Application of novel non-invasive ophthalmic imaging to visualize peripapillary wrinkles, retinal folds and peripapillary hyperreflective ovoid mass-like structures associated with elevated intracranial pressure.

Background: Elevated intracranial pressure (ICP) is a serious and potentially life-threatening condition, for which clinically useful non-invasive measures have been elusive, in some cases due to their inadequate sensitivity and specificity. Our aim was to evaluate novel non-invasive ophthalmic imaging of selected pathological features seen in elevated ICP, namely peripapillary hyperreflective ovoid mass-like structures (PHOMS), peripapillary wrinkles (PPW) and retinal folds (RF) as potential biomarkers of elevated ICP. Methods: This single-center pilot study included subjects with untreated or incompletely treated high ICP. The retinas of these subjects were evaluated with averaged en-face optical coherence tomography (OCT), OCT retinal cross-sections (OCT B-scans), adaptive optics scanning light ophthalmoscopy (AOSLO), and fundus photos. Results: Seven subjects were included in the study. 6 subjects with high ICP (5 idiopathic intracranial hypertension, 1 medication induced, 30.8 ± 8.6 years, 75% female, 5 with papilledema) and 1 control (20-25 years) were included. PHOMS, PPW and RF were present in all subjects with papilledema, but neither in the high ICP subject without papilledema nor in the control subject. Averaged en-face OCT scans and AOSLO were more sensitive for PPW and RF than OCT B-scans and commercial fundus photos. Conclusion: PPW, RF and PHOMS volume have potential as non-invasive biomarkers of ICP. Novel imaging modalities may improve sensitivity. However, lack of automated image acquisition and processing limits current widespread adoption in clinical settings. Further research is needed to validate these structures as biomarkers for elevated ICP and improve clinical utility.

Percutaneous Disc Biopsy versus Bone Biopsy for the Identification of Infectious Agents in Osteomyelitis/Discitis.

PURPOSE: To determine whether sampling of the disc or bone is more likely to yield positive tissue culture results in patients with vertebral discitis and osteomyelitis (VDO). MATERIALS AND METHODS: Retrospective review was performed of consecutive patients who underwent vertebral disc or vertebral body biopsy at a single institution between February 2019 and May 2023. Inclusion criteria were age ≥18 years, presumed VDO on spinal magnetic resonance (MR) imaging, absence of paraspinal abscess, and technically successful percutaneous biopsy with fluoroscopic guidance. The primary outcome was a positive biopsy culture result, and secondary outcomes included complications such as nerve injury and segmental artery injury. RESULTS: Sixty-six patients met the inclusion criteria; 36 patients (55%) underwent disc biopsy, and 30 patients (45%) underwent bone biopsy. Six patients required a repeat biopsy for an initially negative culture result. No significant demographic, laboratory, antibiotic administration, or pain medication use differences were observed between the 2 groups. Patients who underwent bone biopsy were more likely to have a history of intravenous drug use (26.7%) compared with patients who underwent disc biopsy (5.5%; P = .017). Positive tissue culture results were observed in 41% of patients who underwent disc biopsy and 15% of patients who underwent bone biopsy (P = .016). No vessel or nerve injuries were detected after procedure in either group. CONCLUSIONS: Percutaneous disc biopsy is more likely to yield a positive tissue culture result than vertebral body biopsy in patients with VDO.

Pituitary macroadenoma causing vision loss in Wyburn-Mason syndrome: illustrative case.

