Objective: To describe the clinical features and benefits of GPi-DBS approach in two patients with GNAO1 gene mutations to whom several episodes of choreo-dystonia exacerbations were previously associated.

Background: Mutations in the GNAO1 gene lead to a wide range of phenotypes, presenting more commonly during infancy and childhood, that include developmental delay, epileptic encephalopathies and/or movement disorders. In these conditions, progressive and drug-refractory hyperkinetic syndromes occur, marked by periods of severe exacerbation. GPi-DBS has been shown to be effective in these patients.

Method: Clinical and demographic data were obtained from medical records. Bilateral GPi-DBS surgery was performed, using MRI and CT for surgical planning. Macrostimulation testing and neurophysiological analysis were performed during surgery, along with intraoperative radiographic image control, but also using TC O-arm®. Directional electrodes with rechargeable batteries were implanted.

Results: We present the cases of two female patients, currently 9 and 22 years old. Both have confirmed genetic diagnoses of GNAO1 gene mutations, as variants c.736G>A, p.(Glu246Lys) and c.625C>T, p.(Arg209Cys) were identified, in heterozygosity.

In both cases, symptoms started at 6 months of age, with psychomotor development delay and hypotonia. Patients developed a hyperkinetic movement disorder, where chorea and dystonia dominated, with periods of severe exacerbation, often precipitated by infections, which progressively became more difficult to control with medical therapy. Neither case developed epilepsy. The severity of the choreo-dystonic symptoms, along with the inefficacy of multiple medical therapies, justified the therapeutic option of bilateral GPi-DBS. The first patient underwent surgery at 9 years of age (immediate resolution of ongoing exacerbation) and the second at 19, with marked improvement in hyperkinetic symptoms.

Conclusion: In both cases, there was an improvement in choreo-dystonic symptoms with GPi-DBS, one patient experiencing resolution of severe exacerbation and the other experiencing improvement and prevention of exacerbations. As described in the literature, GPi-DBS can be particularly effective in patients with GNAO1 gene mutations and severe chorea or dystonia and must be considered in these patients.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/the-use-of-pallidal-deep-brain-stimulation-gpi-dbs-to-treat-gnao1-gene-associated-hyperkinetic-syndromes/