Progestin-associated shift of meningioma mutational landscape.

Background: Meningiomas are the most common primary tumor of the central nervous system. The relationship between meningioma and progestins is frequently mentioned but has not been elucidated. Patients and methods: We identified 40 female patients operated for a meningioma after long-term progestin therapy and performed targeted next generation sequencing to decipher the mutational landscape of hormone-related meningiomas. A published cohort of 530 meningiomas in women was used as a reference population. Results: Compared with the control population of meningiomas in women, progestin-associated meningiomas were more frequently multiple meningiomas [19/40 (48%) versus 25/530 (5%), P < 10-12] and located at the skull base [46/72 (64%) versus 241/481 (50%), P = 0.03]. We found a higher frequency of PIK3CA mutations [14/40 (35%) versus 18/530 (3%), P < 10-8] and TRAF7 mutations [16/40 (40%) versus 140/530 (26%), P < 0.001] and a lower frequency of NF2-related tumors compared with the control population of meningiomas [3/40 (7.5%) versus 169/530 (32%), P < 0.001]. Conclusion: This shift in mutational landscape indicates the vulnerability of certain meningeal cells and mutations to hormone-induced tumorigenesis. While the relationship between PIK3CA mutation frequency and hormone-related cancers such as breast and endometrial cancer is well-known, this hormonally induced mutational shift is a unique feature in molecular oncology.

Ex vivo optimisation of a heterogeneous speed of sound model of the human skull for non-invasive transcranial focused ultrasound at 1 MHz.

Transcranial brain therapy has recently emerged as a non-invasive strategy for the treatment of various neurological diseases, such as essential tremor or neurogenic pain. However, treatments require millimetre-scale accuracy. The use of high frequencies (typically ≥1 MHz) decreases the ultrasonic wavelength to the millimetre scale, thereby increasing the clinical accuracy and lowering the probability of cavitation, which improves the safety of the technique compared with the use of low-frequency devices that operate at 220 kHz. Nevertheless, the skull produces greater distortions of high-frequency waves relative to low-frequency waves. High-frequency waves require high-performance adaptive focusing techniques, based on modelling the wave propagation through the skull. This study sought to optimise the acoustical modelling of the skull based on computed tomography (CT) for a 1 MHz clinical brain therapy system. The best model tested in this article corresponded to a maximum speed of sound of 4000 m.s-1 in the skull bone, and it restored 86% of the optimal pressure amplitude on average in a collection of six human skulls. Compared with uncorrected focusing, the optimised non-invasive correction led to an average increase of 99% in the maximum pressure amplitude around the target and an average decrease of 48% in the distance between the peak pressure and the selected target. The attenuation through the skulls was also assessed within the bandwidth of the transducers, and it was found to vary in the range of 10 ± 3 dB at 800 kHz and 16 ± 3 dB at 1.3 MHz.

In Vivo Measurement of Brain Tumor Elasticity Using Intraoperative Shear Wave Elastography.

Purpose: Objective Shear wave elastography (SWE) enabled living tissue assessment of stiffness. This is routinely used for breast, thyroid and liver diseases, but there is currently no data for the brain. We aim to characterize elasticity of normal brain parenchyma and brain tumors using SWE. Materials and Methods: Patients with scheduled brain tumor removal were included in this study. In addition to standard ultrasonography, intraoperative SWE using an ultrafast ultrasonic device was used to measure the elasticity of each tumor and its surrounding normal brain. Data were collected by an investigator blinded to the diagnosis. Descriptive statistics, box plot analysis as well as intraoperator and interoperator reproducibility analysis were also performed. Results: 63 patients were included and classified into four main types of tumor: meningiomas, low-grade gliomas, high-grade gliomas and metastasis. Young's Modulus measured by SWE has given new insight to differentiate brain tumors: 33.1 ±â€Š5.9 kPa, 23.7 ±â€Š4.9 kPa, 11.4 ±â€Š3.6 kPa and 16.7 ±â€Š2.5 kPa, respectively, for the four subgroups. Normal brain tissue has been characterized by a reproducible mean stiffness of 7.3 ±â€Š2.1 kPa. Moreover, low-grade glioma stiffness is different from high-grade glioma stiffness (p = 0.01) and normal brain stiffness is very different from low-grade gliomas stiffness (p < 0.01). Conclusion: This study demonstrates that there are significant differences in elasticity among the most common types of brain tumors. With intraoperative SWE, neurosurgeons may have innovative information to predict diagnosis and guide their resection.