BACKGROUND: Wyburn-Mason syndrome (WMS) is a neurocutaneous disorder consisting of vascular malformations of the brain, eye, and skin. These include characteristically high-flow intracranial and intraorbital arteriovenous malformations (AVMs) that present commonly with visual deterioration, headache, and hemiplegia. Complete removal of these lesions is challenging. Most patients are followed closely, and intervention occurs only in the setting of worsening symptoms secondary to AVM growth or hemorrhage. Here the authors present the first known case of a patient with WMS and a pituitary macroadenoma. OBSERVATIONS: A 62-year-old man with a 30-year history of WMS with right basal ganglia and orbital AVMs and right eye blindness presented for new-onset left-sided vision loss. A pituitary adenoma was identified compressing the optic chiasm and left optic nerve. Magnetic resonance imaging and digital subtraction angiography studies were obtained for surgical planning, and the patient underwent an endoscopic transnasal transsphenoidal resection, with significant postoperative vision improvement. LESSONS: Given the variable presentation and poor characterization of this rare syndrome, patients with WMS presenting with new symptoms must undergo evaluation for growth and hemorrhage of known AVMs, as well as new lesions. Further, in patients undergoing intracranial surgery, extensive preoperative imaging and planning are crucial for safe and successful procedures.

Venous thromboembolism rates and risk factors following endoscopic skull base surgery.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal perioperative complication. The objective of this study was to assess the rate and risk factors for VTE in endoscopic skull base surgery (ESBS). METHODS: This was a retrospective review of adults undergoing ESBS at a tertiary academic center. Incidence of VTE in the 30-day postoperative period was recorded. Logistic regression analyses identified factors associated with VTE. RESULTS: A total of 1122 ESBS cases performed at Stanford University School of Medicine between 2009 and 2019 were studied. Almost all cases (96.1%) did not employ perioperative VTE chemoprophylaxis. The overall incidence of VTE was 2.3% (26/1122). Malignant pathologies had a higher rate of VTE compared with nonmalignant pathologies (4.5% vs 2.0%, odds ratio [OR] 2.85, 95% confidence interval [CI] 1.22-6.66). Factors associated with an increased risk of VTE included a Caprini score greater than 5 (OR 1.53, 95% CI 1.28-1.83); multiple preoperative endocrinopathies such as the syndrome of inappropriate antidiuretic hormone secretion (SIADH) (OR 22.48, 95% CI 3.93-128.70), adrenal insufficiency (OR 5.24, 95% CI 1.82-15.03), hypercortisolism (OR 4.46, 95% CI 1.47-13.56), and hypothyroidism (OR 3.69, 95% CI 1.66-8.20); each 10-hour increment of lumbar drain duration (OR 1.16, 95% CI 1.08-1.25); and each 10-hour increment for duration of hospitalization (OR 1.05, 95% CI 1.03-1.06). CONCLUSIONS: The incidence of VTE following ESBS is relatively low at 2.3%. Factors with a higher association of VTE include malignancy, preoperative endocrinopathies, higher Caprini score, prolonged lumbar drain duration, and prolonged hospitalization. Larger, multi-institutional studies are needed to validate these findings and to better refine clinical decision-making regarding perioperative VTE prophylaxis.

Cerebral Perfusion in Pediatric Stroke: Children Are Not Little Adults.

ABSTRACT: Cerebral perfusion imaging provides useful information about the hemodynamic state of the brain that is relevant to a number of neurologic conditions, including stroke, epilepsy, and brain tumors. Multiple imaging modalities have been developed to evaluate brain perfusion, primarily by the use of different tracers to measure cerebral blood volume and cerebral blood flow. Here, we provide an overview of magnetic resonance imaging perfusion techniques; summarize the role of perfusion imaging in adult stroke; describe changes in cerebral blood flow over childhood; and discuss the relevance and future directions of perfusion imaging in pediatric cerebrovascular disorders and stroke.

Spontaneous regression of a vein of Galen aneurysmal malformation in a pediatric patient: illustrative case.

