Deep brain stimulation in post‐traumatic dystonia: A case series study

Abstract Aims Deep brain stimulation (DBS) has been proposed as an effective treatment for drug‐intolerant isolated dystonia, but whether it is also efficacious for posttraumatic dystonia (PTD) is unknown. Reports are few in number and have reached controversial conclusions regarding the efficacy of DBS for PTD treatment. Here, we report a case series of five PTD patients with improved clinical benefit following DBS treatment. Methods Five patients with disabling PTD underwent DBS therapy. The clinical outcomes were assessed with the Burke–Fahn–Marsden dystonia rating scale (BFMDRS) at baseline and the last follow‐up visit (at more than 12 months). Results Patients 1 and 3 received unilateral globus pallidus internus (GPi) DBS for contralateral dystonia. The subthalamic nucleus (STN) was chosen as target for patients 2 and 4, due to a lesion located in the globus pallidus. Patient 5 had an electrode in the ventral intermediate nucleus (VIM) for treating predominant tremor of left upper extremity, with unexpected improvement of focal hand dystonia. The scores of BFMDRS movement exhibited favorable improvement in all five patients at the last follow‐up, ranging from 52.4% to 78.6%. Conclusions Deep brain stimulation may be an effective and safe treatment for medically refractory PTD, but this needs to be confirmed by further studies.


| INTRODUC TI ON
Post-traumatic dystonia (PTD), the dystonia developing after brain injury, occurs in 4.1% of surviving patients. 1 Hemi-dystonia and focal-hand dystonia are the most common forms of dystonia in PTD, while other forms of focal dystonia involving the neck, eyelids, and oral mandible, as well as segmental dystonia, multifocal dystonia, and generalized dystonia have also been reported. [2][3][4] The lesions associated with PTD are usually found on Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) of the brain, with the most common lesions located in the contralateral caudate, putamen, and thalamus. 5 PTD may respond to common traditional dystonia medications. For instance, botulinum toxin injections are effective for focal dystonia. However, some PTD patients show low levels of satisfaction after botulinum toxin injection. 6,7 In recent years, deep brain stimulation (DBS) has become a suitable alternative for medication-refractory isolated dystonia. 8 Moreover, encouraging results of DBS treatment have been observed in tardive dystonia, a type of acquired dystonia. 9,10 However, only limited evidence supporting this treatment modality is available in patients with PTD, and exploratory results have been published mostly in the form of cases or single subjects in heterogeneous studies. 11,12 Here we report the clinical outcomes of our series of patients with disabling PTD who underwent DBS treatment. Furthermore, we review the extant literature on the treatment of PTD. F I G U R E 1 Preoperative brain MR images (T2-weighted sequence) showing structure changes in the right midbrain and temporal lobe (A), the left globus pallidus (GP) (B), the bilateral external capsule (C), the bilateral globus pallidus (GP) and putamen (D), and the right midbrain (E). The location of the lesion is marked by a white arrow in each patient

| Patients
We recruited five patients undergoing DBS surgery at the

| DBS programming
The IPG was turned on one day after implantation. DBS parameters were readjusted from one month after surgery when the local edema disappeared. We chose the most favorable parameters based on the most satisfactory improvement with the fewest stimulation-related side effects, such as paresthesia and dysarthria.

| Statistical analysis
Q oL and MMSE scores at baseline and the last follow-up visit were compared using a two-tailed Mann-Whitney test. Results are expressed as means ± standard deviation (SD). Statistical analysis was performed using GraphPad Prism 6.0 (GraphPad Software).
A P-value of <0.05 was considered statistically significant.

| Clinical characteristics and outcomes
The clinical characteristics of the five participants (one female and four males) are shown in Table 1. The patients received surgery at an age varying from 19 to 41 years. All patients were refractory to common medicines for treating dystonia, and several patients failed to respond to botulinum toxin injection.  Figure 1E).
The BFMDRS movement score of the five patients improved by 65.9% (range from 52.4% to 78.6%) and the disability score by 68.6% (range from 50.0% to 76.5%) ( Table 2). The pain in the affected region also improved significantly in patients 1, 2, and 3, and patient 5 had a near complete tremor reduction. Moreover, all patients showed a remarkable improvement in quality of life evaluated by SF-36 at the last follow-up visit ( Table 3). The cognitive function also remained on baseline at long-term follow-ups ( Table 3). The stimulation parameters at the last follow-up visit are presented in Table 2.

| Adverse events
Overall, the surgical procedures were well tolerated. There were no hardware-related side effects, intracranial hemorrhages, infections,  Currently, there is uncertainty regarding the optimal lead location due to brain lesions existing in patients with PTD. There was no significant difference in degree of improvement between STN and GPi DBS in treating isolated dystonia with no brain lesion, as indicated by our previous study. However, the study by As the mechanism underlying the effects of deep brain stimulation (DBS) procedures are not well understood, we also followed the cognitive status. During the long-term follow-up, DBS had no noticeable influence on patients' perception in our report, which mostly agreed with studies of DBS on isolated dystonia.

| D ISCUSS I ON
The small number of patients tested was a limitation to our study (n = 5). A larger sample population is likely to result in more objective and credible outcomes. Also, the heterogeneity between patients would be a concern for further studies, even if PTD is not a common condition. Further studies may explore the optimal target for surgical treatment of PTD.

| CON CLUS IONS
Based on the limited information available, DBS may be a potential treatment for medically refractory PTD, but this needs further exploration. Furthermore, to assess whether the GPi or the STN is preferable in PTD with GP lesion will require larger studies to reach definitive conclusions.

ACKOWLED G EM ENTS
We would like to thank all patients for participating in this study.