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Article ; Online: Screening for Delirium During Pediatric Brain Injury Rehabilitation.

Watson, William D / Chen, Hsuan-Wei / Svingos, Adrian M / Ortiz, Ana K / Suskauer, Stacy J / Shah, Sudhin A / Traube, Chani

Archives of physical medicine and rehabilitation

2024

Abstract: Objective: To assess feasibility of routine delirium screening using the Cornell Assessment of Pediatric Delirium (CAPD) in children admitted for rehabilitation with acquired brain injury (ABI), report on the prevalence of positive delirium screens in ... ...

Abstract	Objective: To assess feasibility of routine delirium screening using the Cornell Assessment of Pediatric Delirium (CAPD) in children admitted for rehabilitation with acquired brain injury (ABI), report on the prevalence of positive delirium screens in this population, and explore longitudinal trends in CAPD scores and their association with rehabilitation outcomes. Design: Retrospective study. Setting: Pediatric inpatient rehabilitation unit. Participants: 144 children (median 10.8 years) with ABI (N=144). Interventions: Not applicable. Main outcome measures: Percent compliance with twice daily delirium screening; prevalence of positive delirium screens; trajectories in CAPD scores and their relation with FIM for Children (WeeFIM) scores. Results: Screening was feasible (mean 75% compliance for each of 144 children). Of 16,136 delirium screens, 29% were positive. 62% of children had ≥1 positive screen. Four primary patterns of CAPD trajectories were identified: Static Encephalopathy (10%), Episodic Delirium (10%), Improving (32%), and No Delirium (48%). Validity of these trajectories was demonstrated through association with WeeFIM and CALS outcomes. Younger age at admission was associated with positive delirium screens, and rehabilitation length of stay was significantly longer for the Improving group. Conclusions: Delirium occurs frequently in children with ABI during inpatient rehabilitation. Routine delirium screening provides clinically relevant information including the potential to facilitate early detection and intervention for medical complications. Longitudinal ratings of delirium symptoms may also have a role in developing a standardized definition for Post Traumatic Confusional State (PTCS) stage of recovery in children.
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	80057-0
ISSN	1532-821X ; 0003-9993
ISSN (online)	1532-821X
ISSN	0003-9993
DOI	10.1016/j.apmr.2024.02.729
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Article ; Online: Quantitative multimodal imaging in traumatic brain injuries producing impaired cognition.

Shah, Sudhin A / Lowder, Ryan J / Kuceyeski, Amy

Current opinion in neurology

2020 Volume 33, Issue 6, Page(s) 691–698

Abstract: Purpose of review: Cognitive impairments are a devastating long-term consequence following traumatic brain injury (TBI). This review provides an update on the quantitative mutimodal neuroimaging studies that attempt to elucidate the mechanism(s) ... ...

Abstract	Purpose of review: Cognitive impairments are a devastating long-term consequence following traumatic brain injury (TBI). This review provides an update on the quantitative mutimodal neuroimaging studies that attempt to elucidate the mechanism(s) underlying cognitive impairments and their recovery following TBI. Recent findings: Recent studies have linked individual specific behavioural impairments and their changes over time to physiological activity and structural changes using EEG, PET and MRI. Multimodal studies that combine measures of physiological activity with knowledge of neuroanatomical and connectivity damage have also illuminated the multifactorial function-structure relationships that underlie impairment and recovery following TBI. Summary: The combined use of multiple neuroimaging modalities, with focus on individual longitudinal studies, has the potential to accurately classify impairments, enhance sensitivity of prognoses, inform targets for interventions and precisely track spontaneous and intervention-driven recovery.
MeSH term(s)	Brain/diagnostic imaging ; Brain Injuries, Traumatic/complications ; Brain Injuries, Traumatic/diagnostic imaging ; Brain Injuries, Traumatic/psychology ; Cognition/physiology ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/psychology ; Humans ; Longitudinal Studies ; Magnetic Resonance Imaging ; Multimodal Imaging ; Neuroimaging
Language	English
Publishing date	2020-10-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1182686-1
ISSN	1473-6551 ; 1350-7540
ISSN (online)	1473-6551
ISSN	1350-7540
DOI	10.1097/WCO.0000000000000872
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Article ; Online: Diffusion Tensor Imaging Along Perivascular Spaces (DTI-ALPS) to Assess Effects of Age, Sex, and Head Size on Interstitial Fluid Dynamics in Healthy Subjects.

