Globus Pallidus Deep Brain Stimulation in DystoniaDiamond A, Shahed J, Azher S, Vuong KD, Jankovic J

Department of Neurology, Baylor College of Medicine, Houston, Texas

Globus Pallidus Deep Brain Stimulation in DystoniaDiamond A, Shahed J, Azher S, Vuong KD, Jankovic J

Department of Neurology, Baylor College of Medicine, Houston, Texas

BACKGROUND: Since pharmacological treatment is often ineffective in generalized dystonia, globus pallidus deep brain stimulation (GPi-DBS) has become a useful alternative. METHODS: All patients selected for GPi-DBS were prospectively rated pre- and post-DBS with the Unified Dystonia Rating Scale (UDRS). In addition, "blinded" videotape assessments using the Abnormal Involuntary Movement Scale (AIMS) were performed. RESULTS: Eleven patients, 7 male, with mean age at onset of dystonia of 18.4 years and mean duration of symptoms of 17.5 years, had adequate follow-up of up to one year. Compared with pre-DBS scores there were significant improvements in mean total UDRS score: 15.3% (p=0.002) and in the following subscores: neck 18.2% (p=0.027), trunk 32.9% (p=0.004), arm 17.9% (p=0.037), and leg 19.9% (p=0.003). One patient developed a skin infection and erosion requiring surgical debridement. None of our patients had intracranial hemorrhage. CONCLUSION: GPi-DBS is a safe and effective treatment for generalized dystonia in patients who remained impaired despite optimal medical therapy.

ABSTRACT

Unlike ablative surgery, such as thalamotomy and pallidotomy, deep brain stimulation (DBS) is reversible and adjustable; thus, offering a viable alternative for patients with disabling dystonia.(1) Globus pallidus (GPi) DBS has been reported to be effective in patients with primary generalized dystonia,(2-4) segmental dystonia,(5) cervical dystonia,(6,7) cranial dystonia,(8) myoclonus-dystonia,(9) tardive dystonia,(10) and other secondary dystonias.(2,4) We present our experience with GPi-DBS in a heterogeneous dystonia population.

INTRODUCTION

All subjects with severe generalized or hemidystonia who were refractory to oral medication and botulinum toxin injections and were selected for GPi-DBS at Baylor College of Medicine underwent prospective pre-DBS and post-DBS assessments with the Unified Dystonia Rating Scale (UDRS).(11) Functional disability was determined for speaking, writing, drinking, and walking using a 5 point scale (0=none, 1=minimal interference with task, 2=mild interference with task, 3=moderate interference with task, 4=marked interference with task, 5=unable to perform task). When available, videotape assessments using the Abnormal Involuntary Movement Scale (AIMS) (items 1–7) were performed by 2 blinded raters.(12) The two-tailed Wilcoxon Signed Ranks Test was used to compare the pre-DBS and post-DBS scores. Inter-rater consistency was determined with weighted kappa scores. The Mann-Whitney test was utilized to determine baseline differences in UDRS subscores based on DYT1 status in patients with generalized dystonia.

METHODS

Eleven subjects (7 male) with mean age at onset of dystonia 18.4 years (7–63) had a mean follow-up of about 5 months (26–357 days). The mean duration of disease at the time of surgery was 17.5 years (5–50). Ten subjects had generalized dystonia (5 with DYT1 mutation); one had hemidystonia secondary to a basal ganglia hemorrhage. Bilateral GPi-DBS was performed in 9; 2 additional patients with bilateral pallidotomies seven and eight years prior to GPi-DBS were previously included in our pallidotomy report. (13) Six subjects underwent staged implantation. Compared with pre-DBS scores there were significant improvements in mean total UDRS score: 15.3±11.64% (p=0.002) and in the following subscores: neck 18.2±22.6% (p=0.03), trunk 32.9±25.8% (p=0.004), arm 17.9±24.2% (p=0.04), and leg 19.9±16.9% (p=0.003). (Figure 1) In addition, there was a 23.6±21.6% (p=0.008) improvement in walking, but the improvements in other items of functional disability did not reach statistical significance. In patients with generalized dystonia, only larynx/speech UDRS sub-scores showed significant variability depending on DYT1 status (p=0.008).

Five subjects had prospective UDRS and blinded video assessments with the AIMS. The mean improvement for those patients was 15.7±12.3% (p=0.063) on the total UDRS score. The mean improvement in AIMS motor score measured by rater 1 was 15±8.9% (p=0.063) and by rater 2 10.7±23.1% (p=0.38). Inter-rater reliability was average for pre-DBS AIMS motor (r=0.67; p=0.2) and post-DBS AIMS motor (r=0.67; p=0.2). One patient developed a skin infection and erosion requiring surgical debridement. None of our patients had intracranial hemorrhage.

