data on clinical features, morphological parameters, and surgical techniques were collected. Clinical outcomes at 3 and 12 months after surgery were assessed by the Chicago Chiari Outcome Scale. The authors used a hierarchical clustering method to define clusters of patients by considering their anatomical similarities, and then compared outcomes between surgical strategies in each of these clusters. RESULTS: Data from 255 patients were collected. The mean age at surgery was 9.6 ± 5.0 years, syringomyelia was reported in 60.2% of patients, the dura mater was opened in 65.0% of patients, and 17.3% of patients underwent a redo surgery for additional treatment. The mean Chicago Chiari Outcome Scale score was 14.4 ± 1.5 at 3 months (n = 211) and 14.6 ± 1.9 at 12 months (n = 157). The hierarchical clustering method identified three subgroups with potentially distinct mechanisms underlying tonsillar herniation: bony compression, basilar invagination, and foramen magnum obstruction. Each cluster matched with specific outcomes. CONCLUSIONS: This French multicenter retrospective cohort study enabled the identification of three subgroups among pediatric patients who underwent surgery for CM-I, each of which was associated with specific outcomes. This morphological classification of patients might help in understanding the underlying mechanisms and providing personalized treatment.


Subject(s)
Arnold-Chiari Malformation , Arnold-Chiari Malformation/complications , Child , Cohort Studies , Decompression, Surgical/methods , Dura Mater/surgery , Humans , Retrospective Studies , Treatment Outcome
7.
J Med Internet Res ; 23(3): e24373, 2021 03 24.
Article in English | MEDLINE | ID: mdl-33759794

ABSTRACT

BACKGROUND: Language mapping during awake brain surgery is currently a standard procedure. However, mapping is rarely performed for other cognitive functions that are important for social interaction, such as visuospatial cognition and nonverbal language, including facial expressions and eye gaze. The main reason for this omission is the lack of tasks that are fully compatible with the restrictive environment of an operating room and awake brain surgery procedures. OBJECTIVE: This study aims to evaluate the feasibility and safety of a virtual reality headset equipped with an eye-tracking device that is able to promote an immersive visuospatial and social virtual reality (VR) experience for patients undergoing awake craniotomy. METHODS: We recruited 15 patients with brain tumors near language and/or motor areas. Language mapping was performed with a naming task, DO 80, presented on a computer tablet and then in 2D and 3D via the VRH. Patients were also immersed in a visuospatial and social VR experience. RESULTS: None of the patients experienced VR sickness, whereas 2 patients had an intraoperative focal seizure without consequence; there was no reason to attribute these seizures to virtual reality headset use. The patients were able to perform the VR tasks. Eye tracking was functional, enabling the medical team to analyze the patients' attention and exploration of the visual field of the virtual reality headset directly. CONCLUSIONS: We found that it is possible and safe to immerse the patient in an interactive virtual environment during awake brain surgery, paving the way for new VR-based brain mapping procedures. TRIAL REGISTRATION: ClinicalTrials.gov NCT03010943; https://clinicaltrials.gov/ct2/show/NCT03010943.


Subject(s)
Brain Mapping , Brain Neoplasms , Virtual Reality , Brain Neoplasms/surgery , Female , Humans , Male , Prospective Studies , Wakefulness
8.
J Neurooncol ; 151(2): 113-121, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33394262

ABSTRACT

PURPOSE: Neurosurgeons adopt several different surgical approaches to deal with glioblastomas (GB) located in or near eloquent areas. Some attempt maximal safe resection by awake craniotomy (AC), but doubts persist concerning the real benefits of this type of surgery in this situation. We performed a retrospective study to evaluate the extent of resection (EOR), functional and survival outcomes after AC of patients with GB in critical locations. METHODS: Forty-six patients with primary GB treated with the Stupp regimen between 2004 and 2019, for whom brain mapping was feasible, were included. We assessed EOR, postoperative language and/or motor deficits three months after AC, progression-free survival (PFS) and overall survival (OS). RESULTS: Complete resection was achieved in 61% of the 46 GB patients. The median PFS was 6.8 months (CI 6.1; 9.7) and the median OS was 17.6 months (CI 14.8; 34.1). Three months after AC, more than half the patients asymptomatic before surgery remained asymptomatic, and one third of patients with symptoms before surgery experienced improvements in language, but not motor functions. The risk of postoperative deficits was higher in patients with preoperative deficits or incomplete resection. Furthermore, the presence of postoperative deficits was an independent predictive factor for shorter PFS. CONCLUSION: AC is an option for the resection of GB in critical locations. The observed survival outcomes are typical for GB patients in the Stupp era. However, the success of AC in terms of the recovery or preservation of language and/or motor functions cannot be guaranteed, given the aggressiveness of the tumor.


