Effect of frequency on subthalamic nucleus deep brain stimulation in primary dystonia Jill L. Ostrem a, c, * , Leslie C. Markun a, c , Graham A. Glass a, c , Caroline A. Racine b , Monica M. Volz a , Susan L. Heath c , Coralie de Hemptinne b , Philip A. Starr b, c a Department of Neurology, University of California, San Francisco, Surgical Movement Disorders,1635 Divisadero Street, 5th Floor, Suites 520-530, San Francisco, CA 94115, USA b Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave., Rm. M779, San Francisco, CA 94143, USA c Parkinson’s Disease Research, Education, and Clinical Center, San Francisco Veterans Affairs Medical Center, 4150 Clement Street (p-127), San Francisco, CA 94121, USA article info Article history: Received 8 July 2013 Received in revised form 25 September 2013 Accepted 23 December 2013 Keywords: Subthalamic nucleus Deep brain stimulation Primary dystonia Frequency abstract Background: Subthalamic nucleus deep brain stimulation (DBS) is an alternative target choice for treating primary dystonia, but little is known about the most effective programming parameters. Objective: Here we prospectively evaluate the effect of low versus high frequency subthalamic nucleus DBS in patients with predominantly cervical or upper extremity primary dystonia. Methods: Seven patients were stimulated at low frequency stimulation (60 Hz) for the first three months and then switched to high frequency stimulation (130 Hz) until month six. Severity of dystonia was determined by a blinded rater (unaware of the patient’s pre or post-operative status) who scored the Burke Fahn Marsden dystonia rating scale movement score (BFMDRS-M) and the Toronto Western Spasmodic Torticollis Rating Scale severity score (TWSTRS-S) preoperatively, three, six, and twelve months post-surgery. Results: Patients had a lower mean improvement of 16.6% in BFMDRS-M and 9.5% in TWSTRS-S at three months using low frequency stimulation compared to a 52.3% (p ¼ 0.018) and 45.2% (p ¼ 0.028), respectively, noted at six months using high frequency stimulation. At 12 months (using 130 Hz), the BFMDRS-M and TWSTRS-S improved by 51.8% (p ¼ 0.022) and 56% (p ¼ 0.034). Patients developed transient dyskinesia (during low and high frequency stimulation) which improved with programming adjustments. Conclusion: This study offers further support of the effectiveness of subthalamic nucleus DBS in the treatment of primary dystonia and finds that high frequency stimulation was more effective than low frequency stimulation. Published by Elsevier Ltd. 1. Introduction Deep brain stimulation (DBS) therapy to treat severe medication refractory primary dystonia is now a well-established treatment option for patients. Several studies of globus pallidus interna (GPi) stimulation over the last decade have reported a 30e80% improvement in primary dystonia after surgery [1e5]. Despite the major benefit in symptom relief, increasingly recognized is the possibility of stimulation induced bradykinetic side effects from GPi DBS including freezing of gait in previously non-dystonic body re- gions, not attributable to spread of current to nearby corticospinal tract fibers [5e9]. In many cases adjustment of the stimulator set- tings to avoid these side effects was not possible without worsening the control of the dystonia. This observation lead us to study a novel DBS dystonia brain target, the subthalamic nucleus (STN), in a prospective clinical trial with the goal of treatment of dystonia without development of stimulation induced adverse motor effects. The results of the first 9 patients treated in the trial were recently published and demonstrated a robust 61.3% mean improvement in the TWSTRS severity (S) scores after 12 months of high frequency stimulation (HFS) [10]. Although historically HFS has been used in GPi DBS, low frequency (60 Hz) stimulation (LFS) has also been reported to be effective [11e 14]. Thus far only HFS has been described in STN DBS for treatment of dystonia [10,15,16]. In * Corresponding author. Department of Neurology, Surgical Movement Disorders, 1635 Divisadero Street, 5th Floor, Suites 520-530, San Francisco, CA 94115, USA. Tel.: þ1 415 353 2311; fax: þ1 415 353 9060. E-mail address: jill.ostrem@ucsf.edu (J.L. Ostrem). Contents lists available at ScienceDirect Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis 1353-8020/$ e see front matter Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.parkreldis.2013.12.012 Parkinsonism and Related Disorders 20 (2014) 432e438