Supplementary Appendix

Transcription

1 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Elias WJ, Huss D, Voss T, et al. A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med 2013;369: DOI: /NEJMoa

2 Supplementary Appendix A Pilot Study of Focused Ultrasound Thalamotomy for Essential Tremor W. Jeffrey Elias MD 1, Diane Huss PT DPT NCS 2, Tiffini Voss MD 3, Johanna Loomba BS 1, Mohamad Khaled MD 1, Eyal Zadicario Msc 5, Robert C. Frysinger PhD 1, Scott A. Sperling Psy.D 3, Scott Wylie PhD 3, Stephen Monteith MD 1, Jason Druzgal MD PhD 4, Binit B. Shah MD 3, Madaline Harrison MD 3, and Max Wintermark MD 4 1 Departments of Neurosurgery, 2 Physical Therapy, 3 Neurology, and 4 Neuroradiology University of Virginia Health Sciences Center, Charlottesville, VA 5 Insightec Inc., Haifa, Israel 1

3 Table of Contents Table S1. Individual tremor scores: contralateral (treated) upper limb 3 Table S2. Individual tremor scores: Total Clinical Rating Scale for Tremor 4 Table S3. Dynamic Gait Index scores 5 Figure S1. Workflow illustration of transcranial MR-guided focused ultrasound for the treatment of tremor 6 Figure S2. Individual drawing and handwriting tasks 7-22 References 23 2

4 Table S1. Individual Tremor Scores: Contralateral (Treated) Upper Limb Reference # Baseline Tx Day pre Tx Day post 24 Hr 1 Wk 1 Mo 3 Mo 1 Yr % Δ Baseline - 1Yr ET ET ET ET ET ET ET * 85 ET ET ET ET ET ET ET ET Mean St. Dev The maximum score is 32 points for eight items each with a score range from 0-4. The eight items include treated side (contralateral to the thalamotomy) observed tremor in rest, posture and action/intention from part A of the Clinical Rating Scale for Tremor 1 and the part B tasks of handwriting, two targeted spiral drawings, one line drawing, and water pouring. Supplemental results are listed in order of treatment response of the treated hand. Patient reference numbers are consistent throughout the Supplemental Figures and Tables. Note immediate decline in tremor as tested within 30 minutes of completion of treatment (Tx Day post). Ten individuals demonstrated additional decline at one week, likely due to perilesional edema confirmed on MRI at one week. One year after treatment, 11 individuals scored ±2 points of their one month score. While a minimal detectable change score has not been reported for the Clinical Rating Scale for Tremor, the relative stability of their tremor control is consistent with their continued abilities as noted in in part C of the Clinical Rating Scale for Tremor and on the Quality of Life for Essential Tremor Questionnaire. (Figure 1) One person gained 3 points, another 4 points and a third increased by 7 points. Only the later, reported concurrent decline in functional abilities with the increased tremor. The other two continued to report little to no functional disability. *One patient did not return for a one year assessment. His last observed score was carried forward. 3

5 Table S2. Individual Tremor Scores: Total Score Reference # Baseline 1 Wk 1 Mo 3 Mo 1 Yr % Δ Baseline - 1Yr ET ET ET ET ET ET ET * 50 ET ET ET ET ET ET ET ET Mean St. Dev Maximum tremor score from the Clinical Rating Scale for Tremor is 160 with a higher score indicating more overall tremor throughout the body. This score summates overall tremor from contralateral and ipsilateral limbs as well as axial tremors of the head, neck, voice, and trunk. Overall average improvement is 56% with range from 89% to 21%. The greatest degree of tremor suppression on this total/overall score tended to occur in patients with asymmetrical and predominantly appendicular tremor. Given that this is a unilateral treatment and the condition is progressive, it is difficult to discern solely from this Table whether an increasing total tremor score results from recurrence in the treated limb or progression of disease in the untreated regions. *Last observed score carried forward. 4

6 Table S3. Dynamic Gait Index 2 Scores Reference # Baseline 1 Wk 1 Mo 3 Mo 1 Yr ET ET ET ET ET ET ET * 23 ET ET ET ET ET ET ET ET Mean St. Dev Objective declines in gait and balance stability at one week post treatment in four patients (highlighted) which were classified as a gait ataxia. In all four cases, the instability resolved by one month. Five other patients reported temporary unsteadiness without an objective change in their gait performance. The Dynamic Gait Index has a maximum of 24 points with a minimal detectible change score ±2.9 (MDC 95% ). 1 This represents a 95% confidence level that genuine change in function has occurred between two assessments. *Last observed score carried forward. 5

7 Figure S1. Workflow Illustration of Transcranial MR-guided Focused Ultrasound for the Treatment of Tremor. Note that closed loop feedback is available throughout the procedure. (Center) Hemispherical transducer with 1024 elements capable of focusing acoustic energy through the intact cranium. (Left) Stereotactic planning is performed from high resolution 3 Tesla MR images. (Upper) Series of MR thermal images acquired every 3.7 seconds during a single sonication which allows clinicians the ability to measure the intensity of the treatment to within 1⁰ Celsius as well as to monitor the location of the treatment. (Right and bottom) Clinical testing is conducted with each sonication to verify tremor relief or the development of side effects. 6

8 Figure S2. Individual drawing and handwriting samples for all 15 subjects. These samples are obtained from the Clinical Rating Scale for Tremor part B subsection administered at baseline, pretreatment day, immediately posttreatment on the same day, one month, three months, and one year. These drawings and handwriting tasks depict immediate abatement of tremor post treatment with ongoing follow up at one month, three months and one year. Treated hand (contralateral to thalamotomy) and untreated hand (ipsilateral to thalamotomy) are represented. 7

9 ET-001 8

10 ET-002 9

11 ET

12 ET

13 ET

14 ET

15 ET

16 ET

17 ET

18 ET010 17

19 ET

20 ET

21 ET

22 ET

23 ET

24 REFERENCES 1. Fahn S, Tolosa E, Marin C. Clinical Rating Scale for Tremor: Parkinson s Disease and Movement Disorders: edited by Jankovic J and Tolosa E 2 nd ed, Baltimore: Williams and Wilkins; Shumway-Cook A, Woollacott M. Motor Control: Theory and Practical Applications. Baltimore: Williams and Wilkins; Romero S; Bishop MD, Velozo CA, Light K. Minimum detectable change of the Berg Balance Scale and dynamic gait index in older persons at risk for falling. Journal of geriatric physical therapy 2011;34: