Evolution of microneurosurgical anatomy with special reference to the history of anatomy, surgical anatomy, and microsurgery: historical overview.

This article reviews the evolution of microneurosurgical anatomy (MNA) with special reference to the development of anatomy, surgical anatomy, and microsurgery. Anatomy can be said to have started in the ancient Greek era with the work of Hippocrates, Galen, and others as part of the pursuit of natural science. In the sixteenth century, Vesalius made a great contribution in reviving Galenian knowledge while adding new knowledge of human anatomy. Also in the sixteenth century, Ambroise Paré can be said to have started modern surgery. As surgery developed, more detailed anatomical knowledge became necessary for treating complicated diseases. Many noted surgeons at the time were also anatomists eager to spread anatomical knowledge in order to enhance surgical practice. Thus, surgery and anatomy developed together, with advances in each benefiting the other. The concept of surgical anatomy evolved in the eighteenth century and became especially popular in the nineteenth century. In the twentieth century, microsurgery was introduced in various surgical fields, starting with Carl O. Nylen in otology. It flourished and became popularized in the second half of the century, especially in the field of neurosurgery, following Jacobson and Suarez's success in microvascular anastomosis in animals and subsequent clinical application as developed by M.G. Yasargil and others. Knowledge of surgical anatomy as seen under the operating microscope became important for surgeons to perform microneurosurgical procedures accurately and safely, which led to the fuller development of MNA as conducted by many neurosurgeons, among whom A.L. Rhoton, Jr. might be mentioned as representative.

Microsurgical management of midbrain cavernous malformations: does lesion depth influence the outcome?

BACKGROUND: The purpose of this study was to clarify whether the intrinsic depth of midbrain cavernous malformations (MCMs) influenced the surgical outcome. METHODS: The authors conducted a retrospective study of 76 consecutive patients who underwent microsurgical resection of a MCM. The vascular lesions were categorized into 4 distinct groups based on how these lesions had altered the brainstem surface. Additionally, it was verified whether the actual aspect of the brainstem surface could be predicted only by evaluating the pertinent preoperative MRI slices. Clinical outcome was assessed by determining the modified Rankin Scale Score (mRS) before and after surgery. RESULTS: Twenty-three MCMs (30.3%) were located deeply within the midbrain. The overlying midbrain surface appeared to be normal (group nl). In 33 patients (43.4%), the midbrain surface showed only a yellowish discoloration (group yw). In another 14 individuals (18.4%), the midbrain surface was distorted by the underlying MCM and bulging out while the vascular lesion still remained covered by a thin parenchymal layer (group bg). In the smallest group comprising 6 patients (7.9%), the exophytic MCM had disrupted the midbrain surface and was clearly visible at microsurgical exposure (group ex). The mean mRS decreased in the group nl from 1.43 preoperatively to 0.61 at follow-up. CONCLUSION: This study demonstrates in a large patient population that a deep intrinsic MCM location is not necessarily associated with an unfavorable clinical outcome after microsurgical lesionectomy. Predicting the aspect of the midbrain surface by evaluating preoperative MR images alone was not sufficiently reliable.

Improving results in patients with foramen magnum meningiomas by translating surgical experience into a classification system and complexity score.

Foramen magnum meningiomas (FMMs) are challenging lesions and controversy still exists regarding their optimal management. In the present paper, we propose some principles of surgical treatment of FMMs. We analyzed our series of 39 patients: the average maximum diameter was 31.1 mm (sd, 10.7). In two cases, there was extradural extension. We operated all anterior lesions through dorsolateral approach to craniovertebral junction and all posterior lesions through midline suboccipital approach and C1 laminectomy, following the prevalence of side of the tumor. There were no complications except for one case of post-operative hypoglossus paresis. We translated our experience with surgery of foramen magnum meningiomas into a classification system and a complexity score, in order to assign a score to each individual case and plan the surgical strategy. When the complexity score is 5 or more, we propose subtotal removal, in consideration of the benign nature.

Genome-Wide Sequencing Reveals Small Nucleolar RNAs Downregulated in Cerebral Cavernous Malformations.

