Key Points

Abstract

Introduction

Concussion or mild traumatic brain injury (mTBI) accounts for up to 90% of all TBIs.¹ The yearly incidence in Denmark is 457 per 100000 inhabitants²; however, these numbers do not include those who consult general practitioners or do not seek care. The true incidence is estimated to be around 600 per 100000.³

Concussion or mTBI is defined as a transmission of mechanical energy due to a blow to the head, neck, or body that results in disruption of brain function.^4,5 Consensus regarding diagnostic criteria emphasizes at least 1 of the following signs: (1) any alteration of mental state immediately after injury, (2) posttraumatic amnesia for less than 24 hours, (3) loss of consciousness for less than 30 minutes, or (4) other signs of focal and transient neurologic dysfunction.^5,6,7

Most people who sustain a concussion or mTBI recover quickly, but a significant proportion experience long-term symptoms.^8,9,10 According to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10),¹¹ recovery from concussion is expected within the first 2 to 3 weeks, and persistent symptoms are defined as those lasting for more than 4 weeks after injury.¹² Studies indicate that up to 34% to 44% of patients with concussion or mTBI experience symptoms at 3 to 6 months after injury, and between 5% and 20% experience symptoms at 12 months after injury.^8,13,14,15

Persistent postconcussion symptoms (PPCS) comprise a combination of physical (headache, dizziness, blurred vision, sleep disturbance, neck pain, and fatigue), cognitive (slowed thinking, difficulties with attention, concentration, memory, or executive functions), and emotional or behavioral symptoms (changed emotional responsivity, irritability, quickness to anger, disinhibition, or emotional lability),¹⁶ and might be associated with changes in personality and difficulties regarding personal and professional identity.¹⁷ There is an uncertainty regarding the effectiveness of commonly applied nonpharmacological interventions to treat PPCS, and to our knowledge, there is a scarcity of meta-analyses dedicated to this topic. Furthermore, although systematic approaches are in general applied, the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE)¹⁸ approach has only been used sporadically.

The Danish Health Authority commissioned a set of National Clinical Guidelines with the objective to evaluate and summarize the evidence for the effectiveness of nonpharmacological interventions in adults experiencing PPCS and to provide recommendations for clinical practice. The selected areas of interest were (1) early information and advice, (2) graded physical exercise, (3) vestibular rehabilitation, (4) manual treatment of neck and spine, (5) oculomotor vision treatment, (6) psychological treatment, and (7) interdisciplinary coordinated rehabilitative treatment. This article reports the methodology and results of this guideline based on meta-analyses and the GRADE approach.

Methods

The content of this guideline is structured around selected clinical questions in accordance with the Population, Intervention, Comparison, and Outcome (PICO) framework.¹⁹ Making recommendations for diagnostic procedures, care pathways, or providing estimates of associated costs were beyond the scope of this guideline. Recommendations are based on systematic reviews and follow the principles described in GRADE.¹⁸ This guideline followed the AGREE reporting checklist. The complete clinical guideline is available in Danish online.²⁰ A protocol for this systematic review and meta-analysis has been registered in the PROSPERO database.²¹ The protocol for this study was reviewed and approved by the Danish Health Authority. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.

Results

A total of 13097 articles were identified; of those, 109 were excluded as duplicates. Among the remaining 12988 articles, titles and abstracts were screened for inclusion and exclusion criteria. A total of 297 articles received a full-text review, and 11 relevant systematic reviews^{31,32,33,34,35,36,37,38,39,40,41} were identified for 5 of the clinical questions. Only 1 systematic review³³ matched our clinical question (graded physical exercise) and was of sufficient methodological quality(eTable 3 in the Supplement); however, it did not contribute any primary study matching our inclusion and exclusion criteria. The search date for individual studies for this question was then limited to the date of the latest search in the included systematic review,³³ and here we identified 2 relevant RCTs.^42,43 Furthermore, 1 relevant RCT⁴⁴ was identified in a systematic review for manual treatment of neck and back. A total of 19 individual RCTs^{42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60} comprising 2007 participants (1064 women [53.0%]; 943 men [47.0%]) were identified for 6 of the clinical questions. Nine^{43,45,46,47,49,52,53,55,60} of these included a minority of adolescents in the sample. No evidence was identified for the effect of oculomotor vision treatment. Thus, all recommendations were based exclusively on primary studies. For characteristics of the included studies, see eTable 5 in the Supplement. For flowcharts of included literature, see eFigure 1 in the Supplement.

