Evidence of Pericyte Damage in a Cognitively Normal Cohort: Association With CSF and PET Biomarkers of Alzheimer's Disease.

BACKGROUND: Blood-brain barrier (BBB) dysfunction is emerging as an important pathophysiologic factor in Alzheimer's disease (AD). Cerebrospinal fluid (CSF) platelet-derived growth factor receptor-ß (PDGFRß) is a biomarker of BBB pericyte injury and has been implicated in cognitive impairment and AD. METHODS: We aimed to study CSF PDGFRß protein levels, along with CSF biomarkers of brain amyloidosis and tau pathology in a well-characterized population of cognitively unimpaired individuals and correlated CSF findings with amyloid-PET positivity. We performed an institutional review board (IRB)-approved cross-sectional analysis of a prospectively enrolled cohort of 36 cognitively normal volunteers with available CSF, Pittsburgh compound B PET/CT, Mini-Mental State Exam score, Global Deterioration Scale, and known apolipoprotein E (APOE) ε4 status. RESULTS: Thirty-six subjects were included. Mean age was 63.3 years; 31 of 36 were female, 6 of 36 were amyloid-PET-positive and 12 of 36 were APOE ε4 carriers. We found a moderate positive correlation between CSF PDGFRß and both total Tau (r=0.45, P=0.006) and phosphorylated Tau 181 (r=0.51, P=0.002). CSF PDGFRß levels were not associated with either the CSF Aß42 or the amyloid-PET. CONCLUSIONS: We demonstrated a moderate positive correlation between PDGFRß and both total Tau and phosphorylated Tau 181 in cognitively normal individuals. Our data support the hypothesis that BBB dysfunction represents an important early pathophysiologic step in AD, warranting larger prospective studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00094939.

DOTATATE PET/MR Imaging Differentiates Secondary-Progressive from de Novo World Health Organization Grade 3 Meningiomas.

BACKGROUND AND PURPOSE: WHO grade 3 meningiomas are rare and poorly understood and have a higher propensity for recurrence, metastasis, and worsened clinical outcomes compared with lower-grade meningiomas. The purpose of our study was to prospectively evaluate the molecular profile, PET characteristics, and outcomes of patients with World Health Organization grade 3 meningiomas who were imaged with gallium 68 (68Ga) DOTATATE PET/MR imaging. MATERIALS AND METHODS: Patients with World Health Organization grade 3 meningiomas enrolled in our prospective observational cohort evaluating the utility of (68Ga) DOTATATE PET/MR imaging in somatostatin receptor positive brain tumors were included. We stratified patients by de novo-versus-secondary-progressive status and evaluated the differences in the PET standard uptake value, molecular profiles, and clinical outcomes. RESULTS: Patients met the inclusion criteria (secondary-progressive: 7/14; de novo: 7/14). The secondary-progressive cohort had a significantly higher per-patient number of surgeries (4.1 versus 1.6; P = .011) and trended toward a higher number of radiation therapy courses (2.4 versus 1.6; P = .23) and cumulative radiation therapy doses (106Gy versus 68.3Gy; P = .31). The secondary-progressive cohort had a significantly lower progression-free survival compared with the de novo cohort (4.8 versus 37.7 months; P = .004). Secondary-progressive tumors had distinct molecular pathology profiles with higher numbers of mutations (3.5 versus 1.2; P = .024). Secondary-progressive tumors demonstrated higher PET standard uptake values (17.1 versus 12.4; P = .0021). CONCLUSIONS: Our study confirms prior work illustrating distinct clinical outcomes in secondary-progressive and de novo World Health Organization grade 3 meningiomas. Furthermore, our findings support (68Ga) DOTATATE PET/MR imaging as a useful management strategy in World Health Organization grade 3 meningiomas and provide insight into meningioma biology, as well as clinical management implications.

[Ga68] DOTATATE PET/MRI-Guided Radiosurgical Treatment Planning and Response Assessment in Meningiomas.