Cerebral cavernous malformations (CCM) are vascular malformations associated with abnormally dilated blood vessels and leaky capillaries that often result in hemorrhages. Despite recent advances, precise understanding of the cellular and molecular mechanism leading to the pathogenesis of CCM remains elusive. Emerging evidence indicates that small nucleolar RNAs (snoRNAs), belonging to the class of non-coding RNAs, may play a significant role as diagnostic markers in human diseases. However, there is no report till date that studied the role of snoRNAs in CCM biology. The objective of the current study was to identify snoRNAs associated with CCM pathogenesis. Using genome-wide small RNA sequencing, we identified a total of 271 snoRNAs reliably expressed in CCM. By applying additional statistical stringency, three snoRNAs (SNORD115-32, SNORD114-22, and SNORD113-3) were found to be significantly downregulated in CCM patient tissue samples (n = 3) as compared to healthy brains (n = 3). Deregulation of the selected snoRNAs was further validated by qRT-PCR. Further, cellular localization via in situ hybridization also confirmed robust reduction in the expression of SNORD115-32 and SNORD114-22 in CCM tissues as compared to the healthy controls. By applying high-throughput sequencing and cellular localization analyses, we report here for the first time the genome-wide expression profile of snoRNAs in CCM tissues and a robust downregulation of candidate snoRNAs in CCM conditions. Future studies should warrant the screening in large CCM patient cohorts and will be helpful in the development of potential biomarkers and improved clinical diagnosis.

Pediatric intracranial primary anaplastic ganglioglioma.

BACKGROUND: Primary intracranial anaplastic gangliogliomas are rare tumors in the pediatric patient group. Most of them present with symptoms of elevated pressure or symptomatic epilepsy. Extraaxial location is far more common than axial location. On MRI examination, they mimic pilocytic astrocytomas. The outcome after surgery depends mainly on the possible amount of surgical resection, and oncological therapy is necessary to prevent recurrence of the disease. CASE REPORT: An 11-year-old boy presented with headache and double vision due to obstructive hydrocephalus. MRI of the brain revealed an axial partially contrast enhancing lesion in the quadrigeminal plate extending from the cerebellum to the pineal gland and causing hydrocephalus. Subtotal removal of the lesion was performed, and the diagnosis of an anaplastic ganglioglioma was established and confirmed by the reference center. At the latest follow up (3 months), the boy is without any neurological symptoms and scheduled for radiation therapy as well as chemotherapy.

Glioblastoma in the Canton of Zurich, Switzerland revisited: 2005 to 2009.

BACKGROUND: A population-based analysis of patients with glioma diagnosed between 1980 and 1994 in the Canton of Zurich in Switzerland confirmed the overall poor prognosis of glioblastoma. To explore changes in outcome, registry data were reevaluated for patients diagnosed between 2005 and 2009. METHODS: Patients with glioblastoma who were diagnosed between 2005 and 2009 were identified by the Zurich and Zug Cancer Registry. The prognostic significance of epidemiological and clinical data, isocitrate dehydrogenase 1 (IDH1)(R132H) mutation status, and O6 methylguanine DNA methyltransferase (MGMT) promoter methylation status was analyzed using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: A total of 264 patients with glioblastoma were identified, for an annual incidence of 3.9 compared with the previous incidence of 3.7. The mean age of the patients at the time of diagnosis was 59.5 years in the current cohort compared with 61.3 years previously. The overall survival (OS) rate was 46.4% at 1 year, 22.5% at 2 years, and 14.4% at 3 years in the current study compared with 17.7% at 1 year, 3.3% at 2 years, and 1.2% at 3 years as reported previously. The median OS for all patients with glioblastoma was 11.5 months compared with 4.9 months in the former patient population. The median OS was 1.9 months for best supportive care, 6.2 months for radiotherapy alone, 6.7 months for temozolomide alone, and 17.0 months for radiotherapy plus temozolomide. Multivariate analysis revealed age, Karnofsky performance score, extent of tumor resection, first-line treatment, year of diagnosis, and MGMT promoter methylation status were associated with survival in patients with IDH1(R132H) -nonmutant glioblastoma. CONCLUSIONS: The OS of patients newly diagnosed with glioblastoma in the Canton of Zurich in Switzerland markedly improved from 1980 through 1994 to 2005 through 2009. Cancer 2016;122:2206-15. © 2016 American Cancer Society.

Role of Delta-Notch signaling in cerebral cavernous malformations.

