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Vestibular Consequences of Blast-related Mild Traumatic Brain Injury (TBI)

Vestibular Consequences of Blast-related Mild Traumatic Brain Injury

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT01021137
Enrollment
140
Registered
2009-11-26
Start date
2011-05-01
Completion date
2017-12-31
Last updated
2019-08-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Brain Injury, Dizziness

Keywords

vestibular function tests, postural balance, neuroimaging

Brief summary

The purpose of this project is to determine the effects of mild traumatic brain injury and blast exposure on the inner ear balance and central nervous systems.

Detailed description

The goal of this project is to determine the effects of mild traumatic brain injury (mTBI) and blast exposure on the vestibular system and CNS. Dizziness and balance disorders are common symptoms associated with mTBI or head injury. Numerous studies have provided significant evidence that mTBI or head injury can cause damage to the vestibular system; however, most have limited the vestibular evaluation to assessment of horizontal semicircular canal function. Recently, methods have been developed to assess otolith function, and there is some evidence that head injury may affect the otolith organs to a greater degree than the semicircular canals. mTBI has been called the signature condition of Veterans returning from Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF), and the cause is often related to blast exposure from improvised explosive devices, mortars or rocket-propelled grenades. Some investigators have presumed that dizziness and balance disorders following blast exposure are related to CNS damage caused by the TBI rather than the pressure wave from the blast injury. Thus, most research has focused on the vestibular consequences of TBI (or head injury), and there is limited data on the effects of blast exposure on vestibular function or balance. Recently, magnetic resonance imaging techniques have been developed that may allow for testing the assumption that the symptoms of dizziness or imbalance related to head injury or blast exposure are often due to central vestibular or CNS involvement. Specific aims of this project are to determine the effect of mTBI and blast exposure on (1) peripheral vestibular system function (specifically, horizontal semicircular canal function, and otolith organ function), (2) central vestibular/CNS function, (3) postural stability, and (4) dizziness-related quality of life. Four subject groups will include Veterans complaining of dizziness/imbalance with (1) a history of blast exposure, (2) with mTBI, (3) with blast exposure and mTBI, and (4) a control group. Each subject will undergo tests of horizontal semicircular canal function (caloric and rotary chair), tests of otolith function (vestibular evoked myogenic potentials, subjective visual vertical), central vestibular function/CNS function (ocular motor tests, diffusion tensor and susceptibility weighting imaging), gait and balance testing, and the Dizziness Handicap Inventory.

Interventions

None listed

Sponsors

VA Office of Research and Development
Lead SponsorFED

Study design

Observational model
COHORT
Time perspective
CROSS_SECTIONAL

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes

Inclusion criteria

* Complaint of dizziness and/or imbalance * History of blast exposure * Diagnosis of mild traumatic brain injury

Exclusion criteria

* Prior history of vestibular or neurological disorder * Presence of internal metal * Pregnancy

