Complications of Endovascular and Open Aneurysm Surgery in the Era of Flow Diversion.

The techniques used for treatment of intracranial aneurysms have progressed dramatically over the decades. The introduction of modern endovascular techniques and the continued refinement of progressively less invasive neurosurgical approaches have contributed to steadily improving clinical outcomes. Moreover, innovations such as flow-diverting stents have achieved dramatic success and have gained rapid widespread adoption. Particularly in lesions for which the application of conventional treatment techniques is difficult, flow diversion technology has revolutionized aneurysm management. This review provides a discussion on the morbidity and mortality encountered in the treatment of intracranial aneurysms in the modern era. Common adverse events faced in the management of these lesions with open surgery and various endovascular techniques are highlighted.

Nocardial clival osteomyelitis secondary to sphenoid sinusitis: an atypical skull base infection.

Clival osteomyelitis is a life-threatening complication of untreated malignant otitis externa or paranasal sinus infection. Although various pathogens have been implicated, to our knowledge, primary nocardial clival osteomyelitis has never been reported. We describe a 74-year-old woman who presented with headaches, abducens and hypoglossal nerve palsies, facial numbness, photophobia, and neck stiffness. Imaging revealed a heterogeneous mass within the sphenoid sinus with clival extension. The lesion was extirpated via a binostril endoscopic endonasal transsphenoidal approach. Histopathological and microbiological examination revealed a nocardial source. Clival osteomyelitis associated with sphenoid sinusitis should be included in the differential diagnosis of progressive skull base lesions in the setting of an underlying infection. Early recognition and intervention with antibiotics and surgical debridement is essential in the management of this rare entity.

Cerebral venous sinus thrombosis after vestibular schwannoma surgery: a call for evidence-based management guidelines.

OBJECTIVE Postoperative cerebral venous sinus thrombosis (CVST) is an uncommon complication of posterior fossa surgery. The true incidence of and optimal management strategy for this entity are largely unknown. Herein, the authors report their institutional incidence and management experience of postoperative CVST after vestibular schwannoma surgery. METHODS The authors undertook a retrospective review of all vestibular schwannoma cases that had been treated with microsurgical resection at a single institution from December 2011 to September 2017. Patient and tumor characteristics, risk factors, length of stay, surgical approaches, sinus characteristics, CVST management, complications, and follow-up were analyzed. RESULTS A total of 116 patients underwent resection of vestibular schwannoma. The incidence of postoperative CVST was 6.0% (7 patients). All 7 patients developed lateral CVST ipsilateral to the lesion. Four cases occurred after translabyrinthine approaches, 3 occurred after retrosigmoid approaches, and none occurred following middle cranial fossa approaches. Patients were managed with anticoagulation or antiplatelet therapy. Although patients were generally asymptomatic, one patient experienced intraparenchymal hemorrhage, epidural hemorrhage, and obstructive hydrocephalus, likely as a result of the anticoagulation therapy. However, all 7 patients had a modified Rankin scale score of 1 at the last follow-up. CONCLUSIONS Postoperative CVST is an infrequent complication, with an incidence of 6.0% among 116 patients who had undergone vestibular schwannoma surgery at one institution. Moreover, the management of postoperative CVST with anticoagulation therapy poses a serious dilemma to neurosurgeons. Given the paucity of reports in the literature and the low incidence of CVST, additional studies are needed to better understand the cause of thrombus formation and help to establish evidence-based guidelines for CVST management and prevention.

Beyond textbook neuroanatomy: The syndrome of malignant PCA infarction.

Given its limited vascular territory, occlusion of the posterior cerebral artery (PCA) usually does not result in malignant infarction. Challenging this concept, we present 3 cases of unilateral PCA infarction with secondary malignant progression, resulting from extension into what would classically be considered the posterior middle cerebral artery (MCA) territory. Interestingly, these were true PCA infarctions, not "MCA plus" strokes, since the underlying occlusive lesion was in the PCA. We hypothesize that congenital and/or acquired variability in the distribution and extent of territory supplied by the PCA may underlie this rare clinical entity. Patients with a PCA infarction should thus be followed closely and offered early surgical decompression in the event of malignant progression.

Ventriculostomy-associated infection: a new, standardized reporting definition and institutional experience.

