Hope Center Member Publications

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Measures of Intracranial Injury Size Do Not Improve Clinical Decision Making for Children With Mild Traumatic Brain Injuries and Intracranial Injuries(2022) Neurosurgery, 90 (6), pp. 691-699. 

Greenberg, J.K.a , Olsen, M.A.b , Johnson, G.W.a , Ahluwalia, R.c , Hill, M.d , Hale, A.T.c , Belal, A.e , Baygani, S.e , Foraker, R.E.b , Carpenter, C.R.f , Ackerman, L.L.e , Noje, C.g , Jackson, E.M.h , Burns, E.i , Sayama, C.M.i j , Selden, N.R.i j , Vachhrajani, S.d k , Shannon, C.N.d , Kuppermann, N.l m , Limbrick, D.D., Jra

AbstractBACKGROUND: When evaluating children with mild traumatic brain injuries (mTBIs) and intracranial injuries (ICIs), neurosurgeons intuitively consider injury size. However, the extent to which such measures (eg, hematoma size) improve risk prediction compared with the kids intracranial injury decision support tool for traumatic brain injury (KIIDS-TBI) model, which only includes the presence/absence of imaging findings, remains unknown. OBJECTIVE: To determine the extent to which measures of injury size improve risk prediction for children with mild traumatic brain injuries and ICIs. METHODS: We included children ≤18 years who presented to 1 of the 5 centers within 24 hours of TBI, had Glasgow Coma Scale scores of 13 to 15, and had ICI on neuroimaging. The data set was split into training (n = 1126) and testing (n = 374) cohorts. We used generalized linear modeling (GLM) and recursive partitioning (RP) to predict the composite of neurosurgery, intubation >24 hours, or death because of TBI. Each model’s sensitivity/specificity was compared with the validated KIIDS-TBI model across 3 decision-making risk cutoffs (<1%, <3%, and <5% predicted risk). RESULTS: The GLM and RP models included similar imaging variables (eg, epidural hematoma size) while the GLM model incorporated additional clinical predictors (eg, Glasgow Coma Scale score). The GLM (76%-90%) and RP (79%-87%) models showed similar specificity across all risk cutoffs, but the GLM model had higher sensitivity (89%-96% for GLM; 89% for RP). By comparison, the KIIDS-TBI model had slightly higher sensitivity (93%-100%) but lower specificity (27%-82%). CONCLUSION: Although measures of ICI size have clear intuitive value, the tradeoff between higher specificity and lower sensitivity does not support the addition of such information to the KIIDS-TBI model. Copyright © Congress of Neurological Surgeons 2022. All rights reserved.

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Cardiorespiratory Fitness Is Associated with Better White Matter Integrity in Persons Living with HIV(2022) Journal of Acquired Immune Deficiency Syndromes, 89 (5), pp. 558-565. 

Kilgore, C.B.a , Strain, J.F.a , Nelson, B.a , Cooley, S.A.a , Rosenow, A.a , Glans, M.a , Cade, W.T.b , Reeds, D.N.c , Paul, R.H.d , Ances, B.M.a e f

AbstractBackground:Despite improved survival rates, neurocognitive impairment persists in persons living with HIV (PLWH). An active lifestyle is linked to improved cognition among PLWH, yet the neural substrates remain unclear. Diffusion tensor imaging and diffusion basis spectrum imaging measure HIV-related changes in brain white matter integrity. We used these measures of structural brain integrity to assess white matter changes, physical fitness, and cognition in a cross-sectional study of PLWH.Methods:Forty-four virologically well-controlled PLWH were recruited (average age of 56 years, a median recent CD4+count of 682 cells/mm3). Diffusion tensor imaging -derived fractional anisotropy (FA) and diffusion basis spectrum imaging-derived axonal density were calculated. Cardiorespiratory fitness [maximal volume of oxygen consumption (VO2max)] was measured by performing indirect calorimetry during exercise to volitional exhaustion. Cardiovascular risk was assessed by the Framingham risk score. Neuropsychological performance (NP) testing evaluated learning, memory, psychomotor/processing speed, and executive function. Partial correlations assessed the relationships among cardiorespiratory fitness, neuroimaging, NP, and HIV clinical metrics (CD4+count and time since diagnosis).Results:Higher VO2max was associated with higher FA and higher axonal density in multiple white matter tracts, including the corticospinal tract and superior longitudinal fasciculus. Better NP in the motor/psychomotor domain was positively associated with FA and axonal density in diverse tracts including those associated with motor and visuospatial processing. However, higher VO2max was not associated with NP or HIV clinical metrics.Conclusions:An active lifestyle promoting cardiorespiratory fitness may lead to better white matter integrity and decreased susceptibility to cognitive decline in virologically well-controlled PLWH. © 2022 Lippincott Williams and Wilkins. All rights reserved.