Neurostimulation parameters were available for all patients at follow-up. The mean voltage increased from 2.8±0.7 V at the initial evaluation to 3.5±0.9 V. The initial frequency was 150.0±26.8 Hz and 150.8±29.9 Hz at follow-up. The mean pulse width increased from 108.1±64.1 µsec at baseline to 151.5± 98 µsec at follow-up. At follow-up monopolar configuration was used in 17 electrodes and bipolar in 3.

RESULTS

In our population of patients with heterogeneous etiology of dystonia, GPi-DBS was found to be a safe and effective treatment, consistent with previous reports.(2,4) The variable response of cranial dystonia in our patients could be related to genetic heterogeneity, globus pallidus somatotopic arrangement, or electrode positioning.(4,14) One patient had a serious adverse event consisting of skin erosion requiring surgical debridement. This low complication rate is consistent with the experience in other centers.(2,4,15) The lack of improvement in functional disability in our patients was possibly because of the short follow-up. A delay in clinical response after GPi-DBS has been observed by others.(2)

The lack of statistical significance with the blinded video examination was likely due to the relatively low number of patients. Another possibility is that the AIMS is not sensitive enough to detect post-DBS changes. GPi-DBS is a safe and effective treatment in medically resistant patients with dystonia. Long-term follow is needed to determine whether the benefits of the procedure are sustained.

DISCUSSION

1. Yoshor D, Hamilton WJ, Ondo W, Jankovic J, Grossman RG. Comparison of thalamotomy and pallidotomy for the treatment of dystonia. Neurosurgery 2001;48:818-824.

2. Coubes P, Cif L, El-Fertit H et al. Electrical stimulation of the globus pallidus internus in patients with primary generalized dystonia: Long-term results. J Neurosurg 2004;101:189-194.

3. Krauss JK, Loher TJ, Weigel R, Capelle HH, Weber S, Burgunder JM. Chronic stimulation of the globus pallidus internus for treatment of non-dYT1 generalized dystonia and choreoathetosis: 2-year follow up. J Neurosurg 2003;98:785-792.

4. Vidailhet M, Vercueil L, Houeto JL et al. Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. N Engl J Med 2005;352:459-467.

5. Wohrle JC, Weigel R, Grips E, Blahak C, Capelle HH, Krauss JK. Risperidone-responsive segmental dystonia and pallidal deep brain stimulation. Neurology 2003;61:546-548.

6. Bereznai B, Steude U, Seelos K, Botzel K. Chronic high-frequency globus pallidus internus stimulation in different types of dystonia: A clinical, video, and MRI report of six patients presenting with segmental, cervical, and generalized dystonia. Mov Disord 2002;17:138-144.

7. Krauss JK. Deep brain stimulation for cervical dystonia. J Neurol Neurosurg Psychiatry 2003; 74:1598.

8. Capelle HH, Weigel R, Krauss JK. Bilateral pallidal stimulation for blepharospasm-oromandibular dystonia (Meige syndrome). Neurology 2003;60:2017-2018.

9. Trottenberg T, Meissner W, Kabus C et al. Neurostimulation of the ventral intermediate thalamic nucleus in inherited myoclonus-dystonia syndrome. Mov Disord 2001;16:769-771.

10.Trottenberg T, Paul G, Meissner W, Maier-Hauff K, Taschner C, Kupsch A. Pallidal and thalamic neurostimulation in severe tardive dystonia. J Neurol Neurosurg Psychiatry 2001;70:557-559.

11.Comella CL, Leurgans S, Wuu J, Stebbins GT, Chmura T. Rating scales for dystonia: A multicenter assessment. Mov Disord 2003;18:303-312.

12.ECDEU. Assessment Manual for Psychopharmacology: Publication ADM 76-338. Washington, DC: US Department of Health, Education, and Welfare, 1976.

13.Ondo WG, Desaloms JM, Jankovic J, Grossman RG. Pallidotomy for generalized dystonia. Mov Disord 1998;13:693-8.

14.Vayssiere N, van der GN, Cif L et al. Deep brain stimulation for dystonia confirming a somatotopic organization in the globus pallidus internus. J Neurosurg 2004;101:181-188.

15.Hariz MI. Complications of deep brain stimulation surgery. Mov Disord 2002;17 Suppl 3:S162-S166.

REFERENCES

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Figure 1. GPi-DBS in Dystonia