When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 2: Granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Chronic rhinosinusitis is a very common condition. Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (eGPA) are systemic diseases which can contribute to the development of chronic rhinosinusitis in select patients. OBJECTIVE: Characterize the presenting features, diagnostic criteria, workup, and management of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis as they are encountered in otolaryngology clinics. METHODS: Full length manuscripts published 2000 or later were reviewed. A separate search was conducted for each disease. Pertinent clinical features related to sinonasal manifestations of GPA and eGPA were collected and reported in this review. RESULTS: 467 references were discovered during literature review process. In total, 42 references for GPA and 35 references for eGPA were included in this review. CONCLUSION: GPA and eGPA are vasculitis syndromes which commonly present in the context of multisystem disease. For GPA, pulmonary and renal disease are common; for eGPA a history of asthma is nearly ubiquitous. Sinonasal disease is a very common feature for both disease processes and may precede the development of systemic symptoms in many patients. Clinical work up and diagnosis is complex and generally requires multidisciplinary care. Treatment primarily consists of immunosuppressive agents, and a number of steroids, steroid sparing agents, and biologics have been shown to be effective. The role of sinus surgery includes tissue biopsy for diagnosis, functional surgery for symptom management in select cases, and reconstruction of cosmetic and functional defects.

When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 1: IgG4-related disease and sarcoidosis.

BACKGROUND: Chronic rhinosinusitis is a very common condition. IgG4-related disease (IgG4-RD) and sarcoidosis are systemic diseases which can contribute to the development of chronic rhinosinusitis in select patients. OBJECTIVE: Characterize the presenting features, diagnostic criteria, workup, and management of sinonasal IgG4-RD and sarcoidosis as they are encountered in otolaryngology clinics. METHODS: Full length manuscripts published 2000 or later were reviewed. A separate search was conducted for each disease. Pertinent clinical features related to sinonasal manifestations of IgG4-RD and sarcoidosis were collected and reported in this review. RESULTS: 404 references were discovered during literature review process. In total, 42 references for IgG4-RD and 34 references for sarcoidosis were included in this review. CONCLUSION: IgG4-RD and sarcoidosis are autoimmune inflammatory conditions that can affect many systems of the body. For both disease entities, sinonasal disease is a less common presentation which can lead to delayed diagnosis. Sinonasal IgG4-RD commonly presents in the setting of multisystem disease. All with other clinical features, biopsy plays a key role in the diagnosis for both diseases. Treatment for IgG4-RD consists primarily of steroids and rituximab which can lead to excellent and durable remission. A variety of immunosuppressive agents are used in the management of sarcoidosis. Surgery for IgG4-RD is primarily utilized for tissue biopsy, although resection or debulking may be considered. For sarcoidosis, surgery can be used for tissue biopsy and functional sinus surgery can offer symptomatic relief in many patients.

In-hospital imaging utilization after elective endovascular brain aneurysm treatment: a surrogate metric for the value of hospitalization.

OBJECTIVE: Despite the adoption of same-day outpatient surgical procedures in some specialties, it remains common practice to admit patients for monitoring after elective endovascular treatment of brain aneurysms to monitor for complications. The necessity of such monitoring has not been fully characterized. Here, the authors reviewed the utilization of imaging during posttreatment hospitalization, a surrogate measure for workup of suspected complications requiring hospital resources, to infer the value of inpatient monitoring after endovascular aneurysm treatment. METHODS: Clinical and angiographic data from eligible patients were retrospectively assessed for demographic characteristics, imaging indications, timing of imaging, and imaging findings. Patients were included if they underwent elective endovascular brain aneurysm treatment, and patients were excluded if significant intraprocedural complications occurred. The recorded imaging modalities included CT, MRI, catheter-based imaging, and ultrasound; plain radiographs were excluded. Multivariable logistic regression analysis was performed to identify predictors of the need for posttreatment imaging. RESULTS: In total, 1229 elective endovascular procedures for brain aneurysm treatment were included. Patients underwent imaging before discharge in 13.4% (165/1229) of cases, with significant findings in 5.0% (61/1229) of cases. The median (interquartile range) time to first posttreatment imaging was 13.2 (4.2-22.8) hours. The need for imaging during posttreatment hospitalization was positively associated with larger aneurysm size (p < 0.05) and negatively associated with underlying cardiovascular disease (p < 0.05). CONCLUSIONS: More than 1 in 8 patients who underwent elective endovascular brain aneurysm treatment required imaging during posttreatment hospitalization, most within the first 24 hours, and 1 in 20 had significant findings. These results suggest the importance of short-term hospitalization after elective endovascular aneurysm treatment.

Comparative cost analysis of endovascular and open approaches for elective treatment of middle cerebral artery aneurysms.

BACKGROUND: Intracranial aneurysms of the middle cerebral artery can be treated using several open surgical and endovascular approaches. Given the growing evidence of clinical equipoise between these various treatment strategies, there is a need to assess the costs associated with each. METHODS: Cost of aneurysm treatment was divided into two categories for comparison. "Initial cost" comprised the total in-hospital expenses for initial aneurysm treatment and "total cost" comprised initial aneurysm treatment and all expenses relating to readmission due to treatment-related complications, prescribed catheter angiograms for monitoring of treatment stability, and any retreatments needed for a given aneurysm. The open surgical group was subdivided into a pterional approach group and a lateral supraorbital (LSO) approach group for. RESULTS: Median initial cost was $37,152 (IQR $31,318-$44,947) for aneurysms treated with the pterional approach, $29,452 (IQR $27,779-$32,826) for aneurysms treated with the LSO approach, and $19,587 (IQR $14,125-$30,521) for aneurysms treated with endovascular approaches. The median total cost was $39,737 (IQR $33,891-$62,259) for aneurysms treated with the pterional approach, $31,785 (IQR $29,513-$41,099) for aneurysms treated with the LSO approach, and $24,578 (IQR $18,977-$34,547) for aneurysms treated with endovascular approaches. Analysis of variance test demonstrated variance across groups for both initial and total cost (p = 0.004, p = 0.008, respectively). In our subsequent analysis, initial cost and total cost were higher in the pterional group than the endovascular group (p = 0.003 and p = 0.006, respectively). CONCLUSIONS: Endovascular treatment of elective aneurysms has a significantly lower cost than open surgical treatment with the pterional approach, but not with the LSO approach. For aneurysms not amenable to endovascular treatment, a minimally invasive LSO approach carries a lower cost burden than a pterional approach.

A Low Subfrontal Dural Opening for Operative Management of Anterior Skull Base Lesions.

Introduction A low subfrontal dural opening technique that limits brain manipulation was assessed in patients who underwent frontotemporal approaches for anterior fossa lesions. Methods A retrospective review was performed for cases using a low subfrontal dural opening including characterization of demographics, lesion size and location, neurological and ophthalmological assessments, clinical course, and imaging findings. Results A low subfrontal dural opening was performed in 23 patients (17F, 6M), median age of 53 years (range 23-81) with a median follow-up duration of 21.9 months (range 6.2-67.1). Lesions included 22 meningiomas (nine anterior clinoid, 12 tuberculum sellae, and one sphenoid wing), one unruptured internal carotid artery aneurysm clipped during a meningioma resection, and one optic nerve cavernous malformation. Maximal possible resection was achieved in all cases including gross total resection in 16/22 (72.7%), near total in 1/22 (4.5%), and subtotal in 5/22 (22.7%) in which tumor involvement of critical structures limited complete resection. Eighteen patients presented with vision loss; 11 (61%) improved postoperatively, three (17%) were stable, and four (22%) worsened. The mean ICU stay and time to discharge were 1.3 days (range 0-3) and 3.8 days (range 2-8). Conclusion A low sub-frontal dural opening for approaches to the anterior fossa can be performed with minimal brain exposure, early visualization of the optico-carotid cistern for cerebrospinal fluid release, minimizing need for fixed brain retraction, and Sylvian fissure dissection. This technique can potentially reduce surgical risk and provide excellent exposure for anterior skull base lesions with favorable extent of resection, visual recovery, and complication rates.

