Idiopathic Parkinson Disease: Treatment

00:01 How do we treat Parkinson's disease? What's the treatment? Well the workhorse, the gold standard for managing patients with Parkinson's disease is levodopa.

00:10 Levodopa is synthetic dopamine.

00:12 It's the drug of choice in patients with any signs of a Parkinsonism.

00:17 Typically, this levodopa is combined with carbidopa, which reduces the systemic breakdown of levodopa.

00:24 Levodopa readily crosses the blood-brain barrier and gets into the brain.

00:28 It has a relatively quick time of onset, but a short duration of action.

00:33 And only remains in the body for somewhere between 4, 6 or maybe up to 8 hours.

00:39 It's typically dosed to three times a day, given that short half life and the rapid turnover of dopamine in the brain.

00:46 Any patient with a suspected Parkinsonism should initially be challenged with levodopa and evaluated for symptomatic and clinical improvement which is helpful in guiding diagnostic evaluation as well as therapy for that patient.

01:01 In addition to levodopa, we consider a number of other agents that are modulating the circuitry in the direct and indirect pathway.

01:08 Monoamine oxidase type B inhibitors can be used including Selegeline, Rasagiline being the two most common.

01:16 We also can consider non-ergot dopamine agonists, medications like Pramipexole and ropinirole.

01:24 Again, the problem in Parkinson's disease is too little dopamine in the substantia nigra.

01:28 So we give medications to increase dopamine in the brain, either synthetically with levodopa, or with our dopamine agonist to increase production.

01:38 Some of the things we need to think about with dopamine agonists are the side effects.

01:42 We can see increase in gambling and hypersexuality, nausea and vomiting or hypotension, and those would be things we need to worry about or watch for and patients initiating dopamine agonist therapy.

01:55 And typically, these medications should not be stopped abruptly, and patients should taper down slowly of these agents.

02:04 In addition, a number of other agents can be used and we'll see in patients who have Parkinson's disease, Amantadine, anticholinergics, COMT inhibitors, or catechol-o-methyltransferase inhibitors don't activate dopamine, but they reduce the breakdown of dopamine in the brain and can help sustain the action of of levodopa in particular, in the body.

02:29 And then there are also some surgical therapies that can be considered, which can be life-changing for patients with tremor-dominant Parkinson's disease.

02:37 One of those is deep brain stimulation.

02:40 This is where electrodes are placed in and around specific targets within the brain.

02:47 Several of those targets include the subthalamic nucleus, the globus pallidus internus, or sometimes within the thalamus itself.

02:55 You can remember back to that circuitry the direct and indirect pathway.

02:59 And deep brain stimulation is modulating the signals in those key basal ganglia structures to help encourage the foot to come off the brake, to activate the thalamus to initiate movement.

03:13 Deep Brain Stimulation is placed surgically along with an impulse generator.

03:17 That impulse generator is placed underneath the collarbone, and provides power to the electrodes, which alter brain brain signaling.

03:27 The neat thing about deep brain stimulation is it's not lesional.

03:30 It can be turned on and turned off.

03:33 In the clinic, we evaluate patients initially in the office setting, and we'll see severe tremor, bradykinesia as well as as rigidity and postural instability.

03:44 And then using a wand over the impulse generator, the deep brain stimulation can be turned on and magically, the patient's tremor goes away and their movements improve.

03:54 Importantly, when we evaluate someone for deep brain stimulation, we look at their response to levodopa.

04:00 Patients who have a significant lever dopa response are likely to improve with deep brain stimulation, and those with less prominent levodopa responsiveness are less likely to improve with that therapy.

04:13 Most recently, we've seen the entry of MR Guided High Intensity Focused Ultrasound used for Parkinson's disease.

04:21 This is an extremely cool treatment.

04:24 Here we're using ultrasound or sound waves to drive deep through the calvarium, the skull, deep through the brain and target those deep small structures in the basal ganglia.

04:35 This is a minimally minimally invasive surgical procedure.

04:39 We often target things like the ventral intermediate nucleus of the thalamus, the subthalamic nucleus or the globus pallidus internus.

04:47 And remember those are the key structures involved in modulation of movement.

04:52 MR Guided High Intensity Focused Ultrasound is a lesional procedure.

04:56 Using those high intensity sound waves, we lesion a part of the brain.

05:00 So that's no longer involved in the basal ganglia circuitry, and releasing the thalamus to to help the body to move.

05:10 We can also consider alternative surgical approaches.

05:13 The duopa-pump is an implantable pump that bypasses the stomach and provides a steady carbidopa levodopa infusion over 16 hours or more.

05:23 And so here we're using a pump into the gastrointestinal tract to get around that peak effect of giving levodopa every 3 or 4 times a day.

05:34 the duopa-pump delivers steady doses of levodopa and helps to avoid peak dose effects and wearing off from levodopa.

05:43 This reduces fluctuations that we can see from oral administration of carbidopa/levodopa in the bloodstream and improves daily on and off times.

05:53 When you talk to patients with Parkinson's disease, they want to leave it on.

05:56 They want levodopa and dopamine in their system and up in their brain and oral administration of levodopa results in high peak on effects and then wearing off of the medication.

06:08 The duopa pump can be very helpful in smoothing that on and off curve out, giving patients more on time and less off time.