Approaches to the Middle Cerebellar Peduncle for Resection of Pontine Cavernomas.

INDICATIONS CORRIDOR AND LIMITS OF EXPOSURE: The expanded retrosigmoid approach with splitting of the horizontal cerebellar fissure provides a more direct and shorter route for central and dorsolateral pontine lesions while minimizing retraction of tracts, nuclei, and cerebellum. 1-4. ANATOMIC ESSENTIALS NEED FOR PREOPERATIVE PLANNING AND ASSESSMENT: The middle cerebellar peduncle is partially covered by the petrosal surface of the cerebellum. The horizontal cerebellar fissure (petrosal fissure) divides the petrosal surface of the cerebellar hemisphere into superior and inferior parts. Splitting the petrosal fissure separates the superior and inferior petrosal surfaces and exposes the posterolateral middle cerebellar peduncle (posterior and lateral to the root entry zone of CN5). 1-4. ESSENTIALS STEPS OF THE PROCEDURE: Expanded retrosigmoid craniotomy is performed, including unroofing of the sigmoid sinus; petrosal fissure is split to expose the posterolateral middle cerebellar peduncle; entry point for resection of the cavernoma is identified; nims stimulator stimulator is used to confirm the absence of tracts and nuclei; myelotomy is performed; and cavernoma and its draining vein (but not the developmental venous anomaly) are removed using a combination of traction and countertraction against gliotic plane. PITFALLS/AVOIDANCE OF COMPLICATIONS: Wide splitting of the horizontal cerebellar fissure minimizes retraction or resection of the cerebellum and offers the best angle of attack. Knowledge of brainstem anatomy and use of intraoperative navigation are critical to avoid complications. VARIANTS AND INDICATIONS FOR THEIR USE: Far lateral through the middle cerebellar peduncle is a variant that can be used to resect pontine cavernomas if a caudocranial trajectory is preferred.The patient consented to the procedure and to the publication of her image.

Step-by-Step Dissection of the Extreme Lateral Transodontoid Approach to the Anterior Craniovertebral Junction: Surgical Anatomy and Technical Nuances.

BACKGROUND: Multicompartmental lesions of the anterior craniovertebral junction require aggressive management. However, the lesions can be difficult to reach, and the surgical procedure is difficult to understand. The aim of this study was to create a procedural, stepwise microsurgical educational resource for junior trainees to learn the surgical anatomy of the extreme lateral transodontoid approach (ELTOA). METHODS: Ten formalin-fixed, latex-injected cadaveric heads were dissected under an operative microscope. Dissections were performed under the supervision of a skull base fellowship-trained neurosurgeon who has advanced skull base experience. Key steps of the procedure were documented with a professional camera and a high-definition video system. A relevant clinical case example was reviewed to highlight the principles of the selected approach and its application. The clinical case example also describes a rare complication: a pseudoaneurysm of the vertebral artery. RESULTS: Key steps of the ELTOA include patient positioning, skin incision, superficial and deep muscle dissection, vertebral artery dissection and transposition, craniotomy, clivus drilling, odontoidectomy, and final extradural and intradural exposure. CONCLUSIONS: The ELTOA is a challenging approach, but it allows for significant access to the anterior craniovertebral junction, which increases the likelihood of gross total lesion resection. Given the complexity of the approach, substantial training in the dissection laboratory is required to develop the necessary anatomic knowledge and to minimize approach-related morbidity.

Cytokine Profiling of Cyst Fluid and Tumor-Associated Macrophages in Cystic Vestibular Schwannoma.

BACKGROUND: The vestibular schwannoma (VS) secretome can initiate monocyte recruitment and macrophage polarization to M1 (proinflammatory) and/or M2 (protumorigenic) phenotypes, which in turn secrete additional cytokines that contribute to the tumor microenvironment. Profiling cyst fluid and cerebrospinal fluid (CSF) in cystic VS provides a unique opportunity to understand mechanisms that may contribute to tumor progression and cyst formation. HYPOTHESIS: Cystic VSs secrete high levels of cytokines into cyst fluid and express abundant M1 and M2 macrophages. METHODS: Tumor, CSF, and cyst fluid were prospectively collected from 10 cystic VS patients. Eighty cytokines were measured in fluid samples using cytokine arrays and compared with normal CSF from normal donors. Immunofluorescence was performed for CD80 + M1 and CD163 + M2 macrophage markers. Demographic, audiometric, and radiographic information was obtained through retrospective chart review. RESULTS: Cyst fluid expressed more osteopontin and monocyte chemotactic protein-1 (MCP-1; p < 0.0001), when compared with normal CSF. Cyst fluid also expressed more protein ( p = 0.0020), particularly MCP-1 ( p < 0.0001), than paired CSF from the same subjects. MCP-1 expression in cyst fluid correlated with CD80 + staining in VS tissue ( r = 0.8852; p = 0.0015) but not CD163 + staining. CONCLUSION: Cyst fluid from cystic VS harbored high levels of osteopontin and MCP-1, which are cytokines important in monocyte recruitment and macrophage polarization. MCP-1 may have a significant role in molding the tumor microenvironment, by polarizing monocytes to CD80 + M1 macrophages in cystic VS. Further investigations into the role of cytokines and macrophages in VS may lead to new avenues for therapeutic intervention.

