Faculty Bibliography

Background: MOG antibody disorder (MOGAD) is associated with diverse clinical phenotypes, including recurrent and bilateral optic neuritis, acute disseminated encephalomyelitis, and longitudinally extensive transverse myelitis with a predilection for the conus medullaris. Spinal nerve root involvement in this disease has rarely been described.
Objective(s): To describe a case of MOG antibody disorder with an unusual radiographic presentation.
Method(s): A case is described and review of the literature was performed.
Result(s): A 53-year-old previously healthy man presented to our hospital with three weeks of numbness and pain involving his right arm, bilateral lower extremities, and perineum. Neurologic exam was notable for decreased sensation in his right hand and left leg, hyperreflexia in bilateral lower extremities, and an extensor plantar response on the left. MRI spine was notable for multifocal short-segment T2 hyperintense lesions consistent with demyelination. There was also contrast enhancement of the cauda equina nerve roots and focal lobular enhancement of the left S1 nerve root. MRI brain showed several small T2 hyperintense brainstem lesions. He was started on pulse dose intravenous steroids while undergoing extensive work-up for inflammatory, infectious, and neoplastic causes. Serology was notable for mildly elevated ACE. CSF showed elevated protein. Given these laboratory and radiographic findings, an inflammatory etiology such as neurosarcoidosis was initially felt to be most likely. CT chest was negative for evidence of pulmonary sarcoid. He demonstrated clinical improvement with steroids and was discharged on a slow taper. MOG antibody in the serum (by cell-based assay) resulted positive at 1:100, suggestive of demyelination in the setting of MOGAD. The patient opted for monthly IV immunoglobulin (IVIG) maintenance therapy and has been clinically stable. Repeat MRI two months later showed stable areas of spinal nerve root enhancement and decrease in some of the cord lesions.
Conclusion(s): Our case demonstrates that MOGAD should be a diagnostic consideration when MRI shows spinal nerve root enhancement in the appropriate clinical context, especially with the additional presence of CNS lesions that are typical of demyelination. MOGAD can manifest clinically and radiographically in both the central and peripheral nervous system

The minimal mind/brain state is the completion of one cycle of actualization that entails a passage over evolutionary growth planes from instinctual drive to the world surface, from a subjective core to an appearance of external reality. An isolated mental state is an abstraction, not only because it is fleeting and replaced but because a series of states is necessary for intra-psychic content. The state is not a content, a feeling, a statement, or qualia that can be isolated and compared to contents in other minds. Rather, it enfolds a diachronic and recurrent underpinning of actual or virtual contents that arise in the realization of acts and objects. The mind/brain is not a circuit board but an organism, and the process of realization is a becoming-into-being. The endpoint of the state, the configuration that arrives at the motor and perceptual cortices, submits to an adaptive sculpting that transforms endogenous potential to a diversity of world objects. Mental states overlap; they are not concatenated in causal chains. The transition is from potential to actual, cate-gory to member, or whole to part. The specious or illusory present arises in the overlap of mental states and the incomplete revival of their predecessors. Incompleteness is the key to recall as fading states lapse to successive planes of short-and long-term memory. The present arises in the forgetting of perceptions, or the passage of perceptual to memorial content, as the disparity between the floor of the mental state "” the endpoint of with-drawal beneath recall "” and conscious revival "” the ceiling of the mental state "” and the final actuality. This disparity is converted to an epoch of duration. Consciousness is the relation over segments from core self to perceived object. In dream, the absence of agency, the foreshortened, egocentric, and palpable space and fluid image boundaries point to a contracted present in which the state does not fully actualize. The river of Heraclites is not a flow that goes on but a fountain that recurs, with the present a brief suspension of succession in the endless passage of nature.

Since the first confirmed case in Wuhan, China on December 31, 2019, the novel coronavirus (SARS-CoV-2) has spread quickly, infecting 165 million people as of May 2021. Since this first detection, research has indicated that people contracting the virus may suffer neurological and mental disorders and deficits, in addition to the respiratory and other organ challenges caused by COVID-19. Specifically, early evidence suggests that COVID-19 has both mild (e.g., loss of smell (anosmia), loss of taste (ageusia), latent blinks (hete-rophila), headaches, dizziness, confusion) and more severe outcomes (e.g., cognitive impairments, seizures, delirium, psychosis, strokes). Longer-term neurological challenges or damage may also occur. This knowledge should inform clinical guidelines, assessment, and public health planning while more systematic research using biological, clinical, and longitudinal methods provides further insights.

