Faculty Bibliography

OBJECTIVE:To assess telehealth practice for headache visits in the United States. BACKGROUND:The rapid roll out of telehealth during the COVID-19 pandemic impacted headache specialists. METHODS:American Headache Society (AHS) members were emailed an anonymous survey (9/9/20-10/12/20) to complete if they had logged ≥2 months or 50+ headache visits via telehealth. RESULTS:Out of 1348 members, 225 (16.7%) responded. Most were female (59.8%; 113/189). Median age was 47 (interquartile range [IQR] 37-57) (N = 154). The majority were MD/DOs (83.7%; 159/190) or NP/PAs (14.7%; 28/190), and most (65.1%; 123/189) were in academia. Years in practice were 0-3: 28; 4-10: 58; 11-20: 42; 20+: 61. Median number of telehealth visits was 120 (IQR 77.5-250) in the prior 3 months. Respondents were "comfortable/very comfortable" treating via telehealth (a) new patient with a chief complaint of headache (median, IQR 4 [3-5]); (b) follow-up for migraine (median, IQR 5 [5-5]); (c) follow-up for secondary headache (median, IQR 4 [3-4]). About half (51.1%; 97/190) offer urgent telehealth. Beyond being unable to perform procedures, top barriers were conducting parts of the neurologic exam (157/189), absence of vital signs (117/189), and socioeconomic/technologic barriers (91/189). Top positive attributes were patient convenience (185/190), reducing patient travel stress (172/190), patient cost reduction (151/190), flexibility with personal matters (128/190), patient comfort at home (114/190), and patient medications nearby (103/190). Only 21.3% (33/155) of providers said telehealth visit length differed from in-person visits, and 55.3% (105/190) believe that the no-show rate improved. On a 1-5 Likert scale, providers were "interested"/"very interested" in digitally prescribing headache apps (median 4, IQR 3-5) and "interested"/"very interested" in remotely monitoring patient symptoms (median 4, IQR 3-5). CONCLUSIONS:Respondents were comfortable treating patients with migraine via telehealth. They note positive attributes for patients and how access may be improved. Technology innovations (remote vital signs, digitally prescribing headache apps) and remote symptom monitoring are areas of interest and warrant future research.

BACKGROUND:An association between chronic infectious diseases and development of dementia has been suspected for decades, based on the finding of pathogens in postmortem brain tissue and on serological evidence. However, questions remain regarding confounders, reverse causality, and how accurate, reproducible and generalizable those findings are. OBJECTIVE:Investigate whether exposure to Herpes simplex (manifested as herpes labialis), Chlamydophila pneumoniae (C. pneumoniae), Helicobacter pylori (H. pylori), and cytomegalovirus (CMV) modifies the risk of dementia in a populational cohort. METHODS:Questionnaires regarding incidence of herpes infections were administered to Original Framingham Study participants (n = 2,632). Serologies for C. pneumoniae, H. pylori, and CMV were obtained in Original (n = 2,351) and Offspring cohort (n = 3,687) participants. Participants are under continuous dementia surveillance. Brain MRI and neuropsychological batteries were administered to Offspring participants from 1999-2005. The association between each infection and incident dementia was tested with Cox models. Linear models were used to investigate associations between MRI or neuropsychological parameters and serologies. RESULTS:There was no association between infection serologies and dementia incidence, total brain volume, and white matter hyperintensities. Herpes labialis was associated with reduced 10-year dementia risk (HR 0.66, CI 0.46-0.97), but not for the duration of follow-up. H. pylori antibodies were associated with worse global cognition (β -0.14, CI -0.22, -0.05). CONCLUSION:We found no association between measures of chronic infection and incident dementia, except for a reduction in 10-year dementia risk for patients with herpes labialis. This unexpected result requires confirmation and further characterization, concerning antiviral treatment effects and capture of episodes.

