Interplay between spinal cord and cerebral cortex metabolism in amyotrophic lateral sclerosis

Abstract

We recently reported the potential of Hough transform in delineating spinal cord metabolism by 18F-fluorodeoxyglucose PET/CT scanning in amyotrophic lateral sclerosis. The present study aimed to verify the relationship between spinal cord and brain metabolism in 44 prospectively recruited patients affected by amyotrophic lateral sclerosis submitted to 18F-fluorodeoxyglucose brain and whole-body PET/CT. Patients were studied to highlight the presence of brain hypo- or hypermetabolism with respect to healthy controls, and multiple regression analysis was performed to evaluate the correlation between spinal cord and brain metabolism. Our results confirmed higher 18F-fluorodeoxyglucose uptake in both cervical and dorsal spinal cord in patients with amyotrophic lateral sclerosis with respect to controls. This finding was paralleled by the opposite pattern in the brain cortex that showed a generalized reduction in tracer uptake. This hypometabolism was particularly evident in wide regions of the frontal-dorsolateral cortex while it did not involve the midbrain. Bulbar and spinal disease onset was associated with similar degree of metabolic activation in the spinal cord. However, among spinal onset patients, upper limb presentation was associated with a more pronounced metabolic activation of cervical segment. Obtained data suggest a differential neuro-pathological state or temporal sequence in disease progression.

Figure 1

Spinal cord metabolism in upper and lower limb clinical onset. (A and C) 3D reconstructions of spinal cord FDG uptake, in a patient with upper or lower ALS onset, respectively. (B) The corresponding SUV values plotted from cervical slices (top) to lumbar ones (bottom). Tracer retention is higher in cervical segments in upper limb presentation, while the reverse gradient occurs in lower limb onset. (D) Average SUV values in the two spinal cord districts: in patients with upper limb onset tracer uptake in the cervical spinal cord is higher with respect to both the dorsal segment in the same patients and with respect to the same segment in the remaining subjects. This selective localization is confirmed by the ratio cervical/dorso-lumbar tracer uptake reported in E. ns = not significant; SC = spinal cord.

Figure 2

SPM analysis. 3D rendering showing regions in which FDG uptake was significantly lower (A) or higher (B) in ALS patients with respect to controls. (C and D) Results of the multiple regression analysis between brain and cervical or dorsal spinal cord metabolism, respectively. Threshold P < 0.05, corrected for multiple comparisons with the FDR at the voxel level were set in each analysis. Coordinate and regional details are presented in Table 1.

Figure 3

Volumes of interest analysis. BA SUV values in ALS (filled bars) and control subjects (open bars) according to cortical lobes. The y-axes represent BA SUV values. Yellow = frontal lobe; green = parietal lobe; blue = occipital lobe; pink = temporal lobe. *P < 0.05; **P < 0.01.