Deep brain stimulation in children and young adults with secondary dystonia: the Children's Hospital Los Angeles experience.

BACKGROUND: Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. It can be classified as primary or secondary. There is no cure for dystonia and the goal of treatment is to provide a better quality of life for the patient. Surgical intervention is considered for patients in whom an adequate trial of medical treatment has failed. Deep brain stimulation (DBS), specifically of the globus pallidus interna (GPi), has been shown to be extremely effective in primary generalized dystonia. There is much less evidence for the use of DBS in patients with secondary dystonia. However, given the large number of patients with secondary dystonia, the significant burden on the patients and their families, and the potential for DBS to improve their functional status and comfort level, it is important to continue to investigate the use of DBS in the realm of secondary dystonia. OBJECT: The objective of this study is to review a series of cases involving patients with secondary dystonia who have been treated with pallidal DBS. METHODS: A retrospective review of 9 patients with secondary dystonia who received treatment with DBS between February 2011 and February 2013 was performed. Preoperative and postoperative videos were scored using the Barry-Albright Dystonia Scale (BADS) and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) by a neurologist specializing in movement disorders. In addition, the patients' families completed a subjective questionnaire to assess the perceived benefit of DBS. RESULTS: The average age at DBS unit implantation was 15.1 years (range 6-20 years). The average time to follow-up for the BADS evaluation from battery implantation was 3.8 months (median 3 months). The average time to follow-up for the subjective benefit evaluation was 10.6 months (median 9.5 months). The mean BADS scores improved by 9% from 26.5 to 24 (p = 0.04), and the mean BFMDRS scores improved by 9.3% (p = 0.055). Of note, even in patients with minimal functional improvement, there seemed to be decreased contractures and spasms leading to improved comfort. There were no complications such as infections or hematoma in this case series. In the subjective benefit evaluation, 3 patients' families reported "good" benefit, 4 reported "minimal" benefit, and 1 reported no benefit. CONCLUSIONS: These early results of GPi stimulation in a series of 9 patients suggest that DBS is useful in the treatment of secondary generalized dystonia in children and young adults. Objective improvements in BADS and BFMDRS scores are demonstrated in some patients with generalized secondary dystonia but not in others. Larger follow-up studies of DBS for secondary dystonia, focusing on patient age, history, etiology, and patterns of dystonia, are needed to learn which patients will respond best to DBS.

Transient Complete Resolution of Tourette Syndrome Symptoms Following Personalized Depth Electrode Placement.

Treatment refractory Tourette syndrome has been shown to be improved with deep brain stimulation, but with multiple possible stimulation locations and variable and incomplete benefit. This study presents a single case of complete amelioration of motor and verbal tics in a patient with Tourette syndrome during placement of 12 stereo-EEG electrodes to identify optimal targets for permanent stimulating electrodes. Subsequently, substantial improvement in motor and verbal tic frequency occurred with placement and programming of permanent electrodes in bilateral globus pallidus internus and nucleus accumbens, but without the complete resolution seen during depth electrode placement. We suggest that simultaneous stimulation at multiple patient-specific targets could provide effective control of Tourette symptomatology, but further study will be needed.

Case Report: Targeting for Deep Brain Stimulation Surgery Using Chronic Recording and Stimulation in an Inpatient Neuromodulation Monitoring Unit, With Implantation of Electrodes in GPi and Vim in a 7-Year-Old Child With Progressive Generalized Dystonia.

BACKGROUND: Deep brain stimulation for secondary dystonia has been limited by unknown optimal targets for individual children. OBJECTIVES: We report the first case of a 7-year-old girl with severe generalized dystonia due to acquired striatal necrosis in whom we used a new method for identifying targets for deep brain stimulation. METHODS: We implanted temporary depth electrodes in 5 different nuclei bilaterally in the basal ganglia and thalamus, with test stimulation and recording during 1 week while the child was an inpatient in a neuromodulation monitoring unit. RESULTS: Single-unit activity in ventral intermedius Vim, internal globus pallidus (GPi), and subthalamic (STN) nuclei occurred during dystonic spasms and correlated with electromyography. Stimulation in Vim eliminated dystonic spasms. Subsequent implantation of 4 permanent deep brain stimulation electrodes in bilateral Vim and Gpi nuclei resolved dystonic spasms. CONCLUSION: The use of temporary stimulation and recording electrodes to identify deep brain stimulation targets is a promising new technique that could improve outcomes in children with acquired dystonia.

