Age-stratified comorbid and pharmacologic analysis of patients with glioblastoma.

Background: Increased age is a strong and unfavorable prognostic factor for patients with glioblastoma (GBM). However, the relationships between stratified patient age, comorbidities, and medications have yet to be explored in GBM patient survival analyses. Objective: To evaluate co-morbid conditions, tumor-related symptoms, medication prescriptions, and subject age for patients with GBM and to establish potential targets for prospective studies. Methods: Electronic health records for 565 patients with IDHwt GBM were evaluated at a single center between January 1, 2000 and August 9, 2021 were retrospectively assessed. Data were stratified by MGMT promoter methylation status when available and were used to construct multivariable time-dependent cox models and intra-cohort hazards. Results: Younger (<65 years of age) but not older (≥65 years) GBM patients demonstrated a worse prognosis with movement related disabilities (P < 0.0001), gait/balance difficulty (P = 0.04) and weakness (P = 0.007), as well as psychiatric conditions, mental health disorders (P = 0.002) and anxiety (P = 0.001). In contrast, older but not younger GBM patients demonstrated a worse prognosis with epilepsy (P = 0.039). Both groups had worse survival with confusion/altered mental status (P = 0.023 vs < 0.000) and an improved survival with a Temozolomide prescription. Older but not younger GBM patients experienced an improved hazard with a prescription of ace-inhibitor medications (P = 0.048). Conclusion: Age-dependent novel associations between clinical symptoms and medications prescribed for co-morbid conditions were demonstrated in patients with GBM. The results of the current work support future mechanistic studies that investigate the negative relationship(s) between increased age, comorbidities, and drug therapies for differential clinical decision-making across the lifespan of patients with GBM.

Long-term quality of life outcomes in patients undergoing microsurgical resection of vestibular schwannoma.

Background: While previous studies have assessed patient reported quality of life (QOL) of various vestibular schwannoma (VS) treatment modalities, few studies have assessed QOL as related to the amount of residual tumor and need for retreatment in a large series of patients. Objective: To assess patient reported QOL outcomes following VS resection with a focus on extent of resection and retreatment. Methods: A retrospective chart review was performed using single-center institutional data of adult patients who underwent VS resection by the senior authors between 1989-2018 at Loyola University Medical Center. The Penn Acoustic Neuroma Quality of Life (PANQOL) survey was sent to all patients via postal mail. Results: Fifty-five percent of 367 total patients were female with a mean age of 61.6 years (SD 12.63). The mean period between surgery and PANQOL response was 11.4 years (IQR: 4.74-7.37). The median tumor size was 2 cm (IQR: 1.5-2.8). The mean total PANQOL score was 70 (SD 19). Patients who required retreatment reported lower overall scores (µdiff = -10.11, 95% CI: -19.48 to -0.74; p = 0.03) and face domain scores (µdiff = -20.34, 95% CI: -29.78 to -10.91; p < .001). There was no association between extent of resection and PANQOL scores in any domain. Conclusion: In an analysis of 367 patients who underwent microsurgical resection of VS, extent of resection did not affect PANQOL scores in contrast to previous reports in the literature, while the need for retreatment and facial function had a significant impact on patient-reported outcomes.

Arteriovenous malformation presenting as complex regional pain syndrome: illustrative case.

BACKGROUND: Complex regional pain syndrome (CRPS) is typically described as a peripheral nerve disorder in which exaggerated allodynia and hyperalgesia follow a minor injury. Some researchers propose a central mechanism, although current evidence is lacking. OBSERVATIONS: A 14-year-old female presented with classic CRPS symptoms of left upper-extremity weakness and hyperalgesia after a bout of sharp pain in her thumb while shoveling snow. A possible seizure prompted magnetic resonance imaging, revealing a right frontal Spetzler-Martin grade II arteriovenous malformation (AVM) adjacent to the primary motor cortex. Brodmann areas 1, 3a, and 3b, which are responsible for localizing and processing burning and painful sensations, were also involved. The patient underwent transarterial Onyx embolization in two sessions and microsurgical resection, after which her CRPS symptoms completely resolved. LESSONS: To our knowledge, this is the first reported case of a cerebral AVM presenting as CRPS, which supports a central mechanism. The authors propose that rapid growth of the AVM led to a vascular steal phenomenon of surrounding parenchyma, which disrupted the patient's normal motor function and nociceptive processing. Further validation in other series is needed.

Is There a Plateau to the Learning Curve for Acoustic Neuroma Resection?-Experience and Outcomes from a Single Interdisciplinary Team Over Thirty Years.

Objective The evolution of acoustic neuroma (AN) care continues to shift focus on balancing optimized tumor resection and control with preservation of neurological function. Prior learning curve analyses of AN resection have demonstrated a plateau between 20 and 100 surgeries. In this study of 860 consecutive AN surgeries, we investigate the presence of an extended learning curve tail for AN resection. Methods A retrospective cohort study of AN resections by a single interdisciplinary team between 1988 and 2018 was performed. Proportional odds models and restricted cubic splines were used to determine the association between the timing of surgery and odds of improved postoperative outcomes. Results The likelihood of improved postoperative House-Brackmann (HB) scores increased in the first 400 procedures, with HB 1 at 36% in 1988 compared with 79% in 2004. While the probability of a better HB score increased over time, there was a temporary decrease in slope of the cubic spline between 2005 and 2009. The last 400 cases continued to see improvement in optimal HB outcomes: adjusted odds of HB 1 score were twofold higher in both 2005 to 2009 (adjusted odds ratio [aOR]: 2.11, 95% confidence interval [CI]: 1.38-3.22, p < 0.001) and 2010 to 2018 (aOR: 2.18, 95% CI: 1.49-3.19, p < 0.001). Conclusion In contrast to prior studies, our study demonstrates the steepest growth for learning, as measured by rates of preservation of facial function outcomes (HB 1), occurs in the first 400 AN resections. Additionally, improvements in patient outcomes continued even 30 years into practice, underlining the importance of lifelong learning.

Internal Auditory Canal Glioneural Hamartoma: A Rare Mass Masquerading as a Vestibular Schwannoma.

Glioneural hamartomas are exceedingly rare lesions. When localized to the internal auditory canal (IAC), they can cause symptoms referrable to seventh and eighth cranial nerve compression. Here, the authors present a rare case of an IAC glioneural hamartoma. A 57-year-old male presented for evaluation of presumed intracanalicular vestibular schwannomas found on work-up of dizziness and progressive right-sided hearing loss. Surgical intervention pursued progressive symptoms and new onset headaches. The patient underwent uncomplicated retrosigmoid craniectomy for gross total resection. Histopathological evaluation revealed a glioneural hamartoma. A MEDLINE database search used the terms' cerebellopontine angle' OR 'internal auditory canal' AND 'hamartoma' OR 'heterotopia'. Clinicopathological characteristics and outcomes of the present case were compared to those in the literature. The literature review yielded nine articles describing 11 cases (eight females, three males; median age 40 years, range 11-71) of intracanalicular glioneural hamartomas. Patients most commonly presented with hearing loss and were presumed to have a diagnosis of vestibular schwannoma before histologic diagnosis. Glioneural hamartomas are rare lesions that may be found in the IAC. Although benign, they may be safely resected for cranial nerve function preservation goals with a low risk of recurrence.

Occipital Neuralgia following Acoustic Neuroma Resection.

Background While postoperative outcomes of acoustic neuroma (AN) resection commonly consider hearing preservation and facial function, headache is a critical quality of life factor. Postoperative headache is described in the literature; however, there is limited discussion specific to occipital neuralgia (ON) following AN resection. Objective The aim of this study is to investigate the effectiveness of conservative management and surgery. Methods We conducted a retrospective review of 872 AN patients who underwent resection at our institution between 1988 and 2017 and identified 15 patients (1.9%) that met International Classification of Headache Disorders criteria for ON. Results Of the 15 ON patients, surgical approaches included 13 (87%) retrosigmoid (RS), one (7%) translabyrinthine (TL), and one (7%) combined RS + TL. Mean clinical follow-up was 119 months (11-263). Six (40%) patients obtained pain relief through conservative management, while the remaining nine (60%) underwent surgery or ablative procedure. Three (38%) patients received an external neurolysis, four (50%) received a neurectomy, one (13%) had both procedures, and one (13%) received two C2 to 3 radio frequency ablations. Of the nine patients who underwent procedural ON treatment, seven (78%) patients achieved pain relief, one patient (11%) continued to have pain, and one patient (11%) was lost to follow-up. Of the six patients whose pain was controlled with conservative management and nerve blocks, five (83%) found relief by using neuropathic pain medication and one (17%) found relief on nonsteroidal anti-inflammatory drug. Conclusion Our series demonstrates success with conservative management in some, but overall a minority (40%) of patients, reserving decompression only for refractory cases.

