[Prospective longitudinal study on the evolution of autobiographical memory in patients irradiated for benign skull base tumour]. / Étude prospective longitudinale sur l'évolution de la mémoire autobiographique de patients irradiés pour une tumeur bénigne de la base du crâne.

PURPOSE: Cranial irradiation can lead to long-term neurological complications, in particular memory disorders. The aim of this prospective study is to evaluate the impact of irradiation of benign skull base tumours located near the hippocampi on autobiographical memory. PATIENTS AND METHODS: From 2016 to 2019, patients with cavernous sinus meningioma or pituitary adenoma treated with normofractionated irradiation were included. Patients underwent full neuropsychological assessment at baseline, 1year and 2years post-treatment. Neuropsychological tests were converted to Z-Score for comparability. RESULTS: Twelve of the 19 patients included had a complete neuropsychological evaluation at 2years and were analysed. On the "TEMPau" test, no significant difference in autobiographical memory was found at 2years, regardless of the period of autobiographical memory. The mean hippocampal dose had no impact on the variation in autobiographical memory. There was no significant cognitive impairment in the other domains assessed, such as attention, anterograde memory, working memory and executive functions. Autobiographical memory was independent of these other cognitive domains, which justifies its specific study. CONCLUSION: Radiotherapy to the skull base for a benign pathology does not lead to significant cognitive impairment. Longer follow-up would be needed to confirm these results.

Análise morfológica comparativa do côndilo mandibular e outras estruturas da mandíbula e base do crânio em maloclusões classe I, II e III esqueléticas / Comparative morphological analysis of the mandibular condyle and other structures of mandible and cranial base in class I, II and III skeletal malocclusions

O objetivo deste estudo foi comparar o volume condilar em indivíduos com diferentes maloclusões esqueléticas. Também foram realizadas análises das semelhanças morfológicas entre o côndilo mandibular e outras estruturas da mandíbula e base do crânio, por meio de medidas lineares e volumétricas. Essas análises foram realizadas usando Tomografia Computadorizada de Feixe Cônico (TCFC), modelos tridimensionais de côndilos mandibulares e sínfise mandibular de 58 indivíduos foram construídos, e os volumes e áreas foram mensurados. A amostra foi dividida nos seguintes grupos: Classe I (0 ≤ ANB ≥ 4,5°) (n=18), Classe II (ANB > 4,5°) (n=21) e Classe III (ANB < 0°) (n=19). Dezesseis pontos de referência do tecido duro na mandíbula e base do crânio foram identificados por um operador treinado e calibrado. Foram obtidas as distâncias 3D entre os pontos e as projeções nos três planos do espaco (x, y e z). A comparação do volume condilar entre os lados direito e esquerdo foi realizada pelo teste de Wilcoxon (Classe I) e Test t pareado (Classe II e III) e a comparação inter-grupos foi realizada com o teste ANOVA/Tukey (a=0,05). Análises de correlação de Pearson e regressão linear foram realizadas para avaliar a relação entre o volume dos côndilos e a sínfise mandibular, e o volume dos côndilos e as medidas lineares realizadas na mandíbula e base do crânio. Não foi observada diferença estatisticamente significativa entre os volumes condilares dos lados direito e esquerdo em diferentes maloclusões esqueléticas (Classe I: p=0,728; Classe II: p=0,741 e Classe III: p=0,155). Indivíduos de classe III apresentaram maior volume condilar (Classe III: 1990,85 ± 559,42) em comparação aos indivíduos de classe I e II (Classe I: 1835,22 ± 552,15; Classe II: 1725,47 ± 394,64), embora a diferença não tenha sido estatisticamente significativa (p=0,214). Houve uma correlação significativa, mas moderada, entre os volumes condilares e as medidas lineares da sínfise mandibular (p <0,01). Conclui-se que os volumes condilares não variam significativamente em diferentes padrões esqueléticos sagitais e, entre os lados direito e esquerdo. A relação entre o volume condilar e a sínfise mandibular foi moderada e equações de regressão foram desenvolvidas para estimar o volume condilar. (AU)

