Master the ins-and-outs of Parkinson’s Disease! We’re joined by Dr. Albert Hung, who teaches us pearls for the initial history and physical exam in a patient with undiagnosed Parkinson’s, a framework for management of early and advanced motor symptoms, tips for treating autonomic symptoms and cognitive / psychiatric features, and more.
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There are four cardinal signs of parkinsonism that are important to assess for when taking a history and performing a physical exam on a patient with suspected Parkinson’s disease: tremor, bradykinesia, rigidity, and postural instability (Armstrong et al 2020, Bloem et al 2021). The Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) provides a framework for evaluating parkinsonism on physical exam (Goetz et al 2008). Dr. Hung shares pearls for assessing for each of these cardinal symptoms on history and physical exam:
During the office visit, Dr. Hung also stresses that it is important to always ask a patient to walk in order to assess their gait and posture. In early Parkinson’s, gait changes may be subtle, and may manifest with slight slowness, a bit of a stooped posture, and reduced arm swing on the side more affected by parkinsonism. The classic shuffling gait or freezing gait of Parkinson’s disease is usually seen at more advanced stages.
There are three key “pre-motor” symptoms of Parkinson’s Disease that can start more than a decade before the motor symptoms (Bloem et al 2021, Armstrong et al 2020), and are important to ask about on history when evaluating a new suspected diagnosis of Parkinson’s are:
Dr. Hung notes that the accumulation of Lewy bodies (primarily aggregates of alpha-synuclein) that define the dominant pathology of Parkinson’s disease is thought to spread caudally to rostrally, starting lower down in regions such as the gut and gradually spreading to the midbrain where involvement of the substantia nigra causes motor symptoms, and then finally spreading to the cortex where it produces features such as dementia or psychosis (Foffani, 2018).
According to Dr. Hung, once he is convinced that the patient is exhibiting parkinsonism based on evaluating the cardinal symptoms, the next step is to do a thorough medication check to rule out drug-induced parkinsonism (Mena et al 2006, Postuma et al 2015). While first-generation antipsychotics like haloperidol are most classically thought of as causing drug-induced parkinsonism, Dr. Hung notes that even newer generation antipsychotics such as risperidone, aripiprazole, and olanzapine can be culprits. Additionally, dopamine antagonist antiemetics such as metoclopramide or prochlorperazine can also cause drug-induced parkinsonism. According to Dr. Hung, it is important to look not only at the patient’s current medications but also what medications they have been on in the past, as drug-induced parkinsonism can sometimes persist for months after the drug is stopped.
Once drug-induced parkinsonism is ruled out, the next step is to discern whether the patient is more likely to have idiopathic Parkinson’s disease versus another “flavor” of parkinsonism (Postuma et al 2015), as this distinction influences prognosis, likelihood of response to medication, and how to counsel patients. There are several “red flags” that point to another parkinsonian syndrome rather than idiopathic Parkinson’s disease:
For a patient presenting with symptoms of typical idiopathic Parkinson’s disease and no other abnormal exam findings, imaging is usually not necessary.
Dr. Hung notes that he will typically order an MRI in the following situations:
The dopamine transporter scan (DaT scan) is another imaging consideration. This scan is a functional study that involves injection of a ligand that binds to presynaptic dopamine transporters; loss of dopaminergic neurons will result in decreased uptake. Notably, the DaT scan does not help distinguish idiopathic Parkinson’s disease from other atypical neurodegenerative parkinsonian syndromes, as all of these conditions will yield abnormal DaT scans (Armstrong et al 2020, Bloem et al 2021). However, DaT scans can help distinguish neurodegenerative forms of parkinsonism from essential tremor, drug-induced parkinsonism, or vascular parkinsonism, as these conditions should have a normal DaT scan (Bloem et al 2021). In a patient he is confident has idiopathic PD or another neurodegenerative form of parkinsonism, Dr. Hung will usually not order a DaT scan; however, he will consider a DaT scan if there is uncertainty about whether neurodegenerative parkinsonism is present or if the patient isn’t comfortable with a clinical diagnosis of Parkinson’s disease.
In discussing a new diagnosis of Parkinson’s with a patient, Dr. Hung said he makes sure patients understand that there are medications that can help with symptoms, and while we can’t currently cure the disease, we will do our very best to keep them at a high quality of life for as long as possible. Dr. Hung refers his patients to a variety of online resources, including the Parkinson’s Foundation, the Michael J Fox Foundation, and the American Parkinson’s Disease Association.
In an initial visit, Dr. Hung also stresses the importance of exercise (Schenkman et al 2018), and recommends early referral to physical therapists specializing in Parkinson’s Disease. There is growing evidence that exercise not only helps with mobility / motor symptoms in Parkinson’s, but may actually also have neuroprotective effects, and an ongoing trial is randomizing patients to moderate or vigorous exercise to investigate the impact on clinical disease progression and DaT scans.
Carbidopa / levodopa is the oldest and most effective medication for Parkinson’s disease. Dr. Hung notes that if there is limited access to neurology or it is going to take a significant period of time for a patient to see a neurologist, it is reasonable for primary care providers to start carbidopa / levodopa themselves. Starting carbidopa / levodopa will not interfere with the process of making the diagnosis of Parkinson’s disease; in fact, it can actually help diagnostically, as idiopathic Parkinson’s disease should respond to the medication while other parkinsonian syndromes may be more refractory (Postuma et al 2015).
