Deep Brain Stimulation for Status Dystonicus: A Case Series and Review of the Literature.

BACKGROUND: Status dystonicus (SD) is a rare and potentially life-threatening complication of primary or secondary dystonia, characterized by acute worsening of dystonic movements. There is no consensus regarding optimal treatment, which may be medical and/or surgical. METHODS: We present our experience with pallidal deep brain stimulation (DBS) in 5 DYT1-positive patients with SD and provide a review of the literature to examine optimal management. RESULTS: Of the 5 patients treated with pallidal DBS, all experienced postoperative resolution of their dystonic crisis within a range of 1-21 days. Long-term follow-up resulted in 1 patient returning to preoperative baseline, 3 patients improving from baseline, and 1 patient making a complete recovery. Of the 28 SD patients (including our 5 patients) reported in the literature who were treated with DBS or ablative surgery, 26 experienced cessation of their dystonic crisis with a return to baseline function and, in most cases, clinical improvement. CONCLUSION: DBS is an effective therapeutic modality for the treatment of SD. In addition to the long-term benefits of stimulation, early and aggressive treatment may improve the overall outcome.

Defining a therapeutic target for pallidal deep brain stimulation for dystonia.

OBJECTIVE: To create a data-driven computational model that identifies brain regions most frequently influenced by successful deep brain stimulation (DBS) of the globus pallidus (GP) for advanced, medication-resistant, generalized dystonia. METHODS: We studied a retrospective cohort of 21 DYT1 primary dystonia patients treated for at least 1 year with bilateral pallidal DBS. We first created individual volume of tissue activation (VTA) models utilizing neuroimaging and postoperative stimulation and clinical data. These models were then combined into a standardized probabilistic dystonia stimulation atlas (DSA). Finally, we constructed a candidate target volume from electrodes demonstrating at least 75% improvement in contralateral symptoms, utilizing voxels stimulated by least 75% of these electrodes. RESULTS: Pallidal DBS resulted in a median contralateral hemibody improvement of 90% (mean = 83%, standard deviation [SD] = 20) after 1 year of treatment. Individual VTA models of the 42 active electrodes included in the study demonstrated a mean stimulation volume of 501mm ([SD] = 284). The resulting DSA showed that areas most frequently stimulated were located squarely in the middle of the posterior GP, with a common target volume measuring 153mm(3) . INTERPRETATION: Our results provide a map of the region of influence of therapeutic DBS for dystonia and represent a potential target to refine current methods of surgical planning and stimulation parameters selection. Based on their role in alleviating symptoms, these regions may also provide anatomical and physiological information relevant to disease models of dystonia. Further experimental and clinical studies will be needed to validate their importance.

The rationale driving the evolution of deep brain stimulation to constant-current devices.

OBJECTIVE: Deep brain stimulation (DBS) is an effective therapy for the treatment of a number of movement and neuropsychiatric disorders. The effectiveness of DBS is dependent on the density and location of stimulation in a given brain area. Adjustments are made to optimize clinical benefits and minimize side effects. Until recently, clinicians would adjust DBS settings using a voltage mode, where the delivered voltage remained constant. More recently, a constant-current mode has become available where the programmer sets the current and the stimulator automatically adjusts the voltage as impedance changes. METHODS: We held an expert consensus meeting to evaluate the current state of the literature and field on constant-current mode versus voltage mode in clinical brain-related applications. RESULTS/CONCLUSIONS: There has been little reporting of the use of constant-current DBS devices in movement and neuropsychiatric disorders. However, as impedance varies considerably between patients and over time, it makes sense that all new devices will likely use constant current.

Sustained relief of generalized dystonia despite prolonged interruption of deep brain stimulation.

BACKGROUND: Pallidal deep brain stimulation (DBS) is an established treatment for disabling, medication-refractory generalized dystonia. Patients typically regress to their preoperative baseline when stimulation is discontinued. METHODS: Presented are case reports of 2 dystonia patients. RESULTS: Two patients with primary generalized dystonia (1 with the DYT1 mutation) who were treated successfully with bilateral pallidal DBS for periods of 18 months and 5 years retained motor benefit for several months after inadvertent interruption of stimulation. Stimulation was interrupted unilaterally for 3 and 7 months and bilaterally for 2 days and 2 months, respectively. Symptoms of dystonia returned only partially during the period of therapy interruption and rapidly and completely resolved after resuming stimulation. CONCLUSIONS: We report unexpected and prolonged retention of motor benefits despite transient cessation of pallidal DBS in 2 dystonia patients. Factors that appear to differentiate these individuals are young age, short duration of disease, and chronic DBS therapy with relatively low energy of stimulation.

Pallidal deep brain stimulation for DYT6 dystonia.

BACKGROUND: Mutations of the THAP1 gene were recently shown to underlie DYT6 torsion dystonia. Little is known about the response of this dystonia subtype to deep brain stimulation (DBS) at the internal globus pallidus (GPi). METHODS: Retrospective analysis of the medical records of three DYT6 patients who underwent pallidal DBS by one surgical team. The Burke-Fahn-Marsden Dystonia Rating scale served as the primary outcome measure. Comparison is made to 23 patients with DYT1 dystonia also treated with GPi-DBS by the same team. RESULTS: In contrast with the DYT1 patients who exhibited a robust and sustained clinical response to DBS, the DYT6 patients exhibited more modest gains during the first 2 years of therapy, and some symptom regression between years 2 and 3 despite adjustments to the stimulation parameters and repositioning of one stimulating lead. Microelectrode recordings made during the DBS procedures demonstrated no differences in the firing patterns of GPi neurons from DYT1 and DYT6 patients. DISCUSSION: Discovery of the genetic mutations responsible for the DYT6 phenotype allows for screening and analysis of a new homogeneous group of dystonia patients. DYT6 patients appear to respond less robustly to GPi-DBS than their DYT1 counterparts, most likely reflecting differences in the underlying pathophysiology of these distinct genetic disorders. CONCLUSIONS: While early results of pallidal DBS for DYT6 dystonia are encouraging, further research and additional subjects are needed both to optimise stimulation parameters for this population and to elucidate more accurately their response to surgical treatment.

Longitudinal impedance variability in patients with chronically implanted DBS devices.

BACKGROUND: Deep brain stimulation (DBS) is an effective therapy for advanced movement disorders, but its optimal use is still controversial. One factor that could play a role in the proper delivery of therapeutic stimulation by current DBS devices is the variability of the impedance at the interface between the electrode surface and surrounding tissue. OBJECTIVE: To analyze variability and trends in the impedance of chronically-implanted DBS electrodes in subjects with movement disorders. METHODS: We reviewed impedance values from medical records of DBS patients at an academic tertiary-care movement disorders center. The standard deviation of data recorded within individual subjects and single contacts were used as measures of longitudinal impedance variability. A generalized linear mixed model (GLMM) determined if a number of effects had significant influences on impedance. RESULTS: We analyzed 2863 impedance measurements from 94 subjects. Median variability, for subjects with follow-up from 6 months to 5 years (n = 77), was 194 Ω for individual subjects and 141 Ω for individual contacts, with a range spanning from 18 to over 600 Ω. The GLMM, incorporating all subjects (n = 94), identified time, electrical activity, implanted target, contact position on the electrode and side of implantation as significant predictors of impedance. Age and disease duration at surgery, gender or ethnicity were not significant predictors. CONCLUSIONS: Our analysis suggests that a significant amount of impedance variability can be expected in chronically implanted DBS electrodes and indicates a number of factors with possible predictive value. Further studies are needed to link impedance characteristics to clinical outcomes.