The aim of this study was to compare the condylar volume in individuals with different skeletal classes. Analyzes of the morphological similarities between the mandibular condyle and other structures of the mandible and cranial base were also performed, using linear and volumetric measurements. These analyzes were performed using Cone Beam Computed Tomography (CBCT), three-dimensional models of mandibular condyles and mandibular symphysis of 58 individuals were constructed, and volumes and areas were measured. The sample was divided into the following groups: Class I (0 ≤ ANB ≥ 4.5 °) (n = 18), Class II (ANB> 4.5°) (n = 21) and Class III (ANB <0 °) (n = 19). Sixteen hard tissue reference points in the mandible and cranial base were identified by a trained and calibrated operator. 3D distances were obtained between the points and the projections in the three planes of the space (x, y and z). The comparison of the condylar volume between the right and left sides was performed by the Wilcoxon test (Class I) and the paired t-test (Class II and III) and the inter-group comparison was performed with the ANOVA / Tukey test (a = 0, 05). Pearson's correlation analyzes and linear regression were performed to assess the relationship between condylar volume and mandibular symphysis, and condylar volume and linear measurements. There was no statistically significant difference between condylar volumes on the right and left sides in different skeletal malocclusions (Class I: p = 0.728; Class II: p = 0.741 and Class III: p = 0.155). Class III individuals had a higher condylar volume (Class III: 1990.85 ± 559.42) compared to Class I and II individuals (Class I: 1835.22 ± 552.15; Class II: 1725.47 ± 394, 64), although the difference was not statistically significant (p = 0.214). There was a significant, but moderate, correlation between condylar volumes and linear measurements of the mandibular symphysis (p <0.01). It is concluded that the condylar volumes do not vary significantly in different sagittal skeletal patterns and, between the right and left sides. The relationship between the condylar volume and the mandibular symphysis was moderate and regression equations were developed to estimate the condylar volume. (AU)

[Skull base meningioma: Clinical and radiological efficacy based on a quantitative volumetric analysis]. / Méningiomes de la base du crâne : efficacité clinique et radiologique basée sur une analyse volumétrique quantitative.

PURPOSE: To date, no correlation has been found between clinical and radiological efficacy after irradiation of skull base meningiomas. However, the evaluation of the radiological response was most often made by questionable methods that may have underestimated the radiological effectiveness of radiotherapy. The objective of this work is to verify this hypothesis by quantitative volumetric analysis. MATERIAL AND METHODS: Data from 35 patients treated with either helical tomotherapy (45.7%) or fractionated stereotactic radiotherapy (54.3%) were retrospectively analysed. These were mainly women (94%) aged 59 (43-81) with lesions mainly of the cavernous sinus (60%). There was a median of 2 (1-4) symptoms and the main symptoms were visual impairment (39%), cranial nerve deficits (23.4%) and headaches (17.2%). RESULTS: Median tumour volume decreased significantly (P<0.05) from 9.6mL (0.3-36.6) to 6.8mL (0.1-26.5) after median follow-up of 44 months (24-77). Sixty-three percent of patients had an improvement of at least one symptom. In univariate analysis, clinical efficacy (P<0.05), radiotherapy technique (P<0.05), tumor topography (P<0.05) and initial tumor volume (P<0.05) were predictive factors for radiological response. In multivariate analysis, only the inverse correlation between radiological response and initial tumor volume remained significant (ρ: -0.47 95% CI -3.2 to 5.7; P<0.05). CONCLUSION: The quantitative volumetric monitoring demonstrates a major radiological efficiency of radiotherapy. However, no clear correlation between clinical and radiological efficacy was found.

[Base of the skull meningioma: Efficacy, clinical tolerance and radiological evaluation after radiotherapy]. / Méningiomes de la base du crâne : efficacité et tolérance clinique, efficacité radiologique et cinétique tumorale après radiothérapie.

Skull base meningioma leads to functional disturbances, which can significantly alter the quality of life. The optimal management of these lesions, whose goals are neurological preservation and tumour local control, is not yet clearly established. It is widely recognized that the goal of a radical excision should be abandoned despite the advances in the field of microsurgery of skull base lesions. Although less morbid, partial tumour excision would be associated with increased risk of local tumour recurrence. Although discussed both exclusive and adjuvant have proven to be highly successful in terms of clinical improvement and local control. Various radiation techniques have demonstrated their efficacy in the management of this pathology. However, high rates of clinical improvement are in contrast with low rates of radiological improvement. The notion of clinical and radiological dissociation appeared. However, in most of these studies, the analysis of the radiological response could be subject of legitimate criticism. This work proposes to review the local control, the efficacy and the clinical tolerance and the radiological response of the various radiation techniques for the meningioma of the base of the skull and to demonstrate the interest of quantitative volumetric analyses in the follow-up of meningioma after radiotherapy.