Pediatric Deep Brain Stimulation Using Awake Recording and Stimulation for Target Selection in an Inpatient Neuromodulation Monitoring Unit.

Deep brain stimulation (DBS) for secondary (acquired, combined) dystonia does not reach the high degree of efficacy achieved in primary (genetic, isolated) dystonia. We hypothesize that this may be due to variability in the underlying injury, so that different children may require placement of electrodes in different regions of basal ganglia and thalamus. We describe a new targeting procedure in which temporary depth electrodes are placed at multiple possible targets in basal ganglia and thalamus, and probing for efficacy is performed using test stimulation and recording while children remain for one week in an inpatient Neuromodulation Monitoring Unit (NMU). Nine Children with severe secondary dystonia underwent the NMU targeting procedure. In all cases, 4 electrodes were implanted. We compared the results to 6 children who had previously had 4 electrodes implanted using standard intraoperative microelectrode targeting techniques. Results showed a significant benefit, with 80% of children with NMU targeting achieving greater than 5-point improvement on the Burke⁻Fahn⁻Marsden Dystonia Rating Scale (BFMDRS), compared with 50% of children using intraoperative targeting. NMU targeting improved BFMDRS by an average of 17.1 whereas intraoperative targeting improved by an average of 10.3. These preliminary results support the use of test stimulation and recording in a Neuromodulation Monitoring Unit (NMU) as a new technique with the potential to improve outcomes following DBS in children with secondary (acquired) dystonia. A larger sample size will be needed to confirm these results.

Similarity of Involuntary Postures between Different Children with Dystonia.

BACKGROUND: Abnormal involuntary postures are characteristic of dystonia, but the specific postures observed clinically have not previously been categorized or enumerated. The objective of this study was to determine whether there is a set of specific postures that are common between different children with dystonia. METHODS: Videotapes were examined from all children who were seen in a pediatric movement disorders clinic over a 4-year period and had a diagnosis of nonpsychogenic dystonia. In total, 179 children were included in the video review. RESULTS: Visually similar postures were identified in 152 different children. Seven different common postures were identified. All 152 children exhibited at least 1 of these postures, and most had more than 1. CONCLUSIONS: Involuntary postures in childhood dystonia exhibit unexpected similarities despite a wide range of underlying etiology, severity, and developmental experience. This is consistent with the hypothesis that childhood dystonia is a symptom that reflects a shared pathway of expression for multiple anatomic and functional abnormalities.

Deep brain stimulation evoked potentials may relate to clinical benefit in childhood dystonia.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a treatment for severe childhood-onset dystonia. A common challenge for clinicians is determining which contacts of the DBS electrode to stimulate in order to provide maximum future benefit to the patient. OBJECTIVE: To characterize how the cortical responses to DBS relate to stimulation parameters (i.e. electrode contacts, voltage, and pulse width) and clinical outcomes. METHODS: We examined 11 patients with dystonia undergoing DBS therapy (9-21 years old when implanted). We varied the active contacts, voltage, and pulse width of the stimulating electrode and analyzed the deep-brain stimulator evoked potentials (DBSEPs) measured with electroencephalogram, and assessed symptoms with the Barry-Albright dystonia scale. Statistical tests included: Repeated measures ANOVA, Mann-Whitney U test and paired t-test. RESULTS: DBSEPs near sensorimotor areas were larger ipsilaterally than contralaterally (P = 0.007). The rate of DBSEP amplitude increase with respect to stimulator voltage (voltage gain) and pulse width (pulse width gain) varied across subjects and stimulating contacts. Voltage gains were significantly higher among patients who showed larger improvements with DBS (P = 0.038). Additionally, a within-subject comparison of all patients showed that voltage gains were higher for contacts chosen for chronic stimulation as compared to those that were not (P = 0.007). CONCLUSIONS: DBSEPs may be good predictors of therapeutic response to stimulation at different electrode contacts. Furthermore, effective DBS therapy appears to modulate sensorimotor cortex. These findings may help clinicians optimize stimulator programming and may eventually lead to improved targeting during implantation.