Faculty Bibliography

INTRODUCTION/BACKGROUND:Intraoperative neurophysiological monitoring (IONM) is widely used to prevent nervous system injury during surgeries in elderly patients. However, there are no studies that describe the characteristics and changes in neurophysiological tests during the IONM of patients aged 60 years and older. The study aims to describe and compare IONM changes during surgeries in adult patients aged 18 to 59 years with those aged 60 years and older. METHODS:We performed a comparative retrospective study of patients aged 18 to 59 years versus those 60 aged years and older who underwent IONM during 2013 to 2018 in Mexico City. Sociodemographic characteristics were recorded and compared. Intraoperative neurophysiological monitoring techniques, their changes, and surgical procedures for both groups were analyzed and compared using descriptive statistics, Mann-Whitney U, Fisher, and χ tests. The sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS:In total, 195 patients were analyzed: 104 patients, 68.63 ± 6.54 years old (elderly group) and 91 patients, 42.3 ± 10.5 years old (younger group). No differences were found in the rates of signal change during IONM between the group of elderly patients and the younger group. The sensitivity, specificity, and positive and negative predictive values were 80%, 99%, 80%, and 99%, respectively. CONCLUSIONS:Elderly patients have a similar rate of changes in IONM signals compared with younger patients during heterogeneous surgeries guided by IONM.

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure plus cerebellar syndrome and/or parkinsonism. Dysphagia is a frequent and disabling symptom in MSA and its occurrence within 5 years of motor onset is an additional diagnostic feature. Dysphagia can lead to aspiration pneumonia, a recognized cause of death in MSA. Guidelines for diagnosis and management of dysphagia in MSA are lacking. An International Consensus Conference among experts with methodological support was convened in Bologna to reach consensus statements for the diagnosis, prognosis, and treatment of dysphagia in MSA. Abnormalities of the oral and pharyngeal phases of swallowing, esophageal dysfunction and aspiration occur in MSA and worsen as the disease progresses. According to the consensus, dysphagia should be investigated through available screening questionnaires and clinical and instrumental assessment (videofluoroscopic study or fiberoptic endoscopic evaluation of swallowing and manometry) at the time of MSA diagnosis and periodically thereafter. There is evidence that dysphagia is associated with poor survival in MSA, however effective treatments for dysphagia are lacking. Compensatory strategies like diet modification, swallowing maneuvers and head postures should be applied and botulinum toxin injection may be effective in specific conditions. Percutaneous endoscopic gastrostomy may be performed when there is a severe risk of malnutrition and pulmonary complications, but its impact on survival is undetermined. Several research gaps and unmet needs for research involving diagnosis, prognosis, and treatment were identified.

Image labeling using convolutional neural networks (CNNs) are a template-free alternative to traditional morphometric techniques. We trained a 3D deep CNN to label the hippocampus and amygdala on whole brain 700 μm isotropic 3D MP2RAGE MRI acquired at 7T. Manual labels of the hippocampus and amygdala were used to (i) train the predictive model and (ii) evaluate performance of the model when applied to new scans. Healthy controls and individuals with epilepsy were included in our analyses. Twenty-one healthy controls and sixteen individuals with epilepsy were included in the study. We utilized the recently developed DeepMedic software to train a CNN to label the hippocampus and amygdala based on manual labels. Performance was evaluated by measuring the dice similarity coefficient (DSC) between CNN-based and manual labels. A leave-one-out cross validation scheme was used. CNN-based and manual volume estimates were compared for the left and right hippocampus and amygdala in healthy controls and epilepsy cases. The CNN-based technique successfully labeled the hippocampus and amygdala in all cases. Mean DSC = 0.88 ± 0.03 for the hippocampus and 0.8 ± 0.06 for the amygdala. CNN-based labeling was independent of epilepsy diagnosis in our sample (p = .91). CNN-based volume estimates were highly correlated with manual volume estimates in epilepsy cases and controls. CNNs can label the hippocampus and amygdala on native sub-mm resolution MP2RAGE 7T MRI. Our findings suggest deep learning techniques can advance development of morphometric analysis techniques for high field strength, high spatial resolution brain MRI.

