1. Shabalov V 1,Tomskiy A 1, Gamaleya A 1,2, Orlova O 3, Timerbaeva S 4, Isagulyan E 1, Dekopov A 1, Salova E 1, Fedorova N 2 1 Functional Neurosurgery Group, Burdenko Neurosurgical Institute, Moscow, Russian Federation 2 Center for Extrapyramidal Disorders, Russian Medical Academy of Postgraduate Education, Moscow 3 Moscow Medical Sechenov Academy 4 Neurological Research Center, Russian Academy of Medical Scienses, Moscow 14th Annual Meeting Neuromodulation Las-Vegas, US,Hannover, December 2-5, 2010 DBS of GPI in Cases of Primary Generalized and Segmental Dystonia with Different Age of Onset

2. DBS & DYSTONIA DBS of GPi is considered as a preferable therapy in disabling primary dystonia particular outcomes remain varying and unpredictable search for the prognostic criteria

3. Isaias IU et al., Brain 2008 Disease duration showed a significant correlation with DBS outcome at 3 and12 months. Vasques X et al., J. Neurosurg 2009 Prognostic value of globus pallidus internus volume in primary dystonia Borggraefe I et al., Brain Dev. 2010 Predictive factors for a better treatment outcome DYT1-positive status and minor motor impairment before surgery

4. Objective  to evaluate the efficacy of DBS of GPi at a single center  to reveal possible predictors of clinical improvement in different types of dystonia

5. Materials and Methods 31 patients with medically refractory primary dystonia 10 males and 21 females DYT1 + 3 patients Prior destructive surgery: pallidotomy in 1 case thalamotomy 3 cases bilateral implantation of pallidal electrodes for continuous high- frequency stimulation

6. DYSTONIAgeneralized (PGD)segmental (PSD) patients16 patients15 patients age of onset12.4±9.0 years***31.7±15.9 years age at surgery27.8±14.5 years**42.3±13.3 years disease duration15.4±13.5 years10.7±8.8 years Initial BFMDRS47.1±15.3***20.4±5.8 Patients: PGD vs. PSD

7. Surgical technique 1 step – Stereotactic implantation of the leads, without microelectrode recording, intraoperative test-stimulation in awake patient if possible 2 step – Postoperative control (MRI, test-stimulation) 3 step – Implantation of pulse generator 4 step – Postoperative management

8. Complications Migration of pulse generator in 2 cases  correction of generator position Electrode dislocation in to incorrect position - 1 case Correction of primary electrode position - 2 cases Dysarthria under DBS - 3 cases Feeling of the leg tension - 2 cases Distal arm dystonia aggravation - 1 case

9. Results: clinical improvement Mean clinical improvement in BFMDRS motor score in total primary dystonia group (Δ%): – at 3-6 months Δ 53.4±16.0%, – at 9-12 months Δ 64.4±18.5%, – at last follow-up Δ 64.3±19.1% (20.0±13.3 months) P<0.001

10. Results: Global Outcome Scale scores (Lozano 2000) 0 – no effect 1 – minimal relief without improvement of function 2 – moderate relief with or without minimal improvement of function 3 – moderate relief with improvement of function 4 – significant relief with significant improvement of function 0p – no effect 1p – minimal relief without improvement of function 2p – moderate relief with or without minimal improvement of function 3p - moderate relief with improvement of function 4p – significant relief with significant improvement of function Generalized dystonia Segmental dystonia Total group

11. Factors Age of disease onset Age of disease onset Gender Gender Disease duration Disease duration Age at surgery Age at surgery Severity of motor function impact Severity of motor function impact (BFMDRS motor score before surgery, PGD vs. PSD)

12. Factors Age of disease onset Age of disease onset Gender Gender Disease duration Age at surgery Age at surgery Severity of motor function impact Severity of motor function impact (BFMDRS motor score before surgery, PGD vs. PSD)

13. Results: clinical improvement & disease duration Advantageous outcome both at early and long-term follow-up was associated with minor disease duration rs=-0.546, p=0.002

14. DYSTONIAchildhood-onset (<12 years) juvenile-onset (12-26 years) adult-onset (>26 years) patients12 patients8 patients11 patients PGD vs. PSD11PGD / 1PSD4PGD / 4PSD1PGD / 10PSD BFMDRS initial51.1±14.8***26.0±11.621.7±6.9 disease duration19.8±14.5*8.6±4.99.2±8.2 age at surgery27,4±14.925.5±3.649.5±3.0 Patients: age of onset

15. Results: clinical improvement & age of onset Δ 54.7%* P<0.05 ±20.0 Δ 54.7±20.0%* P<0.05 ±14.8 Δ 73.7±14.8% ±18.1 Δ 68.9±18.1%

16. Clinical improvement in patients with childhood-onset (10 patients) ±9.0 Δ72.1±9.0%, p<0.06 ±16.5 Δ 45.9±16.5%

17. Conclusions   DBS of GPi is effective in primary dystonia with sustained significant clinical improvement in generalized as well as in segmental forms in equal proportions   Pure DBS of GPi motor outcome (final BFMDRS score) in generalized compared to segmental dystonia remains respectively worse  Age of onset, age at surgery, gender, initial severity are not of a predictive significance  Disease duration is an important efficacy predictor   DBS of GPi may be recommended to be performed early enough in the course of intractable PGD and PSD   Studies pooling together more patients are still needed