OBJECTIVE: Shortcomings created by the lack of both a uniform definition of ventriculostomy-associated infection (VAI) and reporting standards have led to widely ranging infections rates (2-24%) whose significance is uncertain. We propose a standardized definition of VAI and a consistent reporting format compliant with Centers for Disease Control and Prevention (CDC) for device-related infections. Using those parameters to establish an infection-control surveillance program, we report our 4-year institutional VAI rates. METHODS: In this prospective study covering ventriculostomy utilization (October 2006-December 2010), 498 patients had a total of 4,673 ventriculostomy days. By review of the literature and our institutional analysis, we defined VAI as a positive CSF culture in a patient with ventriculostomy catheter, plus one or more of the following (1) fever recorded >101.5 °F or (2) cerebrospinal fluid (CSF) glucose level, either <50 mg/dL or <50% of a serum glucose level drawn within 24 h of the CSF glucose. In a report format that is CDC compliant, rates of VAI are reported. RESULTS: Among our patients, the CDC-compliant infection rate was 2.14 per 1,000 ventriculostomy days. Of the 10 VAIs occurring in 498 patients during 4,673 ventriculostomy days, this 2.0% infection rate was lower than the previously reported 8.8% composite rates of VAI. Average duration of ventriculostomy was 9.4 days. Neither antibiotic-impregnated catheters nor periprocedural or prophylactic antibiotics were used. CONCLUSIONS: Our standardized VAI definition and CDC format seems promising toward facilitating future study and guideline development. Given our strict protocol of sterile catheter placement and care, and our institution's low 2.0% infection rates, we propose an infection-rate target of ≤5 per 1,000 device days. Our results suggest that the use of antibiotics or antibiotic-impregnated catheters is unwarranted--a positive given concerns of evolving anti-microbial resistance.

Postischemic Trigeminal Neuropathy Treated With Radiofrequency Ablation.

Trigeminal neuralgia is a pain syndrome that is defined by sharp electrical shock-like pain that radiates in the sensory distribution of the trigeminal nerve. The classical cause of this syndrome is vascular compression, but other causes, such as stroke, have also been described. Instances of post-ischemic trigeminal pain have been described as meeting the classic description, and are termed trigeminal neuropathy. The treatment paradigms for trigeminal neuralgia versus neuropathy differ significantly, especially with the consideration of surgical management.We present a case of a 78-year-old man with post-ischemic trigeminal neuropathy that was successfully treated with radiofrequency ablation after failure of conservative management.We also summarize three previous cases of post-ischemic trigeminal neuropathy that were also successfully treated with percutaneous surgical treatment, showing that percutaneous surgical management should be considered in patients with post-ischemic trigeminal neuropathy that fail conservative management.

Local Control and Survival Outcomes After Stereotactic Radiosurgery for Brain Metastases From Gastrointestinal Primaries: An International Multicenter Analysis.

BACKGROUND: There are limited data regarding outcomes for patients with gastrointestinal (GI) primaries and brain metastases treated with stereotactic radiosurgery (SRS). OBJECTIVE: To examine clinical outcomes after SRS for patients with brain metastases from GI primaries and evaluate potential prognostic factors. METHODS: The International Radiosurgery Research Foundation centers were queried for patients with brain metastases from GI primaries managed with SRS. Primary outcomes were local control (LC) and overall survival (OS). Kaplan-Meier analysis was used for univariate analysis (UVA) of prognostic factors. Factors significant on UVA were evaluated with a Cox multivariate analysis proportional hazards model. Logistic regressions were used to examine correlations with RN. RESULTS: We identified 263 eligible patients with 543 brain metastases. Common primary sites were rectal (31.2%), colon (31.2%), and esophagus (25.5%) with a median age of 61.6 years (range: 37-91.4 years) and a median Karnofsky performance status (KPS) of 90% (range: 40%-100%). One-year and 2-year LC rates were 83.5% (95% CI: 78.9%-87.1%) and 73.0% (95% CI: 66.4%-78.5%), respectively. On UVA, age >65 years ( P = .001), dose <20 Gy ( P = .006) for single-fraction plans, KPS <90% ( P < .001), and planning target volume ≥2cc ( P = .007) were associated with inferior LC. All factors other than dose were significant on multivariate analysis ( P ≤ .002). One-year and 2-year OS rates were 68.0% (95% CI: 61.5%-73.6%) and 31.2% (95% CI: 24.6%-37.9%), respectively. Age > 65 years ( P = .006), KPS <90% ( P = .005), and extracranial metastases ( P = .05) were associated with inferior OS. CONCLUSION: SRS resulted in comparable LC with common primaries. Age and KPS were associated with both LC and OS with planning target volume and extracranial metastases correlating with LC and OS, respectively. These factors should be considered in GI cancer patient selection for SRS.

