Neal Hermanowicz, MD

"[We need to] stop this process of neurodegeneration, the loss of neurons that are involved in Parkinson disease, and also find those people who may be at risk. Those people who have REM sleep disorder and impaired sense of smell and get an organized effort to find it early before it becomes such a problem."

The COVID-19 pandemic has lowered the quality of life for many patients with neurological conditions, including those with Parkinson disease (PD). In a newly conducted survey study by the 

Parkinson’s & Movement Disorders (PMD) Alliance

, the increased social isolation because of restrictions around the globe had statistically significant negative associations with the burden of mood and nonmotor symptoms of PD.

Among 718 responders, which included patients with PD (70.6%) and care partners (29.4%), decreased social support from outside of the household during the pandemic had direct impacts on sadness/depression and anxiety. Investigators also observed associations with things like decline in memory, problem solving, or communications, new or worsening confusion, and new or worsening delusions. For patients with PD, the pandemic only elevated the neuropsychiatric symptoms they experience, which in some cases have been known to be more troubling than the motor symptoms.

® to talk about related research for these patients and the emphasis on modifiable activities aimed at improving quality of life. Hermanowicz, a neurologist at Christus St. Vincent Health System, also commented on the need for pharmaceutical help and increased discussion on prevention.

REFERENCE
1. Hermanowicz N, Ospina MC, Torres-Yaghi Y, et al. Impact of isolation during the COVID-19 pandemic on the patient burden of Parkinson disease: a PMD Alliance survey. 

Videos

The neurologist at Christus St. Vincent Health System detailed the areas of research dedicated to understanding more about neuropsychiatric symptoms of Parkinson disease and the root causes of the disease. [WATCH TIME: 3 minutes]

Major Research Goals in Treating Neuropsychiatric Symptoms of Parkinson Disease: Neal Hermanowicz, MD

"Another top symptom that I hear all the time from my patients is the fatigue, and we don’t really have a good grasp on where it’s coming from. What do we do about that?"

In addition to motor symptoms such as slowness of movement, tremor, stiffness, and postural instability, patients with Parkinson disease (PD) face a list of other nonmotor symptoms that can have a significant impact on quality of life. They include things like constipation, cognitive changes, fatigue, hallucinations and delusions, loss of sense of smell or taste, vision problems, and sleep disorders, among others. Some of these symptoms can occur years before the diagnosis of PD.

The treatment toolbox for patients with PD is limited, especially for treating nonmotor symptoms. 

 (Nuplazid; Acadia Pharmaceuticals), a selective serotonin inverse agonist and antagonist, became the first FDA-approved medication for the treatment ofPD psychosis in 2016, and since then, there has been little other progress. 

, a neurologist at Christus St. Vincent Health System, believes there needs to be more attention to the nonmotor symptoms, as many patients feel as though these symptoms are even more bothersome than the motor issues they face.

, he discussed the urgent need for new medications to treat motor and nonmotor symptoms of PD.

The neurologist at Christus St. Vincent Health System provided insight on the desperate need for new medications for both motor and nonmotor symptoms of Parkinson disease. [WATCH TIME: 3 minutes]

The Need to Address Nonmotor Symptoms in Parkinson Disease: Neal Hermanowicz, MD

"Going to museums [and] engaging in cultural activities is good for us. It’s not just that we enjoy it, it’s actually good for our health. At some point, if you’ve lived by the age of 25, you’ve experienced a sense of home sickness or heartbreak, and these are realities. These are not just something in the air, these are things that affect our health and make us feel not so good. Changing those things can have a huge impact on the well-being of people."

Although sometimes difficult to chart, clinicians have traditionally thought that social connectedness has a positive impact on overall health. For patients with Parkinson disease (PD), social isolation, exasperated by the COVID-19 pandemic, has had a significant effect on burden of mood and motor and nonmotor symptoms. This was confirmed in a recently published study by the 

Parkinson and Movement Disorders Alliance

 (PMD Alliance) in which patients with PD and care partners answered questions from a survey.

The analysis also showed that decreased social support from outside of the household during the pandemic was significantly associated with increases in sadness/depression and anxiety, compared with maintained levels of social support (

<.0001 for both comparisons). Lead author 

, neurologist, Christus St. Vincent Health System, believes the study speaks for itself, and the data add more value to the importance of social connectedness.

, he was asked about the precursors to social isolation, in which he stressed the need to encourage the social aspects early on in a patient’s diagnosis. He noted the benefits these interactions may bring, citing a 2019 study that suggested that loneliness was correlated with individual differences in volumes of brain regions that are central to cognitive processing and emotional regulation.

2022;18:633-643. doi:10.2147/NDT.S351691
2. Duzel S, Drewelies J, Gerstorf D, et al. Structural brain correlates of loneliness among older adults. 

