#370 Parkinson’s Disease for Primary Care with Dr. Albert Hung

December 5, 2022 | By Matthew Watto, MD

Video

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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Credits

• Producer, Writer, Show Notes, and Infographic: Malini Gandhi
• Cover Art: Kate Grant 
• Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP   
• Reviewer: Emi Okamoto MD
• Showrunner: Matthew Watto MD, FACP; Paul Williams MD, FACP
• Technical Production: PodPaste
• Guest: Albert Hung MD, PhD

Sponsor: Better Help

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CME Partner: VCU Health CE

Show Segments

• Intro, disclaimer, guest bio
• Guest one-liner
• Case from Kashlak
• Initial history in a patient with undiagnosed Parkinson’s
• “Pre-motor” symptoms of Parkinson’s disease
• Physical exam in Parkinson’s disease
• Drug-induced Parkinsonism
• “Red flags” suggesting atypical parkinsonian syndromes
• Role of imaging in diagnosis
• Typical discussion with patient at initial diagnosis
• Initial management of motor symptoms
• Management of autonomic symptoms
• Management of advanced motor symptoms
• Management of cognitive and psychiatric symptoms
• Outro

Parkinson’s Disease Pearls

1. The four cardinal signs of Parkinson’s disease are tremor, bradykinesia, rigidity, and postural instability.
2. There are several key “pre-motor” symptoms of Parkinson’s disease, including hyposmia, constipation, and REM sleep behavior disorder, which can sometimes precede the onset of motor symptoms by over a decade.
3. When making a diagnosis of Parkinson’s disease, it is important to be aware of “red flags” that point to other atypical parkinsonian syndromes. These red flags include early falls and abnormal eye movements (suggests progressive supranuclear palsy), early severe autonomic dysfunction (suggests multiple system atrophy), and early cognitive issues (suggests dementia with Lewy bodies.)
4. In a classic presentation of idiopathic Parkinson’s disease, imaging is not needed to make the diagnosis. MRI can be helpful if there are atypical symptoms or lower-body predominant parkinsonism, and DaT scans can be useful if there is uncertainty about whether the patient has a neurodegenerative form of parkinsonism.
5. Carbidopa / levodopa is very commonly used for initial therapy. Dopamine agonists are another option, though notably are associated with more short-term side effects including excessive daytime sleepiness and impulse control disorders.
6. A key aspect of Parkinson’s disease management involves treating non-motor features of the disease, including autonomic symptoms and cognitive / psychiatric symptoms.

Parkinson’s Disease for Primary Care – Show Notes 

Diagnosis of Parkinson’s Disease

History and Physical: the cardinal signs

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:

• Tremor: The parkinsonian tremor is classically an asymmetric rest tremor, and usually comes on gradually. Dr. Hung notes that a family member or primary care provider is often the first to mention a tremor, as patients may downplay it as it may not initially interfere with their daily activity. In the office, Dr. Hung stresses that observation is key, as initial tremors in Parkinson’s disease are often subtle, and may not be much more than a twitching of the thumb or a slight shaking of the hand that comes and goes. On exam, Dr. Hung said to make sure the patient’s arm is completely at rest, and take note of the amplitude of the tremor and how much time the tremor is present. He notes that distracting the patient by asking them to do other tasks can sometimes help bring out a subtle tremor. One pearl Dr. Hung shared is that patients with Parkinson’s disease can also have a concurrent postural tremor (i.e. shaking of the hands when the arms are held up.) However, the postural tremor in Parkinson’s disease can be distinguished from the postural tremor in essential tremor by the fact that in essential tremor, the hands will shake immediately when they are brought up, while in Parkinson’s Disease, the hands are initially still when brought up but then start to shake when the position is maintained, a so-called “re-emergent” postural tremor (Armstrong et al 2020, Postuma et al 2015.)
• Bradykinesia: Dr. Hung stresses that bradykinesia is the most important element of parkinsonism, despite the fact that tremor is more well-known. Bradykinesia can be subtle, and is often initially attributed to other issues such as arthritis, frozen shoulder, or depression. On history, Dr. Hung will often ask about changes in a person’s daily routine, including difficulty with fastening buttons / zippers, cutting food, putting their arms into sleeves, or getting in and out of bed or a chair. Small handwriting (micrographia) can also be a common feature of bradykinesia. On exam, the MDS-UPDRS includes five different tasks to assess for bradykinesia: tapping fingers, opening and closing fists, arm pronation / supination, tapping toes with the heel flat on floor, and tapping the entire foot (Goetz et al 2008). Dr. Hung notes that it is important to have the patient perform all of the tasks, as patients may demonstrate bradykinesia with some tasks but not others. For each task, the patient should be instructed to perform a minimum of 10 repetitions. This repetition is important because while in some patients bradykinesia might be characterized by general slowness, in others bradykinesia may manifest with features such as decrement (i.e. where movements are normal at the beginning, but grow increasingly small by the end of the sequence), which may only be brought out with repetition. 
• Rigidity: The rigidity in Parkinson’s disease is velocity-independent, meaning it will be present regardless of whether the examiner is moving the joint quickly or slowly (Armstrong 2020, Postuma et al 2015.) Certain “reinforcement maneuvers” can be used to augment subtle rigidity: for instance, if testing one arm, the examiner can ask the patient to do maneuvers with the opposite arm such as opening / closing the hand or drawing large circles. Cogwheel rigidity may be present, and is essentially a manifestation of tremor superimposed on increased tone (Postuma et al 2015). However, Dr. Hung notes that cogwheel rigidity is not synonymous with parkinsonism, and is not always present: if a patient does not have significant tremor, they may display rigidity without cogwheeling, but still be exhibiting parkinsonism.
• Postural Instability: The “pull test” can be used to assess for postural instability: in this test, the examiner stands behind the patient and gives them a little tug backwards (the pull should be hard enough that a normal person will need to take a step back to keep their balance.) If the patient is able to catch themselves in a step or two, this is considered normal; however, if they need to take more steps to keep their balance, or the examiner needs to catch them, this is considered “retropulsion” and is an indication of postural instability.

