A molecular mechanism regulating the timing of corticogeniculate innervation.

Neural circuit formation demands precise timing of innervation by different classes of axons. However, the mechanisms underlying such activity remain largely unknown. In the dorsal lateral geniculate nucleus (dLGN), axons from the retina and visual cortex innervate thalamic relay neurons in a highly coordinated manner, with those from the cortex arriving well after those from retina. The differential timing of retino- and corticogeniculate innervation is not a coincidence but is orchestrated by retinal inputs. Here, we identified a chondroitin sulfate proteoglycan (CSPG) that regulates the timing of corticogeniculate innervation. Aggrecan, a repulsive CSPG, is enriched in neonatal dLGN and inhibits cortical axons from prematurely entering the dLGN. Postnatal loss of aggrecan from dLGN coincides with upregulation of aggrecanase expression in the dLGN and corticogeniculate innervation and, it is important to note, is regulated by retinal inputs. Taken together, these studies reveal a molecular mechanism through which one class of axons coordinates the temporal targeting of another class of axons.

Gamma Knife surgery for the treatment of patients with asymptomatic meningiomas.

OBJECT: Increasingly, meningiomas are detected incidentally, prior to symptom development. While these lesions are traditionally managed conservatively until symptoms develop or lesion growth occurs, it is conceivable that patients at high risk for symptom development may benefit from earlier intervention prior to the appearance of symptoms. However, little research has been performed to determine whether Gamma Knife surgery (GKS) can alter the rate of symptom development in such patients. METHODS: A retrospective case study was performed by screening the University of Virginia GKS database for patients treated for asymptomatic meningiomas. From the patient's medical records, pertinent demographic and treatment information was obtained. Yearly follow-up MRI had been performed to assess tumor control and detect signs of radiation-induced injury. Clinical follow-up via neurological examination had been performed to assess symptom development. RESULTS: Forty-two patients, 33 females (78.6%) and 9 males (21.4%), with 42 asymptomatic meningiomas were included in the analysis. The median age at GKS was 53 years. The most common lesion location was the cerebral convexities (10 lesions [23.8%]), and the median lesion size was 4.0 ml. The median duration of imaging and clinical follow-ups was 59 and 76 months, respectively. During the follow-up period, 1 tumor (2.4%) increased in size, 2 patients (4.8%) demonstrated symptoms, and 1 patient (2.4%) exhibited possible signs of radiation-induced injury. Thus, actuarial tumor control rates were 100%, 95.7%, and 95.7% for 2, 5, and 10 years, respectively. Actuarial symptom control at 5 and 10 years was 97% and 93.1%, respectively. Overall progression-free survival was 91.1% and 77.8% at 5 and 10 years, respectively. CONCLUSIONS: Compared with published rates of symptom development in patients with untreated meningiomas, results in this study indicated that patients with asymptomatic lesions may benefit from prophylactic radiosurgery prior to the appearance of symptoms. Additionally, GKS is a treatment option that offers low morbidity.