RESUMO
Rett syndrome (RTT) is a neurodevelopmental disability characterized by mutations in the X-linked methyl-CpG-binding protein 2 located at the Xq28 region. The severity is modified in part by X chromosomal inactivation resulting in wide clinical variability. We hypothesized that the ability to perform the activities of daily living (ADL) is correlated with the density of vesicular acetylcholine transporters in the striata of women with RTT. The density of the vesicular acetylcholine transporters in the living human brain can be estimated by single-photon emission-computed tomography (SPECT) after the administration of (-)-5-[¹²³I]iodobenzovesamicol ([¹²³I]IBVM). Twenty-four hours following the intravenous injection of â¼333 MBq (9 mCi) [¹²³ I]IBVM, four women with RTT and nine healthy adult volunteer control participants underwent SPECT brain scans for 60 min. The Vesicular Acetylcholine Transporter Binding Site Index (Kuhl et al., 1994), a measurement of the density of vesicular acetylcholine transporters, was estimated in the striatum and the reference structure, the cerebellum. The women with RTT were assessed for certain ADL. Although the striatal Vesicular Acetylcholine Transporter Binding Site Index was not significantly lower in RTT (5.2 ± 0.9) than in healthy adults (5.7 ± 1.6), RTT striatal Vesicular Acetylcholine Transporter Binding Site Indices and ADL scores were linearly associated (ADL = 0.89*(Vesicular Acetylcholine Transporter Binding Site Index) + 4.5; R² = 0.93; P < 0.01), suggesting a correlation between the ability to perform ADL and the density of vesicular acetylcholine transporters in the striata of women with RTT. [¹²³I]IBVM is a promising tool to characterize the pathophysiological mechanisms of RTT and other neurodevelopmental disabilities.