Comparison of transarterial n-BCA and Onyx embolization of brain arteriovenous malformations: A single-center 18-year retrospective analysis.

OBJECTIVE: Brain arteriovenous malformations (AVM) are commonly treated with endovascular embolization. Due to the rapid evolution of endovascular technology and lack of consistent practice guidelines regarding AVM embolization, further study of AVM embolization outcomes is warranted. METHODS: We conducted a retrospective review of AVMs embolized at a single center from 2002-2019. Patient demographics, AVM characteristics, intention of embolization, and angiographic and clinical outcome after embolization were recorded. We compared the embolization results of those treated with n-butyl cyanoacrylate (n-BCA) and Onyx. RESULTS: Over an 18-year period at our institution, 30 (33%) of 92 AVMs were treated with embolization. n-BCA was used in 12 cases and Onyx in 18 cases. Eighty-seven pedicles were embolized over 47 embolization sessions. Fifty percent of AVMs treated with n-BCA underwent more than one embolization session compared to 22% when Onyx was used. The median total percent volume reduction in the n-BCA AVMs was 52% compared to 51% in Onyx AVMs. There were 2 periprocedural complications in the n-BCA cohort and none in the Onyx cohort. CONCLUSIONS: In this small retrospective series, Onyx and n-BCA achieved similar occlusion results, although n-BCA required more sessions and pedicles embolized to do so.

Survival benefit of concomitant chemoradiation in adult supratentorial primary glioblastoma. A propensity score weighted population-based analysis.

BACKGROUND: This population study aims to assess the impact of the implementation of the original Stupp protocol on overall survival in patients with new-diagnosed supratentorial primary GBM. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to study the survival of histologically confirmed adult supratentorial GBM patients diagnosed between 1998 and 2016. Kaplan-Meier, and a univariate and propensity-score weighted multivariate Cox proportional hazard model adjusted for age at diagnosis, sex, race, marital status and extent of resection was used to assess the survival of patients prior to implementation of the Stupp protocol in 2005 (Pre-Stupp) and following implementation of the Stupp Protocol until 2016 (Post Stupp). RESULTS: Overall, 6390 patients satisfied inclusion exclusion criteria. Median survival times were 13 months for the Pre-Stupp and 15 months for Post-Stupp groups (P<0.001). The 1-, 2-, 5- and 10-year survival rates for the Pre-Stupp group were 51%, 18%, 5% and 2% respectively compared to 59%, 27%, 8% and 4% on the Post-Stupp group. Propensity-score weighted analysis showed a lower mortality risk for patients who underwent concomitant chemoradiation during the Post-Stupp era (HR=0.77, 95% CI 0.62-0.94). There was a 42% relative reduction in the risk of death for patients treated during the Post-Stupp era. CONCLUSIONS: This population-based propensity-score study with long-term follow-up suggests that the implementation of the Stupp protocol in 2005 had a positive impact on the survival of patients with supratentorial GBM. This "real-world" analysis validates the results of the original randomized control trial on which this protocol is based.

Angioarchitectural features amongst patients with unruptured brain arteriovenous malformations presenting with headache: findings from a single center retrospective review of 76 patients.

