Morning Glory Disc Anomaly: Expanding the MR Phenotype.

BACKGROUND AND PURPOSE: Morning glory disc anomaly (MGDA) is a congenital malformation characterized by a funnel-shaped optic disc excavation with radiating vessels and a central glial tuft. Imaging is essential to evaluate associated cephalocele and steno-occlusive vasculopathy. The goal of this study was to assess optic nerve, chiasmatic, and sphenoid bone morphology in MGDA. MATERIALS AND METHODS: This retrospective study examined all subjects with funduscopically confirmed MGDA diagnosed and imaged with brain MR imaging between 2008 and 2023. RESULTS: Thirty-two children met inclusion criteria. Ocular involvement was unilateral in 29 subjects and bilateral in 3. Segmental optic nerve enlargement ipsilateral to the MGDA was seen in 21 subjects, with 3 also demonstrating a segmental reduction in the size of the ipsilateral optic nerve. Segmental reduction in the size of the ipsilateral optic nerve was present in 3 additional subjects, one with bilateral MGDA. The optic chiasm appeared asymmetrically thickened in 21 subjects, often with deformity. The optic nerves appeared normal in signal intensity in all subjects, with faint peripheral chiasmatic enhancement in 4 of 20 patients who received contrast. Optic nerve findings were stable in 15 subjects with multiple examinations. A persistent craniopharyngeal canal was identified in 17 subjects with sphenoid cephalocele in 1 and mild inferior pituitary gland displacement in 4. Tubular or nodular nasopharyngeal lesions were seen in 10 subjects. One subject had an off-midline sphenoid bone cleft, midbrain deformity, and abnormal thickening of and enhancement around the left oculomotor nerve; the oculomotor nerve finding was present in 1 additional patient. CONCLUSIONS: MGDA often manifests with ipsilateral optic nerve thickening, leading to a potential misdiagnosis as optic glioma. MGDA is also commonly associated with a persistent craniopharyngeal canal with variable pituitary gland and infundibular deformity, cephalocele, and tubular or nodular nasopharyngeal lesions.

An expanded series of distal bypass using the distal vein patch technique to improve prosthetic graft performance in critical limb ischemia.

OBJECTIVES: The endovascular first approach has led to increasing complexity for surgical bypass especially in those patients without autogenous conduit. The use of vein interposed at the distal anastomosis has been reported to improve the results of prosthetic grafts. This series expands our initial experience with the distal vein patch technique (DVP) reporting a larger cohort with enhanced follow-up. DESIGN: A retrospective review of prospectively collected data was performed for distal bypasses from July 1995 to November 2008. MATERIALS/METHODS: 1296 tibial bypasses were performed with 270 using the DVP technique. Patient demographics included; 49% diabetes, 20% chronic renal failure, 33% prior failed bypass. Indications for revascularization were claudication (9.3%), rest pain (27.8%), gangrene (22.2%), and non-healing ulceration (40.7%). Lack of vein for the bypass conduit resulted from previous failed grafts (55%), coronary bypass (18%), poor quality vein (23%), or prior vein stripping (8%). Follow-up ranged from 1 to 48 months with graft surveillance by pulse exam, ABI, and Duplex ultrasound. Primary patency and limb salvage ± SE were determined by Kaplan-Meier life-table analysis using Rutherford criteria. RESULTS: Bypasses originated from the external iliac (29%), CFA (55%), SFA (13%), popliteal (1%), and prior grafts (2%). Recipient arteries were below knee popliteal (6%), anterior tibial (25%), posterior tibial (30%), and peroneal (39%). Perioperative graft failure occurred in 13 cases with a total of 41 graft failures leading to 39 major amputations. Primary graft patency from one to four years was 79.8%, 75.6% 65.9%, and 51.2%. Corresponding limb salvage rates were 80.6%, 78.0%, 75.7%, and 67.5%. CONCLUSION: Although not addressed by a randomized trial, we believe this expanded series is a more accurate reflection of expected results confirming that the DVP bypass leads to reasonable long-term results for those challenging patients that require prosthetic distal bypass for lower extremity revascularization.

Stretched and sheared microcatheter retained after onyx embolization of infantile myofibromatosis.

We describe a rare neurointerventional complication, namely a stretched and sheared microcatheter, extending 52 cm from its point of retention within an Onyx cast in an infant patient's neck mass, to the groin. The tumor was an unusual manifestation of infantile myofibromatosis and prior attempts at resection had proven impossible due to bleeding. Recommendations regarding microcatheter selection, diagnostic workup, and management of the ensuing complication are given.

Trigeminocardiac reflex in a child during pre-Onyx DMSO injection for juvenile nasopharyngeal angiofibroma embolization. A case report.

We describe the occurrence of the trigeminocardiac reflex (TCR) during DMSO pre-flushing of the microcatheter in preparation for Onyx embolization via the internal maxillary artery. TCR has not been previously associated with embolization of extradural entities. Familiarity with this clinical reflex and its proper management may help in planning neurointerventional procedures involving DMSO injection in the trigeminal territory.

Safety and clinical efficacy of Onyx for embolization of extracranial head and neck vascular anomalies.

BACKGROUND AND PURPOSE: Onyx was developed for embolization of central nervous system AVMs but is increasingly used extracranially because of its unique physical properties. We review our experience and results with the use of Onyx for the treatment of fast-flow extracranial vascular lesions. MATERIALS AND METHODS: We retrospectively analyzed clinical and imaging records of 22 patients who underwent 71 extracranial embolizations from March 2007 through January 2010. The diagnoses were the following: cervicofacial AVM (n = 18), traumatic fistula (n = 3), and vessel laceration (n = 1). In 62 of 71 procedures (87%), Onyx was the sole embolic agent; it was delivered transarterially in 67/71 and percutaneously in 4/71 procedures. Clinical goals included amelioration of pain and control of bleeding. The clinical efficacy of embolization was judged by symptom control, and adverse events were assessed by clinical examination and history, both postembolization and 4 weeks postprocedure. RESULTS: Cessation of acute bleeding was achieved in 13/14 cases, with 1 case of immediate recurrent massive epistaxis prompting reintubation and further embolization. Control of subacute bleeding episodes and pain was achieved for all patients. Following staged embolization, 7 patients underwent surgical resection without significant blood loss. Surgeons reported high satisfaction with the intraoperative handling properties of Onyx. Transient swelling, local tenderness, or numbness was encountered after 7 procedures. There were no stuck catheters, vessel dissections, or vessel ruptures and no skin discoloration. CONCLUSIONS: Staged Onyx embolization was clinically efficacious in managing extracranial fast-flow vascular malformations and lesions, with low associated morbidity.

The presentation and management of multiple paraganglioma in head and neck.

OBJECTIVE: We report the presentation and management of an 18-year-old male, who presented with bilateral carotid body paragangliomas and a unilateral jugular body paraganglioma. METHOD: A comprehensive review of the medical literature concerning paragangliomas in the pediatric and adult population is discussed. RESULTS: Presentations of multiple paragangliomas in an 18-year-old have never been described. CONCLUSION: This is the first case of multiple paragangliomas in a 18-year-old male, who was treated with embolisation and surgical resection and remains disease free 2 years from surgery.

Interferon-beta is a key regulator of proinflammatory events in experimental autoimmune encephalomyelitis.

BACKGROUND: Interferon (IFN)-ß is an effective therapy for relapsing-remitting multiple sclerosis, yet its mechanism of action remains ill-defined. OBJECTIVES: Our objective was to characterize the role of IFN-ß in immune regulation in experimental autoimmune encephalomyelitis (EAE). METHODS: IFN-ß(+/+) and IFN-ß(-/-) mice were immunized with myelin oligodendrocyte glycoprotein peptide in the presence or absence of IFN-ß, to induce EAE. Disease pathogenesis was monitored in the context of incidence, time of onset, clinical score, and immune cell activation in the brains, spleens and lymph nodes of affected mice. RESULTS: Compared with IFN-ß(+/+) mice, IFN-ß(-/-) mice exhibited an earlier onset and a more rapid progression of EAE, increased numbers of CD11b(+) leukocytes infiltrating affected brains and an increased percentage of Th17 cells in the central nervous system and draining lymph nodes. IFN-ß treatment delayed disease onset and reduced disease severity. Ex vivo experiments revealed that the lack of IFN-ß results in enhanced generation of autoreactive T cells, a likely consequence of the absence of IFN-ß-regulated events in both the CD4(+) T cells and antigen-presenting dendritic cells. Gene expression analysis of IFN-ß-treated bone marrow macrophages (CD11b(+)) identified modulation of genes affecting T cell proliferation and Th17 differentiation. CONCLUSIONS: We conclude that IFN-ß acts to suppress the generation of autoimmune-inducing Th17 cells during the development of disease as well as modulating pro-inflammatory mediators.

The lipid laden macrophage index as a marker of aspiration in patients with type I and II laryngeal clefts.

OBJECTIVES: Laryngeal clefts are uncommon congenital anomalies that may cause pulmonary aspiration, leading to considerable morbidity including recurrent pneumonias. The lipid laden macrophage index (LLMI) is a potential marker of pulmonary aspiration. The objective of this study was to assess the utility of the lipid laden macrophage index as a marker of severity of pulmonary aspiration in children with laryngeal clefts and its role in the management of these patients. METHODS: An institutional review board approved retrospective review of all patients with laryngeal cleft who had also underwent direct laryngoscopy with rigid bronchoscopy and flexible bronchoscopy with bronchoalveolar lavage. The LLMI was measured from the lavage and compared to clinical and radiological data. RESULTS: Forty-four patients with laryngeal clefts (31 type I clefts and 13 type II clefts) underwent assessment with flexible bronchoscopy and bronchoalveolar lavage. The median age at first outpatient visit in our Center for Aero-digestive Disorder was 0.92 years in patients with type I clefts and 1.66 years in patients with type 2 clefts. All patients in this study had at least one modified barium swallow (MBS) performed to assess for aspiration. The mean LLMI was significantly higher in patients with type II (mean+/-SEM) 81.8+/-11.9 clefts compared to type I clefts 44.9+/-5.6. CONCLUSIONS: We recommend obtaining LLMI in patients with laryngeal cleft. The lipid laden macrophage index is increased in patients with more severe laryngeal clefts, thus potentially predicting those patients whom would most benefit from early surgical intervention.

Sinonasal and laryngeal carcinoma in children: correlation of imaging characteristics with clinicopathologic and cytogenetic features.

BACKGROUND AND PURPOSE: Pediatric upper airway carcinoma is uncommon, symptoms are nonspecific, and diagnosis is often delayed. In this study, we describe the imaging, cytogenetics, and clinical courses of 4 patients with pediatric upper airway carcinoma. MATERIALS AND METHODS: Four patients with upper airway carcinoma were identified during a 2.5-year period. CT (n = 4) and MR imaging (n = 3) studies, tumor histopathologic features and cytogenetics, patient treatment, and clinical course were reviewed. RESULTS: Patients were aged 12 to 15 years. One tumor involved the larynx with poorly defined margins and heterogeneous enhancement; 1 heterogeneously enhancing tumor involved the epiglottis with necrotic cervical lymphadenopathy. There were 2 enhancing sinonasal tumors with bony destruction in 1 tumor. Tumors had a relatively short relaxation time on FSEIR MR imaging. Histopathologic examination revealed poorly differentiated squamous cell carcinoma (n = 3) and well-differentiated squamous cell carcinoma (n = 1). Cytogenetic analysis revealed chromosomal abnormalities in 3 tumors: 2 showed a chromosomal translocation t(15;19), and 1 showed a chromosomal translocation t(1;5) and loss of a portion of chromosome 22q. Results of in situ hybridization for EBV were negative (n = 3). Treatment included tumor resection (n = 2), chemotherapy (n = 4), and radiation therapy (n = 3). Patients with t(15;19) died months after diagnosis. Two patients were alive at 8-year follow-up. CONCLUSIONS: Childhood carcinoma of the upper airway is uncommon but should be considered in the diagnosis of upper airway tumors that display aggressive imaging characteristics. Carcinoma with t(15;19) is rare but has been reported, usually in young patients with midline carcinoma of the neck or mediastinum, with a rapidly fatal course.

The needle and the damage done: pericardial effusion with tamponade after needle ingestion in an infant.

OBJECTIVE: Paediatric foreign bodies may present with vague and nonspecific symptoms. It is important to have a high index of suspicion when managing such cases. METHOD: We report the case of a nine-month-old infant who presented with a wheeze, cough and fever following ingestion of a needle. RESULTS: This patient developed pericardial tamponade as a consequence of the needle ingestion, and required a thoracotomy for retrieval. We discuss the pathophysiology involved and the surgery required. CONCLUSION: Pericardial tamponade is a rare but potentially fatal manifestation of an ingested foreign body.

Paediatric aneurysmal bone cysts of the head and neck.

OBJECTIVE: To provide an up to date review of the literature on aneurysmal bone cysts, including their diagnosis, pathology, pathophysiology, radiology and management. METHOD: Retrospective review of six cases over a 15-year period. RESULTS: Six patients (age range, eight months to 17 years; mean, 9.6 years) presented with an aneurysmal bone cyst in the mandible (n = 3), maxilla (n = 2) or occipital soft tissue (n = 1). Each patient underwent primary excision, with one subsequent recurrence. CONCLUSION: Aneurysmal bone cysts are benign but locally destructive entities which may occasionally present to otolaryngologists, since they can involve the head and neck region, in particular the mandible.

