Faculty Bibliography

Many military veterans who experienced blast-related traumatic brain injuries (TBI) in the conflicts in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems including post-traumatic stress disorder (PTSD). Besides static symptoms, new symptoms may emerge or existing symptoms may worsen. TBI is also a risk factor for the later development of neurodegenerative diseases. Rats exposed to repetitive low-level blast overpressure (BOP) develop robust and enduring cognitive and PTSD-related behavioral traits that are present for at least one year after blast exposure. Here we determined the time-course of these traits appearance by testing rats in the immediate post-blast period. Three cohorts of rats examined within the first eight weeks exhibited no behavioral phenotype, or in one cohort features of anxiety. None showed the altered cued fear responses, or impaired novel object recognition characteristic of the fully developed phenotype. Two cohorts retested 36 to 42 weeks after blast exposure exhibited the expanded behavioral phenotype including anxiety as well as altered cued fear learning and impaired novel object recognition. Combined with previous work the chronic behavioral phenotype has been observed in six cohorts of blast-exposed rats studied at 3-4 months or longer after blast injury and the three cohorts studied here document the progressive nature of the cognitive/behavioral phenotype. These studies suggest the existence of a latent, delayed emerging, and progressive blast-induced cognitive and behavioral phenotype. The delayed onset has implications for the evolution of post-blast neurobehavioral syndromes in military veterans and its modeling in experimental animals.

During Mobile Brain-Body Imaging (MoBI) experiments, electroencephalography and motion capture systems are used in concert to record high temporal resolution neural activity and movement kinematics while participants perform demanding perceptual and cognitive tasks in a naturalistic environment. A typical MoBI setup involves positioning multi-channel electrode caps based on anatomical fiducials as well as experimenter and participant intuition regarding the scalp midpoint location (i.e., Cz). Researchers often use the "template" electrode locations provided by the manufacturer, however the "actual" electrode locations can vary based on each participant's head morphology. Accounting for differences in head morphologies could provide more accurate clinical diagnostic information when using MoBI to identify neurological deficits in patients with motor, sensory, or cognitive impairments. Here, we asked whether the existing motion capture system used in a MoBI setup could be easily adapted to improve spatial localization of electrodes across participants without requiring additional or specialized equipment that might impede clinical adoption. Using standard electrode configurations, infrared markers were placed on a subset of electrodes and anatomical fiducials, and the remaining electrode locations were estimated using spherical or ellipsoid models. We identified differences in event-related potentials between "template" and "actual" electrode locations during a Go/No-Go task (p<9.8e-5) and an object-manipulation task (p<9.8e-5). Thus, the motion capture system already used in MoBI experiments can be effectively deployed to accurately register and quantify the neural activity. Improving the spatial localization without needing specialized hardware or additional setup time to the workflow has important real-world implications for translating MoBI to clinical environments.

PURPOSE/OBJECTIVE:Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy (HSAN-3) that is clinically characterized by impaired pain and temperature perception and abnormal autonomic function. Patients with FD have gastrointestinal dysmotility and report a range of gastrointestinal symptoms that have yet to be systematically evaluated. The aim of this study was to establish the frequency and severity of gastrointestinal symptoms in patients with FD. METHODS:The validated National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) survey questionnaire, together with additional FD-specific questions, were distributed to 202 living patients with genetically confirmed FD who had been identified from the New York University FD Patient Registry or, when relevant, to their respective caretaker. As a comparison group, we used a general US adult population for whom PROMIS scores were available (N = 71,812). RESULTS:Of the 202 questionnaires distributed, 77 (38%) were returned, of which 53% were completed by the patient. Median age of the respondents was 25 years, and 44% were male. Gastrostomy tube was the sole nutrition route for 25% of the patients, while 53% were reliant on the gastrostomy tube only for liquid intake. The prevalence of gastrointestinal symptoms was significantly higher in each of the eight domains of PROMIS in patients with FD than in the controls. Gastrointestinal symptoms as measured by raw scores on the PROMIS scale were significantly less severe in the FD patient group than in the control population in all domains with the exception of the abdominal pain domain. The surveys completed by caregivers reported the same burden of symptoms as those completed only by patients. CONCLUSION/CONCLUSIONS:Gastrointestinal symptoms affect nearly all patients with FD. Gastrointestinal symptoms are more prevalent in adult patients with FD than in the average US adult population but are less severe in the former.

Behavioral findings suggest that aging alters the involvement of cortical sensorimotor mechanisms in postural control. However, corresponding accounts of the underlying neural mechanisms remain sparse, especially the extent to which these mechanisms are affected during more demanding tasks. Here, we set out to elucidate cortical correlates of altered postural stability in younger and older adults. 3D body motion tracking and high-density electroencephalography (EEG) were measured while 14 young adults (mean age = 24 years, 43% women) and 14 older adults (mean age = 77 years, 50% women) performed a continuous balance task under four different conditions. Manipulations were applied to base of support (either regular or tandem (heel-to-toe) stance) and visual input (either static visual field or dynamic optic flow). Standing in tandem, the more challenging position, resulted in increased sway for both age groups, but for the older adults only this effect was exacerbated when combined with optic flow compared to the static visual display. These changes in stability were accompanied by neuro-oscillatory modulations localized to midfrontal and parietal regions. A cluster of electro-cortical sources localized to the supplementary motor area showed a large increase in theta spectral power (4-7Hz) during tandem stance, and this modulation was much more pronounced for the younger group. Additionally, the older group displayed widespread mu (8-12Hz) and beta (13-30Hz) suppression as balance tasks placed more demands on postural control, especially during tandem stance. These findings may have substantial utility in identifying early cortical correlates of balance impairments in otherwise healthy older adults.