Ozsahin, Ilker / Zhou, Liangdong / Wang, Xiuyuan / Garetti, Jacob / Jamison, Keith / Xi, Ke / Tanzi, Emily / Jaywant, Abhishek / Patchell, Abigail / Maloney, Thomas / de Leon, Mony J / Kuceyeski, Amy / Shah, Sudhin A / Li, Yi / Butler, Tracy A

Journal of Alzheimer's disease reports

2024 Volume 8, Issue 1, Page(s) 355–361

Abstract: Diffusion tensor imaging along perivascular spaces (DTI-ALPS) is a novel MRI method for assessing brain interstitial fluid dynamics, potentially indexing glymphatic function. Failed glymphatic clearance is implicated in Alzheimer's disease (AD) ... ...

Abstract	Diffusion tensor imaging along perivascular spaces (DTI-ALPS) is a novel MRI method for assessing brain interstitial fluid dynamics, potentially indexing glymphatic function. Failed glymphatic clearance is implicated in Alzheimer's disease (AD) pathophysiology. We assessed the contribution of age and female sex (strong AD risk factors) to DTI-ALPS index in healthy subjects. We also for the first time assessed the effect of head size. In accord with prior studies, we show reduced DTI-ALPS index with aging, and in men compared to women. However, head size may be a major contributing factor to this counterintuitive sex difference.
Language	English
Publishing date	2024-02-20
Publishing country	Netherlands
Document type	Journal Article
ISSN	2542-4823
ISSN (online)	2542-4823
DOI	10.3233/ADR-230143
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Article ; Online: Brain Fluid Clearance After Traumatic Brain Injury Measured Using Dynamic Positron Emission Tomography.

Butler, Tracy / Schubert, Julia / Karakatsanis, Nikolaos A / Hugh Wang, Xiuyuan / Xi, Ke / Kang, Yeona / Chen, Kewei / Zhou, Liangdong / Fung, Edward K / Patchell, Abigail / Jaywant, Abhishek / Li, Yi / Chiang, Gloria / Glodzik, Lidia / Rusinek, Henry / de Leon, Mony / Turkheimer, Federico / Shah, Sudhin A

Neurotrauma reports

2024 Volume 5, Issue 1, Page(s) 359–366

Abstract: Brain fluid clearance by pathways including the recently described paravascular glymphatic system is a critical homeostatic mechanism by which metabolic products, toxins, and other wastes are removed from the brain. Brain fluid clearance may be ... ...

Abstract	Brain fluid clearance by pathways including the recently described paravascular glymphatic system is a critical homeostatic mechanism by which metabolic products, toxins, and other wastes are removed from the brain. Brain fluid clearance may be especially important after traumatic brain injury (TBI), when blood, neuronal debris, inflammatory cells, and other substances can be released and/or deposited. Using a non-invasive dynamic positron emission tomography (PET) method that models the rate at which an intravenously injected radiolabeled molecule (in this case
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ISSN	2689-288X
ISSN (online)	2689-288X
DOI	10.1089/neur.2024.0010
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Article: Brain vital signs as a quantitative measure of cognition: Methodological implementation in a care home environment.

Ighalo, Joshua / Kirby, Eric D / Song, Xiaowei / Fickling, Shaun D / Pawlowski, Gabriela / Hajra, Sujoy Ghosh / Liu, Careesa C / Menon, Carlo / Shah, Sudhin A / Knoefel, Frank / D'Arcy, Ryan C N

Heliyon

2024 Volume 10, Issue 7, Page(s) e28982

Abstract: Introduction: Managing cognitive function in care homes is a significant challenge. Individuals in care have a variety of scores across standard clinical assessments, such as the Mini-Mental Status Exam (MMSE), and many of them have scores that fall ... ...

