High-Level Mobility in Chronic Traumatic Brain Injury and Its Relationship With Clinical Variables and Magnetic Resonance Imaging Findings in the Acute Phase

Accepted Manuscript High-level mobility in chronic traumatic brain injury, and its relationship with clinical variables and MRI findings in the acute phase Kine Therese Moen, MSc Lone Jørgensen, PhD Alexander Olsen, Clin Psychol, Asta Håberg, PhD Toril Skandsen, PhD Anne Vik, PhD Ann-Mari Brubakk, PhD Kari Anne I. Evensen, PhD PII:

S0003-9993(14)00330-X

DOI:

10.1016/j.apmr.2014.04.014

Reference:

YAPMR 55818

To appear in:

ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION

Received Date: 31 March 2014 Accepted Date: 12 April 2014

Please cite this article as: Moen KT, Jørgensen L, Olsen A, Psychol C, Håberg A, Skandsen T, Vik A, Brubakk A-M, Evensen KAI, High-level mobility in chronic traumatic brain injury, and its relationship with clinical variables and MRI findings in the acute phase, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2014), doi: 10.1016/j.apmr.2014.04.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Running title: High-level mobility in chronic TBI.

Title: High-level mobility in chronic traumatic brain injury, and its relationship with

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clinical variables and MRI findings in the acute phase

Authors: Kine Therese Moen, MSc1, Lone Jørgensen, PhD2,3, Alexander Olsen, Clin

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Brubakk, PhD8 and Kari Anne I. Evensen, PhD8,9,10

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Psychol4,6, Asta Håberg, PhD7, Toril Skandsen, PhD4,7, Anne Vik, PhD5,7, Ann-Mari

Stiftelsen CatoSenteret, Department of Medical Rehabilitation Services, Son, Norway.

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Department of Health and Care Sciences and the “Tromsø Endocrine Research Group”,

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University of Tromsø, Tromsø, Norway.

Department of Clinical Therapeutic Services, University Hospital of North Norway,

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Tromsø, Norway.

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Department of Physical Medicine and Rehabilitation, 5 Department of Neurosurgery, St.

Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

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Department of Circulation and Medical Imaging,7 Department of Neuroscience, 8

Department of Laboratory Medicine, Children’s and Women’s Health, 9 Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway

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Department of Physical Therapy, Trondheim Municipality, Norway

conference at the University of Tromsø, Norway, June 2012

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Previous presentation of this material: This material has been presented in part at a national

Acknowledgement of financial support: This study had financial support from the

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Norwegian Research Council.

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Acknowledgments: We want to thank all the participants for their cooperation and interest in this study. We are grateful to Inger Helene Hamborg, MSc, and physiotherapist Sigrun Flækken for their contribution in data collection, and to Kjell Arne Kvistad, Mari

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Folvik and Jana Rydland for their contrubution with the MRI categorisation.

Conflict of interest: There are no financial or other relationships that might lead to a conflict

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of interest.

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On behalf of the authors,

Ms Kine Therese Moen Stiftelsen CatoSenteret Kvartsveien 2 NO/1555 Son, Norway

Phone: (+47) 92281037 mobile and (+47) 64984400 work E-mail: [email protected]

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Title

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High-level mobility in chronic traumatic brain injury, and its relationship

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with clinical variables and MRI findings in the acute phase

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Abstract

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Objectives: To compare high-level mobility in individuals with chronic moderate to severe traumatic brain injury (TBI) with matched healthy controls, and investigate

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whether clinical variables and magnetic resonance imaging (MRI) findings in the acute

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phase can predict high-level motor performance in the chronic phase.

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Design: A longitudinal follow-up study.

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Setting: A level 1 trauma centre.

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Participants: 65 individuals with chronic TBI and 71 healthy matched peers

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Interventions: Not applicable.

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Main Outcome Measures: High-level mobility assessment tool (HiMAT) and the

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revised version of the HiMAT performed at a mean of 2.8 years (range 1.5-5.4) after

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injury

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Results: Participants with chronic TBI had a mean HiMAT score of 42.7 (95% CI 40.2-

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45.2) compared with 47.7 (95% CI 46.1-49.2) in the control group (p<0.01). Group

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differences were also evident using the revised HiMAT (p<0.01). Acute phase clinical

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variables and MRI findings explained 58.8% of the variance in the HiMAT score

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ACCEPTED MANUSCRIPT (p<0.001) and 59.9% in the revised HiMAT score (p<0.001). Lower HiMAT scores were

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associated with female sex (p=0.031), higher age at injury (p<0.001), motor vehicle

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accidents (p=0.030) and post traumatic amnesia >7 days (p=0.048). There was a tendency

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towards an association between lower scores and diffuse axonal injury in the brainstem

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(p=0.075).

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Conclusions: High-level mobility was reduced in participants with chronic moderate and

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severe TBI compared to matched peers. Clinical variables in the acute phase were

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significantly associated with high-level mobility performance in TBI participants, but the

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role of early MRI findings needs to be further investigated. The findings of this study

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suggest that the clinical variables in the acute phase may be useful in predicting high-level

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mobility outcome in the chronic phase.

