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Publication Record


Spatial distribution of multiple sclerosis lesions in the cervical spinal cord.
Eden D, Gros C, Badji A, Dupont SM, De Leener B, Maranzano J, Zhuoquiong R, Liu Y, Granberg T, Ouellette R, Stawiarz L, Hillert J, Talbott J, Bannier E, Kerbrat A, Edan G, Labauge P, Callot V, Pelletier J, Audoin B, Rasoanandrianina H, Brisset JC, Valsasina P, Rocca MA, Filippi M, Bakshi R, Tauhid S, Prados F, Yiannakas M, Kearney H, Ciccarelli O, Smith SA, Andrada Treaba C, Mainero C, Lefeuvre J, Reich DS, Nair G, Shepherd TM, Charlson E, Tachibana Y, Hori M, Kamiya K, Chougar L, Narayanan S, Cohen-Adad J
(2019) Brain 142: 633-646
MeSH Terms: Adult, Brain, Cervical Cord, Disability Evaluation, Disease Progression, Female, Gray Matter, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Relapsing-Remitting, Spatial Analysis, Spinal Cord, Spinal Cord Diseases, White Matter
Show Abstract · Added March 30, 2020
Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T2- and T2*-weighted axial and sagittal MRI scans acquired at 3 or 7 T. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P < 0.001), which was further confirmed by absolute and normalized lesion volumes (P < 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P < 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P < 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P < 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups.
© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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Co-Occurrence of Post-Intensive Care Syndrome Problems Among 406 Survivors of Critical Illness.
Marra A, Pandharipande PP, Girard TD, Patel MB, Hughes CG, Jackson JC, Thompson JL, Chandrasekhar R, Ely EW, Brummel NE
(2018) Crit Care Med 46: 1393-1401
MeSH Terms: Activities of Daily Living, Aged, Cognitive Dysfunction, Critical Care, Critical Illness, Depression, Disability Evaluation, Female, Humans, Male, Middle Aged, Prospective Studies, Respiratory Insufficiency, Shock, Syndrome
Show Abstract · Added June 26, 2018
OBJECTIVES - To describe the frequency of co-occurring newly acquired cognitive impairment, disability in activities of daily livings, and depression among survivors of a critical illness and to evaluate predictors of being free of post-intensive care syndrome problems.
DESIGN - Prospective cohort study.
SETTING - Medical and surgical ICUs from five U.S. centers.
PATIENTS - Patients with respiratory failure or shock, excluding those with preexisting cognitive impairment or disability in activities of daily livings.
MEASUREMENTS AND MAIN RESULTS - At 3 and 12 months after hospital discharge, we assessed patients for cognitive impairment, disability, and depression. We categorized patients into eight groups reflecting combinations of cognitive, disability, and mental health problems. Using multivariable logistic regression, we modeled the association between age, education, frailty, durations of mechanical ventilation, delirium, and severe sepsis with the odds of being post-intensive care syndrome free. We analyzed 406 patients with a median age of 61 years and an Acute Physiology and Chronic Health Evaluation II of 23. At 3 and 12 months, one or more post-intensive care syndrome problems were present in 64% and 56%, respectively. Nevertheless, co-occurring post-intensive care syndrome problems (i.e., in two or more domains) were present in 25% at 3 months and 21% at 12 months. Post-intensive care syndrome problems in all three domains were present in only 6% at 3 months and 4% at 12 months. More years of education was associated with greater odds of being post-intensive care syndrome free (p < 0.001 at 3 and 12 mo). More severe frailty was associated with lower odds of being post-intensive care syndrome free (p = 0.005 at 3 mo and p = 0.048 at 12 mo).
CONCLUSIONS - In this multicenter cohort study, one or more post-intensive care syndrome problems were present in the majority of survivors, but co-occurring problems were present in only one out of four. Education was protective from post-intensive care syndrome problems and frailty predictive of the development of post-intensive care syndrome problems. Future studies are needed to understand better the heterogeneous subtypes of post-intensive care syndrome and to identify modifiable risk factors.