Subject(s)
Brain Neoplasms/mortality , Craniotomy/mortality , Glioblastoma/mortality , Monitoring, Intraoperative/methods , Neurosurgical Procedures/mortality , Wakefulness , Aged , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Female , Follow-Up Studies , Glioblastoma/pathology , Glioblastoma/surgery , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate
9.
World Neurosurg ; 134: e937-e943, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31734424

ABSTRACT

BACKGROUND: Brain mapping by direct electrical stimulation during awake craniotomy is now a standard procedure that reduces the risk of permanent neurologic deficits. Virtual reality technology immerses the patient in a virtually controlled, interactive world, offering a unique opportunity to develop innovative tasks for perioperative mapping of complex cognitive functions. The objective of this prospective single-center study was to evaluate the tolerance and safety of a virtual reality headset (VRH) and immersive virtual experiences in patients undergoing awake craniotomy and brain mapping by direct electrical stimulation. METHODS: The study included 30 patients with a brain tumor near the language area. Language mapping was performed with a naming task, DO 80, presented on a digital tablet and then in two-dimensional and three-dimensional formats through a VRH. During wound closure, different virtual reality experiences were proposed to the patient, offering different types of virtual motion or interaction with an avatar piloted by a neuropsychologist. RESULTS: Two patients could not use the VRH owing to technical issues. No procedure was aborted, no patient experienced virtual reality sickness and all patients reported they would repeat the procedure. Despite a high rate of intraoperative focal seizures, there was no argument to attribute the seizures to VRH use. CONCLUSIONS: This study shows that it is possible during awake brain surgery to immerse the patient in a virtual environment and to interact with the patient, opening the field of new brain mapping procedures for complex cognitive functions.


Subject(s)
Brain Mapping/methods , Brain Neoplasms/surgery , Brain/surgery , Glioma/surgery , Language , Neurosurgical Procedures/methods , Virtual Reality , Wakefulness , Adult , Aged , Astrocytoma/surgery , Brain/physiology , Cerebral Cortex/physiology , Cerebral Cortex/surgery , Electric Stimulation/methods , Female , Frontal Lobe/physiology , Frontal Lobe/surgery , Glioblastoma/surgery , Humans , Intraoperative Complications , Intraoperative Neurophysiological Monitoring/methods , Male , Middle Aged , Oligodendroglioma/surgery , Parietal Lobe/physiology , Parietal Lobe/surgery , Prospective Studies , Seizures , Temporal Lobe/physiology , Temporal Lobe/surgery , Young Adult
10.
PLoS One ; 14(3): e0212107, 2019.
Article in English | MEDLINE | ID: mdl-30849081

