Table 2

Summary of results of studies meeting inclusion criteria

(A) Assessment of persistent symptoms following SRC
Study Method of assessment Key outcome measures Key results Level of evidence
Kozlokski et al (2013)26 Graded exercise test (Balke protocol)Graded symptom checklist, physiological measures (HR, BP, RPE), test durationPersistent symptoms group had lower exercise test duration (8.5±4.4 min vs 17.9±3.6 min; p <0.001), HR (142.8±24.1 vs 175.2+/-17.4; p <0.001) and systolic BP (142.1±18.3 mm Hg vs 155.5±24.5 mm Hg; p=0.02), and higher diastolic BP (78.4±10.2 mm Hg vs 73.5±11.7 mm Hg; p=0.03) compared with controls4
Leddy et al (2015)12 Graded exercise test (Balke protocol)Graded symptom checklistGraded exercise test and clinical examination were used to divide subjects with PCS into ‘physiological PCS’ (abnormal treadmill performance and a normal cervical/vestibular physical examination) or ‘cervicogenic/vestibular PCS’ (normal treadmill performance and an abnormal cervical/vestibular physical examination). No differences were demonstrated between the groups on symptoms alone4
Clausen et al (2016)22 Graded exercise test and measures of cerebral blood flow velocity (CBFV) using transcranial dopplerPhysiological measures during exercise treadmill test (including BP and minute ventilation (VE)), end-tidal CO2 (PETCO2) and CBFVAt baseline, participants with PCS had significantly lower ˙VE (18%) and greater PETCO2 (5%) and CBFV (14%) versus controls at similar workloads in association with appearance of symptoms and premature exercise cessation. Following a 12-week subsymptom threshold aerobic exercise programme ˙VE, PETCO2, CBFV and exercise tolerance normalised4
Ellis et al (2015)27 Vestibular-ocular clinical examination (including evaluation of gross extraocular movements and smooth pursuits, near-point convergence, and horizontal and vertical saccades and modified head-shake test)Graded symptom checklist, presence of VOD22 of the 77 patients (28.6%) with acute SRC and 15 of the 24 (62.5%) with PCS met the clinical criteria for VOD. There was a significant increase in the adjusted odds of developing PCS among patients with acute SRC who had VOD compared with those without VOD (adjusted OR 4.10; 95% CI 1.04 to 16.16)4
Heyer et al (2016)13 Head upright tilt table (HUT) testing - used to divide the groups into ‘normal’, ‘syncope’ and ‘postural tachycardic syndrome (POTS)' groupsGraded symptom checklist; self-reported levels of light-headedness (over preceding 7 days), frequency of symptomsPatients with POTS had higher symptom scores than normal patients (p<0.001) and higher ratings of light-headedness than both normal patients (p=0.015) and patients with syncope (p=0.04). 12 patients with POTS underwent repeat tilt table testing within 3–6 months. 9 of 12 (75%) no longer met POTS diagnostic criteria. All patients with resolution of POTS had corresponding improvements in symptoms, including light-headedness and vertigo.4
Gosselin et al (2012)28 EEG evaluating ERP during a WM) taskAmplitude and latency of frontal (N200 and N350) and parietal (P200 and P300) ERP wavesMild TBI group had a lower percentage of correct answers on behavioural performance on the WM task (p<0.05) and smaller amplitudes of both frontal N350 and parietal P300 ERP components when compared with controls (p<0.05). Smaller ERP amplitudes were associated with slower reaction times and worse accuracy on the WM task among patients with MTBI (p<0.05)4
Chen et al (2007)14 fMRI—using a verbal and non-verbal WM taskfMRI, computerised cognitive test battery (CogState Sport)Accuracy and speed on the cognitive test battery were comparable for the control and low PCS group. The moderate PCS group showed significantly slower response times than the control group on the matching (p<0.05) and one-back tasks (p<0.05). fMRI showed reduced task-related activation patterns in the DLPC for both low and m
oderate PCS groups. Severity of PCS predicted fMRI blood oxygen level-dependent signal changes in cerebral prefrontal regions.
Chen et al (2008)29 Beck depression inventory II used to stratify subjects into no (score 0–9), mild (10–19) or moderate (20–29) depression. Structural MRI (including T1, T2 and fluid-attenuated inversion recovery sequences), fMRI using a WM task.fMRI, response speed and accuracy on the WM task and voxel-based morphometry examining grey matter concentration on structural imagingThere was no performance difference between the groups. Athletes with concussion with depression symptoms showed reduced activation in the DLPC and striatum and attenuated deactivation in medial frontal and temporal regions. The severity of symptoms of depression correlated with neural responses in brain areas that are implicated in major depression.4
Chen et al (2008)30 fMRI —using a verbal and non-verbal WM task.fMRI, response speed and accuracy on the WM task and voxel-based morphometry examining grey matter concentration on structural imagingThere was no performance difference between the groups. Despite normal structural MRI findings, all symptomatic concussed athletes initially showed atypical brain activation patterns in the DLPC. Compared with the initial postinjury evaluation, those athletes at follow-up with PCS resolved showed significant increases in activation in the left DLPC. Concussed athletes whose PCS status remained unchanged at follow-up continued to show atypical activation in DLPC.4
Keightley et al (2014)31 fMRI—using a verbal and non-verbal WM task.fMRI, neuropsychological testingConcussed group had (1) significantly worse performances on the WM tasks, Rey figure delayed recall and verbal fluency; (2) significantly reduced task-related activity in bilateral DLPC, left premotor cortex, supplementary motor area and left superior parietal lobule during performance of verbal and non-verbal WM tasks and (3) less activation in the dorsal anterior cingulate cortex, left thalamus and left caudate nucleus during the non-verbal task.4
Bartnik-Olson et al (2014)32 MRI and MRSPWI, three-dimensional (3D) magnetic resonance spectroscopic imaging and DTIIn the bilateral thalami, patients with SRC showed reduced CBF (p=0.02, p=0.02) and relative cerebral blood volume (CBV; p=0.05 and p=0.03), compared with controls. NAA/creatine (Cr) and NAA/choline (Cho) ratios were reduced in the corpus callosum (p=0.003; p=0.05) and parietal white matter (p<0.001; p=0.006) of subjects with SRC, compared with controls. DTI revealed decreased fractional anisotropy and increased radial diffusivity in patients with persistent symptoms following SRC compared with controls.4
  • BP, blood pressure; CBF, cerebral blood flow; DLPC, the dorsolateral prefrontal cortex; DTI, diffusion tensor imaging; EEG, electroencephalogram, ERP, event-related potential; fMRI, functional MRI; HR, heart rate; MRS, magnetic resonance spectroscopy; MTBI, mild TBI; NAA, N-acetylaspartate; PCS, post-concussion syndrome; PWI, perfusion-weighted imaging; RPE, rating of perceived exertion; SRC, sport-related concussion; TBI, traumatic brain injury; VOD, vestibulo-ocular dysfunction; WM, working memeory.