Publications by authors named "Paul M Vespa"

125 Publications

Ultrasonic thalamic stimulation in chronic disorders of consciousness.

Brain Stimul 2021 Jan 16;14(2):301-303. Epub 2021 Jan 16.

Department of Psychology, University of California Los Angeles, Los Angeles, CA, 90095, USA; Brain Injury Research Center (BIRC), Department of Neurosurgery, University of California Los Angeles, CA, 90095, USA; Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA, 90095, USA. Electronic address:

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http://dx.doi.org/10.1016/j.brs.2021.01.008DOI Listing
January 2021

Memory in repeat sports-related concussive injury and single-impact traumatic brain injury.

Brain Inj 2020 10 29;34(12):1666-1673. Epub 2020 Sep 29.

Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine , Los Angeles, California, USA.

Repeat sports-related concussive/subconcussive injury (RC/SCI) is related to memory impairment. : We sought to determine memory differences between persons with RC/SCI, moderate-to-severe single-impact traumatic brain injury (SI-TBI), and healthy controls. MRI scans from a subsample of participants with SI-TBI were used to identify the neuroanatomical correlates of observed memory process differences between the brain injury groups. : Both brain injury groups evidenced worse learning and recall in contrast to controls, although SI-TBI group had poorer memory than the RC/SCI group. Regarding memory process differences, in contrast to controls, the SI-TBI group evidenced difficulties with encoding, consolidation, and retrieval, while the RC/SCI group showed deficits in consolidation and retrieval. Delayed recall was predicted by encoding, with consolidation as a secondary predictor in the SI-TBI group. In the RC/SCI group, delayed recall was only predicted by consolidation. MRI data showed that the consolidation index we used mapped onto hippocampal atrophy. : RC/SCI is primarily associated with consolidation deficits, which differs from SI-TBI. Given the role of the hippocampus in memory consolidation and the fact that hyperphosphorylated tau tends to accumulate in the medial temporal lobe in RC/SCI, consolidation deficits may be a cognitive marker of chronic traumatic encephalopathy in athletes.
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http://dx.doi.org/10.1080/02699052.2020.1825806DOI Listing
October 2020

The subcortical basis of outcome and cognitive impairment in TBI: A longitudinal cohort study.

Neurology 2020 10 9;95(17):e2398-e2408. Epub 2020 Sep 9.

From the Department of Psychology (E.S.L., M.M.M.) and Department of Psychiatry and Biobehavioral Sciences (M.J.W.), University of California Los Angeles; Brain Injury Research Center (E.S.L., M.J.W., V.S., C.R., D.L.M., M.B.-B., P.M.V., M.M.M.), Department of Neurosurgery, and Department of Neurology (M.B.-B, P.M.V., M.M.M.), David Geffen School of Medicine at UCLA; and Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (M.J.W.), Torrance, CA.

Objective: To understand how, biologically, the acute event of traumatic brain injury gives rise to a long-term disease, we address the relationship between evolving cortical and subcortical brain damage and measures of functional outcome and cognitive functioning at 6 months after injury.

Methods: For this longitudinal analysis, clinical and MRI data were collected in a tertiary neurointensive care setting in a continuous sample of 157 patients surviving moderate to severe traumatic brain injury between 2000 and 2018. For each patient, we collected T1- and T2-weighted MRI data acutely and at the 6-month follow-up, as well as acute measures of injury severity (Glasgow Coma Scale), follow-up measures of functional impairment (Glasgow Outcome Scale-extended), and, in a subset of patients, neuropsychological measures of attention, executive functions, and episodic memory.

Results: In the final cohort of 113 subcortical and 92 cortical datasets that survived (blind) quality control, extensive atrophy was observed over the first 6 months after injury across the brain. However, only atrophy within subcortical regions, particularly in the left thalamus, was associated with functional outcome and neuropsychological measures of attention, executive functions, and episodic memory. Furthermore, when brought together in an analytical model, longitudinal brain measurements could distinguish good from bad outcome with 90% accuracy, whereas acute brain and clinical measurements alone could achieve only 20% accuracy.

Conclusion: Despite great injury heterogeneity, secondary thalamic pathology is a measurable minimum common denominator mechanism directly relating biology to clinical measures of outcome and cognitive functioning, potentially linking the acute event and the longer-term disease of traumatic brain injury.
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http://dx.doi.org/10.1212/WNL.0000000000010825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682912PMC
October 2020

Accounting for Changing Structure in Functional Network Analysis of TBI Patients.

Front Syst Neurosci 2020 7;14:42. Epub 2020 Aug 7.

Department of Psychology, University of California, Los Angeles, Los Angeles, CA, United States.

Over the last 15 years, network analysis approaches based on MR data have allowed a renewed understanding of the relationship between brain function architecture and consciousness. Application of this approach to Disorders of Consciousness (DOC) highlights the relationship between specific aspects of network topology and levels of consciousness. Nonetheless, such applications do not acknowledge that DOC patients present with a dramatic level of heterogeneity in structural connectivity (SC) across groups (e.g., etiology, diagnostic categories) and within individual patients (e.g., over time), which possibly affects the level and quality of functional connectivity (FC) patterns that can be expressed. In addition, it is rarely acknowledged that the most frequently employed outcome metrics in the study of brain connectivity (e.g., degree distribution, inter- or intra-resting state network connectivity, and clustering coefficient) are interrelated and cannot be assumed to be independent of each other. We present empirical data showing that, when the two points above are not taken into consideration with an appropriate analytic model, it can lead to a misinterpretation of the role of each outcome metric in the graph's structure and thus misinterpretation of FC results. We show that failing to account for either SC or the inter-relation between outcome measures can lead to inflated false positives (FP) and/or false negatives (FN) in inter- or intra-resting state network connectivity results (defined, respectively, as a positive or negative result in network connectivity that is present when not accounting for SC and/or outcome measure inter-relation, but becomes not significant when accounting for all variables). Overall, we find that unconscious patients have lower rates of FP and FN for within cortical connectivity, lower rates of FN for cortico-subcortical connectivity, and lower rates of FP for within subcortical connectivity. These lower rates in unconscious patients may reflect differences in their triadic closure and SC metrics, which bias the interpretations of the inter- or intra-resting state network connectivity if the SC metrics and triadic closure are not modeled. We suggest that future studies of functional connectivity in DOC patients (i) incorporate where possible SC metrics and (ii) properly account for the intercorrelated nature of outcome variables.
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http://dx.doi.org/10.3389/fnsys.2020.00042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427444PMC
August 2020