STAT3 is a transcription factor with roles in inflammation and tumorigenicity. A fraction of STAT3 localizes in mitochondria, where it augments tumorigenesis via regulation of mitochondrial functions, including modulation of respiration and redox status. We show a novel mechanism for mitochondrial STAT3 regulation of redox homeostasis in triple negative breast cancer cells. Loss of STAT3 diminished complex I dehydrogenase activity and impaired NAD+ regeneration, leading to impaired expression of glutathione biosynthetic genes and other antioxidant genes. Expressing mitochondrially-restricted STAT3 or replenishment of the cellular NAD pool restored antioxidant gene expression, as did complementation of the NADH dehydrogenase activity by expression of the STAT3-independent yeast dehydrogenase, NDI1. These NAD-regulated processes contributed to malignant phenotypes by promoting clonal cell growth and migration. Proximity interaction and protein pull-down assays identified three components of complex I that associated with mitochondrial STAT3, providing a potential mechanistic basis for how mitochondrial STAT3 affects complex I activity. Our data document a novel mechanism through which mitochondrial STAT3 indirectly controls antioxidant gene regulation through a retrograde NAD+ signal that is modulated by complex I dehydrogenase activity.

[Figure: see text].

OBJECTIVE:To characterize patients with coronavirus disease 2019 (COVID-19) who presented primarily with neurologic symptoms without typical COVID-19 symptoms of fever, cough, and dyspnea. METHODS:We retrospectively identified COVID-19-positive patients 18 years and older that had neurology symptoms on presentation requiring neurology consultation between March 14, 2020 and May 18, 2020. The patients were then classified into those with typical COVID-19 symptoms and those without. Demographic, clinical symptoms, laboratory result, and clinical outcomes were collected. RESULTS:Out of 282 patients who had neurology consult during this period, we identified 56 (mean age 69.2 years, 57% women) who tested COVID-19-positive and had neurologic symptoms on initial presentation. Of these, 23 patients (mean age 65.2 years, 52% women) had no typical COVID-19 symptoms while 33 did (mean age 72.2 years, 60% woman). In both groups, impaired consciousness was the most common initial neurologic symptom, followed by stroke, unsteady gait, headache, seizure, syncopal event, acute vision changes, and intracranial hemorrhage. Out of the 23 patients without typical COVID-19 symptoms on presentation, 10 went on to develop typical symptoms with 8 needing supplemental oxygen and one requiring mechanical ventilation. CONCLUSION/CONCLUSIONS:Patients who have COVID-19 can present with serious neurologic symptoms such as impaired consciousness and stroke even without typical COVID-19 symptoms. Those without typical COVID-19 symptoms can later develop typical symptoms severe enough to need respiratory support.

BACKGROUND AND PURPOSE/OBJECTIVE:Perfusion imaging can risk stratify patients with symptomatic intracranial stenosis. We aim to determine the association between perfusion delay and length of hospital stay (LOS) in symptomatic middle cerebral artery (MCA) stenosis patients. METHODS:This is a retrospective study of consecutive patients admitted to a comprehensive stroke center over 5 years with ischemic stroke or transient ischemic attack (TIA) within 7 days of symptom onset due to MCA stenosis (50-99%) and underwent perfusion imaging. Patients were divided into three groups: mismatch volume ≥ 15 cc based on T max > 6 second delay, T max 4-6 second delay, and <4 second delay. The outcome was LOS, both as a continuous variable and categorical (≥7 days [prolonged LOS] vs. <7 days). We used adjusted regression analyses to determine the association between perfusion categories and LOS. RESULTS:One hundred and seventy eight of 194 patients met the inclusion criteria. After adjusting for age and NIHSS, T max >6 second mismatch was associated with prolonged LOS (OR 2.94 95% CI 1.06-8.18; P = .039), but T max 4-6 second was not (OR 1.45 95% CI .46-4.58, P = .528). We found similar associations when LOS was a continuous variable for T max > 6 second (β coefficient = 2.01, 95% CI .05-3.97, P = .044) and T max 4-6 second (β coefficient = 1.24, 95% CI -.85 to 3.34, P = .244). CONCLUSION/CONCLUSIONS:In patients with symptomatic MCA stenosis, T max > 6 second perfusion delay is associated with prolonged LOS. Prospective studies are needed to validate our findings.

