Objective: To present two cases of GNAO1 related movement disorder associated with life threatening persistent chorea successfully managed with bilateral GPi deep brain stimulation (GPi-DBS) and review previously reported cases in the literature with emphasis on treatment.

Background: Mutations in GNAO1 were first characterized by early-onset epileptic encephalopathy. Since initial reports of this mutation, more than 40 patients have been reported in the literature with phenotypes including neurodevelopmental disability, infantile epileptic encephalopathy, hypotonia, and involuntary movements. The involuntary movements include chorea and/or dystonia resulting in life threatening “storms” requiring several intensive care unit stay due to fractures, lactic acidosis, and rhabdomyolysis. Several treatments have been utilized with varying success including tetrabenazine, neuroleptics, anticonvulsants, benzodiazepines, and others. Many were found to be pharmacoresistant and therefore GPi-DBS has been utilized with promising results.

Method: A literature survey of GNAO1 related movement disorders was performed on PubMed. We describe two cases, a 14 year old male and 3 year old female, admitted to the ICU in the setting of febrile illness associated with life threatening chorea. Both courses were complicated by rhabdomyolysis and respiratory failure. Neither had improvement in chorea with administration of benzodiazepines, tetrabenazine, and other medications. Both had bilateral GPi-DBS emergently implanted with significant improvement.

Results: We present two additional cases of pharmacoresistant chorea in patients with GNAO1 mutations that resulted in significant improvement of symptoms following DBS. While one patient was only recently implanted, the other has not had recurrent ICU admission since implantation three years ago.

Conclusion: GNAO1 mutations have been associated with multiple phenotypes including epileptic encephalopathy and involuntary movements. These movements can have several triggers including fever, pain, etc. and result in storms of chorea/dystonia associated with life threatening complications. These movements have been exceedingly resistant to medications, however, GPi-DBS has had promising results.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/management-of-life-threatening-dyskinesias-in-gnao1-related-movement-disorder-two-new-cases-and-review-of-the-literature/