A review of technological innovations leading to modern endovascular brain aneurysm treatment.

Tools and techniques utilized in endovascular brain aneurysm treatment have undergone rapid evolution in recent decades. These technique and device-level innovations have allowed for treatment of highly complex intracranial aneurysms and improved patient outcomes. We review the major innovations within neurointervention that have led to the current state of brain aneurysm treatment.

Retreatment of previously flow diverted intracranial aneurysms with the pipeline embolization device.

BACKGROUND AND PURPOSE: Flow diversion of intracranial aneurysms with the Pipeline Embolization Device (PED) is frequently performed, but the outcomes of retreatment for aneurysms that failed to occlude after prior treatment with PED have not been well studied. Here, we report the safety and efficacy of PED retreatment after initial failure to occlude. MATERIALS AND METHODS: Clinical and angiographic data from eligible patients were retrospectively assessed for demographics, aneurysm occlusion status, and clinical outcomes. Patients were included in this study if they underwent PED retreatment to treat an aneurysm that had previously been treated with PED. RESULTS: Retreatment of previously flow-diverted aneurysms with PED was performed in 42 cases. At final angiographic follow-up, angiographic improvement was observed after 45% (19/42) of retreatments and complete aneurysm occlusion was observed following 26% (11/42). Significant clinical complications occurred in 10% (4/42) of PED retreatments. CONCLUSIONS: Retreatment of intracranial aneurysms with PED following initial failure to achieve aneurysm occlusion has a low rate of subsequent complete aneurysm occlusion.

Time Line of Occlusion for Intracranial Aneurysms Treated with the Pipeline Embolization Device.

BACKGROUND: Rates of aneurysm occlusion following treatment with flow-diverting stents have been quantified at predefined time points in clinical trials, but data characterizing the continuous temporal progression of aneurysm occlusion are lacking. This study used real-world variability in timing of angiographic follow-up to characterize the time line of aneurysm occlusion following treatment with the Pipeline embolization device (PED). METHODS: All aneurysms treated with a PED at our institution between 2011 and 2020 were screened. Nonsaccular or ruptured aneurysms were excluded. Aneurysm occlusion status and time since treatment were recorded for each follow-up angiogram. Aneurysm occlusion was characterized using Kaplan-Meier and Cox proportional hazards analysis after censoring at last follow-up or subsequent treatment. RESULTS: There were 290 aneurysms in 222 patients analyzed. The median time of observed aneurysm occlusion was 7.5 months, and overall rate of aneurysm occlusion was 77.9%. Larger aneurysms demonstrated a longer median time to occlusion and lower rate of aneurysm occlusion (P = 0.029). There were no observed differences in the time line of occlusion for aneurysms treated with a single PED or multiple PEDs (P = 0.889) or without or with adjunctive coiling (P = 0.771). CONCLUSIONS: Aneurysms treated with a PED had a median time to observed occlusion of 7.5 months. Occlusion of larger aneurysms occurred more slowly than occlusion of smaller aneurysms following flow diversion. The number of PEDs deployed or the use of adjunctive coiling did not affect the time line or likelihood of aneurysm occlusion. These findings may guide optimal timing of follow-up after treatment with a PED.

Management of In-Stent Stenosis with Dual Antiplatelet Therapy Following Pipeline Embolization of Intracranial Aneurysms.