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Keywords: Motor skills, magnetic resonance imaging, diffuse axonal injury

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Abbreviations

45 46 TBI - traumatic brain injury

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MRI - magnetic resonance imaging

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DAI – diffuse axonal injury

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HiMAT – High level Mobility Assessment Tool

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HISS – Head Injury Severity Scale

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GOSE – Glasgow Outcome Score Extended

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MVA – motor vehicle accident

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PTA – post traumatic amnesia

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CI – confidence intervals

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rs – Spearman’s rho

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ACCEPTED MANUSCRIPT Traumatic brain injuries (TBI) are highly prevalent. A recent Norwegian study found

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an annual incidence of 83.3 hospitalized TBI patients per 100 000 inhabitants.1 TBI

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may manifest with motor, cognitive, psychiatric or behavioural problems even in the

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chronic phase2-4 (defined as >1 year post injury).5 Problems in any of these areas can

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affect quality of life and participation in education, work, social activities and sports.3, 6

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Initially rehabilitation focuses on acquiring independence in gait and daily activities.7, 8

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In the chronic phase emphasis typically shifts to resuming vocational and leisure

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activities. High-level mobility can be essential in obtaining these goals.8-10 High-level

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mobility depicts gross motor abilities important for everyday life and leisure activities,

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such as running, jumping, and walking over obstacles.11

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Until recently there has been a paucity of studies investigating higher levels of mobility

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in people post TBI. Several studies report good motor recovery in chronic TBI.4, 8, 12-14

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The majority of these studies used outcome measures with ceiling effects, thereby

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leading to a rather unclear definition of 'good' motor recovery. Limitations in advanced

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gross motor skills are reported even in people who are considered to have good long-

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term recovery from TBI.8 Numerous case studies have shown that people with chronic

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TBI have reduced speed, decreased balance and perform with less motor precision than

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matched controls. 15-19 However, group studies that have focused on high-level mobility

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in chronic TBI,9, 10, 15, 17, 20-24 have included few participants or investigated a narrow

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age range. Moreover, only three previous studies have included a control group.15, 17, 23

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New findings demonstrate a relationship between good gross motor skills, measured

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with the HiMAT, and participation in vocational activities.9 This supports previous

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findings indicating that physical capacity is a predictor for return to work.25 Return to

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work is considered one of the highest levels of participation26, and numbers range from

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18 to 42% of people with severe TBI returning to some level of vocational activity.27, 28

90 The High-level Mobility Assessment Tool (HiMAT) is a comprehensive outcome

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measure of advanced motor skills after TBI.10, 29 Only one study has used the HiMAT

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to compare individuals with very severe chronic TBI to matched controls. This study

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identified a significantly lower mobility capacity in the TBI group compared to

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controls.23 Until now the HiMAT has never been used in a comparative study

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investigating people with both moderate and severe TBI. A revised version of the

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HiMAT, where five items were removed, was developed in 2010.30 No previous study

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has presented findings on the revised HiMAT in a TBI population or in healthy

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individuals.

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Magnetic resonance imaging (MRI) is the best imaging method to demonstrate injury

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to the brain parenchyma in individuals with TBI. MRI has shown that diffuse axonal

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injuries (DAI) are highly prevalent in moderate and severe TBI.31-34 DAI lesions may

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be located in the hemispheric white matter, the corpus callosum or in the brainstem,

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and can impact motor function, especially when found in the brainstem. However, no

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studies have examined whether MRI findings from the acute phase are related to high-

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level mobility performance in the chronic phase.

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The primary aim of this study is to investigate high-level mobility in individuals with

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moderate and severe chronic TBI compared to healthy controls. A secondary aim will

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be to determine if the revised HiMAT has similar properties as the original HiMAT in

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discriminating between individuals with TBI and healthy controls. Lastly we will

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investigate if there is a relationship between the acute phase clinical variables and MRI

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findings with high-level mobility in chronic TBI.

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Materials and methods

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118 Design

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This study was a longitudinal follow-up study of a group of TBI patients admitted to a

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level 1 trauma centre, St. Olavs Hospital in Mid-Norway, compared with a control

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group matched by sex, age and education. St.Olavs Hospital is the only level 1 trauma

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centre in the Mid-Norway health authority, a health region with approximately 680 000

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inhabitants. The study was carried out from May 2009 to September 2010. Assessment

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of high-level mobility was performed as a part of a larger test battery including

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functional MRI, electroencephalography, measures of fine motor function and

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questionnaires on executive and higher cognitive functions.

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TBI participants

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From October 2004 to July 2008, 236 patients with moderate and severe TBI based on

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the Head Injury Severity Scale (HISS) criteria35 were admitted to the Department of

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Neurosurgery at St.Olavs Hospital, Trondheim University Hospital, Norway, and were

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registered in a database. Of these, 95 individuals fit the inclusion criteria of: more than

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Norwegian, and ability to cooperate during functional magnetic resonance imaging

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defined as Glasgow Outcome Score Extended (GOSE) ≥5. Exclusion criteria were

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prior or additional neurological illness and severe or ongoing psychiatric illness. Fifty-

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one of the patients were deceased, 40 were above or below the given age limits and 28

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patients had premorbid illness. Four patients were not fluent in Norwegian and 13 had

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GOSE scores <5. Five patients were only registered with data from the acute phase and

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not asked for follow-up data due to particularly sensitive circumstances.

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The 95 eligible participants were contacted by either letter or phone and informed

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consent was received from 68 individuals (71.6%).Three participants could not perform

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or complete the HiMAT, and were excluded from analysis; one was wheelchair

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dependent, one refrained from testing due to headache, and one participant fell during

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testing, and was unable to continue due to pain. This left 65 participants available for

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analysis.

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Control group

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Healthy peers were recruited from the Mid-Norway region, chosen through a strategic

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sampling from the participants’ families and social networks, hospital employees and

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recruitment through advertisement at various workplaces in Trondheim. Peers were

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matched to the TBI group on sex, age and education. Of the 75 willing participants,

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four were excluded from the analysis due to incomplete data collection during testing.

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This left 71participants available for analysis in the control group.

