Advances in Therapeutic Management for Parkinson Disease and Essential Tremor

Levodopa is widely regarded as the most effective medication for most patients with Parkinson disease (PD) in the clinical setting and is recommended as the primary approach to control severe tremors. However, for patients with PD tremors that do not respond to medication, deep brain stimulation (DBS) and focused ultrasound are also considered first-line therapies. Surgery is another highly effective option for medication-refractory tremors, particularly in selected patients without motor fluctuations. The success of these therapies, though, depends on proper utilization and the collaboration between the provider and the patient.¹

Subcutaneous apomorphine infusion is a device-aided therapy for patients with PD whose motor fluctuations are not adequately managed by oral or transdermal medications. This treatment is less invasive than enteral levodopa, DBS, or focused ultrasound, and is often used when neurosurgical options are not feasible. Successful treatment with apomorphine infusion requires agreement and cooperation from both the patient and their family, as well as clinical support from an experienced medical team, especially during the initial months of therapy.²

At the third annual Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held by the PMD Alliance from June 22-25, 2024, Anvi Gadani, MD, presented on how different therapeutic delivery systems and surgical management options such as DBS, pump therapy, and focused ultrasound, impact management of PD, essential tremor (ET), and dystonia. During her presentation, Gadani talked about how providers can communicate the different treatments available to their patients, comparing the benefits and risks, to manage the disease.

Gadani, an assistant clinical professor of medicine at Medstar Georgetown University Hospital, sat down with NeurologyLive^® in an interview at the Congress to further discuss the main benefits and risks associated with DBS for treating advanced PD. She also talked about how MRI-guided focused ultrasound differs from DBS in terms of procedure and impact on patient care. Gadani, who also serves as a neurologist in the department of movement disorders at Montgomery Medical Center, additionally spoke about considerations clinicians should keep in mind when discussing subcutaneous infusion pumps with patients.

NeurologyLive: Could you give an overview of what you talked about in your presentation on surgical management of movement disorders?

It was an introduction to surgical management as well as other device-aided or device-guided therapies for patients with PD and essential tremor. We focused on deep brain stimulation, which is one of our main go-to therapies now for these patients. You can target the deep structures in the brain that can contribute to these disease processes and stimulate with high frequency modulatory therapy. These therapies help manage these more advanced patients who have had significant disease progression and all the other oral medication therapies have started to become of limited benefit to them. That's one of the main therapies that we talked about. It is a surgical procedure that requires brain surgery. It is invasive and can be something that can take a toll on a patient, especially if they have other preexisting conditions. That's something to take into consideration when you're considering a patient for deep brain stimulation.

The other therapy that we talked about was MRI-guided focused ultrasound. This is not a device that a patient takes home with them but an MRI machine that delivers ultrasound rays that can create a lesion in those deep structures that create these disease processes. It's indicated, again, for patients with PD and essential tremor who have more advanced disease states. It doesn't require surgery, so that's one of the beauties of that. But it is a lesioning technique, something that's a little more permanent and doesn't allow for modulation the way deep brain stimulation does. But again, you'd want to take into consideration with your patient like what their other medical issues are and what their preferences are.

We talked about some of the devices that are available that patients can keep with them that are not necessarily as invasive. Although one of them, carbidopa levodopa intestinal gel, is a little bit more invasive. It's a different surgery where you have a tube that goes into your intestine that delivers continuous carbidopa levodopa gel throughout your waking day. Again, that's indicated specifically for patients with advanced PD who are having a lot of fluctuations in their symptoms throughout the day, and the oral medications have started to become less effective for them.

The 2 other devices that we discussed were pumps, one for subcutaneous apomorphine, which is a dopamine agonist therapy, and the other for foslevodopa/foscarbidopa. These 2 therapies are not FDA approved in the US yet but they are being assessed in phase 1, phase 2, and phase 3 clinical trials. The subcutaneous apomorphine is in use in the UK and Europe for many years now. We're hoping that it will get FDA-approved soon here. The foslevodopa/foscarbidopa is relatively newer but also shows promise in terms of helping our patients with advanced PD with their motor fluctuations and other symptoms like dyskinesias, dystonia, stiffness, and slowness.

There are lots of good things in terms of the advanced therapies that we have available for patients with PD as well as essential tremor. I think that's one of the beauties of coming to a conference like ATMRD, really getting exposed to what we can really offer our patients who have these unfortunate neurodegenerative conditions. But there are certain adverse effects and other patient considerations that you want to take into account when you're considering patients for these therapies.

What advice would you give to clinicians who may be prescribing these different treatment options to their patients or thinking about prescribing them in the future if they do get approved?

The subcutaneous infusion pumps are the least invasive which is exciting because our patients wouldn't have to undergo any advanced lesioning procedure or advanced surgery. I think that's going to change the market and what we have available for our patients once those do become FDA-approved. But I think the main thing for clinicians is that you have to have an informed conversation with your patients and explain to them, provide them all the options that are available. Each patient is different. They may have other medical conditions besides their neurological issue that you have to take into consideration for these therapies. You have to take into consideration what may be potential adverse effects after starting these therapies and what their specific fears may be. They may be absolutely against any surgery, and then these subcutaneous therapies might be better options for them. I think it's just taking into consideration the patient factors and having an informed conversation with your patient because, after all, it is their body and the disease that they're dealing with.

Do you have any closing remarks regarding your presentation or ATMRD?

This is a conference discussing advanced therapeutics in movement and other related disorders. The most important thing when it comes to these conferences is that you have to keep an open mind. That's the beauty of these types of informational sessions that we have available as clinicians, you have to keep educating yourself. You have to keep an open mind about learning what's new and available for your patients because your patients will ask questions. They're educated, they're going to inform themselves about what's available out there, and they will ask you questions. You want to be able to make that informed decision with them. Also, if you keep an open mind, it'll allow you to best help your patient and provide a good quality of life for them.

Click here for more coverage of ATMRD 2024.

REFERENCES
1. Pirker W, Katzenschlager R, Hallett M, Poewe W. Pharmacological Treatment of Tremor in Parkinson's Disease Revisited. J Parkinsons Dis. 2023;13(2):127-144. doi:10.3233/JPD-225060
2. Henriksen T, Katzenschlager R, Bhidayasiri R, Staines H, Lockhart D, Lees A. Practical use of apomorphine infusion in Parkinson's disease: lessons from the TOLEDO study and clinical experience. J Neural Transm (Vienna). 2023;130(11):1475-1484. doi:10.1007/s00702-023-02686-7