BACKGROUND: Vein of Galen aneurysmal malformations (VGAMs) are rare congenital intracranial vascular lesions that represent 30% of all pediatric vascular anomalies. These lesions are associated with severe manifestations, including congestive heart failure, hydrocephalus, and spontaneous hemorrhage. The mainstay of management is medical stabilization followed by endovascular embolization of the lesion. Although VGAM was first reported in 1937, there are few published cases demonstrating spontaneous regression of the lesion. OBSERVATIONS: The authors report the case of a 31-month-old female who presented with an incidentally found VGAM. After initial evaluation, including magnetic resonance imaging and angiography, the patient was lost to follow-up. Upon her return to the clinic at age 12 years, the previously identified VGAM was absent, indicative of involution of the lesion. The patient remained asymptomatic and met appropriate developmental milestones during this interval. LESSONS: This report adds a rare case of the spontaneous resolution of VGAM to the literature. This case may suggest the presence of VGAMs that are asymptomatic, undetected, and regress within the pediatric population. Future studies may benefit from identifying imaging and angiographic findings predictive of spontaneous regression. There may be a role for conservative management in particular cases of asymptomatic and medically stable children with VGAMs.

Efficacy and safety of embolization of dural arteriovenous fistulas via the ophthalmic artery.

INTRODUCTION: Dural arteriovenous fistulae (DAVF) are vascular lesions with arteriovenous shunting that may be treated with surgical obliteration or endovascular embolization. Some DAVF, such as anterior cranial fossa DAVF (AC-DAVF) derive their arterial supply from ophthalmic artery branches in nearly all cases, and trans-arterial embolization carries a risk of vision loss. We determined the efficacy and safety of trans-ophthalmic artery embolization of DAVF. MATERIALS AND METHODS: We performed a retrospective cohort study of all patients with DAVF treated by trans-ophthalmic artery embolization from 2012 to 2020. Primary outcome was angiographic cure of the DAVF. Secondary outcomes included vision loss, visual impairment, orbital cranial nerve injury, stroke, modified Rankin Scale at 90-days, and mortality. RESULTS: 12 patients met inclusion criteria (9 males; 3 females). 10 patients had AC-DAVF. Patient age was 59.7 ± 9.5 (mean ± SD) years. Patients presented with intracranial hemorrhage (4 patients), headache (4 patients), amaurosis fugax (1 patients), or were incidentally discovered (2 patients). DAVF Cognard grades were: II (1 patient), III (6 patients), and IV (5 patients). DAVF were embolized with Onyx (10 patients), nBCA glue (1 patient), and a combination of coils and Onyx (1 patient). DAVF cure was achieved in 11 patients (92%). No patients experienced vision loss, death, or permanent disability. One patient experienced a minor complication of blurry vision attributed to posterior ischemic optic neuropathy. 90-day mRS was 0 (10 patients) and 1 (2 patients). CONCLUSIONS: Trans-ophthalmic artery embolization is an effective and safe treatment for DAVF.

Treatment of posterior circulation fusiform aneurysms.

OBJECTIVE: Perforator arteries, the absence of an aneurysm discrete neck, and the often-extensive nature of posterior circulation fusiform aneurysms present treatment challenges. There have been advances in microsurgical and endovascular approaches, including flow diversion, and the authors sought to review these treatments in a long-term series at their neurovascular referral center. METHODS: The authors performed a retrospective chart review from 1990 to 2018. Primary outcomes were modified Rankin Scale (mRS) scores and Glasgow Outcome Scale (GOS) scores at follow-up. The authors also examined neurological complication rates. Using regression techniques, they reviewed independent and dependent variables, including presenting features, aneurysm location and size, surgical approach, and pretreatment and posttreatment thrombosis. RESULTS: Eighty-four patients met the inclusion criteria. Their mean age was 53 years, and 49 (58%) were female. Forty-one (49%) patients presented with subarachnoid hemorrhage. Aneurysms were located on the vertebral artery (VA) or posterior inferior cerebellar artery (PICA) in 50 (60%) patients, basilar artery (BA) or vertebrobasilar junction (VBJ) in 22 (26%), and posterior cerebral artery (PCA) in 12 (14%). Thirty-one (37%) patients were treated with microsurgical and 53 (63%) with endovascular approaches. Six aneurysms were treated with endovascular flow diversion. The authors found moderate disability or better (mRS score ≤ 3) in 85% of the patients at a mean 14-month follow-up. The GOS score was ≥ 4 in 82% of the patients. The overall neurological complication rate was 12%. In the regression analysis, patients with VA or PICA aneurysms had better functional outcomes than the other groups (p < 0.001). Endovascular strategies were associated with better outcomes for BA-VBJ aneurysms (p < 0.01), but microsurgery was associated with better outcomes for VA-PICA and PCA aneurysms (p < 0.05). There were no other significant associations between patient, aneurysm characteristics, or treatment features and neurological complications (p > 0.05). Patients treated with flow diversion had more complications than those who underwent other endovascular and microsurgical strategies, but the difference was not significant in regression models. CONCLUSIONS: Posterior circulation fusiform aneurysms remain a challenging aneurysm subtype, but an interdisciplinary treatment approach can result in good outcomes. While flow diversion is a useful addition to the armamentarium, traditional endovascular and microsurgical techniques continue to offer effective options.

