Thalamic Deep Brain Stimulation for Secondary Dystonia in Children and Young Adults
Thalamic Deep Brain Stimulation for Secondary Dystonia in Children and Young Adults
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.
Inclusion Criteria:

 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

 Exclusion Criteria:

 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