Double-Blind Clinical Trial of Subthalamic Nucleus Deep Brain Stimulation in Early-Stage Parkinson's Disease

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.
• •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.
• •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.