Effect of Omega-3 Supplementation in Patients With Smell Dysfunction Following Endoscopic Sellar and Parasellar Tumor Resection: A Multicenter Prospective Randomized Controlled Trial.

BACKGROUND: Endoscopic endonasal approaches pose the potential risk of olfactory loss. Loss of olfaction and potentially taste can be permanent and greatly affect patients' quality of life. Treatments for olfactory loss have had limited success. Omega-3 supplementation may be a therapeutic option with its effect on wound healing and nerve regeneration. OBJECTIVE: To evaluate the impact on olfaction in patients treated with omega-3 supplementation following endoscopic skull base tumor resection. METHODS: In this multi-institutional, prospective, randomized controlled trial, 110 patients with sellar or parasellar tumors undergoing endoscopic resection were randomized to nasal saline irrigations or nasal saline irrigations plus omega-3 supplementation. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and at 6 wk, 3 mo, and 6 mo postoperatively. RESULTS: Eighty-seven patients completed all 6 mo of follow-up (41 control arm, 46 omega-3 arm). At 6 wk postoperatively, 25% of patients in both groups experienced a clinically significant loss in olfaction. At 3 and 6 mo, patients receiving omega-3 demonstrated significantly less persistent olfactory loss compared to patients without supplementation (P = .02 and P = .01, respectively). After controlling for multiple confounding variables, omega-3 supplementation was found to be protective against olfactory loss (odds ratio [OR] 0.05, 95% CI 0.003-0.81, P = .03). Tumor functionality was a significant independent predictor for olfactory loss (OR 32.7, 95% CI 1.15-929.5, P = .04). CONCLUSION: Omega-3 supplementation appears to be protective for the olfactory system during the healing period in patients who undergo endoscopic resection of sellar and parasellar masses.

Arterial-spin labeling MRI identifies residual cerebral arteriovenous malformation following stereotactic radiosurgery treatment.

BACKGROUND AND PURPOSE: Brain arteriovenous malformation (AVM) treatment by stereotactic radiosurgery (SRS) is effective, but AVM obliteration following SRS may take two years or longer. MRI with arterial-spin labeling (ASL) may detect brain AVMs with high sensitivity. We determined whether brain MRI with ASL may accurately detect residual AVM following SRS treatment. MATERIALS AND METHODS: We performed a retrospective cohort study of patients who underwent brain AVM evaluation by DSA between June 2010 and June 2015. Inclusion criteria were: (1) AVM treatment by SRS, (2) follow-up MRI with ASL at least 30 months after SRS, (3) DSA within 3 months of the follow-up MRI with ASL, and (4) no intervening AVM treatment between the MRI and DSA. Four neuroradiologists blindly and independently reviewed follow-up MRIs. Primary outcome measure was residual AVM indicated by abnormal venous ASL signal. RESULTS: 15 patients (12 females, mean age 29 years) met inclusion criteria. There were three posterior fossa AVMs and 12 supratentorial AVMs. Spetzler-Martin (SM) Grades were: SM1 (8%), SM2 (33%), SM3 (17%), SM4 (25%), and SM5 (17%). DSA demonstrated residual AVM in 10 patients. The pooled sensitivity, specificity, positive predictive value, and negative predictive value of venous ASL signal for predicting residual AVM were 100% (95% CI: 0.9-1.0), 95% (95% CI: 0.7-1.0), 98% (95% CI: 0.9-1.0), and 100% (95% CI: 0.8-1.0), respectively. High inter-reader agreement as found by Fleiss' Kappa analysis (k = 0.92; 95% CI: 0.8-1.0; P < 0.0001). CONCLUSIONS: ASL is highly sensitive and specific in the detection of residual cerebral AVM following SRS treatment.

