Glioblastoma remodelling of human neural circuits decreases survival.

Gliomas synaptically integrate into neural circuits1,2. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth1-4 and gliomas increasing neuronal excitability2,5-8. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumour tissue biopsies and cell biology experiments, we find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumour-infiltrated cortex well beyond the cortical regions that are normally recruited in the healthy brain. Site-directed biopsies from regions within the tumour that exhibit high functional connectivity between the tumour and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumour cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumour regions compared with tumour regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 using the FDA-approved drug gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively affects both patient survival and performance in language tasks. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumour progression and impairs cognition.

Interactive Effects of Molecular, Therapeutic, and Patient Factors on Outcome of Diffuse Low-Grade Glioma.

PURPOSE: In patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible. METHODS: In a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365). Propensity score analysis of the combined cohorts (n = 757) was used to mimic a randomized clinical trial with varying levels of EOR. RESULTS: Recursive partitioning analysis identified three survival risk groups. Median OS was shortest in two subsets of patients with astrocytoma: those with postoperative tumor volume (TV) > 4.6 mL and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was seen in patients with astrocytoma who had chemotherapy with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL in addition to oligodendroglioma patients with either preoperative TV > 43.1 mL and residual TV ≤ 4.6 mL or postoperative residual volume > 4.6 mL. Longest OS was seen in astrocytoma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL who received no chemotherapy and oligodendroglioma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL. EOR ≥ 75% improved survival outcomes, as shown by propensity score analysis. CONCLUSION: Across both subtypes of LGG, EOR beginning at 75% improves OS while beginning at 80% improves progression-free survival. Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.

Diagnostic radiation-induced regression of a metastatic primary intracranial germinoma: a case report.

Pineal region germinomas are sensitive to radiotherapy. Standard neurosurgical management involves obtaining a tissue biopsy and to relieve the often accompanying obstructive hydrocephalus. We present a patient with a suspected hyper-radiosensitive metastatic primary intracranial germinoma where computed tomography scanning resulted in tumor regression before radiotherapy could be administered.

Correlation of natural language assessment results with health-related quality of life in adult glioma patients.

OBJECTIVE: Impairments of speech are common in patients with glioma and negatively impact health-related quality of life (HRQoL). The benchmark for clinical assessments is task-based measures, which are not always feasible to administer and may miss essential components of HRQoL. In this study, the authors tested the hypothesis that variations in natural language (NL) correlate with HRQoL in a pattern distinct from task-based measures of language performance. METHODS: NL use was assessed using audio samples collected unobtrusively from 18 patients with newly diagnosed low- and high-grade glioma. NL measures were calculated using manual segmentation and correlated with Quality of Life in Neurological Disorders (Neuro-QoL) outcomes. Spearman's rank-order correlation was used to determine relationships between Neuro-QoL scores and NL measures. RESULTS: The distribution of NL measures across the entire patient cohort included a mean ± SD total time speaking of 11.5 ± 2.20 seconds, total number of words of 27.2 ± 4.44, number of function words of 10.9 ± 1.68, number of content words of 16.3 ± 2.91, and speech rate of 2.61 ± 0.20 words/second. Speech rate was negatively correlated with functional domains (rho = -0.62 and p = 0.007 for satisfaction with social roles; rho = -0.74 and p < 0.001 for participation in social roles) but positively correlated with impairment domains (rho = 0.58 and p = 0.009 for fatigue) of Neuro-QoL. CONCLUSIONS: Assessment of NL at the time of diagnosis may be a useful measure in the context of treatment planning and monitoring outcomes for adult patients with glioma.

Functional alterations in cortical processing of speech in glioma-infiltrated cortex.