Cerebral cavernous malformations (CCM) commonly known as cavernous hemangioma are associated with abnormally enlarged thin-walled blood vessels. As a result, these dilated capillaries are prone to leakage and result in hemorrhages. Clinically, such hemorrhages lead to severe headaches, focal neurological deficits, and epileptic seizures. CCM is caused by loss of function mutations in one of the three well-known CCM genes: Krev interaction trapped 1 (KRIT1), OSM, and programmed cell death 10 (PDCD10). Loss of CCM genes have been shown to be synergistically related to decreased Notch signaling and excessive angiogenesis. Despite recent evidences indicating that Notch signaling plays a pivotal role in regulating angiogenesis, the role of Notch in CCM development and progression is still not clear. Here, we provide an update literature review on the current knowledge of the structure of Notch receptor and its ligands, its relevance to angiogenesis and more precisely to CCM pathogenesis. In addition to reviewing the current literatures, this review will also focus on the cross talk between Delta-Notch and vascular endothelial growth factor (VEGF) signaling in angiogenesis and in CCM pathogenesis. Understanding the role of Notch signaling in CCM development and progression might help provide a better insight for novel anti-angiogenic therapies.

Predicting the necessity of anterior communicating artery division in the bifrontal basal interhemispheric approach.

BACKGROUND: The anterior communicating artery (ACoA) often limits surgical exposure in the anterior interhemispheric approach. Although division of the ACoA has been proposed occasionally, it is rarely practiced, and criteria for such a surgical maneuver remain unknown. Our purpose was to identify key factors that allow for predicting the necessity of controlled ACoA division in the bifrontal basal interhemispheric approach. METHOD: Twenty-two consecutive patients who underwent surgery via the bifrontal basal interhemispheric approach for removal of various pathologic brain lesions were examined. First, tumors were dichotomized into central and lateral lesions. Next, three tumor parameters were compared between cases with and without ACoA division in each, the central and lateral lesion groups, respectively: tumor volume, tumor depth (defined as distance between the ACoA and posterior tumor margin) and tumor laterality angle (defined as the geometric angle between the lateral tumor margin and sagittal midline). RESULTS: Tumor volume was not related in a statistically significant manner to ACoA division in both the central (P = 0.06) and lateral (P = 0.13) lesion groups, respectively. However, tumor depth was significantly correlated with ACoA division in the central lesion group (P = 0.01), whereas in the lateral lesion group, the tumor laterality angle showed a significant correlation with ACoA division (P = 0.04). CONCLUSIONS: Our results suggest that controlled ACoA division may be required in central lesions with a depth of 38 mm or more and in lateral lesions with an angle of 23 degrees or more as defined in this study. Two key factors were thus identified that may predict the necessity of controlled ACoA division before surgery.

The Possible Role of Mast Cells and VEGF in Peritumoural Oedema of Secretory Meningioma.

Objective: Secretory meningiomas constitute a relatively rare subtype of meningiomas and present often with massive peritumoural oedema. From our previous report, a high number of mast cells were demonstrable in this subtype of meningiomas. The present study aimed to obtain more information about mast cell derived progangiogenic factors and mediators as well as VEGF receptors in secretory meningioma. Additionally, the correlation of histological factors such as the presence of mast cells and the radiological evidence of surrounding tumour oedema was analysed. Material and Method: Sixteen cases of secretory meningioma were examined. Relevant clinical information was obtained from the patient files. The peritumoural oedema was determined either by CT or MRI scans and graded as mild, moderate and severe. Immunohistochemical studies of histamine, substance P, serotonin, VEGF and VEGF receptors were performed. A double-blind quantitative evaluation of mast cells staining positively for VEGF in a comparison with total mast cells in secretory meningiomas was made by two histopathologists. Results: There was no immunoreactivity against histamine or substance P within the tumour tissue or in mast cells. Fine granules of serotonin were demonstrated within the mast cells and a coarse granular expression of VEGF was found within the mast cells. Our preliminary data demonstrated that tumours with moderate to severe degree of peritumoural oedema usually contained more than 50% of VEGF-staining positive mast cells. Conclusion: Secretory meningiomas are characterized by a significantly increased number of mast cells. VEGF and serotonin might be involved in the pathophysiological process of this vasogenic brain oedema. The preliminary data demonstrated the potential relation between the radiological evidence of increasing oedema and the high numbers of mast cell staining positively for VEGF.

PTEN/PI3K/Akt/VEGF signaling and the cross talk to KRIT1, CCM2, and PDCD10 proteins in cerebral cavernous malformations.