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15 MeSH Terms
Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal cord.
Conrad BN, Barry RL, Rogers BP, Maki S, Mishra A, Thukral S, Sriram S, Bhatia A, Pawate S, Gore JC, Smith SA
(2018) Brain 141: 1650-1664
MeSH Terms: Adult, Correlation of Data, Disability Evaluation, Female, Functional Laterality, Gray Matter, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Nerve Net, Oxygen, Spinal Cord, Young Adult
Show Abstract · Added March 26, 2019
Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.
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16 MeSH Terms
Physical impairment in patients with idiopathic inflammatory myopathies is associated with the American College of Rheumatology functional status measure.
Hanaoka BY, Cleary LC, Long DE, Srinivas A, Jenkins KA, Bush HM, Starnes CP, Rutledge M, Duan J, Fan Q, Fraser N, Crofford LJ
(2015) Clin Rheumatol 34: 1929-37
MeSH Terms: Adult, Aged, Body Composition, Disability Evaluation, Female, Humans, Male, Middle Aged, Motor Activity, Muscle, Skeletal, Myositis, Predictive Value of Tests, Retrospective Studies, Rheumatology, Severity of Illness Index, Societies, Medical, United States
Show Abstract · Added January 21, 2015
The goals of this study were to assess the predictive value of chart-abstracted American College of Rheumatology functional status (ACR-FS) with patient-reported ACR-FS and to relate it with measures of muscle function in a single-institution cohort of patients with idiopathic inflammatory myopathies (IIMs). Demographic and clinical data of 102 patients with IIMs regularly followed in the Rheumatology and Neurology Clinics at the University of Kentucky Medical Center between 2006 and 2012 were obtained through retrospective chart review. Clinical and functional status evaluation, muscle performance testing, and body composition measures were performed on a subset of 21 patients. ACR-FS was obtained by both chart abstraction and direct patient report. Spearman's correlations were used to examine the relationship of ACR-FS derived from chart abstraction with direct patient report, as well as the relationship of measures of physical function and body composition with ACR-FS. ACR-FS derived from chart abstraction was significantly correlated with ACR-FS derived from direct patient report (ρ = 0.78, p < 0.001). ACR-FS derived from chart abstraction was also significantly correlated with patient-reported physical function (ρ = -0.71, p < 0.001) and physical activity (ρ = -0.58, p < 0.05), manual muscle testing (ρ = -0.66, p < 0.01), and skeletal muscle endurance as measured by the functional index-2 test (shoulder flexion ρ = -0.62, p < 0.01; hip flexion ρ = -0.65, p < 0.0; heel lift ρ = -0.67, p < 0.01; and toe lift ρ = -0.68, p < 0.01). The ACR-FS is a simple measure of disability that can be used in chart abstraction studies involving IIM patients. We have demonstrated that ACR-FS correlates well with muscle performance tests of strength and endurance.
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17 MeSH Terms
Proximal nerve magnetization transfer MRI relates to disability in Charcot-Marie-Tooth diseases.
Dortch RD, Dethrage LM, Gore JC, Smith SA, Li J
(2014) Neurology 83: 1545-53
MeSH Terms: Adult, Charcot-Marie-Tooth Disease, Cohort Studies, Disability Evaluation, Disabled Persons, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Myelin Proteins, Sciatic Neuropathy, Statistics as Topic, Young Adult
Show Abstract · Added October 15, 2014
OBJECTIVE - The objectives of this study were (1) to develop a novel magnetization transfer ratio (MTR) MRI assay of the proximal sciatic nerve (SN), which is inaccessible via current tools for assessing peripheral nerves, and (2) to evaluate the resulting MTR values as a potential biomarker of myelin content changes in patients with Charcot-Marie-Tooth (CMT) diseases.