Early brain biomarkers of post-traumatic seizures: initial report of the multicentre epilepsy bioinformatics study for antiepileptogenic therapy (EpiBioS4Rx) prospective study.

J Neurol Neurosurg Psychiatry 2020 Nov 26;91(11):1154-1157. Epub 2020 Aug 26.

Psychology, University of California Los Angeles, Los Angeles, California, USA

Background: Traumatic brain injury (TBI) causes early seizures and is the leading cause of post-traumatic epilepsy. We prospectively assessed structural imaging biomarkers differentiating patients who develop seizures secondary to TBI from patients who do not.

Design: Multicentre prospective cohort study starting in 2018. Imaging data are acquired around day 14 post-injury, detection of seizure events occurred early (within 1 week) and late (up to 90 days post-TBI).

Results: From a sample of 96 patients surviving moderate-to-severe TBI, we performed shape analysis of local volume deficits in subcortical areas (analysable sample: 57 patients; 35 no seizure, 14 early, 8 late) and cortical ribbon thinning (analysable sample: 46 patients; 29 no seizure, 10 early, 7 late). Right hippocampal volume deficit and inferior temporal cortex thinning demonstrated a significant effect across groups. Additionally, the degree of left frontal and temporal pole thinning, and clinical score at the time of the MRI, could differentiate patients experiencing early seizures from patients not experiencing them with 89% accuracy.

Conclusions And Relevance: Although this is an initial report, these data show that specific areas of localised volume deficit, as visible on routine imaging data, are associated with the emergence of seizures after TBI.
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http://dx.doi.org/10.1136/jnnp-2020-322780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572686PMC
November 2020

Evaluating the Clinical Impact of Rapid Response Electroencephalography: The DECIDE Multicenter Prospective Observational Clinical Study.

Crit Care Med 2020 Sep;48(9):1249-1257

Department of Neurology, Harvard Medical School, Boston, MA.

Objectives: To measure the diagnostic accuracy, timeliness, and ease of use of Ceribell rapid response electroencephalography. We assessed physicians' diagnostic assessments and treatment plans before and after rapid response electroencephalography assessment. Primary outcomes were changes in physicians' diagnostic and therapeutic decision making and their confidence in these decisions based on the use of the rapid response electroencephalography system. Secondary outcomes were time to electroencephalography, setup time, ease of use, and quality of electroencephalography data.

Design: Prospective multicenter nonrandomized observational study.

Setting: ICUs in five academic hospitals in the United States.

Subjects: Patients with encephalopathy suspected of having nonconvulsive seizures and physicians evaluating these patients.

Interventions: Physician bedside assessment of sonified electroencephalography (30 s from each hemisphere) and visual electroencephalography (60 s) using rapid response electroencephalography.

Measurements And Main Results: Physicians (29 fellows or residents, eight attending neurologists) evaluated 181 ICU patients; complete clinical and electroencephalography data were available in 164 patients (average 58.6 ± 18.7 yr old, 45% females). Relying on rapid response electroencephalography information at the bedside improved the sensitivity (95% CI) of physicians' seizure diagnosis from 77.8% (40.0%, 97.2%) to 100% (66.4%, 100%) and the specificity (95% CI) of their diagnosis from 63.9% (55.8%, 71.4%) to 89% (83.0%, 93.5%). Physicians' confidence in their own diagnosis and treatment plan were also improved. Time to electroencephalography (median [interquartile range]) was 5 minutes (4-10 min) with rapid response electroencephalography while the conventional electroencephalography was delayed by several hours (median [interquartile range] delay = 239 minutes [134-471 min] [p < 0.0001 using Wilcoxon signed rank test]). The device was rated as easy to use (mean ± SD: 4.7 ± 0.6 [1 = difficult, 5 = easy]) and was without serious adverse effects.

Conclusions: Rapid response electroencephalography enabled timely and more accurate assessment of patients in the critical care setting. The use of rapid response electroencephalography may be clinically beneficial in the assessment of patients with high suspicion for nonconvulsive seizures and status epilepticus.
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http://dx.doi.org/10.1097/CCM.0000000000004428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735649PMC
September 2020

The Curing Coma Campaign: Framing Initial Scientific Challenges-Proceedings of the First Curing Coma Campaign Scientific Advisory Council Meeting.

Neurocrit Care 2020 08;33(1):1-12

Department of Neurology and Neurotherapeutics, University of Texas Southwestern, Dallas, TX, USA.

