PET and SPECT Imaging of ALS: An Educational Review
Table 2
Additional metabolic comparisons across ALS phenotypes beyond Table 1.
Comparison
Result
Reference
Bulbar vs. spinal-onset ALS
Cistaro et al.’s study on bulbar and spinal onset found no significant differences in metabolism [29]. Pagani et al.’s study showed hypometabolism in bulbar patients in the left motor and premotor cortices as compared to spinal patients, but no significant hypermetabolism was found [23]. Sala et al.’s study did find bulbar hypometabolism in the left anterior cingulate, although it was not enough to distinguish between the two groups when performing discriminatory analysis [32]. Canosa et al.’s study found bulbar hypometabolism in the precentral gyrus but no hypermetabolism [37].
Van Laere et al.’s study compared C9ORF72 ALS to all other non-C9ORF72 ALS subjects they had. They found reduced metabolism in C9ORF72 as compared to non-C9ORF72 ALS in the anterior and posterior cingulate, posterior thalamus, right lateral frontal cortex, and right temporoparietal junction. No hypermetabolism was found. However, it is important to note that the researchers had to turn down their preset threshold for significance () to find such hypometabolic results and that their original threshold found no significant differences [25].
Canosa et al.’s study on TARDBP ALS compared TARDBP ALS to a control ALS group, where the control ALS group did not have FTD, had no mutation in major ALS genes, and had no family history of ALS. Compared to this ALS control group, the TARDBP ALS exhibited hypometabolism in the right precentral gyrus, right postcentral gyrus, superior temporal gyrus, middle temporal gyrus, and insula [20].
Comparison of ALS with varying levels of impairment and ALS-FTD
Canosa et al. did an additional study where ALS patients were grouped into multiple categories. These categories were ALS with normal cognition, ALS with impaired cognition, ALS with impaired behavior, ALS with impaired cognition and behavior, and ALS-FTD. Metabolism was compared across these groups. When comparing ALS-FTD to ALS with normal cognition, ALS-FTD hypometabolism was found in the right cingulate gyrus, bilateral middle frontal gyri, right precentral gyrus, bilateral superior frontal gyrus, and bilateral inferior frontal gyri while hypermetabolism was found in the cerebellum and brachia pontis (middle cerebellar peduncle). Cognitive-only impaired ALS patients showed hypometabolism (when the significance threshold was decreased) in the left superior, middle and inferior frontal gyri, superior temporal gyrus, and uncus, with no hypermetabolism as compared with cognitively normal ALS patients. Cognitive and behaviorally impaired ALS compared to cognitively normal ALS exhibited hypometabolism in the bilateral superior and middle frontal gyri, bilateral anterior cingulate gyri, right cingulate gyrus, right medial frontal gyrus, bilateral inferior frontal gyri, right precentral gyrus, and right insula, while there was no hypermetabolism [43].
A study by Sennfält et al. compared patients with a high motor symptom burden to those with a low motor symptom burden. The burden was assessed with a scale of impairment that was applied to several regions of the body. In the high burden group, hypometabolism was seen in the insula and left lingual gyrus [21].
Liu et al. compared ALS cases with genetic mutations in known ALS causing genes to nongenetic ones. In the genetic group, hypometabolism was observed in the postcentral gyrus, middle occipital gyrus, and right precuneus, but no hypermetabolism was seen [36].
