Knee function, knee proprioception and related brain activity following anterior cruciate ligament injury

Abstract: Background: Injury of the anterior cruciate ligament (ACL) may have negative effects on the short- and long-term function and proprioception of the knee joint. However, existing tests of knee function are often sports-related and less relevant for assessment in the very long term and there remains no ‘gold standard’ test of knee proprioception. A growing body of research also suggests neuroplasticity post-ACL injury, but brain response to lower limb proprioception tasks is not established and nor is the potentially related impact of ACL injury. Developing standardised, reliable and valid tests of knee function and proprioception including brain imaging may target rehabilitation interventions more efficiently.Methods: Paper I assesses knee function ~23 years after ACL injury. One ACL-injured group treated with physiotherapy only (ACLD) and one with additional reconstruction (ACLR) were compared to asymptomatic controls for performance and knee kinematics of the One-leg rise (OLR) test. Paper II is a published protocol for Paper III, which is a systematic review and meta-analysis of the psychometric properties (PMPs) of knee joint position sense (JPS) tests among individuals with ACL injury. Paper IV describes the development of one weight-bearing (WB) and one non-weight-bearing (NWB) knee JPS test using motion capture. Test-retest reliability is assessed and errors are compared between an active ACLR group (~23 months after reconstruction) and two asymptomatic groups of different activity levels. Paper V characterises brain response to a knee JPS test using simultaneous functional magnetic resonance imaging and motion capture among individuals ~2 years after ACL reconstruction and controls.Results: ACLD performed significantly fewer repetitions of the OLR with both legs compared to controls and displayed significantly greater knee abduction than ACLR and controls. Meta-analyses found sufficient validity for existing knee JPS tests, particularly those of passive movements, by showing that ACL-injured knees produce significantly greater absolute errors than contralateral asymptomatic knees and those of controls. However, the tests were found not to be responsiveness to intervention and the remaining PMPs, such as reliability, require more evidence to better determine their quality. The novel knee JPS tests of paper IV showed mixed reliability but were better for the WB compared to the NWB test and when absolute rather than variable error was the outcome measure. Post-hoc comparisons revealed significantly greater errors for less-active controls compared to the ACLR group. For Paper V, the knee JPS test recruited brain regions such as the parietal cortex, precentral gyrus and insula. Greater knee JPS errors were correlated with greater activation in the insula, as well as the anterior and middle cingula. The ACLR group showed significantly greater response compared to controls for mainly the precuneus, but only at the uncorrected level.Conclusions: Knee function may be negatively affected more than two decades after ACL injury based on performance and knee kinematics of the OLR test, which offers a clinician-friendly assessment tool of lower limb function but requires further investigation. Existing knee JPS tests seem to discriminate ACL-injured from asymptomatic knees. Passive tests produce greater differences, but current methods are diverse and often poorly reported, complicating recommendation of specific tests for research or clinics. The novel WB and NWB knee JPS tests should be developed for improved reliability, but their outcomes demonstrate the importance of considering activity level when comparing knee JPS between groups, which is rarely done. Brain regions recruited during our knee JPS test have previously been associated with, e.g. sensorimotor processes, interoception and body schema, confirming proprioceptive demands of the task. Correlations between knee JPS errors and response in the insula and cingula suggest they have an important role during such tasks. Subtle differences in brain response between ACLR and CTRL warrant further investigation.