Pallidal Stimulation for Primary Generalised Dystonia: Therapeutic Time-course, Predictive Factors for Improvement and Novel Side Effects of Tremor and Akinesia

  • Dr Stephen Tisch, Department of Neurology, St Vincent's Hospital, Darlinghurst, Sydney, Australia
  • Prof Marwan Hariz, Unit of Functional Neurosurgery, Sobell Department, Institute of Neurology, London, United Kingdom
  • Mr Ludvic Zrinzo, Unit of Functional Neurosurgery, Sobell Department, Institute of Neurology, London, United Kingdom
  • Prof Kailash Bhatia, Sobell Department, Institute of Neurology, London, United Kingdom
  • Dr Patricia Limousin, Unit of Functional Neurosurgery, Sobell Department, Institute of Neurology, London, United Kingdom

    • Objective: To evaluate the time-course and predictive factors for improvement in primary generalised dystonia (PGD) following bilateral globus pallidus internus (GPi) DBS.
    Methods: The therapeutic response of PGD to bilateral GPi DBS in 20 patients (10 DYT1 positive, 14 female, mean age 41 years ± 16, mean duration of symptoms 24 years ± 14) was studied prospectively. Surgery was performed using MRI-based direct targeting without microelectrode recording. Patients were assessed using the Burke-Fahn-Marsden (BFM) score before and 0.5, 1, 3, 6, 12, 24, 36 months after surgery.
    Results: At 6 months, BFM movement score improved by an average of 68% ± 18 and disability score by 55% ± 23 (p<0.00001). Improvement was sustained: 12 months 68% ± 20 (n=16), 2 years 71 % ± 21 (n=16), 3 years 65% ± 25 (n=10. The time-course of improvement was progressive and logarithmic (p=0.0001), independent of changes in DBS electrical parameters. Univariate ANOVA identified DYT1 and orthopaedic deformity as significant positive and negative predictors of outcome, but age and symptom duration were not predictive. No major complications occurred. Reversible, stimulation related side effects included dysarthria, akinesia and tremor.
    Conclusions: The present results confirm GPi DBS performed using MRI based direct targeting without microelectrode recording, to be a safe and effective treatment for PGD. DYT1 is a favourable prognostic factor while orthopaedic deformity appears to confer a worse outcome. The progressive time-course of improvement is independent of adjustments in stimulation parameters and may reflect neural plasticity underlying the therapeutic response.