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TBI non-participants

162 There were no significant differences between TBI participants and individuals with

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TBI who were not able to participate in the study (n=27) regarding age at injury, sex,

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mechanism of injury, severity of TBI defined by HISS or duration of post traumatic

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amnesia (PTA). MRI data were missing for one participant and eight non-participants,

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but cortical contusions, presence and location of DAI did not differ between

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participants and non-participants with MRI data present (p≥0.1).

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Background characteristics

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Information on marital status, current physical activity levels, illness, injury, pain and

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use of medication was collected through interview. Being physically active was defined

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as committing planned, structured, repetitive exercise aiming to improve or maintain

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physical fitness.36 Body mass index (kg/m2) was calculated from weight, weighed to

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the nearest 10 g, and self-reported height.

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Clinical variables and MRI findings in the acute phase

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Age and cause of injury was registered at hospital admission. HISS criteria were used

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to determine severity of injury, based on Glasgow Coma Scale37 examined at or after

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hospital admission, or before intubation during pre-hospital intubation.38, 39 The

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database information was collected at the time of injury by the resident in neurosurgery

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who examined the patient in the emergency room. Duration of PTA was assessed by an

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ACCEPTED MANUSCRIPT experienced consultant in physical medicine and rehabilitation (TS) by review of

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medical notes, interview with patients shortly after resolution of PTA, or by the use of

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validated symptom scales. The latter was most common in patients who were admitted

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to rehabilitation while still in PTA. PTA was divided into short (≤7 days) and long

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PTA (>7 days).40 This grouping was regarded as appropriate for this neurosurgical

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cohort which comprises of both moderate and severe TBI. We anticipated that patients

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in our cohort would have considerably shorter PTA than what has been described in

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cohorts comprising exclusively of patients receiving in-patient rehabilitation.41, 42

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MRI (1.5 Tesla) was conducted as early as practically possible and included T2*

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gradient echo, fluid-attenuated inversion recovery and diffusion-weighted imaging.31, 43

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In this study participants were grouped into the presence of DAI lesions or no-DAI

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lesions, and DAI classified into grade 1; traumatic lesions confined to lobar white

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matter, grade 2; lesions also in the corpus callosum, and in grade 3; lesions in the

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brainstem.44 TS performed the classification in cooperation with three experienced

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neuroradiologists.31

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High-level mobility

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High-level mobility was examined in both groups using HiMAT.45 HiMAT is an

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ordinal scale with 13 items examining a variety of motor skills including negotiating

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stairs, running, skipping, hopping and bounding.11, 45 Item scores are summed to a total

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of 54 points, with higher scores indicating better motor function.45 Participants were

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tested on their preferred leg on items examining the least affected side. If uncertain, the

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leg self-chosen to perform a single leg stance was identified as preferred. The test

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requires a 14 step staircase. However, because this was unavailable at the testing site,

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we used a 12 step staircase. Measured time x 14/12 was used to calculate time on the

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stair items.

213 In the revised HiMAT, five items are removed (including the stair items) resulting in an

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eight item uni-dimensional test with a maximum total score of 32 points.30 The revised

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score was calculated based on performance of the full HiMAT.

Examiners

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Interviews and assessments were performed by three examiners (two physiotherapists,

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one bachelor of sports). Examiners were blinded to whether the participants were in the

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TBI or control group.

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Statistical analyses

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Data analyses were performed using IBM SPSS 19.0. A two-sided p-value <0.05 was

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considered statistically significant. Group differences on normally distributed data were

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analysed with student’s t-test for independent groups, and Mann-Whitney U test for

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non-parametric or not normally distributed data. Chi-square tests were used to examine

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differences in proportions. Correlation analyses between background variables and

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group and/or outcome were performed using Spearman’s rho (rs) to identify potential

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confounding factors. Potential confounders were then included in a univariate general

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linear model. In order to predict high-level mobility performance in the TBI group,

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ACCEPTED MANUSCRIPT acute phase clinical variables were entered simultaneously as covariates in a general

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linear model with total (and revised) HiMAT score as dependent variables. The

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presence of contusions was dichotomised into ‘yes/no’ and entered as a covariate, and

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categories of DAI were entered as a fixed factor, with ‘no DAI’ as the reference

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category.

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Ethics

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This study is part of a large project approved by the Regional Committee for Medical

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Research Ethics in Mid-Norway. Written informed consent was given by all

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participants.

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Results

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Background characteristics

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Background characteristics of both groups are presented in Table 1. The male:female

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ratio was 2.8 in the TBI group and 3.2 in the control group (p=0.92). Participants in the

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control group engaged in more exercise activities than participants in the TBI group,

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but there were no significant differences in age, sex and education indicating successful

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matching. Marital status, presence of recent illness or injury, use of medication and

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being defined as physically active did not differ between groups (data not shown).

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Clinical variables and MRI findings in the acute phase

259 Mean age at injury was 29.2 years (range 13.2-63.3). Mean time since injury was 2.8

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years (range 1.5-5.4). Clinical variables are presented in Table 2. Motor vehicle

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accidents (MVA) were the single most common cause of TBI.

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Sixty-four of the 65 TBI participants had been examined with MRI. Median number of

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days from injury to MRI examination was 6 (range 1-53 days). In two (3.1%)

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participants there were no abnormal findings on MRI. Contusions in the cerebral cortex

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were present in 45 (71.4%) participants and DAI was found in 46 (73%).

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268 HiMAT

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HiMAT item and total scores are presented in Table 3. Mean total score was 42.7 (95%

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CI:40.2-45.2) in the TBI group compared with 47.7 (95% CI:46.1-49.2) in the control

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group on the HiMAT (p<0.01). The TBI participants also had lower scores than the

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controls on the revised HiMAT (Table 3). Except from stair items, all items differed

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significantly between groups. Pain during testing on the HiMAT was reported in 10

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(15.2%) TBI subjects and 9 (13.9%) controls (p=1.00).

