FDG-PET shows weak correlation between focal motor weakness and brain metabolic alterations in ALS

Background Amyotrophic lateral sclerosis (ALS) is a clinically heterogenous disease, typically presenting with focal motor weakness that eventually generalises. There are characteristic findings on various imaging modalities, such as fluorodeoxyglucose-positron emission tomography (FDG-PET) in which patterns of hypometabolism can be seen in frontal areas and hypermetabolism in posterior areas. However, weather there is a correlation between focal motor weakness and metabolic alterations in specific areas of the brain visualized by FDG-PET has not been thoroughly explored and reports on longitudinal assessment are scarce. This is, to the best of our knowledge, the first FDG-PET study to systematically investigate the correlation between focal motor weakness and brain metabolic alterations in ALS and the largest to include longitudinal imaging data. Methods This observational imaging study included 131 ALS patients diagnosed and examined with FDG-PET at the ALS Clinical Research Center at the Karolinska University Hospital in Stockholm, Sweden. Thirteen ALS patients had a second scan and were analysed longitudinally. The findings were compared to 39 healthy controls examined at the University Medical Center of Gröningen, the Netherlands. Results There was a general pattern of brain metabolic alterations consistent with previously reported findings in ALS, namely hypometabolism in the frontal regions and hypermetabolism in posterior regions, compared with healthy controls. An increased symptom burden in the ALS patients was associated with increased hypometabolism but decreased hypermetabolism. However, there was no clear correlation between focal motor weakness and specific metabolic alterations, neither when analysing focal motor weakness with concomitant upper motor neuron signs or when including all focal motor weakness. The longitudinal FDG-PET data showed inconsistent results with little correlation between progression of motor weakness and metabolic alterations. Conclusion This study supports the disease model of ALS as a diffuse process as no clear correlation was seen between focal motor weakness and specific metabolic alterations in the brain. The results also suggest that FDG-PET might be effective as an assessment of global brain metabolic patterns in ALS but may be insensitive to more subtle and localised alterations. However, there is need for further research on a larger number of patients, particularly including longitudinal imaging.