Psychologically Informed Cervicovestibular Rehabilitation (PIC Rehab) for Mild Traumatic Brain Injury: A Feasibility Trial

Problem: Mild traumatic brain injuries and concussions affect over 480,000 or 1.2% of Canadians each year.1-3 While many individuals recover in the initial 4 weeks following mTBI, up to 30% have persisting symptoms and functional impairments, leading to significant disability, decreased quality of life, and reduced participation in education, physical, and occupational related activities.

Dizziness, balance problems, headaches, and neck pain: Headaches and dizziness are consistently the most commonly reported symptoms following mTBI with estimates of up to 95% of individuals reporting headaches and 40-80% reporting dizziness. In a majority of cases, these symptoms are reported concurrently. Standing balance and dynamic balance deficits have consistently been identified following mTBI, some of which resolve early post-injury (within 3-5 days), while some balance problems remain for weeks to months following injury. Dizziness, balance problems, headaches, and neck pain are associated with greater odds of developing persisting symptoms. In addition, persisting dizziness, headaches, neck pain, and balance impairments can lead to decreased participation in recreational, social, occupational, and educational activities as well as lower quality of life. Decreased activity can, in turn, lead to significant morbidity due to secondary health complications. Therefore, treatments aimed at minimizing headaches, dizziness and balance problems following mTBI are urgently needed to minimize the public health burden of this commonly occurring injury.

Treatment of dizziness, balance problems, headaches, and neck pain following mTBI: Previous randomized controlled trials (RCTs) have identified large positive treatment effects following targeted cervical and vestibular rehabilitation (CVPT) for children, adolescents, and adults with dizziness, neck pain, and headaches following mTBI. These treatments are personalized, based on the individual's profile of specific impairments. CVPT includes treatments targeting neuromuscular and sensorimotor control in combination with manual therapy and soft tissue techniques as indicated. Specific rehabilitation exercises are gradually progressed, performed in combination with symptom-tolerated aerobic exercise, and eventually evolve to task, context, and/or sport specific exercises. From a mechanistic standpoint, the goal of this treatment is to facilitate sensorimotor integration (i.e. integration of visual, vestibular, proprioceptive input and resultant motor output) and either reweigh central balancing of stimuli to optimize function of these systems or up-regulate the use of alternate systems in the event that one of the sensory systems is not optimally operating. Recent international consensus recommendations and clinical practice guidelines recommend CVPT as a treatment that has some of the strongest evidence to date to facilitate recovery. However, up to 27% of individuals may not respond to CVPT5, necessitating other treatment options.

Cognitive Behavioural Therapy: For individuals with persisting symptoms following mTBI, evidence supports the use of cognitive behavioural therapy (CBT). CBT is a form of treatment that uses multiple non-pharmacological strategies including education, behavioural and cognitive strategies. This form of non-pharmacological treatment has demonstrated safety and efficacy for a number of different conditions including insomnia, depression, mental health, and more recently for mTBI. For individuals with chronic pain, improvements in anxiety and depressive symptoms have been demonstrated but no difference in pain intensity or pain catastrophizing has been found to date. Patient centred approaches are necessary to optimize effectiveness. In individuals with dizziness, the addition of CBT to physical and/or vestibular rehabilitation may yielded improved outcomes.

Thus, CVPT and CBT in combination may have additive effects for individuals with mTBI. Here we take a transdisciplinary team-based approach to evaluate an integrated combination of CVPT and CBT.

Objectives:

We will conduct a pilot trial using a stepped approach to evaluate the feasibility and patient perceptions of CVPT alone as compared to CVPT in combination with CBT (hereafter referred to as PIC Rehab, or psychologically-informed CVPT) on 1) symptom severity and 2) time to resolution of mTBI related symptoms in adults with symptoms for greater than 14 days following mTBI.

The specific objectives of this study are as follows:

Objective 1: Determine the feasibility of PIC Rehab; Objective 2: Generate preliminary estimates of effect for PIC Rehab on mTBI related symptom resolution compared to CVPT alone; Objective 3: Describe changes by sex in domain specific outcomes of PIC Rehab compared to CVPT alone.

We hypothesize that PIC Rehab will be feasible and will have a greater impact on resolution of symptoms for participants with concomitant anxiety, depression, patient specific functional disability, than CVPT alone.