KEY POINTS/CONCLUSIONS:The corticoreticulospinal tract (CReST) is a descending motor pathway that reorganizes after corticospinal tract (CST) injury in animals. In humans, the pattern of CReST innervation to upper limb muscles has not been carefully examined in healthy individuals or individuals with CST injury. In the present study, we assessed CReST projections to an arm and hand muscle on the same side of the body in healthy and chronic stoke subjects using transcranial magnetic stimulation. We show that CReST connection strength to the muscles differs between healthy and stroke subjects, with stronger connections to the hand than arm in healthy subjects, and stronger connections to the arm than hand in stroke subjects. These results help us better understand CReST innervation patterns in the upper limb, and may point to its role in normal motor function and motor recovery in humans. ABSTRACT/UNASSIGNED:The corticoreticulospinal tract (CReST) is a major descending motor pathway in many animals, but little is known about its innervation patterns in proximal and distal upper extremity muscles in humans. The contralesional CReST furthermore reorganizes after corticospinal tract (CST) injury in animals, but it is less clear whether CReST innervation changes after stroke in humans. We thus examined CReST functional connectivity, connection strength, and modulation in an arm and hand muscle of healthy (n = 15) and chronic stroke (n = 16) subjects. We delivered transcranial magnetic stimulation to the contralesional hemisphere (assigned in healthy subjects) to elicit ipsilateral motor evoked potentials (iMEPs) from the paretic biceps (BIC) and first dorsal interosseous (FDI) muscle. We operationalized CReST functional connectivity as iMEP presence/absence, CReST projection strength as iMEP size and CReST modulation as change in iMEP size by head rotation. We found comparable CReST functional connectivity to the BICs and FDIs in both subject groups. However, the pattern of CReST connection strength to the muscles diverged between groups, with stronger connections to FDIs than BICs in healthy subjects and stronger connections to BICs than FDIs in stroke subjects. Head rotation modulated only FDI iMEPs of healthy subjects. Our findings indicate that the healthy CReST does not have a proximal innervation bias, and its strong FDI connections may have functional relevance to finger individuation. The reversed CReST innervation pattern in stroke subjects confirms its reorganization after CST injury, and its strong BIC connections may indicate upregulation for particular upper extremity muscles or their functional actions.

Oral cannabidiol (CBD) is approved by the Food and Drug Administration (FDA) to treat patients with Dravet and Lennox-Gastaut syndromes, and tuberous sclerosis complex. The therapeutic potential of oral CBD formulations is limited by extensive first-pass hepatic metabolism. Following oral administration, the inactive metabolite blood concentration is ∼40-fold higher than CBD. Inhalation bypasses the pharmacokinetic (PK) variability attributed to irregular gastrointestinal absorption and first-pass hepatic metabolism and may efficiently deliver CBD into systemic circulation. This phase 1 study compared the PK of a dry-powder inhaler (DPI) CBD formulation (10 mg; excipient containing 2.1 mg CBD) with an oral CBD solution (Epidiolex®, 50 mg) in healthy participants. Following a single dose of Epidiolex or DPI CBD (n=10 PK evaluable participants each), the maximum CBD concentration for the inhaled powder was 71-fold higher than that of Epidiolex while administering 24-fold less CBD. The mean time to reach maximum concentration was 3.8 minutes for the DPI CBD formulation compared with 122 minutes for Epidiolex. Both Epidiolex and DPI CBD were generally safe and well-tolerated. These data indicate that DPI CBD provided more rapid onset and increased bioavailability than oral CBD and support further investigations on the use of DPI CBD for acute indications.

Arousal levels perpetually rise and fall spontaneously. How markers of arousal - pupil size and frequency content of brain activity - relate to each other and influence behavior in humans is poorly understood. We simultaneously monitored magnetoencephalography and pupil in healthy volunteers at rest and during a visual perceptual decision-making task. Spontaneously varying pupil size correlates with power of brain activity in most frequency bands across large-scale resting-state cortical networks. Pupil size recorded at prestimulus baseline correlates with subsequent shifts in detection bias (c) and sensitivity (d'). When dissociated from pupil-linked state, prestimulus spectral power of resting state networks still predicts perceptual behavior. Fast spontaneous pupil constriction and dilation correlate with large-scale brain activity as well but not perceptual behavior. Our results illuminate the relation between central and peripheral arousal markers and their respective roles in human perceptual decision-making.

