Faculty Bibliography

Objective: We report a case of concomitant Holmes' tremor (HT) and hemiparkinsonism (HP) attributable to a single structural lesion with robust clinical response to levodopa.
Background(s): HT is a low frequency (<4.5 Hz) tremor at rest that persists or increases with postural change and goal-directed action. It's believed to arise most commonly from structural lesions that disrupt the nigrostriatal pathway in conjunction with either the cerebello-thalamocortical or dentato-rubro-olivary pathway [1]. "Pure" vascular HP stems from injury to the substantia nigra and/or nigrostriatal pathway, causing contralateral rest tremor, bradykinesia, and rigidity [3]. We found only one prior case report of both HT and HP occurring in combination from a single structural lesion resulting in near absence of dopamine transporter binding in the ipsilateral striatum on DaT-SPECT imaging [3]. However, high doses of levodopa provided no clinical improvement despite prior reports of efficacy in HT [4].
Method(s): Case Report.
Result(s): A 48-year-old woman presented with insidious onset of tremor and slowness of movement. She had a known hemorrhagic midbrain cavernous malformation discovered 20 years prior in the setting of acute onset of binocular diplopia and transient left sided hemiparesis. On exam, there was isolated left facial masking, severe left arm and leg bradykinesia and rigidity, and marked reductions in stride length and arm swing when ambulating. There was a coarse, irregular 3 Hz tremor of the left arm present at rest, persisting with postural change, and increasing with goaldirected action. Brain MRI demonstrated a 2 cm cavernous malformation within the right substantia nigra with extension into the red nucleus and crus cerebri [figure 1]. She was examined following ingestion of 100 mg of levodopa. She developed dystonic dyskinesias of the left arm and leg thirty minutes after ingestion followed by resolution of HT and profound improvement of HP at sixty minutes. Symptoms gradually returned three hours after ingestion.
Conclusion(s): This represents the first reported case of concurrent HT and HP due to a single structural lesion with robust symptomatic response to levodopa, presumed secondary to disruption of both the nigrostriatal and dentato-rubro-olivary pathways. It is unclear what drives responsiveness to dopaminergic therapy, which can at times be robust and thus remains the first-line therapeutic approach. (Figure Presented)

Objective: To determine whether newly diagnosed Parkinson's disease (PD) patients with REM sleep behavior disorder (RBD) are more likely to have symptoms of autonomic dysfunction.
Background(s): RBD is highly associated with development of asynucleinopathies but only 51% of PD patients have RBD1,2. We addressed whether PD with and without RBD have different clinical phenotypes and progression.
Method(s): Hypothesis driven analysis of 295 early stage PD patients within 2 years from diagnosis on no PD medications from the Parkinson's Progressive Marker Initiative (PPMI) cohort were obtained. Genetic, SWEED and prodromal subgroups were excluded from analysis. RBDSQ equal or greater than 1 for item 6 (q6) was used to identify patients with RBD as this cutoff has greater sensitivity and specificity for identifying true RBD in PD3,4 Results: Subjects from baseline visit were divided in RBD+ (RBDSQ q6>1, n=128) and RBD- (RBDSQ q6<1, n=167). We considered SCOPA subscores (gastrointestinal(GI), urinary(UR), thermoregulation(THERM), cardiovascular(CV), pupillomotor(PM), sex(SEX)), sense of smell (UPSIT), anxiety (STAIT-trait), depression (GDS), motor (updrs-part3) and cognitive function (MOCA), UPDRS total score. Shapiro-Wilk and Mann-Whitney test for non-parametric data were used for the analyses. SCOPA sub-scores for the majority of the autonomic symptoms (GI, THERM, CV, PM) but not UR and SEX, were significantly higher in the REM+ cohort (p=<0.005). The other traits did not show statistically significant differences. Statistical significance between the two groups for GI, THERM, CV remained consistent using other thresholds for differentiating REM+ vs REM- groups (RBDSQ total score greater than 5 or combined RBDSQ total score and q6).
Conclusion(s): Our hypothesis driven analyses show that early stage PD patients with RBD have greater prevalence of autonomic symptoms, without worse UPDRS motor scores. This suggests that brainstem and peripheral autonomic symptoms cluster together, but are not associated with more diffuse involvement of motor systems and cognitive impairment at this early stage of PD. Prior analyses of PPMI data have identified a "diffuse/ malignant" subtype associated with higher UPDRS motor score, RBDSQ score, autonomic symptoms (SCOPA-AUT) and worse cognitive impairment5.6. These differences might be accounted by our more stringent criteria for RBD or our statistical approach using specific hypothesis versus cluster driven analyses