Endovascular versus medical therapy for large-vessel anterior occlusive stroke presenting with mild symptoms.

BACKGROUND: Acute ischemic stroke patients with a large-vessel occlusion but mild symptoms (NIHSS ≤ 6) pose a treatment dilemma between medical management and endovascular thrombectomy. AIMS: To evaluate the differences in clinical outcomes of endovascular thrombectomy-eligible patients with target-mismatch perfusion profiles who undergo either medical management or endovascular thrombectomy. METHODS: Forty-seven patients with acute ischemic stroke due to large-vessel occlusion, NIHSS ≤ 6, and a target-mismatch perfusion imaging profile were included. Patients underwent medical management or endovascular thrombectomy following treating neurointerventionalist and neurologist consensus. The primary outcome measure was NIHSS shift. Secondary outcome measures were symptomatic intracranial hemorrhage, in-hospital mortality, and 90-day mRS scores. The primary intention-to-treat and as-treated analyses were compared to determine the impact of crossover patient allocation on study outcome measures. RESULTS: Forty-seven patients were included. Thirty underwent medical management (64%) and 17 underwent endovascular thrombectomy (36%). Three medical management patients underwent endovascular thrombectomy due to early clinical deterioration. Presentation NIHSS (P = 0.82), NIHSS shift (P = 0.62), and 90-day functional independence (mRS 0-2; P = 0.25) were similar between groups. Endovascular thrombectomy patients demonstrated an increased overall rate of intracranial hemorrhage (35.3% vs. 10.0%; P = 0.04), but symptomatic intracranial hemorrhage was similar between groups (P = 0.25). In-hospital mortality was similar between groups (P = 0.46), though all two deaths in the medical management group occurred among crossover patients. Endovascular thrombectomy patients demonstrated a longer length of stay (7.6 ± 7.2 vs. 4.3 ± 3.9 days; P = 0.04) and a higher frequency of unfavorable discharge to a skilled-nursing facility (P = 0.03) rather than home (P = 0.05). CONCLUSIONS: Endovascular thrombectomy may pose an unfavorable risk-benefit profile over medical management for endovascular thrombectomy-eligible acute ischemic stroke patients with mild symptoms, which warrants a randomized trial in this subpopulation.

Granular Cell Pituitary Tumor in a Patient with Multiple Endocrine Neoplasia-1.

Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant disorder characterized by parathyroid, pancreatic islet, and pituitary tumors. Approximately 40% of MEN-1 patients harbor a pituitary adenoma. Separately, granular cell tumors (GCTs) of the sellar/parasellar region are an exceedingly rare clinical entity with less than 100 reported cases in the literature. These slow-growing, often asymptomatic lesions are difficult to diagnose and may mimic pituitary adenoma, Rathke cleft cyst, or other sellar/supra-sellar pathology. There is no known association with MEN-1 or any other familial syndrome. A 36-year-old neurologically normal woman with known MEN-1 underwent a screening magnetic resonance imaging (MRI) scan which revealed a 10 mm x 6 mm x 7 mm sellar/suprasellar lesion. She underwent endoscopic endonasal transsphenoidal resection. Subsequent neuropathological analysis was consistent with GCT of the pituitary gland. Here we describe the first report to our knowledge of a GCT of the pituitary gland occurring in a patient with MEN-1.