BACKGROUND: Brain arteriovenous malformations (AVMs) consist of abnormal connections between arteries and veins via an interposing nidus. While hemorrhage is the most common presentation, unruptured AVMs can present with headaches, seizures, neurological deficits, or be found incidentally. It remains unclear as to what AVM characteristics contribute to pain generation amongst unruptured AVM patients with headaches. METHODS: To assess this relationship, the current study evaluates angiographic and clinical features amongst patients with unruptured brain AVMs presenting with headache. Loyola University Medical Center medical records were queried for diagnostic codes corresponding to AVMs. In patients with unruptured AVMs, we analyzed the correlation between the presenting symptom of headache and various demographic and angiographic features. RESULTS: Of the 144 AVMs treated at our institution between 1980 and 2017, 76 were unruptured and had sufficient clinical data available. Twenty-three presented with headaches, while 53 patients had other presenting symptoms. Patients presenting with headache were less likely to have venous stenosis compared to those with a non-headache presentation (13 % vs. 36 %, p = 0.044). CONCLUSIONS: Our study suggests that the absence of venous stenosis may contribute to headache symptomatology. This serves as a basis for further study of correlations between AVM angioarchitecture and symptomatology to direct headache management in AVM patients.

Surgical correction of pediatric spinal deformities with coexisting intraspinal pathology: A case report and literature review.

BACKGROUND: Surgical correction of spinal deformities with coexisting intraspinal pathology (SDCIP) requires special consideration to minimize risks of further injury to an already abnormal spinal cord. However, there is a paucity of literature on this topic. Here, the authors present a pediatric patient with a residual pilocytic astrocytoma and syringomyelia who underwent surgical correction of progressive postlaminectomy kyphoscoliosis. Techniques employed are compared to those in the literature to compile a set of guidelines for surgical correction of SDCIP. METHODS: A systematic MEDLINE search was conducted using the following keywords; "pediatric," "spinal tumor resection," "deformity correction," "postlaminectomy," "scoliosis correction," "intraspinal pathology," "tethered cord," "syringomyelia," or "diastematomyelia." Recommendations for surgical technique for pediatric SDCIP correction were reviewed. RESULTS: The presented case demonstrates recommendations that primarily compressive forces on the convexity of the coronal curve should be used when performing in situ correction of SDCIP. Undercorrection is favored to minimize risks of traction on the abnormal spinal cord. The literature yielded 13 articles describing various intraoperative techniques. Notably, seven articles described use of compressive forces on the convex side of the deformity as the primary mode of correction, while only five articles provided recommendations on how to safely and effectively surgically correct SDCIP. CONCLUSION: The authors demonstrated with their case analysis and literature review that there are no clear current guidelines regarding the safe and effective techniques for in situ correction and fusion for the management of pediatric SDCIP.

Anaplastic Hemangiopericytoma of the Jugular Foramen: Case Report and Systematic Review.

BACKGROUND: Hemangiopericytomas (HPCs) and solitary fibrous tumors (SFTs) are rare tumors of mesenchymal origin. Here, the authors present a rare case of anaplastic HPC in the jugular foramen (JF). The authors also conduct a systematic review of the literature to examine the current fund of knowledge on JF HPC/SFTs. METHODS: A systematic MEDLINE search was conducted using key words "hemangiopericytoma" OR "solitary fibrous tumor" AND "jugular foramen" OR "extracranial" OR "skull base." Clinicopathologic characteristics and outcomes of the present case were reviewed and compared with those in the literature. RESULTS: A 41-year-old male, who had undergone stereotactic radiation therapy 6 years ago for a presumed glomus jugulare tumor, presented to our institution with worsening dysphagia, hoarseness, persistent tongue weakness, and radiographic evidence of tumor progression. The patient underwent uncomplicated gross total resection with sacrifice of the infiltrated hypoglossal nerve. Histopathologic evaluation revealed anaplastic HPC/SFT (World Health Organization grade III). Review of the literature yielded 9 additional cases of JF HPC/SFT in 5 males (56%) and 4 females (44%), with a mean age of 49.6 years old. Patients commonly presented with pain (37.5%) and lower cranial nerve deficits (100%). Preoperative diagnoses included glomus jugulare (n = 2) or JF schwannomas (n = 3). All patients underwent microsurgical resection of the lesion, except for 1 who refused all treatment after diagnostic biopsy. CONCLUSION: The authors present the only reported case of anaplastic HPC of the JF. The illustrative case and those found on systematic review of the literature highlight the importance of tissue diagnosis and appropriate management.

Surgical Management of Trigeminal Neuralgia Induced by Brainstem Infarct: A Systematic Review of the Literature.