ABSTRACT

BACKGROUND: Visual outcome is one of the main issues in the treatment of optic pathway glioma in childhood. Although the prognostic factors of low vision have been discussed extensively, no reliable indicators for visual loss exist. Therefore, we aimed to define initial and evolving factors associated with long-term vision loss. METHODS: We conducted a multicenter historical cohort study of children treated in France with up-front BB-SFOP chemotherapy between 1990 and 2004. Visual acuity performed at the long-term follow-up visit or within 6 months prior was analyzed. Logistic regression analysis was used to estimate the effects of clinical and radiological factors on long-term visual outcome. FINDINGS: Of the 180 patients in the cohort, long-term visual acuity data were available for 132 (73.3%) patients (median follow-up: 14.2 years; range: 6.1-25.6). At the last follow-up, 61/132 patients (46.2%) had impaired vision, and 35 of these patients (57.3%) were partially sighted or blind. Multivariate analysis showed that factors associated with a worse prognosis for long-term visual acuity were an age at diagnosis of < 1 year (OR 3.5 [95% CI: 1.1-11.2], p = 0.04), tumor extent (OR 4.7 [95% CI: 1.2-19.9], p = 0.03), intracranial hypertension requiring one or more surgical procedures (OR 5.6 [95% CI: 1.8-18.4], p = 0.003), and the need for additional treatment after initial BB-SFOP chemotherapy (OR 3.5 [95% CI: 1.1-11.9], p = 0.04). NF1 status did not appear as a prognostic factor, but in non-NF1 patients, a decrease in tumor volume with contrast enhancement after BB-SFOP chemotherapy was directly associated with a better visual prognosis (OR 0.8 [95% CI: 0.8-0.9], p = 0.04). INTERPRETATION: Our study confirms that a large proportion of children with optic pathway glioma have poor long-term outcomes of visual acuity. These data suggest new prognostic factors for visual acuity, but these results need to be confirmed further by large- and international-scale studies.


Subject(s)
Optic Nerve Glioma/therapy , Visual Acuity/physiology , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carboplatin/therapeutic use , Child , Child, Preschool , Cohort Studies , Drug Therapy/methods , Female , Follow-Up Studies , France , Glioma/therapy , Humans , Male , Prognosis , Retrospective Studies , Vincristine/therapeutic use , Vision Disorders/etiology
11.
Dev Med Child Neurol ; 59(10): 1042-1048, 2017 10.
Article in English | MEDLINE | ID: mdl-28815625

ABSTRACT

AIM: The objective of this study was to investigate the involvement of the motor fibres of the corpus callosum after unilateral neonatal arterial ischemic stroke (NAIS) of the middle cerebral artery territory and the relationship to both ipsilesional and contralesional hand function. METHOD: Using high-resolution structural magnetic resonance imaging (MRI), functional MRI, and magnetic resonance diffusion-tractography, we compared the midsagittal area of the motor part of the corpus callosum (defined by the fibres connecting the precentral gyri) between 33 7-year-old children after unilateral NAIS and 31 typically developing 7-year-old children. Hand motor performance was assessed by the box and blocks test. RESULTS: Children after NAIS showed on average significantly smaller motor corpus callosum area compared to typically developing children (p<0.001, without differences of the non-motor corpus callosum area). In addition, there was a significant positive association between the motor part of the corpus callosum and both contralesional (Pr(>|t|)=0.034) and ipsilesional hand motor performance (Pr(>|t|)=0.006) after controlling for lesion volume and sex. In a post-hoc analysis the additional contribution of corticospinal tract damage was evaluated. INTERPRETATION: Compared to typically developing children, children after NAIS exhibited a smaller motor part of their corpus callosum associated with reduced contralesional but also ipsilesional manual dexterity. These results indicate that the affection of transcallosal motor fibres in unilateral NAIS might be of functional relevance and an important part of the involved structural network that should be elucidated in further studies.


Subject(s)
Brain Ischemia/physiopathology , Corpus Callosum/physiopathology , Hand/physiopathology , Motor Activity/physiology , Stroke/physiopathology , Brain Ischemia/diagnostic imaging , Child , Corpus Callosum/diagnostic imaging , Corpus Callosum/growth & development , Diffusion Tensor Imaging , Female , Functional Laterality , Humans , Magnetic Resonance Imaging , Male , Motor Cortex/diagnostic imaging , Motor Cortex/physiopathology , Organ Size , Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/physiopathology , Stroke/diagnostic imaging
13.
Childs Nerv Syst ; 33(9): 1473-1480, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28497184

