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SPIDY

French Stimulation du Pallidum Interne dans la Dystonie (SPIDY) Study: Bilateral Deep-Brain Stimulation of the Globus Pallidus in Primary Generalized Dystonia

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Year of Publication: 2005

Authors: Vidailhet M, Vercueil L, Houeto JL, ..., for the French SPIDY Study Group

Journal: New England Journal of Medicine

Citation: N Engl J Med 2005;352:459-67

Clinical Question

Is bilateral stimulation of the internal globus pallidus safe and effective for treating primary generalized dystonia in adults?

Bottom Line

Bilateral deep-brain stimulation of the internal globus pallidus is safe and effective in selected patients with primary generalized dystonia, resulting in sustained improvement in motor symptoms (51% improvement in movement scores) and functional disability over 12 months without affecting cognition or mood.

Major Points

  • First prospective, controlled, multicenter study with blinded video assessment of bilateral GPi DBS for primary generalized dystonia in adults
  • 22 patients enrolled from 3 French centers (Grenoble, Paris, Lille) with median age 30 years and median disease duration 18 years
  • Movement scores improved by 51% at 12 months (46.3±21.3 to 21.0±14.1, P<0.001) using Burke-Fahn-Marsden Dystonia Scale
  • Disability scores improved from 11.6±5.5 to 6.5±4.9 at 12 months (P<0.001)
  • Double-blind evaluation at 3 months demonstrated worse motor scores without stimulation (34.6±12.3) vs. with stimulation (24.6±17.7, P<0.001)
  • Best responders (>75% improvement) had diffuse phasic hyperkinetic movements preoperatively; patients with severe tonic postures had limited improvement
  • Axial and limb subscores improved by 69% and 52% respectively; facial movements and speech remained unchanged
  • Quality of life improved with significant gains in general health and physical functioning on SF-36
  • No changes in cognition (MMSE) or mood (Beck Depression Inventory) postoperatively
  • Five adverse events in 3 patients, all resolved without permanent sequelae

Design

Study Type: Prospective, controlled, multicenter, self-controlled cohort study with double-blind crossover evaluation

Randomization:

Blinding: Double-blind evaluation at 3 months (stimulation on vs. off in random order); video assessments scored by blinded independent observer

Follow-up Duration: 12 months

Centers: 3

Countries: France

Sample Size: 22

Analysis: Wilcoxon signed-rank test for matched pairs; linear mixed model (ANOVA with random effects) for repeated measures

Inclusion Criteria

  • Clinically diagnosed primary generalized dystonia
  • Combination of segmental crural dystonia (involving one leg and trunk) and involvement of any other segment
  • No secondary causes including birth injury, head trauma, or neuroleptic treatments
  • Normal neurologic examination except for dystonia
  • Normal brain MRI findings
  • No psychiatric disturbances
  • Normal cognitive function (MMSE score ≥24)
  • Severe impairment in activities of daily living despite optimal medical management

Exclusion Criteria

  • Secondary dystonia (birth injury, head trauma, neuroleptic-induced)
  • Abnormal neurologic examination beyond dystonia
  • Abnormal brain MRI findings
  • Psychiatric disturbances
  • Cognitive impairment (MMSE <24)

Arms

FieldBilateral GPi DBS
InterventionBilateral deep-brain stimulation of the posterolateral ventral internal globus pallidus using DBS-3389 Medtronic electrodes connected to Kinetra neurostimulator; frequency 100-185 Hz (mostly 130 Hz); voltage 3.7-3.8 V
Duration12 months follow-up

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Burke-Fahn-Marsden Dystonia Scale movement score (range 0-120, higher scores indicate greater impairment)Primary46.3±21.3 (baseline)21.0±14.1 (12 months)<0.001
Burke-Fahn-Marsden disability score at 12 months (range 0-30)Secondary11.6±5.5 (baseline)6.5±4.9 (12 months)<0.001
Movement score at 3 months with vs without stimulation (double-blind evaluation)Secondary34.6±12.3 (without stimulation)24.6±17.7 (with stimulation)<0.001
Axial subscore (neck and trunk) at 12 monthsSecondary12.5±7.9 (baseline)3.9±4.1 (69% improvement)<0.001
SF-36 General Health score at 12 monthsSecondary47±24 (baseline)63±27 (12 months)0.04
SF-36 Physical Functioning score at 12 monthsSecondary41±28 (baseline)62±29 (12 months)0.007
Patients with >50% improvement in movement score at 12 monthsSecondary14 of 22 (64%)
Transient perioperative frontal lobe edemaAdverse1 patient (asymptomatic, resolved)
Lead fracture with current leakageAdverse1 patient (lead replaced)
Cutaneous necrosis of scalpAdverse1 patient
Localized skin infectionAdverse1 patient (resolved)
Hematoma near neurostimulatorAdverse1 patient (resolved)

Subgroup Analysis

Seven patients with DYT1 mutation vs. 15 without: DYT1 status was not a significant predictor of motor improvement at 12 months. Patients with diffuse phasic hyperkinetic movements had >75% improvement; patients with severe tonic abnormal postures had limited improvement (0-25%) or worsening.

Criticisms

  • Single-arm study without parallel control group (patients served as their own controls)
  • Relatively small sample size (n=22) limited ability to identify predictors of response
  • Variable response to therapy with 4 patients having minimal improvement or worsening
  • Speech and facial movements did not improve, limiting applicability for some patients
  • Washout period of only 10 hours for double-blind evaluation at 3 months may not have been complete
  • Long-term follow-up beyond 12 months not reported

Funding

Supported by a national grant (PHRC 98) from the Direction Régionale de la Recherche Clinique Assistance-Publique-Hôpitaux de Paris, the INSERM Dystonia French National Network, and an additional unrestricted grant from Medtronic

Based on: SPIDY (New England Journal of Medicine, 2005)

Authors: Vidailhet M, Vercueil L, Houeto JL, ..., for the French SPIDY Study Group

Citation: N Engl J Med 2005;352:459-67

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