Design outcomes

Primary

MeasureTime frameDescription
Peripheral Vestibular Function (Utricular-ocular Pathway): Ocular Vestibular Evoked Potential (oVEMP)Up to 20 minutesBone-conducted ocular vestibular evoked potential (oVEMP) inter-ear amplitude asymmetry ratio was used as a measure of otolith organ function (utricular-ocular pathway). Inter-ear amplitude asymmetry ratio was calculated as: \[(\|L\_N1-P1\| - \|R\_N1-P1\|)/ (\|L\_N1-P1\| + \|R\_N1-P1\|)\] x100, where L\_N1-P1 = peak-to-peak oVEMP amplitude of the left eye/right ear and R\_N1-P1 = peak-to-peak oVEMP amplitude of the right eye/left ear. The oVEMP is a contralateral response; therefore, recordings from the left eye reflect the response of the right ear and vice versa. The amplitudes were calculated from oVEMP responses at a stimulus intensity of 155 dB peakFL. The criterion for abnormal oVEMP was defined as an absent oVEMP or a corrected oVEMP amplitude asymmetry ratio greater than or equal to 40%, either of which would indicate a unilateral vestibular loss. A bilateral vestibular loss was indicated by absent oVEMPs bilaterally.
Rotary Chair Slow Harmonic Acceleration (SHA) Gainup to 30 minutesRotary chair slow harmonic acceleration (SHA) vestibulo-ocular reflex (VOR) gain at 0.01 Hz was used as a measure of peripheral vestibular function (VOR/horizontal semicircular canal). VOR gain is defined as the ratio of the slow component velocity eye movement (output) to the velocity of the head movement (input).
Peripheral Vestibular Function (Saccular-collic Pathway): Cervical Vestibular Evoked Potential (cVEMP)Up to 30 minutesAir-conducted cervical vestibular evoked potential (cVEMP) inter-ear amplitude asymmetry ratio was used as a measure of otolith organ function (saccular-collic pathway). Inter-ear amplitude asymmetry ratio was calculated as: \[(\|L\_P1-N1\| - \|R\_P1-N1\|)/ (\|L\_P1-N1\| + \|R\_P1-N1\|)\] x100, where L\_P1-N1 = peak-to-peak cVEMP amplitude of the left side and R\_P1-N1 = peak-to-peak cVEMP amplitude of the right side. The amplitudes were calculated from cVEMP responses at a stimulus intensity of 120 dB peakSPL. The criterion for abnormal cVEMP was defined as an absent cVEMP or a corrected cVEMP amplitude asymmetry ratio greater than or equal to 40%, either of which would indicate a unilateral vestibular loss. A bilateral vestibular loss was indicated by absent cVEMPs bilaterally.
Rotary Chair Slow Harmonic Acceleration (SHA) PhaseUp to 30 minutes (SHA phase is obtained simultaneously with SHA gain)Rotary chair slow harmonic acceleration (SHA) vestibulo-ocular reflex (VOR) phase at 0.01 Hz was used as a measure of peripheral vestibular function (VOR/horizontal semicircular canal). The phase is the timing difference between the velocity of head movement and the slow-phase eye velocity. This parameter is normalized for a full cycle of a sinusoid (360 degrees) and presented in an angular unit of degrees rather than a unit of time. For perfectly compensatory eye movements the phase is 0 degrees, meaning there is no difference between the actual eye velocity and the ideal VOR (by convention, degrees is added to the phase so that the comparison is based on the ideal VOR responses instead of the actual head motion).
Peripheral Vestibular Function (Vestibulo-ocular Reflex/Semicircular Canal): Caloric Weaknessup to 30 minutesThe caloric weakness was determined using monothermal warm inter-ear difference (MWIED) which was calculated as: (\|RW\| - \|LW\| )/( \|RW\| + \|LW\|) x 100, where RW = the maximum slow phase velocity (SPV) of nystagmus induced by warm water irrigation in the right ear and LW = the maximum SPV of nystagmus induced by warm water irrigation in the left ear. For participants with MWIED \> 10, then cool caloric irrigation was also performed and caloric weakness was determined using a bithermal inter-ear difference (BIED) calculated as: (\|RW\| + \|RC\|) - (\|LW\| + \|LC\|) / (\|RW\| + \|RC\| + \|LW\| + \|LC\|) x 100, where RC = maximum SPV of nystagmus induced by cool water irrigation in the right ear and LC = maximum SPV of nystagmus induced by cool water irrigation in the left ear.