Local control and survival after stereotactic radiosurgery for colorectal cancer brain metastases: an international multicenter analysis.

OBJECTIVE: The goal of this study was to characterize local tumor control (LC), overall survival (OS), and safety of stereotactic radiosurgery for colorectal brain metastasis (CRBM). METHODS: Ten international institutions participating in the International Radiosurgery Research Foundation provided data for this retrospective case series. This study included 187 patients with CRBM (281 tumors), with a median age of 62 years and 56.7% being male. Most patients (53.5%) had solitary tumors, although 10.7% had > 5 tumors. The median tumor volume was 2.7 cm3 (IQR 0.22-8.1 cm3), and the median margin dose was 20 Gy (IQR 18-22 Gy). RESULTS: The 3-year LC and OS rates were 72% and 20%, respectively. Symptomatic adverse radiation effects occurred in 1.6% of patients. In the multivariate analysis, age > 65 years and tumor volume > 4.0 cm3 were significant predictors of tumor progression (hazard ratio [HR] 2.6, 95% CI 1.4-4.9; p = 0.003 and HR 3.4, 95% CI 1.7-6.9; p < 0.001, respectively). Better performance status (Karnofsky Performance Scale score > 80) was associated with a reduced risk of tumor progression (HR 0.38, 95% CI 0.19-0.73; p = 0.004). Patient age > 62 years (HR 1.6, 95% CI 1.1-2.3; p = 0.03) and the presence of active extracranial disease (HR 1.7, 95% CI 1.1-2.4; p = 0.009) were significantly associated with worse OS. CONCLUSIONS: Stereotactic radiosurgery offers a high LC rate and a low rate of symptomatic adverse radiation effects for the majority of CRBMs. The OS and LC favored younger patients with high functional performance scores and inactive extracranial disease.

Asparaginyl endopeptidase cleaves TDP-43 in brain.

TAR DNA-binding protein 43 (TDP-43) is a nuclear protein involved in RNA splicing and a major protein component in ubiquitin-positive, tau-negative inclusions of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Under disease conditions, TDP-43 redistributes to the cytoplasm where it can be phosphorylated, ubiquitinated, and proteolytically cleaved. Enzymes responsible for TDP-43 proteolytic processing in brain remain largely unreported. Using a MS approach, we identified two truncated TDP-43 peptides, terminating C-terminal to asparagines 291 (N291) and 306 (N306). The only documented mammalian enzyme capable of cleaving C-terminal to asparagine is asparaginyl endopeptidase (AEP). TDP-43-immunoreactive fragments (~35 and 32 kDa) predicted to be generated by AEP cleavage at N291 and N306 were observed by Western blot analyses of postmortem frontotemporal lobar degeneration brain tissue and cultured human cells over-expressing TDP-43. Studies in vitro determined that AEP can directly cleave TDP-43 at seven sites, including N291 and N306. Western blots of brain homogenates isolated from AEP-null mice and wild-type littermate controls revealed that TDP-43 proteolytic fragments were substantially reduced in the absence of AEP in vivo. Taken together, we conclude that TDP-43 is cleaved by AEP in brain. Moreover, these data highlight the utility of combining proteomic strategies in vitro and in vivo to provide insight into TDP-43 biology that will fuel the design of more detailed models of disease pathogenesis.

Quantitative analysis of the detergent-insoluble brain proteome in frontotemporal lobar degeneration using SILAC internal standards.

