| Eligibility |
Inclusion Criteria:
1. A clinical diagnosis of idiopathic Parkinson's disease (PD). The diagnosis will be
based upon the presence of at least two of the three cardinal motor signs of this
disorder (akinesia/bradykinesia, rest tremor, and rigidity) with at least one of the
signs being rest tremor or bradykinesia.
2. Clear and dramatic beneficial response to dopaminergic therapy, defined as =30% in
UPDRS III with administration of the patient's medication during the screening
neurological examination.
3. Hoehn and Yahr (H&Y) stage II when OFF medication.
4. No contraindications to surgery (i.e., subject does not have uncontrollable medical or
psychiatric illness; Exclusion Criteria).
5. Age between 50 and 75 years old.
6. Dopaminergic therapy for greater than one year and less than four years.
7. Available for follow-up for the entire duration of the study.
8. Informed Consent (Appendix C): The subject is willing and able to provide written
informed consent.
9. MRI within normal range (Exclusion Criteria).
10. Subjects receiving antidepressant medication used specifically for the treatment of
depression must be on stable doses for at least eight weeks prior to enrolling in the
study.
11. Subjects must agree to maintain a stable regimen, if deemed medically appropriate by
the treating physician, of any psychotropic medications throughout the blinded
treatment phase.
Exclusion Criteria:
1. Evidence of an alternative diagnosis or secondary parkinsonism, as suggested by:
- Features unusual early in the clinical course (e.g., prominent postural
instability, freezing phenomena, or hallucinations unrelated to medications in
the first 3 years after symptom onset)
- Dementia preceding motor symptoms
- Neurologic signs of upper motor neuron or cerebellar involvement
- Significant orthostatic hypotension unrelated to medications
- Unequivocal cortical sensory loss (i.e., graphesthesia, sterognosis with intact
primary sensory modalities), clear limb ideomotor apraxia, or progressive aphasia
- Vertical supranuclear gaze palsy, or selective slowing of vertical saccades
- Unequivocal cerebellar abnormalities on examination, such as cerebellar gait,
limb ataxia, or cerebellar oculomotor abnormalities (e.g., sustained gaze-evoked
nystagmus, macro square wave jerks, hypermetric saccades)
- Documentation of a condition known to produce parkinsonism and plausibly
connected to the subject's symptoms (e.g., MRI scan with evidence of significant
brain atrophy, lacunar infarcts, or iron deposits in the putamen; history of
stroke, exposure to toxins, or encephalitis; or neuroleptic use within the past 6
months)
- The expert evaluating physician, based on the full diagnostic assessment,
believes that an alternative syndrome is more likely than PD.
2. Uncontrolled medical condition or clinically significant medical disease that would
increase the risk of developing pre- or postoperative complications (e.g., significant
cardiac or pulmonary disease, uncontrolled hypertension).
3. Dementia as evidenced by a Dementia Rating Score of less than 123.
4. Diagnosis of probable behavioral variant frontotemporal dementia or primary
progressive aphasia.
5. Currently active diagnosis of a major psychiatric disorder.
6. Previous brain operation or injury.
7. Active participation in another clinical trial for the treatment of PD.
8. Subjects with cardiac pacemakers or medical conditions that require repeat MRI scans.
9. Evidence of existing dyskinesia
10. Any current substance use disorder.
11. Any history of recurrent or unprovoked seizures.
12. Any prior movement disorder treatments that involved intracranial surgery or device
implantation.
13. Any other active implanted intracranial device (e.g., cochlear implant) or implanted
device to treat movement disorders (e.g., duodopa pump) whether turned on or off.
14. A condition requiring or likely to require the use of magnetic resonance imaging (MRI)
or diathermy.
15. History of suicide attempt.
16. A female who is breastfeeding or of child-bearing potential with a positive urine
pregnancy test or not using adequate contraception.
17. Inability or unwillingness of subject to give written informed consent.
18. Parkinsonian features restricted to the lower limbs for more than three years.
19. Treatment with a dopamine receptor blocker or a dopamine-depleting agent in a dose and
time course consistent with drug-induced parkinsonism.
20. Normal functional neuroimaging of the presynaptic dopaminergic system, as measured by
DaTSCAN.
21. Rapid progression of gait impairment requiring regular use of a wheelchair.
22. Early bulbar dysfunction, defined as one of severe dysphonia, dysarthria (speech
unintelligible most of the time), or dysphagia (requiring soft food, nasogastric (NG)
tube, or gastrostomy feeding).
23. Inspiratory respiratory dysfunction defined as either diurnal or nocturnal inspiratory
stridor or frequent inspiratory sighs.
24. Recurrent (>1/year) falls because of impaired balance within 3 years of onset.
25. Otherwise unexplained pyramidal tract signs, defined as pyramidal weakness or clear
pathologic hyperreflexia (excluding mild reflex asymmetry in the more affected limb
and isolated extensor plantar response).
26. Bilateral symmetric parkinsonism throughout the disease course. The patient or
caregiver reports bilateral symptom onset with no side predominance, and no side
predominance is observed on objective examination.
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