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.

The Dural Dark-Side Approach for falcine and tentorial meningioma: A surgical series of five patients.

INTRODUCTION: Falcine or tentorial meningioma can be complex to resect. When large meningiomas are located in eloquent areas, a direct ipsilateral surgical approach may cause brain injury and postoperative neurological deficits. In this series, 5 patients were surgically treated using a contralateral transfalcine or transtentorial approach to minimize brain retraction. This strategy was called the Dural Dark-Side Approach (DDSA). The aim was to analyze the quality of tumor resection and postoperative outcome. MATERIAL AND METHODS: In our department, from June 2018 to January 2020, 5 patients underwent microsurgical DDSA for resection of 4 falcine and 1 tentorial meningioma. All tumors were selected on the following two criteria: large>40mm diameter tumor, with surrounding functional cortex. Clinical and radiologic data were retrospectively analyzed. RESULTS AND DISCUSSION: Mean follow-up was 20 months. No patients required use of a rigid retractor during surgery. Gross total resection was performed in 3 patients and near-total resection in 2. All patients had favorable neurologic outcome. Postoperative MRI showed no ipsilateral or contralateral brain lesions. CONCLUSION: This series suggested that meticulous DDSA allows excellent resection in selected large falcine or tentorial meningioma. The approach offered a safe and effective surgical corridor without injuring the surrounding healthy parenchyma.

A unique case of pure lateral spinal cord herniation.

BACKGROUND: Spinal cord herniation (SCH) remains a challenging diagnosis for neuroradiologists and may require treatment challenging for neurosurgeons. Most cord herniations are usually found at anterior thoracic levels. CLINICAL PRESENTATION: A 28-year-old woman presented at our department with a 7-year history of progressive myelopathy. MR analysis showed a displacement of the spinal cord in a lateral thoracic dural defect. The herniated cord was released using a microscope and the patient significantly recovered 6 months after surgery. CONCLUSION: We present a unique case of pure lateral SCH. In the light of reviewed literature and operative findings, the underlying pathophysiological mechanisms are discussed.

[Primitive intracranial trigeminal nerve germinoma. Case report]. / Localisation trigéminale d'un germinome intracrânien primitif. A propos d'un cas.

A 22-year-old man presented headache, asthenia, body weight loss and trigeminal hypoesthesia worsening quickly. Radiological analysis showed an enhanced lesion that originated from the cavernous sinus and extended into the Meckel cave, owing to the fifth cranial nerve's course. The lesion was explored by a temporo-pterional approach and was partially removed. On the basis of histological analysis and negativity of tumor marker levels in serum and cerebrospinal fluid (alpha-fetoprotein alpha, human beta-chorionic gonadotropin), a primitive non-secreting intracranial germinoma was diagnosed. Under combined chemotherapy (carboplatine, ifosfamide, etoposide) followed by focal fractionated radiotherapy delivering 40 Gy to the initial tumor volume, the outcome was excellent. Five years later, the patient was in complete clinical and radiological remission. Primitive intracranial germinomas are rare malignant tumors involving mainly pineal and hypothalamic regions. We report a case of intracranial trigeminal nerve germinoma. To the best of our knowledge, no case of primitive germinoma was previously described in this location. Aspects of diagnosis and treatment are discussed in the light of previous publishing data.

[Endoscope-assisted biopsy for the diagnosis of neurosarcoidosis]. / Biopsie endoscopique diagnostique d'un cas de neurosarcoïdose.

A 56-year-old woman was followed in the neurological department for febrile mental confusion. The diagnosis of sarcoidosis was suggested on the ground of associated abdominal lymphadenopathy, elevated serum angiotensin-converting enzyme level, aseptic meningitis and intracranial hypothalamic lesion. Nevertheless, radiological, biological and histological analyses could not assert the diagnosis of systemic sarcoidosis. Six months later, cerebral MRI showed a recent enhanced nodule, located near the right choroid plexus, inducing a dilatation of the right temporal ventricular horn. A surgical endoscope-assisted biopsy of that lesion was decided. The endoscope was introduced in the right trapped temporal ventricle. The limits between normal and pathological tissues were clearly identified. The biopsy was thus accurately performed. Histological analysis definitely confirmed the diagnosis of neurosarcoidosis. No postoperative complication was noted. We report a case of neurosarcoidosis which was diagnosed by ventricular endoscope-assisted biopsy. The discussion stresses the potential advantages of endoscopy for the diagnosis of small periventricular lesions when ventricular dilatation is associated.