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Engaging in a higher number of exercise activities was the only variable differing

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significantly between the groups, and was also significantly associated with a higher

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HiMAT (rs= 0.26, p<0.01) and revised HiMAT score (rs= 0.28, p<0.01). Included in a

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general linear model, adjusted HiMAT score was 43.0 (95 % CI:40.9-45.1) in the TBI

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group and 47.3 (95% CI:45.4-49.3) in the control group (p=0.02). Adjusted revised

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HiMAT score was 24.3 (95% CI:22.8-25.8) in the TBI group and 27.7 (95% CI:26.3-

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29.1) in the control group (p=0.01).

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High-level mobility and its relationship with clinical variables and MRI findings

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Table 4 shows that the clinical variables and MRI findings in the acute phase were able

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to explain 58.8% of the variance in HiMAT score (p<0.001). Higher age at injury,

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female sex, MVA and a long PTA were significantly associated with lower HiMAT

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score. The same model explained 59.9% of the variance in the revised HiMAT score

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(p<0.001). In the model there was a tendency towards a significant association between

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DAI 3 and a lower HiMAT score (p=0.075), but not with the revised HiMAT

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(p=0.171). Presence of cortical contusions, DAI 1 and DAI 2 were not associated with

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either HiMAT score.

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Discussion

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In this study we found that participants with moderate and severe TBI performed

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significantly worse than the control group on all HiMAT items apart from the stair

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items. Accordingly, the revised eight-item HiMAT score also showed significantly

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poorer performance in the TBI group. Acute phase clinical variables were significantly

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associated with lower high-level mobility performance in the TBI participants. The 13

ACCEPTED MANUSCRIPT MRI findings showed a tendency towards an association between DAI in the brainstem

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and poorer high-level mobility. This study is the first to investigate high-level mobility

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in participants with both moderate and severe chronic TBI compared to healthy peers

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using HiMAT. Furthermore, no other studies have presented results on the revised

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HiMAT either in a TBI or in a healthy population. Another novelty is the use of acute

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phase MRI findings investigating the association with high-level mobility in chronic

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TBI.

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The TBI group had impaired mobility compared to healthy peers, as should be

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expected. Only one previous study presenting HiMAT results has used a control

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group.23 The study of Williams et al23 included chronic very to extremely severe TBI

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and found that they performed significantly worse on the HiMAT compared to the

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control group. Median scores were 31 (range 21-40) and 51 (range 43-53), respectively.

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Other studies have presented mean HiMAT scores ranging from 16.6 to 31.1 points.9, 10,

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17, 21, 24

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diagnostic criteria, and severity of TBI. Our results suggest better high-level mobility

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in chronic moderate and severe TBI than previous studies using HiMAT.9, 10, 17, 21, 23, 24

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However, in most other studies the majority of participants had PTA lasting >28 days,

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suggesting very severe TBI. The difference in severity is likely to explain most of the

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difference between previous findings and our results. In one study severity of TBI was

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not reported, and the participants were older and were tested longer after their initial

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injury compared to our sample.21

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Comparison across studies is challenging due to differing inclusion and

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A recent study by Kleffelgaard et al46 on a cohort of mild TBI patients reported a mean

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total HiMAT score of 46.2 points 3 months post injury, increasing to 47.7 points 6

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cohort than other more severe TBI cohorts, suggesting that they may have reached a

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relatively high level of mobility skills despite a more severe injury. However, in the

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study by Kleffelgaard et al,46 participants with Glasgow Coma Scale score 13 were

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defined as mild TBI, whereas in our study such patients were included in the moderate

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TBI group in accordance with HISS criteria. Thus, some of the participants in the two

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studies might not be very different with regards to severity of injury.

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Results were highly similar for the original and the revised HiMAT. The groups

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differed on all items apart from the stair items. Interestingly, earlier work on HiMAT

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have classified two of four stair items as the easiest items of the test.30, 45 Expert

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clinicians strongly advocated the inclusion of stair mobility in the HiMAT.11, 30. The

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findings from this study suggest that clinicians may have overestimated the difficulty

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of stair mobility due to the clinical relevance of being able to negotiate stairs. Even

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though one of the bound items, differing between the groups in our study, is not

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included in the revised version, our findings suggest that the two versions are equal in

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their ability to discriminate between persons with TBI and healthy peers on high-level

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mobility. As the revised version takes less time to complete and does not require a

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staircase, it may be more feasible in the clinical setting. Based on our findings, the

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revised HiMAT can therefore be recommended for future use in the TBI population.

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Participants in the control group engaged in a higher number of exercise activities.

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Engaging in several activities suggests an active lifestyle, increasing the likelihood of

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being challenged on high-level mobility skills, thereby improving proficiency. It is

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possible that the number of activities is not a confounder, but merely a result of having

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ACCEPTED MANUSCRIPT better high-level mobility. On the other hand it may reflect a smaller range of suitable

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exercise activities for mobility impaired individuals with TBI. This may also be

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supported by the fact that when interviewing both groups, there was no difference

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between TBI and healthy peers in frequency or duration of exercise, pain, current

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illness, injury or use of medication. In additional support, a recent study found no

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significant difference in cardiovascular fitness between a group of subjects with very

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severe TBI and healthy controls.23 Executive impairments like reduced initiative may

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also provide some explanation to why individuals with TBI perform fewer activities.

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Adjusting for number of exercise activities reduced the differences in HiMAT scores

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between the TBI and the control group, however, the differences were still highly

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significant. This indicates that even though number of exercise activities influenced

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the HiMAT scores, it did not explain the overall results in this study.