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Covariance and Correlation Analysis of Resting State Functional Magnetic Resonance Imaging Data Acquired in a Clinical Trial of Mindfulness-Based Stress Reduction and Exercise in Older Individuals(2022) Frontiers in Neuroscience, 16, art. no. 825547, . 

Snyder, A.Z.a b , Nishino, T.c , Shimony, J.S.a , Lenze, E.J.c , Wetherell, J.L.d e , Voegtle, M.c , Miller, J.P.f , Yingling, M.D.f , Marcus, D.a , Gurney, J.a , Rutlin, J.c , Scott, D.g , Eyler, L.e , Barch, D.a b h , the MEDEX Research Groupi

AbstractWe describe and apply novel methodology for whole-brain analysis of resting state fMRI functional connectivity data, combining conventional multi-channel Pearson correlation with covariance analysis. Unlike correlation, covariance analysis preserves signal amplitude information, which feature of fMRI time series may carry physiological significance. Additionally, we demonstrate that dimensionality reduction of the fMRI data offers several computational advantages including projection onto a space of manageable dimension, enabling linear operations on functional connectivity measures and exclusion of variance unrelated to resting state network structure. We show that group-averaged, dimensionality reduced, covariance and correlation matrices are related, to reasonable approximation, by a single scalar factor. We apply this methodology to the analysis of a large, resting state fMRI data set acquired in a prospective, controlled study of mindfulness training and exercise in older, sedentary participants at risk for developing cognitive decline. Results show marginally significant effects of both mindfulness training and exercise in both covariance and correlation measures of functional connectivity. Copyright © 2022 Snyder, Nishino, Shimony, Lenze, Wetherell, Voegtle, Miller, Yingling, Marcus, Gurney, Rutlin, Scott, Eyler and Barch.

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Biallelic Variants in the Ectonucleotidase ENTPD1 Cause a Complex Neurodevelopmental Disorder with Intellectual Disability, Distinct White Matter Abnormalities, and Spastic Paraplegia(2022) Annals of Neurology, . 

Calame, D.G.a b c , Herman, I.a b c av , Maroofian, R.d , Marshall, A.E.e , […] , Jin, S.C.ab , Abbaszadegan, M.R.ac ad , Ebrahimzadeh-Vesal, R.ad , Hosseini, S.ad , Alavi, S.ae , Bahreini, A.af , Zarean, E.ag , Salehi, M.M.ah , Al-Sannaa, N.A.ai , Zifarelli, G.aj , Bauer, P.aj , Robson, S.C.ak , Coban-Akdemir, Z.b al , Travaglini, L.am an , Nicita, F.am an , Jhangiani, S.N.ao , Gibbs, R.A.ao , Posey, J.E.b , Kruer, M.C.j k , Kernohan, K.D.e ap , Morales Saute, J.A.g aq ar , Houlden, H.d , Vanderver, A.r as , Elsea, S.H.b , Pehlivan, D.a b c , Marafi, D.b at , Lupski, J.R.b c ao au

AbstractObjective: Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia is associated with >80 genes, with frequently only few affected individuals described for each gene. Herein, we characterize a large cohort of individuals with biallelic variation in ENTPD1, a gene previously linked to spastic paraplegia 64 (Mendelian Inheritance in Man # 615683). Methods: Individuals with biallelic ENTPD1 variants were recruited worldwide. Deep phenotyping and molecular characterization were performed. Results: A total of 27 individuals from 17 unrelated families were studied; additional phenotypic information was collected from published cases. Twelve novel pathogenic ENTPD1 variants are described (NM 001776.6): c.398_399delinsAA; p.(Gly133Glu), c.540del; p.(Thr181Leufs*18), c.640del; p.(Gly216Glufs*75), c.185 T > G; p.(Leu62*), c.1531 T > C; p.(*511Glnext*100), c.967C > T; p.(Gln323*), c.414-2_414-1del, and c.146 A > G; p.(Tyr49Cys) including 4 recurrent variants c.1109 T > A; p.(Leu370*), c.574-6_574-3del, c.770_771del; p.(Gly257Glufs*18), and c.1041del; p.(Ile348Phefs*19). Shared disease traits include childhood onset, progressive spastic paraplegia, intellectual disability (ID), dysarthria, and white matter abnormalities. In vitro assays demonstrate that ENTPD1 expression and function are impaired and that c.574-6_574-3del causes exon skipping. Global metabolomics demonstrate ENTPD1 deficiency leads to impaired nucleotide, lipid, and energy metabolism. Interpretation: The ENTPD1 locus trait consists of childhood disease onset, ID, progressive spastic paraparesis, dysarthria, dysmorphisms, and white matter abnormalities, with some individuals showing neurocognitive regression. Investigation of an allelic series of ENTPD1 (1) expands previously described features of ENTPD1-related neurological disease, (2) highlights the importance of genotype-driven deep phenotyping, (3) documents the need for global collaborative efforts to characterize rare autosomal recessive disease traits, and (4) provides insights into disease trait neurobiology. ANN NEUROL 2022. © 2022 American Neurological Association.

