V. Michelle Silvera

Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome.

Background: Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor lonafarnib ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation. Methods: Thirty-seven participants with Hutchinson-Gilford progeria syndrome received pravastatin, zoledronic acid, and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial. Results: No participants withdrew because of side effects. Primary outcome success was predefined by improved per-patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P<0.0001). Key cardiovascular and skeletal secondary variables were predefined. Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001–0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0% to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial. Conclusions: Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747.

Image guidance systems for minimally invasive sinus and skull base surgery in children

OBJECTIVE The use of image guidance for sinonasal and skull base surgery has been well-characterized in adults but there is limited information on the use of these systems in the pediatric population, despite their widespread use. The aim of this study is to evaluate the use of image guidance systems to facilitate an endoscopic minimally invasive approach to sinonasal and skull base surgery in a pediatric population. METHODS A retrospective cohort study was performed at a tertiary pediatric hospital. Thirty-three children presented with complications of sinusitis, tumors, traumatic, or congenital lesions of the skull base and underwent endoscopic surgery using image guidance from March 2000 to April 2007. Patient variables including diagnosis, extent of disease, and complications were extracted from paper and computer charts. Additional surgical variables including set-up time, accuracy, surgeon satisfaction index and number of uses per case were also reviewed. RESULTS Twenty-eight patients (85%) underwent sinonasal surgery and five (15%) underwent skull base surgery. Indications included infectious complications of acute sinusitis (N=15), neoplasms (N=12), choanal atresia (N=4), and cerebrospinal fluid leak (N=2). Thirty-one patients (94%) required only one procedure. No surgical complications were reported. Surgeon satisfaction, mean accuracy and number of uses per procedure increased over time (p<0.05). CONCLUSIONS Image guidance systems are safe and effective tools that facilitate a minimally invasive approach to sinonasal and skull base surgery in children. Consistent with adult literature, usage and surgeon comfort increased with experience. The additional anatomical information obtained by image guidance systems facilitates a minimally invasive endoscopic approach for sinonasal and skull base pathologies.

Spinal cord involvement in a child with raccoon roundworm (Baylisascaris procyonis) meningoencephalitis

A 14-month-old previously healthy boy developed progressively worsening neurological symptoms secondary to eosinophilic meningoencephalitis with myelitis caused by raccoon roundworm (Baylisascaris procyonis) infection. MRI demonstrated T2 hyperintensity and enhancement of the cerebral white matter, cerebellum and spinal cord. Prior case reports have described signal abnormality within the brains of patients with raccoon roundworm neural larva migrans (NLM). This is a unique case in which spinal cord involvement was established by imaging. Knowledge of this combination of imaging findings expands the known imaging phenotype of this noteworthy infection.

Pediatric Nodular Fasciitis in the Head and Neck: Evaluation and Management

IMPORTANCE Nodular fasciitis is a rare benign tumor that can present in the head and neck in children. A better understanding of this rare condition is critical to optimize management. OBJECTIVE To review the presentation, evaluation, diagnosis, and management of pediatric nodular fasciitis of the head and neck. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of all patients treated for nodular fasciitis of the head and neck over a 20-year period at a pediatric tertiary care center. INTERVENTION Surgical excision. MAIN OUTCOMES AND MEASURES Clinical data, including age, presenting symptoms, anatomical site(s), evaluation, treatment, and complications. RESULTS Fifteen children with pathologically confirmed nodular fasciitis of the head and neck were identified, including 8 boys and 7 girls. The median (range) age at diagnosis was 9.3 years (2 months to 18 years). Patients most commonly presented with a firm, enlarging soft-tissue mass. Two patients reported pain, and 1 patient presented with erythema. The most common location was the maxillofacial region (5 patients). Other locations included the scalp (3 patients), forehead (2 patients), neck (2 patients), mandible (1 patient), postauricular region (1 patient), and nasal dorsum (1 patient). One patient reported a preceding trauma, and 1 patient, a preceding infection. Presurgical imaging varied; imaging modalities used included computed tomography, magnetic resonance imaging, radiography, ultrasound, and sialography. All patients underwent surgical excision, which focused on excising the mass while preserving surrounding normal tissues. Mean (range) follow-up was 7.69 (0-46) months. Two minor complications were reported: 1 patient who underwent a near-total excisional biopsy experienced residual firmness and tenderness at the site of the lesion and another patient was left with an unfavorable cosmetic scar that necessitated intralesional steroid injection. No patient demonstrated recurrence at follow-up. CONCLUSIONS AND RELEVANCE Although an uncommon diagnosis, nodular fasciitis should be considered in the evaluation and treatment of head and neck soft-tissue masses in children. Preoperative imaging is nonspecific and variable. Pathological findings are necessary for diagnosis. Surgical excisional biopsy is curative, with no instances of recurrence in our series.

Disorders and Tumors of the Salivary Glands in Children

Salivary gland neoplasms are rare in children. In infants most tumors are benign hemangiomas, with some notable exceptions, such as sialoblastomas. An asymptomatic swelling in the periauricular region is the most common presenting complaint in older children. Approximately 50% of these lesions are malignant, which dictates a thorough diagnostic evaluation by a head and neck surgeon. Surgical excision is the primary treatment modality. Prognosis is primarily determined by histopathologic findings. This review discusses neoplastic lesions of the salivary glands in children, and malignant epithelial tumors in particular.

Primary leptomeningeal central nervous system lymphoma in an immunocompetent adolescent: an unusual presentation

We report a case of primary leptomeningeal central nervous system (CNS) lymphoma with atypical imaging features in an immunocompetent adolescent who presented with diplopia, seizures, vomiting and subsequent unresponsiveness. Primary leptomeningeal CNS lymphoma is rare in the pediatric population, and this is one of few reported cases in the literature of large B-cell lymphoma isolated to the leptomeninges in a teenager.

Management of a Large Antenatally Recognized Foregut Duplication Cyst of the Tongue Causing Respiratory Distress at Birth

IMPORTANCE Foregut duplication cysts are benign developmental anomalies occurring along the foregut-derived portion of the alimentary tract. Several cases of foregut duplications in the head and neck region have been reported, most without airway symptoms. This case is an antenatally recognized anterior tongue lesion leading to respiratory difficulties at birth that was successfully managed by a coordinated fetal care team. OBSERVATIONS We describe a 4.16-kg female born at full term whose anterior tongue lesion was noted on routine prenatal ultrasound. An airway management plan was developed by a multidisciplinary fetal care team, and the airway was controlled at the time of cesarean delivery. The lesion was completely excised on the sixth day of life without complications. CONCLUSIONS AND RELEVANCE Given the extensive differential diagnosis of cystic head and neck lesions in neonates, imaging is recommended to localize and characterize the lesion because management of these lesions may differ substantially. For cases that are diagnosed antenatally, coordination of a multidisciplinary fetal care team and early discussions can optimize the predelivery workup and provide clear delivery and airway management plans. We recommend complete surgical excision of oral foregut duplication cysts in the perinatal period to prevent complications such as feeding difficulties, infection, and ulceration.

Nasal Glioma: Prenatal Diagnosis and Multidisciplinary Surgical Approach

Nasal gliomas are congenital, nonmalignant rests of neuroglial tissue that typically present as a craniofacial mass. The differential diagnosis of such masses includes lesions that often require the involvement of various surgical subspecialties, including otolaryngology, neurosurgery, plastic surgery, and ophthalmology. Early surgical excision of these masses is advised to minimize nasal and craniofacial distortion. Accordingly, early diagnosis and management planning are paramount, and advances in prenatal imaging are creating a new role for obstetricians and radiologists in the initiation of diagnostic and therapeutic interventions. We describe the case history of a young patient found to have a craniofacial mass on routine prenatal ultrasound and subsequently managed with a multidisciplinary team approach.