Recent developments in the biology of malignant gliomas have demonstrated that glioma cells interact with neurons through both paracrine signaling and electrochemical synapses. Glioma-neuron interactions consequently modulate the excitability of local neuronal circuits, and it is unclear the extent to which glioma-infiltrated cortex can meaningfully participate in neural computations. For example, gliomas may result in a local disorganization of activity that impedes the transient synchronization of neural oscillations. Alternatively, glioma-infiltrated cortex may retain the ability to engage in synchronized activity in a manner similar to normal-appearing cortex but exhibit other altered spatiotemporal patterns of activity with subsequent impact on cognitive processing. Here, we use subdural electrocorticography to sample both normal-appearing and glioma-infiltrated cortex during speech. We find that glioma-infiltrated cortex engages in synchronous activity during task performance in a manner similar to normal-appearing cortex but recruits a diffuse spatial network. On a temporal scale, we show that signals from glioma-infiltrated cortex have decreased entropy, which may affect its ability to encode information during nuanced tasks such as production of monosyllabic versus polysyllabic words. Furthermore, we show that temporal decoding strategies for distinguishing monosyllabic from polysyllabic words were feasible for signals arising from normal-appearing cortex but not from glioma-infiltrated cortex. These findings inform our understanding of cognitive processing in chronic disease states and have implications for neuromodulation and prosthetics in patients with malignant gliomas.

Balancing task sensitivity with reliability for multimodal language assessments.

OBJECTIVE: Intraoperative tasks for awake language mapping are typically selected based on the language tracts that will likely be encountered during tumor resection. However, diminished attention and arousal secondary to perioperative sedatives may reduce a task's usefulness for identifying eloquent cortex. For instance, accuracy in performing select language tasks may be high preoperatively but decline in the operating room. In the present study, the authors sought to identify language tasks that can be performed with high accuracy in both situational contexts so the neurosurgical team can be confident that speech errors committed during awake language mapping result from direct cortical stimulation to eloquent cortex, rather than from poor performance in general. METHODS: We administered five language tasks to 44 patients: picture naming (PN), text reading (TR), auditory object naming (AN), repetition of 4-syllable words (4SYL), and production of syntactically intact sentences (SYNTAX). Performance was assessed using the 4-point scale of the quick aphasia battery 24 hours preoperatively and intraoperatively. We next determined whether or not accuracy on each task was higher preoperatively than intraoperatively. We also determined whether 1) intraoperative accuracy on a given task predicted intraoperative performance on the other tasks and 2) low preoperative accuracy on a task predicted a decrease in accuracy intraoperatively. RESULTS: Relative to preoperative accuracy, intraoperative accuracy declined on PN (3.90 vs 3.82, p = 0.0001), 4SYL (3.96 vs 3.91, p = 0.0006), and SYNTAX (3.85 vs 3.67, p = 0.0001) but not on TR (3.96 vs 3.94, p = 0.13) or AN (3.70 vs 3.58, p = 0.058). Intraoperative accuracy on PN and AN independently predicted intraoperative accuracy on the remaining language tasks (p < 0.001 and p < 0.01, respectively). Finally, low preoperative accuracy on SYNTAX predicted a decrease in accuracy on this task intraoperatively (R2 = 0.36, p = 0.00002). CONCLUSIONS: While TR lacks sensitivity in identifying language deficits at baseline, accuracy on TR is stable across testing settings. Baseline accuracy on the other four of our five language tasks was not predictive of intraoperative performance, signifying the need to repeat language tests prior to stimulation mapping to confirm reliability.

Convergence of heteromodal lexical retrieval in the lateral prefrontal cortex.