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.

Pre-motor symptoms of Parkinson’s Disease

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:

• Hyposmia (changes in smell)
• Constipation
• REM sleep behavior disorder (RBD): This disorder involves loss of atonia that is normally present during REM sleep, causing individuals to act out their dreams, often kicking or punching while asleep. The bed partner of the patient is frequently the one to first notice RBD. RBD has a high rate of phenoconversion to Parkinson’s disease (Galbiati et al 2019, Howell et al 2015), and there is substantial research interest in studying RBD cohorts to try to identify ways to prevent subsequent development of motor symptoms. 

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).

Drug-induced Parkinsonism 

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.

“Red flags” for other parkinsonian syndromes

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:

• Early falls as well as abnormal eye movements suggest progressive supranuclear palsy
• Early severe autonomic dysfunction suggests multiple system atrophy
• Early cognitive issues (executive dysfunction / visuospatial deficits, hallucinations) suggests dementia with Lewy bodies
• Very rapidly progressive, debilitating symptoms in a couple years is usually too fast for idiopathic Parkinson’s disease

Role of imaging in diagnosis

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:

• Atypical symptoms – some atypical parkinsonian syndromes can have particular MRI correlates that mary be useful (Armstrong et al 2020, Bloem et al 2021)
• Lower-body predominant parkinsonism – For patients with significant lower-body parkinsonism (slow, shuffling, freezing gait) without significant tremor or upper-body bradykinesia, an MRI is important to obtain to rule out the following causes of lower-body parkinsonism (Armstrong et al 2020, Bloem et al 2021): 1) Vascular disease – significant frontal white matter disease can cause symptoms of lower-body parkinsonism, and 2) Normal pressure hydrocephalus –  can cause parkinsonian symptoms involving the gait.

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.

Discussing a new diagnosis of Parkinson’s with patients

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.

Management of motor symptoms

Initial treatment

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.

Treatment of advanced 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:

• Enzyme inhibitors such as COMT inhibitors or MAO-B inhibitors can be added to levodopa to help “stretch out” its effect
• Extended release forms of levodopa can also help prolong the medication’s effect and lessen wearing off
• If patients experience levodopa-induced dyskinesias but cannot tolerate lower doses of levodopa due to wearing off, the medication amantadine can be added to help reduce dyskinesias.
• Deep brain stimulation (DBS) is an option for patients experiencing severe motor fluctuations that cannot be optimized with medication. Notably, patients need to have had a good response to levodopa to be a candidate for DBS (Welter et al 2002). Thus, patients with other forms of neurodegenerative parkinsonism that do not respond to levodopa will also not receive benefit from DBS.
• Less commonly, patients with significant motor fluctuations who are not candidates for DBS may be considered for an enteral gel form of levodopa delivered through a GJ tube (Olanow et al, 2014).
• More recently, a subcutaneous form of levodopa has been developed, which essentially acts as a “levodopa pump” akin to an insulin pump (Giladi 2021). This may be a promising mode of delivery looking to the future, and may provide more reliable medication levels due to its ability to bypass the gut.

Management of autonomic symptoms

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. 

Cognitive and psychiatric manifestations of advanced Parkinson’s

Cognitive impairment

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

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.

Mood and anxiety

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. 

Goal

Listeners will develop a framework for the diagnosis of Parkinson’s disease and the management of both motor and non-motor symptoms.

Learning objectives

After listening to this episode listeners will…

1. Recognize common presenting motor and non-motor symptoms in Parkinson’s disease 
2. Develop an approach to the history and physical exam in patients with suspected Parkinson’s disease
3. Recognize potential clues that point away from a diagnosis of Parkinson’s disease
4. Describe a framework for initial treatment of Parkinson’s disease
5. Implement management strategies for dementia, psychosis, and depression in Parkinson’s Disease
6. Develop an approach to common autonomic symptoms in Parkinson’s disease

Disclosures

Dr. Hung reports no financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

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.