METHODS - MTR was measured in the SN of patients with CMT type 1A (CMT1A, n = 10), CMT type 2A (CMT2A, n = 3), hereditary neuropathy with liability to pressure palsies (n = 3), and healthy controls (n = 21). Additional patients without a genetically confirmed subtype (n = 4), but whose family histories and electrophysiologic tests were consistent with CMT, were also included. The relationship between MTR and clinical neuropathy scores was assessed, and the interscan and inter-rater reliability of MTR was estimated.
RESULTS - Mean volumetric MTR values were significantly decreased in the SN of patients with CMT1A (33.8 ± 3.3 percent units) and CMT2A (31.5 ± 1.9 percent units) relative to controls (37.2 ± 2.3 percent units). A significant relationship between MTR and disability scores was also detected (p = 0.01 for genetically confirmed patients only, p = 0.04 for all patients). From interscan and inter-rater reliability analyses, proximal nerve MTR values were repeatable at the slicewise and mean volumetric levels.
CONCLUSIONS - MTR measurements may be a viable biomarker of proximal nerve pathology in patients with CMT.
© 2014 American Academy of Neurology.
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14 MeSH Terms
Anger arousal and behavioral anger regulation in everyday life among patients with chronic low back pain: Relationships to patient pain and function.
Burns JW, Gerhart JI, Bruehl S, Peterson KM, Smith DA, Porter LS, Schuster E, Kinner E, Buvanendran A, Fras AM, Keefe FJ
(2015) Health Psychol 34: 547-55
MeSH Terms: Adult, Anger, Arousal, Chronic Pain, Disability Evaluation, Female, Humans, Inhibition, Psychological, Low Back Pain, Male, Middle Aged, Pain Measurement, Self Report, Spouses
Show Abstract · Added February 12, 2015
OBJECTIVE - The objective of this study was to determine the degree to which patient anger arousal and behavioral anger regulation (expression, inhibition) occurring in the course of daily life was related to patient pain and function as rated by patients and their spouses.
METHOD - Married couples (N = 105) (one spouse with chronic low back pain) completed electronic daily diaries, with assessments 5 times/day for 14 days. Patients completed items on their own state anger, behavioral anger expression and inhibition, and pain-related factors. Spouses completed items on their observations of patient pain-related factors. Hierarchical linear modeling was used to test concurrent and lagged relationships.
RESULTS - Patient-reported increases in state anger were related to their reports of concurrent increases in pain and pain interference and to spouse reports of patient pain and pain behavior. Patient-reported increases in behavioral anger expression were related to lagged increases in pain intensity and interference and decreases in function. Most of these relationships remained significant with state anger controlled. Patient-reported increases in behavioral anger inhibition were related to concurrent increases in pain interference and decreases in function, which also remained significant with state anger controlled. Patient-reported increases in state anger were related to lagged increases in spouse reports of patient pain intensity and pain behaviors.
CONCLUSIONS - Results indicate that in patients with chronic pain, anger arousal and behavioral anger expression and inhibition in everyday life are related to elevated pain intensity and decreased function as reported by patients. Spouse ratings show some degree of concordance with patient reports.
(c) 2015 APA, all rights reserved).
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14 MeSH Terms
Preoperative Opioid Use as a Predictor of Adverse Postoperative Self-Reported Outcomes in Patients Undergoing Spine Surgery.
Lee D, Armaghani S, Archer KR, Bible J, Shau D, Kay H, Zhang C, McGirt MJ, Devin C
(2014) J Bone Joint Surg Am 96: e89
MeSH Terms: Analgesics, Opioid, Disability Evaluation, Female, Humans, Intraoperative Care, Male, Middle Aged, Pain Management, Pain Measurement, Pain, Postoperative, Prospective Studies, Self Report, Spinal Diseases, Surveys and Questionnaires, Treatment Outcome
Show Abstract · Added February 19, 2015
BACKGROUND - Opioids are commonly used for preoperative pain management in patients undergoing spine surgery. The objective of this investigation was to assess whether preoperative opioid use predicts worse self-reported outcomes in patients undergoing spine surgery.
