Composition of encephalic arteries and origin of the basilar artery are different between vertebrates.

Intracranial arterial anatomy is lacking for most mammalian and non-mammalian model species, especially concerning the origin of the basilar artery (BA). Enhancing the knowledge of this anatomy can improve animal models and help understanding anatomical variations in humans. We have studied encephalic arteries in three different species of birds and eight different species of mammals using formalin-fixed brains injected with arterial red latex. Our results and literature analysis indicate that, for all vertebrates, the internal carotid artery (ICA) supplies the brain and divides into two branches: a cranial and a caudal branch. The difference between vertebrates lies in the caudal branch of the ICA. For non-mammalian, the caudal branch is the origin of the BA, and the vertebral artery (VA) is not involved in brain supply. For mammals, the VA supplies encephalic arteries in two different ways. In the first type of organization, mostly found in ungulates, the carotid rete mirabile supplies the encephalic arteries, the caudal branch is the origin of the BA, and the VA is indirectly involved in carotid rete mirabile blood supply. The second type of encephalic artery organization for mammals is the same as in humans. The caudal branch of the ICA serves as the posterior communicating artery, and the BA originates from both VAs. We believe that knowledge of comparative anatomy of encephalic arteries contributes to a better understanding of animal models applicable to surgical or radiological techniques. It improves the understanding of rare encephalic variations that may be present in humans.

A comprehensive review of the vertebral artery anatomy.

BACKGROUND: The vertebral arteries (VA) play a critical role by supplying nearly one-third of the brain's blood flow, predominantly contributing to the posterior circulation. These arteries may need to be exposed in a various cranial and cervical procedures and offers access to investigate or treat vascular lesions by endovascular means related to the posterior circulation. Given its complex anatomy, which is subject to numerous variations, and its role in supplying vital brain regions, a thorough understanding of the VA's anatomy is paramount for any related procedure. OBJECTIVE: To provide a comprehensive overview of vertebral artery anatomy and its relevance in contemporary clinical practice. METHODS: Dissection of the entire vertebral artery length using cadaveric specimen, combined with a comprehensive literature review. RESULTS: The vertebral artery can be subdivided into four segments. Each of these segments has its own unique topographic anatomy with its variations, anastomoses, and significance in surgery. CONCLUSION: As surgical and endovascular techniques continue to evolve with technological improvements, we are now more equipped than ever to manage complex lesions involving the VA. However, with its increasingly complexity comes the necessity for a deeper and more comprehensive understanding of the VA. Possessing the detailed knowledge of the VA is vital for the successful execution of any procedure involving it.

Spatial Distribution of Immune Cells in Primary and Recurrent Glioblastoma: A Small Case Study.

Only a minority of patients with glioblastoma (GBM) respond to immunotherapy, and always only partially. There is a lack of knowledge on immune distribution in GBM and in its tumor microenvironment (TME). To address the question, we used paired primary and recurrent tumors from GBM patients to study the composition and the evolution of the immune landscape upon treatment. We studied the expression of a handful of immune markers (CD3, CD8, CD68, PD-L1 and PD-1) in GBM tissues in 15 paired primary and recurrent GBM. In five selected patients, we used Nanostring Digital Spatial Profiling (DSP) to obtain simultaneous assessments of multiple biomarkers both within the tumor and the microenvironment in paired primary and recurrent GBM. Our results suggest that the evolution of the immune landscape between paired primary and recurrent GBM tumors is highly heterogeneous. However, our study identifies B3-H7 and HLA-DR as potential targets in primary and recurrent GBM. Spatial profiling of immune markers from matched primary and recurrent GBM shows a nonlinear complex evolution during the progression of cancer. Nonetheless, our study demonstrated a global increase in macrophages, and revealed differential localization of some markers, such as B7-H3 and HLA-DR, between GBM and its TME.

A Simple 3D Cell Culture Method for Studying the Interactions between Human Mesenchymal Stromal/Stem Cells and Patients Derived Glioblastoma.