[Indications and results for protontherapy in cancer treatments]. / Indications et résultats de la protonthérapie dans le traitement des cancers.

Purpose was to summarize results for proton therapy in cancer treatment. A systematic review has been done by selecting studies on the website www.pubmed.com (Medline) and using the following keywords: proton therapy, radiation therapy, cancer, chordoma, chondrosarcoma, uveal melanoma, retinoblastoma, meningioma, glioma, neurinoma, pituitary adenoma, medulloblastoma, ependymoma, craniopharyngioma and nasal cavity. There are several retrospective studies reporting results for proton therapy in cancer treatments in the following indications: ocular tumors, nasal tumors, skull-based tumors, pediatric tumors. There is no prospective study except one phase II trial in medulloblastoma. The use of proton therapy for these indications is due to dosimetric advantages offering better tumor coverage and organ at risk sparing in comparison with photon therapy. Clinical results are historically at least as efficient as photon therapy with a better toxicity profile in pediatric tumors (cognitive and endocrine functions, radiation-induced cancer) and a better tumoral control in tumors of the nasal cavity. Clinical advantages of proton therapy counterbalance its cost especially in pediatric tumors. Proton therapy could be used in other types of cancer. Proton therapy showed good outcome in ocular, nasal tumors, pediatric, skull-based and paraspinal tumors. Because of some dosimetric advantages, proton therapy could be proposed for other indications in cancer treatments.

Extended endoscopic endonasal approach to clival and paraclival tumors: Indications and limits.

OBJECTIVE: To report our experience with the Extended endoscopic endonasal approach (EEEA) for clival and paraclival tumors. DESIGN: Retrospective analysis of a consecutive series of patients. RESULTS: Eleven patients were considered: 3 chordomas, 3 meningiomas, 3 metastatic lesions, one chondroma and one chondrosarcoma. Gross total resection (GTR) was achieved in all chordomas and in chondromas with patients free of disease at the last follow-up. The chondrosarcoma was first operated on using a transfacial approach and endoscopy was performed for local progression with subtotal resection. The meningiomas were treated by a combination of transcranial and endoscopic approach due to their extension. The resection was subtotal and the residue treated by radiosurgery. Two patients with rhinopharyngeal carcinoma underwent palliative debulking. One metastatic melanoma that underwent GTR experienced remission. Two patients had postoperative cranial nerve palsy. No other complications were observed. CONCLUSIONS: EEEA allows a direct access to the skull base. Through a minimal access, it limits the incidence of neurological morbidities. For midline epidural clival tumors, EEEA allows a total excision. It also offers an excellent access to the clival component of intradural lesions. A combined approach permits good tumor control with minimal complications.

Lower third clivus and foramen magnum intradural tumor removal: The plea for a simple posterolateral approach.

BACKGROUND: Anterior or anterolateral lesions of the lower third clivus and/or foramen magnum require a surgical exposure that provides a clear visualization of both pathological and normal anatomy without retraction of neural or vascular structures. The posterolateral approach permits access to the anterolateral intradural aspect of the brainstem. The aim of this study was to stress that there is no need for vertebral artery transposition, occipital condyle drilling, occipitocervical fixation or trans-oro-pharyngeal access to remove these lesions. METHODS: All five consecutive patients treated surgically for an intradural foramen magnum lesion in the Department of Neurosurgery at Angers University Hospital, between May 2012 and January 2015, were included in this retrospective study. In 4 cases, patients were referred to us for a second opinion after an initial surgical proposal at another institution. For all patients, the data collected were age at diagnosis, clinical signs, and quality of rostral and caudal exposure of the lesion, quality of resection, complications and postoperative neurological deficits. RESULTS: All patients were operated on with a control of the rostrocaudal part of the lesion, without touching the vertebral artery, or the use of occipital condyle drilling. There was no need for occipitocervical fixation. Total resection was achieved in 4 cases, subtotal resection in one. All had watertight dural closure with no dural patch, or postoperative neurological deficits. No recurrence occurred between 6 and 30 months after surgery. CONCLUSION: Based on these results, the posterolateral approach was a simple, effective and safe procedure for anterior and anterolateral intradural lesion of the foramen magnum.