Abstract	Introduction: Managing cognitive function in care homes is a significant challenge. Individuals in care have a variety of scores across standard clinical assessments, such as the Mini-Mental Status Exam (MMSE), and many of them have scores that fall within the range associated with dementia. A recent methodological advance, brain vital sign monitoring through auditory event-related potentials, provides an objective and sensitive physiological measurement to track abnormalities, differences, or changes in cognitive function. Taking advantage of point-of-care accessibility, the current study evaluated the methodological feasibility, the assessment of whether a particular research method can be successfully implemented, of quantitatively measuring cognition of care home residents using brain vital signs. Secondarily, the current study examined the relationship between brain vital signs, specifically the cognitive processing associated N400 component, and MMSE scores in care home residents. Materials and methods: Brain vital signs used the established N100 (auditory sensation), P300 (basic attention), and N400 (cognitive processing) event-related potential (ERP) components. A total of 52 residents were enrolled, with all participants evaluated using the MMSE. Participants were assigned into homogeneous groups based on their MMSE scores, and were categorized into low (n = 14), medium (n = 17), and high (n = 13) MMSE groups. Both brain vital sign measures and underlying ERP waveforms were examined. Statistical analyses used partial least squares correlation (PLS) analyses in which both MMSE and age were included as factors, as well as jackknife approaches, to test for significant brain vital sign changes. Results: The current study successfully measured and analyzed standardized, quantifiable brain vital signs in a care home setting. ERP waveform data showed specific N400 changes between MMSE groups as a function of MMSE score. PLS analyses confirmed significant MMSE-related and age-related differences in the N400 amplitude ( Discussion and conclusion: It was possible to acquire brain vital signs measures in care home residents. Additionally, the current study evaluated brain vital signs relative to MMSE in this group. The comparison revealed significant decreasing in N400 response amplitude (cognitive processing) as a function of both MMSE score and age, as well as a slowing of N400 latency. The findings indicate that objective neurophysiological measures of impairment are detectable in care home residents across the span of MMSE scores. Direct comparison to MMSE- and age-related variables represents a critical initial step ahead of future studies that will investigate relative improvements in sensitivity, validity, reliability and related advantages of brain vital sign monitoring.
Language	English
Publishing date	2024-03-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e28982
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Article ; Online: Brain-Computer Interfaces for Communication in Patients with Disorders of Consciousness: A Gap Analysis and Scientific Roadmap.

Schiff, Nicholas D / Diringer, Michael / Diserens, Karin / Edlow, Brian L / Gosseries, Olivia / Hill, N Jeremy / Hochberg, Leigh R / Ismail, Fatima Y / Meyer, Ivo A / Mikell, Charles B / Mofakham, Sima / Molteni, Erika / Polizzotto, Leonard / Shah, Sudhin A / Stevens, Robert D / Thengone, Daniel

Neurocritical care

2024

Abstract: Background: We developed a gap analysis that examines the role of brain-computer interfaces (BCI) in patients with disorders of consciousness (DoC), focusing on their assessment, establishment of communication, and engagement with their environment.: ... ...

Abstract	Background: We developed a gap analysis that examines the role of brain-computer interfaces (BCI) in patients with disorders of consciousness (DoC), focusing on their assessment, establishment of communication, and engagement with their environment. Methods: The Curing Coma Campaign convened a Coma Science work group that included 16 clinicians and neuroscientists with expertise in DoC. The work group met online biweekly and performed a gap analysis of the primary question. Results: We outline a roadmap for assessing BCI readiness in patients with DoC and for advancing the use of BCI devices in patients with DoC. Additionally, we discuss preliminary studies that inform development of BCI solutions for communication and assessment of readiness for use of BCIs in DoC study participants. Special emphasis is placed on the challenges posed by the complex pathophysiologies caused by heterogeneous brain injuries and their impact on neuronal signaling. The differences between one-way and two-way communication are specifically considered. Possible implanted and noninvasive BCI solutions for acute and chronic DoC in adult and pediatric populations are also addressed. Conclusions: We identify clinical and technical gaps hindering the use of BCI in patients with DoC in each of these contexts and provide a roadmap for research aimed at improving communication for adults and children with DoC, spanning the clinical spectrum from intensive care unit to chronic care.
Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2381896-7
ISSN	1556-0961 ; 1541-6933
ISSN (online)	1556-0961
ISSN	1541-6933
DOI	10.1007/s12028-023-01924-w
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Article ; Online: Glymphatic clearance estimated using diffusion tensor imaging along perivascular spaces is reduced after traumatic brain injury and correlates with plasma neurofilament light, a biomarker of injury severity.