ABSTRACT

PURPOSE: Presence of metastases in newly diagnosed pediatric posterior fossa tumors (PFT) is not a rare situation, but optimal treatment of associated hydrocephalus in these children has remained undetermined. METHODS: Twenty-nine children treated between January 2005 and December 2015 for a metastatic PFT associated with hydrocephalus constituted the study cohort. Patients were divided into three groups: ventriculoperitoneal shunt (VPS), endoscopic third ventriculostomy (ETV), and temporary ventricular drainage before or during tumor resection (PVD). RESULTS: There were 4 VPS, 18 ETV, and 7 PVD. The global incidence of CSF diversion failure was 52%. No case of dysfunction or dissemination of metastatic cells occurred in the VPS group. Recurrence of hydrocephalus occurred in 55% of the ETV group. Presence of multiple macroscopic metastases and CSF metastatic cells after tumor surgery was associated with ETV failure. Fifty-seven percent of the children in the PVD group were reoperated after an average time of 53 days. Specific oncologic treatment was initiated earlier in the VPS group (11 days) compared to ETV (27 days) and PVD (23 days) groups. CONCLUSIONS: ETV should be avoided in cases of multiple macroscopic metastases, and children who underwent ETV must be followed carefully when metastatic cells are present in CSF after tumor surgery. External ventricular drainage before or during surgical removal should not be considered as a final option to treat hydrocephalus. VPS remains a safe alternative in this situation and allows an early specific oncologic treatment.


Subject(s)
Cerebrospinal Fluid Leak , Hydrocephalus/etiology , Hydrocephalus/surgery , Infratentorial Neoplasms/complications , Ventriculoperitoneal Shunt/adverse effects , Ventriculostomy/adverse effects , Child , Child, Preschool , Female , Humans , Male , Postoperative Complications/epidemiology , Reoperation , Retrospective Studies , Treatment Outcome
15.
World Neurosurg ; 102: 400-405, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28300707

ABSTRACT

BACKGROUND: Intraoperative direct stimulation during surgery while awake is considered to be the gold standard for identifying eloquent cortical sites. Only a few studies have referenced the psychologic impact of this event in the pediatric population. OBJECTIVE: The aim of this clinical study is to present the psychologic aspects of surgery while awake in children. We question the psychiatric contraindications and age limits, as well as the impact on children, with particular attention to the psychologic conditioning and experience of these patients. METHODS: Seven patients aged 8-16 years old with brain lesions were operated on while awake between 2008 and 2015. Data collected included perception and memories of surgery and diagnosis and also their real-life experience after surgery. Symptoms of posttraumatic stress disorder or acute stress were investigated. RESULTS: None of the children had initial psychiatric problems. No psychiatric diagnosis was made before surgery. The child psychiatrist did not contraindicate any child for this procedure. Patients experienced little anticipatory anxiety. No child presented symptoms of posttraumatic stress disorder or acute stress. CONCLUSIONS: The results are encouraging, allowing us to contemplate using brain surgery while awake for children without particular worries about the psychologic aspect.


Subject(s)
Brain Neoplasms/surgery , Mood Disorders/etiology , Neurosurgical Procedures/adverse effects , Postoperative Complications/etiology , Stress Disorders, Post-Traumatic/etiology , Wakefulness , Adolescent , Brain Neoplasms/psychology , Child , Female , Humans , Male , Neuropsychological Tests , Psychiatric Status Rating Scales , Retrospective Studies
16.
Ann Pathol ; 37(1): 117-126, 2017 Feb.
Article in French | MEDLINE | ID: mdl-28111040

ABSTRACT

Diffuse gliomas represent the most common primary central nervous system (CNS) tumors in adults and children alike. Glioblastoma is the most frequent and malignant form of diffuse glioma with a median overall survival of 15 months despite aggressive treatments. New therapeutic approaches are needed to prolong survival in this always fatal disease. The CNS has been considered for a long time as an immune privileged organ, in part because of the existence of the blood-brain barrier. Nonetheless, immunotherapy is a novel approach in the therapeutic management of glioma patients, which has shown promising results in several clinical trials, especially in the adult population. Vaccination, with or without dendritic cells, blockade of the immune checkpoints, and adoptive T cell transfer are the most studied modalities of diffuse glioma immunotherapy. The future most likely resides in combinatorial approaches, with administration of conventional treatments (surgery, radiochemotherapy) and immunotherapy following yet to determine schedules.


