Faculty Bibliography

Parkinson's disease is the most common age-related motoric neurodegenerative disease. In addition to the cardinal motor symptoms of tremor, rigidity, bradykinesia, and postural instability, there are numerous non-motor symptoms as well. Among the non-motor symptoms, autonomic nervous system dysfunction is common. Autonomic symptoms associated with Parkinson's disease include sialorrhea, hyperhidrosis, gastrointestinal dysfunction, and urinary dysfunction. Botulinum neurotoxin has been shown to potentially improve these autonomic symptoms. In this review, the varied uses of botulinum neurotoxin for autonomic dysfunction in Parkinson's disease are discussed. This review also includes discussion of some additional indications for the use of botulinum neurotoxin in Parkinson's disease, including pain.

Previous multi-center imaging studies with ¹⁸F-FDG PET have established the presence of Parkinson's disease motor- and cognition-related metabolic patterns termed PDRP and PDCP in patients with this disorder. Given that in PD cerebral perfusion and glucose metabolism are typically coupled in the absence of medication, we determined whether subject expression of these disease networks can be quantified in early-phase images from dynamic ¹⁸F-FPCIT PET scans acquired to assess striatal dopamine transporter (DAT) binding. Methods: We studied a cohort of early-stage PD patients and age-matched healthy control subjects who underwent ¹⁸F-FPCIT at baseline; scans were repeated 4 years later in a smaller subset of patients. The early ¹⁸F-FPCIT frames, which reflect cerebral perfusion, were used to compute PDRP and PDCP expression (subject scores) in each subject, and compared to analogous measures computed based on ¹⁸F-FDG PET scan when additionally available. The late ¹⁸F-FPCIT frames were used to measure caudate and putamen DAT binding in the same individuals. Results: PDRP subject scores from early-phase ¹⁸F-FPCIT and ¹⁸F-FDG scans were elevated and striatal DAT binding reduced in PD versus healthy subjects. The PDRP scores from ¹⁸F-FPCIT correlated with clinical motor ratings, disease duration, and with corresponding measures from ¹⁸F-FDG PET. In addition to correlating with disease duration and analogous ¹⁸F-FDG PET values, PDCP scores correlated with DAT binding in the caudate/anterior putamen. PDRP and PDCP subject scores using either method rose over 4 years whereas striatal DAT binding declined over the same time period. Conclusion: Early-phase images obtained with ¹⁸F-FPCIT PET can provide an alternative to ¹⁸F-FDG PET for PD network quantification. This technique therefore allows PDRP/PDCP expression and caudate/putamen DAT binding to be evaluated with a single tracer in one scanning session.

BACKGROUND:The pathogenesis of glioma-related seizures (GRS) is poorly understood. Here in, we aim to identify putative molecular pathways that lead to the development of GRS. METHODS:We determined brain transcriptome from intraoperative human brain tissue of patients with either GRS, glioma without seizures (non-GRS), or with idiopathic temporal lobe epilepsy (iTLE). We performed transcriptome-wide comparisons between disease groups tissue from non-epileptic controls (non-EC) to identify differentially-expressed genes (DEG). We compared DEGs to identify those that are specific or common to the groups. Through a gene ontology analysis, we identified molecular pathways enriched for genes with a Log-fold change ≥1.5 or ≤-1.5 and p-value <0.05 compared to non-EC. RESULTS:We identified 110 DEGs that are associated with GRS vs. non-GRS: 80 genes showed high and 30 low expression in GRS. There was significant overexpression of genes involved in cell-to-cell and glutamatergic signaling (CELF4, SLC17A7, and CAMK2A) and down-regulation of genes involved immune-trafficking (CXCL8, H19, and VEGFA). In the iTLE vs GRS analysis, there were 1098 DEGs: 786 genes were overexpressed and 312 genes were underexpressed in the GRS samples. There was significant enrichment for genes considered markers of oncogenesis (GSC, MYBL2, and TOP2A). Further, there was down-regulation of genes involved in the glutamatergic neurotransmission (vesicular glutamate transporter-2) in the GRS vs. iTLE samples. CONCLUSIONS:We identified a number of altered processes such as cell-to-cell signaling and interaction, inflammation-related, and glutamatergic neurotransmission in the pathogenesis of GRS. Our findings offer a new landscape of targets to further study in the fields of brain tumors and seizures.