Cerebral cavernous malformations (CCM) are common vascular malformation of the brain and are associated with abnormal angiogenesis. Although the exact etiology and the underlying molecular mechanism are still under investigation, recent advances in the identification of the mutations in three genes and their interactions with different signaling pathways have shed light on our understanding of CCM pathogenesis. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is known to play a major role in angiogenesis. Studies have shown that the phosphatase and tensin homologue deleted on chromosome ten (PTEN), a tumor suppressor, is an antagonist regulator of the PI3K/Akt pathway and mediates angiogenesis by activating vascular endothelial growth factor (VEGF) expression. Here, we provide an update literature review on the current knowledge of the PTEN/PI3K/Akt/VEGF signaling in angiogenesis, more importantly in CCM pathogenesis. In addition to reviewing the current literatures, this article will also focus on the structural domain of the three CCM proteins and their interacting partners. Understanding the biology of these proteins with respect to their signaling counterpart will help to guide future research towards new therapeutic targets applicable for CCM treatment.

Brainstem cavernoma surgery with the support of pre- and postoperative diffusion tensor imaging: initial experiences and clinical course of 23 patients.

The spatial complexity of highly vulnerable structures makes surgical resection of brainstem cavernomas (BSC) a challenging procedure. Diffusion tensor imaging (DTI) allows for the visualization of white matter tracts and enables a better understanding of the anatomical location of corticospinal and sensory tracts before and after surgery.We investigated the feasibility and clinical usefulness of DTI-based fiber tractography in patients with BSC.Pre- and postoperative DTI visualization of corticospinal and sensory tracts were retrospectively analyzed in 23 individuals with BSC. Preoperative and postoperative DTI-fiber accuracy were associated to the neurological findings. Preoperatively, the corticospinal tracts were visualized in 90 % of the cases and the sensory tracts were visualized in 74 % of the cases. Postoperatively, the corticospinal tracts were visualized in 97 % of the cases and the sensory tracts could be visualized in 80 % of the cases. In all cases, the BSC had caused displacement, thinning, or interruption of the fiber tracts to various degrees. Tract visualization was associated with pre- and postoperative neurological findings. Postoperative damage of the corticospinal tracts was observed in two patients. On follow-up, the Patzold Rating (PR) improved in 19 out of 23 patients (83 %, p = 0.0002).This study confirms that DTI tractography allows accurate and detailed white matter tract visualization in the brainstem, even when an intraaxial lesion affects this structure. Furthermore, visualizing the tracts adjacent to the lesion adds to our understanding of the distorted intrinsic brainstem anatomy and it may assists in planning the surgical approach in specific cases.

Surgical treatment of tentorial dural arteriovenous fistulae located around the tentorial incisura.

Tentorial dural arteriovenous fistulae (DAVF) are relatively uncommon and are the most dangerous type of DAVF. Because of a high incidence of hemorrhage and subsequent neurological deficits, treatment is mandatory. A consecutive series of nine surgically treated patients with symptomatic tentorial DAVF were analyzed in this study. All lesions were located around the tentorial incisura and were treated microsurgically using a subtemporal approach in eight cases and a supracerebellar approach in one case. The dural bases of the lesions were located adjacent to the tentorial edge in six patients and the tentorial apex in three patients. Complete obliteration was achieved in all treated tentorial DAVF. In one patient, the torcular fistula remained untreated without cortical venous reflux. Postoperative asymptomatic temporal lobe hemorrhage was diagnosed in one patient with a tentorial apex DAVF; however, no new neurological symptoms were present after surgical treatment. The subtemporal approach for unilateral tentorial DAVF is a favorable and direct approach for the highly skilled surgeon. Perimesencephalic venous dilatation or varix is an important finding on MRI to help localize tentorial DAVF in the tentorial edge or apex.

Feasibility of cervical intramedullary diffuse glioma resection using intraoperative magnetic resonance imaging.

Intraoperative magnetic resonance imaging (iopMRI) actually has an important role in the surgery of brain tumors, especially gliomas and pituitary adenomas. The aim of our work was to describe the advantages and drawbacks of this tool for the surgical treatment of cervical intramedullary gliomas. We describe two explicative cases including the setup, positioning, and the complete workflow of the surgical approach with intraoperative imaging. Even if the configuration of iopMRI equipment was originally designed for cranial surgery, we have demonstrated the feasibility of cervical intramedullary glioma resection with the aid of high-field iopMRI. This tool was extremely useful to evaluate the extent of tumor removal and to obtain a higher resection rate, but still need some enhancement in the configuration of the headrest coil and surgical table to allow better patient positioning.

Microsurgical or radiosurgical management of intracranial cavernomas.