Subject(s)
Brain Neoplasms/therapy , Glioblastoma/therapy , Glioma/therapy , Immunotherapy/methods , Adult , Animals , Brain Neoplasms/drug therapy , Brain Neoplasms/immunology , Cancer Vaccines/therapeutic use , Child , Combined Modality Therapy , Drug Screening Assays, Antitumor , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , ErbB Receptors/immunology , Genetic Therapy , Glioblastoma/drug therapy , Glioblastoma/immunology , Glioma/drug therapy , Glioma/immunology , Humans , Immunotherapy, Adoptive , Isocitrate Dehydrogenase/genetics , Isocitrate Dehydrogenase/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Mice , Mice, Transgenic , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/genetics , Neoplasm Proteins/immunology , T-Lymphocyte Subsets/immunology , Tumor Escape
17.
Cerebellum ; 16(5-6): 880-912, 2017 12.
Article in English | MEDLINE | ID: mdl-27766499

ABSTRACT

Surgery of the posterior fossa represents a technical challenge because of the proximity of the vessels of the cerebellum. If the arterial vascularization of the cerebellum is well known, the main arterial variations and the whole venous vascularization are probably under recognized. We describe the vascular organization and the main variations through photographs of colored latex perfused brains, obtained with a surgical microscope. The arterial vascularization of the cerebellum is based on three arteries which all originate from the vertebrobasilar system: the superior cerebellar artery (SCA), the anterior and inferior cerebellar artery (AICA), and the posterior and inferior cerebellar artery (PICA). The main arterial variations involve essentially the origin of these vessels. Concerning the SCA, its origin depends on the embryology. The AICA can arise from a common trunk AICA-PICA. It can be sometimes doubled and rarely absent. The PICA also can arise from a common trunk AICA-PICA and sometimes from the extradural segment of the vertebral artery. Concerning the venous organization, we distinguish the superficial and deep veins. The superficial veins drain the cerebellar cortex and transit on the surface of the cerebellum. The deep veins refer to the veins transiting in the fissures between the cerebellum and the brainstem. All these veins terminate as bridging veins that we can divide in three groups: a superior group emptying into the great vein, a posterior group emptying into the transtentorial sinus, and a lateral group ending into the superior petrosal sinus. The surgical implications are discussed.


Subject(s)
Arteries/anatomy & histology , Cerebellum/anatomy & histology , Cerebellum/blood supply , Veins/anatomy & histology , Cerebellum/surgery , Humans , Latex , Neurosurgical Procedures , Tissue Fixation
18.
Stroke ; 47(6): 1647-50, 2016 06.
Article in English | MEDLINE | ID: mdl-27165960

ABSTRACT

BACKGROUND AND PURPOSE: In children having suffered from neonatal arterial ischemic stroke, the relationship between contralesional hand performance and structural changes in brain areas remote from the infarct site was examined. METHODS: Using voxel-based morphometry, we correlated contralesional gross manual dexterity assessed by the box and block test and whole-brain gray and white-matter volume changes on high-resolution magnetic resonance imaging in 37 7-year-old post-neonatal arterial ischemic stroke children. We also compared the volume of the identified structures with magnetic resonance imaging data of 10 typically developing age-matched children. RESULTS: Areas showing the highest positive correlation with the box and block test scores were ipsilesional mediodorsal thalamus, contralesional cerebellar lobule VIIa Crus I, and ipsilesional corticospinal tract at the level of superior corona radiata, the posterior limb of the internal capsule, and the cerebral peduncle and the ipsilesional body of corpus callosum. When compared with typically developing age-matched children, post-neonatal arterial ischemic stroke children with severe contralesional hand motor deficit exhibited significant volume reductions in these structures (except the cerebellum), whereas no differences were found with those with good manual dexterity. No negative correlation was found between box and block test scores and brain areas. CONCLUSIONS: Contralesional hand performance after neonatal arterial ischemic stroke is correlated with atrophy in brain areas directly or functionally connected but anatomically remote from the infarct. Our study suggests a role of the cerebellar lobule VIIa Crus I and mediodorsal thalamus in manual dexterity. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02511249.