Coma and disordered consciousness are common manifestations of acute neurological conditions and are among the most pervasive and challenging aspects of treatment in neurocritical care. Gaps exist in patient assessment, outcome prognostication, and treatment directed specifically at improving consciousness and cognitive recovery. In 2019, the Neurocritical Care Society (NCS) launched the Curing Coma Campaign in order to address the "grand challenge" of improving the management of patients with coma and decreased consciousness. One of the first steps was to bring together a Scientific Advisory Council including coma scientists, neurointensivists, neurorehabilitationists, and implementation experts in order to address the current scientific landscape and begin to develop a framework on how to move forward. This manuscript describes the proceedings of the first Curing Coma Campaign Scientific Advisory Council meeting which occurred in conjunction with the NCS Annual Meeting in October 2019 in Vancouver. Specifically, three major pillars were identified which should be considered: endotyping of coma and disorders of consciousness, biomarkers, and proof-of-concept clinical trials. Each is summarized with regard to current approach, benefits to the patient, family, and clinicians, and next steps. Integration of these three pillars will be essential to the success of the Curing Coma Campaign as will expanding the "curing coma community" to ensure broad participation of clinicians, scientists, and patient advocates with the goal of identifying and implementing treatments to fundamentally improve the outcome of patients.
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http://dx.doi.org/10.1007/s12028-020-01028-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392933PMC
August 2020

A systematic investigation of the association between network dynamics in the human brain and the state of consciousness.

Neurosci Conscious 2020 14;2020(1):niaa008. Epub 2020 Jun 14.

Department of Psychology, University of California Los Angeles, Los Angeles, CA 90095, USA.

An increasing amount of studies suggest that brain dynamics measured with resting-state functional magnetic resonance imaging (fMRI) are related to the state of consciousness. However, the challenge of investigating neuronal correlates of consciousness is the confounding interference between (recovery of) consciousness and behavioral responsiveness. To address this issue, and validate the interpretation of prior work linking brain dynamics and consciousness, we performed a longitudinal fMRI study in patients recovering from coma. Patients were assessed twice, 6 months apart, and assigned to one of two groups. One group included patients who were unconscious at the first assessment but regained consciousness and improved behavioral responsiveness by the second assessment. The other group included patients who were already conscious and improved only behavioral responsiveness. While the two groups were matched in terms of the average increase in behavioral responsiveness, only one group experienced a categorical change in their state of consciousness allowing us to partially dissociate consciousness and behavioral responsiveness. We find the variance in network metrics to be systematically different across states of consciousness, both within and across groups. Specifically, at the first assessment, conscious patients exhibited significantly greater variance in network metrics than unconscious patients, a difference that disappeared once all patients had recovered consciousness. Furthermore, we find a significant increase in dynamics for patients who regained consciousness over time, but not for patients who only improved responsiveness. These findings suggest that changes in brain dynamics are indeed linked to the state of consciousness and not just to a general level of behavioral responsiveness.
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http://dx.doi.org/10.1093/nc/niaa008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293819PMC
June 2020

Alternative substrate metabolism depends on cerebral metabolic state following traumatic brain injury.

Exp Neurol 2020 07 2;329:113289. Epub 2020 Apr 2.

UCLA Department of Neurosurgery, USA; UCLA Interdepartmental Program for Neuroscience, USA; UCLA Brain Injury Research Center, USA.

Decreases in energy metabolism following traumatic brain injury (TBI) are attributed to impairment of glycolytic flux and oxidative phosphorylation. Glucose utilization post-TBI is decreased while administration of alternative substrates has been shown to be neuroprotective. Changes in energy metabolism following TBI happens in two phases; a period of hyper-metabolism followed by prolonged hypo-metabolism. It is not understood how different cerebral metabolic states may impact substrate metabolism and ultimately mitochondrial function. Adult male or female Sprague Dawley rats were given sham surgery or controlled cortical impact (CCI) and were assigned one of two administration schemes. Glucose, lactate or beta-hydroxybutyrate (BHB) were infused i.v. either starting immediately after injury or beginning 6 h post-injury for 3 h to reflect the hyper- and hypo-metabolic stages. Animals were euthanized 24 h post-injury. The peri-contusional cortex was collected and assayed for mitochondrial respiration peroxide production, and citrate synthase activity. Tissue acetyl-CoA, ATP, glycogen and HMGB1 were also quantified. Sex differences were observed in injury pattern. Administration based on cerebral metabolic state identified that only early lactate and late BHB improved mitochondrial function and peroxide production and TCA cycle intermediates in males. In contrast, both early and late BHB had deleterious effects on all aspects of metabolic measurements in females. These data stress there is no one optimal alternative substrate, but rather the fuel type used should be guided by both cerebral metabolic state and sex.
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http://dx.doi.org/10.1016/j.expneurol.2020.113289DOI Listing
July 2020

Blood Pressure Variability Predicts Poor In-Hospital Outcome in Spontaneous Intracerebral Hemorrhage.

Stroke 2019 08 20;50(8):2023-2029. Epub 2019 Jun 20.

Department of Statistics and Applied Probability, University of California, Santa Barbara (X.L., A.P.).

Background and Purpose- There is increasing evidence that higher systolic blood pressure variability (SBPV) may be associated with poor outcome in patients with intracerebral hemorrhage (ICH). We explored the association between SBPV and in-hospital ICH outcome. Methods- We collected 10-years of consecutive data of spontaneous ICH patients at 2 healthcare systems. Demographics, medical history, laboratory tests, computed tomography scan data, in-hospital treatments, and neurological and functional assessments were recorded. Blood pressure recordings were extracted up to 24 hours postadmission. SBPV was measured using SD, coefficient of variation, successive variation (SV), range and 1 novel index termed functional SV. The effects of SBPV on the functional outcome at discharge were evaluated by multivariate logistic and ordinal regression analyses for dichotomous and trichotomous modified Rankin Scale categorizations, respectively. In secondary analyses, associations between SBPV, history of hypertension, and hematoma expansion were explored. Results- The analysis included 762 subjects. All 5 SBPV indices were significantly associated with the probability of unfavorable outcome (modified Rankin Scale score, 4-6) in logistic models. In ordinal models, SD, coefficient of variation, range, and functional SV were found to have a significant effect on the probabilities of poor (modified Rankin Scale score, 3-4) and severe/death (modified Rankin Scale score, 5-6) outcomes. Normotensive patients had significantly lower mean SBPV compared with the untreated-hypertension cohort for all SBPV indices and compared with treated-hypertension patients for 3 out of 5 SBPV indices. Lower mean SBPV of treated-hypertension subjects compared with untreated-hypertension subjects was only detected in the SV and functional SV indices (P=0.045). None of the SBPV indices were significantly associated with the probability of hematoma expansion. Conclusions- Higher SBPV in the first 24 hours of admission was associated with unfavorable in-hospital outcome among ICH patients. Further prospective studies are warranted to understand any cause-effect relationship and whether controlling for SBPV may improve the ICH outcome.
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http://dx.doi.org/10.1161/STROKEAHA.119.025514DOI Listing
August 2019

Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis.