OBJECTIVE: Flow diversion of intracranial aneurysms with the pipeline embolization device (PED) may produce angiographically apparent stenosis within the PED, which can lead to secondary ischemic complications. In-stent stenosis can be treated medically with dual antiplatelet therapy (DAPT), but the safety and efficacy of this approach are unknown. In this work, we review the safety and efficacy of DAPT to prevent progression of in-stent stenosis or development of cerebral ischemia. METHODS: Clinical and angiographic data from eligible patients were assessed from a prospectively maintained neurointerventional database. Details surrounding in-stent stenosis and DAPT were extracted. Patients were included in this study if in-stent stenosis was detected at any angiographic follow-up and managed with DAPT. The primary efficacy endpoint was lack of angiographic progression of in-stent stenosis or new ipsilateral infarct following initiation of medical therapy. RESULTS: In total, 23 PED constructs developed in-stent stenosis and were managed with DAPT. Follow-up angiography was available for 19 constructs. Eighty-nine percent (17/19) of PED constructs achieved the primary endpoint of lack of stenosis progression and lack of new ipsilateral ischemic events. Of the 2 PED constructs that failed to achieve the primary endpoint of this study, one demonstrated worsening of in-stent stenosis from 55% to 76% over 16 months, while the other developed ipsilateral ischemic stroke 4 months after detection of in-stent stenosis. In addition, one patient experienced intracranial hemorrhage 9 months after the initiation of DAPT. CONCLUSIONS: Progression of in-stent stenosis and new ipsilateral ischemic events are limited in the presence of DAPT. However, hemorrhagic events related to DAPT may occasionally occur.

Genetic and histopathological associations with outcome in pediatric pilocytic astrocytoma.

OBJECTIVE: Pilocytic astrocytomas (PAs) have a generally favorable prognosis; however, progression or recurrence after resection is possible. The prognostic value of histopathological qualifiers (defined below) or BRAF alterations is not well understood. The aim of this study was to identify the prognostic value of genetic and histopathological features of pediatric PAs. METHODS: Patients treated for a WHO grade I PA at a single institution were analyzed for histopathological and genetic features and outcomes. "Histopathological qualifier" refers to designations such as "WHO grade I PA with increased proliferative index." BRAF alterations include gene fusions and point mutations. Patients with neurofibromatosis type 1 were excluded. RESULTS: A total of 222 patients were analyzed (51% female, mean age 9.6 years). Tumors were located in the cerebellum/fourth ventricle (51%), optic pathway/hypothalamus (15%), brainstem (12%), and cerebral cortex (11%). BRAF alterations were screened for in 77 patients and identified in 56 (73%). Histopathological qualifiers were present in 27 patients (14%). Resection was performed in 197 patients (89%), 41 (21%) of whom displayed tumor progression or recurrence after resection. Tumor progression or recurrence was not associated with histopathologic qualifiers (p = 0.36) or BRAF alterations (p = 0.77). Ki-67 proliferative indices were not predictive of progression or recurrence (p = 0.94). BRAF alterations, specifically KIAA1549 fusions, were associated with cerebellar/fourth ventricular tumor location (p < 0.0001) and younger patient age (p = 0.03). Patients in whom gross-total resection was achieved had lower rates of progression and recurrence (p < 0.0001). CONCLUSIONS: Histopathological features/qualifiers and BRAF alterations were not associated with tumor recurrence/progression in pediatric PAs. The extent of resection was the only factor analyzed that predicted outcome.

Comparative study of on-label versus off-label treatment of intracranial aneurysms with the Pipeline embolization device.

