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Get to Know your Parkinson’s – Part 3

Simon Israeli-Korn

Scientific and Medical Senior Director

In the previous article we discussed how to manage your Parkinson’s symptoms. In this article we will elaborate on additional therapeutic options.

Obtaining a strong social support network (family, friends, and fellow people with Parkinson’s), adopting a healthy and active lifestyle, maintaining a healthy mindset, and investing in your own emotional wellbeing. All play a crucial role in managing your Parkinson’s symptoms and in improving your quality of life. Another key success factors is achieving and maintaining a medication regimen that works for you. Still, as the disease progresses, therapies that were beneficial early on may seem to be less effective and symptoms become more difficult to control. At the same time, new advances in research and novel technologies may offer better symptom management with the help of non-oral therapies such as devices that allow the continuous delivery of medications or deep brain stimulation.

Why medications stop working

The main challenge with oral medication containing levodopa is that because it is an intermittent therapy by nature, the drug levels in the blood fluctuate greatly, spiking after taking every pill. Initially the clinical response may be very good but over the long term it becomes very challenging to maintain a steady response from the medication.

It appears that both levodopa and Parkinson’s itself cause the digestive system to work more slowly. This means that it takes longer for oral medication to pass through the stomach and reach the small intestine where it is absorbed. To complicate things further, the slowness of the digestive system results in changes in the types of bacteria in the digestive system, also known as the gut microbiome. These changes in turn affect how levodopa is broken down and absorbed, resulting in longer absorption time and, consequently, a longer time for the drug to reach the brain and alleviate symptoms.

Other medication

In order to address the problem of getting dopamine to the brain without side effects and without too many peaks and troughs, slow release / long-acting formulations have been developed, but even these improvements may not be satisfactory. Another approach is to stimulate and support the dopaminergic system in the brain through different targets, for example by inhibiting one of the enzymes that break down dopamine or inhibiting one of the receptors that takes dopamine back into the cell from the space between the cells where it is having its effect.

When this starts to happen people’s symptoms worsen and there are periods during the day when they may feel like they haven’t taken their medication, leading to the perception that the medication is losing its effect. This state, where patients feel the medications effect has worn off or hasn’t taken effect yet, is often called the “Off" state. To mitigate this, doctors may increase the doses, the number of doses, or the types of medications. This, in turn, increases the risk of side effects caused by higher doses, most notably dyskinesia and confusion. Dyskinesia is the term used to describe uncontrollable and excessive movements. When mild, it is typically non-bothersome for the patient, who might be unaware of it (even though it might be noticeable to other people). When severe, it can be troublesome, affecting normal functioning such as eating and walking and possibly causing pain. 

Device-aided therapies

Sometimes medications cause side effects or offer only a partial solution to the problem. At this point physicians may start encouraging patients to consider alternative approaches. These alternative approaches are termed device-aided therapies and refer to therapeutic interventions that go beyond taking pills. The options include injections, infusions, pumps, and neurosurgical operations. Sometimes the results really can be life changing. On the other hand, there are risks and side-effects involved, and being aware of them is critical in making well-informed decisions.

Pump therapies for continuous dopaminergic stimulation

One type of device-aided therapy, called continuous dopaminergic stimulation, aims to deliver medications continuously. This can be achieved either via a subcutaneous (under the skin) infusion or via a tube in the stomach that connects to the intestine. Both these solutions involve pump technologies as part of the drug delivery system. The other component of the system is the drug itself. At present there is only one available option for intestinal therapy, and its active ingredient is essentially a gel form of the levodopa/carbidopa pills. Currently there is also only one available option for subcutaneous therapy, and its active ingredient is apomorphine. Apomorphine, despite its name, is not related to morphine. It belongs to the class of medications called dopamine agonists. Other dopamine agonists you may have come across are ropinirole and pramipexole.

As for deciding between the two therapies, levodopa intestinal gel is considered preferable over subcutaneous apomorphine infusion if Parkinson's symptoms include impulse control disorder, hallucinations, or cognitive decline.

Rescue therapies for immediate relief

Rescue therapy refers to approaches offering immediate relief during "off" periods".
Rescue therapies include injections of apomorphine, inhaled levodopa or sublingual (rapidly absorbing) apomorphine. And of course, also continuous therapies may offer a solution to off periods.

Surgical options

Brain surgery, often viewed as a last resort, is another option. The most common form of brain surgery is Deep Brain Stimulation (DBS), in which electrodes are inserted deep into an area of the brain called the basal ganglia where there is abnormal brain activity in Parkinson’s patients. These electrodes are connected to a pacemaker which is implanted under the skin in the chest, very similar to heart pacemakers. This pacemaker provides electrical stimulation impulses that reduce the abnormal brain activity in the basal ganglia and essentially offers relief to many of the motor symptoms that respond to levodopa.

Following such operations, doses of medication typically drop by 30% to 50%, but are very rarely stopped completely. And tremors may actually respond better to the operation than to medication.

There are several factors to consider prior to undergoing such a procedure. The first is surgical risk, which is present for everyone but increases with age, frailty, cognitive impairment, and multiple additional medical problems. Another factor is emotional and behavioral health; because of stimulation effects and changes in medications, caution is needed when there are problems relating to depression, anxiety, impulse control, and apathy. Walking problems are another point to consider, because balance impairment, and freezing of gait in particular, rarely respond to DBS. An additional factor is level independence in activities of daily living [1]. Lastly, the presence of speech problems or concern about speech, for example for someone whose profession requires them to speak or sing at a high level, may be a factor to consider since DBS is associated with worsening of speech.