N Engl J Med 2019 06;380(24):2327-2340

From the Departments of Neurology (M.R.W., V.D., S.A.J., F.C.C., J.M.G.), Biochemistry and Biophysics (H.A.S., K.C.Z., J.L.D.), Laboratory Medicine (S.A., G.Y., S.F., D.S., B.B., B.H., S.M., C.Y.C.), and Epidemiology and Biostatistics (J.N.), the Department of Medicine, Division of Infectious Diseases (C.L., C.Y.C.), the Department of Medicine, Division of Hospital Medicine (A.B.), and Weill Institute for Neurosciences (M.R.W., V.D., S.A.J., F.C.C., J.M.G.), University of California, San Francisco (UCSF), UCSF-Abbott Viral Diagnostics and Discovery Center (S.A., G.Y., S.F., D.S., B.B., C.Y.C.), the Chan Zuckerberg Biohub (C.L., J.L.D.), and Zuckerberg San Francisco General Hospital (B.H.), San Francisco, the School of Public Health, University of California, Berkeley, Berkeley (B.D.F.), Children's Hospital Los Angeles (S.N.N., J.B., J.D.B.), the Department of Medicine, Division of Infectious Diseases (J.M., M.C., T.V., P.R.A., J.D.K.), and the Departments of Neurology (P.M.V.) and Pathology and Laboratory Medicine (S.C., R.M.H.), University of California, Los Angeles, Los Angeles, and the Departments of Pathology and Laboratory Medicine (C.D.G., F.M., N.A.O., C.R.P.) and Neurological Surgery (L.L.Z.) and the Department of Internal Medicine, Division of Infectious Diseases (S.H.C., C.R.P.), University of California, Davis, Davis - all in California; the Children's National Medical Center and George Washington University School of Medicine, Washington, DC (R.L.D.); St. Jude Children's Research Hospital, Memphis, TN (R.D., G.M., R.H.); and Children's Hospital Colorado, Aurora (K.M., S.R.D.).

Background: Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test.

Methods: In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review.

Results: We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment.

Conclusions: Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, NCT02910037.).
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http://dx.doi.org/10.1056/NEJMoa1803396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764751PMC
June 2019

Critical Care Ultrasound Should Not Be a Priority First-Line Assessment Tool in the Management of Neurocritically Ill Patients.

Crit Care Med 2019 06;47(6):837-839

Division of Neurosurgery and Department of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, CA.

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http://dx.doi.org/10.1097/CCM.0000000000003736DOI Listing
June 2019

Antiseizure medications in critical care: an update.

Curr Opin Crit Care 2019 04;25(2):117-125

Division of Neurocritical Care, Department of Neurology.

Purpose Of Review: Seizures and status epilepticus are very common diagnoses in the critically ill patient and are associated with significant morbidity and mortality. There is an abundance of research on the utility of antiseizure medications in this setting, but limited randomized-controlled trials to guide the selection of medications in these patients. This review examines the current guidelines and treatment strategies for status epilepticus and provides an update on newer antiseizure medications in the critical care settings.

Recent Findings: Time is brain applies to status epilepticus, with delays in treatment corresponding with worsened outcomes. Establishing standardized treatment protocols within a health system, including prehospital treatment, may lead to improved outcomes. Once refractory status epilepticus is established, continuous deep sedation with intravenous anesthetic agents should be effective. In cases, which prove highly refractory, novel approaches should be considered, with recent data suggesting multiple recently approved antiseizure medications, appropriate therapeutic options, as well as novel approaches to upregulate extrasynaptic γ-aminobutyric acid channels with brexanolone.

Summary: Although there are many new treatments to consider for seizures and status epilepticus in the critically ill patient, the most important predictor of outcome may be rapid diagnosis and treatment. There are multiple new and established medications that can be considered in the treatment of these patients once status epilepticus has become refractory, and a multidrug regimen will often be necessary.
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http://dx.doi.org/10.1097/MCC.0000000000000587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800132PMC
April 2019

pH-weighted molecular MRI in human traumatic brain injury (TBI) using amine proton chemical exchange saturation transfer echoplanar imaging (CEST EPI).

Neuroimage Clin 2019 25;22:101736. Epub 2019 Feb 25.

Dept. of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Cerebral acidosis is a consequence of secondary injury mechanisms following traumatic brain injury (TBI), including excitotoxicity and ischemia, with potentially significant clinical implications. However, there remains an unmet clinical need for technology for non-invasive, high resolution pH imaging of human TBI for studying metabolic changes following injury. The current study examined 17 patients with TBI and 20 healthy controls using amine chemical exchange saturation transfer echoplanar imaging (CEST EPI), a novel pH-weighted molecular MR imaging technique, on a clinical 3T MR scanner. Results showed significantly elevated pH-weighted image contrast (MTR at 3 ppm) in areas of T2 hyperintensity or edema (P < 0.0001), and a strong negative correlation with Glasgow Coma Scale (GCS) at the time of the MRI exam (R = 0.4777, P = 0.0021), Glasgow Outcome Scale - Extended (GOSE) at 6 months from injury (R = 0.5334, P = 0.0107), and a non-linear correlation with the time from injury to MRI exam (R = 0.6317, P = 0.0004). This evidence suggests clinical feasibility and potential value of pH-weighted amine CEST EPI as a high-resolution imaging tool for identifying tissue most at risk for long-term damage due to cerebral acidosis.
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http://dx.doi.org/10.1016/j.nicl.2019.101736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396390PMC
December 2019

Neurocritical Care Coding for Neurologists.