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Attention is thought to be the gateway between information and learning, yet there is much we do not understand about how students pay attention in the classroom. Leveraging ideas from cognitive neuroscience and psychology, we explore a framework for understanding attention in the classroom, organized along two key dimensions: internal/external attention and on-topic/off-topic attention. This framework helps us to build new theories for why active-learning strategies are effective teaching tools and how synchronized brain activity across students in a classroom may support learning. These ideas suggest new ways of thinking about how attention functions in the classroom and how different approaches to the same active-learning strategy may vary in how effectively they direct students' attention. We hypothesize that some teaching approaches are more effective than others because they leverage natural fluctuations in students' attention. We conclude by discussing implications for teaching and opportunities for future research.

BACKGROUND CONTEXT: MBDs are often implicated in or contribute to degenerative disc disease (DDD). Yet, there is limited long-term, postoperative outcome data on the impact of MBDs on 2-year outcomes following 2-3-level lumbar fusion for DDD. PURPOSE: To determine if DDD patients with MBDs have comparable outcomes to those without MBDs following lumbar fusion. STUDY DESIGN/SETTING: Retrospective cohort. PATIENT SAMPLE: New York State Statewide Planning and Research Cooperative System was reviewed from 2009-2013 to identify all patients with DDD who underwent short, lumbar fusion (2-3-levels) with >=2-year follow-up OUTCOME MEASURES: Two-year outcome rates (medical/surgical complications and reoperations).
METHOD(S): The New York State Statewide Planning and Research Cooperative System was reviewed from 2009-2013 to identify all patients with DDD who underwent short, lumbar fusion (2-3 levels) with >=2-year follow-up. Patients with and without MBD (vitamin D deficiency, hyperparathyroidism, osteomalacia, and rickets) were identified. Any patients with osteoporosis or other systemic/endocrine disorders affecting bone quality were excluded. Traumatic, infectious, and neoplastic surgical indications were excluded. Cohorts were compared for demographics and 2-year outcome rates (medical/surgical complications and reoperations). Logistic regression was used to identify covariates associated with medical/surgical complications and revisions.
RESULT(S): A total of 28,959 patients were included (MBD, n=380 (1.33%); no-MBD, n=28,579). MBD pts were older (56.4 vs 53.1 years) and more often female (65.5% vs 49.80%) than no-MBD pts (all p<0.001). MBD pts had longer hospital stays (4.57 days vs 4.11 days, p=0.026), but charges were similar. MBD pts incurred higher rates of wound complications (11.8% vs 6.0%), acute renal failure (11.1% vs 4.7%), pneumonia (9.2% vs 4.4%), and implant related complications (12.1% vs 7.0%); all p<0.001. Rates of pseudarthrosis, PE, pulmonary complications, and UTI were similar between groups. MBDs were associated with developing both medical complications (OR=1.55) and surgical complications (OR=1.79), both p<0.001.
CONCLUSION(S): MBD patients have an increased risk of 2-year postop comps and reoperations following short lumbar fusion for DDD compared to patients without MBD when controlling for demographics and comorbidity profile. These data underscore the importance of preoperative screening and optimization in this patient population. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
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OBJECTIVE:Spinal cord infarction due to interruption of the spinal vascular supply during anterior thoracolumbar surgery is a rare but devastating complication. Here, the authors sought to summarize the data on this complication in terms of its incidence, risk factors, and operative considerations. They also sought to summarize the relevant spinal vascular anatomy. METHODS:They performed a systematic literature review of the PubMed, Scopus, and Embase databases to identify reports of spinal cord vascular injury related to anterior thoracolumbar spine procedures as well as operative adjuncts and considerations related to management of the segmental artery ligation during such anterior procedures. Titles and abstracts were screened, and studies meeting inclusion criteria were reviewed in full. RESULTS:Of 1200 articles identified on the initial screening, 16 met the inclusion criteria and consisted of 2 prospective cohort studies, 10 retrospective cohort studies, and 4 case reports. Four studies reported on the incidence of spinal cord ischemia with anterior thoracolumbar surgery, which ranged from 0% to 0.75%. Eight studies presented patient-level data for 13 cases of spinal cord ischemia after anterior thoracolumbar spine surgery. Proposed risk factors for vasculogenic spinal injury with anterior thoracolumbar surgery included hyperkyphosis, prior spinal deformity surgery, combined anterior-posterior procedures, left-sided approaches, operating on the concavity side of a scoliotic curve, and intra- or postoperative hypotension. In addition, eight studies analyzed operative considerations to reduce spinal cord ischemic complications in anterior thoracolumbar surgery, including intraoperative neuromonitoring and preoperative spinal angiography. CONCLUSIONS:While spinal cord infarction related to anterior thoracolumbar surgery is rare, it warrants proper consideration in the pre-, intra-, and postoperative periods. The spine surgeon must be aware of the relevant risk factors as well as the pre- and intraoperative adjuncts that can minimize these risks. Most importantly, an understanding of the relevant spinal vascular anatomy is critical to minimizing the risks associated with anterior thoracolumbar spine surgery.

