A realistic aneurysm clipping simulation combining 3D-printed and placenta-based models-how I do it.

INTRODUCTION: Neurovascular surgery, particularly aneurysm clipping, is a critical skill for aspiring neurosurgeons. However, hands-on training opportunities are limited, especially with the growing popularity of endovascular techniques. To address this challenge, we present a novel neurovascular surgical training station that combines synthetic 3D-printed models with placental vascular structures to create a semi-realistic surgical field. METHODS: Our model consists of three components: a 3D-printed skull replica with anatomical landmarks, a malleable silicone parenchyma with a Sylvian fissure, and vascular layers (placenta). The placental vascular layer is catheterized and perfused to replicate pulsatile flow, offering a realistic aneurysm simulation. This innovative training station provides a cost-effective solution (approximately 200 USD once) without ethical constraints. Surgeons can practice essential skills such as Sylvian fissure dissection, managing anatomical constraints like bone, and achieving proximal vascular control. The model's realism allows for training in various scenarios, including clipping with different hand orientations and handling ruptures realistically. CONCLUSION: Our neurovascular surgical station bridges the gap between existing training models, offering affordability, ecological considerations, and minimal ethical concerns. It empowers neurosurgery residents to refine their skills in handling both emergencies and elective cases under close-to-real surgical conditions, with the potential for independent practice and senior supervision.

Safety and practicality study of using an exoskeleton in acute neurosurgery patients.

INTRODUCTION: Early mobilization is key in neurologically impaired persons, limiting complications and improving long-term recovery. Self-balanced exoskeletons are used in rehabilitation departments to help patients stand and walk. We report the first case series of exoskeleton use in acute neurosurgery and intensive care patients, evaluating safety, clinical feasibility and patients' satisfaction. METHODS: We report a retrospective observational study including individuals hospitalized in the neurosurgical intensive care and neurosurgery departments. We included patients with a medical prescription for an exoskeleton session, and who met no contraindication. Patients benefited from standing sessions using a self-balanced exoskeleton (Atalante, Wandercraft, France). Patients and sessions data were collected. Safety, feasibility and adherence were evaluated. RESULTS: Seventeen patients were scheduled for 70 standing sessions, of which 27 (39%) were completed. They were typically hospitalized for intracranial hemorrhage (74%) and presented with unilateral motor impairments, able to stand but with very insufficient weight shifting to the hemiplegic limb, requiring support (MRC 36.2 ± 3.70, SPB 2.0 ± 1.3, SPD 0.7 ± 0.5). The average duration of standing sessions was 16 ± 9 min. The only side effect was orthostatic hypotension (18.5%), which resolved with returning to seating position. The most frequent reason for not completing a session was understaffing (75%). All patients were satisfied and expressed a desire to repeat it. CONCLUSIONS: Physiotherapy using the exoskeleton is safe and feasible in the acute neurosurgery setting, although it requires adaptation from the staff to organize the sessions. An efficacy study is ongoing to evaluate the benefits for the patients.

Preservation of frontal white matter tracts in ventricular surgery: favoring an anterior interhemispheric transcallosal approach vs a transcortical transfrontal transventricular approach.