BACKGROUND: Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery. METHODS: Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6-12 months post radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVRSSS) referencing superior sagittal sinus (SSS) blood pool were obtained. Size change was determined by Response Assessment in Neuro-Oncology (RANO) criteria. Association of SUVRSSS change magnitude and PFS was evaluated using Cox regression. RESULTS: 27 patients with 64 tumors (26% WHO-1, 41% WHO-2, 26% WHO-3, 7% WHO-unknown) were prospectively followed post stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) (mean dose: 30 Gy, modal dose 35 Gy, mean of 5 fractions). Post-irradiation SUV and SUVRSSS decreased by 37.4% and 44.4%, respectively (p < 0.0001). Size product decreased by 8.9%, thus failing to reach the 25% significance threshold as determined by RANO guidelines. Mean follow-up time was 26 months (range: 6-44). Overall mean PFS was 83% and 100%/100%/54% in WHO-1/-2/-3 subcohorts, respectively, at 34 months. At maximum follow-up (42-44 months), PFS was 100%/83%/54% in WHO-1/-2/-3 subcohorts, respectively. Cox regression analyses revealed a hazard ratio of 0.48 for 10-unit reduction in SUVRSSS in the SRS cohort. CONCLUSIONS: DOTATATE PET SUV and SUVRSSS demonstrated marked, significant decrease post radiosurgery. Lesion size decrease was statistically significant, however it was not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising imaging biomarker for response assessment in meningiomas treated with radiosurgery.

Statistical Parametric Mapping in Amyloid Positron Emission Tomography.

Alzheimer's disease (AD), the most common cause of dementia, has limited treatment options. Emerging disease modifying therapies are targeted at clearing amyloid-ß (Aß) aggregates and slowing the rate of amyloid deposition. However, amyloid burden is not routinely evaluated quantitatively for purposes of disease progression and treatment response assessment. Statistical Parametric Mapping (SPM) is a technique comparing single-subject Positron Emission Tomography (PET) to a healthy cohort that may improve quantification of amyloid burden and diagnostic performance. While primarily used in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET, SPM's utility in amyloid PET for AD diagnosis is less established and uncertainty remains regarding optimal normal database construction. Using commercially available SPM software, we created a database of 34 non-APOE ε4 carriers with normal cognitive testing (MMSE > 25) and negative cerebrospinal fluid (CSF) AD biomarkers. We compared this database to 115 cognitively normal subjects with variable AD risk factors. We hypothesized that SPM based on our database would identify more positive scans in the test cohort than the qualitatively rated [11C]-PiB PET (QR-PiB), that SPM-based interpretation would correlate better with CSF Aß42 levels than QR-PiB, and that regional z-scores of specific brain regions known to be involved early in AD would be predictive of CSF Aß42 levels. Fisher's exact test and the kappa coefficient assessed the agreement between SPM, QR-PiB PET, and CSF biomarkers. Logistic regression determined if the regional z-scores predicted CSF Aß42 levels. An optimal z-score cutoff was calculated using Youden's index. We found SPM identified more positive scans than QR-PiB PET (19.1 vs. 9.6%) and that SPM correlated more closely with CSF Aß42 levels than QR-PiB PET (kappa 0.13 vs. 0.06) indicating that SPM may have higher sensitivity than standard QR-PiB PET images. Regional analysis demonstrated the z-scores of the precuneus, anterior cingulate and posterior cingulate were predictive of CSF Aß42 levels [OR (95% CI) 2.4 (1.1, 5.1) p = 0.024; 1.8 (1.1, 2.8) p = 0.020; 1.6 (1.1, 2.5) p = 0.026]. This study demonstrates the utility of using SPM with a "true normal" database and suggests that SPM enhances diagnostic performance in AD in the clinical setting through its quantitative approach, which will be increasingly important with future disease-modifying therapies.

Sleep quality and health among pregnant smokers.