PURPOSE/OBJECTIVE:Schools provide access to mental health services for traditionally underserved youth. However, there is variability in the types of school-based services students receive (e.g., school counseling, services in separate classrooms, or schools serving students with psychiatric disorders). Prior research has typically not distinguished among these different types of school-based services. The present study examines sociodemographic characteristics and disorders associated with the types of services received in schools. METHODS:Data were analyzed from a sample of adolescent-parent pairs in the U.S. National Comorbidity Survey Adolescent Supplement who received school mental health services (N = 1,204). DSM-IV diagnoses were based on the Composite International Diagnostic Interview administered to adolescents and questionnaires self-administered to parents. Adolescents (aged 13-18 years) and parents also responded to questions about lifetime school-based mental health service receipt. RESULTS:Among those receiving school-based mental health services, almost one-third (29.7%) received services in a separate classroom and almost one-fourth (22.3%) in a separate school. Increased likelihood of lifetime placement in a separate classroom or school was detected among older youth, males, blacks, Latinos, youth with learning disabilities, those whose parents had fewer years of education, and those who received community-based mental health services. Oppositional defiant disorder was associated with increased lifetime placement in a separate school. CONCLUSIONS:The results advance the evidence base by indicating that racial/ethnic minority youth and those whose parents have fewer years of education were more likely to receive school-based mental health services in separate settings. These results provide more context to studies of school-based mental health service receipt.

Development, physiological functions, and pathologies of the brain depend on tight interactions between neurons and different types of glial cells, such as astrocytes, microglia, oligodendrocytes, and oligodendrocyte precursor cells. Assessing the relative contribution of different glial cell types is required for the full understanding of brain function and dysfunction. Over the recent years, several technological breakthroughs were achieved, allowing "glio-scientists" to address new challenging biological questions. These technical developments make it possible to study the roles of specific cell types with medium or high-content workflows and perform fine analysis of their mutual interactions in a preserved environment. This review illustrates the potency of several cutting-edge experimental approaches (advanced cell cultures, induced pluripotent stem cell (iPSC)-derived human glial cells, viral vectors, in situ glia imaging, opto- and chemogenetic approaches, and high-content molecular analysis) to unravel the role of glial cells in specific brain functions or diseases. It also illustrates the translation of some techniques to the clinics, to monitor glial cells in patients, through specific brain imaging methods. The advantages, pitfalls, and future developments are discussed for each technique, and selected examples are provided to illustrate how specific "gliobiological" questions can now be tackled.

Objective: To confirm: 1) clinical efficacy and safety of once-daily oral ampreloxetine in a 4-week double-blind (