Secondary to the creation of a surgical corridor and retraction, white matter tracts degenerate, causing long-term scarring with potential neurological consequences. Third and lateral ventricle tumors require surgery that may lead to cognitive impairment. Our objective is to compare the long-term consequences of a transcortical transfrontal approach and an interhemispheric transcallosal approach on corpus callosum and frontal white matter tracts degeneration. Surgical patients with ventricular tumor accessible through both approaches were included and clinico-radiological data were retrospectively analyzed. The primary endpoint was the callosotomy length at 3-month post-operative T1 MRI, corrected by the extension of the tumor and the use of neuronavigation. Secondary outcomes included perioperative criteria such as bleeding, use of retractors and duration, FLAIR hypersignal on 3-month MRI, and re-do surgeries. To assess white matter tract interruption, 3-month FLAIR hypersignal was superposed to a tractography atlas. Seventy patients were included, 57 (81%) in the transfrontal group and 13 (19%) in the interhemispheric group. There was no difference in the mean callosotomy length on 3-month MRI (12.3 mm ± 5.60 transfrontal vs 11.7 mm ± 3.92 interhemispheric, p = 0.79) on univariate and multivariate analyses. The callosotomy length was inferior by - 3.13 mm for tumors located exclusively in the third ventricle (p = 0.016), independent of the approach. Retractors were used more often in transfrontal approaches (60% vs 33%, p < 0.001). The extent of frontal FLAIR hypersignal was higher after transfrontal approach (14.1 mm vs 0.525 mm, p < 0.001), correlated to the use of retractors (p < 0.05). After the interhemispheric approach, no tract other than corpus callosum was interrupted, whereas, after the transfrontal approach, frontal arcuate fibers and projections from the thalamus were interrupted in all patients, the cingulum in 19 (33%), the superior fronto-occipital fasciculus in 15 (26%), and the superior longitudinal fasciculus in 2 (3%). Transfrontal and interhemispheric approaches to the third and lateral ventricles both lead to the same long-term damage to the corpus callosum, but the transfrontal approach interrupts several white matter tracts essential to cognitive tasks such as attention and planning, even in the non-dominant hemisphere. These results encourage all neurosurgeons to be familiar with both approaches and favor the interhemispheric approach when both can give access to the tumor with a comparable risk. Neuropsychological studies are necessary to correlate these anatomical findings to cognitive outcomes.

Molecular description of meningeal solitary fibrous tumors/hemangiopericytomas compared to meningiomas: two completely separate entities.

INTRODUCTION: Meningeal solitary fibrous tumors (SFT), like all SFT, are defined by NAB2-STAT6 fusion and share clinicopathologic similarities with meningiomas, the most frequent meningeal tumors. Our aim is to establish the molecular identity of meningeal SFT and seek molecular prognostic factors. METHODS: RNA sequencing and whole exome sequencing were performed in STAT6-positive SFT and grade 2-3 meningiomas, and data concerning other soft tissues tumors was obtained from the local database. Uniform manifold approximation and projection, individual gene expression and Gene Set Enrichment Analysis were performed. RESULTS: RNA clustering shows that SFT share a common molecular signature, different from any other type of tumoral tissue. Meningeal SFT aggregate with other SFT, with no clinical or histological subgroup. Comparison of genes expressions suggests significant over-expressions of ZIC2, ZIC3, ZIC5, GABBR2, TP53 in CNS-SFT. The pathogenic TP53 c.743G>T variant, previously undescribed in SFT, was found in one sample of meningeal SFT during malignant progression. CONCLUSIONS: Meningeal SFT are molecular counterparts of extra-meningeal SFT, completely separate from meningiomas. They might develop from the same tissues and benefit from the same treatments as SFT.

Interhemispheric transcallosal approach: going further based on the vascular anatomy.

Preserving cortical frontal bridging veins draining into the superior sagittal sinus is a factor of good neurological outcome in anterior interhemispheric transcallosal approaches, classically performed to reach intraventricular tumors. Challenging the idea that veins are utterly variable, we propose a statistical analysis of 100 selective cerebral angiographies to determine where to place the craniotomy in order to expose the most probable vein-free area. The mean distance to the first pre-coronal vein was 6.66 cm (± 1.73, 1.80 to 13.00) and to the first post-coronal vein 0.94 cm (± 0.92, 0 to 3.00) (p < 0.001). The probability of absence of bridging veins was 92.0% at 4 cm anterior to the coronal suture versus 37.5% at 1 cm and 12.5% at 2 cm posteriorly. The length of the surgical corridor (distance between the first pre-coronal and post-coronal vein) was 7.60 cm (± 1.72, 3.00 to 14.10). Overall, the ideal centering point of the craniotomy was 2.86 cm (± 1.08, - 0.65 to 6.50) ahead of the coronal suture. The mean number of veins within 6 cm behind the coronal suture was 8.47 (± 2.11, from 3 to 15) versus 0.530 (± 0.82, from 0 to 3) ahead of the coronal suture (p < 0.001). These findings support a purely pre-coronal 5 cm craniotomy for interhemispheric approaches.

