Macrophagic myofasciitis (MMF) is characterized by abnormal long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Patients present with diffuse arthromyalgias, chronic fatigue, and cognitive dysfunction. The aim of this study was to characterize brain PET metabolic abnormalities in patients with aluminum hydroxide adjuvant-induced macrophagic myofasciitis, and relation with cognitive dysfunction.

FDG-PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (mean age, 45.9±11.8 y; women, 74%) followed in our Reference Center for Rare Neuromuscular Diseases. Images were analyzed using statistical parametric mapping (SPM12). Using ANCOVA analysis, all FDG-PET brain images of MMF patients were compared to normal reference samples from 44 healthy subjects matched for age (p=0.87) and gender (p=0.88) with the whole population of patients (mean age, 45.4±16 y; women, 73%). All results were collected at a p-value<0.005 at the voxel level, for clusters k≥200 voxels (corrected for cluster volume) with adjustment for age and gender. The neuropsychological assessment identified four categories of patients with: (i) no significant cognitive impairment (n=42); (ii) frontal sub-cortical (FSC) dysfunction (n=29); (iii) papezian dysfunction (n=22); and (iv) callosal disconnection (n=7).

In comparison with healthy subjects, ANCOVA analysis of the whole population of patients with MMF exhibited a pattern of hypometabolism (p<0.001) involving occipital lobes, temporal lobes, limbic system, cerebellum and frontoparietal cortices. The subgroup of patients with FSC dysfunction exhibited larger extents of involved area (35,223 voxels vs. 13,680 voxels in the subgroup with papezian dysfunction and 5453 voxels in patients without cognitive impairment).

Our study identified a cerebral glucose metabolic biomarker in patients with long-lasting aluminum hydroxide-induced MMF. The pattern appeared mostly marked in MMF patients with FSC dysfunction.