BACKGROUND: Although cases of trigeminal neuralgia (TN) induced by brainstem infarct have been reported, the neurosurgical literature lacks a comprehensive review for this subpopulation of patients. We present the first systematic review of the literature to discuss pathology, surgical management, and future directions for therapeutic innovation in this population. METHODS: Our systematic review was conducted according to PRISMA guidelines. Resulting articles were screened for those that presented cases of TN associated with brainstem infarct. RESULTS: A review of the literature identified 18 case reports of 21 patients with TN induced by brainstem infarct: 14 pontine infarcts and 7 medullary infarcts. Although many cases of ischemic brainstem lesions are caused by acute stroke, cerebral small vessel disease also plays a role in certain cases, and the relationship between these chronic lesions and TN is more likely to be overlooked. Furthermore, we found that reports of self-resolving TN pain after brainstem infarct is disproportionately biased, as most case reports published their data within the first few months after initial presentation. Reports with follow-up periods >13 months reported eventual pain recurrence that necessitated surgical intervention. Microvascular decompression was not sufficient to treat TN pain associated with concurrent neurovascular compression and brainstem infarct. CONCLUSIONS: Brainstem infarcts affecting the trigeminal pathway represent an understudied pathologic cause of TN. Although the neurosurgical literature lacks a clear picture of the most efficacious interventions in this population, we are optimistic that this review will encourage further investigation into the best treatment for these patients.

Trigeminal neuralgia induced by brainstem infarction treated with pontine descending tractotomy: illustrative case.

BACKGROUND: While cases of trigeminal neuralgia induced by a brainstem infarct have been reported, the neurosurgical literature lacks clear treatment recommendations in this subpopulation. OBSERVATIONS: The authors present the first case report of infarct-related trigeminal neuralgia treated with pontine descending tractotomy that resulted in durable pain relief after multiple failed surgical interventions, including previous microvascular decompressions and stereotactic radiosurgery. A neuronavigated pontine descending tractotomy of the spinal trigeminal tract was performed and resulted in successful pain relief for a 50-month follow-up period. LESSONS: While many cases of ischemic brainstem lesions are caused by acute stroke, the authors assert that cerebral small vessel disease also plays a role in certain cases and that the relationship between these chronic ischemic brainstem lesions and trigeminal neuralgia is more likely to be overlooked. Furthermore, neurovascular compression may obscure the causative mechanism of infarct-related trigeminal neuralgia, leading to unsuccessful decompressive surgeries in cases in which neurovascular compression may be noncontributory to pain symptomatology. Pontine descending tractotomy may be beneficial in select patients and can be performed either alone or concurrently with microvascular decompression in cases in which the interplay between ischemic lesion and neurovascular compression in the pathophysiology of disease is not clear.

Fetal Bovine Collagen Grafts for Repair of Tegmen Defects and Encephaloceles Via Middle Cranial Fossa Approach.

To evaluate the use of commercially available allogenic dural graft materials made of fetal bovine collagen, we present an analysis of our case series with use of autologous and allogenic graft materials. Patients who underwent surgical repair of a tegmen tympani defect associated with ipsilateral conductive hearing loss and cerebrospinal fluid (CSF) otorrhea using a middle cranial fossa (MCF) approach from 2004 to 2018 at Loyola University Medical Center were included. Resolution of CSF otorrhea, audiologic outcomes, facial nerve preservation, and surgical complications was analyzed. Thirty-three patients with an average age of 55.3 years (range: 21-78, standard deviation [SD]: 12.9) and body mass index of 34.4 (range: 22-51, SD: 7.4) underwent an MCF repair of a tegmen and dural defect. All patients presented with CSF otorrhea and conductive hearing loss ipsilateral to the defect. Repairs were made with combinations of allograft and autograft in 17 cases, allograft only in 15 cases, and autograft only in 5 cases. Improvement in hearing was noted in 33 cases, and resolution of CSF otorrhea was noted in 36 cases; one patient required repeat surgery which resolved CSF otorrhea. Three patients had minor complications; all these were in the autograft group. The MCF approach coupled with the use of fetal bovine collagen grafts is a safe and viable method to repair tegmen tympani and associated dural defects with salutary outcomes and low morbidity.

Glomus Vagale Tumor Resection: 2-Dimensional Operative Video.

