Convection-Enhanced Delivery to Study the Pathophysiology Underlying the Clinical Features of Parkinson s Disease

This is an interventional treatment trial for Parkinson's Disease focused on measuring Muscimol, Convection-Enhanced Delivery, Parkinson's Disease, Deep Brain Stimulation, Parkinson Disease, PD Read More

• INCLUSION CRITERIA:

Diagnosed with idiopathic PD by UK criteria:

Bradykinesia: At least one of the following:

1. Muscular rigidity
2. 4-6 Hz resting tremor
3. Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction

Three or more required in addition to above for the diagnosis of idiopathic PD:

1. Unilateral onset
2. Rest tremor present
3. Progressive disorder
4. Persistent asymmetry affecting side of onset most
5. Excellent response (70-100%) to levodopa
6. Severe levodopa-induced chorea
7. Levodopa response for 5 years or more

8. Clinical course of ten years or more

   The above clinical features must not be due to trauma, brain tumor, infection, cerebrovascular disease, other known neurological disease (e.g., multiple system atrophy, progressive supranuclear palsy, striatonigral degeneration, Huntington s disease, Wilson s disease, hydrocephalus) or due to known drugs, chemicals or toxicants.

   Disability present despite optimal antiparkinsonian medication therapy.

   Unequivocal responsiveness to levodopa, based on the single-dose levodopa test (as described in the CAPIT and CAPSIT guidelines). In addition to a 33% or greater improvement in one of the timed tasks, a 30% or greater improvement in the UPDRS total motor score will be required to establish unequivocal responsiveness to levodopa.

   Patients must demonstrate at least 6 hours of non-on time and medication side-effects such as levodopa-induced dyskinesias or motor fluctuations.

   Neuropsychological evaluation does not indicate substantial depression or cognitive dysfunction.

   Able to provide proper Informed Consent.

   EXCLUSION CRITERIA:

   Presence of prominent oculomotor palsy, cerebellar signs, vocal cord paresis, orthostatic hypotension (> 20 mm Hg drop on standing), pyramidal tract signs or amyotrophy.

   Presence of dementia (Clinical Dementia Rating Scale score > 1.0 or Mini Mental Status Examination Score < 25).

   Presence or history of psychosis, including if induced by anti-PD medications.

   Presence of untreated or suboptimally treated depression (Hamilton Depression Scale score >10) or a history of a serious mood disorder (for example, requiring psychiatric hospitalization or a prior suicide attempt).

   Presence of substance (drug, alcohol) abuse.

   Presence of hypointensity in the striatum on T2-weighted MR-imaging.

   Contraindication to MR-imaging and/or gadolinium.

   Coagulopathy, anticoagulant therapy, low platelet count, or inability to temporarily stop any antithrombotic medication.

   Prior brain surgery, including gene therapy, radiofrequency ablation or deep brain stimulation.

   Male or female with reproductive capacity who is unwilling to use contraception throughout the study.

   History of stroke or poorly controlled cardiovascular disease.

   Uncontrolled hypertension or diabetes or any other acute or chronic medical condition that would increase the risks of a neurosurgical procedure.

   Clinically active infection, including acute or chronic scalp infection.

   Received investigational agent within 12 weeks prior to screening.

   Unable to comply with the procedures of the protocol, including frequent and prolonged follow-up.

   Baseline hematology, chemistry or coagulation values out of normal range unless not clinically significant with respect to surgery.