(B) Treatment of persistent symptoms following SRC
Study	Treatment modality	Key outcome measures	Key results	Level of evidence	Downs and Black score
Moser et al (2012)36	Rest	Graded symptom checklist, computerised cognitive test battery (ImPACT)	Performance on ImPACT prerest and postrest demonstrated improved cognitive function (verbal memory, visual memory, processing speed) p=0.001 and total symptoms p=0.001.	4	11
Moser et al (2015)33	Rest	Graded symptom checklist, computerised cognitive test battery (ImPACT).	Significant difference between prerest and postrest scores in all four IMPACT composite scores (verbal memory p=0.004. Visual memory p=0.002. Reaction time p=0.006. Motor speed p=0.017 and in the total symptoms score (p=0.02).	4	11
Gagnon et al (2009)16	Subsymptom threshold activity	Graded symptom checklist, time to return to normal physical activity	All subjects were reported to recover (ie, return to normal lifestyle and sport participation). Mean duration of intervention=4.4 weeks (SD 2.6).	4	5
Gagnon et al (2016)17	Subsymptom threshold activity	Graded symptom checklist, Beck Depression Inventory, Paediatric Quality of Life Multidimensional Fatigue Scale, balance and coordination, computerised cognitive test battery (ImPACT).	Symptoms decreased between start of intervention and the 6-week follow-up assessment (p=0.004). Subjects recovered in a mean of 6.8 weeks (range of 2–15 weeks).	4	9
Leddy et al (2010)23	Subsymptom threshold activity	Graded symptom checklist, exercise duration, time to return to work/sport	Overall symptom reduction from baseline to post-treatment (p=0.002); all individuals were reported to have recovered at 1.6–16 weeks. Exercise time improved significantly from a baseline mean of 9.75 (6.38) min to 18.67 (2.53) min at treatment termination (p=0.001)	4	10
Leddy et al (2013)24	Subsymptom threshold activity	fMRI using a math task from the Automated Neuropsychological Assessment Metrics (ANAM), performance on ANAM, HR on treadmill test, number of symptoms on post-concussion symptom scale.	After treatment, the exercise group did not differ from healthy controls, but the stretching group had less activity in the cerebellum (p<0.05), the anterior cingulate gyrus and thalamus (p<0.001) than healthy controls. Following treatment, the exercise group had greater exercise HR (p<0.001) and less symptoms (p<0.0004) compared with stretching group. Cognitive performance did not differ by group or time.	3	11
Kurowski et al (2016)21	Subsymptom threshold activity	Graded symptom checklist	Patients in the active treatment group demonstrated a greater rate of symptom improvement than the stretching group (p=0.044). The effect size for the difference between the groups was moderate to large (Cohens d 0.81 across time points and 0.51 at week 7).	2	23
Hugentobler et al (2015)34	Physical therapy	Graded symptom checklist, clinical evaluation of the cervical spine, oculomotor screen and postural control assessment (BESS)	All patients had lower resting symptom severity at the final session. 4/6 patients made fewer errors on the BESS. Improvements were also observed in symptom scores, gaze stability, balance and postural control measures and patient self-management of symptoms. One patient had returned to full preinjury activity levels at the time of their final assessment. 4/6 had returned to preinjury levels within 3–6 months of discharge from physical therapy.	4	4
Schneider et al (2014)11	Physical therapy	Primary outcome = time to medical clearance to return to sport (as determined by blinded study sport medicine physician according to best practice guidelines). Secondary outcome measures=11 point Numeric Pain Rating Scale score, Activities-specific Balance Confidence Scale, Dizziness Handicap Index, SCAT2, Dynamic Visual Acuity, Head Thrust Test, modified Motion Sensitivity Test, Functional Gait Assessment, Cervical Flexor Endurance and Joint Position Error test.	73% (11/15) in intervention group were medically cleared compared with 7% (1/14) of the control group. Individuals in the treatment group were 3.91 (95% CI 1.34 to 11.34) times more likely to be medically cleared to return to sport by 8 weeks when compared with the control group	2	23
McCarty et al (2016)20	Collaborative care including CBT	Primary outcome measures: graded symptom checklist, PHQ-9 to assess depressive symptoms, PROMIS-PA8 (version a) to assess anxiety symptoms, Paediatric Quality of Life Inventory (PedsQL), self-reported satisfaction with care	‘Collaborative care’ group experienced clinically and statistically significant improvements in postconcussive symptoms in addition to functional gains at 6 months compared with ‘Usual care’. Six months after the baseline assessment, 13.0% of intervention patients and 41.7% of control patients reported high levels of postconcussive symptoms (p=0.03), and 78% of intervention patients and 45.8% of control patients reported≥50% reduction in depression symptoms (relative risk 1.71, 95% CI 1.05 to 2.79, p=0.02). No changes between groups were demonstrated in anxiety symptoms. Median number of CBT sessions=8 (range 0–12). 1/3 of patients received subsequent medications.	2	23
Sohlberg and Ledbetter (2015)25	Cognitive rehabilitation	Client selected functional goal	83% of clients achieved self-selected functional goals	4	3
Reddy et al (2013)18	Amantadine	Graded symptom checklist, computerised cognitive test battery (ImPACT) performed at the time of initial assessment and 40–50 days postinjury	At the pretest the amantadine treated group were significantly lower than controls on verbal memory (p=0.007) and visual memory (p=0.04). and higher on total symptoms (p=0.01). Participants in both groups reported a decrease in symptoms and demonstrated improvement in verbal and visual memory, visual processing speed and reaction time scores from pre to post-test. Improvements were larger in the amantadine treatment group on verbal memory (p=0.07), visual memory (p=0.04) and total symptoms (p=0.01)	4	12
Dubrovsky et al (2014)35	Nerve blocks for persistent headache	Review of clinical history and patient satisfaction survey to assess response to injection; ‘good’ therapeutic effect defined as benefit sustained >24 hours and/or requested repeat injection, partial therapeutic benefit defined as benefit <24 hours.	Patients received 1–6 injections (mean 2.1), all patients reported reduction in headache intensity. Mean (SD) preinjection and postinjection headache scores were 5.6 (1.6) and 0.4 (0.9); 93% good therapeutic effect, 7% partial effect. 23/28 responded to the survey (82%), 83% recalled immediate relief of headaches, 61% indicated improved or resolved headaches in days to weeks following injection	4	5
Bramley et al (2015)19	Amitriptyline for persistent headache	Review of clinical history to assess response to medication	Median time to recovery=80 days for females versus 34 days for males, n=68 (17%) were prescribed amitriptyline— 82% (95% CI 70% to 91%) reported improvement in their symptoms, 23% (95% CI 12% to 38%) reported side effects.	4	6

BESS, balance error scoring system; CBT, cognitive behavioural therapy; PHQ-9, patient health questionnaire 9; PROMIS, patient reported outcome measurement information system; RCT, randomised controlled trial; SCAT, sport concussion assessment tool; SRC, sport-related concussion.