Objective: To report the negative outcome of bilateral centromedian-parafascicular (CM-Pf) DBS in a pediatric patient with drug-refractory Rapid-onset Dystonia-Parkinsonism (RDP) harboring an ATP1A3 mutation.

Background: Caused by ATP1A3 mutations, RDP features abrupt rostro-caudal dystonia and parkinsonism. It typically resists pharmacotherapy and traditional DBS targets [e.g., globu pallidus interna (GPi), subthal amic nucleus (STN)]. Recently, the CM-Pf complex emerged as a promising alternative target. We present an RDP case where CM-Pf DBS yielded no clinical benefit.

Method: A 13-year-old male presented with acute psychiatric symptoms, rapidly progressing to severe dysarthria, generalized dystonia, and gait instability within one month. Examination revealed a rostro-caudal dystonia gradient and pyramidal signs (hyperreflexia, Babinski signs, clonus). Extensive workup (MRI, CSF, autoimmune, metabolic) was unremarkable. Whole-exome sequencing identified a heterozygous pathogenic ATP1A3 variant (c.829G>A, p.Glu277Lys), confirming RDP

Results: Refractory to levodopa, anticholinergics, and benzodiazepines, the patient became bedridden. Given the phenotype severity, bilateral CM-Pf DBS was performed. Despite accurate electrode placement and 6 months of systematic programming, he exhibited no significant clinical improvement. Motor function remained profoundly impaired, with negligible changes in Global Dystonia Severity Rating Scale (GDS) scores (Pre-operation: 83 vs. Post-operation: 75).

Conclusion: While CM-Pf DBS showed promise in isolated reports, it lacked efficacy in this acute-onset RDP case with pyramidal involvement. This highlights the phenotypic heterogeneity of ATP1A3 disorders. The severe network disruption in certain RDP subtypes—potentially involving cerebellar and descending pyramidal pathways—may extend beyond the thalamostriatal circuit’s modulatory capacity. Cautious patient selection and further mechanistic exploration are warranted for DBS in ATP1A3 spectrum disorders.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/treatment-of-bilateral-centromedian-parafascicular-cm-pf-deep-brain-stimulation-in-a-pediatric-case-of-rapid-onset-dystonia-parkinsonism/