Secondary

MeasureTime frameDescription
Postural Stability: Sensory Organization Test (SOT)Up to 20 minutesThis measure is the composite equilibrium score from six conditions of the sensory organization test obtained with the Neurocom Equitest. Results of the SOT were calculated based on maximum peak-to-peak anterior-posterior sway expressed as an equilibrium score ranging from 0 to 100, with 0 indicating loss of balance (i.e., required support of harness, took a step, touched walls for support or opened eyes in eyes closed conditions) and 100 indicating perfect stability. The outcome measure was the equilibrium composite score and was calculated by the software as the weighted average of the equilibrium scores for the six conditions. For ages 18-59 years, the normative value (mean - 1.67 SD) for the composite score is at least 70 (NeuroCom, 2011).
Dizziness Handicap InventoryUp to 10 minutesThe Dizziness Handicap Inventory (DHI) was used as a quality of life measure.The DHI measures the subject's self-perceived dizziness. The scale has 25 questions with 3 possible answers each: Yes = 4 points, Sometimes = 2 points, and No = 0 points. The minimum number of points that a subject can score is 0 and the maximum number of points is 100. The subject's self-perceived dizziness is reported as a percentage with a range of 0-100%, and is calculated by: subject's total number of points/maximum number of points (100) x 100%. The higher the score on the DHI, the worse a patient's self-perceived dizziness.
Central Vestibular/Central Nervous System (CNS) Function: Visual Fixation Suppression1 minuteVisual fixation suppression was used as a measure of central vestibular/CNS function. Visual fixation suppression is a measure of vestibulo-ocular reflex (VOR) gain obtained during visual fixation at 0.16 Hz slow harmonic acceleration on the rotary chair. VOR gain was defined as the ratio of the slow component velocity eye movement (output) to the velocity of the head movement (input). Visual fixation suppression was considered normal if VOR gain is suppressed \> 50% with visual fixation compared to no fixation.

Countries

United States

Participant flow

Recruitment details

140 Veterans were recruited for this study. Participants included Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans and healthy, age & gender matched controls. Veteran participants had a history of traumatic brain injury (TBI), blast exposure, or both.

Pre-assignment details

Six participants were consented to participate in the study, but did not return to complete the protocol. Case history was not collected and therefore, the participants could not be assigned to any of the study groups.

Participants by arm

ArmCount
TBI & Blast
OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure and a diagnosis of mild TBI
52
Blast Only
OEF/OIF Veterans complaining of dizziness and/or imbalance with history of blast exposure without TBI
16
TBI Only
OEF/OIF Veterans complaining of dizziness and/or imbalance with a history of mild TBI and no blast exposure
9
Healthy Controls
Age and gender matched control subjects with no complaints of dizziness and/or imbalance or history of TBI or blast exposure
32
Total109

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Overall StudyLost to Follow-up9426
Overall StudyWithdrawal by Subject1003

Baseline characteristics

CharacteristicBlast OnlyTBI OnlyTBI & BlastHealthy ControlsTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants1 Participants0 Participants1 Participants
Age, Categorical
Between 18 and 65 years
16 Participants9 Participants51 Participants32 Participants108 Participants
Age, Continuous40.5 years
STANDARD_DEVIATION 10.5
39.7 years
STANDARD_DEVIATION 10.9
37.1 years
STANDARD_DEVIATION 9.9
31.2 years
STANDARD_DEVIATION 9.8
35.9 years
STANDARD_DEVIATION 10.6
Region of Enrollment
United States
16 Participants9 Participants52 Participants32 Participants109 Participants
Sex: Female, Male
Female
1 Participants1 Participants1 Participants4 Participants7 Participants
Sex: Female, Male
Male
15 Participants8 Participants51 Participants28 Participants102 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
0 / 620 / 200 / 110 / 41
other
Total, other adverse events
0 / 620 / 200 / 110 / 41
serious
Total, serious adverse events
0 / 620 / 200 / 110 / 41

Outcome results

Primary

Peripheral Vestibular Function (Saccular-collic Pathway): Cervical Vestibular Evoked Potential (cVEMP)

Air-conducted cervical vestibular evoked potential (cVEMP) inter-ear amplitude asymmetry ratio was used as a measure of otolith organ function (saccular-collic pathway). Inter-ear amplitude asymmetry ratio was calculated as: \[(\|L\_P1-N1\| - \|R\_P1-N1\|)/ (\|L\_P1-N1\| + \|R\_P1-N1\|)\] x100, where L\_P1-N1 = peak-to-peak cVEMP amplitude of the left side and R\_P1-N1 = peak-to-peak cVEMP amplitude of the right side. The amplitudes were calculated from cVEMP responses at a stimulus intensity of 120 dB peakSPL. The criterion for abnormal cVEMP was defined as an absent cVEMP or a corrected cVEMP amplitude asymmetry ratio greater than or equal to 40%, either of which would indicate a unilateral vestibular loss. A bilateral vestibular loss was indicated by absent cVEMPs bilaterally.

