Thalamic Deep Brain Stimulation for Secondary Dystonia in Children and Young Adults
Condition: Dystonia
MeSH terms: Dystonia; Dystonic Disorders
Study type: Interventional

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.
    

Detailed description: 
      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.
    

Intervention name(s): Activa PC Primary Cell Neurostimulator - (Model 37601); Activa RC Rechargeable Neurostimulator - (Model 37612); Activa SC Single Cell Neurostimulator (Models 37602/37603); DBS Lead - (Model 3387; DBS Extension - (Models 37085/6); Patient Programmer - (Model 37642); Test Stimulator - (Model 3625); N'Vision Clinician Programmer - (Model 8840); N'Vision Software Application Card - (Model 8870)
Intervention type(s): Device; Device; Device; Device; Device; Device; Device; Device; Device
Intervention description(s): 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.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment