Trametinib for orbital plexiform neurofibromas in young children with neurofibromatosis type 1.

INTRODUCTION: Plexiform neurofibromas (PNF) in neurofibromatosis type 1 (NF1) are usually diagnosed in childhood and can grow rapidly during this period. In 10% of patients, PNF involve the orbital-periorbital area and may cause visual problems including glaucoma, visual loss from amblyopia (deprivational, strabismic, or refractive), optic nerve compression, or keratopathy. Ptosis, proptosis, and facial disfigurement lead to social problems and decreased self-esteem. Complete surgical removal involves significant risks and mutilation, and regrowth after debulking is not uncommon. Inhibitors of the RAS/MAPK pathway have recently been investigated for their activity in PNF. We administered the oral MEK inhibitor trametinib to five young children with NF1 and PNF of the orbital area, with visual compromise and progressive tumor growth; and followed them clinically and by volumetric MRI. METHODS: Treatment was initiated at a mean age of 26.8 months (SD ± 12.8) and continued for a median 28 months (range 16-51). Doses were 0.025 mg/kg/day for children aged > 6 years and 0.032 mg/kg/day for those aged < 6 years. RESULTS: Volumetric MRI measurements showed a reduction of 2.9-33% at 1 year after treatment initiation, with maximal reductions of 44% and 49% in two patients, at 44 and 36 months, respectively. No change in visual function was recorded during treatment. One child reported decreased orbital pain after 2 weeks; and another, with involvement of the masseters, had increased ability to chew food. Toxicities were mostly to skin and nails, grades 1-2. CONCLUSIONS: Trametinib can decrease tumor size in some young children with orbital PNF and may prevent progressive disfigurement.

Neuroimaging in Children with Ophthalmological Complaints: A Review.

Pediatric patients are commonly referred to imaging following abnormal ophthalmological examinations. Common indications include papilledema, altered vision, strabismus, nystagmus, anisocoria, proptosis, coloboma, and leukocoria. Magnetic resonance imaging (MRI) of the brain and orbits (with or without contrast material administration) is typically the imaging modality of choice. However, a cranial CT scan is sometimes initially performed, particularly when MRI is not readily available. Familiarity with the various ophthalmological conditions may assist the radiologist in formulating differential diagnoses and proper MRI protocols afterward. Although MRI of the brain and orbits usually suffices, further refinements are sometimes warranted to enable suitable assessment and accurate diagnosis. For example, the assessment of children with sudden onset anisocoria associated with Horner syndrome will require imaging of the entire oculosympathetic pathway, including the brain, orbits, neck, and chest. Dedicated orbital scans should cover the area between the hard palate and approximately 1 cm above the orbits in the axial plane and extend from the lens to the midpons in the coronal plane. Fat-suppressed T2-weighted fast spin echo sequences should enable proper assessment of the globes, optic nerves, and perioptic subarachnoid spaces. Contrast material should be given judiciously, ideally according to clinical circumstances and precontrast scans. In this review, we discuss the major indications for imaging following abnormal ophthalmological examinations.

Not only appendicitis: rare appendix disorders manifesting as surgical emergencies in children.

Acute appendicitis is the most common cause of acute abdominal pathology in children. However, other rare non-inflammatory non-neoplastic disorders involving the appendix may manifest as surgical emergencies. This study aimed to describe these atypical entities and present representative cases. The database of a tertiary children's medical center was reviewed for all the patients aged 0-18 years who underwent urgent appendectomy between June 2014 and December 2019, for rare disorders of the appendix unrelated to inflammatory or neoplastic processes. Of 1367 patients who underwent appendectomy, 1345 were operated urgently or emergently. Of these, six, all males, mean age 32.6 months (range 0.7-76), underwent appendectomy for rare surgical complications that involved the appendix. These included torsion of the appendix (2), a strangulated internal hernia through an appendicular ring (1) or through a mesoappendix gap (1), an incarcerated appendix in an acute hernia sac (1), and appendiceal intussusception (1). In all cases, the role of the appendix in the pathologic process was unexpected and came as a surprise to the surgeon. During a median follow-up of 4.2 months (range 1-8 months), one patient underwent relaparotomy for small bowel obstruction 4 weeks after the original procedure.Conclusion: The appendix in children can be the source of rare pathological disorders that present as surgical emergencies. Familiarity with these entities may aid in achieving accurate preoperative diagnosis and contribute to surgical team orientation on exploratory laparotomy. However, correct diagnosis is often only established during timely surgical intervention.

Imaging features of primary hyperoxaluria.

Primary hyperoxaluria (PH) is a group of autosomal recessive diseases that affect the metabolism of glyoxalate and oxalate. As a result of the enzymatic deficiency, there is overproduction and urinary excretion of oxalate with progressive renal damage and subsequent deposition of oxalate salts in various tissues. The definitive treatment in cases of end-stage kidney disease is a combined liver and kidney transplant. Imaging features are diverse and reflect the multiple organs that might be affected. These include nephrolithiasis and nephrocalcinosis, oxalate osteopathy, as well as other findings, such as splenomegaly and oxalate deposition in the heart. In this review article, we present various imaging findings that may appear in patients with PH.

Preferential sites of metastatic relapse on MRI of initially localized ependymoma in children.

OBJECTIVE: Relapse of ependymoma in childhood portends a grave prognosis. While the detection of local recurrence is usually simple, spotting leptomeningeal metastasis might be challenging. We aimed to evaluate possible "hotspots" where metastasis tend to appear. MATERIALS AND METHODS: Medical records and Magnetic Resonance (MR) studies of all patients diagnosed with brain ependymomas between the years 2000-2015 were reviewed. RESULTS: Leptomeningeal spread was detected among 42% of relapsed patients. The most common sites were spine and hypothalamic area (26% each). CONCLUSION: A meticulous assessment of the brain and spine including a thorough evaluation of the hypothalamic area is recommended.