Neuroimaging selection for thrombectomy in pediatric stroke: a single-center experience.

BACKGROUND: The extended time window for endovascular therapy in adult stroke represents an opportunity for stroke treatment in children for whom diagnosis may be delayed. However, selection criteria for pediatric thrombectomy has not been defined. METHODS: We performed a retrospective cohort study of patients aged <18 years presenting within 24 hours of acute large vessel occlusion. Patient consent was waived by our institutional IRB. Patient data derived from our institutional stroke database was compared between patients with good and poor outcome using Fisher's exact test, t-test, or Mann-Whitney U-test. RESULTS: Twelve children were included: 8/12 (66.7%) were female, mean age 9.7±5.0 years, median National Institutes of Health Stroke Scale (NIHSS) 11.5 (IQR 10-14). Stroke etiology was cardioembolic in 75%, dissection in 16.7%, and cryptogenic in 8.3%. For 2/5 with perfusion imaging, Tmax >4 s appeared to better correlate with NIHSS. Nine patients (75%) were treated: seven underwent thrombectomy alone; one received IV alteplase and thrombectomy, and one received IV alteplase alone. Favorable outcome was achieved in 78% of treated patients versus 0% of untreated patients (P=0.018). All untreated patients had poor outcome, with death (n=2) or severe disability (n=1) at follow-up. Among treated patients, older children (12.8±2.9 vs 4.2±5.0 years, P=0.014) and children presenting as outpatient (100% vs 0%, P=0.028) appeared to have better outcomes. CONCLUSIONS: Perfusion imaging is feasible in pediatric stroke and may help identify salvageable tissue in extended time windows, though penumbral thresholds may differ from adult values. Further studies are needed to define criteria for thrombectomy in this unique population.

Surgical Treatment of Recurrent Previously Coiled and/or Stent-Coiled Intracerebral Aneurysms: A Single-Center Experience in a Series of 75 Patients.

BACKGROUND: Endovascular treated cerebral aneurysms have a greater recurrence rate compared with microsurgical clip ligation. Despite recent endovascular advances, microsurgical clip ligation might be the treatment of choice for certain previously endovascular treated recurrent aneurysms. We report on our single-center experience with 76 previously coiled and/or stent-coiled aneurysms. OBJECTIVE: To analyze the surgical and radiologic outcome after clipping of previous endovascular treated recurrent cerebral aneurysms. METHODS: Patients were retrospectively identified. Demographic data, aneurysm size, location, perioperative coil extraction, occlusion rate, and complication rate were recorded. Patients were divided into a previously coiled-only group (COG) and a previously stent-assisted coiled group (SAC). RESULTS: Seventy-five patients with 76 aneurysms were included. Sixty-nine patients were included in the COG, 7 patients in the SAC group. Complete or acceptable near-complete occlusion was obtained in 95% of patients in the COG and 57% in the SAC group. Two patients in the COG (2.9%) died postoperatively of a major stroke. One patient died of rehemorrhage after wrapping of an aneurysm. Minor complications occurred in 8.7%. In the SAC group, the mortality was 0%, with 1 major stroke (14.2%), 1 minor stroke (14.2%), and 1 cranial nerve palsy (14.2%). Intraoperative coil extraction and previous stent-assisted coiling were significant predictors of complication rate (P = 0.025 and P = 0.0036 respectively). Previous stent-assisted coiling was a significant predictor of incomplete occlusion (P = 0.036). CONCLUSIONS: Microsurgical clipping of previously endovascular treated recurrent aneurysms is an effective treatment with high obliteration rates. Previously stent-assisted coiling and intraoperative coil extraction are predictors of worse outcome and incomplete occlusion.

