Faculty Bibliography

Objective/UNASSIGNED:Optical coherence tomography (OCT)-derived measures of the retina correlate with disability and cortical gray matter atrophy in multiple sclerosis (MS); however, whether such measures predict long-term disability is unknown. We evaluated whether a single OCT and visual function assessment predict the disability status 10 years later. Methods/UNASSIGNED: = 150; 87%). All participants had Expanded Disability Status Scale (EDSS) assessments at baseline and at 10-year follow-up. We applied generalized linear regression models to assess associations between baseline TMV, peripapillary retinal nerve fiber layer (pRNFL) thickness, and LCLA with 10-year EDSS scores (linear) and with clinically significant EDSS worsening (binary), adjusting for age, sex, optic neuritis history, and baseline disability status. Results/UNASSIGNED:= 0.008). pRNFL and LCLA predicted the 10-year EDSS scores only in univariate models. Interpretation/UNASSIGNED:Lower baseline TMV measured by OCT significantly predicts higher disability at 10 years, even after accounting for baseline disability status.

The entorhinal-hippocampal circuit is a strategic hub for cognition and the first site affected by Alzheimer's disease (AD). We investigated magnetic resonance imaging patterns of brain atrophy and functional connectivity in an Alzheimer's Disease Neuroimaging Initiative data set that included healthy controls, mild cognitive impairment (MCI), and patients with AD. Individuals with MCI were clinically evaluated 24Â months after the first magnetic resonance imaging scan, and the cohort subdivided into sets of individuals who either did or did not convert to AD. The MCI group was also divided into patients who did show or not the presence of AD-related alterations in the cerebrospinal fluid. Patients with AD exhibited the collapse of the long-range hippocampal/entorhinal connectivity, pronounced cortical/subcortical atrophy, and a dramatic decline in cognitive performances. Patients with MCI who converted to AD or patients with MCI who showed the presence of AD-related alterations in the cerebrospinal fluid showed memory deficits, entorhinal/hippocampal hypoconnectivity, and concomitant atrophy of the two regions. Patients with MCI who did not convert to AD or patients with MCI who did not show the presence of AD-related alterations in the cerebrospinal fluid had no atrophy but showed hippocampal/entorhinal hyperconnectivity with selected neocortical/subcortical regions involved in memory processing and brain metastability. This hyperconnectivity may represent a compensatory strategy against the progression of cognitive impairment.

BACKGROUND:The phenotypic presentation of multiple sclerosis (MS) may predict long-term outcomes and little is known about factors contributing to heterogeneity at MS onset. Given temporality, it is likely MS risk factors also influence presentation of the disease near onset. METHODS:Using a retrospective cross-sectional study of MS cases, we investigated: age of onset (AOO), number of impaired functional domains (NIFDs), time to second relapse (TT2R), and early relapse activity (ERA). Machine learning variable selection was applied to epidemiologic data for each outcome, followed by multivariable regression models. The models were further adjusted for HLA-DRB1*15:01 carrier status and a MS genetic risk score (GRS). The TT2R and ERA analyses were restricted to relapsing remitting MS cases. RESULTS:HLA-DRB1*15:01, GRS, and smoking were associated with earlier AOO. Cases who were male, obese, had lower education, or had primary progressive MS were older at onset. For NIFDs, those with relapsing remitting MS and of lower SES had increased NIFDs. Among relapsing remitting cases, those who were older at onset, obese, and had polyfocal presentation had shorter TT2R, while ERA was greater among those younger at onset and who were obese. CONCLUSION/CONCLUSIONS:Individual characteristics including age, genetic profiles, obesity, and smoking status contribute to heterogeneity in disease presentation and modulate early disease course evolution.