MR-guided adaptive focusing of therapeutic ultrasound beams in the human head.

PURPOSE: This study aims to demonstrate, using human cadavers the feasibility of energy-based adaptive focusing of ultrasonic waves using magnetic resonance acoustic radiation force imaging (MR-ARFI) in the framework of non-invasive transcranial high intensity focused ultrasound (HIFU) therapy. METHODS: Energy-based adaptive focusing techniques were recently proposed in order to achieve aberration correction. The authors evaluate this method on a clinical brain HIFU system composed of 512 ultrasonic elements positioned inside a full body 1.5 T clinical magnetic resonance (MR) imaging system. Cadaver heads were mounted onto a clinical Leksell stereotactic frame. The ultrasonic wave intensity at the chosen location was indirectly estimated by the MR system measuring the local tissue displacement induced by the acoustic radiation force of the ultrasound (US) beams. For aberration correction, a set of spatially encoded ultrasonic waves was transmitted from the ultrasonic array and the resulting local displacements were estimated with the MR-ARFI sequence for each emitted beam. A noniterative inversion process was then performed in order to estimate the spatial phase aberrations induced by the cadaver skull. The procedure was first evaluated and optimized in a calf brain using a numerical aberrator mimicking human skull aberrations. The full method was then demonstrated using a fresh human cadaver head. RESULTS: The corrected beam resulting from the direct inversion process was found to focus at the targeted location with an acoustic intensity 2.2 times higher than the conventional non corrected beam. In addition, this corrected beam was found to give an acoustic intensity 1.5 times higher than the focusing pattern obtained with an aberration correction using transcranial acoustic simulation-based on X-ray computed tomography (CT) scans. CONCLUSIONS: The proposed technique achieved near optimal focusing in an intact human head for the first time. These findings confirm the strong potential of energy-based adaptive focusing of transcranial ultrasonic beams for clinical applications.

Pressure Cooker Technique for Endovascular Treatment of Spinal Arteriovenous Fistulas: Experience in 15 Cases.

BACKGROUND AND PURPOSE: Spinal arteriovenous fistulas are challenging to cure by endovascular means, with a risk of incomplete occlusion or delayed recurrence. The authors report herein their preliminary experience using the pressure cooker technique for the embolization of spinal arteriovenous fistulas. MATERIALS AND METHODS: Fifteen patients (8 men; mean age, 60.3 years) underwent an endovascular treatment of a spinal arteriovenous fistula (12 dural spinal arteriovenous fistulas and 3 epidural spinal arteriovenous fistulas) in 2 different institutions using the pressure cooker technique. Two microcatheters could be navigated in the segmental artery in all patients using 2 guiding catheters. A proximal plug was achieved with highly concentrated cyanoacrylate ± coils. The liquid embolic agent injected to cure the fistula was diluted cyanoacrylate (n = 11) or ethylene-vinyl alcohol (n = 4). Technical and clinical complications were systematically recorded. Clinical and angiographic outcomes were systematically evaluated at follow-up. RESULTS: One (6.7%) procedure-related complication was recorded, which consisted of a transient radicular deficit, related to nerve root ischemia. Clinical improvement was observed in 10/14 (71%) patients for whom clinical follow-up was available. Complete spinal arteriovenous fistula occlusion on a follow-up angiography was observed in 11/12 patients (91.7%) for whom angiographic follow-up was available. One patient (8.3%) presented with a delayed recurrence at 29 months. CONCLUSIONS: The pressure cooker technique is feasible, with either glue or ethylene-vinyl alcohol, for the embolization of spinal arteriovenous fistulas. Our results suggest the safety and effectiveness of this technique.

