ABSTRACT
AIMS: To study stereotactic magnetic resonance imaging (MRI) features of the basal ganglia in DYT1 primary dystonia. METHODS: Twenty-five genetically confirmed DYT1 dystonia patients (age range, 8-66 years; mean age, 22 years) underwent brain MRI under general anesthesia at the time of globus pallidus internus (GPi) deep brain stimulation (DBS) surgery. MR images were retrospectively reviewed for signal intensity alterations. Clinical improvement of patients was assessed by comparing pre- and postoperative Burke-Fahn-Marsden Dystonia Rating Scale scores. RESULTS: Seventeen patients out of 25 (68%) exhibited T(1)-weighted hypointense/T(2)-weighted hyperintense signal abnormalities in the putamen and globus pallidus on MR images. Signals were isointense with cerebrospinal fluid in all sequences. The mean volume of focal signal abnormalities was 15 mm(3) (maximum, 154.5 mm(3)). The total volume of focal signal abnormalities in the basal ganglia was correlated with the duration of the disease (p = 0.01). Although clinical outcome did not differ as a function of the presence of focal signal abnormalities overall, patients with signals within the GPi tended to show lesser improvement (p = 0.04). CONCLUSIONS: T(1)-hypointense/T(2)-hyperintense signal abnormalities are common findings in the putamen and globus pallidus of DYT1 patients but do not contraindicate DBS. However, their presence within the GPi may reduce the efficacy of DBS treatment.
Subject(s)
Basal Ganglia/physiopathology , Deep Brain Stimulation , Dystonia Musculorum Deformans/genetics , Dystonia Musculorum Deformans/therapy , Magnetic Resonance Imaging , Molecular Chaperones/genetics , Stereotaxic Techniques , Adolescent , Adult , Aged , Basal Ganglia/metabolism , Child , Deep Brain Stimulation/methods , Dystonia Musculorum Deformans/physiopathology , Female , Globus Pallidus/metabolism , Globus Pallidus/physiopathology , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Molecular Chaperones/physiology , Preoperative Care/methods , Retrospective StudiesABSTRACT
The simplistic idea that seven transmembrane receptors are single monomeric proteins that interact with heterotrimeric G-proteins after agonist binding is definitively out of date. Indeed, GPCRs (G-protein-coupled receptors) are part of multiprotein networks organized around scaffolding proteins. These GIPs (GPCR-interacting proteins) are either transmembrane or cytosolic proteins. Proteomic approaches can be used to get global pictures of these 'receptosomes'. This approach allowed us to identify direct but also indirect binding partners of serotonin receptors. GIPs are involved in a wide range of functions including control of the targeting, trafficking and signalling of GPCRs. One of them, Shank, which is a secondary and tertiary partner of metabotropic and ionotropic glutamate receptors, respectively, can induce the formation of a whole functional glutamate 'receptosome' and the structure to which it is associated, the dendritic spine.