Lexical retrieval requires selecting and retrieving the most appropriate word from the lexicon to express a desired concept. Few studies have probed lexical retrieval with tasks other than picture naming, and when non-picture naming lexical retrieval tasks have been applied, both convergent and divergent results emerged. The presence of a single construct for auditory and visual processes of lexical retrieval would influence cognitive rehabilitation strategies for patients with aphasia. In this study, we perform support vector regression lesion-symptom mapping using a brain tumor model to test the hypothesis that brain regions specifically involved in lexical retrieval from visual and auditory stimuli represent overlapping neural systems. We find that principal components analysis of language tasks revealed multicollinearity between picture naming, auditory naming, and a validated measure of word finding, implying the existence of redundant cognitive constructs. Nonparametric, multivariate lesion-symptom mapping across participants was used to model accuracies on each of the four language tasks. Lesions within overlapping clusters of 8,333 voxels and 21,512 voxels in the left lateral prefrontal cortex (PFC) were predictive of impaired picture naming and auditory naming, respectively. These data indicate a convergence of heteromodal lexical retrieval within the PFC.

Central Nervous System Plasticity Influences Language and Cognitive Recovery in Adult Glioma.

Gliomas exist within the framework of complex neuronal circuitry in which network dynamics influence both tumor biology and cognition. The generalized impairment of cognition or loss of language function is a common occurrence for glioma patients. The interface between intrinsic brain tumors such as gliomas and functional cognitive networks are poorly understood. The ability to communicate effectively is critically important for receiving oncological therapies and maintaining a high quality of life. Although the propensity of gliomas to infiltrate cortical and subcortical structures and disrupt key anatomic language pathways is well documented, there is new evidence offering insight into the network and cellular mechanisms underpinning glioma-related aphasia and aphasia recovery. In this review, we will outline the current understanding of the mechanisms of cognitive dysfunction and recovery, using aphasia as an illustrative model.

The Relationship Between Stimulation Current and Functional Site Localization During Brain Mapping.

BACKGROUND: Gliomas are often in close proximity to functional regions of the brain; therefore, electrocortical stimulation (ECS) mapping is a common technique utilized during glioma resection to identify functional areas. Stimulation-induced seizure (SIS) remains the most common reason for aborted procedures. Few studies have focused on oncological factors impacting cortical stimulation thresholds. OBJECTIVE: To examine oncological factors thought to impact stimulation threshold in order to understand whether a linear relationship exists between stimulation current and number of functional cortical sites identified. METHODS: We retrospectively reviewed single-institution prospectively collected brain mapping data of patients with dominant hemisphere gliomas. Comparisons of stimulation threshold were made using t-tests and ANOVAs. Associations between oncologic factors and stimulation threshold were made using multivariate regressions. The association between stimulation current and number of positive sites was made using a Poisson model. RESULTS: Of the 586 patients included in the study, SIS occurred in 3.92% and the rate of SIS events differed by cortical location (frontal 8.5%, insular 1.6%, parietal 1.3%, and temporal 2.8%; P = .009). Stimulation current was lower when mapping frontal cortex (P = .002). Stimulation current was not associated with tumor plus peritumor edema volume, world health organization) (WHO grade, histology, or isocitrate dehydrogenase (IDH) mutation status but was associated with tumor volume within the frontal lobe (P = .018). Stimulation current was not associated with number of positive sites identified during ECS mapping (P = .118). CONCLUSION: SISs are rare but serious events during ECS mapping. SISs are most common when mapping the frontal lobe. Greater stimulation current is not associated with the identification of more cortical functional sites during glioma surgery.

The influence of race and socioeconomic status on therapeutic clinical trial screening and enrollment.

PURPOSE: Under-enrollment in clinical trials significantly limits valid analyses of clinical interventions and generalizability of findings. Often it results in premature study termination, with estimates of 22% to 50% of clinical trials terminated due to poor accrual. Currently, there are limited reports addressing the influence of race/ethnicity and socioeconomic status on clinical trial enrollment in adult glioma patients. The goal of this study was to test the hypothesis that race and socioeconomic status negatively impact therapeutic clinical trial enrollment. METHODS: 988 adult patients were identified from the UCSF Tumor Board Registry and analyzed to determine the rate of therapeutic clinical trial screening and study enrollment. RESULTS: At initial diagnosis, 43.6% and 17.5% of glioma patients were screened and enrolled in a therapeutic clinical trial, respectively. At recurrence, 49.8% and 26.3% of patients were screened and enrolled in a clinical trial, respectively. Thirty-three percent of the study population belonged to a NIH-designated underrepresented minority group; Asian/Pacific-Islander comprised 19.6% of the overall cohort. On univariate analysis, only in-state location, distance to the hospital, and WHO grade were associated with enrollment at initial diagnosis and recurrence. Minority status, insurance type, median household income, and percent below poverty were not associated with clinical trial enrollment. CONCLUSION: Minority and socioeconomic status did not impact adult glioma clinical trial enrollment. Proximity to the tertiary care cancer center may be an important consideration for minority patients. Patient screening should be carefully considered in order to avoid bias based on minority and socioeconomic status.