Primary pineal melanoma with leptomeningeal spreading: case report and review of the literature.

OBJECTIVE: Primary melanomas of the pineal region are exceedingly rare and may be difficult to diagnose. Clinical, radiological and pathological features as well as diagnostic procedures are discussed. CASE HISTORY We report herein on a 44-year-old man who presented with uncontrolled epileptic seizures. Magnetic resonance imaging revealed a pineal mass hyperintense on T1-weighted and isointense on T2-weighted sequences with diffuse leptomeningeal involvement and intense homogeneous contrast enhancement after gadolinium administration. A frontal leptomeningeal and cortical biopsy was performed. Histological examination showed a malignant melanocytic tumor cell proliferation expressing Melan-A, but not HMB-45 or S100 protein. Even if we have no proof that the tumor actually arose in the pineal gland, based on the radiological and histological findings, and on the unremarkable dermatologic and ophthalmologic examinations, a primary pineal melanoma with leptomeningeal dissemination was diagnosed. The patient received temozolomide-based chemotherapy followed by whole brain irradiation. The patient died 52 weeks after disease onset and 13 weeks after treatment initiation. CONCLUSION: A diagnosis of pineal melanoma should be considered in the presence of a pineal mass that appears hyperintense on T1-weighted images and hypo- to isointense on T2-weighted images. The diagnosis is provided by pathological examination of tumor specimens obtained at surgical resection or at leptomeningeal biopsy. However, immunochemistry using anti-Melan-A, -S100 protein and/or -HMB45 antibodies on cerebrospinal fluid and leptomeningeal samples may be helpful in diagnosing such a disease. The prognosis of primary pineal melanoma is variable but meningeal spreading carries a dismal prognosis. The best therapeutic management is yet to be defined.

[Early epidural hematoma after CSF shunt for obstructive hydrocephalus]. / Hématome extradural précoce après dérivation interne du liquide céphalorachidien pour hydrocéphalie non communicante.

We present the first case of early epidural hematoma after CSF shunt probably caused by defective material. A 26-year-old man was treated for obstructive hydrocephalus associated with a tonsillar herniation, revealed by headaches and papillary edema. Ventriculoperitoneal shunt was preferred to endoscopic ventriculostomy. Three hours after the operation, the patient fell into a coma, developing a voluminous bifrontal epidural hematoma that was evacuated immediately. The patient completely recovered neurologically. One month later, to treat persistent hydrocephalus, endoscopic ventriculostomy was performed without incident. Then the shunt was removed and an opening threshold close to zero was discovered. Distant MRI showed a reduction in ventricular size, normalization of the tonsils' position and a tumor of the tectal plate. To our knowledge, this is the only case of early epidural hematoma after ventriculoperitoneal shunt. We discuss the choice of treatments for obstructive hydrocephalus and its risks and complications.

[Acute visual loss related to sphenoid meningioma]. / Troubles visuels aigus associés aux méningiomes sphénoïdaux.

Meningiomas represent about 20% of intracranial tumors. Involvement of the medial sphenoid wing includes anterior clinoid, cavernous sinus and superior orbital fissure meningiomas. Due to the proximity of these tumors to the optic nerve, typically progressive unilateral vision loss, over several months to years, is the classic clinical presentation. We report three cases of acute monocular vision loss, two transient and one permanent, ipsilateral to a sphenoid meningioma. Ophthalmological involvement with sphenoid meningiomas is most often chronic, due to interruption of axoplasmic flow and demyelination of the optic nerve by local compression. However, vascular involvement with ischemia of the optic nerve or transient low blood flow secondary to compression of the carotid branches vascularizing these structures is another possible mechanism. In our series, two patients had amaurosis fugax, and one patient had sudden, persistent visual loss in relation to acute anterior ischemic optic neuropathy on the side of the meningioma. The mean age of patients with acute visual manifestations was 62 years. These ischemic and non-compressive visual symptoms, ipsilateral to sphenoid meningiomas, are difficult to interpret. Whether these temporary visual disturbances of vascular origin should be considered an early sign of future severe or permanent visual impairment when no optic nerve compression is observed is not certain. The place of these acute visual disturbances in the therapeutic decision, particularly surgical, remains to be defined. Larger multicentric prospective studies are needed to better understand the role of local circulatory factors attributable to meningioma in the occurrence of these acute visual signs.

