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Summary

for people ages 7–25 (full criteria)
at San Francisco, California
study started
estimated completion:
Amy R Viehoever

Description

Summary

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.

Details

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.

Keywords

Dystonia

Eligibility

You can join if…

Open to people ages 7–25

  1. Ability to give informed consent or assent for the study
  2. Dystonia symptoms that are sufficiently severe, in spite of best medical therapy, to warrant surgical implantation of deep brain stimulators according to standard clinical criteria
  3. Age 7-25
  4. Stable doses of anti-dystonia medications (such as levodopa, baclofen, or diazepam)for at least 30 days prior to baseline assessment
  5. If patient receives botulinum toxin injections, patient should be on a stable injection regimen
  6. Intact thalamic anatomy as determined by standard clinical MRI

You CAN'T join if...

  1. Pregnancy or breast feeding
  2. Major comorbidity increasing the risk of surgery (severe hypertension, severe diabetes, or need for chronic anticoagulation other than aspirin)
  3. Inability to comply with study follow-up visits
  4. Any prior intracranial surgery
  5. Uncontrolled epilepsy
  6. Immunocompromised
  7. Has an active infection
  8. Requires diathermy, electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) to treat a chronic condition
  9. Has an existing implanted neurostimulator or cardiac pacemaker.
  10. Dystonia caused by known genetic mutation in any DYT genes

Location

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
Links
Safety and efficacy of stereotactic ventrooral-thalamotomy for musician's dystonia
ID
NCT03078816
Phase
Phase 1
Lead Scientist
Amy R Viehoever
Study Type
Interventional
Last Updated
May 1, 2017
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