Methods:

Thirty-four adults aged 18-70 years with symptoms of dizziness, neck pain and/or headaches for at least 14 days following mTBI who are referred for cervicovestibular physiotherapy with one or more impairments related to the vestibular, oculomotor, sensorimotor, cervical spine, neuromuscular control, will be invited to participate. The participants who are included in this study are those with impairments that have previously been shown to respond to cervicovestibular rehabilitation. Patients who have previously undergone a session of cervicovestibular physiotherapy will be excluded from the study. The first 15 participants will complete typical CVPT and the next "step" of the study will have the following 15 participants complete PIC Rehab. Participants will be recruited consecutively in the order they are referred/approached based on their initial symptom reports of headaches, dizziness and/or neck pain at the time of presentation to the clinic, inclusive of both sexes and all genders, with the aim to have equal numbers of male and female participants.

Participants will be eligible for participation if they are referred to or seek treatment at Evidence Sport and Spinal Therapy for cervicovestibular rehabilitation following mTBI. For the purposes of this pilot feasibility trial we will limit our recruitment to one clinic with multiple therapists to enable future study of a larger trial at multiple clinics and, thus, avoid the chance of contamination between control and intervention groups. Consent to contact will be obtained in clinic for those patients meeting the inclusion criteria as part of the initial intake to the clinic and a member of the research team will follow-up and contact the patient by phone.

Eligibility Screen: Patients who agree to be contacted will undergo an eligibility screen with questionnaires (e.g., PCSS) by telephone with a research assistant. If the patient meets the eligibility for the trial they will then be sent a consent form to review and sign online followed by the initial demographic forms, questionnaires and subsequently scheduled for the initial assessment. After completing the initial assessment, the RA will confirm eligibility. It is possible that participants may have pre-existing relationships with the researchers or clinicians that are part of the research team as participants will be recruited through community sport medicine and/or physiotherapy clinics. Thus, all potential participants will be made aware that their choice to participate in this study will in no way affect the care that they receive and that they are free to decline participation at any time.

Protocol:

Participants will be blinded to the hypothesis of the study and to the opposite treatment group to which they are assigned. Thus, two separate consent forms will be used in the study - one for each type of treatment received. Both treatment groups will be seen once weekly for 8 weeks or until the time of symptom resolution and medical clearance to return to sport/learn/occupation and outcomes will be repeated at the 8 week time point. All of the physiotherapists who are participating in the study will undergo a standard CVPT training course. Following recruitment of the initial 15 patients, all therapists will undergo and online and in person training course for PIC Rehab. To facilitate recruitment in a timely fashion and prevent delays between arms, the first 3 of 6 therapists who complete treatment with their participants will complete the PIC Rehab training and the second 3/6 will complete a later training course for PIC Rehab.

CVPT alone: The control intervention will be the typical standard of care of CVPT (Schneider et al 2014, 2018) including individualized cervical and vestibular rehabilitation based on the patient's presentation, including symptom-tolerated exercise.

PIC Rehab: The Psychological Informed-CVPT (PIC Rehab) intervention (modified from Herdman et al) will include education, goal setting, distraction techniques, reattribution of symptoms, relaxation, in vivo exposure, cognitive therapy and problem solving. Collaborative training for physiotherapist providing the PIC Rehab will occur with the study team (KS, NS, KOY, CP).

The stepped process of the treatments will minimize contamination by therapist knowing the principles of the PIC Rehab. Adherence to the intervention will be assessed using scheduled audio recordings of the treatment sessions (to measure therapist adherence to the protocol) and patient reports of completion of home exercises (patient adherence). As this is a pilot feasibility study, a sample of 30 participants (15 in each group) allowing for two drop outs per group based on previous studies done at our centre was deemed to be pragmatic with in a 6 month time frame.

Initial Assessment: The initial assessment will take approximately 90 minutes and participants will complete a series of in person outcomes with the study physiotherapist as listed below that are specific to domains that may be affected by concussion. Where relevant, additional questions and health history information and clinically relevant outcomes will be gathered in keeping with the current standard of care.