Female gender and exogenous progesterone exposition as risk factors for spheno-orbital meningiomas.

OBJECTIVE: The great heterogeneity of meningiomas is challenging and we need to distinguish relevant subgroups. Spheno-orbital osteomeningiomas (SOOM) constitute a clinically specific entity, with slow-growing benign osteo-meningiomatous tumors, which recur after surgery in one fourth of cases. Neurosurgical daily practice, supported by the literature, shows that the vast majority of patients with SOOM are women, and we explored whether their epidemiological and hormonal profiles suggest a progesterone influence. METHODS: We retrospectively documented all radiologically and histologically confirmed cases of SOOM operated in 2005-2019 in our institution. We completed the clinical and hormone history by systematic telephone interviews. RESULTS: In the literature, SOOM occur significantly more often in women than other meningiomas (749/847, 86.4% versus 73.8%, p = 0.002). Among 175 cases, we included 124 patients, 93.5% were women, younger than men (51 ± 5 versus 63 ± 8, p = 0.02). Women' meningiomas showed more progesterone receptors (96.4% versus 50%, p < 0.001). Exogenous hormonal intake, reliable in 82 cases, concerned 83.3% (64/78) of women, with frequent progesterone intake: 13 oestroprogestogenic treatment only, with old-generation progesterone analogs, 41 progesterone analogs (cyproterone acetate, nomegestrol acetate, chlormadinone, promegestone, etonogestrel, levonogestrel), 7 substitutive hormonal therapy for menopause, 3 others. Duration of treatment was 2-40 years, median 10 years. CONCLUSIONS: SOOM develop preferentially in women in their fifties, who often received progesterone analogs, and show progesterone receptors. Progesterone analogs are incriminated in skull base meningiomas, and this is the first report on the prevalence of exogenous hormone therapy specifically in SOOM. Whether SOOM reduce after treatment discontinuation, in particular the osteoma part, needs to be explored. Anti-progesterone treatments may represent an avenue for future research in soom.

Covidom, a Telesurveillance Solution for Home Monitoring Patients With COVID-19.

In a matter of months, COVID-19 has escalated from a cluster of cases in Wuhan, China, to a global pandemic. As the number of patients with COVID-19 grew, solutions for the home monitoring of infected patients became critical. This viewpoint presents a telesurveillance solution-Covidom-deployed in the greater Paris area to monitor patients with COVID-19 in their homes. The system was rapidly developed and is being used on a large scale with more than 65,000 registered patients to date. The Covidom solution combines an easy-to-use and free web application for patients (through which patients fill out short questionnaires on their health status) with a regional control center that monitors and manages alerts (triggered by questionnaire responses) from patients whose health may be deteriorating. This innovative solution could alleviate the burden of health care professionals and systems while allowing for rapid response when patients trigger an alert.

Could propranolol be beneficial in adult cerebral cavernous malformations?

Surgery is the only therapeutic option for cerebral cavernous malformations (CCM) and is proposed, whenever possible, after haemorrhagic events, neurological symptoms, or epilepsy, radiosurgery being a controversial alternative in some cases. However, there is no treatment for non-accessible lesions, such as brainstem CCM, multiple CCM, or those located in functional areas. Propranolol, a non-selective beta-blocker used as first-line treatment for infantile haemangiomas, has proved spectacularly effective in a few cases of adult patients with CCM. We herein review the histological, in vitro data and clinical findings that support the idea of propranolol as a potential treatment for CCM. Since one retrospective study has not been conclusive, we support the idea that prospective trials are necessary.

Pazopanib efficacy in recurrent central nervous system hemangiopericytomas.

