Faculty Bibliography

BACKGROUND:Clinical research indicates that successful posttraumatic stress disorder (PTSD) treatment does not lead to improvements in alcohol use outcomes in comorbid PTSD and alcohol use disorder (AUD). Emerging theory suggests that treating PTSD may not disrupt an association between negative affect and alcohol craving, which underlies negative reinforcement drinking. The goal of the current study was to determine the respective influences of PTSD symptoms, coping motives, and negative affect on trauma and alcohol cue reactivity to inform theoretical models of co-occurring PTSD and AUD. METHODS:The sample consisted of 189 young adults (50.3% women; 49.2% current PTSD; 84.0% current AUD) who endorsed interpersonal trauma (e.g., sexual/physical assault) and current weekly alcohol use. Participants completed a trauma and alcohol cue reactivity assessment, in which subjective (e.g., craving, affect) and physiological (i.e., salivation) measures were recorded in response to 4 narrative (i.e., personalized trauma or standard neutral) and in vivo beverage (i.e., personalized alcohol or water) cue combinations. RESULTS:Forward-fitted linear mixed-effects (LME) models confirmed that trauma cue-elicited craving was elevated among those high but not low in PTSD symptoms, consistent with prior research and theory. Trauma cue-elicited craving was fully explained by increases in negative affect, with no evidence of a direct effect of trauma cue on craving. PTSD symptoms moderated an association between trauma cue and negative affect (but not negative affect and craving), and coping motives for alcohol moderated an association between negative affect and craving (but not trauma cue and negative affect). CONCLUSIONS:This study provides novel laboratory evidence for the respective contributions of negative affect, PTSD symptoms, and coping motives on alcohol craving in trauma-exposed drinkers. It offers a methodological framework in which to evaluate novel strategies that aim to disrupt negative reinforcement drinking in individuals with co-occurring PTSD and AUD.

BACKGROUND:H3K27M-mutant midline lesions were recently reclassified by the World Health Organization (WHO) as "diffuse midline glioma" (DMG) based entirely on their molecular signature. DMG is one of the most common and most lethal pediatric brain tumors; terminal progression is typically caused by local midbrain or brainstem progression, or secondary leptomeningeal dissemination. H3K27M mutations have also been infrequently associated with a histologically and prognostically diverse set of lesions, particularly spinal masses with early leptomeningeal spread. CASE PRESENTATION/METHODS:A 15-year-old girl after 1 week of symptoms was found to have a T2/FLAIR-hyperintense and contrast-enhancing thalamic mass accompanied by leptomeningeal enhancement along the entire neuraxis. Initial infectious workup was negative, and intracranial biopsy was inconclusive. Spinal arachnoid biopsy revealed an H3K27M-mutant lesion with glioneuronal features, classified thereafter as DMG. She received craniospinal irradiation with a boost to the thalamic lesion. Imaging 1-month post-radiation demonstrated significant treatment response with residual enhancement at the conus. CONCLUSIONS:This case report describes the unique presentation of an H3K27M-mutant midline lesion with significant craniospinal leptomeningeal spread on admission and atypical glioneuronal histopathological markers. With such florid leptomeningeal disease, spinal dural biopsy should be considered earlier given its diagnostic yield in classifying the lesion as DMG. Consistent with similar prior reports, this lesion additionally demonstrated synaptophysin positivity-also potentially consistent with a diagnosis of diffuse leptomeningeal glioneuronal tumor (DLGNT). In atypical DMG cases, particularly with leptomeningeal spread, further consideration of clinical and histopathological context is necessary for accurate diagnosis and prognostication.

PURPOSE/OBJECTIVE:To describe the temporal association of specific acute neurological symptoms in pediatric patients with confirmed SARS-CoV-2 infection between May and August 2020. METHODS:We performed a recollection of all the clinical and laboratory data of patients having acute neurological symptoms temporally associated with SARS-CoV-2 infection at a third-level referral hospital in Mexico City (Instituto Nacional de Pediatría). Patients in an age group of 0-17 years with acute neurological signs (including ascending weakness with areflexia, diminished visual acuity, encephalopathy, ataxia, stroke, or weakness with plasma creatinine kinase (CK) elevation) were evaluated. RESULTS:Out of 23 patients with neurological manifestations, 10 (43%) had a confirmed SARS-CoV-2 infection. Among the infected patients, 5 (50%) were males aged 2-16 years old (median age 11.8 years old). Four (40%) patients confirmed a close contact with a relative positive for SARS-CoV-2, while 6 (60%) cases had a history of SARS-CoV-2-related symptoms over the previous 2 weeks. The following diagnoses were established: 3 cases of GBS, 2 of ON, 2 of AIS, one of myositis with rhabdomyolysis, one ACA, and one of anti-NMDA-R encephalitis. CONCLUSIONS:Neurological manifestations temporally associated with SARS-CoV-2 infection were noticed in the pediatric population even without respiratory symptoms. In this study, 2 of 6 symptomatic patients had mild respiratory symptoms and 4 had unspecific symptoms. During this pandemic, SARS-CoV-2 infection should be considered as etiology in patients with acute neurological symptoms, with or without previous respiratory manifestations, particularly in teenagers.

