Different subregional metabolism patterns in patients with cerebellar ataxia by 18F-fluorodeoxyglucose positron emission tomography

Abstract

We evaluated cerebellar subregional metabolic alterations in patients with cerebellar ataxia, a representative disease involving the spinocerebellum. We retrospectively analyzed 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) images in 44 patients with multiple system atrophy of the cerebellar type (MSA-C), 9 patients with spinocerebellar ataxia (SCA) type 2, and 14 patients with SCA type 6 and compared with 15 patients with crossed cerebellar diaschisis (CCD) and 89 normal controls. Cerebellar subregional metabolism was assessed using 13 cerebellar subregions (bilateral anterior lobes [ANT], superior/mid/inferior posterior lobes [SUPP/MIDP/INFP], dentate nucleus [DN], anterior vermis [ANTV], and superior/inferior posterior vermis [SUPV/INFV]) to determine FDG uptake ratios. MSA-C and SCA type 2 showed severely decreased metabolic ratios in all cerebellar subregions compared to normal controls (ANT, 0.58 ± 0.08 and 0.50 ± 0.06 vs. 0.82 ± 0.07, respectively, p < 0.001). SCA type 6 showed lower metabolic ratios in almost all cerebellar subregions (ANT, 0.57 ± 0.06, p < 0.001) except INFV. Anterior-posterior lobe ratio measurements revealed that SCA type 2 (Right, 0.81 ± 0.05 vs. 0.88 ± 0.04, p < 0.001; Left, 0.83 ± 0.05 vs. 0.88 ± 0.04, p = 0.003) and SCA type 6 (Right, 0.72 ± 0.05 vs. 0.88 ± 0.04, p < 0.001; Left, 0.72 ± 0.05 vs. 0.88 ± 0.04, p < 0.001) showed preferential hypometabolism in the anterior lobe compared to normal controls, which was not observed in CCD and MSA-C. Asymmetric indices were higher in CCD and MSA-C than in normal controls (p < 0.001), whereas such differences were not found in SCA types 2 and 6. In summary, quantitative analysis of cerebellar subregional metabolism ratios revealed preferential involvement of the anterior lobe, corresponding to the spinocerebellum, in patients with cerebellar ataxia, whereas patients with CCD and MSA-C exhibited more asymmetric hypometabolism in the posterior lobe.

Neuroimaging Biomarkers in SCA2 Gene Carriers

“…All the small size studies that used PET and 18 F-fluorodeoxyglucose demonstrated severely decreased metabolism in the cerebellar cortex, with preferential involvement of the anterior lobe, the dentate nucleus and brainstem in symptomatic SCA2 gene carriers [52][53][54] (Figure 7); that was comparatively more pronounced than in SCA3 and SCA6 patients in one study (53). Decreased glucose uptake was observed also in the parahippocampal, frontal and parietal cortices [52,53].…”

Positron Emission Tomography in the Inflamed Cerebellum: Addressing Novel Targets among G Protein-Coupled Receptors and Immune Receptors

“…Only one of the clinically used inhibitors (Cangrelor) is suitable for intravenous application [ 81 ]. The first P2Y12 antagonist for potential PET investigations was [ 11 C] C2 [ 27 ] ( Figure 6 : [ 26 ]). Results of the evaluation of an analogue (C5) of this compound were recently published ( Figure 6 : [ 27 ]) [ 79 ].…”

“…The first P2Y12 antagonist for potential PET investigations was [ 11 C] C2 [ 27 ] ( Figure 6 : [ 26 ]). Results of the evaluation of an analogue (C5) of this compound were recently published ( Figure 6 : [ 27 ]) [ 79 ]. P2Y12 receptors have been shown to be overexpressed in activated M2 type of microglia [ 28 ] but reduced in microglia close to plaques of Alzheimer’s disease or lesions of multiple sclerosis.…”

“…For C5, it was shown that binding was increased in IL4-stimulated tissue but not following stimulation with lipopolysaccharides (LPS). The first oral clinical inhibitor of P2Y12 [ 82 ], AZD6140 ( Figure 6 : [ 24 ]), remains in its main indication as an inhibitor of platelet aggregation in contest with clopidogrel, while C5 ( Figure 6 : [ 27 ]) could provide a useful lead structure for further evaluation and development as a tracer of microglial inflammatory activity.…”

“…The recent plurality of reports concerned with in vivo imaging of cerebellar function use MRI methods [ 17 , 26 ] and [ 18 F]FDG investigations [ 27 ] (see Figure 1 ). However, more and more details on subregional cerebellar functional patterns are provided.…”