We have developed a 3D biosphere model using patient-derived cells (PDCs) from glioblastoma (GBM), the major form of primary brain tumors in adult, plus cancer-activated fibroblasts (CAFs), obtained by culturing mesenchymal stem cells with GBM conditioned media. The effect of MSC/CAFs on the proliferation, cell-cell interactions, and response to treatment of PDCs was evaluated. Proliferation in the presence of CAFs was statistically lower but the spheroids formed within the 3D-biosphere were larger. A treatment for 5 days with Temozolomide (TMZ) and irradiation, the standard therapy for GBM, had a marked effect on cell number in monocultures compared to co-cultures and influenced cancer stem cells composition, similar to that observed in GBM patients. Mathematical analyses of spheroids growth and morphology confirm the similarity with GBM patients. We, thus, provide a simple and reproducible method to obtain 3D cultures from patient-derived biopsies and co-cultures with MSC with a near 100% success. This method provides the basis for relevant in vitro functional models for a better comprehension of the role of tumor microenvironment and, for precision and/or personalized medicine, potentially to predict the response to treatments for each GBM patient.

Mitochondria transfer from tumor-activated stromal cells (TASC) to primary Glioblastoma cells.

The tumor microenvironment (TME) controls many aspects of cancer development but little is known about its effect in Glioblastoma (GBM), the main brain tumor in adults. Tumor-activated stromal cell (TASC) population, a component of TME in GBM, was induced in vitro by incubation of MSCs with culture media conditioned by primary cultures of GBM under 3D/organoid conditions. We observed mitochondrial transfer by Tunneling Nanotubes (TNT), extracellular vesicles (EV) and cannibalism from the TASC to GBM and analyzed its effect on both proliferation and survival. We created primary cultures of GBM or TASC in which we have eliminated mitochondrial DNA [Rho 0 (ρ0) cells]. We found that TASC, as described in other cancers, increased GBM proliferation and resistance to standard treatments (radiotherapy and chemotherapy). We analyzed the incorporation of purified mitochondria by ρ0 and ρ+ cells and a derived mathematical model taught us that ρ+ cells incorporate more rapidly pure mitochondria than ρ0 cells.

Dural arteries of the dorsoclival area.

OBJECTIVE: In the literature, there is a lack of complete description of dural arteries of the dorsoclival area with contradictory data. However, dorsoclival area is a site of tumors and vascular malformation or the skull base. That is why, the knowledge of dural arteries is very important. METHODS: Using a colored silicone mix preparation, fifteen sides of eight cranial bases were studied using 4-20× magnification of the surgical microscope. RESULTS: Dorsoclival area is supplying by three arterial complexes, internal carotid artery complex with always the dorsal meningeal artery for the superior two-third of the clivus, medial clival artery for the dorsum sellae, the external carotid artery complex with the hypoglossal and jugular branches of the ascending pharyngeal artery for the inferior one-third of the clivus, and the vertebral artery complex with the anterior meningeal artery for the most inferior part of the clivus and the anterior edge of the foramen magnum. Moreover, there are many anastomoses between those three arterial complexes at this area. CONCLUSION: Dural arterial supply of the dorsoclival area is very opulent. Its knowledge is important for surgical approaches and endovascular procedures.

Drug resistance in glioblastoma: are persisters the key to therapy?

Glioblastoma (GBM) represents the main form of brain tumors in adults, and one of the most aggressive cancers overall. The treatment of GBM is a combination of surgery (when possible), chemotherapy (usually Temozolomide, TMZ) and radiotherapy (RT). However, despite this heavy treatment, GBM invariably recur and the median length of survival following diagnosis is 12 to 15 months, with less than 10% of people surviving longer than five years. GBM is extremely resistant to most treatments because of its heterogeneous nature, which is associated with extreme clonal plasticity and the presence of cancer stem cells, refractory to TMZ- and RT-induced cell death. In this review, we explore the mechanisms by which cancer cells, and especially GBM, can acquire resistance to treatment. We describe and discuss the concept of persister/tolerant cells that precede and/or accompany the acquisition of resistance. Persister/tolerant cells are cancer cells that are not eliminated by treatment(s) because of different mechanisms ranging from dormancy/quiescence to senescence. We discuss the possibility of targeting these mechanisms in new therapeutic regimen.

Implication of the inferolateral trunk of the cavernous internal CAROTID artery in cranial nerve blood supply: Anatomical study and review of the literature.