Meningioma of the skull base: long-term outcome after image-guided stereotactic radiotherapy.

PURPOSE: The purpose of this study was to analyse the feasibility, safety, and long-term efficacy of linear accelerator-based fractionated stereotactic radiotherapy for meningiomas of the skull base. We evaluated the long-term clinical outcome of patients and identified prognostic factors after fractionated stereotactic radiotherapy. PATIENTS AND METHODS: Between 10/1995 and 03/2009, 136 patients with a median age of 57 years with skull base meningioma received fractionated stereotactic radiotherapy. A total of 34 patients had a grade I meningioma, in 102 cases no histology was obtained (grade 0). Fractionated stereotactic radiotherapy was delivered as primary treatment for 57 patients and postoperatively for 79. The patients received a mean total dose of 56.95 (min/max 32.4/63)Gy. RESULTS: Median follow-up was 44.9 months. Overall progression-free survival was 96.9% after 3 years, 93.8% after 5 years, and 91.5% after 10 years. Patients with unknown histology showed progression-free survival rates of 100%, 98.7%, and 93.5% at 3, 5, and 10 years and patients with biopsy-proven grade I meningioma showed rates of 100% after 3 years, 91.7% after 5 years and 85.9% after 10 years. Patients with adjuvant radiotherapy showed significantly worse progression-free survival rates than patients who had been treated with primary radiotherapy (P=0.043), progression-free survival rates were independent of tumour size. The most common acute grade I symptoms were headache, fatigue, and local alopecia. The most common chronic grade I symptoms were fatigue and headache. CONCLUSIONS: This large study showed that fractionated stereotactic radiotherapy is an effective and safe treatment modality with high progression-free survival rates for intracranial meningioma. We identified "prior surgery" as significant poor prognostic factor.

Augmented reality-assisted skull base surgery.

Neuronavigation is widely considered as a valuable tool during skull base surgery. Advances in neuronavigation technology, with the integration of augmented reality, present advantages over traditional point-based neuronavigation. However, this development has not yet made its way into routine surgical practice, possibly due to a lack of acquaintance with these systems. In this report, we illustrate the usefulness and easy application of augmented reality-based neuronavigation through a case example of a patient with a clivus chordoma. We also demonstrate how augmented reality can help throughout all phases of a skull base procedure, from the verification of neuronavigation accuracy to intraoperative image-guidance.

[Chordoma]. / Les chordomes.

