Dystonia is a movement disorder seen in both children and adults that is characterized by "sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both." Secondary dystonia is far more common in pediatric populations than primary dystonia, and far more recalcitrant to standard pharmacologic and surgical treatments including Deep Brain Stimulation (DBS). There exists a large unmet need to develop new therapeutics, treatment strategies, and outcome measures for pediatric secondary dystonia. The investigators are proposing to investigate the ventralis oralis posterior nucleus (Vop) of the thalamus as a new target for DBS in secondary dystonia. Prior to the development of DBS, the main surgical treatment of dystonia was thalamotomy. Although there were many different targets in the thalamus, often done in staged procedures, the most common and successful targeted nuclei was the Vop, which is traditionally thought to be the pallidal receiving area. Previous lesioning of Vop produced improvements in dystonia but intolerable side effects, especially when implanted bilaterally. However, given that secondary dystonia patients were often reported to have superior results to primary dystonia it is reasonable to believe that if the side effects can be modulated, that targeting of the Vop nucleus with DBS could be a viable alternative to Globus Pallidus interna (GPi). Given that Deep Brain Stimulation is a treatment that is inherently adjustable, it is conceivable that settings on the Deep Brain Stimulation could be adjusted to allow for clinical benefit with minimal side effects. Indeed, there have been several scattered successful case reports attesting to this possibility.
Dystonia is a movement disorder seen in both children and adults that is characterized by "sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both." Secondary dystonia has evolved to refer to dystonia resulting from damage to the nervous system or degenerative disease processes. While primary dystonia is generally thought to arise from genetic causes, secondary dystonias have a variety of causes including perinatal injuries (cerebral palsy), central nervous system infections, traumatic brain injuries, and many different metabolic, neurodegenerative, and mitochondrial conditions. Secondary dystonia is far more common in pediatric populations than primary dystonia, and far more recalcitrant to standard pharmacologic and surgical treatments including Deep Brain Stimulation. Given that most treatments for dystonia are developed for primary dystonia and then applied to secondary dystonia, it is not surprising that this effectiveness gap exists. Thus, there exists a large unmet need to develop new therapeutics, treatment strategies, and outcome measures for pediatric secondary dystonia. Deep Brain Stimulation (DBS) is one such therapeutic intervention that has potential to improve secondary dystonia. DBS is a surgical treatment for several different movement disorders that evolved from functional stereotactic neurosurgery techniques initially used to lesion specific deep brain structures. While Essential Tremor and Idiopathic Parkinson's Disease have predictable and consistent response rates to DBS in carefully selected patients, response rates of dystonia have been much more inconsistent. One predictor of success has been the presence of DYT-1 mutation, the most common known genetic cause of primary dystonia. Success rates in DYT-1 dystonia are consistently high with reductions in dystonia typically greater than 80%. However, the results in secondary dystonia have been much more modest and inconsistent. A recent meta-analysis found that on average, dystonia symptoms as measured by common rating scales improve 23% following DBS for dystonic cerebral palsy (the most common cause of secondary dystonia), however there are frequent cases of non-responders. Additionally, there have been very few examination, radiological or laboratory predictors of good response to DBS, except for genetic confirmation of DYT-119. However, across both primary and secondary dystonia, younger age at the time of surgery (less than 21 years old) and shorter duration of symptoms (less than 15 years) have been shown to be the most likely predictive factors for a good postoperative outcome. This has led many to suggest that DBS should be offered earlier in the course of intractable dystonia, prior to the development of permanent complications such as orthopedic contractures. Thus, we are setting an upper age limit of 25 to account for the concern that earlier implantation leads to improved outcomes. The lower age limit of 7 reflects the fact that the current humanitarian exemption for DBS for dystonia currently goes down to age 7. Thus, there exists a need to both improve patient selection as well as application of DBS for secondary dystonia in children.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
University of California San Francisco Hospital
San Francisco, California, United States
Change From Baseline in Burke-Fahn-Marsden Dystonia Rating Scale
Rating scale that measures movement and disability related to dystonia, range 0-120 motor, 0-30 disability , higher number indicates more severe dystonia Change from Baseline in Burke-Fahn-Marsden Dystonia Rating Scale
Time frame: Change from baseline to 12 months postoperatively
Percent Change in Pediatric Quality of Life Inventory (PedsQL)
Quality of life measure, scored 0-100, larger scores indicate greater hinderance (ie. lower quality of life)
Time frame: baseline to 12 months postoperatively
Change in Barry Albright Dystonia Rating Scale
Severity scale for secondary dystonia, range 0-32, higher scores indicates more severe dystonia
Time frame: Change from baseline to 12 months postoperatively
Change in Blinded Burke-Fahn-Marsden Dystonia Rating Scale
Rating scale that measures movement and disability related to dystonia, range 0-120 motor, 0-30 disability , higher number indicates more severe dystonia. These ratings were carried out retroactively by a neurologist who was unfamiliar with the four study participants and who had no knowledge of their unblinded scores.
Time frame: change from baseline to 12 months postoperatively
Change in Modified Ashworth Scale - Upper Limbs
Measure of spasticity, range 0-32, higher values indicate more spasticity
Time frame: Change from baseline to 12 months postoperatively
Change in Diadochokinetic Syllable Rates
Articulation, range (min 6- no upper limit), longer times indicate less articulation/more difficulty with speech
Time frame: Change from baseline to 12 months postoperatively
Children's Memory Scale
Will include the following subtests: Memory for Faces, Dot Locations, and Digit Span
Time frame: Change from baseline to 12 months postoperatively
Change in Behavioral Assessment System, 3rd Edition: Self Report of Personality
Mood and behavior assessment, main use as a screening tool for depression.
Time frame: Change from baseline to 12 months postoperatively
Change in Modified Ashworth Scale Spasticity Ratings - Lower Limbs
This scale is used to measure spasticity, which is a velocity-dependent increase in muscle stretch reflexes associated with increased muscle tone as a component of upper motor neuron syndrome. It is scored 0-4 with higher scores indicating greater severity.
Time frame: Change from baseline to 12 months postoperatively
Change in Kaufman Brief Intelligence Test - Second Addition
Kaufman Brief Intelligence Test Second Edition (KBIT-2) is a brief measure of verbal and nonverbal intelligence used with individuals ages 4 through 90 years, raw scores 0 - unlimited, with higher scores indicating higher ability.
Time frame: baseline to 12 months postoperatively
Change in Burke-Fahn-Marsden Dystonia Disability Subscale
This scale is a measurement of quality of life related to dystonia, with lower scores indicating greater quality of life and high scores indicating more hinderance. It is scored 0-100.
Time frame: baseline to 12 months postoperatively
Change in Modified Unified Parkinson's Disease Rating Scale - Second Edition
This scale is a measurement of quality of life related to dystonia, with lower scores indicating greater quality of life and high scores indicating more hinderance. It is scored 0-199
Time frame: baseline to 12 months posoperatively
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