INTRODUCTION: There is currently no treatment for solitary fibrous tumors/hemangiopericytomas (SFT/H) of the central nervous system recurring after multiple surgeries and radiotherapies. The NAB2-STAT6 gene fusion is the hallmark of these tumors, and upregulates Early Growth Factor, activating several growth pathways. METHODS: We treated two patients presenting pluri-recurrent meningeal SFT/H with Pazopanib, a broad-spectrum tyrosine kinase inhibitor. We analyzed the exome and RNA sequencing data of one of them and, in addition to another meningeal SFT/H, compared it to the transcriptomic profiling of 5 systemic SFT/H. RESULTS: A dramatic clinical and radiological response was observed in both cases, respectively 84 and 43% decrease after 3 months. As a comparison, Pazopanib has only a stabilizing effect in systemic SFT/H. Indeed, central nervous system SFT/H show overexpression of different tyrosine kinases targeted by Pazopanib. CONCLUSIONS: Two consecutive patients with untreatable central nervous system SFT/H showed a spectacular partial response to Pazopanib, an unprecedented result in SFT/H. This result could be explained by differences in expression profiles and calls for a confirmation in a larger cohort of patients.

Incomplete copolymer degradation of in situ chemotherapy.

In situ carmustine wafers containing 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are commonly used for the treatment of recurrent glioblastoma to overcome the brain-blood barrier. In theory, this chemotherapy diffuses into the adjacent parenchyma and the excipient degrades in maximum 8 weeks but no clinical data confirms this evolution, because patients are rarely operated again. A 75-year-old patient was operated twice for recurrent glioblastoma, and a carmustine wafer was implanted during the second surgery. Eleven months later, a third surgery was performed, revealing unexpected incomplete degradation of the wafer. 1H-Nuclear Magnetic Resonance was performed to compare this wafer to pure BCNU and to an unused copolymer wafer. In the used wafer, peaks corresponding to hydrophobic units of the excipient were no longer noticeable, whereas peaks of the hydrophilic units and traces of BCNU were still present. These surprising results could be related to the formation of a hydrophobic membrane around the wafer, thus interfering with the expected diffusion and degradation processes. The clinical benefit of carmustine wafers in addition to the standard radio-chemotherapy remains limited, and in vivo behavior of this treatment is not completely elucidated yet. We found that the wafer may remain after several months. Alternative strategies to deal with the blood-brain barrier, such as drug-loaded liposomes or ultrasound-opening, must be explored to offer larger drug diffusion or allow repetitive delivery.

Similarities and differences in neuroplasticity mechanisms between brain gliomas and nonlesional epilepsy.

OBJECTIVE: To analyze the conceptual and practical implications of a hodotopic approach in neurosurgery, and to compare the similarities and the differences in neuroplasticity mechanisms between low-grade gliomas and nonlesional epilepsy. METHODS: We review the recent data about the hodotopic organization of the brain connectome, alongside the organization of epileptic networks, and analyze how these two structures interact, suggesting therapeutic prospects. Then we focus on the mechanisms of neuroplasticity involved in glioma natural course and after glioma surgery. Comparing these mechanisms with those in action in an epileptic brain highlights their differences, but more importantly, gives an original perspective to the consequences of surgery on an epileptic brain and what could be expected after pathologic white matter removal. RESULTS: The organization of the brain connectome and the neuroplasticity is the same in all humans, but different pathologic mechanisms are involved, and specific therapeutic approaches have been developed in epilepsy and glioma surgery. We demonstrate that the "connectome" point of view can enrich epilepsy care. We also underscore how theoretical and practical tools commonly used in epilepsy investigations, such as invasive electroencephalography, can be of great help in awake surgery in general. SIGNIFICANCE: Putting together advances in understanding of connectomics and neuroplasticity, leads to significant conceptual improvements in epilepsy surgery.

Neuroplasticity and the brain connectome: what can Jean Talairach's reflections bring to modern psychosurgery?