Neurogenic orthostatic hypotension (nOH) is one of the most debilitating nonmotor symptoms in patients with Parkinson disease and other synucleinopathies. Patients with Parkinson disease and nOH suffer from more hospitalizations, emergency room visits, more telephone calls and e-mails to providers, and have a significantly shorter survival compared to patients with Parkinson disease and no nOH. Overall, health-related costs in patients with Parkinson disease and OH are 2.5-fold higher compared to patients with Parkinson disease without OH. Therefore, the development of effective therapies for patients with Parkinson disease and nOH should be a research priority. In recent years, better understanding of the pathophysiology of nOH has resulted in the identification of novel therapeutic targets and the development and approval of effective drug therapies, such as midodrine and droxidopa. We here review the design and endpoint selection for clinical trials of nOH in patients with Parkinson disease and other synucleinopathies, recapitulate the results of completed and ongoing clinical trials for nOH, and discuss common challenges and their potential remedies.
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The use of virtual surgical planning and computer-aided design/computer-aided manufacturing has gained popularity in the surgical correction of craniosynostosis. This study expands the use of virtual surgical planning and computer-aided design/computer-aided manufacturing in cranial vault reconstruction by using these methods to reconstruct the anterior vault using a single endocortically-plated unit constructed from the posterior calvarium. This technique was designed to reduce the risk of undesirable contour deformities that can occur when multiple bone grafts are used to reconstruct the anterior vault and fronto-orbital rim. Six patients were included in this study, all of which had nonsyndromic craniosynostosis. Excellent aesthetic outcomes were obtained in all patients, without complication. Additionally, the placement of a single reconstructive unit constructed from the posterior calvarium was efficient, aesthetically pleasing, and minimized postoperative contour deformities secondary to bone gaps, resorption, and often palpable resorbable plates.

OBJECTIVE:Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young adults. Automated Infrared Pupillometry (AIP) has shown promising results in predicting neural damage in aneurysmal subarachnoid hemorrhage and ischemic stroke. We aimed to explore potential uses of AIP in triaging TBI patients. We hypothesized that a brain injury severe enough to require an intervention would show neurological pupillary index (NPI) changes. METHODS:We conducted a prospective pilot study at a Level-1 Trauma Center between November 2019 and February 2020. AIP readings of consecutive patients seen in the emergency department with blunt TBI and abnormal imaging findings on computed tomography were recorded by the assessing Neurosurgery resident. The relationship between NPI and surgical intervention was studied. RESULTS:Thirty-six patients were enrolled, 9 of which received an intervention. NPI was dichotomized into normal (≥3.0) versus abnormal (<3.0) and was predictive of intervention (Fishers exact test; p<0.0001). Six of the nine patients had a GCS ≤8, and imaging signs of increased ICP and underwent craniectomy (n=4) or ICP-monitor placement (n=2) and had an abnormal NPI. Three patients underwent ICP-monitor placement for GCS ≤8 in accordance with TBI guidelines despite minimal imaging findings and had a normal NPI. The GCS of these patients improved within 24-hours requiring ICP-monitor removal. NPI was normal in all patients who did not require intervention. CONCLUSIONS:AIP could potentially be useful in triaging comatose patients after blunt TBI. An NPI ≥3.0 may be reassuring in patients with no signs of mass-effect or increased ICP.

BACKGROUND:Middle meningeal artery (MMA) embolization has emerged as a promising treatment for chronic subdural hematoma (cSDH). OBJECTIVE:To determine the safety and efficacy of MMA embolization. METHODS:Consecutive patients who underwent MMA embolization for cSDH (primary treatment or recurrence after conventional surgery) at 15 centers were included. Clinical details and follow-up were collected prospectively. Primary clinical and radiographic outcomes were the proportion of patients requiring additional surgical treatment within 90 d after index treatment and proportion with > 50% cSDH thickness reduction on follow-up computed tomography imaging within 90 d. National Institute of Health Stroke Scale and modified Rankin Scale were also clinical outcomes. RESULTS:A total of 138 patients were included (mean age: 69.8, 29% female). A total of 15 patients underwent bilateral interventions for 154 total embolizations (66.7% primary treatment). At presentation, 30.4% and 23.9% of patients were on antiplatelet and anticoagulation therapy, respectively. Median admission cSDH thickness was 14 mm. A total of 46.1% of embolizations were performed under general anesthesia, and 97.4% of procedures were successfully completed. A total of 70.2% of embolizations used particles, and 25.3% used liquid embolics with no significant outcome difference between embolization materials (P > .05). On last follow-up (mean 94.9 d), median cSDH thickness was 4 mm (71% median thickness reduction). A total of 70.8% of patients had >50% improvement on imaging (31.9% improved clinically), and 9 patients (6.5%) required further cSDH treatment. There were 16 complications with 9 (6.5%) because of continued hematoma expansion. Mortality rate was 4.4%, mostly unrelated to the index procedure but because of underlying comorbidities. CONCLUSION/CONCLUSIONS:MMA embolization may provide a safe and efficacious minimally invasive alternative to conventional surgical techniques.

OBJECTIVE:To determine the prevalence and associated mortality of well-defined neurologic diagnoses among COVID-19 patients, we prospectively followed hospitalized SARS-Cov-2 positive patients and recorded new neurologic disorders and hospital outcomes. METHODS:We conducted a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between COVID-19 patients with and without neurologic disorders. RESULTS:Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all P<0.05). After adjusting for age, sex, SOFA-scores, intubation, past history, medical complications, medications and comfort-care-status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (Hazard Ratio[HR] 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001). CONCLUSIONS:Neurologic disorders were detected in 13.5% of COVID-19 patients and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.