2019;9(1):13569. doi:10.1038/s41598-019-49888-2

The neurologist at Christus St. Vincent Health System provided commentary on the importance of emphasizing social connectedness following diagnosis of Parkinson disease, along with the signs to look for in social isolation. [WATCH TIME: 4 minutes]

Precursors to Social Isolation in Parkinson Disease: Neal Hermanowicz, MD

"Some people with this diagnosis tend to pull back on their social connections, and that’s not good. All of us who’ve been doing this for a while have had that intuitive sense, but now we have data from our study showing that this is an important component."

Although the benefit of socializing has been difficult to quantify, many experts agree that social support is beneficial for patients with movement disorders. Because of the restrictions caused by the COVID-19 pandemic, social isolation has become a more common theme for these patients and remains a challenge that clinicians are attempting to tackle. One study performed by the 

Parkinson’s and Movement Disorder (PMD) Alliance

 found that decreased social support from outside of the household during this time was associated with increases in sadness/depression and anxiety for patients with Parkinson disease (PD), compared with maintained levels of social support (

The data also revealed that this decline was associated with the burden of several motor PD symptoms as well as nonmotor symptoms, such as decline in memory, problem solving, or communication (

 < 0.0001), and new or worsening delusions (

 = 0.018). Lead investigator Neal Hermanowicz, MD, believes that above all the findings, the greatest takeaway should be the valued importance of social connectedness. As a neurologist at Christus St. Vincent Health System, he admitted that it can be difficult to remind patients about its importance, but that it is something of which all clinicians, caregivers, and patients alike should be cognizant.

, Hermanowicz discussed the ways the clinician community can improve the social support patients with PD receive, along with the benefits social connectedness that may not be portrayed through data. He also stressed emphasizing this aspect of care to young neurologists in education, noting that many of the conversations have traditionally been dominated by studying the pathology and pharmacology of this disease.

The neurologist at Christus St. Vincent Health System discussed why social behaviors are an important component of optimal care for patients with Parkinson disease and the need to improve social support for this population.[WATCH TIME: 3 minutes]

Improving Social Support, Recognizing Importance of Social Interaction in Parkinson Disease: Neal Hermanowicz, MD

The symptoms experienced by people with Parkinson disease (PD) are extensive, and it can be daunting even for an experienced clinician to sort through the diverse symptoms that patients present with. In addition to problems with mobility patients often experience fatigue, weight loss, sleep disorders, bladder and bowel dysfunction, mood disturbance, cognitive decline, and psychosis.

During these visits, providers must prioritize and be especially attentive to those symptoms that have the potential to be particularly disruptive to the patients and their caregivers. Although the list of problems associated with PD is long, only a small number may be especially and acutely derailing. Although this includes falls and associated injuries, infections, stool impaction and bowel obstruction, in this article, I focus on psychosis.

Psychosis symptoms in PD consist of hallucinations and delusions. The hallucinations are most commonly visual but may involve any of the senses. When hallucinations are initially present, they typically manifest as a sense that someone is standing beside or behind them, or that someone or something has passed through the periphery of their vision. Patients may also have visual illusions, seeing an object differently than what it truly is. A roadside fire hydrant might appear to be a child, or a potted plant appears to be an animal.

Although initially infrequent and nonthreatening, over time the hallucinations generally occur more often, are more complex, involve other senses and become distressing. Patients with PD psychosis symptoms may buy food and set their table for hallucinated guests; refuse to enter their bedrooms or their bathrooms because of their perception that strangers are lurking there; flee their homes to escape, call the police, or arm themselves because the hallucinated intruders are perceived as intending to harm them.

PD psychosis delusions often have content that is paranoid or consists of spousal infidelity. Theft of money or possessions, poisoning by food or medications, including by spouses, family members, or caregivers, are recurrent themes of delusions. Spousal infidelity with hired caregivers, friends and neighbors is a common delusion.

The psychosis symptoms can turn a difficult situation of coping with PD into an untenable one. They worsen quality of life for patients and caregivers, they are a common reason that PD patients present to emergency departments and are admitted to a hospital, and they are the leading reason that PD patients leave their homes for continued care in a skilled nursing facility.

Psychosis symptoms are common in patients with PD. Reported prevalence of psychosis is variable and time dependent-it increases with the duration of illness. One relatively small prospective multicenter 

 reported that 74% of PD patients experienced visual hallucinations at the 20-year follow up.

Although psychosis symptoms were previously regarded as adverse effects of dopaminergic medication, it has become clear that this is not entirely correct. Medications do play a role, but neither the medication type nor dosage are clearly correlated with psychosis. Moreover, psychosis symptoms have been 

 in patients who have not received any medications for PD.