[Craniopharyngiomas]. / Les craniopharyngiomes.

Craniopharyngiomas are rare benign epithelial tumors, arising from the pituitary stalk or gland and developing in the sellar and suprasellar region, affecting both adults and children. Incidence is 0.5 to 2 new cases per million inhabitants. Clinical features essentially include visual disturbances, endocrine deficiencies, and neurological signs. Initial signs are often visual loss and increased intracranial pressure in children, growth and pubertal delay in teenagers, visual disturbances or cognitive impairment in adults. Diagnosis is made on MRI and CT scan, demonstrating a sellar or suprasellar tumor, heterogeneous, with frequent calcifications. Craniopharyngiomas can be classified depending on their locations from the sella, the diaphragma sellae, and upon their origins from the pituitary stalk or the infundibulum. They can also be classified depending on the location from the optic chiasm and the third ventricle. This classification allows surgical series comparison, which is of importance since developments and extensions of the tumor can explain surgical difficulties. The management of this lesion is still controversial. Because it is an extra-cerebral benign lesion, the ideal goal of treatment should be complete tumor removal with improvement of altered visual functions, minimal deterioration of endocrine function, and no neuropsychological impairment. But the situation of the tumor, its relationship with third ventricle, hypothalamus, optic tract, vascular structures make its removal often difficult. However, great progresses have been realized in surgical treatment, resulting in a dramatic improvement of the prognosis of craniopharyngiomas. Nowadays, one can expect total removal in 60 to 70% of patients, subtotal removal in 20 to 30%, and partial removal in 10%. When total removal is impossible, radiotherapy may reduce the risk of a poor evolution. Recurrences are a problem in 15% of patients with total removal, 35% in subtotal removal, 70% in partial removal. If radiotherapy has not been performed as first treatment, it is efficient in 80% of recurrences. Long term follow up is necessary in these patients, due to medical management of endocrine, visual and psychological problems, and risk of late recurrence. With close involvement in this management, most of patients may enjoy a good outcome, 80% being able to return to normal active life.

Giant and large peripheral cerebral aneurysms: etiopathologic considerations, endovascular treatment, and long-term follow-up.

BACKGROUND AND PURPOSE: Giant/large peripheral cerebral aneurysms beyond the circle of Willis and middle cerebral artery (MCA) bifurcation are rare lesions, their etiopathogenesis is not completely elucidated, and their treatment is often difficult. We reviewed the etiopathologic findings available in the literature and report the results and long-term follow-up in 10 patients with a giant/large peripheral aneurysm treated by parent artery occlusion. METHODS: Four aneurysms were on the MCA, 2 on the anterior cerebral artery, and 4 on the posterior cerebral artery (PCA). Two patients presented with bleeding. An occlusion test was performed in 7 patients. Occlusion of the parent artery was performed by using coils in 8 patients; and liquid coils and glue, in 2. Imaging follow-up was available from 1.5 to 4.5 years; and clinical outcome, from 1.5 to 7 years. RESULTS: All aneurysms were excluded. One patient developed a partial homonymous hemianopsia after PCA occlusion. A transient deficit was observed in 2 other patients. In the partially thrombosed aneurysms, follow-up imaging showed shrinkage of the thrombosed compartment of the aneurysm and disappearance of the mass effect. No patient experienced progression of symptoms and/or bleeding during the follow-up period. At long-term follow-up, 6 patients presented with a modified Rankin Scale score of 0; 3, with score of 1; and 1, with score of 2. CONCLUSION: The endovascular occlusion of the parent artery appears a relatively safe and efficacious technique in the treatment of these lesions. Long-term follow-up studies confirm persistent exclusion of the aneurysm and good clinical tolerance to the vessel occlusion.

Role of the supplementary motor area in motor deficit following medial frontal lobe surgery.