The impact of high functional connectivity network hub resection on language task performance in adult low- and high-grade glioma.

OBJECTIVE: Gliomas are intrinsic brain tumors with the hallmark of diffuse white matter infiltration, resulting in short- and long-range network dysfunction. Preoperative magnetoencephalography (MEG) can assist in maximizing the extent of resection while minimizing morbidity. While MEG has been validated in motor mapping, its role in speech mapping remains less well studied. The authors assessed how the resection of intraoperative electrical stimulation (IES)-negative, high functional connectivity (HFC) network sites, as identified by MEG, impacts language performance. METHODS: Resting-state, whole-brain MEG recordings were obtained from 26 patients who underwent perioperative language evaluation and glioma resection that was guided by awake language and IES mapping. The functional connectivity of an individual voxel was determined by the imaginary coherence between the index voxel and the rest of the brain, referenced to its contralesional pair. The percentage of resected HFC voxels was correlated with postoperative language outcomes in tasks of increasing complexity: text reading, 4-syllable repetition, picture naming, syntax (SYN), and auditory stimulus naming (AN). RESULTS: Overall, 70% of patients (14/20) in whom any HFC tissue was resected developed an early postoperative language deficit (mean 2.3 days, range 1-8 days), compared to 33% of patients (2/6) in whom no HFC tissue was resected (p = 0.16). When bifurcated by the amount of HFC tissue that was resected, 100% of patients (3/3) with an HFC resection > 25% displayed deficits in AN, compared to 30% of patients (6/20) with an HFC resection < 25% (p = 0.04). Furthermore, there was a linear correlation between the severity of AN and SYN decline with percentage of HFC sites resected (p = 0.02 and p = 0.04, respectively). By 2.2 months postoperatively (range 1-6 months), the correlation between HFC resection and both AN and SYN decline had resolved (p = 0.94 and p = 1.00, respectively) in all patients (9/9) except two who experienced early postoperative tumor progression or stroke involving inferior frontooccipital fasciculus. CONCLUSIONS: Imaginary coherence measures of functional connectivity using MEG are able to identify HFC network sites within and around low- and high-grade gliomas. Removal of IES-negative HFC sites results in early transient postoperative decline in AN and SYN, which resolved by 3 months in all patients without stroke or early tumor progression. Measures of functional connectivity may therefore be a useful means of counseling patients about postoperative risk and assist with preoperative surgical planning.

Facial Nerve Preservation for Supraorbital Approaches: Anatomical Mapping Based on Consistent Landmarks.