Follow-up appointments: All participants will complete a brief set of questionnaires on REDCap at the time of each follow-up appointment to capture current symptoms, completion of home program exercises and any additional treatment that has been undertaken since the time of the previous appointment. In the event that new symptoms are present, the relevant self report and in person clinical outcomes related to the specific symptoms will be repeated. Treating physiotherapists will complete an adherence questionnaire after each session and record all subcomponents of treatment individualized to the patient.

Outcome assessments: Outcome assessments, both self report and in person clinical outcomes, will be repeated 8 weeks after the initial baseline assessment. Following participation in the trial, participants and therapists will be invited to take part in semi-structured interviews to share their experiences as part of the trial, including barriers and facilitators to the rehabilitation protocols.

Outcomes:

Primary feasibility outcomes will include recruitment, retention rate, adverse events, clinical implementation barriers and facilitators faced, and adherence to protocol (therapist).

Secondary outcomes of recovery including time to resolution of symptoms (days) to inform a phase 2 clinical trial. In keeping with international recommendations, and exploratory outcomes that assess impairment specific factors that may change with treatment (i.e. cervical spine, vestibulo-ocular, dynamic balance, etc) will be included.

Secondary outcomes will include change in symptom severity scores on the PCSS (/132), time to resolution of symptoms (days), time to medical clearance to return to sport, learn and work (days) (as relevant) to inform a phase 2 clinical trial. These outcomes will be defined as per the latest international consensus recommendations (page 702). Return to work (RTW) will be defined in the same was as return-to-learn and will be defined as: return to pre-injury occupational activities with no new support, including occupational accommodations or modifications.

Exploratory outcomes are outcomes that are part of typical clinical care and will include impairment based/domain specific outcomes that are the current best available outcomes and aligned with previous trials in the area. All outcomes will also be described by sex. Exploratory outcomes will include the following:

• Fear Avoidance Behaviour after Traumatic Brain Injury Questionnaire (FAB-TBI)
• World Health Organization Disability Assessment Schedule (WHODAS) 2.0 12 item self-report version
• Anxiety (Generalized Anxiety Disorder-7, GAD-7)
• Depression (Personal Health Questionnaire-9, PHQ-9)
• Sleep Screen
• Post Concussion Symptom Scale from the Sport Concussion Assessment Tool 6 (SCAT6)
• Test of Memory Malingering (TOMM)
• Dizziness Handicap Inventory
• Modified Dizziness Questionnaire
• Neck Disability Index
• Neck Pain Questionnaire
• Patient Specific Functional Scale (PSFS)
• Post Traumatic Headache Questionnaire
• Subjective Units of Discomfort Scale (SUDS)
• Neurological screen including cranial nerve, cerebellar and long track signs
• Cervical Spine: Cervical Spine range of motion, cervical flexor endurance, cervical flexion rotation test, craniocervical flexion test, manual spinal examination, palpation for segmental tenderness, extension rotation test, palpation of tender trigger points, palpation of greater and lesser occipital nerves
• Tests done with fixation removed including spontaneous nystagmus, gaze evoked, fixation, hyperventilation, intracranial pressure, head shaking, positional testing (including Dix-Hallpike and Roll tests right and left).
• Vestibulo-ocular reflex tests: head thrust test, dynamic visual acuity
• Quantified Vestibular Ocular Motor Screen (qVOMS)
• Motion sensitivity Test
• Dynamic Balance: functional gait assessment (FGA) and advanced FGA
• Balance Error Scoring System (BESS)
• Buffalo Concussion Treadmill Test (BCTT) or Bike Test (BCBT) as appropriate depending on the patient preference
• Orthostatic Vital Signs

Data Analysis:

Primary feasibility outcomes will be summarized using descriptive statistics [means (standard deviations) or medians/modes (ranges or interquartile ranges) or proportions] as appropriate. Secondary outcomes will be summarized descriptively by treatment group. In addition, exploratory Kaplan Meier survival analysis curves will be constructed by group for time to resolution of symptoms, return to sport, learn, occupation will be evaluated using Kaplan Meier survival analysis curves with the outcome of 8 weeks. Exploratory outcomes will be described by treatment group and sex using descriptive statistics as appropriate based on the outcome and the distribution of the data. Thematic analysis will be used to evaluate barriers and facilitators to PIC Rehab for both participants and providers.