Shabalov V1,Tomskiy A1, Gamaleya A1,2, Orlova O3, Timerbaeva S4, Isagulyan E1,

Dekopov A1, Salova E1, Fedorova N2

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 Academy4 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

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

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

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

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

DYSTONIA generalized (PGD) segmental (PSD)

patients 16 patients 15 patients

age of onset 12.4±9.0 years*** 31.7±15.9 years

age at surgery 27.8±14.5 years** 42.3±13.3 years

disease duration 15.4±13.5 years 10.7±8.8 years

Initial BFMDRS 47.1±15.3*** 20.4±5.8

Patients: PGD vs. PSD

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

ComplicationsComplications 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

Results: clinical improvementResults: clinical improvement

0

5

10

15

20

25

30

35

40

45

50

before GPi-DBS 3-6 months 9-12 months last follow-up(20.0±13.3

months)follow-up

mea

n B

FM

DR

S

generalized dystonia

segmental dystonia

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

P<0.001

Results: Global Outcome Scale scores Results: Global Outcome Scale scores (Lozano 2000)(Lozano 2000)

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

9; 56,3%4; 25,0%

3; 18,8%

Generalized dystonia Segmental dystonia

Total group

8; 53,3%5; 33,3%

2; 13,3%

17; 54,8%9; 29,0%

5; 16,1%

FactorsFactors

Age of disease onsetAge of disease onset GenderGender Disease durationDisease 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)(BFMDRS motor score before surgery, PGD vs. PSD)

FactorsFactors

Age of disease onsetAge of disease onset GenderGender 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)(BFMDRS motor score before surgery, PGD vs. PSD)

Results: Results: clinical improvement & disease durationclinical improvement & disease duration

0

10

20

30

40

50

60

70

80

90

100

0 10 20 30 40 50 60

disease duration, years

cli

nic

al

imp

rov

em

en

t, %

Advantageous outcome both at early and long-term follow-up was associated with minor disease duration

rs=-0.546, p=0.002

DYSTONIA childhood-onset (<12 years)

juvenile-onset (12-26 years)

adult-onset (>26 years)

patients 12 patients 8 patients 11 patients

PGD vs. PSD 11PGD / 1PSD 4PGD / 4PSD 1PGD / 10PSD

BFMDRS initial 51.1±14.8*** 26.0±11.6 21.7±6.9

disease duration 19.8±14.5* 8.6±4.9 9.2±8.2

age at surgery 27,4±14.9 25.5±3.6 49.5±3.0

Patients: age of onset

Results: Results: clinical improvement & age of onsetclinical improvement & age of onset

Δ 54.7±20.0±20.0%*P<0.05

Δ 73.7±14.8±14.8% Δ 68.9±18.1±18.1%

0

10

20

30

40

50

60

childhood-onset juvenile-onset adult-onset

me

an

BF

MD

RS

before GPi-DBS

last follow-up

0

10

20

30

40

50

60

до 3-6 months 9-12 months last follow-up(20.0±13.3 months)follow-up

mea

n B

FM

DR

S

childhood-onset

juvenile-onset

adult-onset

Clinical improvement in patients with childhood-onset(10 patients)

0

10

20

30

40

50

60

< 20 years > 20 yearsdisease duration

mea

n B

FM

DR

S

before

after GPi-DBS

Δ72.1±9.0±9.0%, p<0.06 Δ 45.9±16.5±16.5%

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