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Changes in GABA-receptor binding among cognitively impaired MS patients

Presented by
Prof. Hanneke Hulst, Amsterdam UMC, the Netherlands
[11C]flumazenil (FMZ) positron emission tomography (PET) demonstrated higher GABA-receptor binding for cognitively unimpaired MS patients, compared with cognitively impaired MS patients and healthy controls. In addition, cognitively impaired patients showed lower perfusion rates, suggesting possible brain atrophy. These results suggest that [11C]FMZ may have clinical applicability in MS patients with cognitive impairment [1].

Cognitive impairment is frequently observed in patients with MS and changes in the GABAergic system have been associated with cognitive impairment in this population [2,3]. This study aimed to investigate GABA-receptor binding via [11C]FMZ PET. The optimal method of analysis was assessed for [11C]FMZ PET in MS patients and the GABA-receptor binding between cognitively impaired and cognitively unimpaired patients was compared. MS patients (n=17: cognitively impaired, n=11; cognitively unimpaired, n=6) and healthy controls (n=11) underwent 60-minute dynamic PET, using plasma input data. Two models (1-tissue 2-rate-constant (1T2K); 2T4K) measured the influx rate and volume of distribution of 7 brain regions relevant for cognitive function. Akaike information criterion was used to determine the best-fitting model.

By margins, the 2T4K model was preferred over the 1T2K model: in 55.6% of the analysed brain regions, the 2T4K model outperformed the 1T2K model. However, Prof. Hanneke Hulst (Amsterdam UMC, the Netherlands) argued that both models could reliably estimate radiotracer delivery. Mean perfusion rates were significantly lower for cognitively impaired patients (0.29 μL/min) compared with cognitively unimpaired patients (0.33) and healthy controls (0.33). The volume of distribution was higher in cognitively unimpaired patients (5.73 mL of plasma/cm3 of tissue) than in cognitively impaired patients (4.95) and healthy controls (4.87). This implicates a higher GABA-receptor binding in cognitively unimpaired patients.

  1. Hulst H. [11C]flumazenil positron emission tomography in multiple sclerosis: model validation and clinical applicability in cognitive impairment. LB188, ECTRIMS 2021 Virtual Congress, 13–15 October.
  2. Benedict RHB, et al. Lancet Neurol. 2020;19(10):860–871.
  3. Freeman L, et al. Ann Neurol. 2015;78(4):554–567.


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