In our study, patients with sCJD showed glucose hypometabolism in extensive cortical regions, including bilateral frontal, parietal, and occipital areas, compared with normal controls. This finding is consistent with DWI studies in sCJD [1
]. One of the most interesting finding was that the basal ganglia as well as the thalamus, two areas commonly involved in sCJD (particularly the basal ganglia) in MRI studies [1
], were unaffected in the context of metabolism. This result is compatible with a previous 18
F-FDG PET group study based on a ROIs method that found the putamen and thalamus were less affected in 9 patients [16
] and with most case reports, which did not show involvement of deep gray matter [6
]. Another PET study showed that only 1 out of total 8 patients with sCJD demonstrated involvement of the cerebellum, which is also be compatible with our results [15
All the patients underwent brain MRIs and 18
F-FDG PET scans on almost the same day, and 9 out of 11 patients with sCJD demonstrated increased signal intensities of the basal ganglia on DWI sequences. Even though the cause of high signal changes on DWI in sCJD remains unclear, several studies have reported that these MR changes correlate with certain neuropathological findings, particularly vacuolation and prion (PrPSc
) accumulation, regardless of cortical and subcortical lesions [21
]. Therefore, the reason why the basal ganglia, which was detected as having high signal intensities on DWI that were similar to other cortical regions, did not demonstrate hypometabolism on 18
F-FDG PET remains unclear. One possibility is that vacuolation and/or prion deposition do not always correlate with neuronal dysfunction and hypometabolism. Furthermore, as MRI abnormalities in most sCJD cases appear first cortically and then move subcortically over time, this suggests that the cortex is affected earlier and thus longer than subcortical structures. The deep nuclei in this cohort thus might be less affected physiologically at the times of the FDG-PET scans. It is possible that if patients were followed longitudinally to later stages of disease that subcortical involvement would be evident on FDG-PET imaging.
Another interesting finding of our study was that patients with sCJD did not show hypometabolism in the medial temporal area e.g. hippocampus and amygdala, which is also consistent with a previous PET study showing the temporal area was relatively less affected in sCJD [16
] and with a pathological study suggesting possible resistance of hippocampus to the prion deposits in CJD [25
In our study, the glucose hypometabolism of patients with the Heidenhain variant was found mainly in the parietooccipital areas, which agreed with the results of the previous studies [7
]. This finding may explain the clinical symptoms of patients with the variant.
To our knowledge, there have been few published studies on PET findings according to the molecular subtypes of sCJD [27
]. Although we did not have prion typing data, all five patients tested for codon 129 polymorphism were MM and we suspect that most were MM given its prevalence in the Korean sCJD population [28
]. A recent MRI study of a large number of patients with sCJD described that the basal ganglia, frontal lobes, parietal lobes, and cingulate gyri were frequently affected in the MM1 subtype, while the thalamus, cerebellum, and temporal lobes were frequently involved in the MM2 subtype [29
]. Regarding the asymmetric involvement with right-sided predominance in our study (), there have been several reports regarding asymmetric cortical involvement in sCJD, but the results were inconsistent [30
]. One recent DWI MRI study of 49 sCJD subjects suggests the possibility of left-sided involvement to be more common [1
Although MR DWI is the most sensitive imaging tool for the clinical diagnosis of CJD, functional imaging remains a useful technique that supports DWI findings [11
]. It is interesting to see if 18
F-FDG PET has diagnostic utility in CJD, however, rare group studies using 18
F-FDG PET in CJD have been reported.
Our study has limitations including a small sample size and lack of pathological confirmation of most diagnoses. Also, because the patients in this study had had an average disease duration of 10.6 ± 11.6 months with FDG-PET scans performed at an average of 2.9 ± 2.3 months after onset of clinical symptoms and no patients had follow-up FDG-PET scans, we could not exclude the possibility if the subjects had longer duration of symptoms prior to FDG-PET scans, they might have had demonstrated further neuronal damage extend to basal ganglia or thalamus on FDG-PET. Despite of these limitations, we think that our findings provide useful information regarding the functional neuroimaging findings of sCJD and that these findings will be confirmed in future studies with larger, pathology-confirmed series. The lack of deep nuclei hypometabolism on 18
F-FDG PET despite DWI involvement needs to be explored further. Although this study did not assess whether FDG-PET is helpful for diagnosis, in some cases even might reveal abnormalities earlier than MRI [36
] and at a minimum might improve our understanding of the physiological processes underlying sCJD.