Faculty Bibliography

Neuroimaging provides a window on the biological events underlying dementia. Amyloid PET is positive in Alzheimer disease (AD) and some cases of diffuse Lewy body disease, but negative in the frontotemporal dementias (FTDs). Tau PET using the current tracers shows the greatest signal in AD and a lesser signal in FTD. Quantifying volume loss with MRI and measuring metabolism with fluorodeoxyglucose PET helps separate different causes of dementia and follow their progression. Brain inflammation can be assessed with PET. Some of these techniques, still investigational, are likely to find their clinical niche in the near future.

OBJECTIVES/OBJECTIVE:To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN/METHODS:A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS:The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS:The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 49 research priorities were identified. CONCLUSIONS:A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

This paper describes ten core features of a neuropsychological assessment with the aim of helping neurologists understand the unique contribution the evaluation can make within the wider context of diagnostic methods in epilepsy. The possibilities, limitations and cautions associated with the investigation are discussed under the headings below: 1. A neuropsychological assessment is a collaborative investigation. 2. Assessment prior to treatment allows for the accurate assessment of treatment effects. 3. The nature of an underlying lesion and its neurodevelopmental context play an important role in shaping the associated neuropsychological deficit. 4. Cognitive and behavioural impairments result from the essential comorbidities of epilepsy which can be considered as much a disorder of cognition and behaviour as of seizures. 5. Patient's subjective complaints can help us understand objective cognitive impairments and their underlying neuroanatomy, resulting in improved patient care. At other times, patient complaints reflect other factors and require careful interpretation. 6. The results from a neuropsychological assessment can be used to maximise the educational and occupational potentials of people with epilepsy. 7. Not all patients are able to engage with a neuropsychological assessment. 8. There are limitations in assessments conducted in a second language with tests that have been standardized on different populations to that of the patient. 9. Adequate intervals between assessments maximise sensitivity to meaningful change. 10. Patients should be fully informed about the purpose of the assessment and have realistic expectations of the outcome prior to referral.

Automated production of an fluorine-18 labeled tryptophan analogue, 1-(2-[¹⁸F]fluoroethyl)-l-tryptophan (1-L-[¹⁸F]FETrp) in a current Good Manufacturing Practice facility was achieved. 1-L-[¹⁸F]FETrp was produced by a one-pot, two-step strategy with an overall synthesis time of approximately 100 min, a radiochemical yield of 20 ± 5% (decay corrected), radiochemical purity and enantiomeric excess over 90%, and a molar activity of 103 ± 15 GBq/μmol at the end of synthesis (EOS). The dose mass of 1-L-FETrp in four consecutive batches was less than 5 μg. The radiopharmaceutical product met all quality control criteria for clinical use.

BACKGROUND/UNASSIGNED:The relationship between early trauma, hyperarousal and aberrant salience has been investigated exclusively in specific clinical samples, such as post-traumatic stress disorder (PTSD) and psychotic patients, and the results suggest that both dimensions are trauma-induced events, which may lead to the later onset, or increase the vulnerability to psychiatric disorders. The aim of the present research was to evaluate the possible relationships among early childhood trauma subtypes and the dimensions of hyperarousal and aberrant salience in an adult sample of psychiatric patients. MATERIALS AND METHODS/UNASSIGNED:One-hundred psychiatric adult outpatients were assessed by Early Trauma Inventory Self Report-Short Form (ETISR-SF), Aberrant Salience Inventory (ASI) and Hyperarousal Scale (H-Scale). A linear regression analysis was performed in order to investigate which early traumatic events were a predictor of the aberrant salience and the hyperarousal. RESULTS/UNASSIGNED: = .031), whereas other ETISR-SF variables did not give a significant additional contribution to the prediction of aberrant salience and the hyperarousal dimension. CONCLUSIONS/UNASSIGNED:These findings support the role of emotional abuse as predictor of hyperarousal, a basic dimension associated with general vulnerability to mental illness. The awareness of the psychiatric consequences of early childhood trauma leads us to consider the need for better identification of children at risk, to develop effective interventions for the protection of minors from violent and/or inappropriate behaviors and to promote the development of protective resilience factors against re-victimization.

