Deep Brain Stimulation for GNAO1-Associated Dystonia: A Systematic Review and Meta-Analysis

Neuromodulation. 2024 Apr;27(3):440-446. doi: 10.1016/j.neurom.2023.10.187. Epub 2023 Nov 24.

Abstract

Objectives: Guanine nucleotide-binding protein alpha-activating activity polypeptide O (GNAO1) syndrome, a rare congenital monogenetic disorder, is characterized by a neurodevelopmental syndrome and the presence of dystonia. Dystonia can be very pronounced and even lead to a life-threatening status dystonicus. In a small number of pharmaco-refractory cases, deep brain stimulation (DBS) has been attempted to reduce dystonia. In this study, we summarize the current literature on outcome, safety, and outcome predictors of DBS for GNAO1-associated dystonia.

Materials and methods: We conducted a systematic review and meta-analysis on individual patient data. We included 18 studies describing 28 unique patients.

Results: The mean age of onset of symptoms was 2.4 years (SD 3.8); 16 of 28 patients were male, and dystonia was nearly always generalized (20/22 patients). Symptoms were present before DBS for a median duration of 19.5 months, although highly variable, occurring between 3 and 168 months. The exact phenotype, genotype, and radiologic abnormalities varied and seemed to be of little importance in terms of DBS outcome. All studies described an improvement in dystonia. Our meta-analysis focused on pallidal DBS and found an absolute and relative improvement in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) of 32.5 points (37.9%; motor part; p = 0.001) and 5.8 points (21.5%; disability part; p = 0.043) at last follow-up compared with preoperative state; 80% of patients were considered responders (BFMDRS-M reduction by ≥25%). Although worsening over time does occur, an improvement was still observed in patients after >10 years. All reported cases of status dystonicus resolved after DBS surgery. Skin erosion and infection were observed in 18% of patients.

Conclusion: Pallidal DBS can be efficacious and safe in GNAO1-associated dystonia.

Keywords: DBS; GNAO1; deep brain stimulation; dystonia; meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Child
  • Child, Preschool
  • Deep Brain Stimulation*
  • Dystonia* / genetics
  • Dystonia* / therapy
  • Dystonic Disorders* / genetics
  • Dystonic Disorders* / therapy
  • Female
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Globus Pallidus / physiology
  • Heredodegenerative Disorders, Nervous System*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Treatment Outcome

Substances

  • GNAO1 protein, human
  • GTP-Binding Protein alpha Subunits, Gi-Go

Supplementary concepts

  • Fatty Acid Hydroxylase-Associated Neurodegeneration