Faculty Bibliography

This study cross-validated the Medical Symptom Validity Test (MSVT) in a mixed neuropsychiatric sample and examined its accuracy for identifying invalid neuropsychological performance using a known-groups design. Cross-sectional data from 129 clinical patients who completed the MSVT were examined. Validity groups were established using six, independent criterion performance validity tests, which yielded 98 patients in the valid group and 31 in the invalid group. All MSVT subtest scores were significantly lower in the invalid group (η

BACKGROUND:To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS:Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS:A total of 230 COVID-19 patients with AIS were included. 67.0% (154/230) were older than 60 years, while 33.0% (76/230) were younger. Median (IQR) National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.0 (17.0) and 42.8% (89/208) presented with large vessel occlusion (LVO). Approximately 50.2% (102/203) of the patients had poor outcomes with an observed mortality rate of 38.8% (35/219). Age >60 years (aOR: 4.60, 95% CI 1.89 to 12.15, p=0.001), diabetes mellitus (aOR: 2.53, 95% CI 1.14 to 5.79, p=0.025), increased NIHSS at admission (aOR: 1.10, 95% CI 1.05 to 1.16, p<0.001), LVO (aOR: 3.02, 95% CI 1.27 to 7.44, p=0.014) and no IV tPA (aOR: 2.76, 95% CI 1.06 to 7.64, p=0.043) were significantly associated with poor functional outcome. CONCLUSION/CONCLUSIONS:There may be a relationship between COVID-19 associated AIS and severe disability or death. We identified several factors that predict worse outcomes, and these outcomes were more frequent compared with global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-dimer, predicted both morbidity and mortality.

While the COVID-19 pandemic has catalyzed the expansion of telemedicine into nearly every specialty of medicine, few articles have summarized current practices and recommendations for integrating virtual care in the practice of neuro-oncology. This article identifies current telemedicine practice, provides practical guidance for conducting telemedicine visits, and generates recommendations for integrating virtual care into neuro-oncology practice. Practical aspects of telemedicine are summarized including when to use and not use telemedicine, how to conduct a virtual visit, who to include in the virtual encounter, unique aspects of telehealth in neuro-oncology, and emerging innovations.

BACKGROUND:The relationship between cardiac function and mortality after thrombectomy for acute ischemic stroke is not well elucidated. METHODS:We analyzed the relationship between cardiac function and mortality prior to discharge in a cohort of patients who underwent thrombectomy for acute ischemic stroke at two large medical centers in New York City between December 2018 and November 2020. All analyses were performed using Welch's two sample t-test and logistic regression accounting for age, initial NIHSS and post-procedure ASPECTS score, where OR is for each unit increase in the respective variables. RESULTS:Of 248 patients, 41 (16.5%) died prior to discharge. Mortality was significantly associated with higher initial heart rate (HR; 89 ± 19 bpm vs 80 ± 18 bpm, p = 0.004) and higher maximum HR over entire admission (137 ± 26 bpm vs 114 ± 25 bpm, p < 0.001). Mortality was also associated with presence of NSTEMI/STEMI (63% vs 29%, p < 0.001). When age, initial NIHSS score, and post-procedure ASPECTS score were included in multivariate analysis, there was still a significant relationship between mortality and initial HR (OR 1.03, 95% CI 1.01- 1.05, p = 0.02), highest HR over the entire admission (OR 1.03, 95% CI 1.02-1.05, p < 0.001), and presence of NSTEMI/STEMI (OR 3.76, 95% CI 1.66-8.87, p = 0.002). CONCLUSIONS:Tachycardia is associated with mortality in patients who undergo thrombectomy. Further investigation is needed to determine whether this risk is modifiable.

Transcranial Alternating Current Stimulation (tACS) is a promising noninvasive electrical stimulation therapy for neuropsychiatric diseases. Invasive neuromodulation using alternating current has been efficacious for drug-resistant epilepsy, but it is associated with surgical and medical complications. We aimed to explore the safeness and effectivity on seizure frequency reduction of two tACS protocols against placebo in patients with multifocal refractory epilepsy. This was a randomized, double-blinded, placebo-controlled clinical trial with 3-arm parallel-group (placebo, 30 min/2 mA daily sessions for 3 days [tACS-30], and 60 min/2 mA weekday sessions [tACS-60]). The main outcome was considered a change in reducing seizure frequency at 2 months after the intervention. Secondary outcomes were the apparition of any adverse effects during follow-up. At the second month, we observed a nonsignificant reduction in the seizure frequency in the placebo (7.3 ± 40.4%, p > 0.05) and the tACS-60 (26 ± 37.7%, p > 0.05). While the tACS-30 group showed a nonsignificant increase in seizure frequency (63.6 ± 155.3%, p > 0.05). No changes were statistically different from the placebo group. Otherwise, participants experienced only minor adverse events - the most common being an initial local transient tingling sensation (21%). This pilot study of tACS raises no severe safety issues, but provides negligible evidence for efficacy using this brief treatment protocol. Therefore, more studies are warranted testing different parameters to further verify the safety and effectivity of tACS in multifocal epilepsy.