A hallmark of neurodegeneration is the aggregation of disease related proteins that are resistant to detergent extraction. In the major pathological subtype of frontotemporal lobar degeneration (FTLD), modified TAR-DNA binding protein 43 (TDP-43), including phosphorylated, ubiquitinated, and proteolytically cleaved forms, is enriched in detergent-insoluble fractions from post-mortem brain tissue. Additional proteins that accumulate in the detergent-insoluble FTLD brain proteome remain largely unknown. In this study, we used proteins from stable isotope-labeled (SILAC) human embryonic kidney 293 cells (HEK293) as internal standards for peptide quantitation across control and FTLD insoluble brain proteomes. Proteins were identified and quantified by liquid-chromatography coupled with tandem mass spectrometry (LC-MS/MS) and 21 proteins were determined to be enriched in FTLD using SILAC internal standards. In parallel, label-free quantification of only the unlabeled brain derived peptides by spectral counts (SC) and G-test analysis identified additional brain-specific proteins significantly enriched in disease. Several proteins determined to be enriched in FTLD using SILAC internal standards were not considered significant by G-test due to their low total number of SC. However, immunoblotting of FTLD and control samples confirmed enrichment of these proteins, highlighting the utility of SILAC internal standard to quantify low-abundance proteins in brain. Of these, the RNA binding protein PTB-associated splicing factor (PSF) was further characterized because of structural and functional similarities to TDP-43. Full-length PSF and shorter molecular weight fragments, likely resulting from proteolytic cleavage, were enriched in FTLD cases. Immunohistochemical analysis of PSF revealed predominately nuclear localization in control and FTLD brain tissue and was not associated with phosphorylated pathologic TDP-43 neuronal inclusions. However, in a subset of FTLD cases, PSF was aberrantly localized to the cytoplasm of oligodendrocytes. These data raise the possibility that PSF directed RNA processes in oligodendrocytes are altered in neurodegenerative disease.

Multiplex SILAC analysis of a cellular TDP-43 proteinopathy model reveals protein inclusions associated with SUMOylation and diverse polyubiquitin chains.

Transactive response (TAR) DNA-binding protein 43 (TDP-43) is a major protein component within ubiquitin-positive inclusions of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Although TDP-43 is a nuclear DNA/RNA-binding protein, in pathological conditions, TDP-43 has been reported to redistribute to the cytoplasm where it is cleaved and forms insoluble, ubiquitinated, and phosphorylated inclusions. Here we present a cellular model in which full-length human TDP-43 or a splicing isoform (TDP-S6) that lacks the C terminus is overexpressed in a human cell line and mouse primary neurons. Whereas recombinant and endogenous TDP-43 was primarily localized in the nucleus, the shorter TDP-S6 formed highly insoluble cytoplasmic and nuclear inclusions reminiscent of disease-specific pathology. Western blot analysis of detergent-insoluble extracts showed an increase in high molecular weight immunoreactive species for TDP-S6 compared with TDP-43, consistent with ubiquitination or ubiquitin-like modifications. We used a multiplex stable isotope labeling with amino acids in cell culture approach to compare the detergent-insoluble proteome from mock-, TDP-43-, and TDP-S6-transfected cells. TDP-S6 overexpression caused a concomitant increase in both ubiquitin (Ub) and the small Ub-like modifier-2/3 (SUMO-2/3) within the insoluble proteome. Similarly, full-length TDP-43 overexpression also resulted in the elevation of SUMO-2/3. Immunofluorescence showed strong co-localization of endogenous Ub with both cytoplasmic and nuclear TDP-S6 inclusions, whereas SUMO-2/3 was co-localized mainly with the nuclear inclusions. Quantitative mass spectrometry further revealed that mixed Lys-48 and Lys-63 polyUb linkages were associated with the TDP insoluble fractions. Together our data indicate that expression of a TDP-43 splice variant lacking a C terminus recapitulates many of the cellular and biochemical features associated with disease pathology and that the interplay of ubiquitination and SUMOylation may have an important role in TDP-43 regulation.

A Case Study Using Papaya Leaf Extract to Reverse Chemotherapy-Induced Thrombocytopenia in a GBM Patient.

