18-fluorodeoxyglucose-positron emission tomography (FDG-PET) evaluation of nodular lesions in patients with Neurofibromatosis type 1 and plexiform neurofibromas (PN) or malignant peripheral nerve sheath tumors (MPNST).

BACKGROUND: Individuals with Neurofibromatosis type 1 (NF1) are at risk for developing malignant peripheral nerve sheath tumors (MPNST), which frequently arise in preexisting plexiform neurofibromas (PN). Magnetic resonance imaging (MRI) with volumetric analysis and 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) were utilized to monitor symptomatic nodular lesions. PROCEDURE: Patients with NF1 and PN on a NCI natural history trial were monitored for total body tumor volume (TTV) using volumetric MRI. FDG-PET was performed in individuals with a nodular well-demarcated lesion ≥3 cm if they were growing, painful, or there was a prior history of MPNST (target lesions). Asymptomatic nodular lesions were evaluated as non-target lesions. RESULTS: Fifteen patients (8m, 7f) median age of 18.3 years (range, 10-45 years) had a single target and non-target (n = 46) nodular lesions identified on MRI. Target lesions arose within (n = 8) or outside (n = 3) a PN, and all but 1 had increased FDG uptake. FDG uptake was increased in non-target lesions but to a lesser degree. FDG uptake in the surrounding PN was low, similar to background activity. Pathologic evaluation performed in 11 patients demonstrated neurofibroma (n = 6), atypical neurofibroma (n = 2) and malignancy (n = 3). CONCLUSIONS: Nodular target lesions identified on MRI in individuals with NF1 and PN demonstrate increased FDG uptake similar to MPNST, but may be benign on biopsy. Nodular target lesions may be at greater risk for malignant transformation, but their biologic and clinical behavior has not been well studied. Careful longitudinal evaluation will be required to better understand the malignant potential of these lesions.

Wavefront-guided photorefractive keratectomy after radial keratotomy in nine eyes.

PURPOSE: To investigate the refractive outcomes of wavefront-guided photorefractive keratectomy (PRK) in patients with previous radial keratotomy (RK). METHODS: This study is a retrospective review of consecutive cases from August 2004 until February 2007 of PRK after RK. The VISX STAR S4 excimer laser was used. Visual acuity, manifest refraction, and slit-lamp microscopy were reviewed preoperatively and 3 and 12 months postoperatively. RESULTS: Nine eyes, five hyperopic and four myopic, of six consecutively treated patients were evaluated. Myopic spherical equivalent refractive treatments averaged -2.08 diopters (D) (range: -0.80 to -3.36 D) and hyperopic treatments averaged + 2.20 D (range: +1.28 to +3.12 D). No eyes lost any lines of Snellen best spectacle-corrected visual acuity (BSCVA) and three (33%) eyes gained one line of BSCVA. Two (22%) eyes showed grade 0.5 level haze (not in the visual axis) and the remaining seven eyes showed no haze. Seven (77%) of nine eyes were within +/- 0.25 D of the targeted spherical equivalent refraction at 3 months postoperative. Six (66%) of nine eyes had > or = +/- 0.50 D (range: +0.50 to+2.25) of astigmatism prior to PRK and all astigmatic errors were significantly reduced, with the highest residual astigmatic error of 0.75 D in one eye and 0.50 D in two eyes. CONCLUSIONS: Wavefront-guided PRK after RK for myopic, hyperopic, and astigmatic refractive errors targeting emmetropia in six eyes and myopia in three eyes yielded accurate refractive outcomes in this consecutive series. Three (33%) of nine eyes gained one line of BSCVA with no eyes losing BSCVA. Seven of nine eyes were within +/- 0.25 D of targeted spherical equivalent refraction at 3 months postoperative.

Calcium channel alpha2delta1 subunit mediates spinal hyperexcitability in pain modulation.

Mechanisms of chronic pain, including neuropathic pain, are poorly understood. Upregulation of voltage-gated calcium channel (VGCC) alpha2delta1 subunit (Ca(v)alpha2delta1) in sensory neurons and dorsal spinal cord by peripheral nerve injury has been suggested to contribute to neuropathic pain. To investigate the mechanisms without the influence of other injury factors, we have created transgenic mice that constitutively overexpress Ca(v)alpha2delta1 in neuronal tissues. Ca(v)alpha2delta1 overexpression resulted in enhanced currents, altered kinetics and voltage-dependence of VGCC activation in sensory neurons; exaggerated and prolonged dorsal horn neuronal responses to mechanical and thermal stimulations at the periphery; and pain behaviors. However, the transgenic mice showed normal dorsal horn neuronal responses to windup stimulation, and behavioral responses to tissue-injury/inflammatory stimuli. The pain behaviors in the transgenic mice had a pharmacological profile suggesting a selective contribution of elevated Ca(v)alpha2delta1 to the abnormal sensations, at least at the spinal cord level. In addition, gabapentin blocked VGCC currents concentration-dependently in transgenic, but not wild-type, sensory neurons. Thus, elevated neuronal Ca(v)alpha2delta1 contributes to specific pain states through a mechanism mediated at least partially by enhanced VGCC activity in sensory neurons and hyperexcitability in dorsal horn neurons in response to peripheral stimulation. Modulation of enhanced VGCC activity by gabapentin may underlie at least partially its antihyperalgesic actions.