Brain hypermetabolism in amyotrophic lateral sclerosis: a FDG PET study in ALS of spinal and bulbar onset.

Purpose: To identify the neurobiological traits of amyotrophic lateral sclerosis (ALS) and to elucidate functional differences between ALS of spinal and bulbar onset. We hypothesized that glucose metabolism distribution might vary between groups.

Methods: The study groups comprised 32 patients with ALS of either bulbar (n = 13) or spinal (n = 19) onset and 22 subjects as controls. They were investigated by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (FDG PET), comparing the patient groups with each other and with the controls by statistical parametric mapping.

Results: Highly significant relative increases in glucose metabolism distribution were found in the group comprising all 32 ALS patients as compared with the controls in the bilateral amygdalae, midbrain, pons and cerebellum. Relative hypermetabolism was also found in patients with spinal onset as compared with the controls in the right midbrain. In patients with bulbar onset compared with the controls and with patients with spinal onset, large relatively hypometabolic areas were found in the bilateral frontal cortex, right insula, anterior cingulate, precuneus and inferior parietal lobe. Patients with spinal onset had significantly higher scores in a neuropsychological test assessing verbal fluency compared with patients with bulbar onset.

Conclusion: This large FDG PET investigation provided unprecedented evidence of relatively increased metabolism in the amygdalae, midbrain and pons in ALS patients as compared with control subjects, possibly due to local activation of astrocytes and microglia. Highly significant relative decreases in metabolism were found in large frontal and parietal regions in the bulbar onset patients as compared with the spinal onset patients and the controls, suggesting a differential metabolic and neuropsychological state between the two conditions.