Chemotherapy-induced thrombocytopenia (CIT) is a critical condition in which platelet counts are abnormally reduced following the administration of chemotherapeutic compounds. CIT poses a treatment conundrum to clinicians given the increased risk of spontaneous bleeding, obstacles to surgical management of tumors, and exclusion from clinical trials. Treatment of CIT involves the removal of the offending agent combined with platelet infusion or thrombopoietin agonist treatment. However, due to the autoimmune and infection risks associated with infusions, this treatment is only reserved for patients with critically low platelet counts. One potential solution for patients in the mid to low platelet count range is Carica papaya leaf extract (CPLE). In this case, we report the novel use of CPLE as a method of bolstering platelet counts in a patient presenting with CIT. The patient was initiated on CPLE therapy consisting of 1 tablespoon twice daily with meals. Following CPLE treatment, the patient's platelet counts rebounded from less than 10,000/µL to 113,000/µL. This clinical vignette supports the use of CPLE in the clinical context of CIT when thrombopoietin agonists are not a viable option. The potential benefits of CPLE as a method for increasing platelet count deserve further exploration, especially as a treatment option for refractory patients or those ill-suited for other traditional thrombocytopenia therapies.

Pearls & Oy-sters: Pivoting Treatment Regimens of Pediatric Atypical Teratoid Rhabdoid Tumors to Optimize Care in Adult ATRT: A Case Report.

Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant embryonal tumor of the CNS, largely affecting pediatric patients, with exceedingly rare cases in adults at an estimated annual incidence of 1/1,000,000. We report a unique case of ATRT in a 43-year-old female patient who first presented with progressive focal headaches. Imaging revealed a sellar mass with suprasellar extensions, which was partially removed via a transsphenoidal resection. The tumor aggressively recurred just 1 month postoperatively. Her care team pursued a novel treatment plan by using a slightly modified COG ACNS 0332 regimen, which involved radiation, followed by 4 cycles of monthly chemotherapy including vincristine, cyclophosphamide, and cisplatin. Hematopoietic stem cells were collected between radiation and chemotherapy in the event that the patient required stem cell salvage therapy postadjuvant chemotherapy. The MRIs taken at 2 and 4 months postrecurrence indicated a substantial decrease in tumor volume, with corresponding clinical improvements to cranial nerve deficits. Given the scarcity of literature on adult cases of ATRT and the lack of a standard of care for these cases, discussing the efficacy of our patient's treatment plan may aid clinical decision making for adult ATRT cases.

Spontaneous Cerebrospinal Fluid Rhinorrhea from a Prolactin-Secreting Pituitary Macroadenoma.

Cerebrospinal fluid (CSF) rhinorrhea is a rare complication of macroprolactinomas that, in the vast majority of cases, is subsequent to either medical or surgical intervention. Here, we present the successful management of a rare case of spontaneous, noniatrogenic CSF rhinorrhea in a patient with an untreated macroprolactinoma. A 27-year-old man with no significant medical history presented with six months of persistent CSF rhinorrhea, which was confirmed by testing for beta-2-transferrin. He had had decreased libido since adolescence and impaired growth of secondary sexual characteristics. Workup revealed an elevated prolactin level, and imaging demonstrated erosion of the anterior sellar floor and soft tissue within the sphenoid sinus, concerning for tumor. The patient underwent surgical repair of the CSF leak via a transnasal transsphenoidal approach, with resection and biopsy of tumor material within the sinus. No tumor was noted within the sella itself. The patient tolerated the procedure well and had subsequent normalization of his prolactin level with no further CSF egress. Spontaneous noniatrogenic CSF rhinorrhea, although rare, should be considered in the differential diagnosis of invasive pituitary macroadenomas, especially prolactinomas. The mechanism of CSF leak from a prolactinoma is not completely understood, but the CSF leak should be urgently repaired through a transnasal transsphenoidal approach. Concurrently, tumor resection should be performed and a postoperative lumbar puncture or lumbar drain should be considered to reinforce the skull base reconstruction.

Repeat Resection of a Cavernous Malformation of the Optic Nerve/Chiasm via a Frontotemporal Approach: 2-Dimensional Operative Video.

