Cervico-vestibular Rehabilitation for Mild Traumatic Brain Injury
Cervico-vestibular Rehabilitation for Mild Traumatic Brain Injury
Neck pain, dizziness and headache are common symptoms following mild traumatic brain injury
 (mTBI). The efficacy of cervical spine and vestibular-ocular system impairments intervention
 need to be determined. In this randomized clinical trial, a 6-week personalized clinical
 rehabilitation program on subacute mTBI will be compare to a conventional approach. The
 rehabilitation program will include cervical spine exercise combined with manual therapy as
 well as vestibular-ocular rehabilitation. Overall symptoms will be measured by the
 Post-Concussion Symptoms Scale (PCSS). Disability and symptoms severity related with neck
 pain, headache and dizziness will also be evaluated after the treatment period and at 6-week
 post-treatment.
BACKGROUND

 Mild traumatic brain injury (mTBI) is an acknowledged public health problem. It is estimated
 that between 1.6 to 3.8 million brain injuries occur annually in the United States, with up
 to 75% classified as mild. The majority of mTBI resolves within 10 to 14 days. However, up to
 31% of pediatric cases and 25% of adult cases present post concussive syndrome (PCS), which
 is a persistence of somatic (for example: headache, neck pain, dizziness, nausea, balance
 dysfunction), cognitive (for example: memory loss and slowed reaction time), and/or
 psychological (for example: depression and anxiety) symptoms. Among these symptoms, headache
 and dizziness are the most commonly reported, followed by nausea and neck pain. Many of these
 PCS symptoms could be explained by injuries to structures near or in the head, other than the
 brain itself. For example, following a trauma, structures such as the cervical spine, the
 vestibular ocular system and the temporomandibular joint can be injured. The energy needed to
 produce an mTBI can be transferred to the neck and produce an injury mechanism similar to the
 one observed in whiplash associated disorders (WAD). Neck pain, headaches, dizziness and
 balance dysfunction are common symptoms associated with both mTBI and WAD. Specific
 interventions for these injuries are therefore needed when present.

 For individuals presenting persistent post-concussion symptoms, the most recent international
 consensus statement (2017 Berlin consensus on concussion in sport) recommends the addition of
 an individualized rehabilitation approach to the usual rest and sub-symptoms gradual
 activation strategies. However, this new recommendation is based on weak evidence as well as
 expert recommendations. Therefore, the effects of adding individualized rehabilitation
 interventions for the treatment of potential impairments of body function associated with
 neck pain, headache and dizziness, needs to be evaluated in individuals with mTBI. The
 treatment of neck pain, cervicogenic headache, dizziness and balance dysfunction with
 multimodal rehabilitation interventions or vestibular rehabilitation has been demonstrated
 effective in several systematic and Cochrane reviews; however none of the randomized control
 trials (RCT) included in these reviews included individuals with mTBI. Two RCTs have
 partially looked at the effects of rehabilitation interventions in some subgroups of mTBI
 patients. One RCT (n=31) has demonstrated that patients with sport-related concussion treated
 with a standardized combination of vestibular and cervical physiotherapy were quicker to be
 medically cleared to return to sport than a control group who was resting and gradually
 returning to activities. However, the intervention used in that study was not individualized
 to the specific impairments of the participants. Another RCT recruited 41 sport-related
 concussion patients with dizziness as the main symptom and found that a rehabilitation
 treatment targeting dizziness was more effective in terms of time to medical clearance than a
 minimal intervention (subtherapeutic and non-progressive therapeutic techniques). However, as
 a most likely multifactorial condition, mTBI treatments arguably need to be individualized to
 the patient's clinical presentation and the outcomes need to encompass all types of symptoms.
 In that context, there is a need for further RCTs evaluating the effect of a personalized
 patient-centered rehabilitation approach (based on the Berlin consensus) on mTBI.

 Objectives and hypothesis: The primary objective of the current RCT is to compare the
 addition of a 6-week personalized patient-centered clinical rehabilitation program to a
 conventional approach in adults with subacute (> than 3 weeks post TBI) headache, neck pain
 and /or dizziness-related to mTBI on the severity and impact of symptoms as measured by the
 Post-Concussion Symptoms Scale (PCSS). The secondary outcomes will be: clearance to return to
 usual activities, number of recurrence episode, functional level, neck pain, headache and
 dizziness. Our hypothesis is that the personalized patient-centered clinical rehabilitation
 program will improve overall symptoms, time to return to activities as well as function
 faster than the conventional approach and between group differences will be observed at week
 6, 12 and 26.

 METHODS

 Study Design: This single-blind, parallel-group RCT will include 8 supervised treatments
 during a 6-week rehabilitation program (2 sessions/week the first 2 weeks, then 1
 session/week for the last 4 week) and four evaluation sessions over 26 weeks (baseline, week
 6 [immediately after the rehabilitation program], week 12 [6 week after the end of the
 rehabilitation program] and week 26). All participants will take part in the baseline
 evaluation. After giving an informed consent, they will first complete a questionnaire on
 sociodemographic (age, gender, type of sport or physical activities, number of years playing
 sport and/or other activities), symptomatology (mechanism of injury, history of previous
 mTBI, history of dizziness, headache, neck pain and unsteadiness) and comorbidity, as well as
 self-administered questionnaires that evaluate symptoms and functional limitations, including
 the PCSS (primary outcome). Once baseline data collected, participants will be randomly
 assigned to the control or intervention group. The control group will receive a the 6-week
 conventional intervention based on sub-symptoms gradual cardio-vascular exercise program. The
 experimental group will receive a 6-week personalized patient-centered clinical
 rehabilitation program in addition to the same intervention as the control group. Between
 week 6 and week 12, participants will be asked to continue their exercises and follow the
 advice given at the last meeting with the health professional. Six, 12 and 26 weeks after
 randomization, all the outcomes will be revaluated. The evaluation sessions will be carried
 out at the Centre interdisciplinaire de recherche en réadaptation et en intégration sociale
 (CIRRIS) by a research assistant blinded to group assignment, while the interventions will be
 given at Clinique Cortex by experienced physiotherapists, neuropsychologists and
 kinesiologists.