The inferolateral trunk (ILT) is one of the two more common branches of the cavernous internal carotid artery (ICA). Its knowledge is important for skull base surgery and endovascular interventional procedures. The ILT is described with superior, anterior and posterior branch, which is the complete form. These branches vascularize the oculomotor, trochlear, trigeminal and abducens nerves into the cavernous sinus and superior orbital fissure (SOF) courses, and through the foramens rotundum and ovale. We performed 21 injected embalmed cadaveric dissections combined with six specimen tomodensitometry. The ILT originates from the horizontal ICA segment and passes above the abducens nerve. Three branches arise from the ILT between the cavernous ICA and the ophthalmic and maxillary nerves initial courses. The main differences with the literature are the number of branches and their cranial nerves' blood supply. The more frequent ILT conformation is the incomplete form with anterior and posterior branch (13/21); the complete form is present in 5/13 sides (38%) and the ILT is in common with the meningohypophyseal trunk in 3/21 (14%) sides. The anterior branch always vascularizes the cranial nerves into the SOF course and most often the maxillary nerve through the foramen rotundum. The posterior branch always vascularizes the mandibular nerve through the foramen ovale course and sometimes the maxillary nerve. This study has demonstrated that there are anastomoses between these branches and arteries arising from the external carotid. This study explains why the sacrifice of a branch of the ILT does not implicate cranial nerve palsy.

Trigeminal Ganglion Metastasis of Renal Clear Cell Carcinoma: Cases Report and Review of the Literature.

BACKGROUND: The trigeminal ganglion is an atypical site for metastasis, especially for renal clear cell carcinoma. CASE DESCRIPTION: We report 2 clinical cases of a 66-year-old man and a 58-year-old man with trigeminal symptoms. Both patients had a history of renal clear cell (RCC) that was considered to be cured at 6 and 9 years, respectively. Brain magnetic resonance imaging (MRI) showed a trigeminal ganglion lesion with increased gadolinium enhancement associated with petrous apex erosion. The main diagnostic hypothesis based on MRI was trigeminal schwannoma for both patients. One patient underwent subtotal removal, the other a biopsy. Histologic examinations resulted in the diagnosis of RCC metastasis. Body computed tomography revealed pancreatic metastasis for both but no renal recurrence. The patients were treated by local radiotherapy, and 1 of the patients had associated chemotherapy. We added to these clinical cases a literature review of skull base metastasis of RCC. Trigeminal ganglion metastasis of RCC is very rare and can persist until 10 years after the first RCC diagnosis. It seems that the best treatment is surgical removal. To date, the role of local radiotherapy is not demonstrated, and the prognosis seems to be poor. CONCLUSIONS: In the case of trigeminal symptoms, rapid tumoral growth on brain MRI, or a history of RCC, we think that a body computed tomography should be performed, and surgery should be considered.

Descriptive and dynamic study of the medial patellofemoral ligament (MPFL).

PURPOSE: The goal of this study was to evaluate the anatomy of the medial patellar retinaculum and the medial patellofemoral ligament (MPFL) to provide an anatomical validation of a pediatric reconstruction technique. METHODS: Fifteen knees were dissected to study the MPFL and its relationship with the medial patellar retinaculum and the femoral insertion of the medial collateral ligament (MCL). The distances between the insertions of the MPFL of eight knees, and the patellar insertion of the MPFL and the femoral insertion of the MCL of four knees, were measured during the flexion to evaluate the isometricity of the native and reconstructed MPFL. RESULTS: The medial patellar retinaculum includes four structures: the fascia, fibrous expansions of the vastus muscles, the MPFL and the medial patellomeniscal ligament. The femoral insertion of the MPFL was located just behind the femoral insertion of the MCL in 12 knees. During flexion, the distance between the insertion on the upper patella and the femoral insertion of the MPFL increased while the distance between the insertion on the lower patella and the femoral insertion of the MPFL decreased. The variation in the distances measured during the flexion was greater between the MPFL insertions (nsup = 6.5 mm, ninf = 6.5 mm) than between the patellar insertion of the MPFL and the femoral insertion of the MCL (n'sup = 2.5 mm, n'inf = 5.75 mm). CONCLUSION: The MPFL is not isometric. Even though the results were obtained from knees of elderly specimens, this study demonstrates reconstruction of the MPFL should take into account its anatomy and biomechanical role in the knee.