Butler, Tracy / Zhou, Liangdong / Ozsahin, Ilker / Wang, Xiuyuan Hugh / Garetti, Jacob / Zetterberg, Henrik / Blennow, Kaj / Jamison, Keith / de Leon, Mony J / Li, Yi / Kuceyeski, Amy / Shah, Sudhin A

Brain communications

2023 Volume 5, Issue 3, Page(s) fcad134

Abstract: The glymphatic system is a perivascular fluid clearance system, most active during sleep, considered important for clearing the brain of waste products and toxins. Glymphatic failure is hypothesized to underlie brain protein deposition in ... ...

Abstract	The glymphatic system is a perivascular fluid clearance system, most active during sleep, considered important for clearing the brain of waste products and toxins. Glymphatic failure is hypothesized to underlie brain protein deposition in neurodegenerative disorders like Alzheimer's disease. Preclinical evidence suggests that a functioning glymphatic system is also essential for recovery from traumatic brain injury, which involves release of debris and toxic proteins that need to be cleared from the brain. In a cross-sectional observational study, we estimated glymphatic clearance using diffusion tensor imaging along perivascular spaces, an MRI-derived measure of water diffusivity surrounding veins in the periventricular region, in 13 non-injured controls and 37 subjects who had experienced traumatic brain injury ∼5 months previously. We additionally measured the volume of the perivascular space using
Language	English
Publishing date	2023-04-25
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcad134
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Article: Objective Neurophysiologic Markers of Cognition After Pediatric Brain Injury.

Kim, Nayoung / Watson, William / Caliendo, Eric / Nowak, Sophie / Schiff, Nicholas D / Shah, Sudhin A / Hill, N Jeremy

Neurology. Clinical practice

2022 Volume 12, Issue 5, Page(s) 352–364

Abstract: Background and objectives: Following brain injury, clinical assessments of residual and emerging cognitive function are difficult and fraught with errors. In adults, recent American Academy of Neurology (AAN) practice guidelines recommend objective ... ...

Abstract	Background and objectives: Following brain injury, clinical assessments of residual and emerging cognitive function are difficult and fraught with errors. In adults, recent American Academy of Neurology (AAN) practice guidelines recommend objective neuroimaging and neurophysiologic measures to support diagnosis. Equivalent measures are lacking in pediatrics-an especially great challenge due to the combined heterogeneity of both brain injury and pediatric development. Therefore, we aim to establish quantitative, clinically practicable measures of cognitive function following pediatric brain injury. Methods: Participants with and without brain injury were aged 8-18 years, clinically classified according to cognitive recovery state: N = 8 in disorders of consciousness (DoC), N = 7 in confusional state, N = 19 cognitively impaired, and N = 13 typically developing uninjured controls. We prospectively measured electroencephalographic markers of sensory processing and attention in an auditory oddball paradigm, and of covert movement attempts in a command-following paradigm. Results: In 3 participants with DoC, EEG markers of active attempted command following revealed cognitive function that clinical assessment had failed to detect. These same 3 individuals could also be distinguished from the rest of their group by 2 event-related potentials that correlate with sensory processing and orienting attention in the oddball paradigm. Considered across the whole participant group, magnitudes of these 2 ERP markers significantly increased as cognitive recovery progressed (ANOVA: each Discussion: Despite heterogeneity of brain injuries and brain development, our objective EEG markers reflected cognitive recovery independent of motor function. Two of these markers required no active participation. Together, they allowed us to identify 3 individuals who meet the criteria for cognitive-motor dissociation. To diagnose, prognose, and track cognitive recovery accurately, such markers should be used in pediatrics.
Language	English
Publishing date	2022-11-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2645818-4
ISSN	2163-0933 ; 2163-0402
ISSN (online)	2163-0933
ISSN	2163-0402
DOI	10.1212/CPJ.0000000000200066
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Article ; Online: Association Between the Attention Network Test, Neuropsychological Measures, and Disability in Post-Acute Traumatic Brain Injury.

Jaywant, Abhishek / Blunt, Emily / Jamison, Keith / Kim, Nayoung / RoyChoudhury, Arindam / Schiff, Nicholas D / Kuceyeski, Amy / Dams-O'Connor, Kristen / Shah, Sudhin

Neurotrauma reports

2023 Volume 4, Issue 1, Page(s) 318–329

Abstract: Cognitive impairment after traumatic brain injury (TBI) is persistent and disabling. Assessing cognitive function in a reliable and valid manner, using measures that are sensitive to the integrity of underlying neural substrates, is crucial in clinical ... ...