Continuum (Minneap Minn) 2018 12;24(6):1800-1809

Coding specifies the work performed when providing patient care. Critical care services mostly use code 99291, and other codes specify additional time and procedures. Current Procedural Terminology defines critically ill as "a high probability of imminent or life-threatening deterioration in the patient's condition," a condition necessary for use of the critical care code. A patient may be critically ill for neurologic reasons even when stable from a cardiorespiratory status. Rules govern who can use these codes, whether they can be used by more than one physician, the locations where the code may be used, and what services are included and excluded. Physicians need to document the medical necessity of visits and nature of critical illness or high-risk medical decision making because auditors may not understand the nature of serious neurologic illness.
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http://dx.doi.org/10.1212/CON.0000000000000667DOI Listing
December 2018

The epilepsy bioinformatics study for anti-epileptogenic therapy (EpiBioS4Rx) clinical biomarker: Study design and protocol.

Neurobiol Dis 2019 03 23;123:110-114. Epub 2018 Jul 23.

David Geffen School of Medicine at UCLA, United States.

The Epilepsy Bioinformatics Study for Anti-epileptogenic Therapy (EpiBioS4Rx) is a longitudinal prospective observational study funded by the National Institute of Health (NIH) to discover and validate observational biomarkers of epileptogenesis after traumatic brain injury (TBI). A multidisciplinary approach has been incorporated to investigate acute electrical, neuroanatomical, and blood biomarkers after TBI that may predict the development of post-traumatic epilepsy (PTE). We plan to enroll 300 moderate-severe TBI patients with a frontal and/or temporal lobe hemorrhagic contusion. Acute evaluation with blood, imaging and electroencephalographic monitoring will be performed and then patients will be tracked for 2 years to determine the incidence of PTE. Validation of selected biomarkers that are discovered in planned animal models will be a principal feature of this work. Specific hypotheses regarding the discovery of biomarkers have been set forth in this study. An international cohort of 13 centers spanning 2 continents will be developed to facilitate this study, and for future interventional studies.
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http://dx.doi.org/10.1016/j.nbd.2018.07.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344322PMC
March 2019

Acute EEG spectra characteristics predict thalamic atrophy after severe TBI.

J Neurol Neurosurg Psychiatry 2019 05 28;90(5):617-619. Epub 2018 Jun 28.

Department of Psychology, University of California, Los Angeles, Los Angeles, California, USA

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http://dx.doi.org/10.1136/jnnp-2017-317829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310668PMC
May 2019

Network Analysis in Disorders of Consciousness: Four Problems and One Proposed Solution (Exponential Random Graph Models).

Front Neurol 2018 12;9:439. Epub 2018 Jun 12.

Department of Psychology, University of California, Los Angeles, Los Angeles, CA, United States.

In recent years, the study of the neural basis of consciousness, particularly in the context of patients recovering from severe brain injury, has greatly benefited from the application of sophisticated network analysis techniques to functional brain data. Yet, current graph theoretic approaches, as employed in the neuroimaging literature, suffer from four important shortcomings. First, they require arbitrary fixing of the number of connections (i.e., density) across networks which are likely to have different "natural" (i.e., stable) density (e.g., patients vs. controls, vegetative state vs. minimally conscious state patients). Second, when describing networks, they do not control for the fact that many characteristics are interrelated, particularly some of the most popular metrics employed (e.g., nodal degree, clustering coefficient)-which can lead to spurious results. Third, in the clinical domain of disorders of consciousness, there currently are no methods for incorporating structural connectivity in the characterization of functional networks which clouds the interpretation of functional differences across groups with different underlying pathology as well as in longitudinal approaches where structural reorganization processes might be operating. Finally, current methods do not allow assessing the dynamics of network change over time. We present a different framework for network analysis, based on Exponential Random Graph Models, which overcomes the above limitations and is thus particularly well suited for clinical populations with disorders of consciousness. We demonstrate this approach in the context of the longitudinal study of recovery from coma. First, our data show that throughout recovery from coma, brain graphs vary in their natural level of connectivity (from 10.4 to 14.5%), which conflicts with the standard approach of imposing arbitrary and equal density thresholds across networks (e.g., time-points, subjects, groups). Second, we show that failure to consider the interrelation between network measures does lead to spurious characterization of both inter- and intra-regional brain connectivity. Finally, we show that Separable Temporal ERGM can be employed to describe network dynamics over time revealing the specific pattern of formation and dissolution of connectivity that accompany recovery from coma.
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http://dx.doi.org/10.3389/fneur.2018.00439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005847PMC
June 2018

Education Research: Variation in priorities for neurocritical care education expressed across role groups.

Neurology 2018 06;90(24):1117-1122

From Tulane University School of Medicine (A.S.C.), New Orleans, LA; Department of Neurology (S.I.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (M.A.K.), University of Pennsylvania, Philadelphia; Department of Public Health Sciences (C.J.J.), Loyola University, Chicago, IL; Departments of Neurology and Neurotherapeutics (S.A.F., C.E.H.) and Anesthesiology, Neurology, and Neurosurgery (D.L.M.), UT Southwestern, Dallas, TX; Department of Neurology (M.B.M.), Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Neurology (D.P.L.), Lahey Clinic, Burlington, MA; Departments of Neurology and Neurosurgery (P.M.V.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Departments of Critical Care Medicine, Neurology & Neurosurgery (L.A.S.), University of Pittsburgh School of Medicine/UPMC, PA; and Department of Neurology (E.S.R.), Massachusetts General Hospital, Boston.