Contrary to common psychosurgical practice in the 1950s, Dr. Jean Talairach had the intuition, based on clinical experience, that the brain connectome and neuroplasticity had a role to play in psychosurgery. Due to the remarkable progress of pharmacology at that time and to the technical limits of neurosurgery, these concepts were not put into practice. Currently, these concepts are being confirmed by modern techniques such as neuroimaging and computational neurosciences, and could pave the way for therapeutic innovation in psychiatry. Psychosurgery commonly uses a localizationist approach, based on the idea that a lesion to a specific area is responsible for a deficit opposite to its function. To psychosurgeons such as Walter Freeman, who performed extensive lesions causing apparently inevitable deficit, Talairach answered with clinical data: complex psychic functions cannot be described that simply, because the same lesion does not provoke the same deficit in different patients. Moreover, cognitive impairment did not always follow efficacious psychosurgery. Talairach suggested that selectively destructing part of a network could open the door to a new organization, and that early psychotherapy could encourage this psychoplasticity. Talairach did not have the opportunity to put these concepts into practice in psychiatric diseases because of the sudden availability of neuroleptics, but connectomics and neuroplasticity gave rise to major advances in intraparenchymal neurosurgery, from epilepsy to low-grade glioma. In psychiatry, alongside long-standing theories implicating focal lesions and diffuse pathological processes, neuroimaging techniques are currently being developed. In mentally healthy individuals, combining diffusion tensor imaging with functional MRI, magnetoencephalography, and electroencephalography allows the determination of a comprehensive map of neural connections in the brain on many spatial scales, the so-called connectome. Ultimately, global neurocomputational models could predict physiological activity, behavior, and subjective feeling, and describe neuropsychiatric disorders. Connectomic studies comparing psychiatric patients with controls have already confirmed the early intuitions of Talairach. As a striking example, massive dysconnectivity has been found in schizophrenia, leading some authors to propose a "dysconnection hypothesis." Alterations of the connectome have also been demonstrated in obsessive-compulsive disorder and depression. Furthermore, normalization of the functional dysconnectivity has been observed following clinical improvement in several therapeutic interventions, from psychotherapy to pharmacological treatments. Provided that mental disorders result from abnormal structural or functional wiring, targeted psychosurgery would require that one be able: 1) to identify the pathological network involved in a given patient; 2) to use neurostimulation to safely create a reversible and durable alteration, mimicking a lesion, in a network compatible with neuroplasticity; and 3) to predict which functional lesion would result in adapted neuronal plasticity and/or to guide neuronal plasticity to promote recovery. All these conditions, already suggested by Talairach, could now be achievable considering modern biomarkers and surgical progress.

Disseminated Tuberculosis Revealed by Conus Medullaris Tuberculoma.

A 29-year-old man from Comoros presented with rapidly progressive paraplegia and sexual dysfunction. Magnetic resonance imaging (MRI) showed a contrast-enhanced conus medullaris lesion. Differential diagnoses included tumors, abscesses, and inflammatory diseases. Neurosurgery was delayed to complete examinations. Cerebral MRI showed three abscesses. Body computed tomography scan showed supracentimetric polyadenopathies, pulmonary nodules, prostatic lesion, and enhanced seminal vesicle, with hypermetabolism on positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose scan. Histology of lymph node biopsy showed granulomatous infiltration without acid-fast bacilli, and positive polymerase chain reaction for Mycobacterium tuberculosis. Lymph node culture was positive after 2 months, urine culture after 3 weeks, but cerebrospinal fluid and sputum cultures were negative. A 1-year antituberculosis therapy was initiated, associated with corticosteroids because the patient developed tuberculosis-immune reconstitution syndrome, revealed by the recurrence of neurological symptoms. After 2 months the patient completely recovered and could run. MRI showed stability of the voluminous tuberculoma with decrease of medullary edema. Avoiding surgery in those cases may prevent iatrogenic neurological deterioration.

Achieving Gross Total Resection in Neurosurgery: A Review of Intraoperative Techniques and Their Influence on Surgical Goals.