Abstract	Cognitive impairment after traumatic brain injury (TBI) is persistent and disabling. Assessing cognitive function in a reliable and valid manner, using measures that are sensitive to the integrity of underlying neural substrates, is crucial in clinical research. The Attention Network Test (ANT) is one such assessment measure that has demonstrated associations with neural regions involved in attention; however, clinical utility of the ANT is limited because its relationship with neuropsychological measures of cognitive function (i.e., its construct validity) has not yet been established in TBI. We evaluated the association between the ANT and 1) a neuropsychological battery assessing executive function and memory and 2) global function assessed by the Glasgow Outcome Scale-Extended (GOSE). Forty-eight adults with complicated mild-severe TBI were evaluated ∼5 months post-injury. Using principal component analysis and multi-variate linear regression adjusted for age, gender, education, and cause of injury, we found that ANT reaction time and executive network scores predicted a principal component assessing processing speed and executive function. Conversely, the ANT did not predict a principal component assessing memory. The ANT was weakly associated with the GOSE. Among persons with TBI during the post-acute phase of recovery, the ANT has good construct validity as evidenced by its associations with neuropsychological measures of processing speed and executive function, but not memory. Given that ANT networks are known to relate to specific neuroanatomical regions, the ANT may be a useful outcome measure for evaluating novel therapeutics targeting attention and executive functions after TBI.
Language	English
Publishing date	2023-05-15
Publishing country	United States
Document type	Journal Article
ISSN	2689-288X
ISSN (online)	2689-288X
DOI	10.1089/neur.2022.0068
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Article ; Online: Reduction in Constitutively Activated Auditory Brainstem Microglia in Aging and Alzheimer's Disease.

Journal of Alzheimer's disease : JAD

2024 Volume 99, Issue 1, Page(s) 307–319

Abstract: Background: Alzheimer's disease (AD) pathology is considered to begin in the brainstem, and cerebral microglia are known to play a critical role in AD pathogenesis, yet little is known about brainstem microglia in AD. Translocator protein (TSPO) PET, ... ...

Abstract	Background: Alzheimer's disease (AD) pathology is considered to begin in the brainstem, and cerebral microglia are known to play a critical role in AD pathogenesis, yet little is known about brainstem microglia in AD. Translocator protein (TSPO) PET, sensitive to activated microglia, shows high signal in dorsal brainstem in humans, but the precise location and clinical correlates of this signal are unknown. Objective: To define age and AD associations of brainstem TSPO PET signal in humans. Methods: We applied new probabilistic maps of brainstem nuclei to quantify PET-measured TSPO expression over the whole brain including brainstem in 71 subjects (43 controls scanned using 11C-PK11195; 20 controls and 8 AD subjects scanned using 11C-PBR28). We focused on inferior colliculi (IC) because of visually-obvious high signal in this region, and potential relevance to auditory dysfunction in AD. We also assessed bilateral cortex. Results: TSPO expression was normally high in IC and other brainstem regions. IC TSPO was decreased with aging (p = 0.001) and in AD subjects versus controls (p = 0.004). In cortex, TSPO expression was increased with aging (p = 0.030) and AD (p = 0.033). Conclusions: Decreased IC TSPO expression with aging and AD-an opposite pattern than in cortex-highlights underappreciated regional heterogeneity in microglia phenotype, and implicates IC in a biological explanation for strong links between hearing loss and AD. Unlike in cerebrum, where TSPO expression is considered pathological, activated microglia in IC and other brainstem nuclei may play a beneficial, homeostatic role. Additional study of brainstem microglia in aging and AD is needed.
MeSH term(s)	Humans ; Alzheimer Disease/pathology ; Alzheimer Disease/metabolism ; Microglia/metabolism ; Microglia/pathology ; Male ; Aged ; Female ; Aging/pathology ; Brain Stem/metabolism ; Brain Stem/pathology ; Receptors, GABA/metabolism ; Aged, 80 and over ; Middle Aged ; Positron-Emission Tomography ; Isoquinolines ; Adult
Chemical Substances	Receptors, GABA ; TSPO protein, human ; Isoquinolines ; PK 11195 (YNF83VN1RL)
Language	English
Publishing date	2024-04-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-231312
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