 Population: 46 adults presenting to the Clinique Cortex (Concussion clinic) with a diagnosis
 of mTBI (based on the definition of the Berlin 2016 international consensus statement) and
 persistent symptoms of dizziness, neck pain and/or headaches (reported on the PCSS)17 lasting
 for more than 3 weeks will be recruited. The reported symptoms must 1) have started in the
 first 72 hours following an impact, 2) include one or more cognitive symptom(s), as found in
 the PCSS).

 Sample size calculation is based on changes evidenced by the PCSS for individuals with mTBI.
 According to sample size calculation (G*Power 3.1.9.2; α=0.05, effect size=0.8, power
 [1-β]=0.80, Standard Deviation(SD)=20.0 PCSS points, Minimal Detectable Change (MDC)=12.3
 PCSS points, 10% attrition), a minimum of 23 patients are needed in each group. Therefore, 46
 participants with mTBI will be recruited.

 Inclusion and exclusion criteria are described elsewhere in the form.

 Randomisation/Blinding: A randomisation list will be generated by an independent research
 assistant (not involved in data collection) prior to the initiation of the study using a
 random number generator. Allocation will be concealed in sealed and opaque envelopes that
 will be sequentially numbered. A blocked randomisation will be used to make sure that two
 equal groups of 23 participants are obtained. Stratification will be done according to sex to
 ensure women and men are equally represented in each group as it has been shown that women
 tend to recover more slowly than man from a mTBI. Given that it is not possible to blind the
 treating physiotherapist and the participants, a single-blind design will be used as only the
 evaluator will be blinded. One of the Principal Investigator (PI) will open the randomisation
 envelope indicating the participant's assignment and will send the information to the
 treating therapist. The physiotherapists, neuropsychologists and the kinesiologists will be
 blinded to the baseline evaluation results. To evaluate the effectiveness of blinding, the
 evaluator will complete a question related to her/his opinion of the allocation. Participants
 will be unaware of the treatment provided to other participants. Participants will be
 instructed not to reveal or discuss treatment with the evaluator. To assess blinding
 effectiveness, the evaluator will answer the following question at the week-6 evaluation: "In
 your opinion, which intervention this participant received?" The possible answers are: 1)
 conventional (comparison group); 2) intervention testing the personalized patient-centered
 clinical rehabilitation program (experimental group); 3) I have no idea.

 The outcome measures are well described elsewhere in the form.

 Statistical Analyses: Descriptive statistics will be used for all outcome measures at each
 measurement time to summarize results. Baseline demographic data will be compared
 (independent t-test and Chi-squared tests) to establish the comparability of groups. All data
 will be tested to check the distributional assumptions for the inferential statistical
 analyses. An intention-to-treat analysis will be used in which all participants will be
 analysed in the group to which they were originally assigned. Per protocol analysis will also
 be performed. All dropouts and the reason for dropping out of the study will be reported. Any
 harm or unintended effects during the programs will be recorded. A 2-way ANOVA (2 Groups
 [Group 1 or 2] x 4 Time [week 0, 6, 12, 26]) will be used to analyse the effects of the
 rehabilitation programs on the primary outcome and on most of the secondary outcomes (SPSS
 22, proc GENLIN). We expect no group effects, as the groups should be equal at baseline. A
 time effect should be observed, as both groups should improve given they will both receive an
 interventions. Finally, we expect a significant Time x Group interaction since the groups
 should react differently over time, with a faster recovery for the Experimental group seen at
 week 6 and 12. This will be statistically detailed with post-hoc tests (Bonferroni
 correction). An independent t-test will be used to analyse the effects of the rehabilitation
 programs on clearance to return to function.
Inclusion Criteria:

 -  Between 18 and 65 years of age;

 -  Sustained a mTBI in the past 3 to 12 weeks;

 -  Having ongoing post-concussion symptoms from the list in the PCSS that started 72
 hours or less after an impact;

 -  Having felt at least one or more cognitive symptoms that started 72 hours or less
 after an impact;

 -  Having abnormalities on one of the following test : the cervical physical examination
 (eg, tenderness/spasm on segmental testing, or reduced motion), the vestibular
 evaluation (eg, Dix hallpike test, vestibulo-ocular reflex test, or head thrust test)
 or the ocular motor evaluation (eg, convergence, smooth visual pursuits, or saccades).

 Exclusion Criteria:

 -  Patients with more than 30 minutes of loss of consciousness for the current episode;

 -  Patients with more than 24 hours of post-traumatic amnesia;

 -  Glasgow Coma Scale score lower than 14 at the time of injury;

 -  Patients with radiographic evidence of subdural hemorrhage, epidural hemorrhage,
 intraparenchymal hemorrhage, and cerebral or cerebellar contusion;

 -  Post-injury hospitalization for more than 48 hours;

 -  Fracture (head, neck and spine);

 -  Having a neurological condition, other than the actual mTBI;

 -  Having a cognitive or behavioural impairment with participation in the study;

 -  Have had general anesthesia during the three-month period prior to the study;

 -  Having received physiotherapy tretament for the currwnt episode.