PURPOSES: To review in the literature, all the epidemiological, clinical, radiological, histological and therapeutic data regarding chordomas as well as various notochordal entities: ecchordosis physaliphora, intradural and intraparenchymatous chordomas, benign notochordal cell tumors, parachordomas and extra-axial chordomas. To identify different types of chordomas, including familial forms, associations with tuberous sclerosis, Ollier's disease and Maffucci's syndrome, forms with metastasis and seeding. To assess the recent data regarding molecular biology and progress in targeted therapy. To compare the different types of radiotherapy, especially protontherapy and their therapeutic effects. To review the largest series of chordomas in their different localizations (skull base, sacrum and mobile spine) from the literature. MATERIALS: The series of 136 chordomas treated and followed up over 20 years (1972-2012) in the department of neurosurgery at Lariboisière hospital is reviewed. It includes: 58 chordomas of the skull base, 47 of the craniocervical junction, 23 of the cervical spine and 8 from the lombosacral region. Similarly, 31 chordomas in children (less than 18 years of age), observed in the departments of neurosurgery of les Enfants-Malades and Lariboisière hospitals, are presented. They were observed between 1976 and 2010 and were located intracranially (n=22 including 13 with cervical extension), 4 at the craniocervical junction level and 5 in the cervical spine. METHODS: In the entire Lariboisière series and in the different groups of localization, different parameters were analyzed: the delay of diagnosis, of follow-up, of occurrence of metastasis, recurrence and death, the number of primary patients and patients referred to us after progression or recurrence and the number of deaths, recurrences and metastases. The influence of the quality of resection (total, subtotal and partial) on the prognosis is also presented. Kaplan-Meier actuarial curves of overall survival and disease free survival were performed in the entire series, including the different groups of localization based on the following 4 parameters: age, primary and secondary patients, quality of resection and protontherapy. In the pediatric series, a similar analysis was carried-out but was limited by the small number of patients in the subgroups. RESULTS: In the Lariboisière series, the mean delay of diagnosis is 10 months and the mean follow-up is 80 months in each group. The delay before recurrence, metastasis and death is always better for the skull base chordomas and worse for those of the craniocervical junction, which have similar results to those of the cervical spine. Similar figures were observed as regards the number of deaths, metastases and recurrences. Quality of resection is the major factor of prognosis with 20.5 % of deaths and 28 % of recurrences after total resection as compared to 52.5 % and 47.5 % after subtotal resection. This is still more obvious in the group of skull base chordomas. Adding protontherapy to a total resection can still improve the results but there is no change after subtotal resection. The actuarial curve of overall survival shows a clear cut in the slope with some chordomas having a fast evolution towards recurrence and death in less than 4 years and others having a long survival of sometimes more than 20 years. Also, age has no influence on the prognosis. In primary patients, disease free survival is better than in secondary patients but not in overall survival. Protontherapy only improves the overall survival in the entire series and in the skull base group. Total resection improves both the overall and disease free survival in each group. Finally, the adjunct of protontherapy after total resection is clearly demonstrated. In the pediatric series, the median follow-up is 5.7 years. Overall survival and disease free survival are respectively 63 % and 54.3 %. Factors of prognosis are the histological type (atypical forms), localization (worse for the cervical spine and better for the clivus) and again it will depend on the quality of resection. CONCLUSIONS: Many different pathologies derived from the notochord can be observed: some are remnants, some may be precursors of chordomas and some have similar features but are probably not genuine chordomas. To-day, immuno-histological studies should permit to differentiate them from real chordomas. Improving knowledge of molecular biology raises hopes for complementary treatments but to date the quality of surgical resection is still the main factor of prognosis. Complementary protontherapy seems useful, especially in skull base chordomas, which have better overall results than those of the craniocervical junction and of the cervical spine. However, we are still lacking an intrinsic marker of evolution to differentiate the slow growing chordomas with an indolent evolution from aggressive types leading rapidly to recurrence and death on which more aggressive treatments should be applied.

[Geometrical growth models of the fetal forebrain, cerebellum, brainstem and change of the cranial base angles during fetal period]. / Modèles géométriques de croissance du cerveau, cervelet, tronc cérébral et modification des angles de la base du crâne au cours de la période fœtale.

INTRODUCTION: Brain growth plays likely an important role for the skull growth. In the fetus, there exists an heterochrony for the growth of supratentorial (forebrain) and infratentorial regions (brainstem and cerebellum). The aim of the study was thus to model geometrically the growth of these two regions and to compare it with the inflection of the base of skull. MATERIAL AND METHODS: Brain growth measurements were performed from midsagittal photographs of fetal brains obtained from an Anatomical Atlas over a period from 10 to 40 amenorrhea weeks (AW). After countouring and pointing anatomical and geometrical landmarks, we have developed a linear growth model based on principal component analysis (PCA). Besides, the variation of the sphenoidal and clivo-foraminal angles was studied from anatomical midsagittal slices of fetal heads sampled over a period from 16 to 39 AW. RESULTS: The PCA model brings to light the radial expansion of the forebrain growth (first component) associated with an inferior and posterior rotation of the occipital lobe. The growth of the infratentoriel region presents an inferior and posterior expansion associated with a second component corresponding to inferior and anterior expansions. From the 17 AW, appears an heterochrony between the supra- and infratentorial growths and an inversion of the ratio between the infra- and supratentorial dimensions after 30 AW. The sphenoidal and clivo-foraminal angles decrease slightly until 25 AW, and then increase quickly until the 39 AW. CONCLUSIONS: The growth of brain is accompanied by morphological change between the compartments supra- and infratentoriel but also on the level of the base of skull. The possible interactions will be discussed.