STUDY OBJECTIVES: We aimed to examine (1) sleep quality trends of pregnant smokers and (2) their associations with health outcomes. METHODS: A secondary analysis of 88 participants from the University at Buffalo Pregnancy and Smoking Cessation Study (nonrandomized clinical study) was performed. Sleep quality was measured with the Pittsburgh Sleep Quality Index (higher scores, worse quality) and sleep duration was self-reported repeatedly during pregnancy at preintervention, postintervention, and end-of-pregnancy visits. Participants were divided into 3 groups (until preintervention, until postintervention, until end-of-pregnancy). Maternal outcomes included gestational weight gain and smoking cessation. Infant outcomes included birth weight, gestational age, and Apgar score. RESULTS: There was a significant increase (P = .046) in Pittsburgh Sleep Quality Index score from postintervention (mean, 5.5 [standard deviation (SD), 2.6]) to end of pregnancy (6.6 [SD, 2.8]). Mean gestational weight gain was significantly lower for participants with poor sleep quality than those with good sleep quality (19.0 kg [SD, 21.3] vs 36.1 kg [SD, 22.8]; P = .008). Newborns with poor maternal sleep quality had a significantly lower mean 5-minute Apgar score (8.1 [SD, 1.3] vs 9.0 [SD, 0.0]; P = .021) than newborns with good maternal sleep quality. Preintervention sleep quality was not associated with smoking cessation, birth weight, or gestational age. Smoking cessation was almost half as prevalent in participants with insufficient sleep (< 7 hours/night) vs sufficient sleep duration (47.4% vs 92.3%, P = .011). CONCLUSIONS: Sleep quality worsened toward the end of pregnancy among smokers. Poor sleep might negatively influence gestational weight gain and Apgar score. Insufficient preintervention sleep might negatively influence smoking cessation. CITATION: Danilov M, Issany A, Mercado P, Haghdel A, Muzayad JK, Wen X. Sleep quality and health among pregnant smokers. J Clin Sleep Med. 2022;18(5):1343-1353.

A Change from a Spinal Immobilization to a Spinal Motion Restriction Protocol was Not Associated with an Increase in Disabling Spinal Cord Injuries.

BACKGROUND: Over the past decade, Emergency Medical Service (EMS) systems decreased backboard use as they transition from spinal immobilization (SI) protocols to spinal motion restriction (SMR) protocols. Since this change, no study has examined its effect on the neurologic outcomes of patients with spine injuries. OBJECTIVES: The object of this study is to determine if a state-wide protocol change from an SI to an SMR protocol had an effect on the incidence of disabling spinal cord injuries. METHODS: This was a retrospective review of patients in a single Level I trauma center before and after a change in spinal injury protocols. A two-step review of the record was used to classify spinal cord injuries as disabling or not disabling. A binary logistic regression was used to determine the effects of protocol, gender, age, level of injury, and mechanism of injury (MOI) on the incidence of significant disability from a spinal cord injury. RESULTS: A total of 549 patients in the SI period and 623 patients in the SMR period were included in the analysis. In the logistic regression, the change from an SI protocol to an SMR protocol did not demonstrate a significant effect on the incidence of disabling spinal injuries (OR: 0.78; 95% CI, 0.44 - 1.36). CONCLUSION: This study did not demonstrate an increase in disabling spinal cord injuries after a shift from an SI protocol to an SMR protocol. This finding, in addition to existing literature, supports the introduction of SMR protocols and the decreased use of the backboard.

Cervical Spine Trauma in East Africa: Presentation, Treatment, and Mortality.