BACKGROUND:Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS:Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS:Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS:In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

The human brain functions at the center of a network of systems aimed at providing a structural and immunological layer of protection. The cerebrospinal fluid (CSF) maintains a physiological homeostasis that is of paramount importance to proper neurological activity. CSF is largely produced in the choroid plexus where it is continuous with the brain extracellular fluid and circulates through the ventricles. CSF movement through the central nervous system has been extensively explored. Across numerous animal species, the involvement of various drainage pathways in CSF, including arachnoid granulations, cranial nerves, perivascular pathways, and meningeal lymphatics, has been studied. Among these, there is a proposed CSF clearance route spanning the olfactory nerve and exiting the brain at the cribriform plate and entering lymphatics. While this pathway has been demonstrated in multiple animal species, evidence of a similar CSF egress mechanism involving the nasal cavity in humans remains poorly consolidated. This review will synthesize contemporary evidence surrounding CSF clearance at the nose-brain interface, examining across species this anatomical pathway, and its possible significance to human neurodegenerative disease. Our discussion of a bidirectional nasal pathway includes examination of the immune surveillance in the olfactory region protecting the brain. Overall, we expect that an expanded discussion of the brain-nose pathway and interactions with the environment will contribute to an improved understanding of neurodegenerative and infectious diseases, and potentially to novel prevention and treatment considerations.

Artificial intelligence (AI)-based diagnostic algorithms have achieved ambitious aims through automated image pattern recognition. For neurological disorders, this includes neurodegeneration and inflammation. Scalable imaging technology for big data in neurology is optical coherence tomography (OCT). We highlight that OCT changes observed in the retina, as a window to the brain, are small, requiring rigorous quality control pipelines. There are existing tools for this purpose. Firstly, there are human-led validated consensus quality control criteria (OSCAR-IB) for OCT. Secondly, these criteria are embedded into OCT reporting guidelines (APOSTEL). The use of the described annotation of failed OCT scans advances machine learning. This is illustrated through the present review of the advantages and disadvantages of AI-based applications to OCT data. The neurological conditions reviewed here for the use of big data include Alzheimer disease, stroke, multiple sclerosis (MS), Parkinson disease, and epilepsy. It is noted that while big data is relevant for AI, ownership is complex. For this reason, we also reached out to involve representatives from patient organizations and the public domain in addition to clinical and research centers. The evidence reviewed can be grouped in a five-point expansion of the OSCAR-IB criteria to embrace AI (OSCAR-AI). The review concludes by specific recommendations on how this can be achieved practically and in compliance with existing guidelines.

Undiagnosed concussions increase the risk of additional concussion and persistent symptoms from concussion. Because there are no reliable objective markers of concussion, self-reporting of subjective and non-visible symptoms are critical to ensuring proper concussion management. For this reason, educational interventions target concussion reporting, but the majority of studies have examined the efficacy of single educational interventions or compared interventions to one another. This randomized crossover study sought to identify whether there was benefit to administering multiple concussion education programs in tandem, back to back. The study randomized 313 male high school football players to first receive CrashCourse concussion education (CC) or Centers for Disease Control and Prevention video concussion education (CDC) followed by crossover with the other education. Athlete concussion-reporting intention, attitudes, subjective norms, perceived behavioral control, and enjoyment of education were assessed at baseline and after each intervention. There were statistically significant improvements across all measures, both after single intervention and crossover (all p < 0.001). Secondary analyses examining differences between education found that athletes reported higher enjoyment of concussion education immediately after participating in CC, as compared to CDC (p < 0.001). These findings demonstrate an additive benefit to implementing CC and CDC education in tandem, without decrement in enjoyment of concussion education after experiencing dual educations; in fact, enjoyment of concussion education improved after receiving education programs back to back. These educational programs appear to complement one another, and the results support the use of multi-modal concussion education to differentially target and maximize concussion reporting.