Intracerebral hemorrhage (ICH) can be a devastating complication of coronavirus disease (COVID-19). We aimed to assess risk factors associated with ICH in this population. We performed a retrospective cohort study of adult patients admitted to NYU Langone Health system between March 1 and April 27 2020 with a positive nasopharyngeal swab polymerase chain reaction test result and presence of primary nontraumatic intracranial hemorrhage or hemorrhagic conversion of ischemic stroke on neuroimaging. Patients with intracranial procedures, malignancy, or vascular malformation were excluded. We used regression models to estimate odds ratios and 95% confidence intervals (OR, 95% CI) of the association between ICH and covariates. We also used regression models to determine association between ICH and mortality. Among 3824 patients admitted with COVID-19, 755 patients had neuroimaging and 416 patients were identified after exclusion criteria were applied. The mean (standard deviation) age was 69.3 (16.2), 35.8% were women, and 34.9% were on therapeutic anticoagulation. ICH occurred in 33 (7.9%) patients. Older age, non-Caucasian race, respiratory failure requiring mechanical ventilation, and therapeutic anticoagulation were associated with ICH on univariate analysis (p < 0.01 for each variable). In adjusted regression models, anticoagulation use was associated with a five-fold increased risk of ICH (OR 5.26, 95% CI 2.33-12.24, p < 0.001). ICH was associated with increased mortality (adjusted OR 2.6, 95 % CI 1.2-5.9). Anticoagulation use is associated with increased risk of ICH in patients with COVID-19. Further investigation is required to elucidate underlying mechanisms and prevention strategies in this population.

Military service members are frequently subjected to subconcussive blast events during training and deployment. Emerging evidence suggests blast exposures of these magnitudes may have long-term consequences for dimensions of cognitive function. Less is known about cognitive sequelae acutely following deployment-related subconcussive blast events. The current study addressed this knowledge gap by assessing the extent to which subconcussive blast exposure affected performance on the Automated Neuropsychological Assessment Metrics 4 TBI-MIL (ANAM). Baseline-referenced and normative comparisons of archival ANAM data were analyzed for a cohort of personnel who were exposed to blast (blast group; n = 27) and personnel who were not exposed to blast (no-blast group; n = 36) that were otherwise asymptomatic for a concussion. The blast group exhibited statistically significant lower scores compared to the no-blast group (between-subjects), baseline assessments (within-subjects), and an age-matched normative population. Normative comparisons revealed that the scores for the reaction time subtests (i.e., procedural and both simple reaction time tasks) were outside the range of normal functioning (1 SD) and reliable change indices revealed clinically meaningful change only for simple reaction time. The results highlight covert effects of subconcussive blast exposure that may warrant further monitoring in the immediate aftermath of a blast event.

Movement disorders encompass various conditions affecting the nervous system. The pathological processes underlying movement disorders lead to aberrant synaptic plastic changes, which in turn alter the functioning of large-scale brain networks. Therefore, clinical phenomenology does not only entail motor symptoms but also cognitive and motivational disturbances. The result is the disruption of motor learning and motor behaviour. Due to this complexity, the responsiveness to standard therapies could be disappointing. Specific forms of rehabilitation entailing goal-based practice, aerobic training and the use of non-invasive brain stimulation techniques could "restore" neuroplasticity at motor-cognitive circuitries, leading to clinical gains. This is probably associated with modulations occurring at both molecular (synaptic) and circuitry levels (networks). Several gaps remain in our understanding of the relationships among plasticity and neural networks and how neurorehabilitation could promote clinical gains is still unclear. In this review, we outline first the networks involved in motor learning and behaviour and analyse which mechanisms link the pathological synaptic plastic changes with these networks' disruption in movement disorders. Therefore, we provide theoretical and practical bases to be applied for treatment in rehabilitation.