The definition of complete resection in neurosurgery depends on tumor type, surgical aims, and postoperative investigations, directly guiding the choice of intraoperative tools. Most common tumor types present challenges in achieving complete resection due to their infiltrative nature and anatomical constraints. The development of adjuvant treatments has altered the balance between oncological aims and surgical risks. We review local recurrence associated with incomplete resection based on different definitions and emphasize the importance of achieving maximal safe resection in all tumor types. Intraoperative techniques that aid surgeons in identifying tumor boundaries are used in practice and in preclinical or clinical research settings. They encompass both conservative and invasive techniques. Among them, morphological tools include imaging modalities such as intraoperative magnetic resonance imaging, ultrasound, and optical coherence tomography. Fluorescence-guided surgery, mainly using 5-aminolevulinic acid, enhances gross total resection in glioblastomas. Nuclear methods, including positron emission tomography probes, provide tumor detection based on beta or gamma emission after a radiotracer injection. Mass spectrometry- and spectroscopy-based methods offer molecular insights. The adoption of these techniques depends on their relevance, effectiveness, and feasibility. With the emergence of positron emission tomography imaging for use in recurrence benchmarking, positron emission tomography probes raise particular interest among those tools. While all such tools provide valuable insights, their clinical benefits need further evaluation.

Embolization of the middle meningeal artery for the prevention of chronic subdural hematoma recurrence in high-risk patients: a randomized controlled trial-the EMPROTECT study protocol.

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

Surgical treatment of hemifacial spasms: how to predict failure and complications through a series of 200 patients.

Primary hemifacial spasm (pHFS) is a benign but disabling movement disorder caused by a neurovascular conflict involving the facial nerve. Surgical treatment by microvascular decompression (MVD) is the most effective therapeutic. Predictors of surgical failure and surgical complications are still lacking. The aim of this study is to identify such predictors through the retrospective analysis of a series of 200 consecutive patients. All patients who underwent MVD for pHFS from January 1991 to December 2017 were included. All patients had at least two years follow-up. In addition to the demographic data, the outcome and the complications were collected. The primary outcome analysis showed that 7.5% of patients had a recurrence. Multiple and AICA related neurovascular conflicts were statistically associated to a higher recurrence rate after MVD (respectively p < 0.001 and p = 0.02). Permanent facial palsy occurred in 2.5% of patients, hearing loss in 9.0% (2.0% of complete unilateral impairment) and dizziness in 2.5%. The risk of each of these peripheral neurological impairments was statistically increased by a long duration between the first pHFS symptom and the MVD (p < 0.001). In case of recurrence, a second MDV was offered. Long term follow-up showed that all patients had a complete resolution of the HFS. Post-operative complication rate was not significantly increased after a second MVD. Multiple and AICA related neurovascular conflicts are associated to a higher risk of surgical failure. When a pHFS recurrence occurs, a second surgical procedure is associated with excellent outcome without significant increase of post-operative complications and should therefore be recommended.

Cthrc1 is a negative regulator of myelination in Schwann cells.

The analysis of the molecular mechanisms involved in the initial interaction between neurons and Schwann cells is a key issue in understanding the myelination process. We recently identified Cthrc1 (Collagen triple helix repeat containing 1) as a gene upregulated in Schwann cells upon interaction with the axon. Cthrc1 encodes a secreted protein previously shown to be involved in migration and proliferation in different cell types. We performed a functional analysis of Cthrc1 in Schwann cells by loss-of- and gain-of-function approaches using RNA interference knockdown in cell culture and a transgenic mouse line that overexpresses the gene. This work establishes that Cthrc1 enhances Schwann cell proliferation but prevents myelination. In particular, time-course analysis of myelin formation intransgenic animals reveals that overexpression of Cthrc1 in Schwann cells leads to a delay in myelin formation with cells maintaining a proliferative state. Our data, therefore, demonstrate that Cthrc1 plays a negative regulatory role, fine-tuning the onset of peripheral myelination.