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A higher age at injury, being female, sustaining a head injury through a MVA and

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having a PTA >7 days were significantly associated with worse HiMAT scores. Age

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and sex were entered in the model as known covariates with mobility levels. No

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previous study has investigated high-level motor function specifically in relationship to

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injury mechanisms. Yet, better general outcome47, 48 or no association with outcome49

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has been suggested when involved in a MVA. It is therefore interesting that MVA was

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associated with reduced high-level mobility performance in our study. Our finding that

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a longer duration of PTA was associated with poorer HiMAT score is in accordance

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with other studies where duration of PTA has been associated with a worse outcome.32,

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ACCEPTED MANUSCRIPT DAI located in the brainstem showed a tendency towards being associated with

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HiMAT score, but not with the revised HiMAT score. This might indicate that DAI in

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the brainstem is related to stair mobility and bound onto the most affected leg. This is

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particularly interesting in light of the earlier discussed complexity of stair mobility.

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However, as this finding only represents a tendency it needs further investigation.

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Previous findings have indicated that DAI in the brainstem is a prime variable

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associated with poor general outcome.31, 52-55 However, our findings were not as clear

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cut. Additionally, neither DAI 1 nor DAI 2 contributed significantly in the linear

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regression model, nor did the presence of cortical contusions. We believe that this

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finding, suggesting that diffuse axonal injury in the brain stem may predict chronic

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high-level mobility, is interesting and requires further study.

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Increased knowledge of high-level mobility performance in chronic TBI is important,

392

as it may warrant further rehabilitation efforts for some patients considered to be

393

clinically well recovered. Better mobility is associated with return to work9, 25 and

394

targeted rehabilitation aiming to improve high-level motor function in the chronic

395

phase may enable more individuals to return to vocational activities, thereby increasing

396

productivity and reducing total costs for both the individual and society at large.

398 399

EP

AC C

397

TE D

391

Study limitations

400

Although blinding of examiners reduced the risk of information bias the possibility of

401

examiners being able to identify TBI subjects based on clinical experience cannot be

402

excluded. However, as the item measures are objective measures of time and length,

403

we consider chances for information bias unlikely. Additionally, our sample is only

17

ACCEPTED MANUSCRIPT 404

representative for individuals with TBI that were relatively healthy before the injury, as

405

individuals with prior neurological or severe or ongoing psychiatric illness, were

406

excluded in this study.

407 DAI lesions depicted with MRI in the fluid-attenuated inversion recovery sequence

409

tend to attenuate over time56, and it would have strengthened the study if time from

410

injury to scanning was equal in all cases and performed even earlier. However, this is

411

not always practically possible in a clinical setting due to medical and logistic reasons.

412

Hence, we can not exclude that some non-hemorrhagic lesions have been missed in

413

patients examined late.

M AN U

SC

RI PT

408

414

415

Conclusions

TE D

416 417

With this study we have confirmed that individuals with chronic moderate and severe

419

TBI have poorer high-level mobility than matched healthy peers. Clinical findings in

420

the acute phase were significantly associated with high-level mobility performance in

421

individuals with TBI, suggesting that these findings can assist prediction of high-level

422

mobility outcome in the chronic phase. This study is also the first to include MRI

423

findings in relation to high-level mobility. The MRI findings were not conclusive

424

predictors of high-level mobility in the chronic phase of TBI, but the presence of DAI

425

in the brainstem showed a tendency towards significance which warrants further

426

investigation.

AC C

EP

418

427

18

ACCEPTED MANUSCRIPT

References

428

429 430 1.

Andelic N, Sigurdardottir S, Brunborg C, Roe C. Incidence of hospital-treated

432

traumatic brain injury in the Oslo population. Neuroepidemiology 2008;30:120-8.

RI PT

431

433 2.

Dikmen SS, Machamer JE, Powell JM, Temkin NR. Outcome 3 to 5 years after

435

moderate to severe traumatic brain injury. Arch Phys Med Rehabil 2003;84:1449-57.

SC

434

M AN U

436 437

3.

Ponsford J, Draper K, Schönberger M. Functional outcome 10 years after traumatic

438

brain injury: its relationship with demographic, injury severity, and cognitive and emotional

439

status. J Int Neuropsychol Soc 2008;14:233-42.

TE D

440 441

4.

Jacobsson LJ WM, Söderberg S, Lexell J. Functioning and disability 6-15 years

442

after traumatic brain injuries in northern Sweden. Acta Neurol Scand 2009;120:389-95.

5.

445

1996;77:198-207.

446

Malec JF, Basford JS. Postacute brain injury rehabilitation. Arch Phys Med Rehabil

AC C

444

EP

443

447

6.

Temkin NR, Corrigan JD, Dikmen SS, Machamer J. Social functioning after

448

traumatic brain injury. J Head Trauma Rehabil 2009;24:460-7.

449 450

7.

Hellweg S, Johannes S. Physiotherapy after traumatic brain injury: a systematic

451

review of the literature. Brain Inj 2008;22:365-73.

452 19

ACCEPTED MANUSCRIPT 453

8.

Walker WC, Pickett TC. Motor impairment after severe traumatic brain injury: a

454

longitudinal multicenter study. J Rehabil Res Dev 2007;44:975-82.

455 9.

Williams G, Willmott C. Higher levels of mobility are associated with greater

457

societal participation and better quality-of-life. Brain Inj 2012;26:1065-71.

458 10.

Williams G, Morris M. High-level mobility outcomes following acquired brain

460

injury: a preliminary evaluation. Brain Inj 2009;23:307-12.

SC

459

RI PT

456

461 11.

Williams G RV, Greenwood K, Goldie P, Morris ME. The high-level mobility

463

assessment tool (HiMAT) for traumatic brain injury. Part 1: Item generation. Brain Inj

464

2005;19:925-32.

M AN U

462

465 12.

