Authors:
Dr. Joel Fundaun | University of Oxford | United Kingdom
Dr. Colette Ridehalgh | Brighton and Sussex Medical School, University of Sussex | United Kingdom
Dr. Georgios Baskozos | University of Oxford | United Kingdom
Prof. Stephen Bremner | University of Brighton | United Kingdom
Prof. Andrew Dilley | Brighton and Sussex Medical School, University of Sussex | United Kingdom
Prof. Dr. Annina Schmid | University of Oxford | United Kingdom
Background: The most common type of whiplash injury is Whiplash-Associated Disorder grade 2 (WAD2), which includes pain and musculoskeletal signs without frank nerve injury. Approximately 50% of people with WAD2 develop persistent pain. However, we have limited knowledge of prognostic factors that provide pathological insights.
Purpose: To assess the temporal profile of nerve pathology using clinical, serologic, and skin testing. A secondary objective was to assess if nerve pathology can predict recovery at six-months.
Methods: Participants aged 18-85 with acute WAD2 were recruited within 4 weeks of injury and re-evaluated six-months later. Exclusion criteria included: pregnancy; previous cervical/arm pain lasting >3 months; pre-existing peripheral neuropathy. We also included 55 healthy controls without a history of whiplash or treatment for neck, spine or upper limb pain in the past 3 months.
Upper extremity neurological assessment included light touch, pin prick, thermal sensation, myotomal strength and deep-tendon reflexes (nerve roots C5-T1).
Quantitative sensory testing (QST) included sensory detection and pain thresholds over the index finger.
Serum neurofilament light chain (NfL) concentrations were measured using Simoa assay.
Intraepidermal nerve fibre density (IENFD) was evaluated from skin samples taken from the index finger.
Analysis: Neurologic examination is presented as percentages of patients with normal, loss, or gain of function. Changes in NfL and QST between acute, follow-up, and controls were assessed using ANOVA or Kruskal-Wallis with post hoc testing. Prognostic ability of NfL was assessed using linear regression controlling for age, sex, and initial Neck Disability index (NDI).
Results:
Our current cohort consists of 130 people with acute WAD2 (median age: 36 years, 58% female), 50 WAD2 follow-ups, and 55 healthy controls (median age: 31, 56% female).
Neurological assessment: Neurologic dysfunction was identified in 63% acutely and 37% at follow-up WAD2.
QST: There was a significant decrease in detection thresholds for cold (p < 0.001), warm (p < 0.001), mechanical (p < 0.001), and vibration detection (p < 0.001) in people with acute WAD2 compared to controls. At follow-up, sensory detection remained impaired for cold (p < 0.01), warm (p < 0.05), mechanical detection (p < 0.001) as well as mechanical (p < 0.01) and pressure pain thresholds (p < 0.001) compared to controls. There were no differences in any QST measures between acute and follow-up timepoints, besides reduced pressure pain at follow-up (p < 0.001).
NfL: There was significantly increased serum NfL concentrations in people with acute WAD2 (P < 0.05) but no difference at six-months compared to acute WAD2 or controls.
IENFD: There was no significant difference in nerve fibre density at the index finger in acute WAD2 compared to controls.
Prognosis: Acute serum NfL was not prognostic for neck-related disability at 6-months (adjusted r2= 0.248; coefficient estimate: 0.325, standard error: 2.96).
Conclusions: Our findings suggest clinical signs of acute nerve pathology in a subgroup of people, with the NfL resolving while functional deficits largely remain. Acute NfL did not appear prognostic for WAD2.
Implications: A comprehensive clinical neurological examination is critical for assessing signs of nerve pathology in WAD2.