An increasing number of identified Parkinson's disease (PD) risk loci contain genes highly expressed in innate immune cells, yet their role in pathology is not understood. We hypothesize that PD susceptibility genes modulate disease risk by influencing gene expression within immune cells. To address this, we have generated transcriptomic profiles of monocytes from 230 individuals with sporadic PD and healthy subjects. We observed a dysregulation of mitochondrial and proteasomal pathways. We also generated transcriptomic profiles of primary microglia from brains of 55 subjects and observed discordant transcriptomic signatures of mitochondrial genes in PD monocytes and microglia. We further identified 17 PD susceptibility genes whose expression, relative to each risk allele, is altered in monocytes. These findings reveal widespread transcriptomic alterations in PD monocytes, with some being distinct from microglia, and facilitate efforts to understand the roles of myeloid cells in PD as well as the development of biomarkers.

Background and Purpose:Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there is emerging evidence for the role of short-term dual antiplatelet therapy (DAPT) in preventing recurrent stroke. Methods:We conducted a systematic review and study-level meta-analyses of randomized controlled trials comparing outcomes of early initiation of short-term DAPT (aspirin+P2Y12 inhibitor for up to 3 months) versus aspirin alone in patients with acute stroke or transient ischemic attack. Primary efficacy outcome was risk of recurrent stroke and primary safety outcome was incidence of major bleeding. Secondary outcomes studied were risk of any ischemic stroke, hemorrhagic stroke, major adverse cardiovascular events, and all-cause death. Pooled risk ratios (RRs) and CIs were calculated using a random-effects model. Results:Four trials with a total of 21 459 patients were included. As compared to aspirin alone, DAPT had a lower risk of recurrent stroke (RR, 0.76 [95% CI, 0.68–0.83]; P<0.001; I2=0%) but a higher risk of major bleeding events (RR, 2.22 [95% CI, 1.14–4.34], P=0.02, I2=46.5%). Patients receiving DAPT had a lower risk of major adverse cardiovascular events (RR, 0.76 [95% CI, 0.69–0.84], P<0.001, I2=0%) and recurrent ischemic events (RR, 0.74 [95% CI, 0.67–0.82], P<0.001, I2=0%). Conclusions:As compared to aspirin alone, short-term DAPT within 24 hours of high-risk transient ischemic attack or mild-moderate ischemic stroke reduces the risk of recurrent stroke at the expense of higher risk of major bleeding.

BACKGROUND:It is estimated that up to 40% of Alzheimer's Disease and Related Dementias cases can be prevented or delayed by addressing modifiable factors including those that influence vascular risk (hypertension, obesity, smoking, physical activity, diabetes). Prevention may be particularly important in the vascular dementia subtypes. Despite the supporting evidence, the rates of medical therapy to reduce vascular risk are not well described. METHOD/METHODS:We assessed the utilization of statins, aspirin, and blood pressure (BP) medications in adults age ≥65 years cared for at NYU Langone Health, as recorded in the electronic health record. We included two cohorts: cohort 1 included patients who were diagnosed with vascular dementia (VaD) at NYU Langone Barlow Center for Memory Evaluation between January 1, 2015 and June 24, 2019. Cohort 2 extended the inclusion to seniors with VD diagnosis by any NYU Langone physician. Definitions for vascular dementia, the covariates assessed, and medications that we included in each category are shown in Tables 1-3. RESULT/RESULTS:We included 419 and 3745 patients in cohort 1 and cohort 2, respectively. Table 4 shows the characteristics and medication adherence in cohorts 1 and 2. In cohort 1, the prescription rates for statins, aspirin, and BP medications were 66%, 66%, 70%. In cohort 2, the rates for statin, aspirin, and BP medications were 56%, 46%, and 65%, respectively. The differences between prescription rates in cohort 1 and 2 for the three medication groups were statistically significant (p<0.05). CONCLUSION/CONCLUSIONS:Our analysis of the utilization of cardiovascular medications among patients with vascular dementia illuminates potential gaps both among patients who receive care at specialty clinics, as well as the overall population with vascular dementia. The rates of medication utilization are higher for patients under the care of cognitive neurologists. Electronic health records can help identify large cohorts of patients who may benefit from improved access to preventative measures including cardiovascular medications.