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

Abstract

Objective: Amyotrophic lateral sclerosis (ALS) is a clinically heterogenous disease, typically presenting with focal motor weakness that eventually generalizes. Weather there is a correlation between focal motor weakness and metabolic alterations in specific areas of the brain has not been thoroughly explored. This study aims to systematically investigate this by using fluorodeoxyglucose-positron emission tomography (FDG-PET), including longitudinal imaging. 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 analyzed 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 frontal regions and hypermetabolism in posterior regions. A higher symptom burden was associated with increased hypometabolism and decreased hypermetabolism. However, there was no clear correlation between focal motor weakness and specific metabolic alterations, neither when analyzing focal motor weakness with concomitant upper motor neuron signs or when including all focal motor weakness. Longitudinal FDG-PET imaging showed inconsistent results with little correlation between progression of motor weakness and metabolic alterations. Conclusion: Our results support the disease model of ALS as a diffuse process since no clear correlation was seen between focal motor weakness and specific metabolic alterations. However, there is need for further research on a larger number of patients, particularly including longitudinal imaging.

Keywords:

• Amyotrophic lateral sclerosis
• ALS
• FDG-PET
• weakness
• glucose metabolism

Acknowledgements

We are grateful for the generosity of Dr. Sanne K Meles, Dr Fransje Reesink, and Professor Klaus L. Leenders, (Department of Neurology and Nuclear Medicine at the University of Groningen, University Medical Center of Gröningen, Groningen (UMCG), The Netherlands) for sharing FDG-PET data in 39 healthy controls. We thank Mustafa Ismail and Jenny Hellqvist for data handling.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing for this article.

Data availability statement

Data on patient characteristics and imaging can be obtained from the original data sources or from the authors with the appropriate approval from a research ethics board.

Additional information

Funding

The study was funded by Ulla-Carin Lindqvist foundation, Neuro Sweden, Frimuarstiftelsen, ALF medicin, CIMED and Bjorklunds fund.