Time frame: Up to 30 minutes

Population: Cervical VEMP could not be evaluated on 2 participants in the TBI \& Blast group and 3 participants in the Blast Only group.

ArmMeasureValue (MEAN)Dispersion
TBI & BlastPeripheral Vestibular Function (Saccular-collic Pathway): Cervical Vestibular Evoked Potential (cVEMP)26.1 percentage of inter-ear asymmetryStandard Deviation 26.2
Blast OnlyPeripheral Vestibular Function (Saccular-collic Pathway): Cervical Vestibular Evoked Potential (cVEMP)31.2 percentage of inter-ear asymmetryStandard Deviation 32.3
TBI OnlyPeripheral Vestibular Function (Saccular-collic Pathway): Cervical Vestibular Evoked Potential (cVEMP)45.1 percentage of inter-ear asymmetryStandard Deviation 36.5
Healthy ControlsPeripheral Vestibular Function (Saccular-collic Pathway): Cervical Vestibular Evoked Potential (cVEMP)20.1 percentage of inter-ear asymmetryStandard Deviation 15.9
Primary

Peripheral Vestibular Function (Utricular-ocular Pathway): Ocular Vestibular Evoked Potential (oVEMP)

Bone-conducted ocular vestibular evoked potential (oVEMP) inter-ear amplitude asymmetry ratio was used as a measure of otolith organ function (utricular-ocular pathway). Inter-ear amplitude asymmetry ratio was calculated as: \[(\|L\_N1-P1\| - \|R\_N1-P1\|)/ (\|L\_N1-P1\| + \|R\_N1-P1\|)\] x100, where L\_N1-P1 = peak-to-peak oVEMP amplitude of the left eye/right ear and R\_N1-P1 = peak-to-peak oVEMP amplitude of the right eye/left ear. The oVEMP is a contralateral response; therefore, recordings from the left eye reflect the response of the right ear and vice versa. The amplitudes were calculated from oVEMP responses at a stimulus intensity of 155 dB peakFL. The criterion for abnormal oVEMP was defined as an absent oVEMP or a corrected oVEMP amplitude asymmetry ratio greater than or equal to 40%, either of which would indicate a unilateral vestibular loss. A bilateral vestibular loss was indicated by absent oVEMPs bilaterally.

Time frame: Up to 20 minutes

Population: Ocular VEMP could not be obtained from 4 participants from the TBI \& Blast group.

ArmMeasureValue (MEAN)Dispersion
TBI & BlastPeripheral Vestibular Function (Utricular-ocular Pathway): Ocular Vestibular Evoked Potential (oVEMP)22.0 percentage of inter-aural asymmetryStandard Deviation 21.2
Blast OnlyPeripheral Vestibular Function (Utricular-ocular Pathway): Ocular Vestibular Evoked Potential (oVEMP)15.7 percentage of inter-aural asymmetryStandard Deviation 14.3
TBI OnlyPeripheral Vestibular Function (Utricular-ocular Pathway): Ocular Vestibular Evoked Potential (oVEMP)39.1 percentage of inter-aural asymmetryStandard Deviation 28.3
Healthy ControlsPeripheral Vestibular Function (Utricular-ocular Pathway): Ocular Vestibular Evoked Potential (oVEMP)18.0 percentage of inter-aural asymmetryStandard Deviation 14.6
Primary

Peripheral Vestibular Function (Vestibulo-ocular Reflex/Semicircular Canal): Caloric Weakness

The caloric weakness was determined using monothermal warm inter-ear difference (MWIED) which was calculated as: (\|RW\| - \|LW\| )/( \|RW\| + \|LW\|) x 100, where RW = the maximum slow phase velocity (SPV) of nystagmus induced by warm water irrigation in the right ear and LW = the maximum SPV of nystagmus induced by warm water irrigation in the left ear. For participants with MWIED \> 10, then cool caloric irrigation was also performed and caloric weakness was determined using a bithermal inter-ear difference (BIED) calculated as: (\|RW\| + \|RC\|) - (\|LW\| + \|LC\|) / (\|RW\| + \|RC\| + \|LW\| + \|LC\|) x 100, where RC = maximum SPV of nystagmus induced by cool water irrigation in the right ear and LC = maximum SPV of nystagmus induced by cool water irrigation in the left ear.