OBJECTIVE: The Pipeline embolization device (PED) is widely used for the treatment of intracranial aneurysms, including in off-label applications. In this work, the authors compared the real-world efficacy and safety of PED use in on-label and off-label aneurysm treatments. METHODS: Clinical and angiographic data of patients who underwent PED placement at a high-volume academic medical center were retrospectively obtained. Treatments were classified as on-label if they fell within the applications approved by the United States Food and Drug Administration as of 2021. Recorded outcomes included aneurysm occlusion, procedural complications, ischemic events, in-stent stenosis, intracranial hemorrhage, postprocedural functional status, and death. RESULTS: In total, 416 aneurysms in 330 patients were treated with PED, comprising 256 aneurysms that received on-label treatments and 160 that received off-label treatments. The overall rate of complete aneurysm occlusion was 76.4% for on-label aneurysms and 75.6% for off-label aneurysms (p = 0.898). The risk of ischemic stroke in patients who underwent off-label treatments was 15.2%, which was higher than the 4.2% rate in patients who underwent on-label treatment (p = 0.003). All other clinical complications, procedural complications, and long-term functional status were comparable between the on-label and off-label groups. CONCLUSIONS: In real-world practice, off-label use of PED is common and can achieve similar efficacy as on-label use. However, in aggregate, off-label use was found to carry an increased rate of ischemic complications. With judicious attention to safety and individual patient characteristics, these results highlight the scale and general feasibility of off-label PED use by experts.

The value of long-term angiographic follow-up following Pipeline embolization of intracranial aneurysms.

BACKGROUND: Flow diversion of intracranial aneurysms with the Pipeline Embolization Device (PED) is commonly performed, but the value of long-term angiographic follow-up has not been rigorously evaluated. Here we examine the prevalence of actionable findings of aneurysm recurrence and development of in-stent stenosis in a cohort of patients that underwent long-term angiographic follow-up at multiple time points. METHODS: Angiographic data from eligible patients were retrospectively assessed for aneurysm occlusion, in-stent stenosis, and aneurysm regrowth or recurrence. Patients were included in this study if they underwent angiographic imaging at 6 months post-treatment and at least one later time point. RESULTS: 100% (132/132) of aneurysms occluded at 6 months remained occluded at final follow-up. 85.7% (6/7), 56.3% (27/48), and 25% (6/24) of aneurysms with entry remnant, subtotal filling, and total filling, respectively, at 6 months were completely occluded at final follow-up. 98.7% (147/149) of PED constructs that demonstrated no stenosis at 6 months demonstrated no stenosis at final angiography, while 44.4% (8/18) of PED constructs demonstrating in-stent stenosis at 6 months had resolution of stenosis on final angiography. CONCLUSIONS: Among patients who undergo treatment of intracranial aneurysms with PED, the value of long-term angiography in patients demonstrating complete aneurysm occlusion and no in-stent stenosis on 6 month post-treatment angiography is low.

IgG4-Related Disease of the Skull and Skull Base-A Systematic Review and Report of Two Cases.

OBJECTIVE: IgG4-related disease (IgG4-RD) is an inflammatory process that uncommonly can present in the skull base and calvarium and mimic a tumor but the nature of this condition is not well summarized in the neurosurgical literature. METHODS: A review was performed of 2 cases of IgG4-RD in the skull base highlighting the diagnostic challenges with assessment of these skull base lesions, and a systematic review of relevant literature was carried out. RESULTS: A systematic review of the literature conducted in accordance with PRISMA guidelines identified 113 articles, with 184 cases of IgG4-RD in the skull base or calvarium. The most commonly affected locations include the meninges, cavernous sinus, base of the posterior fossa, clivus, and mastoid bone. Headache, visual and auditory disturbances, cranial nerve dysfunction, and seizures were the most common presenting symptoms. Medical treatment was highly successful and most commonly consisted of corticosteroids coadministered with immunosuppressive agents such as rituximab. Prevalence seemed to be equal between sexes, and serum IgG4 levels were increased in 61% of patients. Delayed diagnosis and a need for multiple biopsies were reported in numerous cases. Two cases of skull base IgG4-RD from the authors' institution show the variable presentations of this disease. More invasive surgical biopsies were required in both cases, and corticosteroid treatment led to significant clinical improvement. CONCLUSIONS: IgG4-RD is an uncommon condition with an increasing body of reported cases that can affect the skull base and calvarium and should be in the differential diagnosis, because delay in diagnosis and treatment may be common.