BACKGROUND: The supraorbital keyhole approach (SOKA) provides a safe and advantageous access to the anterior cranial fossa. The implemented skin incision varies depending on surgeon's preferences and requirements. Facial nerve (FN) injury might appear in up to 5.6% of patients. There is a lack of validated tenets for avoiding FN injury. OBJECTIVE: To define a safety area for FN preservation during a SOKA. METHODS: Ten dried skulls and 5 injected cadaveric heads (10 sides) were used. A Cartesian frame was created with its horizontal axis at the level of the supraorbital notch and the vertical axis just lateral to the frontozygomatic junction (FZj). FNs were dissected and points along their course were registered and transferred to the Cartesian frame. RESULTS: Ten microscopic dissections of the FN were performed preserving all branches. A safety area could be defined 8 mm superior and 10 mm inferior to the FZj extending medially to the supraorbital notch and beyond. A 20 mm2 area superior and lateral to the FZj provided low probability (≤10%) of injuring the FN. Similarly, starting 4 mm inferior to the FZj, a lateral safety area was also found. A probabilistic colored heat map was built to represent the results. CONCLUSION: We provide a "safety zone" for a SOKA incision in which the probability to encounter the FN is low. Clinical studies following our method may validate our findings and add evidence to the tenets for minimizing morbidity related to the SOKA incision.

BDNF, COMT, and DRD2 polymorphisms and ability to return to work in adult patients with low- and high-grade glioma.

BACKGROUND: Cognitive and language dysfunction is common among patients with glioma and has a significant impact on survival and health-related quality of life (HRQOL). Little is known about the factors that make individual patients more or less susceptible to the cognitive sequelae of the disease. A better understanding of the individual and population characteristics related to cognitive function in glioma patients is required to appropriately stratify patients, prognosticate, and develop more efficacious treatment regimens. There is evidence that allelic variation among genes involved in neurotransmission and synaptic plasticity are related to neurocognitive performance in states of health and neurologic disease. METHODS: We studied the association of single-nucleotide polymorphism variations in brain-derived neurotrophic factor (BDNF, rs6265), dopamine receptor 2 (DRD2, rs1076560), and catechol-O-methyltransferase (COMT, rs4680) with neurocognitive function and ability to return to work in glioma patients at diagnosis and at 3 months. We developed a functional score based on the number of high-performance alleles that correlates with the capacity for patients to return to work. RESULTS: Patients with higher-performing alleles have better scores on neurocognitive testing with the Repeatable Battery for the Assessment of Neuropsychological Status and Stroop test, but not the Trail Making Test. CONCLUSIONS: A better understanding of the genetic contributors to neurocognitive performance in glioma patients and capacity for functional recovery is necessary to develop improved treatment strategies based on patient-specific factors.

Presurgical simulation for neuroendoscopic procedures: Virtual study of the integrity of neurological pathways using diffusion tensor imaging tractography.

BACKGROUND: White matter (WM) transgression is an unexplored concept in neuroendoscopy. Diffusion tensor image (DTI) tractography could be implemented as a planning and postoperative evaluation tool in functional disconnection procedures (FDPs), which are, currently, the subject of technological innovations. We intend to prove the usefulness of this planning method focused on the assessment of WM injury that is suitable for planning FDPs. METHODS: Ten cranial magnetic resonance studies (20 sides) without pathological findings were processed. Fascicles were defined by two regions of interest (ROIs) using the fiber assignment method by the continuous tracking approach. Using three-dimensional (3D) simulation and DTI tractography, we created an 8-mm virtual endoscope and an uninjured inferior fronto-occipital fasciculus (IFOF) from two ROIs. The injured tract was generated using a third ROI built from the 3D model of the intersection of the oriented trajectory of the endoscope with the fascicle. Data and images were quantitatively and qualitatively analyzed. RESULTS: The average percentage of the injured fibers was 32.0% (range: 12.4%-70%). The average intersected volume was 1.1 cm3 (range: 0.3-2.3 cm3). Qualitative analysis showed the inferior medial quadrant of the inferior fronto-occipital fasciculus (IFOF) as the most frequently injured region. No hemispherical asymmetry was found (P > 0.5). CONCLUSION: DTI tractography is a useful surgical planning tool that could be implemented in several endoscopic procedures. Together with a functional atlas, the presented technique provides a noninvasive method to assess the potential sequelae and thus to optimize the surgical route. The suggested method could be implemented to analyze pathological WM fascicles and to assess the surgical results of FDP such as hemispherotomy or amygdalohippocampectomy. More studies are needed to overcome the limitations of the tractography based information and to develop more anatomically and functionally reliable planning systems.