Time frame: up to 30 minutes

Population: Caloric weakness could not be obtained from 1 participant in the Blast Only group and 2 participants in the Healthy Control group.

ArmMeasureValue (MEAN)Dispersion
TBI & BlastPeripheral Vestibular Function (Vestibulo-ocular Reflex/Semicircular Canal): Caloric Weakness8.8 percentage of caloric weaknessStandard Deviation 8.5
Blast OnlyPeripheral Vestibular Function (Vestibulo-ocular Reflex/Semicircular Canal): Caloric Weakness14.7 percentage of caloric weaknessStandard Deviation 20.8
TBI OnlyPeripheral Vestibular Function (Vestibulo-ocular Reflex/Semicircular Canal): Caloric Weakness12.3 percentage of caloric weaknessStandard Deviation 5.6
Healthy ControlsPeripheral Vestibular Function (Vestibulo-ocular Reflex/Semicircular Canal): Caloric Weakness7.1 percentage of caloric weaknessStandard Deviation 6
Primary

Rotary Chair Slow Harmonic Acceleration (SHA) Gain

Rotary chair slow harmonic acceleration (SHA) vestibulo-ocular reflex (VOR) gain at 0.01 Hz was used as a measure of peripheral vestibular function (VOR/horizontal semicircular canal). VOR gain is defined as the ratio of the slow component velocity eye movement (output) to the velocity of the head movement (input).

Time frame: up to 30 minutes

Population: Rotary chair slow harmonic acceleration (SHA) VOR gain at 0.01 Hz was not evaluated in 1 participant in the TBI \& Blast group.

ArmMeasureValue (MEAN)Dispersion
TBI & BlastRotary Chair Slow Harmonic Acceleration (SHA) Gain.4 UnitlessStandard Deviation 0.1
Blast OnlyRotary Chair Slow Harmonic Acceleration (SHA) Gain.4 UnitlessStandard Deviation 0.1
TBI OnlyRotary Chair Slow Harmonic Acceleration (SHA) Gain.4 UnitlessStandard Deviation 0.1
Healthy ControlsRotary Chair Slow Harmonic Acceleration (SHA) Gain.4 UnitlessStandard Deviation 0.1
Primary

Rotary Chair Slow Harmonic Acceleration (SHA) Phase

Rotary chair slow harmonic acceleration (SHA) vestibulo-ocular reflex (VOR) phase at 0.01 Hz was used as a measure of peripheral vestibular function (VOR/horizontal semicircular canal). The phase is the timing difference between the velocity of head movement and the slow-phase eye velocity. This parameter is normalized for a full cycle of a sinusoid (360 degrees) and presented in an angular unit of degrees rather than a unit of time. For perfectly compensatory eye movements the phase is 0 degrees, meaning there is no difference between the actual eye velocity and the ideal VOR (by convention, degrees is added to the phase so that the comparison is based on the ideal VOR responses instead of the actual head motion).

Time frame: Up to 30 minutes (SHA phase is obtained simultaneously with SHA gain)

Population: Rotary chair slow harmonic acceleration (SHA) phase at 0.01 Hz was not calculated for 2 participants in the TBI \& Blast group and 1 participant in the Blast Only group. Phase at 0.01 Hz could not be calculated for individuals with bilateral vestibular loss.