Although the Uniform Determination of Death Act (UDDA) has served as a model statute for 40 years, there is a growing recognition that the law must be updated. One issue being considered by the Uniform Law Commission's Drafting Committee to revise the UDDA is whether the text "all functions of the entire brain, including the brainstem" should be changed. Some argue that the absence of diabetes insipidus indicates that some brain functioning continues in many individuals who otherwise meet the "accepted medical standards" like the American Academy of Neurology's. The concern is that the legal criteria and the medical standards used to determine death by neurological criteria are not aligned. We argue for the revision of the UDDA to more accurately specify legal criteria which align with the medical standards: brain injury leading to permanent loss of a) the capacity for consciousness, b) the ability to breathe spontaneously, and c) brainstem reflexes. We term these criteria "neuro-respiratory criteria" and show that they are well-supported in the literature for physiological and social reasons justifying their use in the law.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Loneliness is common and its prevalence is rising. The relationship of loneliness with subsequent dementia and the early preclinical course of Alzheimer disease and related dementia (ADRD) remains unclear. Thus, the primary objective of this study was to determine the association of loneliness with 10-year all-cause dementia risk and early cognitive and neuroanatomic imaging markers of ADRD vulnerability. METHODS:Retrospective analysis of prospectively collected data from the population-based Framingham Study cohorts (09/09/1948-12/31/2018). Eligible participants had loneliness assessed and were dementia-free at baseline. Loneliness was recorded using the Center for Epidemiologic Studies Depression Scale; defined conservatively as feeling lonely ≥3 days in the past week. The main outcomes were incident dementia over a 10-year period, cognition, and MRI brain volumes and white-matter injury. RESULTS:Of 2308 participants (mean age, 73 [SD, 9] years; 56% women) who met eligibility in the dementia sample, 14% (329/2308) developed dementia; 6% (144/2308) were lonely. Lonely (versus not lonely) adults had higher 10-year dementia risk (age-, sex-, and education-adjusted hazard ratio, 1.54; 95% CI, 1.06-2.24). Lonely participants younger than age 80 without APOE ε4 alleles had a three-fold greater risk (adjusted hazard ratio, 3.03; 95% CI, 1.63-5.62). Among 1875 persons without dementia who met eligibility in the cognition sample (mean age, 62 [SD, 9] years; 54% women), loneliness associated with poorer executive function, lower total cerebral volume, and greater white-matter injury. DISCUSSION/CONCLUSIONS:Over 10 years of close clinical dementia surveillance in this cohort study, loneliness was associated with increased dementia risk; this tripled in adults whose baseline risk would otherwise be relatively low based on age and genetic risk, representing a majority of the US population. Loneliness was also associated with worse neurocognitive markers of ADRD vulnerability, suggesting an early pathogenic role. These findings may have important clinical and public health implications given observed loneliness trends. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class I evidence that loneliness increases the 10-year risk of developing dementia.

Seizure risk is 10-fold higher in Alzheimer's disease patients than the general population, yet the mechanisms underlying this susceptibility and the effects of seizures on Alzheimer's disease are poorly understood. To elucidate our proposed bidirectional relationship between Alzheimer's disease and seizures, we studied Alzheimer's disease human brain samples (n = 34) and found that patients with a history of seizures (n = 14) had increased β-amyloid and tau pathology, and upregulation of the mechanistic target of rapamycin (mTOR) pathway compared to cases without known seizure history (n = 20). To establish whether seizures could accelerate Alzheimer's disease progression, we induced chronic hyperexcitability in the 5XFAD Alzheimer's disease mouse model by kindling with the chemoconvulsant pentylenetetrazol and observed that 5XFAD mice displayed higher seizure severity compared to wild type. Furthermore, kindled seizures exacerbated later cognitive impairment, Alzheimer's disease neuropathology and mTORC1 activation. Finally, we demonstrate that administration of the mTOR inhibitor rapamycin following kindled seizures rescued enhanced remote and long-term memory deficits associated with earlier kindling and prevented the seizure-induced increases in Alzheimer's disease neuropathology. These data demonstrate an important link between chronic hyperexcitability and progressive Alzheimer's disease pathology and suggest a mechanism whereby rapamycin may serve as an adjunct therapy to attenuate Alzheimer's disease progression.

Somatostatin (SS) is a peptide hormone with diverse physiological roles. By investigating a deep-water clade of fish-hunting cone snails, we show that predator-prey evolution has generated a diverse set of SS analogs, each optimized to elicit specific systemic physiological effects in prey. The increased metabolic stability, distinct SS receptor activation profiles, and chemical diversity of the venom analogs make them suitable leads for therapeutic application, including pain, cancer, and endocrine disorders. Our findings not only establish the existence of SS-like peptides in animal venoms but also serve as a model for the synergy gained from combining molecular phylogenetics and behavioral observations to optimize the discovery of natural products with biomedical potential.