Haploinsufficiency of Progranulin (PGRN), a gene encoding a secreted glycoprotein, is a major cause of frontotemporal lobar degeneration with ubiquitin (FTLD-U) positive inclusions. Single nucleotide polymorphisms in the TMEM106B gene were recently discovered as a risk factor for FTLD-U, especially in patients with PGRN mutations. TMEM106B is also associated with cognitive impairment in amyotrophic lateral sclerosis patients. Despite these studies, little is known about TMEM106B at molecular and cellular levels and how TMEM106B contributes to FTLD. Here, we show that TMEM106B is localized in the late endosome/lysosome compartments and TMEM106B levels are regulated by lysosomal activities. Ectopic expression of TMEM106B induces morphologic changes of lysosome compartments and delays the degradation of endocytic cargoes by the endolysosomal pathway. Furthermore, overexpression of TMEM106B correlates with elevated levels of PGRN, possibly by attenuating lysosomal degradation of PGRN. These results shed light on the cellular functions of TMEM106B and the roles of TMEM106B in the pathogenesis of FTLD-U with PGRN mutations.

Purpose: To compare the visual outcomes and associated morbidity of patients with Fuchs endothelial corneal dystrophy who were treated with either Descemet membrane endothelial keratoplasty (DMEK) or descemetorhexis without endothelial keratoplasty (DWEK). Methods: This is a retrospective comparative cohort study of 27 eyes with mild to moderate Fuchs dystrophy (with corneal guttae/edema limited to the central cornea with relatively clear periphery) that were treated at the University of Pittsburgh Medical Center from 2015 to 2017 with either DMEK (n = 15) or DWEK (n = 12). Descemetorhexis was performed by removing the central 4 mm of diseased Descemet membrane at the end of phacoemulsification for cataract surgery. Visual acuity was measured using the Snellen chart and then converted to logMAR for analysis. Results: Average postoperative pinhole visual acuity was 20/25 − 1 (logMAR 0.16 ± 0.09) for DMEK eyes and 20/30 + 1 (logMAR 0.13 ± 0.10) for DWEK eyes (P = 0.44). The average time to 20/40 vision for DMEK was 2.2 ± 2.8 weeks compared with 7.1 ± 2.7 weeks for DWEK (P < 0.01). In our DMEK group, 8 (53%) patients had adverse events, including increased intraocular pressure (n = 7), anterior chamber inflammation (n = 1), and graft nonadherence (n = 1), with 1 patient requiring anterior chamber paracentesis (6.7%) and 1 patient (6.7%) requiring a rebubbling procedure. Our DWEK group had no adverse events (P < 0.01). Conclusions: DWEK effectively treats select patients with mild to moderate Fuchs dystrophy with equivalent visual outcomes compared with the current standard of care, DMEK. Although the recovery time may be longer, DWEK patients had reduced adverse events and need for additional procedures and did not require long-term immunosuppression or donor corneal tissue.

This study provides Class IV evidence that in patients with medically refractory trigeminal neuralgia, early stereotactic radiosurgery as the initial procedure provides faster, better, and longer pain relief.

V estibular schwannomas (VSs), also known as acoustic neuromas, are benign primary intracranial tumors that arise from the Schwann cells of the vestibulocochlear nerve. The incidence of VS is estimated to be 1 per 100,000 individuals per year, and it accounts for approximately 8% of all intracranial tumors in adults. 3,14 These tumors are typically slow growing (0-3.9 mm per year), but without management, most VS tumors will grow within 3 years. 4,6,14,15,18,20 For many years, microsurgical resection remained the most commonly recommended treatment for patients with newly diagnosed unilateral VS. 3,20 Although surgical outcomes have improved over the last 30 years, resection of VS was frequently associated with impaired facial nerve function and loss of hearing. 7,13,20,22 The recurrence rate of VS has been shown to be 2.6%-11.0% after gross-total resection, and 20%-50% of VS tumors progress after subtotal resection. 1,2,12,19,20,22,24,25,26,28 Since the development of the Gamma Knife (GK) technology, stereotactic radiosurgery (SRS) has become an increasingly used alternative or adjuvant VS management tool that eliminates many risks associated with resection.14,23 Initial SRS for VS has improved hearing retention rates in 60%-90% of patients and reduced facial neuropa-ABBREVIATIONS GK = Gamma Knife; G-R = Gardner-Robertson; HB = House-Brackmann; QOL = quality of life; SRS = stereotactic radiosurgery; VS = vestibular schwannoma. The Center for Image-Guided Neurosurgery and the Departments of 1 Neurological Surgery and 2 Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania OBJECTIVE The goal of this retrospective cohort study was to assess long-term outcomes in patients with vestibular schwannoma (VS) who underwent stereotactic radiosurgery (SRS) after initial microsurgical resection. METHODS From the authors' database of 1770 patients with VS, the authors retrospectively analyzed data from 173 Gamma Knife SRS procedures for VS after 1 (128 procedures) or multiple (45 procedures) microsurgical resections. The median length of the interval between the last resection and SRS was 42 months (range 2-329 months). The median length of clinical follow-up was 74 months (range 6-285 months). Progression-free survival after SRS was determined with Kaplan-Meier analysis. RESULTS At the time of SRS, the hearing of 161 patients (93%) was Gardner-Robertson Class V, and 81 patients (47%) had facial neuropathy (i.e., facial function with House-Brackmann [HB] grades of III-VI), 87 (50%) had trigeminal neuropathy, and 71 (41%) reported imbalance or disequilibrium disorders. The median tumor volume was 2.7 cm 3 (range 0.2-21.6 cm 3 ), and the median dose to the tumor margin was 13 Gy (range 11-20 Gy). Radiosurgery controlled growth of 163 (94%) tumors. Progression-free survival after SRS was 97% at 3 years, 95% at 5 years, and 90% at 10 years. Four patients with delayed tumor progression underwent repeat SRS at a median of 35 months (range 23-64 months) after the first SRS. Four patients (2.3%) w...