Ornithine decarboxylase, the rate-limiting enzyme of polyamine synthesis, modifies brain pathology in a mouse model of tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant neurodevelopmental disorder characterized by variable expressivity. TSC results from inactivating variants within the TSC1 or TSC2 genes, leading to constitutive activation of mechanistic target of rapamycin complex 1 signaling. Using a mouse model of TSC (Tsc2-RG) in which the Tsc2 gene is deleted in radial glial precursors and their neuronal and glial descendants, we observed increased ornithine decarboxylase (ODC) enzymatic activity and concentration of its product, putrescine. To test if increased ODC activity and dysregulated polyamine metabolism contribute to the neurodevelopmental defects of Tsc2-RG mice, we used pharmacologic and genetic approaches to reduce ODC activity in Tsc2-RG mice, followed by histologic assessment of brain development. We observed that decreasing ODC activity and putrescine levels in Tsc2-RG mice worsened many of the neurodevelopmental phenotypes, including brain growth and neuronal migration defects, astrogliosis and oxidative stress. These data suggest a protective effect of increased ODC activity and elevated putrescine that modify the phenotype in this developmental Tsc2-RG model.

Single stage near total resection of massive pediatric head and neck plexiform neurofibromas.

OBJECTIVE: Plexiform neurofibromas of the head and neck in neurofibromatosis type 1 (NF 1) carry a significant morbidity with substantial loss of function as well as significant cosmetic problems. We describe our experience with early aggressive surgical intervention in such patients in order to avert these problems. METHODS: Retrospective review of four consecutive pediatric patients with massive head and neck plexiform neurofibromas who underwent single stage near total or sub-total tumor resections. RESULTS: All four patients were referred for obstructive airway symptoms. Each patient experienced complete relief of symptoms and return of function without additional neurological deficits. There were two minor complications and no major complications of surgical resection. There have been no recurrences to date, with follow-up ranging from 15 months to 5 years. CONCLUSIONS: Early surgical intervention of NF 1 patients with plexiform neurofibromas of the head and neck with a goal of near total resection avoids the loss of function associated with these tumors, such as tracheostomy dependence, swallowing difficulty, and speech problems, and prevents the inexorable progression of substantial cosmetic deformity. Successful management of these complex lesions requires detailed preoperative planning, advanced surgical techniques, and vigilant postoperative care.

Sagittal Plane Correction Using the Lateral Transpsoas Approach: A Biomechanical Study on the Effect of Cage Angle and Surgical Technique on Segmental Lordosis.

STUDY DESIGN: Cadaveric biomechanical study. OBJECTIVE: To determine the degree of segmental correction that can be achieved through lateral transpsoas approach by varying cage angle and adding anterior longitudinal ligament (ALL) release and posterior element resection. SUMMARY OF BACKGROUND DATA: Lordotic cage insertion through the lateral transpsoas approach is being used increasingly for restoration of sagittal alignment. However, the degree of correction achieved by varying cage angle and ALL release and posterior element resection is not well defined. METHODS: Thirteen lumbar motion segments between L1 and L5 were dissected into single motion segments. Segmental angles and disk heights were measured under both 50 N and 500 N compressive loads under the following conditions: intact specimen, discectomy (collapsed disk simulation), insertion of parallel cage, 10° cage, 30° cage with ALL release, 30° cage with ALL release and spinous process (SP) resection, 30° cage with ALL release, SP resection, facetectomy, and compression with pedicle screws. RESULTS: Segmental lordosis was not increased by either parallel or 10° cages as compared with intact disks, and contributed small amounts of lordosis when compared with the collapsed disk condition. Placement of 30° cages with ALL release increased segmental lordosis by 10.5°. Adding SP resection increased lordosis to 12.4°. Facetectomy and compression with pedicle screws further increased lordosis to approximately 26°. No interventions resulted in a decrease in either anterior or posterior disk height. CONCLUSION: Insertion of a parallel or 10° cage has little effect on lordosis. A 30° cage insertion with ALL release resulted in a modest increase in lordosis (10.5°). The addition of SP resection and facetectomy was needed to obtain a larger amount of correction (26°). None of the cages, including the 30° lordotic cage, caused a decrease in posterior disk height suggesting hyperlordotic cages do not cause foraminal stenosis. LEVEL OF EVIDENCE: N/A.

Steady-state response audiometry in a group of patients with steeply sloping sensorineural hearing loss.

OBJECTIVES: The purpose of this study was to examine the predictive value of auditory steady-state response (ASSR) evoked potential thresholds and predicted behavioral thresholds in a group of children with steeply sloping sensorineural hearing loss (HL). STUDY DESIGN: Case series. METHODS: Twenty-nine children with sloping sensorineural HL underwent behavioral audiometric evaluation, impedance testing, distortion product otoacoustic emissions, and steady-state response testing. A t test was performed to compare the means of ASSR predicted behavioral thresholds and behavioral responses. Pearson correlation coefficients were calculated at each tested frequency, 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz, using the same data. RESULTS: Bracketed thresholds were obtained at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz. Nineteen ears were used in this evaluation. A comparison of threshold difference as a function of bracketing revealed that the means were statistically different (P < .05). The mean threshold differences were calculated, and Pearson r values were determined between the behavioral thresholds and the predicted thresholds using the Rance 95 algorithm. The results revealed no difference of means at 500 Hz between predicted and measured behavioral thresholds. Linear regression analysis revealed strong correlation at 500 Hz, 1,000 Hz, and 2,000 Hz. CONCLUSIONS: The GSI Audera appears to predict the configuration of HL in children with steeply sloping sensorineural HLs and over-predicts the severity of the loss by 15 to 20 dB above 500 Hz at each test frequency (1,000, 2,000, and 4,000 Hz). Correlation coefficients display a strong correlation at 500 Hz, 1,000 Hz, and 2,000 Hz.

Outpatient intravenous antibiotics for methicillin-resistant Staphylococcus aureus sinusitis.

BACKGROUND: The widespread use of broad-spectrum antibiotics has resulted in an increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA). Its presence in sinonasal cultures in patients with sinusitis suggests its pathogenicity. However, the efficacy and safety of treatment modalities for MRSA sinusitis remain incompletely described. METHODS: A retrospective chart review of six patients treated for MRSA sinusitis with outpatient intravenous (i.v.) antibiotics was performed for patient demographics, history of antibiotic use, history of prior sinus surgery, and treatment-related complications. A quality-of-life survey and endoscopically guided cultures before and after therapy were used to measure treatment outcomes. RESULTS: The cohort consisted of five women and one man with a mean age of 50.8 years. All patients had undergone multiple sinus procedures with a mean number of 2.7 procedures per patient (range, 1-6 procedures). Five patients (83.3%) experienced negative cultures after outpatient i.v. antibiotics. The single patient who had persistent cultures experienced clinical and endoscopic improvement in her symptoms. The quality-of-life scores improved in five of the six patients (83.3%) after therapy. Four patients (66.7%) experienced five adverse events including allergic reaction (four events) and neutropenia (one event), all of which resolved with a change in medication. CONCLUSION: Outpatient i.v. antibiotics may be an effective therapy for the treatment of MRSA sinusitis. The occurrence of adverse events requires a dedicated protocol to therapy. Future studies are required to investigate long-term efficacy.