Assessment of wakefulness during awake craniotomy to predict intraoperative language performance.

OBJECTIVE: Maximal safe tumor resection in language areas of the brain relies on a patient's ability to perform intraoperative language tasks. Assessing the performance of these tasks during awake craniotomies allows the neurosurgeon to identify and preserve brain regions that are critical for language processing. However, receiving sedation and analgesia just prior to experiencing an awake craniotomy may reduce a patient's wakefulness, leading to transient language and/or cognitive impairments that do not completely subside before language testing begins. At present, the degree to which wakefulness influences intraoperative language task performance is unclear. Therefore, the authors sought to determine whether any of 5 brief measures of wakefulness predicts such performance during awake craniotomies for glioma resection. METHODS: The authors recruited 21 patients with dominant hemisphere low- and high-grade gliomas. Each patient performed baseline wakefulness measures in addition to picture-naming and text-reading language tasks 24 hours before undergoing an awake craniotomy. The patients performed these same tasks again in the operating room following the cessation of anesthesia medications. The authors then conducted statistical analyses to investigate potential relationships between wakefulness measures and language task performance. RESULTS: Relative to baseline, performance on 3 of the 4 objective wakefulness measures (rapid counting, button pressing, and vigilance) declined in the operating room. Moreover, these declines appeared in the complete absence of self-reported changes in arousal. Performance on language tasks similarly declined in the intraoperative setting, with patients experiencing greater declines in picture naming than in text reading. Finally, performance declines on rapid counting and vigilance wakefulness tasks predicted performance declines on the picture-naming task. CONCLUSIONS: Current subjective methods for assessing wakefulness during awake craniotomies may be insufficient. The administration of objective measures of wakefulness just prior to language task administration may help to ensure that patients are ready for testing. It may also allow neurosurgeons to identify patients who are at risk for poor intraoperative performance.

Contralateral Transfalcine Versus Ipsilateral Anterior Interhemispheric Approach for Midline Arteriovenous Malformations: Surgical and Anatomical Assessment.

BACKGROUND: The contralateral anterior interhemispheric approach (CAIA) is considered to provide surgical advantages to access deep midline lesions: wider working angle, gravity enhanced dissection and retraction, more efficient lighting, and ergonomics. Our team has previously published on the merits of using a contralateral trajectory for medial frontoparietal arteriovenous malformations (AVMs) compared with the conventional anterior interhemispheric approach (IAIA). In this article, we compare the IAIA and CAIA for the resection of medial frontoparietal AVMs using quantitative surgical and anatomical analysis. METHODS: Two models were designed mimicking the most common features of midline AVMs. The CAIA and IAIA were performed bilaterally in 10 specimens. Variables to compare technical feasibility (surgical window [SW] and surgical freedom [SF], target exposure, and angle of attack) were independently assessed using stereotactic navigation. The average SW, SF, and angle of attack were compared with the Student t test. Significance threshold was set at 0.05. RESULTS: The CITA and IAIA were similar in terms of SW, target exposure, and SF in the superior aspect of the AVM. In the depth of the interhemispheric fissure, the CAIA was significantly superior to IAIA in both AVM models: 77% wider AA for the inferior aspect of the AVM (P < 0.01) and greater SF for the draining vein (54%, P = 0.01), ipsilateral (98%, P = 0.02), and contralateral ACA (117%, P < 0.01). CONCLUSIONS: This study suggests technical superiority of the CAIA for the resection of deep midline AVMs. No objective difference was noted in the superficial areas of our models, denoting that IAIA is a safer choice for superficial AVMs. Our results set the foundation for further clinical analysis comparing both approaches.

Assessment of the endoscopic endonasal approach to the basilar apex region for aneurysm clipping.