467

physical health and mental health 1 year after traumatic brain injury. Disabil Rehabil

468

2010;32:1122-31.

EP

469

Andelic N, Sigurdardottir S, Schanke AK, Sandvik L, Sveen U, Roe C. Disability,

TE D

466

13.

McFadyen BJ, Cantin J-F, Swaine B, Duchesneau G, Doyon J, Dumas D, et al.

471

Modality-spesific, multitask locomotor deficits persist despite good recovery after a

472

traumatic brain injury. Arch Phys Med Rehabil 2009;90:1596-606.

AC C

470

473 474

14.

Hillier SL, Sharpe MH, Metzer J. Outcomes 5 years post-traumatic brain injury

475

(with further reference to neurophysical impairment and disability). Brain Inj 1997;11:661-

476

75.

477

20

ACCEPTED MANUSCRIPT 478

15.

Rinne MB, Pasanen ME, Vartiainen MV, Lehto TM, Sarajuuri JM, Alaranta HT.

479

Motor performance in physically well-recovered men with traumatic brain injury. J Rehabil

480

Med 2006;38:224-9.

481 16.

Williams G, Morris ME, Schache A, McCrory PR. People preferentially increase hip

483

joint power generation to walk faster following traumatic brain injury. Neurorehabil Neural

484

Repair 2010;24:550-8

RI PT

482

SC

485 17.

Williams G, Morris M, Schache A, McCrory P. Incidence of gait abnormalities after

487

traumatic brain injury. Arch Phys Med Rehabil 2009;90:587-93.

M AN U

486

488 18.

McFadyen BJ, Swaine B, Dumas D, Durand A. Residual effects of a traumatic brain

490

injury on locomotor capacity. A first study of spatiotemporal patterns during unobstructed

491

and obstructed walking. J Head Trauma Rehabil 2003;18:512-25.

TE D

489

492 19.

494

instability during obstacle crossing following traumatic brain injury. Gait Posture

495

2004;20:245-54.

AC C

496

Chou LS, Kaufman KR, Walker-Rabatin AE, Brey RH, Basford JR. Dynamic

EP

493

497

20.

Peterson MD. A case-oriented approach exploring the relationship between visual

498

and vestibular disturbances and problems of higher-level mobility in persons with traumatic

499

brain injury. J Head Trauma Rehabil 2010;25:193-205.

500

21

ACCEPTED MANUSCRIPT 501

21.

McCulloch KL, Buxton E, Hackney J, Lowers S. Balance, attention, and dual-task

502

performance during walking after brain injury: associations with falls history. J Head

503

Trauma Rehabil 2010;25:155-63.

504 22.

Williams G, Goldie P. Validity of motor tasks for predicting running ability in

506

acquired brain injury. Brain Inj 2001;15:831-41.

RI PT

505

507 23.

Williams G, Weragoda N, Paterson K, Clark R. Cardiovascular fitness is unrelated

509

to mobility limitations in ambulant people with traumatic brain injury. J Head Trauma

510

Rehabil 2013;28: E1-7.

M AN U

SC

508

511 24.

Williams GP, Schache AG, Morris ME. Mobility after traumatic brain injury:

513

Relationships with ankle joint power generation and motor skill level. J Head Trauma

514

Rehabil 2013;28:371-8.

TE D

512

515 25.

Saltychev M, Eskola M, Tenovuo O, Laimi K. Return to work after traumatic brain

517

injury: Systematic review. Brain Inj 2013;27:1516-27.

EP

516

518 26.

520

injury: trends and challenges. Disabil Rehabil 2007;29:1387-95.

521

Shames J, Treger I, Ring H, Giaquinto S. Return to work following traumatic brain

AC C

519

522

27.

Ruff R, Marshall L, Crouch J, Klauber M, Levin H, Barth J, et al. Predictors of

523

outcome following severe head trauma: follow-up data from the Traumatic Coma Data

524

Bank. Brain Inj 1993;7:101-11.

525

22

ACCEPTED MANUSCRIPT 526

28.

Jourdan C, Bosserelle V, Azerad S, Ghout I, Bayen E, Aegerter P, et al. Predictive

527

factors for 1-year outcome of a cohort of patients with severe traumatic brain injury (TBI):

528

Results from the PariS-TBI study. Brain Inj 2013;27:1000-7.

529 29.

Williams G, Robertson V, Greenwood K, Goldie P, Morris M. The concurrent

531

validity and responsiveness of the high-level mobility assessment tool for measuring the

532

mobility limitations of people with traumatic brain injury. Arch Phys Med Rehabil

533

2006;87:437-42.

SC

RI PT

530

534 30.

Williams G, Pallant J, Greenwood K. Further development of the high-level

536

mobility assessment tool (HiMAT). Brain Inj 2010;24:1027-31.

M AN U

535

537 31.

539

impact of diffuse axonal injury in patients with moderate and severe head injury: a cohort

540

study of early magnetic resonance imaging findings and 1-year outcome. J Neurosurg

541

2010;113:556-63.

EP

542

Skandsen T, Kvistad KA, Solheim O, Strand IH, Folvik M, Vik A. Prevalence and

TE D

538

32.

544

traumatic brain injury. J Head Trauma Rehabil 2005;20:76-94.

545

Povlishock JT, Katz DI. Update of neuropathology and neurological recovery after

AC C

543

546

33.

Johnson VE, Stewart W, Smith DH. Axonal pathology in traumatic brain injury.

547

Exp Neurol 2013;246:35-43.

548

23

ACCEPTED MANUSCRIPT 549

34.

Marquez de la Plata C, Ardelean A, Koovakkattu D, Srinivasan P, Miller A, Phuong

550

V, et al. Magnetic resonance imaging of diffuse axonal injury: quantitative assessment of

551

white matter lesion volume. J Neurotrauma 2007;24:591-8.