Interferons and viruses: signaling for supremacy.

Interferon (IFN)-alpha and IFN-beta are critical mediators of host defense against microbial challenges, directly interfering with viral infection and influencing both the innate and adaptive immune responses. IFNs exert their effects in target cells through the activation of a cell-surface receptor, leading to a cascade of signaling events that determine transcriptional and translation regulation. Understanding the circuitry associated with IFN-mediated signal transduction that leads to a specific biological outcome has been a major focus of our laboratory. Through the efforts of graduate students, postdoctoral fellows, a skilled research technologist, and important collaborations with investigators elsewhere, we have provided some insights into the complexity of the IFN system-and the elegance and simplicity of how protein-protein interactions define biological function.

Endoscopic sinus surgery in cystic fibrosis: do patients benefit from surgery?

OBJECTIVE: To examine the effects of endoscopic sinus surgery on the pulmonary status of cystic fibrosis (CF) patients through the objective parameters of steroid use, pulmonary function tests (PFTs), and inpatient hospital days (IHDs). METHODS: Retrospective chart review of all patients with CF who underwent endoscopic sinus surgery from 1993 to 1999 at a tertiary care children's hospital. Preoperative pulmonary function, inhaler and steroid use, and IHDs were compared to postoperative parameters within a 1-year period. RESULTS: Sixty-six patients, including eight lung transplant patients, underwent a total of 112 endoscopic sinus surgery procedures; 25 patients underwent more than one procedure. Patients were taking oral steroids preoperatively in 28% of procedures and inhaled steroids in 40%. Postoperatively, there was no statistically significant change in oral or inhaled steroid use, or in postoperative pulmonary function. If the index hospitalization, which was often for reasons not related to sinus disease, was considered part of the preoperative time period, endoscopic sinus surgery (ESS) was noted to result in a marked reduction (9.5 days (adjusted), P=0.001) in hospital days during the subsequent 6 months. If the date of the procedure alone was used to define pre- and postoperative time periods, the reduction in postoperative days was more modest and not statistically significant (3.5 days (adjusted), P=0.21). CONCLUSIONS: Although we found no statistically significant difference in PFTs, or steroid requirements following ESS, ESS may have resulted in a reduced need for hospitalization in the 6 months following the procedure. Future prospective studies in a larger number of patients and using more detailed outcome measures are needed to better evaluate the effects of endoscopic sinus surgery in pediatric patients with CF.

Combinatorial control of prion protein biogenesis by the signal sequence and transmembrane domain.

The prion protein (PrP) is synthesized in three topologic forms at the endoplasmic reticulum. (sec)PrP is fully translocated into the endoplasmic reticulum lumen, whereas (Ntm)PrP and (Ctm)PrP are single-spanning membrane proteins of opposite orientation. Increased generation of (Ctm)PrP in either transgenic mice or humans is associated with the development of neurodegenerative disease. To study the mechanisms by which PrP can achieve three topologic outcomes, we analyzed the translocation of proteins containing mutations introduced into either the N-terminal signal sequence or potential transmembrane domain (TMD) of PrP. Although mutations in either domain were found to affect PrP topogenesis, they did so in qualitatively different ways. In addition to its traditional role in mediating protein targeting, the signal was found to play a surprising role in determining orientation of the PrP N terminus. By contrast, the TMD was found to influence membrane integration. Analysis of various signal and TMD double mutants demonstrated that the topologic consequence of TMD action was directly dependent on the previous, signal-mediated step. Together, these results reveal that PrP topogenesis is controlled at two discrete steps during its translocation and provide a framework for understanding how these steps act coordinately to determine the final topology achieved by PrP.

Craniofacial, temporal bone, and audiologic abnormalities in the spectrum of hemifacial microsomia.

OBJECTIVES: To evaluate the clinical, audiologic, and temporal bone computed tomograpic findings in patients with hemifacial microsomia and to use the OMENS (each letter of the acronym indicates 1 of the following 5 dysmorphic manifestations: O, orbital asymmetry; M, mandibular hypoplasia; E, auricular deformity; N, nerve involvement; and S, soft tissue deficiency) grading system to assess possible correlations between the severity of dysmorphic features with the type of abnormalities in the temporal bone and with degree of hearing deficit. DESIGN: Retrospective study. SETTING: Tertiary care children's hospital. PATIENT: Forty patients with hemifacial microsomia. RESULT: Mandibular hypoplasia and auricular abnormalities were the most common clinical manifestations, present in 39 patients (97%) and 38 patients (95%), respectively. Conductive hearing loss was noted in 35 patients (86%) and sensorineural hearing loss in 4 patients (10%). Facial nerve weakness was present in 20 patients (50%). Twenty patients had unilateral aural atresia, 12 patients had unilateral aural stenosis, and 7 patients had bilateral anomalies. Moderate hypoplasia or atresia of the middle ear was noted in 36 patients (90%) and ossicles were malformed in 30 patients (75%). Hypoplasia of the oval window was the most common inner ear abnormality. CONCLUSIONS: Severity of craniofacial features (total OMENS score) significantly correlated with the degree of temporal bone abnormality, but no correlation was noted with the degree or type of hearing loss. We recommend the following: (1) use of the OMENS classification system for documentation and analysis of dysmorphic finding in hemifacial microsomia; (2) complete audiologic evaluation in all patients with hemifacial microsomia regardless of the type of craniofacial abnormalities; and (3) temporal bone computed tomography for further evaluation of hearing deficit.

Management of orbital subperiosteal abscess in children.

OBJECTIVES: To present guidelines for the management of an orbital subperiosteal abscess (SPA) in children and to assess the efficacy and safety of transnasal endoscopic drainage of an orbital SPA. SETTING: Tertiary care children's hospital. PATIENTS: Nineteen patients treated for an SPA between July 1997 and December 1999. The age of the patients ranged from 17 months to 14 years (mean, 6 years). The male-female ratio was 10:9. Treatment modalities included transnasal endoscopic drainage (n = 11), external drainage (n = 3), and intravenous antibiotics alone (n = 5). RESULTS: Bilateral pansinusitis was the most common cause. All patients received an initial trial of intravenous antibiotics. Based on the Fisher exact test, no statistically significant differences were detected for age, sex, presence of gaze restriction, and radiographic findings. Based on multiple logistic regression, degree of proptosis was the only significant multivariate predictor of surgery (P =.003). The estimated probability of surgery was 6% when there was no proptosis, and 92% for 2 mm of proptosis. The location of the SPA determined the route of surgical drainage. Eleven patients with a medially based SPA underwent drainage via the transnasal endoscopic approach, and 3 with a superior SPA underwent drainage externally. The external approach was associated with a longer hospital stay (median, 7 days) than either the endoscopic or the intravenous antibiotic approach (median, 5 days).

Mitomycin: effects on laryngeal and tracheal stenosis, benefits, and complications.

The management of laryngeal and tracheal stenosis continues to challenge us, despite advances in surgical techniques and better understanding of the wound healing process. Injury to the airway mucosa is the inciting event, regardless of the cause of the stenosis. Mitomycin-C is an antineoplastic antibiotic that acts as an alkylating agent by inhibiting DNA and protein synthesis. It can inhibit cell division, protein synthesis, and fibroblast proliferation. Topical application of mitomycin-C (0.4 mg/mL) was used as an adjuvant treatment in the endoscopic laser management of laryngeal and tracheal stenosis in 15 patients. Fourteen patients (93%) have shown improvement of their airway and resolution of their preoperative symptoms. After a mean follow-up of 18 months, no complication was noted with regard to the application of mitomycin-C. This study gives promising findings on the efficacy and safety of mitomycin-C as an adjuvant treatment in the management of selected cases of laryngeal and tracheal stenosis.

Preliminary results of intraoperative mitomycin-C in the treatment and prevention of glottic and subglottic stenosis.

Mitomycin-C is an antineoplastic antibiotic that acts as an alkylating agent by inhibiting DNA and protein synthesis. It can inhibit cell division, protein synthesis, and fibroblast proliferation. The purpose of this pilot study is to investigate intraoperative applications of topical mitomycin-C in treatment and prevention of glottic and subglottic stenosis. Eight patients with posterior glottic and/or subglottic stenosis were treated with endoscopic CO2 laser excision followed by topical application of 0.5 cc of 0.4 mg mitomycin-C per milliliter of saline for 4 minutes at the surgical site. After mean follow-up of 15 months (10-20) all patients had clinical improvement of their airway and resolution of their preoperative symptoms. No complications were noted in this study. Although a longer follow-up and further controlled studies are needed, the use of topical mitomycin-C may prove useful in the treatment and prevention of subsequent restenosis and scar formation in the larynx and trachea.