OBJECTIVEThe expanded endoscopic endonasal approach (EEA) has shown promising results in treatment of midline skull base lesions. Several case reports exist on the utilization of the EEA for treatment of aneurysms. However, a comparison of this approach with the classic transcranial orbitozygomatic approach to the basilar apex (BAX) region is missing.The present study summarizes the results of a series of cadaveric surgical simulations for assessment of the EEA to the BAX region for aneurysm clipping and its comparison with the transcranial orbitozygomatic approach as one of the most common approaches used to treat BAX aneurysms.METHODSFifteen cadaveric specimens underwent bilateral orbitozygomatic craniotomies as well as an EEA (first without a pituitary transposition [PT] and then with a PT) to expose the BAX. The following variables were measured, recorded, and compared between the orbitozygomatic approach and the EEA: 1) number of perforating arteries counted on bilateral posterior cerebral arteries (PCAs); 2) exposure and clipping lengths of the PCAs, superior cerebellar arteries (SCAs), and proximal basilar artery; and 3) surgical area of exposure in the BAX region.RESULTSExcept for the proximal basilar artery exposure and clipping, the orbitozygomatic approach provided statistically significantly greater values for vascular exposure and control in the BAX region (i.e., exposure and clipping of ipsilateral and contralateral SCAs and PCAs). The EEA with PT was significantly better in exposing and clipping bilateral PCAs compared to EEA without a PT, but not in terms of other measured variables. The surgical area of exposure and PCA perforator counts were not significantly different between the 3 approaches. The EEA provided better exposure and control if the BAX was located ≥ 4 mm inferior to the dorsum sellae.CONCLUSIONSFor BAX aneurysms located in the retrosellar area, PT is usually required to obtain improved exposure and control for the bilateral PCAs. However, the transcranial approach is generally superior to both endoscopic approaches for accessing the BAX region. Considering the superior exposure of the proximal basilar artery obtained with the EEA, it could be a viable option when surgical treatment is considered for a low-lying BAX or mid-basilar trunk aneurysms (≥ 4 mm inferior to dorsum sellae).

The pterygoclival ligament: a novel landmark for localization of the internal carotid artery during the endoscopic endonasal approach.

Objective: The transpterygoid extension of the endoscopic endonasal approach provides exposure of the petrous apex, Meckel's cave, paraclival area, and the infratemporal fossa. Safe and efficient localization of the lacerum segment of the internal carotid artery (ICA) is a crucial part of such exposure. The aim of this study is to introduce a novel landmark for localization of the lacerum ICA. Methods: Ten cadaveric heads were prepared for transnasal endoscopic dissection. The floor of the sphenoid sinus was drilled to expose an extension of the pharyngobasilar fascia between the sphenoid floor and the pterygoid process (the pterygoclival ligament). Several features of the pterygoclival ligament were assessed. In addition, 31 dry skulls were studied to assess features of the bony groove harboring the pterygoclival ligament. Results: The pterygoclival ligament was identified bilaterally during drilling of the sphenoid floor in all specimens. The ligament started a few millimeters posterior to the posterior end of the vomer alae and invariably extended posterolaterally and superiorly to blend into the fibrous tissue around the lacerum ICA. The mean length of the ligament was 10.5 ± 1.7 mm. The mean distance between the anterior end of the ligament and midline was 5.2 ± 1.2 mm. The mean distance between the posterior end of the ligament and midline was 12.3 ± 1.4 mm. The bony pterygoclival groove was identified at the confluence of the vomer, pterygoid process of the sphenoid, and basilar part of the occipital bone, running from posterolateral to anteromedial. The mean length of the groove was 7.7 ± 1.8 mm. Its posterolateral end faced the anteromedial aspect of the foramen lacerum medial to the posterior end of the vidian canal. A clinical case illustration is also provided. Conclusions: The pterygoclival ligament is a consistent landmark for localization of the lacerum ICA. It may be used as an adjunct or alternative to the vidian nerve to localize the ICA during endoscopic endonasal surgery.