In terms of initial dosing of carbidopa / levodopa (25 mg / 100 mg), Dr. Hung recommends starting at a low dose and gradually increasing. He usually starts a patient on ½ tablet twice per day (once in the morning before breakfast and the next before lunch), then increasing to ½ tablet three times per day (adding in a dose before dinner), and then finally increasing to 1 tablet three times per day. He advises patients to take levodopa / carbidopa before meals, since taking the medication with food (especially a protein-rich meal) can interfere with absorption.
There are several additional classes of medications that can be used for initial therapy. Dopamine agonists including pramipexole and ropinirole, can be used, though they are less effective than carbidopa / levodopa and have more significant short-term side-effects (Stowe et al 2008), including nausea, excessive daytime sleepiness, and impulse control disorders (Corvol et al 2018). Impulse control disorders most commonly manifest as compulsive gambling, hypersexuality, compulsive buying, and binge eating; it is very important to tell patients ahead of time to watch out for any signs of these when prescribing a dopamine agonist, as patients will not usually bring these symptoms up with physicians otherwise. Use of dopamine agonists has also been associated with dopamine agonist withdrawal syndrome (DAWS), which is most likely in patients with impulse control disorders (Rabinak et al 2010, Pondal et al 2013). These side effects of dopamine agonists have “swung the pendulum” back towards using carbidopa / levodopa as initial treatment, according to Dr. Hung. Another option for initial therapy is MAO-B inhibitors (including selegiline, rasagiline, and safinamide), though these agents have a low potency for treating motor symptoms.
In more advanced Parkinson’s disease, patients will often experience a shorter window of time in which levodopa / carbidopa is effective, and tend to develop “on / off” fluctuations in which they experience “wearing off” of the medication towards the end of the dose (Armstrong 2020). This is because levodopa has a short half life in the blood (several hours); while in earlier stages of Parkinson’s disease the body can accommodate this, in later stages the accommodation is less robust, and “wearing off” will occur. Additionally, when patients do take enough medication to achieve an “on” state, they may exhibit too much movement, known as levodopa-induced dyskinesias (Armstrong 2020), which can include writhing, swaying, and bobbing. Thus, the challenge in managing motor symptoms in advanced Parkinson’s disease is trying to strike a balance between “wearing off” (a sign of not enough medication at certain points in the day) and levodopa-induced dyskinesias (a sign of too much medication at certain points in the day.) When patients reach this point, a movement disorder specialist should be involved in management.
In thinking about management of advanced motor symptoms, Dr. Hung notes that thinking about pharmacokinetics is key: essentially, considering how to stretch out the duration of action of levodopa to prevent so many highs and lows. There are several strategies in treating motor symptoms in advanced Parkinson’s disease:
Autonomic symptoms, including constipation, urinary symptoms, and orthostatic hypotension, are very common in Parkinson’s disease. Collaboration between multiple specialties, including urology, GI, neurology, and primary care, is crucial. Notably, dopamine replacement can exacerbate autonomic symptoms, and in more advanced Parkinson’s disease the dose of dopaminergic agents may need to be decreased if autonomic symptoms are an issue. Constipation can be severe, and often require harnessing the full arsenal of bowel medications. Orthostatic hypotension is also a concern, and physicians should have a low threshold to check orthostatics in the office and encourage fluid / salt intake if there are hints of issues with dizziness on standing. More severe orthostatic hypotension may require agents like fludrocortisone or midodrine.
Unlike Alzheimer’s disease, which primarily affects memory / recall, cognitive impairment in advanced Parkinson’s disease usually involves executive dysfunction and visuospatial deficits. The treatment of choice for dementia in Parkinson’s disease is cholinesterase inhibitors; rivastigmine is the one FDA-approved agent to treat Parkinson’s disease dementia (Emre et al 2004). Unfortunately, the response to cholinesterase inhibitors is not very strong.
Psychosis in Parkinson’s Disease is a major risk factor for ending up in a nursing home. Notably, use of antipsychotics can worsen parkinsonian motor symptoms, and antipsychotic agents such as olanzapine and risperidone should be avoided. The three main options for anti-psychotic treatment: quetiapine, pimavanserin, and clozapine (Seppi et al 2019.) Quetiapine is usually the agent of choice for psychosis in Parkinson’s disease. Pimavanserin is another option, though it takes several weeks for medication levels to reach steady-state and often months to see clinical benefit, which is not ideal for the acute setting. Clozapine has good efficacy for psychosis in Parkinson’s Disease, though is often not utilized due to the need to monitor for agranulocytosis.
Anxiety and mood disorders are very common in Parkinson’s disease. In particular, apathy, lack of motivation, and anhedonia are frequent symptoms of depression in Parkinson’s disease. In general, the same agents that are used in the general population for these disorders are also utilized in Parkinson’s disease, including SSRIs, SNRIs, bupropion, and TCAs. Dr. Hung notes that bupropion also has some dopaminergic activity, which can help with apathy and fatigue.
Listeners will develop a framework for the diagnosis of Parkinson’s disease and the management of both motor and non-motor symptoms.
After listening to this episode listeners will…
Dr. Hung reports no financial disclosures. The Curbsiders report no relevant financial disclosures.
Gandhi MM, Hung A, Grant K, Williams PN, Watto MF. “#370: Parkinson’s Disease for Primary Care”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list December 5, 2022.
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