ArmMeasureValue (MEAN)Dispersion
TBI & BlastRotary Chair Slow Harmonic Acceleration (SHA) Phase41.3 degreesStandard Deviation 8.1
Blast OnlyRotary Chair Slow Harmonic Acceleration (SHA) Phase40.1 degreesStandard Deviation 6.4
TBI OnlyRotary Chair Slow Harmonic Acceleration (SHA) Phase40.1 degreesStandard Deviation 8.8
Healthy ControlsRotary Chair Slow Harmonic Acceleration (SHA) Phase42.2 degreesStandard Deviation 8.3
Secondary

Central Vestibular/Central Nervous System (CNS) Function: Visual Fixation Suppression

Visual fixation suppression was used as a measure of central vestibular/CNS function. Visual fixation suppression is a measure of vestibulo-ocular reflex (VOR) gain obtained during visual fixation at 0.16 Hz slow harmonic acceleration on the rotary chair. VOR gain was defined as the ratio of the slow component velocity eye movement (output) to the velocity of the head movement (input). Visual fixation suppression was considered normal if VOR gain is suppressed \> 50% with visual fixation compared to no fixation.

Time frame: 1 minute

Population: VOR gain during a visual fixation task and 0.16 Hz could not be obtained on 2 participants in the TBI \& Blast group and 3 participants in the Blast Only group.

ArmMeasureValue (MEAN)Dispersion
TBI & BlastCentral Vestibular/Central Nervous System (CNS) Function: Visual Fixation Suppression0.069 unitlessStandard Deviation 0.049
Blast OnlyCentral Vestibular/Central Nervous System (CNS) Function: Visual Fixation Suppression0.058 unitlessStandard Deviation 0.034
TBI OnlyCentral Vestibular/Central Nervous System (CNS) Function: Visual Fixation Suppression0.059 unitlessStandard Deviation 0.034
Healthy ControlsCentral Vestibular/Central Nervous System (CNS) Function: Visual Fixation Suppression0.065 unitlessStandard Deviation 0.041
Secondary

Dizziness Handicap Inventory

The Dizziness Handicap Inventory (DHI) was used as a quality of life measure.The DHI measures the subject's self-perceived dizziness. The scale has 25 questions with 3 possible answers each: Yes = 4 points, Sometimes = 2 points, and No = 0 points. The minimum number of points that a subject can score is 0 and the maximum number of points is 100. The subject's self-perceived dizziness is reported as a percentage with a range of 0-100%, and is calculated by: subject's total number of points/maximum number of points (100) x 100%. The higher the score on the DHI, the worse a patient's self-perceived dizziness.

Time frame: Up to 10 minutes

ArmMeasureValue (MEAN)Dispersion
TBI & BlastDizziness Handicap Inventory48.7 score on a scaleStandard Deviation 23.1
Blast OnlyDizziness Handicap Inventory48.6 score on a scaleStandard Deviation 25.5
TBI OnlyDizziness Handicap Inventory41.6 score on a scaleStandard Deviation 15.7
Healthy ControlsDizziness Handicap Inventory0 score on a scaleStandard Deviation 0
Secondary

Postural Stability: Sensory Organization Test (SOT)

This measure is the composite equilibrium score from six conditions of the sensory organization test obtained with the Neurocom Equitest. Results of the SOT were calculated based on maximum peak-to-peak anterior-posterior sway expressed as an equilibrium score ranging from 0 to 100, with 0 indicating loss of balance (i.e., required support of harness, took a step, touched walls for support or opened eyes in eyes closed conditions) and 100 indicating perfect stability. The outcome measure was the equilibrium composite score and was calculated by the software as the weighted average of the equilibrium scores for the six conditions. For ages 18-59 years, the normative value (mean - 1.67 SD) for the composite score is at least 70 (NeuroCom, 2011).

Time frame: Up to 20 minutes

Population: The composite equilibrium score of the sensory organization test was not obtained for 4 participants in the TBI \& Blast group, 2 participants in the Blast Only group and 2 participants in the Healthy Control group.

ArmMeasureValue (MEAN)Dispersion
TBI & BlastPostural Stability: Sensory Organization Test (SOT)65 units on a scaleStandard Deviation 18.8
Blast OnlyPostural Stability: Sensory Organization Test (SOT)62 units on a scaleStandard Deviation 19.3
TBI OnlyPostural Stability: Sensory Organization Test (SOT)61 units on a scaleStandard Deviation 16.1
Healthy ControlsPostural Stability: Sensory Organization Test (SOT)81 units on a scaleStandard Deviation 5.1

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026