Objective: To define expectations for neurocritical care (NCC) core competencies vs competencies considered within the domain of other subspecialists.

Methods: An electronic survey was disseminated nationally to NCC nurses, physicians, fellows, and neurology residents through Accreditation Council for Graduate Medical Education neurology residency program directors, United Council for Neurologic Subspecialties neurocritical care fellowship program directors, and members of the Neurocritical Care Society.

Results: A total of 268 neurocritical care providers and neurology residents from 30 institutions responded. Overall, >90% supported NCC graduates independently interpreting and managing systemic and cerebral hemodynamic data, or performing brain death determination, neurovascular ultrasound, vascular access, and airway management. Over 75% endorsed that NCC graduates should independently interpret EEG and perform bronchoscopies. Fewer but substantial respondents supported graduates being independent performing intracranial bolt (45.8%), ventriculostomy (39.0%), tracheostomy (39.8%), or gastrostomy (19.1%) procedures. Trainees differed from physicians and program directors, respectively, by advocating independence in EEG interpretation (92.8%, 61.8%, and 65.3%) and PEG placement (29.3%, 9.1%, and 8.5%).

Conclusions: Broad support exists across NCC role groups for wide-ranging NCC competencies including skills often performed by other neurology and non-neurology subspecialties. Variations highlight natural divergences in expectations among trainee, physician, and nurse role groups. These results establish expectations for core competencies within NCC and initiate dialogue across subspecialties about best practice standards for the spectrum of critically ill patients requiring neurologic care.
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http://dx.doi.org/10.1212/WNL.0000000000005682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996833PMC
June 2018

Early seizures and temporal lobe trauma predict post-traumatic epilepsy: A longitudinal study.

Neurobiol Dis 2019 03 1;123:115-121. Epub 2018 Jun 1.

David Geffen School of Medicine at UCLA, United States. Electronic address:

Objective: Injury severity after traumatic brain injury (TBI) is a well-established risk factor for the development of post-traumatic epilepsy (PTE). However, whether lesion location influences the susceptibility of seizures and development of PTE longitudinally has yet to be defined. We hypothesized that lesion location, specifically in the temporal lobe, would be associated with an increased incidence of both early seizures and PTE. As secondary analysis measures, we assessed the degree of brain atrophy and functional recovery, and performed a between-group analysis, comparing patients who developed PTE with those who did not develop PTE.

Methods: We assessed early seizure incidence (n = 90) and longitudinal development of PTE (n = 46) in a prospective convenience sample of patients with moderate-severe TBI. Acutely, patients were monitored with prospective cEEG and a high-resolution Magnetic Resonance Imaging (MRI) scan for lesion location classification. Chronically, patients underwent a high-resolution MRI, clinical assessment, and were longitudinally monitored for development of epilepsy for a minimum of 2 years post-injury.

Results: Early seizures, occurring within the first week post-injury, occurred in 26.7% of the patients (n = 90). Within the cohort of subjects who had evidence of early seizures (n = 24), 75% had a hemorrhagic temporal lobe injury on admission. For longitudinal analyses (n = 46), 45.7% of patients developed PTE within a minimum of 2 years post-injury. Within the cohort of subjects who developed PTE (n = 21), 85.7% had a hemorrhagic temporal lobe injury on admission and 38.1% had early (convulsive or non-convulsive) seizures on cEEG monitoring during their acute ICU stay. In a between-group analysis, patients with PTE (n = 21) were more likely than patients who did not develop PTE (n = 25) to have a hemorrhagic temporal lobe injury (p < 0.001), worse functional recovery (p = 0.003), and greater temporal lobe atrophy (p = 0.029).

Conclusion: Our results indicate that in a cohort of patients with a moderate-severe TBI, 1) lesion location specificity (e.g. the temporal lobe) is related to both a high incidence of early seizures and longitudinal development of PTE, 2) early seizures, whether convulsive or non-convulsive in nature, are associated with an increased risk for PTE development, and 3) patients who develop PTE have greater chronic temporal lobe atrophy and worse functional outcomes, compared to those who do not develop PTE, despite matched injury severity characteristics. This study provides the foundation for a future prospective study focused on elucidating the mechanisms and risk factors for epileptogenesis.
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http://dx.doi.org/10.1016/j.nbd.2018.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274611PMC
March 2019

Cerebral microhemorrhages due to traumatic brain injury and their effects on the aging human brain.

Neurobiol Aging 2018 06 6;66:158-164. Epub 2018 Mar 6.

Departments of Neurosurgery and Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Although cerebral microbleeds (CMBs) are frequently associated with traumatic brain injury (TBI), their effects on clinical outcome after TBI remain controversial and poorly understood, particularly in older adults. Here we (1) highlight major challenges and opportunities associated with studying the effects of TBI-mediated CMBs; (2) review the evidence on their potential effects on cognitive and neural outcome as a function of age at injury; and (3) suggest priorities for future research on understanding the clinical implications of CMBs. Although TBI-mediated CMBs are likely distinct from those due to cerebral amyloid angiopathy or other neurodegenerative diseases, the effects of these 2 CMB types on brain function may share common features. Furthermore, in older TBI victims, the incidence of TBI-mediated CMBs may approximate that of cerebral amyloid angiopathy-related CMBs, and thus warrants detailed study. Because the alterations effected by CMBs on brain structure and function are both unique and age-dependent, it seems likely that novel, age-tailored therapeutic approaches are necessary for the adequate clinical interpretation and treatment of these ubiquitous and underappreciated TBI sequelae.
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http://dx.doi.org/10.1016/j.neurobiolaging.2018.02.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924627PMC
June 2018

Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

J Neuroimaging 2018 05 27;28(3):283-288. Epub 2018 Feb 27.

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Background And Purpose: The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy.

Methods: We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes.