BACKGROUND: Cervical spine trauma (CST) leads to devastating neurologic injuries. In a cohort of CST patients from a major East Africa referral center, we sought to (a) describe presentation and operative treatment patterns, (b) report predictors of neurologic improvement, and (c) assess predictors of mortality. METHODS: A retrospective, cohort study of CST patients presenting to a tertiary hospital in Dar Es Salaam, Tanzania, was performed. Demographic, injury, and operative data were collected. Neurologic exam on admission/discharge and in-hospital mortality were recorded. Univariate/multivariate logistic regression assessed predictors of operative treatment, neurologic improvement, and mortality. RESULTS: Of 101 patients with CST, 25 (24.8%) were treated operatively on a median postadmission day 16.0 (7.0-25.0). Twenty-six patients (25.7%) died, with 3 (12.0%) in the operative cohort and 23 (30.3%) in the nonoperative cohort. The most common fracture pattern was bilateral facet dislocation (26.7%). Posterior cervical laminectomy and fusion and anterior cervical corpectomy were the 2 most common procedures. Undergoing surgery was associated with an injury at the C4-C7 region versus occiput-C3 region (odds ratio [OR] 6.36, 95% confidence interval [CI] 1.71-32.28, P = .011) and an incomplete injury (OR 3.64; 95% CI 1.19-12.25; P = .029). Twelve patients (15.8%) improved neurologically, out of the 76 total patients with a recorded discharge exam. Having a complete injury was associated with increased odds of mortality (OR 11.75, 95% CI 3.29-54.72, P < .001), and longer time from injury to admission was associated with decreased odds of mortality (OR 0.66, 95% CI 0.48-0.85, P = .006). CONCLUSIONS: Those most likely to undergo surgery had C4-C7 injuries and incomplete spinal cord injuries. The odds of mortality increased with complete spinal cord injuries and shorter time from injury to admission, probably due to more severely injured patients dying early within 24-48 hours of injury. Thus, patients living long enough to present to the hospital may represent a self-selecting population of more stable patients. These results underscore the severity and uniqueness of CST in a less-resourced setting. LEVEL OF EVIDENCE: 4.

Ventral Tonsillar Herniation Predicts Headaches in Adults With Chiari Malformation.

BACKGROUND: Radiographic characterization of Chiari malformation (CM) has historically focused on caudal tonsillar herniation (CH) below the foramen magnum. Previously, we published evidence linking ventral tonsillar herniation (VH) and medullary symptoms in very young children. We sought to extend that investigation by studying the radiographic and clinical significance of VH in adults diagnosed with CM. METHODS: We retrospectively reviewed adults with cerebellar ectopia who underwent posterior fossa decompression with or without duraplasty (PFD/D) at our institution. VH was defined as tonsils crossing a line bisecting the caudal medulla at the level of the foramen magnum on axial MRI. Degree of VH was measured as distance between this bisecting line and the ventral tip of the herniated tonsil. Dorsal brainstem compression was qualitatively determined by assessing for obliteration of CSF space between the dorsal brainstem and the tonsils. RESULTS: Out of 89 cases reviewed, 54 had some degree of VH. Compared with those without VH, the VH group was significantly older in age and more likely to also present with dorsal brainstem compression and headaches. No correlation was observed between degrees of CH and VH in the VH group. The degree of VH significantly decreased 3 months after PFD/D. CONCLUSIONS: VH is relatively common in CM patients and might be an important independent radiographic metric to evaluate and consider as part of the decision-making process, especially in those presenting with Chiari-like symptomatology referable to the medulla but who do not meet the traditional criteria of cerebellar ectopia greater than 5 mm.

Self-reported health without clinically measurable benefits among adult users of multivitamin and multimineral supplements: a cross-sectional study.

OBJECTIVE: Multiple clinical trials fail to identify clinically measurable health benefits of daily multivitamin and multimineral (MVM) consumption in the general adult population. Understanding the determinants of widespread use of MVMs may guide efforts to better educate the public about effective nutritional practices. The objective of this study was to compare self-reported and clinically measurable health outcomes among MVM users and non-users in a large, nationally representative adult civilian non-institutionalised population in the USA surveyed on the use of complementary health practices. DESIGN: Cross-sectional analysis of the effect of MVM consumption on self-reported overall health and clinically measurable health outcomes. PARTICIPANTS: Adult MVM users and non-users from the 2012 National Health Interview Survey (n=21 603). PRIMARY AND SECONDARY OUTCOME MEASURES: Five psychological, physical, and functional health outcomes: (1) self-rated health status, (2) needing help with routine needs, (3) history of 10 chronic diseases, (4) presence of 19 health conditions in the past 12 months, and (5) Kessler 6-Item (K6) Psychological Distress Scale to measure non-specific psychological distress in the past month. RESULTS: Among 4933 adult MVM users and 16 670 adult non-users, MVM users self-reported 30% better overall health than non-users (adjusted OR 1.31; 95% CI 1.17 to 1.46; false discovery rate adjusted p<0.001). There were no differences between MVM users and non-users in history of 10 chronic diseases, number of present health conditions, severity of current psychological distress on the K6 Scale and rates of needing help with daily activities. No effect modification was observed after stratification by sex, education, and race. CONCLUSIONS: MVM users self-reported better overall health despite no apparent differences in clinically measurable health outcomes. These results suggest that widespread use of multivitamins in adults may be a result of individuals' positive expectation that multivitamin use leads to better health outcomes or a self-selection bias in which MVM users intrinsically harbour more positive views regarding their health.