So, how to decide which therapy is right for me?

Although there are no research-backed guidelines for precisely matching therapies to patients, many movement disorder specialists have published their experiences and their recommendation [2]. Often the decision is not clear-cut and may come down to the patients' particular personality and risk preferences. It is of upmost importance that patients be given enough time to consider all these options and not make any hasty decisions, since once a certain direction is pursued, it may be hard to go back and start again. Reading up on treatments, speaking with others, and taking advantage of local patient support groups as a resource, all may be helpful in deciding on a treatment path. Additionally, patients are encouraged to consult with their family and with their multidisciplinary team to come to a decision. Sometimes mental health professionals can be very helpful for a patient to reach a decision. Nurses in clinics are also a helpful resource with comprehensive understanding of all the factors involved in this decision. Having realistic expectations is key. Many find it helpful to speak to someone who has undergone the procedure that they are considering, as it can help them envision life after the intervention and thus come to a decision. Nothing is better than hearing things first-hand, but bear in mind that nothing is guaranteed. Every person has their own condition and their own response to treatment which is often hard to predict.

Anxiety and dealing with uncertainty – leaping into the unknown

After being controlled with pills and tablets, making the switch to a different course of treatment can be quite nerve-wracking. Some people prefer the familiar and making a change may actually be a harder pill to swallow than the pills themselves! On the other hand, these therapies have all been studied extensively and have been in use for many years, and most people report significant improvements in their quality of life.

There is much apprehension and anxiety surrounding Parkinson’s. People worry about their future, and they worry about the side effects of their treatments. When it comes to treatments that are considered more invasive than pills and tablets, the concern is even greater. Fear of side effects and complications result in people being under-treated as they avoid more advanced, safe treatments that may offer considerable benefit. Most people, even those who may have a high chance of benefiting from such treatments, decline the option of device-aided therapies; the unknown is often perceived as being just too much of a risk. On the other hand, if after considering all of the options you are still unsure, now may not be the time. Like all things in life, the timing has to feel right.

Exercise, sport, dance, and physiotherapy offer many benefits to brain health (including emotional wellbeing) as well as to other systems in the body, including the heart, lungs, bones and more. All this is relevant for people with Parkinson’s, with many added benefits such as maintaining muscle strength, flexibility, balance, and general fitness. All these are key to mitigating the motor symptoms of Parkinson’s: slow movements, small movements, poor balance, and a tendency for prolonged sitting, and bending forward or to the side when walking. If you track your performance, it can be incredibly rewarding to see an improvement in the face of a condition that should be causing a decline.

Many symptoms – such as tremors and difficulty walking – worsen with anxiety, fear of falling or simply by being nervous around people. Some people may feel like their feet are frozen to the ground - a phenomenon called “Freezing of Gait”. This is why in many cases most remedies that are designed to relieve anxiety, actually alleviate motor symptoms as well, and may even break the vicious cycle of tremors and walking problems causing anxiety and vice-versa. Relaxation techniques too can be used to relieve anxiety, with a focus on your breathing and inner voice. Adding exercises to improve walking and your balance will build your self-confidence, anxiety will subside, and many symptoms will often follow suit. With practice and persistence, the vicious cycle can not only be broken but even be transformed into a positive loop.

Other critical aspects of keeping a healthy lifestyle that may help with curbing the effects of Parkinson's include maintaining a healthy diet, sleeping well, and engaging in enjoyable social activities. On a higher level, the feelings of purpose and contribution resulting from those activities provide much satisfaction, joy, and meaning to life. Some people attain this through their work, others through their families, their hobbies or volunteering activities.

[1] Metta V, Batzu L, Leta V, Trivedi D, Powdleska A, Mridula KR, Kukle P, Goyal V, Borgohain R, Chung-Faye G, Chaudhuri KR. Parkinson's Disease: Personalized Pathway of Care for Device-Aided Therapies (DAT) and the Role of Continuous Objective Monitoring (COM) Using Wearable Sensors. J Pers Med. 2021 Jul 19;11(7):680. doi: 10.3390/jpm11070680. PMID: 34357147; PMCID: PMC8305099.

[2] Volkmann J, Albanese A, Antonini A, et al. Selecting deep brain stimulation or infusion therapies in advanced Parkinson's disease: an evidence-based review. J Neurol. 2013;260(11):2701-2714. doi:10.1007/s00415-012-6798-6
Merola A, Espay AJ, Romagnolo A, Bernardini A, Rizzi L, Rosso M, Espay KJ, Zibetti M, Lanotte M, Lopiano L. Advanced therapies in Parkinson's disease: Long-term retrospective study. Parkinsonism Relat Disord. 2016 Aug;29:104-8. doi: 10.1016/j.parkreldis.2016.05.015. Epub 2016 May 17. PMID: 27215392.

THIS ARTICLE DOES NOT PROVIDE MEDICAL ADVICE and is not a substitute for professional medical advice, diagnosis or treatment. If you or any other person has a medical concern, you should consult with your health care provider or seek other professional medical treatment immediately. Never disregard professional medical advice or delay in seeking it because of something that you have read on this website or in any linked article, blog or other materials.


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