Cranial cavernous malformations (CCMs) constitute a heterogeneous group of lesions that tend to change dynamically over time with related periods of repeated exacerbation and alternating periods of remission. The decision on their management is based on estimating the inherent risk of further morbidity and the risk/benefit related to the particular treatment mode. Incidentally detected CCMs or lesions in asymptomatic patients presenting without major hemorrhage are best followed up. Complete resection of a CCM is the only healing option and is indicated for symptomatic or hemorrhagic lesions. In the large published series 83-92 % of the patients improved or remained unchanged after surgery, with only 8-11 % showing significant deterioration. For most patients, quality of life is improved. Analysis of the risk/benefit ratio for radiosurgery shows that it should not be regarded as an alternative option: It confers limited protection against bleeding and is related to a certain morbidity risk. In the subgroup of patients with symptomatic or hemorrhagic CCMs in locations that preclude surgical resection with acceptable risks, we recommend follow-up. The senior author is following a group of more than 80 such patients, and the vast majority remain free of hemorrhage and symptoms.

Intra-operative high frequency ultrasound improves surgery of intramedullary cavernous malformations.

Intra-operative ultrasound (ioUS) is a very useful tool in surgery of spinal lesions. Here we focus on modern ioUS to analyze its use for localisation, visualisation and resection control in intramedullary cavernous malformations (IMCM). A series of 35 consecutive intradural lesions were operated in our hospital in a time period of 24 months using modern ioUS with a high frequency 7-15 MHz transducer and a true real time 3D transducer (both Phillips iU 22 ultrasound system). Six of those cases were treated with the admitting diagnosis of a deep IMCM (two cervical, four thoracic lesions). IoUS images were performed before and after the IMCM resection. Pre-operative and early postoperative MRI images were performed in all patients. In all six IMCM cases a complete removal of the lesion was achieved microsurgically resulting in an improved neurological status of all patients. High frequency ioUS emerged to be a very useful tool during surgery for localization and visualization. Excellent resection control by ultrasound was possible in three cases. Minor resolution of true real time 3D ioUS decreases the actual advantage of simultaneous reconstruction in two planes. High frequency ioUS is the best choice for intra-operative imaging in deep IMCM to localize and to visualize the lesion and to plan the perfect surgical approach. Additionally, high frequency ioUS is suitable for intra-operative resection control of the lesion in selected IMCM cases.

Differences in the MRI Signature and ADC Values of Diffuse Midline Gliomas with H3 K27M Mutation Compared to Midline Glioblastomas.

We conducted a two-center retrospective survey on standard MRI features including apparent diffusion coefficient mapping (ADC) of diffuse midline gliomas H3 K27M-mutant (DMG) compared to midline glioblastomas H3 K27M-wildtype (midGBM-H3wt). We identified 39 intracranial DMG and 18 midGBM-H3wt tumors. Samples were microscopically re-evaluated for microvascular proliferations and necrosis. Image analysis focused on location, peritumoral edema, degree of contrast enhancement and DWI features. Within DMG, MRI features between tumors with or without histomorphological GBM features were compared. DMG occurred in 15/39 samples from the thalamus (38%), in 23/39 samples from the brainstem (59%) and in 1/39 tumors involving primarily the cerebellum (2%). Edema was present in 3/39 DMG cases (8%) versus 78% in the control (midGBM-H3wt) group (p < 0.001). Contrast enhancement at the tumor rim was detected in 17/39 DMG (44%) versus 67% in control (p = 0.155), and necrosis in 24/39 (62%) versus 89% in control (p = 0.060). Strong contrast enhancement was observed in 15/39 DMG (38%) versus 56% in control (p = 0.262). Apparent diffusion coefficient (ADC) histogram analysis showed significantly higher skewness and kurtosis values in the DMG group compared to the controls (p = 0.0016/p = 0.002). Minimum relative ADC (rADC) values, as well as the 10th and 25th rADC-percentiles, were lower in DMGs with GBM features within the DMG group (p < 0.001/p = 0.012/p = 0.027). In conclusion, DMG cases exhibited markedly less edema than midGBM-H3wt, even if histomorphological malignancy was present. Histologically malignant DMGs and midGBM-H3wt more often displayed strong enhancement, as well as rim enhancement, than DMGs without histomorphological malignancy. DMGs showed higher skewness and kurtosis values on ADC-histogram analysis compared to midGBM-H3wt. Lower minimum rADC values in DMGs indicated malignant histomorphological features, likely representing a more complex tissue microstructure.

