Title: Does peripheral neuroinflammation predict chronicity following whiplash?
Funder: Versus Arthritis

Abstract: The incidence and socioeconomic consequences of whiplash appear undiminished. Most whiplash cases are considered grade 2 whiplash associated disorder (WAD2), which refers to patients with neck complaints and musculoskeletal tenderness but importantly, who have no clinical sign of nerve injury. Approximately 50% of these patients develop chronic symptoms, and it has been suggested that they may have a neuropathic condition despite the lack of overt nerve injury on routine clinical tests. Several lines of evidence suggest that peripheral neuroinflammation may contribute to symptoms, which include findings from animal models of neuroinflammation, clinical signs of nerve trunk mechanical sensitivity and increased T2-weighted MRI signal of the brachial plexus and median nerve in a cohort of patients with chronic WAD2. In this study, we aim to establish the contribution of peripheral neuroinflammation to WAD2 and its role in prognosis. We will determine 1) the presence of peripheral neuroinflammation during the acute stage, 2) whether it predicts chronicity, 3) the time course of peripheral neuroinflammation from acute to chronic stages, and 4) whether cost-effective clinical tests could be used as markers of neuroinflammation. This two-centre three-year prospective longitudinal study will use MR neurography to assess peripheral neuroinflammation and nerve fibre integrity of the brachial plexus and median nerves, combined with clinical tests that are associated with neuroinflammation. One hundred and fifteen patients will be recruited within one month following injury, as well as 32 healthy volunteers. The following assessments will be conducted on all participants: clinical examination, quantitative sensory testing, nerve trunk mechanosensitivity testing to pressure and stretch, measurement of serum inflammatory proteins and MRI neurography of the brachial plexus and median nerve. MR imaging will include T1-weighted, T2-weighted and diffusion tensor imaging, which will be used to assess nerve morphology, inflammation and nerve integrity respectively. Patients will also be asked to complete the painDETECT, neck disability index (NDI) and the post-traumatic stress inventory questionnaires at initial assessment. By comparing MRI findings between patients and controls we can determine the extent of neuroinflammation in the acute stage. At six months, patients will be asked to repeat the NDI questionnaire, and grouped into recovered/non-recovered based on their scores. This will allow us to determine whether neuroinflammation in the acute stage predicts chronicity. Twenty five recovered and twenty five non-recovered patients will be reimaged at six months to establish the course of neuroinflammation. Finally, by correlating clinical measures to MRI findings, we hope to determine whether a cost-effective clinical test could be used to identify nerve inflammation. In summary, the ability to predict chronicity based on the presence of nerve inflammation would enable clinicians to ‘red flag’ such patients early after injury. The early identification of such patients would enable intervention strategies with targeted treatment approaches to be employed.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL;NEUROLOGICAL