The brain substrate enabling hallucinations appears to include parkinsonism with Lewy body pathology, and an increased density of serotonin receptors in the temporal cortex. Risk factors identified for PDP include REM sleep behavior disorder, dementia, depression, patient age as well as duration and severity of PD.

Interestingly, patients and caregivers do not necessarily report these symptoms during their appointments with their treating provider. There are several possible explanations for this: lack of recognition that hallucinations and delusions are part of PD, embarrassment about mental health issues, or that there are too many PD symptoms to discuss in a visit with time constraints.

Nonpharmacological treatments for PD psychosis such as reassurance and discussion with the patient are being explored but have not yet been firmly established. Some basic points are worth considering. One of the most important things is making sure that the patient does not have access to guns or other weapons. In addition, it is important to keep in mind that abother acute or subacute illness may cause these symptoms to emerge or increase-symptoms may be due to a simple problem such as a urinary tract infection or something more complex such as a subdural hematoma. Since hallucinations tend to occur in the evening and nighttime with lower light, well lighted rooms and a nightlight may provide some benefit.

Another important factor to consider is how medications are contributing to PD psychosis. Anticholinergic medications (eg, diphenhydramine, oxybutynin) that enter the CNS should be avoided. When possible, reduce or eliminate Parkinson medications, all of which may have a provocative effect on psychosis. Opinions vary on the which medications to reduce or discard, but most experts agree anticholinergics such as trihexyphenidyl and benztropine mesylate should be the first to go.

There is less agreement about the sequence for reduction/elimination of other medications such as amantadine, dopamine agonists, and MAO and COMT inhibitors. Levodopa is generally regarded as the centerpiece for treatment of motor symptoms of PD, and therefore is usually the last medication to be reduced, but seldom, if ever, removed. The method of addressing psychosis symptoms by PD medication adjustment has not been examined in a large clinical study and therefore the success rate, complications, and time course have not been reliably established.

Pharmacological choices to actively treat PDP symptoms have historically included quetiapine and, less commonly, clozapine. Although quetiapine has been commonly prescribed for PD psychosis, studies have been small and short in duration with 

 Clozapine, on the other hand, has demonstrated efficacy for psychosis in two clinical trials, although, again, relatively small and of short duration.

Although clozapine was found to be efficacious for PD psychosis, there is 

 Clozapine is infrequently prescribed, presumably because of the burdensome requirement for monitoring blood counts for the small but potentially fatal risk of neutropenia. Many people, including experienced clinicians, feel that quetiapine has been beneficial for PD psychosis. The discrepancy between formal studies and anecdotal observations is difficult to explain.

Pimavanserin was developed specifically to treat PD psychosis by its action at serotonin receptors, a quality 

 Pimavanserin was also developed to avoid interactions with other neurotransmitters, particularly dopamine. Pimavanserin has a relatively long half-life of 57 hours, compared with about 6 hours and 14 hours for quetiapine and clozapine, respectively. This means clinical response to pimavanserin may require several weeks to fully assess its efficacy. On the other hand, the long half-life allows for once daily dosing, which is attractive for patients who may be taking several other medications numerous times daily.

 that led to FDA approval of pimavanserin for PD psychosis, mean improvement of psychosis symptoms of 37% was seen with the active treatment compared with 14% for placebo.

 Adverse effects included confusion, peripheral edema, and increased hallucinations. As with quetiapine and clozapine, and, for that matter, all antipsychotic medications, pimavanserin has a black box warning about increased risk of death in elderly patients with dementia-related psychosis. However, unlike other antipsychotics, the warning further states that pimavanserin is 

 only for hallucinations and delusions associated with PD psychosis.

 The FDA label also carries a warning regarding QT interval prolongation.

At the time of this writing, the lay press was reporting that a number of patients with PD psychosis had died after being treated with pimavanserin. It has not been established that pimavanserin played a causative role in these deaths-no additional cautions have been issued by the FDA regarding associated risks. PD psychosis itself is an 

Routine querying of patients and caregivers about PDP symptoms is essential for optimal care of patients with PD. Identification of PD psychosis symptoms and earlier treatment may prevent escalation to crises situations and attendant evaluations in emergency departments and hospitalizations, and conceivably allow care to continue at home.

This article was originally published on May 29, 2018, in our partner publication, 

Dr Hermanowicz reports that he is on the Speakers Bureau and a Consultant for Acadia.

The Sydney multicenter study of Parkinson disease: the inevitability of dementia at 20 years

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Minor hallucinations occur in drug-naive Parkinson's disease patients, even from the premotor phase

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On the discovery and development of pimavanserin: a novel drug candidate for Parkinson's psychosis

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Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial

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What predicts mortality in Parkinson disease? A prospective population-based long-term study

Articles

Psychosis symptoms in patients with Parkinson disease can turn a difficult situation into an untenable one: they are the leading reason that patients leave their homes for continued care in a skilled nursing facility.