Long-term functional outcomes and complications of microsurgical resection of brainstem cavernous malformations: a systematic review and meta-analysis.

Brainstem cavernous malformations (CMs) encompass up to 20% of all intracranial CMs and are considered more aggressive than cerebral CMs because of their high annual bleeding rates. Microsurgical resection remains the primary treatment modality for CMs, but long-term functional outcomes and complications are heterogenous in the literature. The authors performed a systematic review on brainstem CMs in 4 databases: PubMed, EMBASE, Cochrane library, and Google Scholar. We included studies that reported on the long-term functional outcomes and complications of brainstem CMs microsurgical resection. A meta-analysis was performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search yielded 4781 results, of which 19 studies met our inclusion criteria. Microsurgery was performed on 940 patients (mean age 35 years, 46.9% females). Most of the brainstem CMs were located in the pons (n = 475). The pooled proportions of improved, stable, and worsened functional outcomes after microsurgical resection of brainstem CMs were 56.7% (95% CI 48.4-64.6), 28.6% (95% CI 22.4-35.7), and 12.6% (95% CI 9.6-16.2), respectively. CMs located in the medulla were significantly (p = 0.003) associated with a higher proportion of improved outcome compared with those in the pons and midbrain. Complete resection was achieved in 93.3% (95% CI 89.8-95.7). The immediate postoperative complication rate was 37.2% (95% CI 29.3-45.9), with new-onset cranial nerve deficit being the most common complication. The permanent morbidity rate was 17.3% (95% CI 10.5-27.1), with a low mortality rate of 1% from the compiled study population during a mean follow-up of 58 months. Our analysis indicates that microsurgical resection of brainstem CMs can result in favorable long-term functional outcomes with transient complications in the majority of patients. Complete microsurgical resection of the CM is associated with a lower incidence of CM hemorrhage and the morbidity related to it.

Cotargeting Phosphoinositide 3-Kinase and Focal Adhesion Kinase Pathways Inhibits Proliferation of NF2 Schwannoma Cells.

Neurofibromatosis Type 2 (NF2) is a tumor predisposition syndrome caused by germline inactivating mutations in the NF2 gene encoding the merlin tumor suppressor. Patients develop multiple benign tumor types in the nervous system including bilateral vestibular schwannomas (VS). Standard treatments include surgery and radiation therapy, which may lead to loss of hearing, impaired facial nerve function, and other complications. Kinase inhibitor monotherapies have been evaluated clinically for NF2 patients with limited success, and more effective nonsurgical therapies are urgently needed. Schwannoma model cells treated with PI3K inhibitors upregulate activity of the focal adhesion kinase (FAK) family as a compensatory survival pathway. We screened combinations of 13 clinically relevant PI3K and FAK inhibitors using human isogenic normal and merlin-deficient Schwann cell lines. The most efficacious combination was PI3K/mTOR inhibitor omipalisib with SRC/FAK inhibitor dasatinib. Sub-GI50 doses of the single drugs blocked phosphorylation of their major target proteins. The combination was superior to either single agent in promoting a G1 cell-cycle arrest and produced a 44% decrease in tumor growth over a 2-week period in a pilot orthotopic allograft model. Evaluation of single and combination drugs in six human primary VS cell models revealed the combination was superior to the monotherapies in 3 of 6 VS samples, highlighting inter-tumor variability between patients consistent with observations from clinical trials with other molecular targeted agents. Dasatinib alone performed as well as the combination in the remaining three samples. Preclinically validated combination therapies hold promise for NF2 patients and warrants further study in clinical trials.