Morphometric study of the posterior longitudinal ligament at the lumbar spine.

PURPOSE: There are only two descriptions of posterior longitudinal ligament (PLL) at the lumbar spine level but its morphologic characteristics are different to cervical and thoracic levels. METHOD: Spine explantation (from Th12 to L5) followed by resection of the neural arch and the dural sheath in 13 fresh cadavers was performed. The PLL was isolated from other epidural structures and its width was measured and compared to the vertebral body width at each vertebral levels. It was conducted at a microanatomic study concerning the PLL and the posterior outer annulus fibrosus. RESULTS: The PLL width was reduced craniocaudaly significantly, becoming thin from L4. The average width of PLL was 7.8 mm at L1 and 1.9 mm at L5. The width decreased gradually from L1 to L5 or abruptly from L4. The ratio of PLL width compared to the vertebral body width was 21% at L1 and 3% at L5. Microanatomic study confirmed that the PLL is less thick at its annulus fibrosus adhesion at L4-L5 and L5-S1. The relationship between the PLL and other epidural structures are discussed. CONCLUSIONS: The presence and function of the ilio-lumbar ligaments and the articular process orientation of L5-S1 may be explanations for PLL width decrease at L4-L5 and L5-S1. Furthermore, this aspect may be considered as one factor contributing to the occurrence of disc herniations at these levels, which levels are more frequently involved in this pathology.

Long-Term Follow-Up Comparative Study of Hydroxyapatite and Autologous Cranioplasties: Complications, Cosmetic Results, Osseointegration.

OBJECTIVE: A three-dimensional reconstruction technique using the CustomBone (CB) prosthesis allows custom-made cranioplasty (CP) possessing osseointegration properties owing to its porous hydroxyapatite (HA) composition. This reconstruction technique has replaced less expensive techniques such as subcutaneously preserved autologous bone (SP). Our primary objective was to evaluate complications between CB and SP CP techniques. A secondary objective was to assess cosmetic results and osseointegration of CPs. METHODS: This single-center study comprised patients undergoing delayed CB or SP CP after craniectomy between 2007 and 2014. A prospective interview was conducted to collect all data, including 2-year follow-up clinical and radiologic data. Cosmetic results were assessed by a qualitative score, and osseointegration was assessed by measuring relative fusion at the CP margins. RESULTS: Of 100 patients undergoing CB or SP CP between 2007 and 2014, 92 (CB, n = 44; SP, n = 48) participated in the prospective interview. No significant difference in complication rates was observed between the 2 groups. The main complication specific to the CB group was fracture of the prosthesis observed in 20.8% patients. A higher rate of good cosmetic results was observed in the CB group (92.5% vs. 74.3%, P = 0.031). In the CB group, 51% of patients demonstrated no signs of bone fusion of the CP. CONCLUSIONS: Although the CB prosthesis is associated with cosmetic advantages, the porous hydroxyapatite composition makes it fragile in the short-term and long-term, and effective osseointegration remains uncertain.

Extrinsic and intrinsic blood supply to the optic chiasm.

Although there have been many studies of the arterial cerebral blood supply, only seven have described the optic chiasm (OC) blood supply and their results are contradictory. The aim of this study was to analyze the extrinsic and intrinsic OC blood supply on cadaveric specimens using dissections and microcomputer tomography (Micro-CT). Thirteen human specimens were dissected and the internal or common carotid arteries were injected with red latex, China Ink with gelatin or barium sulfate. Three Micro-CTs were obtained to reveal the intrinsic blood supply to the OC. The superior hypophyseal arteries (SupHypA) (13/13) and posterior communicating artery (PCoA) (12/13) supplied the pial network on the inferior side of the OC. The first segment of the anterior cerebral artery (ACA) (10/10), SupHypA (7/10), the anterior communicating artery (ACoA) (9/10), and PComA (1/10) supplied the pial network of its superior side. The intrinsic OC blood supply was divided into three networks (two lateral and one central). Capillaries entering the OC originated principally from the inferior pial network. The lateral network capillaries had the same orientation as the visual lateral pathways, but the central network was not correlated with the nasal fibers crossing into the OC. There was no anastomosis in the pial or intrinsic networks. Only SupHypA, PCoA, ACoA, and ACA were involved in the OC blood supply. Because there was no extrinsic or intrinsic anastomosis, all arteries should be preserved. Tumor compression of the inferior intrinsic arterial network could contribute to visual defects. Clin. Anat. 31:432-440, 2018. © 2017 Wiley Periodicals, Inc.