[Temporary vessel occlusion]. / Clampage vasculaire temporaire.

UNLABELLED: In many situations, temporary artery occlusion is an integral component of aneurysm surgery. The use of temporary clip may allow safer and easier aneurysmal dissection and clipping. Several points, concerning the duration and overall risks of temporary occlusion and the method of choice for cerebral function monitoring have to be discussed. MATERIAL AND METHODS: Non exhaustive review of neurosurgical literature. DISCUSSION: Temporary clip application decreases the risk of intraoperative aneurysmal rupture. The analysis of data published in the literature showed that several questions remain open concerning the optimal method of neuroprotection and cerebral function monitoring, as well as the limit of occlusion duration. Other clinical trials are needed to assess the efficacy and safety of this technique.

[Endoscope-assisted microsurgery for invasive endo- and suprasellar pituitary macroadenomas: a consecutive retrospective study with 13 patients]. / Endoscopie et traitement chirurgical des macroadénomes hypophysaires endo- et suprasellaires invasifs. Une série consécutive rétrospective de 13 patients.

BACKGROUND AND PURPOSE: Surgery of invasive endo- and suprasellar pituitary macroadenomas remains difficult. The records of 13 consecutive patients who underwent transsphenoidal surgery were analyzed in order to evaluate advantages and limitations of endoscopy for surgery of invasive pituitary macroadenomas. METHODS: A transseptal transsphenoidal intersepto-columellar approach was performed with a nasal 0-degree endoscope. Removal of the macroadenoma was performed under the control of a microscope. When the tumor seemed to be completely removed with microscope, a rigid 30-degree endoscope was inserted in the intrasellar and suprasellar regions in order to detect residual adenoma tissue. These residues were removed when technically possible. RESULTS: No rhinologic complication was noted. In 7 patients, the intra- and suprasellar endoscopic view detected a tumor residue which could be removed in each case. Two cases of cerebrospinal fluid leakage occurred during the complementary tumor resection. Two cases of diabetes insipidus and two of rhinorrhea were reported postoperatively. The analysis of the postoperative MRIs showed a complete removal in 23% of the patients (3/13), 75 to 100% removal in 54% of the patients (7/13), 50 to 75% removal in 8% of the patients (1/13) and 50% removal in 15% of the patients (2/13). More than 75% removal was thus achieved in 77% of the patients (10/13). The mean follow-up was 27.2 months. CONCLUSIONS: Rhinologic morbidity was reduced with the endoscopic endonasal approach. Endoscopy complemented with a microscope offered an optimal view of the intra- and suprasellar regions. Endoscopy also improved tumor resection of the invasive endo- and suprasellar pituitary macroadenomas by visualizing hidden suprasellar tumor residues. However, endoscopy was associated with a higher rate of postoperative rhinorrhea.

Tokuhashi score and other prognostic factors in 260 patients with surgery for vertebral metastases.

BACKGROUND: Metastatic disease of the spine is an increasingly common public health problem. Surgery should be an integral component of the overall cancer treatment plan and, importantly, must neither delay not jeopardize any of the other components. The prognosis governs the choice of the surgical strategy. Tokuhashi et al. developed a prognostic score in 1990, then revised it in 2000 and 2005. Here, our objective was to evaluate the performance of the Tokuhashi score in a cohort of 260 patients and to look for other variables that might improve preoperative outcome prediction. MATERIAL AND METHOD: We retrospectively established a single-centre cohort of 260 patients who underwent spinal metastasis surgery between 1998 and 2008. For each patient, the following data were collected prospectively: socio-demographic features, history of the malignancy, variables needed to determine the Tokuhashi score, and treatments used. SAS 9.0 software was chosen for the statistical analysis. Variables were described as mean ± SD, overall survival was estimated using the Kaplan-Meier method, and survivals in subgroups were compared by the log-rank test. To assess agreement between survival predicted by the Tokuhashi score and observed survival, we computed Cohen's kappa and interpreted the results according to Landis and Koch. RESULTS: There were 143 females and 117 males with a mean age of 59 years and overall median survival of 10 months. Median observed survivals in the three Tokuhashi score categories (< 6, 6-12, and > 12 months predicted survival) were 5, 10, and 36 months, respectively. These survival times differed significantly (P < 0.0001). Cohen's kappa indicated moderate agreement between predicted and observed survivals. Other factors associated with significant survival differences were time from cancer diagnosis to metastasis diagnosis (synchronous, < 2 years, 2-5 years, or > 5 years; P < 0.0001) and age (< 70 years or ≥ 70 years, P = 0.0053). CONCLUSION: Our cohort study supports the validity and reproducibility of the Tokuhashi score. Our finding that shorter time to metastasis diagnosis and age ≥ 70 years were also significantly associated with survival in our population invites further efforts to improve and update the Tokuhashi score.