Results: Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P < .001), parenchymal hematoma (OR 20.57; 95% CI 5.64-74.99; P < .001), and poor outcome at discharge (OR 2.35; 95% CI 1.09-5.07; P = .03). The association of BBB disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome.

Conclusions: Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome.
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http://dx.doi.org/10.1111/jon.12504DOI Listing
May 2018

Traumatic Brain Injury Severity, Neuropathophysiology, and Clinical Outcome: Insights from Multimodal Neuroimaging.

Front Neurol 2017 5;8:530. Epub 2017 Oct 5.

Laboratory of Neuro Imaging, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.

Background: The relationship between the acute clinical presentation of patients with traumatic brain injury (TBI), long-term changes in brain structure prompted by injury and chronic functional outcome is insufficiently understood. In this preliminary study, we investigate how acute Glasgow coma score (GCS) and epileptic seizure occurrence after TBIs are statistically related to functional outcome (as quantified using the Glasgow Outcome Score) and to the extent of cortical thinning observed 6 months after the traumatic event.

Methods: Using multivariate linear regression, the extent to which the acute GCS and epileptic seizure occurrence (predictor variables) correlate with structural brain changes (relative cortical atrophy) was examined in a group of 33 TBI patients. The statistical significance of the correlation between relative cortical atrophy and the Glasgow Outcome Score was also investigated.

Results: A statistically significant correlative relationship between cortical thinning and the predictor variables (acute GCS and seizure occurrence) was identified in the study sample. Regions where the statistical model was found to have highest statistical reliability in predicting both gray matter atrophy and neurological outcome include the frontopolar, middle frontal, postcentral, paracentral, middle temporal, angular, and lingual gyri. In addition, relative atrophy and GOS were also found to be significantly correlated over large portions of the cortex.

Conclusion: This study contributes to our understanding of the relationship between clinical descriptors of acute TBI, the extent of injury-related chronic brain changes and neurological outcome. This is partly because the brain areas where cortical thinning was found to be correlated with GCS and with seizure occurrence are implicated in executive control, sensory function, motor acuity, memory, and language, all of which may be affected by TBI. Thus, our quantification suggests the existence of a statistical relationship between acute clinical presentation, on the one hand, and structural/functional brain features which are particularly susceptible to post-injury degradation, on the other hand.
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http://dx.doi.org/10.3389/fneur.2017.00530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633783PMC
October 2017

Restoration of thalamo-cortical connectivity after brain injury: recovery of consciousness, complex behavior, or passage of time?

J Neurosci Res 2018 04 12;96(4):671-687. Epub 2017 Aug 12.

Department of Psychology, University of California Los Angeles, Los Angeles, CA, 90095, USA.

In 2000, a landmark case report described the concurrent restoration of consciousness and thalamo-frontal connectivity after severe brain injury (Laureys et al., ). Being a single case however, this study could not disambiguate whether the result was specific to the restoration of consciousness per se as opposed to the return of complex cognitive function in general or simply the temporal evolution of post-injury pathophysiological events. To test whether the restoration of thalamo-cortical connectivity is specific to consciousness, 20 moderate-to-severe brain injury patients (from a recruited sample of 42) underwent resting-state functional magnetic resonance imaging within a week after injury and again six months later. As described in the single case report, we find thalamo-frontal connectivity to be increased at the chronic, compared with the acute, time-point. The increased connectivity was independent of whether patients had already recovered consciousness prior to the first assessment or whether they recovered consciousness in-between the two. Conversely, we did find an association between restoration of thalamo-frontal connectivity and the return of complex cognitive function. While we did replicate the findings of Laureys et al. (), our data suggests that the restoration of thalamo-frontal connectivity is not as tightly linked to the reemergence of consciousness per se. However, the degree to which the return of connectivity is linked to the return of complex cognitive function, or to the evolution of other time-dependent post-injury mechanisms, remains to be understood.
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http://dx.doi.org/10.1002/jnr.24115DOI Listing
April 2018

Quality improvement in neurology: Inpatient and emergency care quality measure set: Executive summary.

Neurology 2017 08 21;89(7):730-735. Epub 2017 Jul 21.

From the Department of Neurology (S.A.J.), University of California San Francisco; Vassar Brothers Medical Center (J.F.), Poughkeepsie, NY; Massachusetts General Hospital (A.C.), Department of Neurology, Boston; Department of Neurology (A.W.), Emory School of Medicine, Atlanta, GA; American Academy of Neurology (E.L.), Minneapolis, MN; and Department of Neurology (P.M.V.), University of California Los Angeles.

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http://dx.doi.org/10.1212/WNL.0000000000004230DOI Listing
August 2017

Inpatient quality metrics in neurology: A grand challenge.

Neurology 2017 08 21;89(7):646-649. Epub 2017 Jul 21.

From the Department of Neurology (P.M.V.), University of California Los Angeles; Vassar Brothers Medical Center (J.F.), Poughkeepsie, NY; and Department of Neurology (S.A.J.), University of California San Francisco.

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http://dx.doi.org/10.1212/WNL.0000000000004244DOI Listing
August 2017

Acute glucose and lactate metabolism are associated with cognitive recovery following traumatic brain injury.

J Neurosci Res 2018 04 13;96(4):696-701. Epub 2017 Jun 13.

University of California, Los Angeles, Department of Psychiatry and Biobehavioral Sciences.