552 35.

Stein S, Spettell C. The head injury severity scale (HISS): a practical classification

554

of closed-head injury. Brain Inj 1995;9:437-44.

RI PT

553

555 36.

Caspersen C, Powell K, Christenson G. Physical activity, exercise and physical

557

fitness: definitions and distinctions for health-related research. Public Health Reports

558

1985;100:126-31.

M AN U

SC

556

559 560

37.

Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical

561

scale. Lancet 1974;2:81-4.

TE D

562 38.

Ingebrigtsen T, Romner B, Kock-Jensen C. Scandinavian guidelines for initial

564

management of minimal, mild, and moderate head injuries. The Scandinavian Neurotrauma

565

Committee. J Trauma 2000;48:760-6.

EP

563

566 39.

568

1992;77:562-4.

569

Stein S, Ross S. Moderate head injury: a guide to initial management. J Neurosurg

AC C

567

570

40.

Corrigan JD, Selassie AW, Orman JA. The epidemiology of traumatic brain injury. J

571

Head Trauma Rehabil 2010;25:72-80.

572

24

ACCEPTED MANUSCRIPT 573

41.

Nakase-Richardson R, Sepehri A, Sherer M, Yablon SA, Evans C, Mani T.

574

Classification schema of posttraumatic amnesia duration-based injury severity relative to 1-

575

year outcome: analysis of individuals with moderate and severe traumatic brain injury. Arch

576

Phys Med Rehabil 2009;90:17-9.

RI PT

577 42.

Corrigan J, Selassie A, Lineberry L, Millis S, Wood K, Pickelsimer E, et al.

579

Comparison of the traumatic brain injury (TBI) model systems national dataset to a

580

population-based cohort of TBI hospitaliztions. Arch Phys Med Rehabil 2007;88:418-26.

SC

578

581 43.

Skandsen T, Finnanger TG, Andersson S, Lydersen S, Brunner JF, Vik A. Cognitive

583

impairment 3 months after moderate and severe traumatic brain injury: a prospective

584

follow-up study. Arch Phys Med Rehabil 2010;91:1904-13.

M AN U

582

585 44.

Gentry L. Imaging of closed head injury. Radiology 1994;191:1-17.

588

45.

Williams G, Robertson V, Greenwood K, Goldie P, Morris M. The high-level

589

mobility assessment tool (HiMAT) for traumatic brain injury. Part 2: Content validity and

590

discriminability. Brain Inj 2005;19:833-43.

TE D

586

591

AC C

EP

587

592

46.

Kleffelgaard I, Roe C, Sandvik L, Hellstrom T, Soberg HL. Measurement Properties

593

of the High-Level Mobility Assessment Tool for Mild Traumatic Brain Injury. Phys Ther

594

2013 Mar 15.

595

25

ACCEPTED MANUSCRIPT 596

47.

Bushnik T, Hanks RA, Kreutzer J, Rosenthal M. Etiology of traumatic brain injury:

597

characterization of differential outcomes up to 1 year postinjury. Arch Phys Med Rehabil

598

2003;84:255-62.

599 48.

Majdan M, Mauritz W, Brazinova A, Rusnak M, Leitgeb J, Janciak I, et al. Severity

601

and outcome of traumatic brain injuries (TBI) with different causes of injury. Brain Inj

602

2011;25:797-805.

RI PT

600

SC

603 49.

Butcher I, McHugh GS, Lu J, Steyerberg EW, Hernandez AV, Mushkudiani N, et al.

605

Prognostic value of cause of injury in traumatic brain injury: results from the IMPACT

606

study. J Neurotrauma 2007;24:281-6.

607

M AN U

604

50.

Brown AW, Malec JF, McClelland RL, Diehl NN, Englander J, Cifu DX. Clinical

609

elements that predict outcome after traumatic brain injury: a prospective multicenter

610

recursive partitioning (decision-tree) analysis. J Neurotrauma 2005;22:1040-51.

TE D

608

611 51.

Walker WC, Ketchum JM, Marwitz JH, Chen T, Hammond F, Sherer M, et al. A

613

multicentre study on the clinical utility of post-traumatic amnesia duration in predicting

614

global outcome after moderate-severe traumatic brain injury. J Neurol Neurosurg

615

Psychiatry 2010;81:87-9.

AC C

EP

612

616 617

52.

Skandsen T, Kvistad KA, Solheim O, Lydersen S, Strand IH, Vik A. Prognostic

618

value of magnetic resonance imaging in moderate and severe head injury: a prospective

619

study of early MRI findings and one-year outcome. J Neurotrauma 2011;28:691-9.

620

26

ACCEPTED MANUSCRIPT 621

53.

Lee SY, Kim SS, Kim CH, Park SW, Park JH, Yeo M. Prediction of outcome after

622

traumatic brain injury using clinical and neuroimaging variables. J Clin Neurol 2012;8:224-

623

9.

624 54.

Hilario A, Ramos A, Millan JM, Salvador E, Gomez PA, Cicuendez M, et al. Severe

626

traumatic head injury: prognostic value of brain stem injuries detected at MRI. AJNR Am J

627

Neuroradiol 2012;33:1925-31.

RI PT

625

SC

628 55.

Adams JH, Jennett B, Murray LS, Teasdale GM, Gennarelli TA, Graham DI.

630

Neuropathological findings in disabled survivors of a head injury. J Neurotrauma

631

2011;28:701-9.

M AN U

629

632 56.

Moen KG, Skandsen T, Folvik M, Brezova V, Kvistad KA, Rydland J, et al. A

634

longitudinal MRI study of traumatic axonal injury in patients with moderate and severe

635

traumatic brain injury. J Neurol Neurosurg Psychiatry 2012;83:1193-200.