The available evidence was limited for all interventions, ranging from low to very low mainly owing to risk of bias, imprecision (few studies identified or few patients included), and indirectness (patients aged <18 years included) (Table 3). For results of meta-analyses, see eFigure 2 in the Supplement. For summary of findings table, including the rating of the evidence and risk of bias assessment, see eTable 4 in the Supplement. For recommendations including the supporting evidence, see Table 4.

Discussion

This guideline considered 7 clinical questions regarding nonpharmacological management of PPCS. Based on very low to low certainty of evidence, the guideline panel provided weak recommendations for early information and advice, graded physical exercise, vestibular rehabilitation for persistent vestibular dysfunction, manual treatment of the neck and back, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. A consensus-based recommendation was provided for oculomotor vision treatment to treat persistent visual symptoms. The guideline panel concluded that intensified research into all intervention types is needed.

Given that concussion or mTBI can be associated with persistent symptoms and disability,^65,66,67,68 there has been a shift from passively awaiting symptom remission to recommending active management when symptoms persist. Thus, our recommendations align with the Synthesis of Practice Guidelines from the American Congress of Rehabilitation Medicine’s Mild TBI task force⁴; the American Physical Therapy Association’s (APTA) guideline for physical therapy evaluation and treatment after concussion or mild TBI⁶⁹; the third edition of the Ontario Neurotrauma Foundation’s (ONF) Guideline for concussion or mild TBI and persistent symptoms⁵; and the latest update on the consensus statement published by the Concussion in Sports Group (CISG).⁷⁰ However, compared with our guideline, these guidelines have different scopes and include pediatric and adolescent populations. Furthermore, although these guidelines apply a systematic approach to guideline generation, they do not apply the GRADE approach.

Early information and advice was recommended based on 7 RCTs,^{45,46,47,48,49,50,51} of which 6 were included in the meta-analysis. The study by Ponsford et al⁴⁹ was not included because it was presented as a short report. Collectively, the studies concluded that information should be tailored to individual patient needs and that information and advice are particularly beneficial if provided over a longer period of time. This recommendation aligns with the Synthesis of Practice Guidelines⁴ as well as with the ONF⁵ and APTA⁶⁹ guidelines that give a grade A, or strong, recommendation. The CISG guideline⁷⁰ does not address this question. Our guideline provides a weak recommendation based on GRADE owing to possible risks of bias in the included studies as well as indirectness.

Graded physical exercise was recommended based on 2 RCTs.^42,43 In both, the intervention was part of interdisciplinary rehabilitation programs with several interventions applied in parallel. Critical outcomes included physical functioning, which presumably reflected the effect of graded physical exercise. Both the APTA⁶⁹ and the CISG guideline⁷⁰ recommend graded physical exercise as a treatment of autonomic instability or physical deconditioning, with the APTA⁶⁹ indicating level A, or strong evidence. The ONF guideline⁵ recommends exercise below symptom threshold in management of posttraumatic fatigue (grade C). The Synthesis of Practice Guidelines⁴ advocates exercise in general. Our guideline arrived at a weak recommendation based on GRADE.

Vestibular rehabilitation was recommended based on 2 RCTs.^52,53 In both, participants also received exercise and manual treatment of the cervical and thoracic spine. The ONF⁵ and APTA guidelines⁶⁹ give a grade A, or strong, recommendation for dealing with benign paroxysmal positional vertigo. Furthermore, the ONF guideline gives a grade A recommendation for treatment of unilateral peripheral vestibular dysfunction, whereas the APTA guideline indicates level B, or moderate evidence, for vestibular rehabilitation in conjunction with oculomotor rehabilitation. The ONF guideline gives a grade C consensus-based recommendation, and APTA indicates level C, or weak evidence, for treatment of functional balance impairment. The CISG guideline⁷⁰ recommends a targeted physical therapy program for patients with vestibular dysfunction without further specification.

Manual treatment of the neck and back, ie, mobilization and/or manipulation, is recommended based on 2 small RCTs,^44,52 of which only one⁵² could be included in the meta-analysis owing to poor reporting in the other.⁴⁴ The 2 studies indicate possible beneficial outcomes regarding pain and return to sport, resulting in a weak recommendation. The Synthesis of Practice Guidelines⁴ and the ONF guideline⁵ do not include manual treatment of the neck and back. The APTA guideline recommends that practitioners address cervical and thoracic spine dysfunction, including manual treatment based on level B, or moderate, evidence.⁶⁹ The CISG guideline recommends targeted physical therapy in patients with cervical dysfunction without further details.⁷⁰

Oculomotor vision treatment is recommended based on consensus in the guideline panel. Low-quality studies without appropriate control groups, however, do exist and report positive effects.^61,62,63,64 The ONF guideline⁵ gives grade C, or a consensus-based recommendation, for vision assessment and treatment, whereas the APTA guideline⁶⁹ indicates level B, or moderate, evidence. However, this guideline deals with oculomotor rehabilitation in combination with vestibular treatment, which may explain the discrepancy. The CISG guideline⁷⁰ does not address this question.