Treatment of Chiari malformations with craniovertebral junction anomalies: Where do we stand today?

Background: Chiari malformation type 1 (CM-1) is characterized by cerebellar tonsil herniation through the foramen magnum and can be associated with additional craniovertebral junction anomalies (CVJA). The pathophysiology and treatment for CM-1 with CVJA (CM-CVJA) is debated. Objective: To evaluate the trends and outcomes of surgical interventions for patients with CM-CVJA. Methods: A systematic review of the literature was performed to obtain articles describing surgical interventions for patients with CM-CVJA. Articles included were case series describing surgical approach; reviews were excluded. Variables evaluated included patient characteristics, approach, and postoperative outcomes. Results: The initial query yielded 403 articles. Twelve articles, published between 1998-2020, met inclusion criteria. From these included articles, 449 patients underwent surgical interventions for CM-CVJA. The most common CVJAs included basilar invagination (BI) (338, 75.3%), atlantoaxial dislocation (68, 15.1%) odontoid process retroflexion (43, 9.6%), and medullary kink (36, 8.0%). Operations described included posterior fossa decompression (PFD), transoral (TO) decompression, and posterior arthrodesis with either occipitocervical fusion (OCF) or atlantoaxial fusion. Early studies described good results using combined ventral and posterior decompression. More recent articles described positive outcomes with PFD or posterior arthrodesis in combination or alone. Treatment failure was described in patients with PFD alone that later required posterior arthrodesis. Additionally, reports of treatment success with posterior arthrodesis without PFD was seen. Conclusion: Patients with CM-CVJA appear to benefit from posterior arthrodesis with or without decompressive procedures. Further definition of the pathophysiology of craniocervical anomalies is warranted to identify patient selection criteria and ideal level of fixation.

Contralateral transfalcine approach for resection of right medial frontal AVM.

Brain arteriovenous malformations (AVMs) are high flow vascular lesions that can cause significant morbidity and mortality [1-6]. We present a case of a 23-year-old woman who initially presented to an outside institution with a ruptured right medial frontal Spetzler Martin grade II AVM. An EVD was placed and a diagnostic angiogram with partial embolization was performed. She was then transferred to our institution two months post rupture for further care. On arrival, she was trached with eyes opening to voice and localizing in bilateral upper extremities and withdrawing in bilateral lower extremities. Diagnostic angiogram demonstrated arterial supply from the right pericallosal and callosomarginal artery, right posterior cerebral artery callosomarginal branch, distal left anterior cerebral artery (ACA) branches with venous drainage via a cortical vein to the superior sagittal sinus. The patient underwent preoperative embolization of the ACA feeders followed by a contralateral interhemispheric transfalcine approach. An interhemispheric dissection was performed down to the corpus callosum and AVM feeders and draining veins were identified. The falx was then incised to expose the right medial frontal lobe. The AVM was circumferentially dissected and resected. Postoperative imaging demonstrated complete resection of the AVM. She remained at her neurological baseline immediately postoperatively and was discharged to inpatient rehab. The patient made a remarkable recovery and at three months follow up, she no longer required a tracheostomy and was neurologically intact with no complaints except for mild memory difficulties. In this video, we demonstrate the step-by-step surgical technique and review the benefits of the contralateral transfalcine approach for resection of a ruptured right medial frontal Spetzler Martin grade II AVM. The patient consented to the procedure and to the publication of her imaging in this surgical video.

Intraoperative venous congestion and brainstem venous hemorrhagic infarction during retrosigmoid for acoustic neuroma.

Venous hemorrhagic infarction is rare but can occur during acoustic neuroma resection [1-5]. We present the case of a 27-year-old male with 1.5 years of progressive headaches, tinnitus, imbalance and hearing loss. Imaging revealed a left Koos 4 acoustic neuroma. The patient underwent a retrosigmoid approach for resection. During surgery, a vein of significant size within the capsule of the tumor was encountered and was necessary to take to proceed with resection. After coagulation of the vein, intraoperative venous congestion with cerebellar edema and hemorrhagic infarction ensued, requiring resection of a portion of the cerebellum. Given the hemorrhagic nature of the tumor, continuing tumor resection was necessary to prevent postoperative hemorrhage. This was carried out until hemostasis was achieved. 85 % resection was achieved, leaving a residual against the brainstem and cisternal course of the facial nerve. Postoperatively, the patient required 5 weeks hospitalization followed by 1 month of rehabilitation. At discharge to rehabilitation, patient had trach, PEG, left House-Brackmann 5 facial weakness, left sided deafness, and right upper extremity hemiparesis (1/5). At 7 months follow up, he continued to have left House-Brackmann 5 facial weakness and left sided deafness but trach and PEG had been removed and strength had improved to 5/5. We demonstrate in this video the unfortunate and rare occurrence of intraoperative venous hemorrhagic infarction during acoustic neuroma resection - particularly for large tumors in young patients - and discuss its etiology and surgical steps that are necessary to partially remedy its devastating impact on the patient. The patient consented to the procedure and participating in this surgical video.