Cavernous malformations are benign vascular lesions that can arise throughout the central nervous system. The occurrence of a cavernous malformation within the optic nerve or chiasm, however, is extremely uncommon. The case described in this video involved a 36-yr-old woman who presented 3 mo after undergoing a left frontotemporal craniotomy for resection of an optic nerve cavernous malformation. She had initially presented to an outside hospital with vision loss, and the left optic nerve lesion was identified and resected. Although her vision had reportedly improved slightly postoperatively, she awoke 3 mo later with bilateral subjective blurriness and new visual field deficits. Magnetic resonance imaging revealed enlargement of the left optic apparatus hemorrhagic lesion, corresponding to residual cavernous malformation. Given the recurrence of hemorrhage and the associated visual symptoms, the patient underwent a redo left frontotemporal craniotomy for resection of the optic nerve and chiasmal lesion. Histopathologic evaluation revealed thick-walled vessels with focal intervening glial tissue, an absence of neoplastic cells, and hemorrhage, consistent with a cavernous malformation. The patient tolerated the procedure well. Postoperatively, she experienced immediate amelioration in her visual symptoms. She was discharged home on postoperative day 3, and her bitemporal visual field deficit continued to progressively improve through her last ophthalmologic appointment 14 mo after surgery. Postoperative and subsequent surveillance neuroimaging demonstrated complete resection of the cavernous malformation without evidence of recurrence. This case demonstrates the techniques utilized to ensure complete resection of the malformation in this very eloquent region. The patient provided consent for publication.

Internal Auditory Canal Variability: Anatomic Variation Affects Cisternal Facial Nerve Visualization.

BACKGROUND: The internal auditory canal (IAC) is an important landmark during surgery for lesions of the cerebellopontine angle. There is significant variability in the position and orientation of the IAC radiographically, and the authors have noted differences in surgical exposure depending on the individual anatomy of the IAC. OBJECTIVE: To test the hypothesis that IAC position and orientation affects the surgical exposure of the IAC and facial nerve, especially when performing the translabyrinthine approach. METHODS: The authors retrospectively reviewed magnetic resonance imaging studies of 50 randomly selected patients with pathologically confirmed vestibular schwannomas. Measurements, including the anterior (APD) and posterior (PPD) petrous distances, the anterior (APA) and posterior (PPA) petro-auditory angles, and the internal auditory angle (IAA), were obtained to quantify the position and orientation of the IAC within the petrous temporal bone. RESULTS: The results quantitatively demonstrate tremendous variability of the position and orientation of the IAC in the petrous temporal bone. The measurement ranges were APD 10.2 to 26.1 mm, PPD 15.1 to 37.2 mm, APA 104 to 157°, PPA 30 to 96°, and IAA -5 to 40°. CONCLUSION: IAC variability can have a substantial effect on the surgical exposure of the IAC and facial and vestibulocochlear nerves. Specifically, a horizontally oriented IAC with a small IAA may have significant impact on visualization of the facial nerve within its cisternal segment with the translabyrinthine approach. The retrosigmoid approach is less affected with IAC variability in position and angle.

Outcomes of decompressive surgery for cavernous sinus meningiomas: long-term follow-up in 50 patients.

OBJECTIVE: Cavernous sinus meningiomas are complex tumors that offer a perpetual challenge to skull base surgeons. The senior author has employed a management strategy for these lesions aimed at maximizing tumor control while minimizing neurological morbidity. This approach emphasizes combining "safe" tumor resection and direct decompression of the roof and lateral wall of the cavernous sinus as well as the optic nerve. Here, the authors review their experience with the application of this technique for the management of cavernous sinus meningiomas over the past 15 years. METHODS: A retrospective analysis was performed for patients with cavernous sinus meningiomas treated over a 15-year period (2002-2017) with this approach. Patient outcomes, including cranial nerve function, tumor control, and surgical complications were recorded. RESULTS: The authors identified 50 patients who underwent subtotal resection via frontotemporal craniotomy concurrently with decompression of the cavernous sinus and ipsilateral optic nerve. Of these, 25 (50%) underwent adjuvant radiation to the remaining tumor within the cavernous sinus. Patients most commonly presented with a cranial nerve (CN) palsy involving CN III-VI (70%), a visual deficit (62%), headaches (52%), or proptosis (44%). Thirty-five patients had cranial nerve deficits preoperatively. In 52% of these cases, the neuropathy improved postoperatively; it remained stable in 46%; and it worsened in only 2%. Similarly, 97% of preoperative visual deficits either improved or were stable postoperatively. Notably, 12 new cranial nerve deficits occurred postoperatively in 10 patients. Of these, half were transient and ultimately resolved. Finally, radiographic recurrence was noted in 5 patients (10%), with a median time to recurrence of 4.6 years. CONCLUSIONS: The treatment of cavernous sinus meningiomas using surgical decompression with or without adjuvant radiation is an effective oncological strategy, achieving excellent tumor control rates with low risk of neurological morbidity.

