Outcomes of Bilateral Globus Pallidus Internus Deep Brain Stimulation in <scp> <i>GNAO1</i> </scp> ‐Related Disorder: An International Multicenter Experience

OBJECTIVE: GNAO1-related disorder is a severe childhood-onset hyperkinetic movement disorder punctuated by life-threatening dyskinetic crises. Small series suggest benefit from bilateral globus pallidus internus deep brain stimulation (GPi-DBS), but optimal timing, patient selection, long-term outcomes, and genotype-specific response remain unclear. We define the clinical impact of GPi-DBS in the largest cohort assembled to date. METHODS: Retrospective multicenter cohort study conducted through the DBSMatchMaker platform, including children and young adults with genetically confirmed GNAO1-related disorder treated with bilateral GPi-DBS across 17 centers. The primary outcome was change in dyskinetic crisis burden; secondary outcomes included BFMDRS, Clinical Global Impression (CGI), functional classifications, medication burden, and complications. RESULTS: Forty-six patients underwent implantation at a mean age of 10.4 ± 4.8 years with mean follow-up of 4.5 ± 3.7 years (longest = 17 years). Over half (52.2%) were implanted emergently during dyskinetic status. Dyskinetic crises were reduced in 38 of 40 patients (95%) and intensive care unit (ICU) admissions in 86.1%. The Burke Fahn Marsden Dystonia Rating Scale (BFMDRS) motor scores improved by 27.5% (p < 0.001, Cohen's d = 1.12); CGI was improved in 93.5%, with greater benefit for chorea than dystonia. Pain, sleep, and medication burden improved; functional classification was largely unchanged. Complications occurred in 19.6%, predominantly in emergent cases. INTERPRETATION: Bilateral GPi-DBS was associated with sustained prevention of dyskinetic crises and reduction of overall disease burden in GNAO1-related disorder, with limited impact on functional classification. These findings support earlier elective neuromodulation before recurrent crises drive cumulative morbidity and identify GPi-DBS as a crisis-preventive, symptom-modifying intervention rather than a restorative one. ANN NEUROL 2026.

Authors

Institutions

Publication Details

Journal
Annals of Neurology
Published
2026-07-27
DOI
https://doi.org/10.1002/ana.78310
Primary Topic
Genomics and Rare Diseases
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Outcomes of Bilateral Globus Pallidus Internus Deep Brain Stimulation in GNAO1 ‐Related Disorder: An International Multicenter Experience

Carolina Gorodetsky, Elizabeth Jennions, Kathryn Yang, Daniel Edward Lumsden et al.
Annals of Neurology
Genomics and Rare Diseases
article

Outcomes of Bilateral Globus Pallidus Internus Deep Brain Stimulation in GNAO1 ‐Related Disorder: An International Multicenter Experience

Carolina Gorodetsky, Elizabeth Jennions, Kathryn Yang, Daniel Edward Lumsden, Giacomo Garone, Anne Koy, Agathe Roubertie, Harutomo Hasegawa, Jana Domínguez‐Carral, Darius Ebrahimi‐Fakhari, Lindsey M. Vogt, Jean‐Pierre Lin, Ibrahim Gh, Alonso Zea Vera, Daniela Muñoz, Wei Kang Lim, Juan Darío Ortigoza‐Escobar, Neil Mahant, Weston T. Northam, Katerina Bernardi, Margaret Kaminska, Emilie Chan Seng, Shekeeb S. Mohammad, Moritz Thiel, Joke M. Dijk, Micaela Pauni, Joshua Rong, Josefina Rodríguez, María Concepción Miranda‐Herrero, Hannah F. Jones, Laura A. van de Pol, Eline Chauvet‐Piat, Rick Schuurman, Martijn Beudel, Beatriz De la Casa‐Fages, Gaetan Poulen
article en

Abstract

OBJECTIVE: GNAO1-related disorder is a severe childhood-onset hyperkinetic movement disorder punctuated by life-threatening dyskinetic crises. Small series suggest benefit from bilateral globus pallidus internus deep brain stimulation (GPi-DBS), but optimal timing, patient selection, long-term outcomes, and genotype-specific response remain unclear. We define the clinical impact of GPi-DBS in the largest cohort assembled to date. METHODS: Retrospective multicenter cohort study conducted through the DBSMatchMaker platform, including children and young adults with genetically confirmed GNAO1-related disorder treated with bilateral GPi-DBS across 17 centers. The primary outcome was change in dyskinetic crisis burden; secondary outcomes included BFMDRS, Clinical Global Impression (CGI), functional classifications, medication burden, and complications. RESULTS: Forty-six patients underwent implantation at a mean age of 10.4 ± 4.8 years with mean follow-up of 4.5 ± 3.7 years (longest = 17 years). Over half (52.2%) were implanted emergently during dyskinetic status. Dyskinetic crises were reduced in 38 of 40 patients (95%) and intensive care unit (ICU) admissions in 86.1%. The Burke Fahn Marsden Dystonia Rating Scale (BFMDRS) motor scores improved by 27.5% (p < 0.001, Cohen's d = 1.12); CGI was improved in 93.5%, with greater benefit for chorea than dystonia. Pain, sleep, and medication burden improved; functional classification was largely unchanged. Complications occurred in 19.6%, predominantly in emergent cases. INTERPRETATION: Bilateral GPi-DBS was associated with sustained prevention of dyskinetic crises and reduction of overall disease burden in GNAO1-related disorder, with limited impact on functional classification. These findings support earlier elective neuromodulation before recurrent crises drive cumulative morbidity and identify GPi-DBS as a crisis-preventive, symptom-modifying intervention rather than a restorative one. ANN NEUROL 2026.

Annals of Neurology
Boston Children's Hospital (US), Hospital Sant Joan de Déu Barcelona (ES), Children's Hospital of Philadelphia (US), Harvard University (US), Inserm (FR), King's College London (GB), Universidad de Los Andes, Chile (CL), Université de Montpellier (FR), Guy's and St Thomas' NHS Foundation Trust (GB), Hospital for Sick Children (CA), Hospital Italiano de Buenos Aires (AR), Children's Hospital at Westmead (AU), Hospital General Universitario Gregorio Marañón (ES), University of Malaya (MY), Centre Hospitalier Universitaire de Montpellier (FR), Emma Kinderziekenhuis (NL), University Hospital of Geneva (CH), King's College Hospital NHS Foundation Trust (GB), Hôpital Gui de Chauliac (FR), Bambino Gesù Children's Hospital (IT), Institute for Neurosciences of Montpellier (FR), ERN GUARD-Heart (NL), Starship Children's Health (NZ), University Hospital Cologne (DE), Hospital San Borja Arriarán (CL), Geneva College (US), Vrije Universiteit Amsterdam (NL), University of Gothenburg (SE), University of Amsterdam (NL)
Openalex Percentile: Top 9%
Genomics and Rare Diseases
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.