Thalamic Neurometabolite Alterations in Patients with Knee Osteoarthritis Before and After Total Knee Replacement

The weak association between disability levels and "peripheral" (ie, knee) findings suggests that central nervous system alterations may contribute to the pathophysiology of knee osteoarthritis (KOA). Here, we evaluated brain metabolite alterations in patients with KOA, before and after total knee arthroplasty (TKA), using 1H-magnetic resonance spectroscopy (MRS). Thirty-four presurgical patients with KOA and 13 healthy controls were scanned using a PRESS sequence (TE = 30 ms, TR = 1.7 seconds, voxel size = 15 × 15 × 15 mm). In addition, 13 patients were rescanned 4.1 ± 1.6 (mean ± SD) weeks post-TKA. When using creatine (Cr)-normalized levels, presurgical KOA patients demonstrated lower N-acetylaspartate (NAA) (P < 0.001), higher myoinositol (mIns) (P < 0.001), and lower Choline (Cho) (P < 0.05) than healthy controls. The mIns levels were positively correlated with pain severity scores (r = 0.37, P < 0.05). These effects reached statistical significance also using water-referenced concentrations, except for the Cho group differences (P ≥ 0.067). Post-TKA patients demonstrated an increase in NAA (P < 0.01), which returned to the levels of healthy controls (P > 0.05), irrespective of metric. In addition, patients demonstrated postsurgical increases in Cr-normalized (P < 0.001), but not water-referenced mIns, which were proportional to the NAA/Cr increases (r = 0.61, P < 0.05). Because mIns is commonly regarded as a glial marker, our results are suggestive of a possible dual role for neuroinflammation in KOA pain and post-TKA recovery. Moreover, the apparent postsurgical normalization of NAA, a putative marker of neuronal integrity, might implicate mitochondrial dysfunction, rather than neurodegenerative processes, as a plausible pathophysiological mechanism in KOA. More broadly, our results add to a growing body of literature suggesting that some pain-related brain alterations can be reversed after peripheral surgical treatment.