Brain metabolic signatures in patients with genetic and nongenetic amyotrophic lateral sclerosis

Abstract

Aims To study the brain metabolic signature in Chinese amyotrophic lateral sclerosis (ALS) patients and compare the difference in brain metabolic patterns between ALS with and without genetic variants. Methods We included 146 patients with ALS and 128 healthy controls (HCs). All patients with ALS underwent genetic testing to screen for ALS related genetic variants and were then divided into genetic (n = 22) and nongenetic ALS (n = 93) subgroups. All participants underwent brain 18F‐FDG‐PET scans. Group comparisons were performed using the two‐sample t‐test model of SPM12. Results We identified a large of hypometabolic clusters in ALS patients as compared with HCs, especially in the bilateral basal ganglia, midbrain, and cerebellum. Moreover, hypometabolism in the bilateral temporal lobe, precentral gyrus and hypermetabolism in the left anterior cingulate, occipital lobe, and bilateral frontal lobe were also found in ALS patients as compared with HCs. Compared with nongenetic ALS patients, genetic ALS patients showed hypometabolism in the right postcentral gyrus, precuneus, and middle occipital gyrus. The incidence of sensory disturbance in patients with genetic ALS was higher than that in patients with nongenetic ALS (5 of 22 [22.72%] vs. 7 of 93 [7.52%], p = 0.036). Conclusions Our investigation provided unprecedented evidence of relative hypometabolism in the midbrain and cerebellum in ALS patients. Genetic ALS patients showed a specific signature of brain metabolism and a higher incidence of sensory disturbance, indicating that genetic factors may be an underlying cause affecting the brain metabolism and increasing the risk of sensory disturbance in ALS.

Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier

“…In contrast, some studies have reported decreased FC in the left and right cerebellar lobule VI in ALS participants 302,303 . Additionally, studies have investigated metabolic levels in the cerebellum of ALS patients, although the findings remain inconsistent 304–307 …”

“…302,303 Additionally, studies have investigated metabolic levels in the cerebellum of ALS patients, although the findings remain inconsistent. [304][305][306][307]…”

PET and SPECT Imaging of ALS: An Educational Review

“…In addition to the discussion of variable regions above, there was a study by Liu et al that appears to flip the commonly seen metabolic pattern in ALS. In this study, hypometabolism was found in the cerebellum and midbrain, while hypermetabolism was observed in the anterior cingulate and the prefrontal lobe [ 36 ]. This is a pattern much different from what other studies have found.…”

“… The structure of [ 18 F]FDG, which has uncovered a specific signature of glucose hypermetabolism and hypometabolism in ALS, along with being applied to a number of other purposes [ 18 – 34 , 36 – 38 , 42 – 47 ]. …”