Non neurologic burst thoracolumbar fractures fixation: Case-control study.

STUDY DESIGN: Burst fractures not associated with any neurological deficits are frequent but not therapeutic agreement on their management is available to date. This case-control study was conducted to try to help guide therapeutic decision in the treatment of such fractures. MATERIALS AND METHODS: This case-control study includes consecutive retrospective evaluation of 25 case-patients treated by posterior short-segment fixation associated with kyphoplasty (SFK) in the treatment of A3 thoracolumbar unstable fractures, as compared to a control-group composed of 82 patients treated by long-segment (LF) pedicle screws. RESULTS: SFK patients bled significantly less than the LF patients (p=0.04). Assessment of deformation progression, vertebral height restoration and reduction of the regional kyphotic angle in the SFK and LF groups revealed no statistically significant superiority of one approach on another. In contrast, the height of endplates was significantly increased in the SFK group (p=0.006). The patients' pain levels were significantly improved in the SFK group (p=0.002). However, patients from the SFK group stood earlier postoperatively (1.7 vs 3.7days, p=0.001). CONCLUSION: We believe that SFK in vertebral fractures is as efficient as LF for bone consolidation and spine stabilization. In addition, SFK patients may use fewer analgesics.

Entrapment of the posterior femoral cutaneous nerve and its inferior cluneal branches: anatomical basis of surgery for inferior cluneal neuralgia.

PURPOSE: The apparent failure of pudendal nerve surgery in some patients has led us to suggest the possibility of entrapment of other adjacent nerve structures, leading to the concept of inferior cluneal neuralgia. Via its numerous collateral branches, the posterior femoral cutaneous nerve innervates a very extensive territory including the posterior surface of the thigh, the infragluteal fold, the skin over the ischial tuberosity, but also the lateral anal region, scrotum or labium majus via its perineal branch. METHODS: We described the pathophysiological features of cluneal neuralgia, the surgical technique and our preliminary results. RESULTS: We performed a transmuscular approach leading to the fat of the deep gluteal region. Exploration was continued cranially underneath the piriformis, looking for potential entrapments affecting the posterior femoral cutaneous nerve and the sciatic nerve. Nerve decompression on the lateral surface of the ischial tuberosity was then performed. A constant anatomical finding must be highlighted: the presence of a lateral fibrous expansion from the ischium passing behind the nerves and vessels, especially the posterior femoral cutaneous nerve and its perineal branches. In our patients, release of this expansion allowed decompression of the nerve trapped by this expansion. CONCLUSION: Cluneal neuralgia constitutes a distinct entity of perineal pain, which must be identified and distinguished from pudendal neuralgia. Surgery should be performed via a transgluteal approach. A lateral ischial obstacle must be investigated, in the form of a constant fibrous expansion, which, like a retinaculum, can cause nerve entrapment.

Overall Survival in Spine Myeloma Metastases: Difficulties in Predicting With Prognostic Scores.

