Intracerebral Administration of Adeno-Associated Viral Vector Serotype rh.10 Carrying Human SGSH and SUMF1 cDNAs in Children with Mucopolysaccharidosis Type IIIA Disease: Results of a Phase I/II Trial.

Mucopolysaccharidosis type IIIA is a severe degenerative disease caused by an autosomal recessive defect of a gene encoding a lysosomal heparan-N-sulfamidase, the N-sulfoglycosamine sulfohydrolase (SGSH), the catalytic site of which is activated by a sulfatase-modifying factor (SUMF1). Four children (Patients 1-3, aged between 5.5 and 6 years; Patient 4 aged 2 years 8 months) received intracerebral injections of an adeno-associated viral vector serotype rh.10-SGSH-IRES-SUMF1 vector in a phase I/II clinical trial. All children were able to walk, but their cognitive abilities were abnormal and had declined (Patients 1-3). Patients 1-3 presented with brain atrophy. The therapeutic vector was delivered in a frameless stereotaxic device, at a dose of 7.2x10(11) viral genomes/patient simultaneously via 12 needles as deposits of 60l over a period of 2hr. The vector was delivered bilaterally to the white matter anterior, medial, and posterior to the basal ganglia. Immunosuppressive treatment (mycophenolate mofetil and tacrolimus) was initiated 15 days before surgery and maintained for 8 weeks (mycophenolate mofetil) or throughout follow-up (tacrolimus, with progressive dose reduction) to prevent elimination of transduced cells. Safety data collected from inclusion, during the neurosurgery period and over the year of follow-up, showed good tolerance, absence of adverse events related to the injected product, no increase in the number of infectious events, and no biological sign of toxicity related to immunosuppressive drugs. Efficacy analysis was necessarily preliminary in this phase I/II trial on four children, in the absence of validated surrogate markers. Brain atrophy evaluated by magnetic resonance imaging seemed to be stable in Patients 1 and 3 but tended to increase in Patients 2 and 4. Neuropsychological evaluations suggested a possible although moderate improvement in behavior, attention, and sleep in Patients 1-3. The youngest patient was the most likely to display neurocognitive benefit

Epiglottic masses identified on CT imaging: A case report and review of the broad differential diagnosis

Epiglottic masses may be cystic, granulomatous, infectious, benign or malignant neoplastic, or manifestations of a systemic disease. When large in size, the airway may become obstructed, and when accompanied by suspicious features such as cartilaginous invasion, extension to the pre-epiglottic or para-glottic spaces, or lymphadenopathy, the radiologist must consider malignancy as a primary differential diagnosis. However, when only benign features are identified, the differential diagnosis is broad. We present a 65-year-old female with an incidental 1 cm exophytic, pedunculated, papillomatous lesion on the laryngeal surface of the epiglottis discovered upon endoscopic evaluation for dyspepsia and heartburn. Because of her risk factors for malignancy, CT scan was requested and revealed only benign features. Subsequent excisional biopsy revealed a benign squamous papilloma; however, multiple additional differential considerations were entertained preoperatively