The visual field region where a stimulus evokes a neural response is called the receptive field (RF). Analytical tools combined with functional MRI can estimate the receptive field of the population of neurons within a voxel. Circular population RF (pRF) methods accurately specify the central position of the pRF and provide some information about the spatial extent (diameter) of the receptive field. A number of investigators developed methods to further estimate the shape of the pRF, for example whether the shape is more circular or elliptical. There is a report that there are many pRFs with highly elliptical pRFs in early visual cortex (V1-V3; Silson et al., 2018). Large aspect ratios (>2) are difficult to reconcile with the spatial scale of orientation columns or visual field map properties in early visual cortex. We started to replicate the experiments and found that the software used in the publication does not accurately estimate RF shape: it produces elliptical fits to circular ground-truth data. We analyzed an independent data set with a different software package that was validated over a specific range of measurement conditions, to show that in early visual cortex the aspect ratios are less than 2. Furthermore, current empirical and theoretical methods do not have enough precision to discriminate ellipses with aspect ratios of 1.5 from circles. Through simulation we identify methods for improving sensitivity that may estimate ellipses with smaller aspect ratios. The results we present are quantitatively consistent with prior assessments using other methodologies.SIGNIFICANCE STATEMENT:We evaluated whether the shape of many population receptive fields in early visual cortex is elliptical and differs substantially from circular. We evaluated two tools for estimating elliptical models of the pRF; one tool was valid over the measured compliance range. Using the validated tool, we found no evidence that confidently rejects circular fits to the pRF in visual field maps V1, V2 and V3. The new measurements and analyses are consistent with prior theoretical and experimental assessments in the literature.

Low levels of engagement in implementation science (IS) among health researchers is a multifaceted issue. With the aim of guiding efforts to increase engagement in IS research, we sought to identify barriers to engagement in IS within the health research community. We performed an online survey of health researchers in the United States in 2018. Basic science researchers were excluded from the sample. IS engagement was measured by self-reported conduct of or collaboration on an IS study in the past 5 years. Potential barriers tested were (a) knowledge and awareness of IS, (b) attitudes about IS research, (c) career benefits of IS, (d) research community support, and (e) research leadership support. We performed simple logistic regressions and tested multivariable logistic regression models of researcher characteristics and potential barriers as predictors of IS engagement. Of the 1,767 health researchers, 49.7% indicated they engaged in an implementation study. Being able to define IS (aOR 3.42, 95%CI 2.68-4.36, p < .001) and having attended IS training (aOR 3.77, 95%CI 2.96-4.81, p < .001) were associated with engaging in IS research. Among other potential barriers tested, perceptions that engaging in IS would not be good for their career (aOR 0.29, 95%CI 0.2-0.41, p < .001) was strongly associated with decreased engagement in IS research. Efforts to increase researcher familiarity with IS methods and foster support for IS within research communities, along with decreasing barriers to funding and publishing, are likely to be most effective for increasing engagement in IS research.

OBJECTIVE:The SARS-Cov2 virus is protean in its manifestations, affecting nearly every organ system. However, nervous system involvement and its impact on disease outcome are poorly characterized. The objective of the study is to determine if neurological syndromes are associated with increased risk of inpatient mortality. METHODS:581 hospitalized patients with confirmed SARS-Cov2 infection, neurological involvement and brain-imaging were compared to hospitalized non-neurological COVID-19 patients. Four patterns of neurological manifestations were identified -acute stroke, new or recrudescent seizures, altered mentation with normal imaging, and neuro-COVID-19 complex. Factors present on admission were analyzed as potential predictors of in-hospital mortality, including sociodemographic variables, pre-existing comorbidities, vital-signs, laboratory values, and pattern of neurological manifestations. Significant predictors were incorporated into a disease-severity score. Patients with neurological manifestations were matched with patients of the same age and disease severity to assess the risk of death. RESULTS:4711 patients with confirmed SARS-Cov2 infection were admitted to one medical system in New York City during a 6-week period. Of these, 581 (12%) had neurological issues of sufficient concern to warrant neuro-imaging. These patients were compared to 1743 non-neurological COVID-19 patients matched for age and disease-severity admitted during the same period. Patients with altered mentation (n=258, p =0.04, OR 1.39, CI 1.04 - 1.86) or radiologically confirmed stroke (n=55, p = 0.001, OR 3.1, CI 1.65-5.92) had a higher risk of mortality than age and severity-matched controls. CONCLUSIONS:The incidence of altered mentation or stroke on admission predicts a modest but significantly higher risk of in-hospital mortality independent of disease severity. While other biomarker factors also predict mortality, measures to identify and treat such patients may be important in reducing overall mortality of COVID-19.

Initially developed for large and giant wide-necked aneurysms of the internal carotid artery, flow diverter devices are now used in almost every location safely and with effectiveness.1-5 This video demonstrates a unique case of a giant aneurysm of the right petrous internal carotid artery in a 20-yr-old patient. This is an extremely rare location, and most of patients are asymptomatic.3-6 Signs of compression of the seventh and eight cranial nerves can be present and even Horner syndrome and lower cranial nerves neuropathies. Nevertheless, rupture can lead to epistaxis and otorrhagia, and ultimately to hemorrhagic shock. The patient in the current report was otherwise healthy but presented with lightheadedness and dizziness for 10 d. The patient consented to the procedure. There was no history of major trauma or head and neck infection. A transradial endovascular flow diversion embolization of a giant aneurysm of the petrous internal carotid artery is herein demonstrated in a stepwise manner. A triaxial system was used to deploy 3 overlapping devices. Concepts of J-wire technique, multiple coverage,1 and the so-called weld technique are emphasized. The role of adjunctive coiling and main reasons for failure are also discussed.7,8 Brief cases of flow diversion embolization of aneurysms of different morphologies at different locations are used to highlight the importance of assessing vessel wall apposition and follow-up imaging.