TE D

633

AC C

637

EP

636

27

ACCEPTED MANUSCRIPT

Table 1. Background characteristics of the traumatic brain injury group and the control group. Variable n TBI (n=65) (SD)

Mean

p

(SD)

136

32.2

(14.0)

34.4

(13.7)

0.36

Education (years)

136

11.9

(2.1)

12.1

(2.1)

0.60

Height (cm)

134

178.9

(9.1)

179.4

(8.0)

0.75

134

79.4

(14.8)

82.9

(13.5)

0.15

Body mass index (kg/m )

133

24.7

(3.4)

25.7

(4.0)

0.11

Current pain (visual analogue scale, cm)

135

1.2

(2.0)

0.7

(1.8)

0.12

Exercise (times pr week)

135

2.6

(2.8)

3.0

(2.7)

0.42

Exercise length pr time (minutes)

132

58.6

(65.1)

70.6

(53.4)

0.25

Exercise activities (number)

135

1.3

(1.3)

1.8

(1.4)

0.02

Weight (kg)

TE D

2

M AN U

Age (years)

SC

RI PT

Mean

Control (n=71)

AC C

EP

Student’s t-test for independent samples, two-tailed. Significance level p<0.05.

ACCEPTED MANUSCRIPT

Table 2. Clinical variables and MRI findings in the acute phase in traumatic brain injury participants. Variable Value n (%) 37 (56.9)

Severe TBI

28 (43.1)

Motor vehicle accident

30 (46.2)

Fall

26 (40.0) 9 (13.8)

≤7 days 8-14 days 15-21 days

Diffuse axonal injury (n=63)

10 (15.4) 8 (12.3) 12 (18.4) 29 (44.6)

Severe level of trauma

36 (55.4)

EP

Cortical contusions (n=63)

34 (53.1)

Moderate level of trauma

Unilateral

17 (27.0)

Bilateral

28 (44.4)

No DAI

17 (27.0)

DAI 1

18 (28.6)

DAI 2

20 (31.7)

DAI 3

8 (12.7)

AC C

Injury Severity Score category (n=65)

TE D

≥22 days

M AN U

Other Duration of post traumatic amnesia (n=64)

RI PT

Injury mechanism (n=65)

Moderate TBI

SC

Head Injury Severity Scale category (n=65)

ACCEPTED MANUSCRIPT

Mean (95% CI)

Walk*

3.4 (3.2-3.5)

3.7 (3.5-3.8)

0.01

Walk backwards*

3.6 (3.4-3.7)

3.9 (3.8-3.9)

<0.01

Walk on toes*

3.3 (3.1-3.6)

3.8 (3.7-3.9)

<0.01

Walk over obstacle*

3.2 (3.0-3.4)

3.7 (3.5-3.8)

<0.01

Run*

2.5 (2.2-2.8)

3.0 (2.8-3.3)

0.01

Skip*

2.3 (2.0-2.7)

3.0 (2.6-3.3)

0.01

Hop forward (most affected/non-dominant leg)*

2.6 (2.3-3.0)

3.3 (3.0-3.6)

<0.01

Bound (most affected/non-dominant leg)

3.1 (2.7-3.4)

3.6 (3.3-3.8)

0.03

Bound (least affected/dominant leg)*

3.1 (2.8-3.5)

3.7 (3.5-3.9)

<0.01

Up stairs dependent

4.9 (4.8-5.0)

4.9 (4.8-5.0)

0.93

Up stairs independent

3.0 (2.7-3.3)

3.1 (2.7-3.4)

0.80

Down stairs dependent

4.8 (4.7-4.9)

4.9 (4.9-5.0)

0.14

2.9 (2.5-3.2)

3.3 (3.0-3.6)

0.06

24.0 (22.2-25.8)

27.9 (26.8-29.1)

<0.01

42.7 (40.2-45.2)

47.7 (46.1-49.2)

<0.01

Total revised HiMAT score* Total HiMAT score

M AN U

AC C

Down stairs independent

EP

Items

SC

(95% CI)

TE D

Mean

RI PT

Table 3. Mean item and total score with 95% confidence intervals (95% CI) on the HiMAT and revised HiMAT for the traumatic brain injury group and the control group. TBI (n=65) Control (n=71)

Mann-Whitney U test. Significance level p<0.05. * Item is included in the revised HiMAT.

P

ACCEPTED MANUSCRIPT

P

4.020

<0.001

37.787

2.813

<0.001

Age at injury (years)

-0.333

0.070

<0.001

-0.237

0.049

<0.001

Sex (female/male)

-4.943

2.229

0.031

-3.686

1.560

0.022

MVA (yes/no)

-4.559

2.040

0.030

-4.034

1.427

0.007

PTA (>7 days/≤7 days)

-4.368

2.157

0.048

-2.975

1.509

0.054

Cortical contusions (yes/no)

2.406

2.172

0.273

1.671

1.519

0.276

DAI 1

1.958

2.607

0.456

1.461

1.824

0.427

DAI 2

-0.790

0.756

0.143

1.767

0.936

DAI 3

-6.127 3.371 2 R =0.588

0.075 <0.001

-3.270 R2=0.599

2.359

0.171 <0.001

2.525

AC C

Model fit

General linear model. Significance level p<0.05.

M AN U

61.659

TE D

(Constant)

SC

p

Unstandardized coefficients B SE

EP

Variable in model

Unstandardized coefficients B SE

RI PT

Table 4. Relationship between total HiMAT score and revised HiMAT score in the chronic phase and clinical variables and MRI findings in the acute phase in traumatic brain injury participants. Total HiMAT score Revised HiMAT score