Management of a dural arteriovenous fistula versus arteriovenous malformation of the internal auditory canal with radiosurgery.

We present a case of a 61-year-old male who presented with an 8-month history of left hypacusis, tinnitus, and gait imbalance. MRI showed a vascular lesion in the left internal auditory canal (IAC). Angiogram showed a vascular lesion filling from the ascending pharyngeal and anterior inferior cerebellar artery (AICA) with drainage into the sigmoid sinus suggestive of either a dural arteriovenous malformation (dAVF) vs arteriovenous malformation (AVM) of the IAC. The decision was made to operate to prevent risk of future hemorrhage [1-5]. Endovascular options were not as ideal given access transarterially through the AICA would be risky, access transvenously would be difficult and it was unclear whether this lesion was a dAVF or AVM. The patient underwent a retrosigmoid approach. A tuft of arterialized vessels surrounding CN7/8 was identified and no true nidus was found so it was thought that this lesion was a dAVF. The plan was to clip the arterialized vein as is normally done for dAVF. However, there was engorgement of the vascular lesion upon clipping of the arterialized vein indicating risk of rupture if the clip was left insitu. It was too risky to drill the posterior wall of the IAC to expose the fistulous point more proximally. As a result, 2 clips were placed on the AICA branches. Postoperative angiogram showed some slowing of the vascular lesion but it was still present. Given the AICA feeder, it was decided that this lesion was a dAVF with mixed features of an AVM and the decision was made to gamma knife the lesion 3 months postoperatively. Patient underwent gamma knife targeting the dura superior to the IAC with 18 Gy at the 50 % isodose line. At 2 years follow up, the patient's symptoms improved and he remained neurologically intact. Imaging revealed complete obliteration of the dAVF. This case illustrates the step by step management of a dAVF that mimicked a true pial AVM. The patient consented to the procedure and participating in this surgical video.

Malignant Transformation of an Intracranial Epidermoid Cyst 25 Years After Initial Surgery: A Case Report and Systematic Review.

OBJECTIVE: We report a unique case of a suspected recurrent intracranial epidermoid cyst (EDC) that was found on pathology to have undergone malignant transformation to squamous cell carcinoma (SCC) approximately 25 years after initial resection. Additionally, we performed a systematic review including 94 studies reporting intracranial EDC to SCC transformation. METHODS: Ninety-four studies were included in our systematic review. PubMed, Scopus, Cochrane Central, and EMBASE were searched in April 2020 for studies regarding histologically confirmed SCC arising within an EDC. Kaplan-Meier estimations were used to estimate time to event including survival, and log rank tests were used to test for significance. All analyses were conducted using STATA 14.1 (StataCorp, College Station, Texas, USA); tests were two-sided, and statistical significance was defined using the alpha threshold of 0.05. RESULTS: The overall median time to transformation was 60 months (95% confidence interval {CI}, 12-96). Transformation time was significantly shorter in the no surgery group (10 months, 95% CI undefined) versus the other 2 groups (60 months, 95% CI, 12-72 in surgery only and 70 months, 95% CI, 9-180 in surgery + adjuvant therapy group, both P < 0.01). Overall survival was significantly longer in the surgery + adjuvant therapy group (13 months, 95% CI, 9-24) versus the other 2 groups (3 months, 95% CI, 1-7 in surgery only and 6 months, 95% CI, 1-12 in the no surgery group, both P < 0.01). CONCLUSIONS: We report a rare case of delayed malignant transformation of an intracranial EDC to SCC, occurring nearly 25 years after initial resection. Transformation time in the no-surgery group was statistically significantly shorter as compared to the surgery only and surgery + adjuvant therapy groups. Overall survival was statistically significantly higher in the surgery + adjuvant therapy group as compared to the surgery only and no surgery groups.