Genetic Profile and Symptom Pattern Explain Variability of Deep Brain Stimulation Effect in Dystonia
ABSTRACT Objective Bilateral globus pallidus pars interna deep brain stimulation (GPi‐DBS) is a recognized and effective treatment option for drug‐resistant dystonia patients. However, the clinical GPi‐DBS outcomes vary significantly. Herein, we explored the pre‐implant factors affecting GPi‐DBS eff...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-08-01
|
| Series: | Annals of Clinical and Translational Neurology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/acn3.70098 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849404835717185536 |
|---|---|
| author | Mahboubeh Ahmadipour Luigi M. Romito Antonio E. Elia Nico Golfré Andreasi Roberto Eleopra Alberto Mazzoni Fabiana Colucci |
| author_facet | Mahboubeh Ahmadipour Luigi M. Romito Antonio E. Elia Nico Golfré Andreasi Roberto Eleopra Alberto Mazzoni Fabiana Colucci |
| author_sort | Mahboubeh Ahmadipour |
| collection | DOAJ |
| description | ABSTRACT Objective Bilateral globus pallidus pars interna deep brain stimulation (GPi‐DBS) is a recognized and effective treatment option for drug‐resistant dystonia patients. However, the clinical GPi‐DBS outcomes vary significantly. Herein, we explored the pre‐implant factors affecting GPi‐DBS effectiveness. Methods Genetic profiles, symptom distribution, age at onset, disease duration, and severity of a cohort of 31 GPi‐DBS dystonia patients were collected. Dystonia motor severity was evaluated before and after GPi‐DBS using the Burke–Fahn–Marsden Dystonia‐Rating‐Scale (BFMDRS‐M). We assessed the interplay of the aforementioned factors in determining the BFMDRS‐M improvement through a multilinear regression analysis. Results BFMDRS‐M score showed a significant improvement (47.8%) since the first year, remaining stable at 5 years (54.3%). Lower limb (0.20), upper limb (0.16) and trunk (0.24) symptoms showed a significantly larger improvement compared to cranial symptoms (0.07, p < 0.05). Consequently, patients with more pronounced lower limb motor symptoms displayed a greater GPi‐DBS effect (p < 0.01). However, pre‐treatment localization of motor symptoms accounted only for 31% of the Inter‐Patient Variability (IPV) in post‐GPi‐DBS improvement. Amelioration varied also across genetic profiles, with the largest improvement reported for DYT‐TOR1A patients (n = 9, 64.2% in the first year), predicting 36% of IPV. Interestingly, combining motor and genetic profiles predicted 73% of the IPV. Including the clinical profile of the patient (age at onset, disease severity and duration) increased prediction accuracy to 81%. Interpretation Our results suggest that motor and genetic profiles contribute independently to the efficacy of the GPi‐DBS treatment. These results may support a personalized prediction of DBS outcomes in dystonia patients. |
| format | Article |
| id | doaj-art-4170af393fcb49dc8064c37fc154d4a5 |
| institution | Kabale University |
| issn | 2328-9503 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj-art-4170af393fcb49dc8064c37fc154d4a52025-08-20T03:36:49ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-08-011281660166910.1002/acn3.70098Genetic Profile and Symptom Pattern Explain Variability of Deep Brain Stimulation Effect in DystoniaMahboubeh Ahmadipour0Luigi M. Romito1Antonio E. Elia2Nico Golfré Andreasi3Roberto Eleopra4Alberto Mazzoni5Fabiana Colucci6The Biorobotics Institute Scuola Superiore Sant'Anna Pisa ItalyMovement Disorders Department Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyMovement Disorders Department Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyMovement Disorders Department Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyMovement Disorders Department Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyThe Biorobotics Institute Scuola Superiore Sant'Anna Pisa ItalyMovement Disorders