Parkinson's disease (PD) results in a complex deterioration of motor behavior. Effective pharmacological or surgical treatments addressing the whole spectrum of both motor and cognitive symptoms are lacking. The cumulative functional impairment may have devastating socio-economic consequences on both patients and caregivers. Comprehensive models of care based on multidisciplinary approaches may succeed in better addressing the overall complexity of PD. Neurorehabilitation is a highly promising non-pharmacological intervention for managing PD. The scientific rationale beyond rehabilitation and its practical applicability remain to be established. In the present perspective, we aim to discuss the current evidence supporting integrated motor-cognitive and aerobic rehabilitation approaches for patients with PD while suggesting a practical framework to optimize this intervention in the next future.

INTRODUCTION/BACKGROUND:The glial-lymphatic pathway is a fluid-clearance pathway consisting of a para-arterial route for the flow of cerebrospinal fluid along perivascular spaces and subsequently toward the brain interstitium. In this case series we aim to investigate an empirical demonstration of glymphatic clearance of extravasated iodine following perforation incurred during endovascular therapy on serial CT. METHODS AND RESULTS/RESULTS:Six consecutive cases of endovascular perforation during thrombectomy performed between 2005 and 2018 were retrospectively collected by searching our internal database of total 446 thrombectomies. Two cases were excluded because care was withdrawn shortly following the procedure and no follow-up imaging was available. One case was excluded because a ventricular drain was placed. Three cases were hence included in this analysis. All three cases demonstrated progressive absorption of contrast by the brain parenchyma with eventual contrast disappearance. CONCLUSION/CONCLUSIONS:We described a likely in vivo CT correlate of the glymphatic system in a cohort of patients who sustained intraprocedural extravasation during thrombectomy for acute ischemic stroke.

Multiple lines of evidence suggest that illness development in schizophrenia and other psychotic disorders predates the first psychotic episode by many years. In this study, we examined a sample of 15 pre-adolescent children, ages 7 through 12 years, who are at familial high-risk (FHR) because they have a parent or sibling with a history of schizophrenia or related psychotic disorder. Using multi-voxel pattern analysis (MVPA), a data-driven fMRI analysis, we assessed whole-brain differences in functional connectivity in the FHR sample as compared to an age- and sex-matched control (CON) group of 15 children without a family history of psychosis. MVPA analysis yielded a single cluster in right posterior superior temporal gyrus (pSTG/BA 22) showing significant group-differences in functional connectivity. Post-hoc characterization of this cluster through seed-to-voxel analysis revealed mostly reduced functional connectivity of the pSTG seed to a set of language and default mode network (DMN) associated brain regions including Heschl's gyrus, inferior temporal gyrus extending into fusiform gyrus, (para)hippocampus, thalamus, and a cerebellar cluster encompassing mainly Crus I/II. A height-threshold of whole-brain p < .001 (two-sided), and FDR-corrected cluster-threshold of p < .05 (non-parametric statistics) was used for post-hoc characterization. These findings suggest that abnormalities in functional communication in a network encompassing right STG and associated brain regions are present before adolescence in at-risk children and may be a risk marker for psychosis. Subsequent changes in this functional network across development may contribute to either disease manifestation or resilience in children with a familial vulnerability for psychosis.

Orthostatic hypotension (OH) is a sustained fall in blood pressure on standing that can cause symptoms of organ hypoperfusion. OH is associated with increased morbidity and mortality and leads to a significant number of hospital admissions. OH can be caused by volume depletion, blood loss, cardiac pump failure, large varicose veins, medications, or defective activation of sympathetic nerves and reduced norepinephrine release upon standing. Neurogenic OH is a frequent and disabling problem in patients with synucleinopathies such as Parkinson disease, multiple system atrophy, and pure autonomic failure, and it is commonly associated with supine hypertension. Several therapeutic options are available.