Faculty Bibliography

BACKGROUND:Chromosomal instability is associated with earlier progression in isocitrate dehydrogenase (IDH)-mutated astrocytomas. Here we evaluated the prognostic significance of polysomy in gliomas tested for 1p19q status. METHODS:We analyzed 412 histologic oligodendroglial tumors with use of 1p19q testing at 8 institutions from 1996 to 2013; fluorescence in situ hybridization (FISH) for 1p19q was performed. Polysomy was defined as >2 1q and 19p signals in cells. Tumors were divided into groups on the basis of their 1p19q status and polysomy and were compared for progression-free survival (PFS) and overall survival (OS). RESULTS:In our cohort, 333 tumors (81%) had 1p19q loss; of these, 195 (59%) had concurrent polysomy and 138 (41%) lacked polysomy, 79 (19%) had 1p19q maintenance; of these, 30 (38%) had concurrent polysomy and 49 (62%) lacked polysomy. In agreement with prior studies, the group with 1p19q loss had significantly better PFS and OS than did the group with 1p19q maintenance (p < 0.0001 each). Patients with 1p19q loss and polysomy showed significantly shorter PFS survival than patients with 1p19q co-deletion only (p-<0.0001), but longer PFS and OS than patients with 1p19q maintenance (p < 0.01 and p<0.0001). There was no difference in survival between tumors with >30% polysomic cells and those with <30% of polysomic cells. Polysomy had no prognostic significance on progression-free or overall survival in patients with 1p19q maintenance. CONCLUSIONS:The presence of polysomy in oligodendroglial tumors with co-deletion of 1p19q predicts early recurrence and short survival in patients with 1p19q co-deleted tumors.

Vision relies on both specific knowledge of visual attributes, such as object categories, and general brain states, such as those reflecting arousal. We hypothesized that these phenomena independently influence recognition of forthcoming stimuli through distinct processes reflected in spontaneous neural activity. Here, we recorded magnetoencephalographic (MEG) activity in participants (N = 24) who viewed images of objects presented at recognition threshold. Using multivariate analysis applied to sensor-level activity patterns recorded before stimulus presentation, we identified two neural processes influencing subsequent subjective recognition: a general process, which disregards stimulus category and correlates with pupil size, and a specific process, which facilitates category-specific recognition. The two processes are doubly-dissociable: the general process correlates with changes in criterion but not in sensitivity, whereas the specific process correlates with changes in sensitivity but not in criterion. Our findings reveal distinct mechanisms of how spontaneous neural activity influences perception and provide a framework to integrate previous findings.

Dynamic functional connectivity captures temporal variations of functional connectivity during MRI acquisition and it may be a suitable method to detect cognitive changes in Parkinson's disease. In this study, we evaluated 118 patients with Parkinson's disease matched for age, sex and education with 35 healthy control subjects. Patients with Parkinson's disease were classified with normal cognition (n = 52), mild cognitive impairment (n = 46), and dementia (n = 20) based on an extensive neuropsychological evaluation. Resting state functional MRI and a sliding-window approach were used to study the dynamic functional connectivity. Dynamic analysis suggested two distinct connectivity 'States' across the entire group: a more frequent, segregated brain state characterized by the predominance of within-network connections, State I, and a less frequent, integrated state with strongly connected functional internetwork components, State II. In Parkinson's disease, State I occurred 13.89% more often than in healthy control subjects, paralleled by a proportional reduction of State II. Parkinson's disease subgroups analyses showed the segregated state occurred more frequently in Parkinson's disease dementia than in mild cognitive impairment and normal cognition groups. Further, patients with Parkinson's disease dementia dwelled significantly longer in the segregated State I, and showed a significant lower number of transitions to the strongly interconnected State II compared to the other subgroups. Our study indicates that dementia in Parkinson's disease is characterized by altered temporal properties in dynamic connectivity. In addition, our results show that increased dwell time in the segregated state and reduced number of transitions between states are associated with presence of dementia in Parkinson's disease. Further studies on dynamic functional connectivity changes could help to better understand the progressive dysfunction of networks between Parkinson's disease cognitive states.

Deficits of convergence and accommodation are common following traumatic brain injury, including mild traumatic brain injury, though the mechanism and localization of these deficits have been unclear and supranuclear control of the near-vision response has been incompletely understood. We describe a patient who developed profound instability of the near-vision response with inability to maintain convergence and accommodation following mild traumatic brain injury, who was identified to have a structural lesion on brain MRI in the pulvinar of the caudal thalamus, the pretectum, and the rostral superior colliculus (SC). We discuss the potential relationship between post-traumatic clinical near-vision response deficits and the MRI lesion in this patient. We further propose that the MRI lesion location, specifically the rostral superior colliculus, participates in neural integration for convergence holding, given its proven anatomic connections with the central mesencephalic reticular formation (cMRF) and C-group medial rectus motoneurons in the oculomotor nucleus which project to extraocular muscle non-twitch fibers specialized for fatigue-resistant, slow, tonic activity such as vergence holding.

Continuous subcutaneous apomorphine infusion (CSAI) is a well-recognized therapeutic option for the management of motor fluctuations in Parkinson's disease (PD), although clinical experience suggests that most patients discontinue CSAI after a variable amount of time due to several causes and circumstances. The objective of the present study was to evaluate the reasons of CSAI discontinuation and to investigate which treatment was adopted afterwards. Two independent raters retrospectively reviewed the electronic medical record of 114 patients treated with CSAI for at least 6 months. The records were reviewed regarding efficacy, safety, and evolution of CSAI treatment. Most of PD patients on CSAI had a significant improvement in their clinical condition. Lack of improvement of dyskinesia was the most frequent causes of treatment discontinuation. The second reason for CSAI discontinuation was cognitive deterioration. At CSAI discontinuation, younger patients were more likely to undergo deep brain stimulation (DBS), while older patients and patients with cognitive impairment were more likely switched to oral therapy alone (OTA). CSAI is an effective treatment that unfortunately must be discontinued in a great number of patients with advanced PD. As older age is the main limiting factor for accessing second-level therapies at CSAI discontinuation, CSAI treatment should not be postponed to older age. CSAI might be considered a good first-line and fast strategy in patients undergoing rapid deterioration of their quality of life while waiting for DBS or levodopa/carbidopa intestinal gel therapy.