METHODS - Five hundred and eighty-three patients undergoing lumbar, thoracolumbar, or cervical spine surgery to treat a structural lesion were included in this prospective cohort study. Self-reported preoperative opioid consumption data were obtained at the preoperative visit and were converted to the corresponding daily morphine equivalent amount. Patient-reported outcome measures were assessed at three and twelve months postoperatively via the 12-Item Short-Form Health Survey and the EuroQol-5D questionnaire, as well as, when appropriate, the Oswestry Disability Index and the Neck Disability Index. Separate multivariable linear regression analyses were then performed.
RESULTS - At the preoperative evaluation, of the 583 patients, 56% (326 patients) reported some degree of opioid use. Multivariable analyses controlling for age, sex, diabetes, smoking, surgery invasiveness, revision surgery, preoperative Modified Somatic Perception Questionnaire score, preoperative Zung Depression Scale score, and baseline outcome score found that increased preoperative opioid use was a significant predictor (p < 0.05) of decreased 12-Item Short-Form Health Survey and EuroQol-5D scores, as well as of increased Oswestry Disability Index and Neck Disability Index scores at three and twelve months postoperatively. Every 10-mg increase in daily morphine equivalent amount taken preoperatively was associated with a 0.03 decrease in the 12-Item Short-Form Health Survey physical component summary and mental component summary scores, a 0.01 decrease in the EuroQol-5D score, and a 0.5 increase in the Oswestry Disability Index and Neck Disability Index score at twelve months postoperatively. Higher preoperative Modified Somatic Perception Questionnaire and Zung Depression Scale scores were also significant negative predictors (p < 0.05).
CONCLUSIONS - Increased preoperative opioid consumption, Modified Somatic Perception Questionnaire score, and Zung Depression Scale score prior to undergoing spine surgery predicted worse patient-reported outcomes. This suggests the potential benefit of psychological and opioid screening with a multidisciplinary approach that includes weaning of opioid use in the preoperative period and close opioid monitoring postoperatively.
LEVEL OF EVIDENCE - Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.
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15 MeSH Terms
A systematic review of functional and quality of life assessment after major lower extremity amputation.
Hawkins AT, Henry AJ, Crandell DM, Nguyen LL
(2014) Ann Vasc Surg 28: 763-80
MeSH Terms: Activities of Daily Living, Amputation, Amputees, Disability Evaluation, Exercise Test, Humans, Lower Extremity, Peripheral Arterial Disease, Predictive Value of Tests, Quality of Life, Recovery of Function, Surveys and Questionnaires, Treatment Outcome
Show Abstract · Added September 27, 2016
BACKGROUND - When judging the success or failure of major lower extremity (MLE) amputation, the assessment of appropriate functional and quality of life (QOL) outcomes is paramount. The heterogeneity of the scales and tests in the current literature is confusing and makes it difficult to compare results. We provide a primer for outcome assessment after amputation and assess the need for the additional development of novel instruments.
METHODS - MEDLINE, EMBASE, and Google Scholar were searched for all studies using functional and QOL instruments after MLE amputation. Assessment instruments were divided into functional and QOL categories. Within each category, they were subdivided into global and amputation-specific instruments. An overall assessment of instrument quality was obtained.
RESULTS - The initial search revealed 746 potential studies. After a review of abstracts, 102 were selected for full review, and 40 studies were then included in this review. From the studies, 21 different assessment instruments were used 63 times. There were 14 (67%) functional measures and 7 (33%) QOL measures identified. Five (36%) of the functional instruments and 3 (43%) of the QOL measures were specific for MLE amputees. Sixteen instruments were used >1 time, but only 5 instruments were used >3 times. An additional 5 instruments were included that were deemed important by expert opinion. The 26 assessment instruments were rated. Fourteen of the best-rated instruments were then described.
CONCLUSIONS - The heterogeneity of instruments used to measure both functional and QOL outcomes make it difficult to compare MLE amputation outcome studies. Future researchers should seek to use high-quality instruments. Clinical and research societies should endorse the best validated instruments for future use in order to strengthen overall research in the field.