A 37-yr-old female with prior transient left facial paralysis presented with hearing loss, headaches, and resolved transient right facial paralysis. The neurological examination demonstrated normal facial movement, left hearing loss, and left vocal cord weakness. Magnetic resonance imaging demonstrated a >3 cm left paraganglioma traversing the jugular foramen. After obtaining informed consent from the patient, the tumor was embolized and then resected via a combined left postauricular infratemporal fossa and transcervical approach with cranial nerve monitoring. The ossicles were removed and the vertical segment of the facial nerve was skeletonized. The jugular bulb was identified in the hypotympanum and the petrous carotid artery was exposed. The digastric muscle was reflected inferiorly and the extratemporal facial nerve was identified. The stylomandibular ligament was transected to unlock the exposure to the infratemporal fossa. The external carotid branches were ligated. The vagus nerve and cervical sympathetic chain were infiltrated with tumor, requiring resection. The presigmoid dura and occluded jugular bulb were opened to complete the tumor resection, while preserving the medial wall. Despite anatomic preservation, the glossopharyngeal, accessory, and hypoglossal nerves were postoperatively weak and a facial paralysis recovered after 1 wk. Magnetic resonance imaging at 1 yr demonstrated a clean jugular foramen, although a thin rim of tumor remained around the petrous carotid.

Pediatric vestibular schwannomas: case series and a systematic review with meta-analysis.

OBJECTIVE: Sporadic unilateral vestibular schwannomas are rare in the pediatric population. Little has been reported in the literature on the presentation, tumor size, response to surgical treatment, and recurrence rates in these younger patients. The authors' goal was to describe their institutional experience with pediatric sporadic vestibular schwannomas and to conduct a meta-analysis of the existing literature to provide further insight into the presentation, tumor characteristics, and surgical outcomes for these rare tumors to help direct future treatment strategies. METHODS: The authors performed a retrospective review of all patients 21 years of age or younger with unilateral vestibular schwannomas and without neurofibromatosis type 2 who underwent resection by the senior authors between 1997 and 2019. A systematic review of the literature and meta-analysis was also performed by entering the search terms "pediatric" and "vestibular schwannoma" or "acoustic neuroma," as well as "sporadic" into PubMed. Presentation, treatment, clinical outcomes, and follow-up were analyzed. RESULTS: Fifteen patients were identified at the authors' institution, ranging in age from 12 to 21 years (mean 16.5 years). Common presenting symptoms included hearing loss (87%), headache (40%), vertigo (33%), ataxia (33%), and tinnitus (33%). At the time of surgery, the mean tumor size was 3.4 cm, with four 1-cm tumors. Four patients had residual tumor following their first surgery, 3 (75%) of whom had significant radiographic regrowth that required further treatment. The literature review identified an additional 81 patients from 26 studies with patient-specific clinical data available for analysis. This resulted in a total of 96 reported patients with an overall average age at diagnosis of 12.1 years (range 6-21 years) and an average tumor size of 4.1 cm. CONCLUSIONS: Pediatric vestibular schwannomas present similarly to those in adults, although symptoms of mass effect are more common, as these tumors tend to be larger at diagnosis. Some children are found to have small tumors and can be successfully treated surgically. Residual tumors in pediatric patients were found to have a higher rate of regrowth than those in their adult counterparts.

Osteoradionecrosis of the skull base.

Radiation therapy (RT) is often necessary for the treatment of head and neck cancers. Osteoradionecrosis (ORN) is a rare, but potentially serious complication of RT. RT leads to the destruction of vasculature in radiated tissue causing hypoxia and tissue necrosis. ORN can occur in any bone, but bones with naturally poor blood supply appear to be more susceptible. Bones of the skull base are susceptible, with ORN occurring in the anterior, central, and lateral skull base. Risk factors include cancer type and location, radiation dose, and a variety of patient factors. Patients often present with pain, bleeding, and foul odor and are typically found to have exposed and necrotic bone. Treatment options vary depending on the severity, but typically include pentoxifylline and vitamin E as well as surgical debridement, with less evidence supporting hyperbaric oxygen therapy. Recognition and prompt treatment of ORN will allow for improved patient outcomes.