STUDY DESIGN: Fifty-one patients with spinal multiple myeloma (MM) metastases were operated and followed between January 2004 and July 2014. OBJECTIVE: The aim of this study was to consider the efficiency of surgical prognosis scores in the management of spinal metastases myelomas. SUMMARY OF BACKGROUND DATA: The spine is the most common site of bone metastases in MM. Surgery in spine metastases MM is a matter of debate and its impact on the increase of a patient's survival time is not clear. Several surgical survival scores have been developed to determine the best treatment in these patients. METHODS: We studied 51 patients operated for spinal MM metastases between January 2004 and July 2014. We determined the Tokuhashi and Tomita survival scores and compared them with documented patient survivals. The two scores were also compared with the International Staging System (ISS). RESULTS: Median survival (MS) was 108 months [standard deviation (SD) 62] for ISS I, 132.2 (SD 40) for ISS II, and 45.5 months (SD 16.3) for ISS III (P = 0.09). According to Tokuhashi survival score, 21 patients (41.2%) will survive <6 months, 6 (11.8%) 6 to 12 months, and 24 (47%) >12 months. According to Tomita et al., 50 patients (98%) will survive >49.9 months and 1 patient (2%) <15 months. Regardless of the ISS grade prognosis, Tokuhashi survival score, and to a lesser extent Tomita score, underestimated the actual survival very significantly [P < 0.0001, Log Rank (Mantel-Cox)]. CONCLUSION: We suggest that spine surgical prognosis scores are not accurate and are not able to predict the survival of patients with spine myeloma metastases. Spine surgeons have to be guided not by the initial ISS stage but rather by spinal instability and neurological status. LEVEL OF EVIDENCE: N/A.

Predictors of survival in patients with surgical spine multiple myeloma metastases.

BACKGROUND: Multiple myeloma (MM) is the most common primary malignant tumor of the spine and bone. Spinal metastases are part of the evolution and progression of the MM disease. Therefore, this study aims at investigating prognostic factors associated with overall survival (OS) in patients with symptomatic spine MM metastases. METHODS: Consecutive spine surgery procedures were performed in the largest series reported to date and comprising 51 patients with osteolytic vertebral compression fractures resulting from MM, diagnosed by either bone marrow or tumor biopsy. RESULTS: The mean age of patients was 61.1 years and mean follow-up was 31.9 months. Through univariate analyses, ISS stage (p < 0.0001), preoperative spine instability (SINS score) (p < 0.03), posterior osteosynthesis fixation (p < 0.002), preoperative adjuvant therapy (p < 0.02), postoperative adjuvant treatment (p < 0.001), bone marrow transplant (p < 0.03) and newly MM diagnosed (p < 0.03) emerged as powerful predictors of survival. Cox multivariate proportional hazard model indicated that only ISS Stage and stabilization surgery such as osteosynthesis were two independent predictive factors for OS [hazard ratio (HR): 0.268, 95% confidence interval (CI) 0.07-0.536; p < 0.006 for the former and HR: 0.184, 95% confidence interval (CI) 0.03-0.89; p < 0.04 for the latter]. CONCLUSION: Stabilization surgery combined to ISS staging should be considered as an important prognostic survival factor for patients with symptomatic MM spine metastases.

Management of aneurysmal subarachnoid haemorrhage with intracerebral hematoma: Is there an indication for coiling first? Study of 44 cases.

BACKGROUND: Aneurysmal subarachnoid haemorrhage (ASH) with intracerebral hematoma (ICH) has a poor prognosis. The treatment is to secure the aneurysm and do an ICH evacuation. OBJECTIVE: The aim of the study was to determine if aneurysm coiling followed by ICH evacuation is a viable alternative treatment compared to exclusive surgery, regardless of the clinical or paraclinical presentations. METHODS: A retrospective study was conducted between 2004 and 2014, which included 44 patients. The patients were divided up in four groups. Two were principal groups: The clipped group (aneurysm clipping with ICH evacuation) and the coiled group (aneurysm coiling, followed by ICH evacuation); and two were subgroups of the latter: Aneurysm coiling with ICH evacuation after 24 hours and ICH evacuation followed by aneurysm coiling. We studied the demographic and radiologic characteristics, and the 3-month outcome. RESULTS: We included 17 patients in the coiled group: The outcome was better for the patients with World Federation of Neurosurgery (WFNS) scores of 1, 2 and 3; compared to the patients with WFNS scores 4 and 5. We included 16 patients in the clipped group: The outcome was better, compared the coiled group, for those patients with WFNS scores 4 and 5. Six patients were treated with aneurysm coiling, followed by ICH evacuation after 24 hours: 33% had a good outcome. Five patients were treated by ICH evacuation, followed by aneurysm coiling: None had a good outcome. CONCLUSIONS: It was necessary to realise a prospective study to compare the outcomes of patients with WFNS scores of 1, 2 or 3; between those with aneurysm coiling followed by ICH evacuation and aneurysm clipping with ICH evacuation, to determine the potential of using the coiling first, for these patients.