Traumatic brain injury (TBI) is associated with acute cerebral metabolic crisis (ACMC). ACMC-related atrophy appears to be prominent in frontal and temporal lobes following moderate-to-severe TBI. This atrophy is correlated with poorer cognitive outcomes in TBI. The current study investigated ability of acute glucose and lactate metabolism to predict long-term recovery of frontal-temporal cognitive function in participants with moderate-to-severe TBI. Cerebral metabolic rate of glucose and lactate were measured by the Kety-Schmidt method on days 0-7 post-injury. Indices of frontal-temporal cognitive processing were calculated for six months post-injury; 12 months post-injury; and recovery (the difference between the six- and 12-month scores). Glucose and lactate metabolism were included in separate regression models, as they were highly intercorrelated. Also, glucose and lactate values were centered and averaged and included in a final regression model. Models for the prediction frontal-temporal cognition at six and 12 months post-injury were not significant. However, average glucose and lactate metabolism predicted recovery of frontal-temporal cognition, accounting for 23% and 22% of the variance, respectively. Also, maximum glucose metabolism, but not maximum lactate metabolism, was an inverse predictor in the recovery of frontal-temporal cognition, accounting for 23% of the variance. Finally, the average of glucose and lactate metabolism predicted frontal-temporal cognitive recovery, accounting for 22% of the variance. These data indicate that acute glucose and lactate metabolism both support cognitive recovery from TBI. Also, our data suggest that control of endogenous fuels and/or supplementation with exogenous fuels may have therapeutic potential for cognitive recovery from TBI.
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http://dx.doi.org/10.1002/jnr.24097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729060PMC
April 2018

Mild cognitive impairment and structural brain abnormalities in a sexagenarian with a history of childhood traumatic brain injury.

J Neurosci Res 2018 04 20;96(4):652-660. Epub 2017 May 20.

Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.

In this report, we present a case study involving an older, female patient with a history of pediatric traumatic brain injury (TBI). Magnetic resonance imaging and diffusion tensor imaging volumes were acquired from the volunteer in question, her brain volumetrics and morphometrics were extracted, and these were then systematically compared against corresponding metrics obtained from a large sample of older healthy control (HC) subjects as well as from subjects in various stages of mild cognitive impairment (MCI) and Alzheimer disease (AD). Our analyses find the patient's brain morphometry and connectivity most similar to those of patients classified as having early-onset MCI, in contrast to HC, late MCI, and AD samples. Our examination will be of particular interest to those interested in assessing the clinical course in older patients having suffered TBI earlier in life, in contradistinction to those who experience incidents of head injury during aging.
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http://dx.doi.org/10.1002/jnr.24084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696124PMC
April 2018

Lactate supplementation in severe traumatic brain injured adults by primed constant infusion of sodium L-lactate.

J Neurosci Res 2018 04 20;96(4):688-695. Epub 2017 May 20.

UCLA Brain Injury Research Center and the Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California, USA.

Carbohydrate fuel augmentation following traumatic brain injury may be a viable treatment to improve recovery when cerebral oxidative metabolism of glucose is depressed. We performed a primed constant sodium L-lactate infusion in 11 moderate to severely brain injured adults. Blood was collected before and periodically during the infusion study. We quantified global cerebral uptake of glucose and lactate and other systemic metabolites associated with energy metabolism. Our hypothesis was that cerebral lactate uptake, as measured by the arteriovenous difference of lactate (AVDlac), would increase in severely injured TBI patients in the neurocritical care unit. Infusion of sodium L-lactate changed net cerebral lactate release, where the arteriovenous difference of lactate is negative, to net cerebral lactate uptake. Results from a mixed effects model of AVDlac with the fixed effects of infusion time, arterial lactate concentration, arterial glucose concentration and arteriovenous difference of glucose shows that doubling arterial lactate concentration (from .92 to 1.84 mM) results in an increase in AVDlac from -.078 mM to .090 mM. We did not detect changes in systemic glucose during the course of the infusion study and observed significant changes in alanine (30% [20 39]), glutamine (34% [24 43]), acetate (87% [60 113]), valine (40% [28 51]), and leucine (24% [16 32]) from baseline levels. Further studies are required to establish the impact of lactate supplementation on cerebral and systemic flux of lactate, on gluconeogenesis, and on the impact on cerebral energetics following injury. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jnr.24085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696121PMC
April 2018

Multi-delay ASL can identify leptomeningeal collateral perfusion in endovascular therapy of ischemic stroke.

Oncotarget 2017 Jan;8(2):2437-2443

Department of Neurology, UCLA Stroke Center, Los Angeles, California, USA.

Background And Purpose: Multi-delay arterial spin-labeling (ASL) perfusion imaging has been used as a promising modality to evaluate cerebral perfusion. Our aim was to assess the association of leptomeningeal collateral perfusion scores based on ASL parameters with outcome of endovascular treatment in patients with acute ischemic stroke (AIS) in the middle cerebral artery (MCA) territory.

Materials And Methods: ASL data at 4 post-labeling delay (PLD) times (PLD = 1.5, 2, 2.5, 3 s) were acquired during routine clinical magnetic resonance examination on AIS patients prior to endovascular treatment. A 3-point scale of leptomeningeal collateral perfusion grade on 10 anatomic regions was determined based on arterial transit times (ATT), cerebral blood flow (CBF), and arterial cerebral blood volume (CBV), estimated by the multi-delay ASL protocol. Based on a 90-day modified Rankin Scale (mRS), the patients were dichotomized to moderate/good (mRS 0-3) and poor outcome (mRS 4-6) and the regional collateral flow scores were compared.

Results: Fifty-five AIS patients with unilateral MCA stroke (mean 73.95±14.82 years) including 23 males were enrolled. Compared with poor outcome patients, patients with moderate to good outcomes had a significantly higher leptomeningeal collateral perfusion scores on CBV (3.01±2.11 vs. 1.82±1.51, p=0.024) but no differences on scores on CBF (2.31±1.61 vs. 1.66±1.32, p=0.231) and ATT (2.67±2.33 vs. 3.42±3.37, p=0.593).

Conclusions: Higher leptomeningeal collateral perfusion scores on CBV images by ASL may be a specific marker of clinical outcome after endovascular treatment in patients with acute MCA ischemic stroke. Further study with larger sample size is warranted.
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http://dx.doi.org/10.18632/oncotarget.13898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356813PMC
January 2017