OBJECTIVE: Patients undergoing surgical resection of medial frontal lesions may present a transient postoperative deficit that remains largely unpredictable. The authors studied the role of the supplementary motor area (SMA) in the occurrence of this deficit using fMRI. METHODS: Twenty-three patients underwent a preoperative fMRI before resection of medial frontal lesions. Tasks included self-paced flexion/extension of the left and right hand, successively. Preoperative fMRI data were compared with postoperative MRI data and with neurologic outcome. RESULTS: Following surgery, 11 patients had a motor deficit from which all patients recovered within a few weeks or months. The deficit was similar across patients, consisting of a global reduction in spontaneous movements contralateral to the operated side with variable severity. SMA activation was observed in all patients. The deficit was observed when the area activated in the posterior part of the SMA (SMA proper) was resected. CONCLUSIONS: fMRI is able to identify the area at risk in the SMA proper whose resection is highly related to the occurrence of the motor deficit. The clinical characteristics of this deficit support the role of the SMA proper in the initiation and execution of the movement.

Craniopharyngiomas in two consanguineous siblings: case report.

OBJECTIVE AND IMPORTANCE: We describe a double case of craniopharyngioma in consanguineous siblings, suggesting the disease is sometimes genetic. CLINICAL PRESENTATION: Two typical adamantine craniopharyngiomas were observed in two consanguineous siblings. The brother and the sister, whose parents were first cousins, developed the tumors at the same age. INTERVENTION: The male patient was operated on using a frontopterional approach, and the tumor was completely resected. The patient remained free from recurrence 9 years after surgery. His older sister died after tumor removal was attempted at another institution. CONCLUSION: To our knowledge, such a connection has never been reported in the literature. It suggests that craniopharyngioma, which is usually sporadic, can also be transmitted in an autosomal recessive manner.

Mechanical dysfunction of ventriculoperitoneal shunts caused by calcification of the silicone rubber catheter.

OBJECT: The authors studied new and calcified shunt catheters to identify the prevalence of failures caused by aging materials in the shunt. Complications associated with these devices have various origins. Among late complications, fracture or migration of the system is related to the subcutaneous adhesion of the distal tubing in a growing child. A review of a cohort of 64 children who underwent shunt placement in 1980 with barium-impregnated distal catheters showed that 10 of these patients underwent reoperation for complications related to aging of the shunt material. This group represents 15% of the whole series and 30% of those children who were followed for more than 3 years. The true impact of aging of materials on shunt function is probably underestimated. METHODS: The authors performed physical, chemical, and mechanical analyses of the retrieved aged catheters and also of new catheters, resulting in the following findings: 1) calcifications were observed only on the external surface of the catheter, predominantly in its subcutaneous segment at the level of the neck and anterior chest wall; 2) calcifications contained particles of free silicon and barium sulfate, signifying fragmentation of the polymer; 3) the microstructure of the silicone polymer was modified: microfractures and alteration of the polymeric network were observed; 4) silanol groups were observed on the external surface of the catheter; and 5) the mechanical properties of the silicone rubber were degraded, and the aged catheters were more brittle than the new ones, with ruptures at elongations and fracture energy much lower than that seen in new catheters. Furthermore, in vitro testing with a metastable solution of simulated body fluid demonstrated the critical impact of pH variations in liquid media and surface degradation of the catheters on the precipitation of hydroxylapatite crystals. CONCLUSIONS: Although most shunt complications can be addressed by better patient management and surgical technique, late complications appear to be partly related to aging of the material. Distal tubing calcifications have been observed in barium-impregnated catheters. The industry recently responded to these observations by introducing plain silicone-coated shunt tubing; further evaluation will show what improvement can be expected.

[Craniopharyngiomas in adults and children. Study of a surgical series of 106 consecutive cases]. / Crâniopharyngiomes de l'adulte et de l'enfant. Etude d'une série chirurgicale de 106 cas consécutifs.