Subject(s)
Brain Ischemia/complications , Gray Matter/diagnostic imaging , Hand/physiopathology , Magnetic Resonance Imaging/methods , Motor Skills/physiology , Stroke/complications , White Matter/diagnostic imaging , Atrophy/diagnostic imaging , Brain Ischemia/pathology , Brain Ischemia/physiopathology , Child , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases , Male , Stroke/pathology , Stroke/physiopathology
19.
Eur J Paediatr Neurol ; 20(3): 403-11, 2016 May.
Article in English | MEDLINE | ID: mdl-26831357

ABSTRACT

Cerebral Palsy (CP) is a group of permanent motor disorders due to non-progressive damage to the developing brain. Poor tactile discrimination is common in children with unilateral CP. Previous findings suggest the crucial role of structural integrity of the primary (S1) and secondary (S2) somatosensory areas located in the ipsilesional hemisphere for somatosensory function processing. However, no focus on the relationship between structural characteristics of ipsilesional S1 and S2 and tactile discrimination function in paretic hands has been proposed. Using structural MRI and a two-point discrimination assessment (2 PD), we explore this potential link in a group of 21 children (mean age 13 years and 7 months) with unilateral CP secondary to a periventricular white matter injury (PWMI) or middle cerebral artery infarct (MCA). For our whole sample there was a significant negative correlation between the 2 PD and the gray matter volume in the ipsilesional S2 (rho = -0.50 95% confidence interval [-0.76, -0.08], one-tailed p-value = 0.0109) and in the ipsilesional S1 (rho = -0.57, 95% confidence interval [-0.81, -0.19], one-tailed p-value = 0.0032). When studying these relationships with regard to the lesion types, we found these correlations were non-significant in the patients with PWMI but stronger in patients with MCA. According to our results, the degree of sensory impairment is related to the spared gray matter volume in ipsilesional S1 and S2 and is marked after an MCA stroke. Our work contributes to a better understanding of why some patients with CP have variable somatosensory deficit following an early brain lesion.


Subject(s)
Cerebral Palsy/pathology , Cerebral Palsy/physiopathology , Perceptual Disorders/pathology , Perceptual Disorders/physiopathology , Touch Perception/physiology , Adolescent , Adult , Cerebral Palsy/complications , Child , Female , Humans , Magnetic Resonance Imaging , Male , Perceptual Disorders/etiology , Young Adult
20.
Neuroradiology ; 58(2): 197-208, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26518314

ABSTRACT

INTRODUCTION: Magnetic resonance (MR) images from children with optic pathway glioma (OPG) are complex. We initiated this study to evaluate the accuracy of MR imaging (MRI) interpretation and to propose a simple and reproducible imaging classification for MRI. METHODS: We randomly selected 140 MRIs from among 510 MRIs performed on 104 children diagnosed with OPG in France from 1990 to 2004. These images were reviewed independently by three radiologists (F.T., 15 years of experience in neuroradiology; D.L., 25 years of experience in pediatric radiology; and J.L., 3 years of experience in radiology) using a classification derived from the Dodge and modified Dodge classifications. Intra- and interobserver reliabilities were assessed using the Bland-Altman method and the kappa coefficient. These reviews allowed the definition of reliable criteria for MRI interpretation. RESULTS: The reviews showed intraobserver variability and large discrepancies among the three radiologists (kappa coefficient varying from 0.11 to 1). These variabilities were too large for the interpretation to be considered reproducible over time or among observers. A consensual analysis, taking into account all observed variabilities, allowed the development of a definitive interpretation protocol. Using this revised protocol, we observed consistent intra- and interobserver results (kappa coefficient varying from 0.56 to 1). The mean interobserver difference for the solid portion of the tumor with contrast enhancement was 0.8 cm(3) (limits of agreement = -16 to 17). CONCLUSION: We propose simple and precise rules for improving the accuracy and reliability of MRI interpretation for children with OPG. Further studies will be necessary to investigate the possible prognostic value of this approach.


Subject(s)
Algorithms , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Optic Nerve Glioma/diagnostic imaging , Child, Preschool , Female , Humans , Male , Observer Variation , Reproducibility of Results , Sensitivity and Specificity
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