Flipping through social media feeds, viewing exhibitions in a museum, or walking through the botanical gardens, people consistently choose to engage with and disengage from visual content. Yet, in most laboratory settings, the visual stimuli, their presentation duration, and the task at hand are all controlled by the researcher. Such settings largely overlook the spontaneous nature of human visual experience, in which perception takes place independently from specific task constraints and its time course is determined by the observer as a self-governing agent. Currently, much remains unknown about how spontaneous perceptual experiences unfold in the brain. Are all perceptual categories extracted during spontaneous perception? Does spontaneous perception inherently involve volition? Is spontaneous perception segmented into discrete episodes? How do different neural networks interact over time during spontaneous perception? These questions are imperative to understand our conscious visual experience in daily life. In this article we propose a framework for spontaneous perception. We first define spontaneous perception as a task-free and self-paced experience. We propose that spontaneous perception is guided by four organizing principles that grant it temporal and spatial structures. These principles include coarse-to-fine processing, continuity and segmentation, agency and volition, and associative processing. We provide key suggestions illustrating how these principles may interact with one another in guiding the multifaceted experience of spontaneous perception. We point to testable predictions derived from this framework, including (but not limited to) the roles of the default-mode network and slow cortical potentials in underlying spontaneous perception. We conclude by suggesting several outstanding questions for future research, extending the relevance of this framework to consciousness and spontaneous brain activity. In conclusion, the spontaneous perception framework proposed herein integrates components in human perception and cognition, which have been traditionally studied in isolation, and opens the door to understand how visual perception unfolds in its most natural context.

Advanced Parkinson's disease (PD) often brings a set of motor and non-motor features that are particularly challenging to manage. Medication options can be limited by side-effects and quality of life can be severely affected by an accumulating burden of nonmotor symptoms. Here, we reviewed the literature and our clinical experience with the aim of providing a practical approach to the management of advanced PD. We provide guidelines for treatment of physical and neurobehavioral concerns, that occur in advanced PD.

There are racial and socioeconomic disparities in the care of patients with Parkinson's disease (PD). Bellevue Hospital Center (BHC) in New York City is the oldest public hospital in the United States providing care to a multiracial, socioeconomically diverse and medically underserved population. We investigated racial and social disparities in providing care to patients with PD and related disorders at BHC compared to a NYU Langone Health, a Parkinson's Foundation Center of Excellence. Retrospective chart review of patients with diagnosis of PD or PD-related disorders evaluated at BHC or at NYU outpatient clinics from January 2012 to August 2017. 100 patients were enrolled from each site: BHC (55% men); NYU (49% men). The majority of patients at NYU were White (77%), compared to 14% at BHC; Hispanic patients comprised the majority at BHC (56%) (p < 0.001). BHC patients had more clinic visits per year compared to the NYU cohort (2.88 vs. 2.40, p = 0.001). BHC patients were less likely to self-report exercise (p = 0.047) or participation in physical therapy (p = 0.015). There were no clinically significant differences in diagnosis type, time to diagnosis, average Hoehn & Yahr or levodopa equivalent dose. Compared to a Parkinson's Foundation Center of Excellence, PD patients in a public hospital system are more racially diverse, are less likely to be insured, have higher rates of care utilization and are less likely to access necessary interventions such as physical therapy and exercise.

OBJECTIVE:To report two cases of hemicrania continua (HC) in a mother and daughter. BACKGROUND:HC is a rare primary headache disorder belonging to the family of trigeminal autonomic cephalalgias (TACs). Unlike migraine, familial cases of TACs are rare, and we know relatively little of their inheritance pattern and genetic mechanisms. METHODS:We present a mother and daughter with HC. We compare the similarities and differences between this family and the first report of familial HC and discuss the implications for future studies. RESULTS:Both the mother and daughter presented with a constant, side-locked headache of moderate intensity, with episodic exacerbations of more severe pain that are associated with ipsilateral cranial autonomic activation. After negative workup, both patients were started on indomethacin and achieved absolute response at different doses, confirming HC. CONCLUSIONS:Our report further corroborates other reports of familial TACs that TACs are primary headaches possibly attributable to genetic factors, albeit detailed mechanisms remain elusive. Nevertheless, whether clinical presentation and treatment responses would be substantially different between sporadic and familial HCs remain unclear.