Department Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyABSTRACT Objective Bilateral globus pallidus pars interna deep brain stimulation (GPi‐DBS) is a recognized and effective treatment option for drug‐resistant dystonia patients. However, the clinical GPi‐DBS outcomes vary significantly. Herein, we explored the pre‐implant factors affecting GPi‐DBS effectiveness. Methods Genetic profiles, symptom distribution, age at onset, disease duration, and severity of a cohort of 31 GPi‐DBS dystonia patients were collected. Dystonia motor severity was evaluated before and after GPi‐DBS using the Burke–Fahn–Marsden Dystonia‐Rating‐Scale (BFMDRS‐M). We assessed the interplay of the aforementioned factors in determining the BFMDRS‐M improvement through a multilinear regression analysis. Results BFMDRS‐M score showed a significant improvement (47.8%) since the first year, remaining stable at 5 years (54.3%). Lower limb (0.20), upper limb (0.16) and trunk (0.24) symptoms showed a significantly larger improvement compared to cranial symptoms (0.07, p < 0.05). Consequently, patients with more pronounced lower limb motor symptoms displayed a greater GPi‐DBS effect (p < 0.01). However, pre‐treatment localization of motor symptoms accounted only for 31% of the Inter‐Patient Variability (IPV) in post‐GPi‐DBS improvement. Amelioration varied also across genetic profiles, with the largest improvement reported for DYT‐TOR1A patients (n = 9, 64.2% in the first year), predicting 36% of IPV. Interestingly, combining motor and genetic profiles predicted 73% of the IPV. Including the clinical profile of the patient (age at onset, disease severity and duration) increased prediction accuracy to 81%. Interpretation Our results suggest that motor and genetic profiles contribute independently to the efficacy of the GPi‐DBS treatment. These results may support a personalized prediction of DBS outcomes in dystonia patients.https://doi.org/10.1002/acn3.70098deep brain stimulationdystoniaoutcome predictorsvariability |
| spellingShingle | Mahboubeh Ahmadipour Luigi M. Romito Antonio E. Elia Nico Golfré Andreasi Roberto Eleopra Alberto Mazzoni Fabiana Colucci Genetic Profile and Symptom Pattern Explain Variability of Deep Brain Stimulation Effect in Dystonia Annals of Clinical and Translational Neurology deep brain stimulation dystonia outcome predictors variability |
| title | Genetic Profile and Symptom Pattern Explain Variability of Deep Brain Stimulation Effect in Dystonia |
| title_full | Genetic Profile and Symptom Pattern Explain Variability of Deep Brain Stimulation Effect in Dystonia |
| title_fullStr | Genetic Profile and Symptom Pattern Explain Variability of Deep Brain Stimulation Effect in Dystonia |
| title_full_unstemmed | Genetic Profile and Symptom Pattern Explain Variability of Deep Brain Stimulation Effect in Dystonia |
| title_short | Genetic Profile and Symptom Pattern Explain Variability of Deep Brain Stimulation Effect in Dystonia |
| title_sort | genetic profile and symptom pattern explain variability of deep brain stimulation effect in dystonia |
| topic | deep brain stimulation dystonia outcome predictors variability |
| url | https://doi.org/10.1002/acn3.70098 |
| work_keys_str_mv | AT mahboubehahmadipour geneticprofileandsymptompatternexplainvariabilityofdeepbrainstimulationeffectindystonia AT luigimromito geneticprofileandsymptompatternexplainvariabilityofdeepbrainstimulationeffectindystonia AT antonioeelia geneticprofileandsymptompatternexplainvariabilityofdeepbrainstimulationeffectindystonia AT nicogolfreandreasi geneticprofileandsymptompatternexplainvariabilityofdeepbrainstimulationeffectindystonia AT robertoeleopra geneticprofileandsymptompatternexplainvariabilityofdeepbrainstimulationeffectindystonia AT albertomazzoni geneticprofileandsymptompatternexplainvariabilityofdeepbrainstimulationeffectindystonia AT fabianacolucci geneticprofileandsymptompatternexplainvariabilityofdeepbrainstimulationeffectindystonia |