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Lidocaine Nerve Block Diminishes the Effects of Therapeutic Electrical Stimulation to Enhance Nerve Regeneration in Rats(2022) Hand, .

Keane, G.C.a , Marsh, E.B.a , Hunter, D.A.a , Schellhardt, L.a , Walker, E.R.b , Wood, M.D.a

AbstractBackground: Although electrical stimulation (ES) can improve nerve regeneration, the impact of nerve block, such as lidocaine (Lido), on the therapeutic benefits of ES remains unclear. We used a rat tibial nerve transection-and-repair model to explore how either preoperative (PreOp) or postoperative (PostOp) nerve block affects ES-related improvement in regeneration. Methods: Lewis rats were used in 1 of 2 studies. The first evaluated the effects of extraneural Lido on both healthy and injured nerves. In the second study, rats were randomized to 5 experimental groups: No ES (negative control), PreOp Lido, ES + PreOp Lido, PostOp + ES, and ES (positive control). All groups underwent tibial nerve transection and repair. In both studies, nerves were harvested for histological analysis of regeneration distal to the injury site. Results: Application of extraneural Lido did not damage healthy or injured nerve based on qualitative histological observations. In the context of nerve transection and repair, the ES group exhibited improved axon regeneration at 21 days measured by the total number of myelinated fibers compared with No ES. Fiber density and percentage of neural tissue in the ES group were greater than those in both No ES and PreOp Lido + ES groups. ES + PostOp Lido was not different from No ES or ES group. Conclusions: Extraneural application of Lido did not damage nerves. Electrical stimulation augmented nerve regeneration, but Lido diminished the ES-related improvement in nerve regeneration. Clinical studies on the effects of ES to nerve regeneration may need to consider nerve block as a variable affecting ES outcome. © The Author(s) 2022.

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Smartphone assessment uncovers real-time relationships between depressed mood and daily functional behaviors after stroke(2022) Journal of Telemedicine and Telecare

Bui, Q.a , Kaufman, K.J.b , Munsell, E.G.S.b c , Lenze, E.J.d , Lee, J.-M.e , Mohr, D.C.f , Fong, M.W.M.e g h , Metts, C.L.i , Tomazin, S.E.b , Pham, V.d , Wong, A.W.K.b j

AbstractIntroduction: The impact of depressed mood in daily life is difficult to investigate using traditional retrospective assessments, given daily or even within-day mood fluctuations in various contexts. This study aimed to use a smartphone-based ambulatory assessment to examine real-time relationships between depressed mood and functional behaviors among individuals with stroke. Methods: A total of 202 participants with mild-to-moderate stroke (90% ischemic, 45% female, 44% Black) completed an ecological momentary assessment five times per day for 2 weeks by reporting their depressed mood and functional behaviors regarding where, with whom, and what activity was spent. Results: Participants spent 28% of their wake-up time participating in passive leisure activities but spent the least time in physical (4%) and vocational (9%) activities. Depressed mood was concurrently lower when participants engaged in social activities (β = −0.023 ± 0.011) and instrumental activities of daily living (β = −0.061 ± 0.013); spent time with family members (β = −0.061 ± 0.014), spouses (β = −0.043, ± 0.016), friends (β = −0.094, ± 0.021), and coworkers (β = −0.050 ± 0.021); and were located in restaurants (β = −0.068 ± 0.029), and homes of family members (β = −0.039 ± 0.020) or friends (β = −0.069 ± 0.031). Greater depressed mood was associated with worse ratings in satisfaction, performance, and engagement of activities in concurrent (βs = −0.036 ± 0.003, −0.053 ± 0.003, −0.044 ± 0.003) and time-lagged models (βs = −0.011 ± 0.004, −0.012 ± 0.004, −0.013 ± 0.004). Discussion: Smartphone-based ambulatory assessment can elucidate functional behaviors and associated mood after stroke. Findings support behavioral activation treatments to schedule social and instrumental activities for stroke survivors to reduce their depressed mood. © The Author(s) 2022.

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Posted on June 8, 2022
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