This work is devoted to a 20-year retrospective study of 106 surgical cases of craniopharyngiomas in adults and children treated and followed by the same neurosurgeon. The mean follow-up was 7.2 years. In this homogeneous series, the aim was total microsurgical removal of the tumor, without post-operative radiotherapy. The operation was usually performed through a fronto-pterional approach, and, in some particular cases, through a transsphenoidal approach. The tumor removal was total in 59 cases, subtotal in 31 cases, partial in 16 cases. Even when the removal was not total, radiotherapy was not systematically administered, but was reserved for relapses. We have studied clinical signs, operation characteristics, ophthalmological, endocrinological and functional outcome, as well as recurrence risk and long-term survival. The functional results of our patients were excellent in 82%, good in 9%, fair in 8% (usually due to ophthalmological sequellae), and poor in 1%. Twenty-five patients recurred, but the salvage treatment, by reoperation or radiotherapy, was successful in almost 75%. The actuarial survival was 91% after 5 years, and 80% after 10 years. These results compare favorably with the literature data, suggesting that radical surgery of craniopharyngiomas allows good outcome in terms of survival, full recovery and quality of life, for both adults and children.

[Radionecrosis of the optic chiasma. A clinical and radiological study of 3 cases]. / Radionécrose du chiasma. Etude clinique et radiologique. A propos de trois cas.

The paper reports three cases of optic chiasmal radionecrosis due to radiotherapy of the sellar region. These three cases are compared with 34 ones found in literature. The use of M.R.I. is shown to dramatically improve diagnosis. Corticoids are useful in the treatment. The gravity of the complication, which implies visual prognosis, focuses on a strict use of radiotherapy. For benign or slowly evoluting lesions, surgery and/or regular controls by modern imaging techniques would often be more eligible than systematic earliest irradiation.

[Diabetes insipidus after endoscopic third ventriculostomy. A case report and review of the literature]. / Diabète insipide après ventriculocisternostomie par voie endoscopique. A propos d'un cas et revue de la littérature.

Endoscopic third ventriculostomy has been found to be successful for treating occlusive hydrocephalus. The complication rate ranges from 6 to 12%. Intraoperative bleeding is the most common incident. Endocrinological failures are rare, mainly due to the proximity of the hypothalamic structures. We report the case of a 33-year-old man who was referred in emergency for subacute hydrocephalus related to a tentorium meningioma. The hydrocephalus was treated by endoscopic third ventriculostomy. During the procedure, the floor of the third ventricle was found to be thick but fenestration was performed without incident. After surgery, the clinical signs of hydrocephalus disappeared but diabetes insipidus was diagnosed the same day. There were no other endocrinology disorders. Medical treatment with vasopressin allowed resolution of the diabetes insipidus in fifteen days. Surgical debulking of the meningioma was then achieved via a subtemporal approach. There was no recurrence of the endocrinology disorder. Diabetes insipidus is an unpredictable complication of third ventriculostomy. The mechanism is not well known. It is however a transient disorder that can easily be treated with vasopresin and therefore should not modify the indications of third ventriculostomy, especially in tumor-related hydrocephalus.

[An unusual cause of compressive optic neuropathy]. / Une cause inhabituelle de neuropathie optique compressive.

Clinical manifestations of hydrocephalus vary according to the level of intracranial pressure, the speed of onset, and the etiological mechanism involved. We report the case of a 32-year-old patient with isolated compressive optic neuropathy associated with a dilated third ventricle, revealing congenital hydrocephalus.

[Focused ultrasound therapy: current status and potential applications in neurosurgery]. / La thérapie par ultrasons focalisés : état actuel et applications potentielles en neurochirurgie.

High Intensity Focused Ultrasound (HIFU) therapy is an innovative approach for tissue ablation, based on high intensity focused ultrasound beams. At the focus, HIFU induces a temperature elevation and the tissue can be thermally destroyed. In fact, this approach has been tested in a number of clinical studies for the treatment of several tumors, primarily the prostate, uterine, breast, bone, liver, kidney and pancreas. For transcranial brain therapy, the skull bone is a major limitation, however, new adaptive techniques of phase correction for focusing ultrasound through the skull have recently been implemented by research systems, paving the way for HIFU therapy to become an interesting alternative to brain surgery and radiotherapy.