Medical Student Concerns Relating to Neurosurgery Education During COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has created significant obstacles within medical education. For medical students interested in pursuing neurosurgery as a specialty, the educational policies surrounding COVID-19 have resulted in unique challenges. The present study used a nationwide survey to identify the concerns of medical students interested in pursuing neurosurgery during the COVID-19 pandemic. METHODS: Students who had previously registered for medical student neurosurgery training camps were sent an online Qualtrics survey requesting them to assess how the COVID-19 pandemic was affecting their neurosurgical education. The Pearson χ2 test and post hoc pairwise Fisher exact test were used for analysis of categorical variables, and the 2-tailed paired Student t test was used for continuous variables. RESULTS: The survey was distributed to 852 medical students, with 127 analyzed responses. Concerns regarding conferences and networking opportunities (63%), clinical experience (59%), and board examination scores (42%) were most frequently cited. Of the third-year medical students, 76% reported ≥1 cancelled or postponed neurosurgery rotation. On average, students were more likely to take 1 year off from medical school after than before the start of the COVID-19 pandemic, measured from 0 to 100 (25.3 ± 36.0 vs. 39.5 ± 37.5; P = 0.004). Virtual mentorship pairing was the highest rated educational intervention suggested by first- and second-year medical students. The third- and fourth-year medical students had cited virtual surgical skills workshops most frequently. CONCLUSIONS: The results from the present nationwide survey have highlighted the concerns of medical students regarding their neurosurgery education during the COVID-19 pandemic. With these findings, neurosurgery organizations can consider targeted plans for students of each year to continue their education and development.

A multicomponent behavioral intervention for smoking cessation during pregnancy: a nonconcurrent multiple-baseline design.

Given serious consequences of maternal smoking, we aimed to develop and test a multicomponent behavioral intervention to enhance smoking cessation during pregnancy. In this nonconcurrent, multiple-baseline intervention pilot study, 48 daily smoking pregnant women (mean 13.7 weeks of gestation) were recruited from Buffalo, NY, USA. Upon completion of the repeated baseline smoking monitoring (up to 3 weeks), 30 continuous smokers received a contingent financial incentive-based intervention with three additional components (education and counseling, monitoring and feedback, and family support). After the quit date, participants met with counselors (~1 hr/visit) daily for 2 weeks and twice a week for another 6 weeks. Twenty-one out of 30 participants quit smoking completely (verified by urine cotinine) after receiving the intervention, and the other nine nonquitters decreased smoking substantially. The estimated smoking cessation rate was 70.0% (21/30) at the second week of the intervention, and 63.3% (19/30) at the conclusion of the 8-week intervention assuming the dropouts as smoking. In interrupted time series analysis, the mean daily number of cigarettes smoked among quitters decreased by 6.52, 5.34, and 4.67 among early, delayed, and late intervention groups, respectively. Quitters' mean urine cotinine level maintained stably high before the intervention but decreased rapidly to the nonsmoking range once the intervention was initiated. Most participants (85.7%) reported meeting or exceeding expectations, and 100% would recommend the program to others. This pilot multicomponent intervention was feasible and acceptable to most participants, resulting in a high smoking cessation rate among pregnant smokers who were unlikely to quit spontaneously.