AUTHOR=Domínguez Carral Jana , Reinhard Carola , Ebrahimi-Fakhari Darius , Dorison Nathalie , Galosi Serena , Garone Giacomo , Malenica Masa , Ravelli Claudia , Serdaroglu Esra , van de Pol Laura A. , Koy Anne , Leuzzi Vincenzo , Roubertie Agathe , Lin Jean-Pierre , Doummar Diane , Cif Laura , Ortigoza-Escobar Juan Darío 

TITLE=Dyskinetic crisis in GNAO1-related disorders: clinical perspectives and management strategies

JOURNAL=Frontiers in Neurology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1403815

DOI=10.3389/fneur.2024.1403815

ISSN=1664-2295

ABSTRACT=<sec id="sec1"><title>Background</title><p><italic>GNAO1</italic>-related disorders (<italic>GNAO1</italic>-RD) encompass a diverse spectrum of neurodevelopmental and movement disorders arising from variants in the <italic>GNAO1</italic> gene. Dyskinetic crises, marked by sudden and intense exacerbations of abnormal involuntary movements, present a significant challenge in <italic>GNAO1</italic>-RD.</p></sec><sec id="sec2"><title>Objectives</title><p>This study aimed to establish a standardized framework for understanding dyskinetic crises, addressing crucial aspects such as definition, triggers, diagnostic criteria, complications, and management strategies.</p></sec><sec id="sec3"><title>Methods</title><p>A Delphi consensus process was conducted involving international experts in <italic>GNAO1</italic>-RD. The panel of thirteen experts participated in three voting rounds, discussing 90 statements generated through a literature review and clinical expertise.</p></sec><sec id="sec4"><title>Results</title><p>Consensus was achieved on 31 statements, defining dyskinetic crises as abrupt, paroxysmal episodes involving distinct abnormal movements in multiple body regions, triggered by emotional stress or infections. Dyskinetic crises may lead to functional impairment and complications, emphasizing the need for prompt recognition. While individualized pharmacological recommendations were not provided, benzodiazepines and clonidine were suggested for acute crisis management. Chronic treatment options included tetrabenazine, benzodiazepines, gabapentin, and clonidine. Deep brain stimulation should be considered early in the treatment of refractory or prolonged dyskinetic crisis.</p></sec><sec id="sec5"><title>Conclusion</title><p>This consensus provides a foundation for understanding and managing dyskinetic crises in <italic>GNAO1</italic>-RD for clinicians, caregivers, and researchers. The study emphasizes the importance of targeted parental and caregiver education, which enables early recognition and intervention, thereby potentially minimizing both short- and long-term complications. Future research should concentrate on differentiating dyskinetic crises from other neurological events and investigating potential risk factors that influence their occurrence and nature. The proposed standardized framework improves clinical management, stakeholder communication, and future <italic>GNAO1</italic>-RD research.</p></sec>