BACKGROUND:Older patients undergoing thrombectomy for emergent large vessel occlusion have worse outcomes. However, complete or near-complete reperfusion (modified Thrombolysis in Cerebral Ischemia (mTICI) score of 2 c/3) is associated with improved outcomes compared with partial recanalisation (mTICI 2b). OBJECTIVE:To examine the relationship between outcomes and age separately for the mTICI 2c/3, 2b and 0-2a groups in patients undergoing thrombectomy for anterior circulation emergent large vessel occlusion. METHODS:Retrospective review of 157 consecutive patients undergoing thrombectomy at a single centre with an occlusion of the internal carotid artery (ICA), M1 or proximal M2 segments of the middle cerebral artery (MCA). Angiograms were graded in a blinded fashion. Patients were divided into three groups: mTICI 0-2a, mTICI 2b, and mTICI 2c/3. Demographics and workflow parameters were compared. Outcomes at 90 days were compared as a function of age, using both the conventional modified Rankin scale (mRs) and utility weighted mRs (UWmRs). RESULTS:There were 72, 61 and 24 patients in the mTICI 2c/3, 2b and 0-2a groups, respectively. Outcomes were significantly worse with increasing age for the mTICI 2b group, but not for the mTICI 0-2a and 2c/3 groups (P=0.0002). With increasing age, outcomes of the mTICI 2b group approached those of the mTICI 0-2a group. However, outcomes of the mTICI 2c/3 groups were similar for all ages. This association was present for both the original mRs and UWmRs. CONCLUSION/CONCLUSIONS:Increasing age was associated with worse outcomes for those with partial (mTICI 2b) recanalisation, not in patients with complete (mTICI 2c/3) recanalisation.

The T2-FLAIR mismatch sign, in which a low-grade glioma is hyperintense on T2-weighted MR and centrally hypointense on T2-weighted FLAIR MR, has been reported as 100% specific for IDH-mutant astrocytomas in several series. We report several cases of "false positive" T2-FLAIR mismatch sign occurring outside the context of IDH-mutant astrocytomas, predominantly in children or young adults with pediatric-type gliomas. These results suggest caution in the interpretation of the T2-FLAIR mismatch sign in the pediatric glioma population.

OBJECTIVE:Current brain-computer interface (BCI) studies demonstrate the potential to decode neural signals obtained from structured and trial-based tasks to drive actuators with high performance within the context of these tasks. Ideally, to maximize utility, such systems will be applied to a wide range of behavioral settings or contexts. Thus, we explore the potential to augment such systems with the ability to decode abstract behavioral contextual states from neural activity. APPROACH/METHODS:To demonstrate the feasibility of such context decoding, we used electrocorticography (ECoG) and stereo-electroencephalography (sEEG) data recorded from the cortical surface and deeper brain structures, respectively, continuously across multiple days from three subjects. During this time, the subjects were engaged in a range of naturalistic behaviors in a hospital environment. Behavioral contexts were labeled manually from video and audio recordings; four states were considered: engaging in dialogue, rest, using electronics, and watching television. We decode these behaviors using a factor analysis and support vector machine (SVM) approach. MAIN RESULTS/RESULTS:We demonstrate that these general behaviors can be decoded with high accuracies of 73% for a four-class classifier for one subject and 71% and 62% for a three-class classifier for two subjects. SIGNIFICANCE/CONCLUSIONS:To our knowledge, this is the first demonstration of the potential to disambiguate abstract naturalistic behavioral contexts from neural activity recorded throughout the day from implanted electrodes. This work motivates further study of context decoding for BCI applications using continuously recorded naturalistic activity in the clinical setting.

Background: Surgical resection of pituitary adenomas is associated with a 10 to 30% rate of temporary diabetes insipidus with ~50% resolving within 1 week and 80% resolving at 3 months.[1] Adrenal insufficiency occurs in ~ 5 % of patients and can result in an Addisonian crisis if left undiagnosed postoperatively.[1] [2] Many studies have been performed looking at readmission rates after pituitary surgery. A review of over 1,200 cases demonstrated a readmission rate of 8.5% with the most common cause being hyponatremia (29.5%).[3] To reduce the rate of readmission for hyponatremia, some groups have demonstrated the effective use of outpatient fluid restriction criteria during the first week post-op.[4] These guidelines are intended for the management of standard postoperative hormonal fluctuations which do not necessitate endocrine consultation during hospitalization.
Objective(s): Retrospectively evaluate patients undergoing endoscopic endonasal resection of pituitary adenomas to identify areas for quality improvement through the development of more standardized postoperative guidelines.
Method(s): A retrospective review of 75 patients who underwent endoscopic endonasal resection of pituitary adenomas at a single academic center from 2013 to 2018. We evaluated the average length of stay, number of laboratory studies performed, need for hormone supplementation long term and short term, rate of gross-total resection, rate of cerebrospinal fluid leak, rate of infection, and 30-day readmission rate ([Table 1]). From this, we have developed a change in guidelines aimed at reducing length of stay, redundant laboratory studies, and reduced rate of readmission.
Conclusion(s): Although our current outcomes for resection of pituitary adenoma are on par with published data, we have identified areas of possible quality improvement which have since been implemented