Advantages and limitations of intraoperative 3D ultrasound in neurosurgery. Technical note.

Three-dimensional ultrasound (US) technology is supposed to help combat some of the orientation difficulties inherent to two-dimensional US. Contemporary navigation solutions combine reconstructed 3D US images with common navigation images and support orientation. New real-time 3D US (without neuronavigation) is more time effective, but whether it further assists in orientation remains to be determined. An integrated US system (IGSonic, VectorVision, BrainLAB, Munich Germany) and a non-integrated system with real-time 3D US (iU22, Philips, Bothell, USA) were recently compared in neurosurgical procedures in our group. The reconstructed navigation view was time-consuming, but images were displayed in familiar planes (e.g., axial, sagittal, coronal). Further potential applications of US angiography and pure US navigation are possible. Real-time 3D images were displayed without the need for an additional acquisition and reconstruction process, but spatial orientation remained challenging in this preliminary testing phase. Reconstructed 3D US navigation appears to be superior with respect to spatial orientation, and the technique can be combined with other imaging data. However, the potential of real-time 3D US imaging is promising.

Motor-evoked potentials (MEP) during brainstem surgery to preserve corticospinal function.

BACKGROUND: Brainstem surgery bears a risk of damage to the corticospinal tract (CST). Motor-evoked potentials (MEPs) are used intraoperatively to monitor CST function in order to detect CST damage at a reversible stage and thus impede permanent neurological deficits. While the method of MEP is generally accepted, warning criteria in the context of brainstem surgery still have to be agreed on. METHOD: We analyzed 104 consecutive patients who underwent microsurgical resection of lesions affecting the brainstem. Motor grade was documented prior to surgery, early postoperatively and at discharge. A baseline MEP stimulation intensity threshold was defined and intraoperative testing aimed to keep MEP response amplitude constant. MEPs were considered deteriorated and the surgical team was notified whenever the threshold was elevated by ≥20 mA or MEP response fell under 50%. FINDINGS: On the first postoperative day, 18 patients experienced new paresis that resolved by discharge in 11. MEPs deteriorated in 39 patients, and 16 of these showed new postoperative paresis, indicating a 41% risk of new paresis. In the remaining 2/18 patients, intraoperative MEPs were stable, although new paresis appeared postoperatively. In one of these patients, intraoperative hemorrhage caused postoperative swelling, and the new motor deficit persisted until discharge. Of all 104 patients, 7 deteriorated in motor grade at discharge, 92 remained unchanged, and 5 patients have improved. CONCLUSIONS: Adjustment of surgical strategy contributed to good motor outcome in 33/39 patients. MEP monitoring may help significantly to prevent motor deficits during demanding neurosurgical procedures on the brainstem.

Diffuse midline gliomas, H3 K27M-mutant are associated with less peritumoral edema and contrast enhancement in comparison to glioblastomas, H3 K27M-wildtype of midline structures.

PURPOSE: The entity 'diffuse midline glioma, H3 K27M-mutant (DMG)' was introduced in the revised 4th edition of the 2016 WHO classification of brain tumors. However, there are only a few reports on magnetic resonance imaging (MRI) of these tumors. Thus, we conducted a retrospective survey focused on MRI features of DMG compared to midline glioblastomas H3 K27M-wildtype (mGBM-H3wt). METHODS: We identified 24 DMG cases and 19 mGBM-H3wt patients as controls. After being retrospectively evaluated for microscopic evidence of microvascular proliferations (MVP) and tumor necrosis by two experienced neuropathologists to identify the defining histological criteria of mGBM-H3wt, the samples were further analyzed by two experienced readers regarding imaging features such as shape, peritumoral edema and contrast enhancement. RESULTS: The DMG were found in the thalamus in 37.5% of cases (controls 63%), in the brainstem in 50% (vs. 32%) and spinal cord in 12.5% (vs. 5%). In MRI and considering MVP, DMG were found to be by far less likely to develop peritumoral edema (OR: 0.13; 95%-CL: 0.02-0.62) (p = 0.010). They, similarly, were associated with a significantly lower probability of developing strong contrast enhancement compared to mGBM-H3wt (OR: 0.10; 95%-CL: 0.02-0.47) (P = 0.003). CONCLUSION: Despite having highly variable imaging features, DMG exhibited markedly less edema and lower contrast enhancement in MRI compared to mGBM-H3wt. Of these features, the enhancement level was associated with evidence of MVP.