Psychological treatment is recommended based on 9 RCTs,^{42,43,54,55,56,57,58,59,60} of which 8 were included in the meta-analysis.^{42,43,54,55,56,57,58,59,60} Tiersky et al⁵⁹ was not included owing to insufficient reporting. Psychological interventions may be applied for multiple reasons, eg, to treat mental health disorders (primarily anxiety and depression), to address cognitive symptoms, and/or to change maladaptive behavioral strategies. Accordingly, the RCTs applied a combination of different approaches, such as psychoeducation, counseling, cognitive behavioral therapy, computer-based cognitive remediation training, and energy management. The Synthesis of Practice Guidelines⁴ emphasizes primarily an active approach to mental health disorders, with fast initiation of cognitive behavioral therapy and/or pharmacotherapy. The ONF guideline⁵ gives a grade B recommendation regarding a routine screen for depression and anxiety followed by a specialist treatment, and a grade B recommendation is given for cognitive behavioral therapy as a supplementary intervention for patients with psychological risk factors. The ONF guideline⁵ gives a grade A recommendation for neuropsychological assessment, grade B recommendation for treatment of persistent cognitive difficulties, and grade C recommendation for stress management techniques. The CISG guideline⁷⁰ recommends cognitive behavioral therapy for persistent mood disorders or behavioral issues.

Interdisciplinary coordinated rehabilitation was recommended based on 3 RCTs.^42,43,60 Their results indicate its usefulness regarding the primary outcome (collective burden of symptoms) as well as several secondary outcomes (Table 4). The Synthesis of Practice Guidelines⁴ highlights the need for individually tailored interdisciplinary treatment. The ONF guideline⁵ gives a grade A recommendation for evidence-based neurorehabilitation for patients with cognitive impairment and a grade B recommendation for interdisciplinary vocational assessment for those who do not resume preinjury work duties. The CISG guideline⁷⁰ recommends a psychological, cervical, and vestibular rehabilitation performed in a collaborative manner based on detailed assessment of physical and psychosocial factors.

Even though the development of the guideline followed a rigorous methodology, our confidence in the recommendations is low or very low. This low confidence is due to scarcity and inadequacies of the underlying literature wherein studies have risk of bias due to investigating the effects of experiential interventions with difficulties related to blinding of participants and therapists. Moreover, in clinic, interventions were often used in combination as part of a multimodal approach with multiple interventions given in parallel.^10,42

The weak recommendations call for shared decision-making, involving a discussion with the patient. People with PPCS represent a heterogeneous group regarding both their trauma-induced consequences and their premorbid functioning levels, coping strategies, and life situation in general.⁷¹

Expert groups have used the lack of evidence for benefit or harm for a particular intervention as an argument for not putting forward a recommendation.⁷² Such positions have, however, been met with frustration by health care professionals who look to expert groups for guidance.⁷³ Fortunately, the GRADE approach accommodates these circumstances because it provides interpretations for patients, clinicians, and policy makers.³⁰ Faced with either no or weak evidence, it is important that patients know that their particular preference among the various treatments should guide choice of intervention; clinicians must recognize that different interventions may be appropriate for different patients and help each patient to arrive at a management decision consistent with their values. Policy makers must involve relevant professional groups and stakeholders when determining design-of-care pathways.³⁰ Importantly, guideline panels should not refrain from making recommendations because individual patients and clinicians will make different choices when faced with a weak recommendation. In fact, this is to be expected. Consequently, the GRADE Working Group encourages panels to make recommendations whenever possible whether they are based on solid evidence or not.³⁰

Conclusions

There is an urgent need for more methodologically robust research evaluating the outcomes of nonpharmacological treatments for persistent symptoms after concussion or mTBI. Given the best available evidence to date, and based on the findings of this systematic review and meta-analysis, active management and treatment of PPCS is recommended, both through individual disciplines targeting specific problems and through interdisciplinary rehabilitation. There was agreement on this recommendation across the available guidelines, including the one presented here, regardless of their applied methodology.

Notes

References