Delivering healthcare to people living with Parkinson's disease (PD) may be challenging in face of differentiated care needs during a PD journey and a growing complexity. In this regard, integrative care models may foster flexible solutions on patients' care needs whereas Parkinson Nurses (PN) may be pivotal facilitators. However, at present hardly any training opportunities tailored to the care priorities of PD-patients are to be found for nurses. Following a conceptual approach, this article aims at setting a framework for training PN by reviewing existing literature on care priorities for PD. As a result, six prerequisites were formulated concerning a framework for training PN. The proposed training framework consist of three modules covering topics of PD: (i) comprehensive care, (ii) self-management support and (iii) health coaching. A fourth module on telemedicine may be added if applicable. The framework streamlines important theoretical concepts of professional PD management and may enable the development of novel, personalized care approaches.

A large number of stroke survivors suffer from a significant decrease in upper extremity (UE) function, requiring rehabilitation therapy to boost recovery of UE motion. Assessing the efficacy of treatment strategies is a challenging problem in this context, and is typically accomplished by observing the performance of patients during their execution of daily activities. A more detailed assessment of UE impairment can be undertaken with a clinical bedside test, the UE Fugl-Meyer Assessment, but it fails to examine compensatory movements of functioning body segments that are used to bypass impairment. In this work, we use a graph learning method to build a visualization tool tailored to support the analysis of stroke patients. Called NE-Motion, or Network Environment for Motion Capture Data Analysis, the proposed analytic tool handles a set of time series captured by motion sensors worn by patients so as to enable visual analytic resources to identify abnormalities in movement patterns. Developed in close collaboration with domain experts, NE-Motion is capable of uncovering important phenomena, such as compensation while revealing differences between stroke patients and healthy individuals. The effectiveness of NE-Motion is shown in two case studies designed to analyze particular patients and to compare groups of subjects.

Excessive beta-band oscillations in the subthalamic nucleus are key neural features of Parkinson's disease. Yet the distinctive contributions of beta low and high bands, their dependency on striatal dopamine, and their correlates with movement kinematics are unclear. Here, we show that the movement phases of the reach-to-grasp motor task are coded by the subthalamic bursting activity in a maximally-informative beta high range. A strong, three-fold correlation linked beta high range bursts, imbalanced inter-hemispheric striatal dopaminergic tone, and impaired inter-joint movement coordination. These results provide new insight into the neural correlates of motor control in parkinsonian patients, paving the way for more informative use of beta-band features for adaptive deep brain stimulation devices.

Neuroinflammation is associated with Alzheimer's disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer's Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered (p = 0.027) and independent (p = 0.038) cohorts of people with mild cognitive impairment due to predicted Alzheimer's disease, while higher soluble TREM2 levels associated with slower decline in the dementia stage of Alzheimer's disease. These inflammatory proteins thus provide prognostic information independent of established Alzheimer's markers.

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.

Members of a disintegrin and metalloproteinases with thrombospondin motif (ADAMTS) family have been implicated in various vascular diseases. However, their functional roles in early embryonic vascular development are unknown. In this study, we showed that Adamts18 is highly expressed at E11.5-E14.5 in cells surrounding the embryonic aortic arch (AOAR) and the common carotid artery (CCA) during branchial arch artery development in mice. Adamts18 deficiency was found to cause abnormal development of AOAR, CCA, and the third and fourth branchial arch appendages, leading to hypoplastic carotid body, thymus, and variation of middle cerebral artery. Adamts18 was shown to affect the accumulation of extracellular matrix (ECM) components, in particular fibronectin (Fn), around AOAR and CCA. As a result of increased Fn accumulation, the Notch3 signaling pathway was activated to promote the differentiation of cranial neural crest cells (CNCCs) to vascular smooth muscle cells. These data indicate that Adamts18-mediated ECM homeostasis is crucial for the differentiation of CNCCs.