Copyright © 2014 Elsevier Inc. All rights reserved.
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A primer for workers' compensation.
Bible JE, Spengler DM, Mir HR
(2014) Spine J 14: 1325-31
MeSH Terms: American Medical Association, Disability Evaluation, Guidelines as Topic, Humans, Insurance Claim Review, Physician's Role, Return to Work, United States, Workers' Compensation
Show Abstract · Added February 15, 2016
BACKGROUND CONTEXT - A physician's role within a workers' compensation injury extends far beyond just evaluation and treatment with several socioeconomic and psychological factors at play compared with similar injuries occurring outside of the workplace. Although workers' compensation statutes vary among states, all have several basic features with the overall goal of returning the injured worker to maximal function in the shortest time period, with the least residual disability and shortest time away from work.
PURPOSE - To help physicians unfamiliar with the workers' compensation process accomplish these goals.
METHODS - Educational review.
RESULTS - The streamlined review addresses the topics of why is workers' compensation necessary; what does workers' compensation cover; progression after work injury; impairment and maximum medical improvement, including how to use the sixth edition of American Medical Association's (AMA) Guides to the evaluation of permanent impairment (Guides); completion of work injury claim after impairment rating; independent medical evaluation; and causation.
CONCLUSIONS - In the "no-fault" workers' compensation system, physicians play a key role in progressing the claim along and, more importantly, getting the injured worker back to work as soon as safely possible. Physicians should remain familiar with the workers' compensation process, along with how to properly use the AMA Guides.
Copyright © 2014 Elsevier Inc. All rights reserved.
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9 MeSH Terms
Pediatric intracerebral hemorrhage score: a simple grading scale for intracerebral hemorrhage in children.
Beslow LA, Ichord RN, Gindville MC, Kleinman JT, Engelmann K, Bastian RA, Licht DJ, Smith SE, Hillis AE, Jordan LC
(2014) Stroke 45: 66-70
MeSH Terms: Adolescent, Age Factors, Brain, Cerebral Hemorrhage, Cerebral Ventricles, Child, Child, Preschool, Cohort Studies, Disability Evaluation, Female, Humans, Hydrocephalus, Infant, Infant, Newborn, Male, Neurosurgical Procedures, Predictive Value of Tests, Prognosis, Prospective Studies, ROC Curve, Recovery of Function, Sex Factors, Treatment Outcome
Show Abstract · Added March 24, 2020
BACKGROUND AND PURPOSE - The intracerebral hemorrhage (ICH) score is the most commonly used clinical grading scale for outcome prediction after adult ICH. We created a similar scale in children to inform clinical care and assist in clinical research.
METHODS - Children, full-term newborns to 18 years, with spontaneous ICH were prospectively enrolled from 2007 to 2012 at 3 centers. The pediatric ICH score was created by identifying factors associated with poor outcome. The score's ability to detect moderate disability or worse and severe disability or death was examined with sensitivity, specificity, and area under the receiver operating characteristic curve.
RESULTS - The pediatric ICH score components include ICH volume>2% to 3.99% of total brain volume (TBV): 1 point; ICH volume≥4% TBV: 2 points; acute hydrocephalus: 1 point; herniation: 1 point; and infratentorial location: 1 point. The score ranges from 0 to 5. At 3-month follow-up of 60 children, 10 were severely disabled or dead, 30 had moderate disability, and 20 had good recovery. A pediatric ICH score≥1 predicted moderate disability or worse with a sensitivity of 75% (95% confidence interval [CI], 59% to 87%) and a specificity of 70% (95% CI, 46% to 88%). A pediatric ICH score≥2 predicted severe disability or death with a sensitivity and specificity of 90% (95% CI, 55% to 99%) and 68% (95% CI, 53% to 80%), respectively. The area under the receiver operating characteristic curve for classifying outcome as severe disability or death was 0.88 (95% CI, 0.78-0.97).
CONCLUSIONS - The pediatric ICH score is a simple clinical grading scale that may ultimately be used for risk stratification, clinical care, and research.
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