Cognitive impairment in Parkinson's disease (PD) is related to the reorganization of brain topology. Although drug challenge studies have proven how levodopa treatment can modulate functional connectivity in brain circuits, the role of chronic dopaminergic therapy on cognitive status and functional connectivity has never been investigated. We sought to characterize brain functional topology in mid-stage PD patients under chronic antiparkinson treatment and explore the presence of correlation between reorganization of brain architecture and specific cognitive deficits. We explored networks topology and functional connectivity in 16 patients with PD and 16 matched controls through a graph theoretical analysis of resting state-functional MRI data, and evaluated the relationships between network metrics and cognitive performance. PD patients showed a preserved small-world network topology but a lower clustering coefficient in comparison with healthy controls. Locally, PD patients showed lower degree of connectivity and local efficiency in many hubs corresponding to functionally relevant areas. Four disconnected subnetworks were also identified in regions responsible for executive control, sensory-motor control and planning, motor coordination and visual elaboration. Executive functions and information processing speed were directly correlated with degree of connectivity and local efficiency in frontal, parietal and occipital areas. While functional reorganization appears in both motor and cognitive areas, the clinical expression of network imbalance seems to be partially compensated by the chronic levodopa treatment with regards to the motor but not to the cognitive performance. In a context of reduced network segregation, the presence of higher local efficiency in hubs regions correlates with a better cognitive performance.

The International Genomics of Alzheimer's Project (IGAP) is a consortium for characterizing the genetic landscape of Alzheimer's disease (AD). The identified and/or confirmed 19 single-nucleotide polymorphisms (SNPs) associated with AD are located on non-coding DNA regions, and their functional impacts on AD are as yet poorly understood. We evaluated the roles of the IGAP SNPs by integrating data from many resources, based on whether the IGAP SNP was (1) a proxy for a coding SNP or (2) associated with altered mRNA transcript levels. For (1), we confirmed that 12 AD-associated coding common SNPs and five nonsynonymous rare variants are in linkage disequilibrium with the IGAP SNPs. For (2), the IGAP SNPs in CELF1 and MS4A6A were associated with expression of their neighboring genes, MYBPC3 and MS4A6A, respectively, in blood. The IGAP SNP in DSG2 was an expression quantitative trait loci (eQTL) for DLGAP1 and NETO1 in the human frontal cortex. The IGAP SNPs in ABCA7, CD2AP, and CD33 each acted as eQTL for AD-associated genes in brain. Our approach for identifying proxies and examining eQTL highlighted potentially impactful, novel gene regulatory phenomena pertinent to the AD phenotype.

BACKGROUND AND PURPOSE/OBJECTIVE:New-onset refractory status epilepticus is a clinical condition characterized by acute and prolonged pharmacoresistant seizures without a pre-existing relevant neurologic disorder, prior epilepsy, or clear structural, toxic, or metabolic cause. New-onset refractory status epilepticus is often associated with antineuronal antibodies and may respond to early immunosuppressive therapy, reflecting an inflammatory element of the condition. FDG-PET is a useful diagnostic tool in inflammatory and noninflammatory encephalitis. We report here FDG-PET findings in new-onset refractory status epilepticus and their correlation to disease activity, other imaging findings, and outcomes. MATERIALS AND METHODS/METHODS:Twelve patients who met the criteria for new-onset refractory status epilepticus and who had FDG-PET and MR imaging scans and electroencephalography at a single academic medical center between 2008 and 2017 were retrospectively identified. Images were independently reviewed by 2 radiologists specialized in nuclear imaging. Clinical characteristics and outcome measures were collected through chart review. RESULTS:= .028). CONCLUSIONS:Both FDG-PET hypometabolism and hypermetabolism are seen in the setting of new-onset refractory status epilepticus and may represent markers of disease activity.