Surgical Management of Multifocal Trigeminal Schwannomas.

BACKGROUND: Isolated trigeminal schwannomas occur in 0.07% to 0.3% of intracranial tumors and account for 0.8% to 8% of intracranial schwannomas and 1/3 of Meckel cave tumors. The presence of multisegmental schwannoma is rare, resulting in a limited understanding of its optimal management. OBJECTIVE: To describe potential surgical options to manage this rare entity. METHODS: A 2-institution retrospective review of all patients with pathologically confirmed trigeminal schwannoma managed with resection from January 2009 through January 2019 was conducted. A manual chart review was performed to verify patients' inclusion and collect data about age, sex, tumor size, tumor site, treatment modality, surgical approach, complications, and follow-up duration and status. RESULTS: A total of 4 patients (age range 12-50 yr) who underwent a variety of cranial and orbitocranial approaches for tumor resection were identified. Patients achieved good outcomes with improvement of visual outcomes. One case of infection and 1 case of partial tumor recurrence requiring reresection were identified. CONCLUSION: Multisegmental trigeminal schwannoma is a rare and unique entity, often associated with trigeminal schwannomatosis. Interdisciplinary management has been shown to be the most effective method for improving patient outcomes with these complex and poorly understood diseases.

Proteomics analysis reveals novel components in the detergent-insoluble subproteome in Alzheimer's disease.

Neurodegenerative diseases are often defined pathologically by the presence of protein aggregates. These aggregates, including amyloid plaques in Alzheimer's disease (AD), result from the abnormal accumulation and processing of proteins, and may ultimately lead to neuronal dysfunction and cell death. To date, conventional biochemical studies have revealed abundant core components in protein aggregates. However, rapidly improving proteomics technologies offer opportunities to revisit pathologic aggregate composition, and to identify less abundant but potentially important functional molecules that participate in neurodegeneration. The purpose of this study was to establish a proteomic strategy for the profiling of neurodegenerative disease tissues for disease-specific changes in protein abundance. Using high resolution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), we analyzed detergent-insoluble frontal cortex samples from AD and unaffected control cases. In addition, we analyzed samples from frontotemporal lobar degeneration (FTLD) cases to identify AD-specific changes not present in other neurodegenerative diseases. We used a labeling-free quantification technique to compare the abundance of identified peptides in the samples based on extracted ion current (XIC) of their corresponding ions. Of the 512 identified proteins, quantitation demonstrated significant changes in 81 AD-specific proteins. Following additional manual filtering, 11 proteins were accepted with high confidence as increased in AD compared to control and FTLD brains, including beta-amyloid, tau and apolipoprotein E, all well-established AD-linked proteins. In addition, we identified and validated the presence of serine protease 15, ankyrin B, and 14-3-3 eta in the detergent-insoluble fraction. Our results provide further evidence for the capacity of proteomics applications to identify conserved sets of disease-specific proteins in AD, to enhance our understanding of disease pathogenesis, and to deliver new candidates for the development of effective therapies for this, and other, devastating neurodegenerative disorders.

A Modified Lateral Orbitotomy Approach to the Superior Orbital Fissure: A Video Case Report and Review of Anatomy.

BACKGROUND: The lateral orbitotomy approach (LOA) is often used for accessing the orbital contents and middle skull base; however, most prior descriptions of the LOA involve complete drilling of the lateral orbital wall. This practice requires retraction of the orbital contents and produces postoperative diplopia that the patient experiences for a limited time. OBJECTIVE: To describe a modified LOA with partial sparing of the lateral orbital wall for accessing lesions of the superior orbital fissure (SOF). METHODS: One patient with a progressively enlarging SOF lesion and visual loss underwent a modified LOA for resection. The orbital rim lateral to the SOF was removed as a bone flap, and the greater wing of the sphenoid inferior to the SOF was drilled to expose the lesion. The lateral orbital wall was thinned but was not completely removed. The orbital rim was resecured with miniplates and screws. RESULTS: Gross total resection of the SOF mass was achieved without unnecessary exposure or retraction of the orbital contents. Histopathologic analysis of the resected mass was consistent with a cavernous hemangioma. The patient had a good cosmetic outcome without complication. CONCLUSION: Modified LOA with partial sparing of the lateral orbital wall is a feasible approach for lesions of the SOF.