High-resolution 3D volumetric contrast-enhanced MR angiography with a blood pool agent (ferumoxytol) for diagnostic evaluation of pediatric brain arteriovenous malformations.

OBJECTIVE Patients with brain arteriovenous malformations (AVMs) often require repeat imaging with MRI or MR angiography (MRA), CT angiography (CTA), and digital subtraction angiography (DSA). The ideal imaging modality provides excellent vascular visualization without incurring added risks, such as radiation exposure. The purpose of this study is to evaluate the performance of ferumoxytol-enhanced MRA using a high-resolution 3D volumetric sequence (fe-SPGR) for visualizing and grading pediatric brain AVMs in comparison with CTA and DSA, which is the current imaging gold standard. METHODS In this retrospective cohort study, 21 patients with AVMs evaluated by fe-SPGR, CTA, and DSA between April 2014 and August 2017 were included. Two experienced raters graded AVMs using Spetzler-Martin criteria on all imaging studies. Lesion conspicuity (LC) and diagnostic confidence (DC) were assessed using a 5-point Likert scale, and interrater agreement was determined. The Kruskal-Wallis test was performed to assess the raters' grades and scores of LC and DC, with subsequent post hoc pairwise comparisons to assess for statistically significant differences between pairs of groups at p < 0.05. RESULTS Assigned Spetzler-Martin grades for AVMs on DSA, fe-SPGR, and CTA were not significantly different (p = 0.991). LC and DC scores were higher with fe-SPGR than with CTA (p < 0.05). A significant difference in LC scores was found between CTA and fe-SPGR (p < 0.001) and CTA and DSA (p < 0.001) but not between fe-SPGR and DSA (p = 0.146). A significant difference in DC scores was found among DSA, fe-SPGR, and CTA (p < 0.001) and between all pairs of the groups (p < 0.05). Interrater agreement was good to very good for all image groups (κ = 0.77-1.0, p < 0.001). CONCLUSIONS Fe-SPGR performed robustly in the diagnostic evaluation of brain AVMs, with improved visual depiction of AVMs compared with CTA and comparable Spetzler-Martin grading relative to CTA and DSA.

Porcine small intestine submucosal grafts improve remucosalization and progenitor cell recruitment to sites of upper airway tissue remodeling.

BACKGROUND: To better understand upper airway tissue regeneration, the exposed cartilage and bone at donor sites of tissue flaps may serve as in vivo "Petri dishes" for active wound healing. The pedicled nasoseptal flap (NSF) for skull-base reconstruction creates an exposed donor site within the nasal airway. The objective of this study is to evaluate whether grafting the donor site with a sinonasal repair cover graft is effective in promoting wound healing. METHODS: In this multicenter, prospective trial, subjects were randomized to intervention (graft) or control (no graft) intraoperatively after NSF elevation. Individuals were evaluated at 2, 6, and 12 weeks postintervention with endoscopic recordings. Videos were graded (Likert scale) by 3 otolaryngologists blinded to intervention on remucosalization, crusting, and edema. Scores were analyzed for interrater reliability and cohorts compared. Biopsy and immunohistochemistry at the leading edge of wound healing was performed in select cases. RESULTS: Twenty-one patients were randomized to intervention and 26 to control. Subjects receiving the graft had significantly greater overall remucosalization (p = 0.01) than controls over 12 weeks. Although crusting was less in the small intestine submucosa (SIS) group, this was not statistically significant (p = 0.08). There was no overall effect on nasal edema (p = 0.2). Immunohistochemistry demonstrated abundant upper airway basal cell progenitors in 2 intervention samples, suggesting that covering grafts may facilitate tissue proliferation via progenitor cell expansion. CONCLUSION: This prospective, randomized, controlled trial indicates that a porcine SIS graft placed on exposed cartilage and bone within the upper airway confers improved remucosalization compared to current practice standards.