Diaphragm recovery by laryngeal innervation after bilateral phrenicotomy or complete C2 spinal section in rats.

This study aimed to highlight the functional aspects of diaphragm reinnervation by laryngeal motoneurons after bilateral phrenicotomy or complete cervical transection. The left recurrent laryngeal nerve was connected to the left phrenic nerve in 14 rats. Five months later, all bridged rats presented a substantial ipsilateral diaphragm recovery (74.2 +/- 10% of contralateral activity) whereas the diaphragm remained paralysed in non-bridged rats (n = 5/5). After additional right phrenicotomy, functional breathing persisted in bridged rats whereas all non-bridged died. After complete C2 spinal transection, diaphragm respiratory discharges persisted in bridged rats. The reinnnervation by laryngeal motoneurons was confirmed by retrograde labeling, stimulus-elicited diaphragm response by vagal stimulation and diaphragm inactivation after vagotomy. In conclusion, the recurrent-phrenic nerve anastomosis induces a reliable functional diaphragm outcome even after contralateral diaphragm denervation or complete high cervical spinal cord injury, and could be considered as a clinical repair strategy for re-establishing diaphragm autonomy following spinal cord trauma.

Multimodal cerebral monitoring and decompressive surgery for the treatment of severe bacterial meningitis with increased intracranial pressure.

Bacterial meningitis is still associated with a high mortality, mainly because of cerebral herniation as a result of increased intracranial pressure. Published data stress the necessity of an early diagnosis and immediate start of antibiotic therapy. Nevertheless, there are only few reports in which therapeutic strategy was based on the monitoring and the reduction of intracranial pressure (ICP). We report one case of bacterial meningitis caused by Neisseria meningitidis with an initial ICP value of 60 mmHg, which was treated by large hemicraniectomy and ventriculostomy, leading to a favorable neurological long-term result. The surgical decision was accelerated by an accurate ICP evaluation based on cerebral monitoring [transcranial Doppler ultrasonography (TCD) and intracranial ICP-device]. In selected patients with bacterial meningitis and clinical and radiological evidence of elevated ICP, cerebral monitoring and aggressive reduction of ICP may be crucial to improve survival and neurological outcome. When maximal medical ICP treatment fails to reduce severe intracranial hypertension, decompressive craniectomy should be rapidly proposed.

A new model of upper cervical spinal contusion inducing a persistent unilateral diaphragmatic deficit in the adult rat.

Research on spinal cord trauma requires models reflecting the contusion mechanisms encountered in clinical situation. The aim of this study was to develop in the adult rat a reproducible model of upper cervical spinal cord contusion inducing persistent unilateral diaphragm deficit. After dura and pia matter removal, weight drop and compression were targeted at the ventro-lateral funiculi which contain the bulbospinal descending respiratory pathways that command the phrenic motoneurons innervating the diaphragm. At 7 days post-injury, the left diaphragm activity recorded in contused rats (27.4 +/- 5.1% of the contralateral activity) was significantly lower than in the sham group (97.6 +/- 1.2%). This respiratory deficit still persisted 1 month later. Histology showed a reproducible left C2-lateralized lesion that involved both white and gray matter including the ventro-lateral funiculi. This C2 contusion model provides a basis for testing both regenerative and neuroprotective strategies aimed at improving functional respiratory recovery after spinal cord trauma.