11/11/2015

Nonmotor Symptoms of Parkinson's Disease: Recognition, Diagnosis, and Treatment

MULTISPECIALTY
Faculty and Disclosures

CME Information

Print

Excessive daytime sleepiness is, again, a very frequent complaint for

patients with Parkinson's disease and is probably more common than in
the general population. The estimated prevalence is between 15% and
50% of Parkinson's disease patients. The reasons for excessive daytime
sleepiness are, again, likely multifactorial. These may include insomnia;
mood or anxiety disorders; dementia; as well as dopaminergic
medications in terms of a class effect, as opposed to any 1 specific
medication. Risk factors for excessive daytime sleepiness include
increased disease duration and severity, male gender, and dopaminergic
load.

(Enlarge Slide)

One thing that is important to discuss in terms of excessive daytime

sleepiness is what has been termed "sleep attacks," that being the
sudden onset of sleep. This can include naps occurring at inappropriate
times, such as while driving, and these may be sudden and without
warning. There is some controversy whether or not sleep attacks are
true entities in and of themselves or whether they are extensions of
excessive daytime drowsiness. Most studies that have specifically looked
at sleep attacks, especially with respect to driving, have correlated high
Epworth Sleep Scale scores with sleep episodes while driving,
suggesting that the issue really is excessive drowsiness prior to falling

(Enlarge Slide)

asleep, as opposed to a true sleep attack. True sleep attacks likely are
very rare, estimated in approximately 1% of Parkinson's disease patients.
Regardless, it is very important to discuss the issue of excessive daytime
drowsiness and falling asleep at the wheel with all patients with
Parkinson's disease.
The treatment for excessive daytime sleepiness begins with good sleep
hygiene. This includes regular bedtime and waking times and an
appropriate amount of time in bed, which is over 7 hours. During the day,
patients should be exposed to bright light and daytime activities should
be maximized. Likewise, nap frequency and duration should be reduced
during the day, and people should avoid caffeinated and alcoholic
products in the evening. If good sleep hygiene is not enough to improve
symptoms of excessive daytime sleepiness, the reduction of some of the
dopaminergic medications should be considered. Finally, it may be
necessary to add alerting medications, such as modafinil,

(Enlarge Slide)

methylphenidate, or possibly bupropion.

Insomnia, again, is fairly common in patients with Parkinson's disease
and is estimated to occur in 30% of patients. It is most commonly due to
sleep fragmentation and early awakening, as opposed to difficulty falling
asleep. Treatment for insomnia also relates to good sleep hygiene.
Sometimes hypnotic medications may be used, such as zolpidem.
Benzodiazepines have some benefit and sedating antidepressants, such

http://www.medscape.org/viewarticle/527867_5

1/7

11/11/2015

Nonmotor Symptoms of Parkinson's Disease: Recognition, Diagnosis, and Treatment

as trazodone or amitriptyline, are often used.

(Enlarge Slide)
Nightmares are not an unusual occurrence in Parkinson's disease and
are thought to occur in 30% of patients. Nightmares are correlated with
disease severity and levodopa dose. Treatment includes reduction in
dosage of the medications that may be partially causing the nightmares.

(Enlarge Slide)
One promising treatment that may alleviate some aspects of sleep
dysfunction that occur in Parkinson's disease is deep brain stimulation.
Though there has not been much work done on the impact of deep brain
stimulation on sleep, 1 prospective study was recently published. In this
study, the authors examined and performed polysomnographic testing on
5 patients before and 3 months following subthalamic nucleus deep brain
stimulation for Parkinson's disease. This study found that following deep
brain stimulation, there was an increase in total sleep time, with the
lengthening of the longest period of uninterrupted sleep. In addition,
there was a reduction in wakefulness after sleep onset. However, there

(Enlarge Slide)

was no impact on REM behavior disorder or periodic leg movements of

sleep.
Sensory Nonmotor Symptoms
We are now going to shift gears and talk about sensory nonmotor
symptoms, again a very prevalent problem in patients with Parkinson's
disease. These can be thought of as complaints of pain or as other
sensory symptoms, such as burning, tingling, numbness, stabbing,
aching, or itching. These are very difficult symptoms to study, as they are
subjective. The literature is relatively limited with respect to sensory
problems in Parkinson's disease. However, anecdotally it appears that
many patients complain of sensory symptoms prior to the onset of motor
features of Parkinson's.

(Enlarge Slide)

Despite the limited data, there has been a recent study that tried to
quantitatively assess pain perception in Parkinson's disease patients. In
this study, 51 patients with Parkinson's disease were evaluated for
endogenous pain using a visual analog scale, as well as objective
measures, such as heat and pain thresholds (HPTs) and mechanical and
warmth sensory thresholds.

(Enlarge Slide)

http://www.medscape.org/viewarticle/527867_5

2/7

11/11/2015

Nonmotor Symptoms of Parkinson's Disease: Recognition, Diagnosis, and Treatment

The results of the study showed that patients with Parkinson's disease
have significantly lower HPTs than control subjects. The results also
showed that patients with painful Parkinson's disease had significantly
lower HPTs compared with patients with pain-free Parkinson's disease.
Heat and pain thresholds were significantly lower in the more affected
limb, regardless of the presence or absence of pain, and no difference
was found in HPTs between the on- or the off-medication state.

(Enlarge Slide)
Some theories regarding the mechanism of altered pain perception in
Parkinson's disease include that the basal ganglia neurons have
somatic-sensory function. In addition, basal ganglia neurons may
modulate pain.
Sensory Symptom Fluctuation and Summary

(Enlarge Slide)
In contrast to the findings from the previous study, another study
documented that some sensory symptoms may indeed fluctuate during
the day, depending on plasma dopaminergic level. The majority of
complaints occurred in the "off" state.

(Enlarge Slide)
The same study that surveyed these Parkinson's patients for fluctuating
nonmotor symptoms also found that there was a correlation between the
number of sensory fluctuations, the severity of disease, and the level of
disability. Some of the patients also reported that the sensory
fluctuations were the most incapacitating of all nonmotor fluctuating
symptoms.

(Enlarge Slide)
In further support for the impact of sensory symptoms on quality of life,
our group at the University of Pennsylvania has been working to develop
a valid and reliable rating scale to measure the presence, severity, and
impact of nonmotor fluctuations in patients with Parkinson's disease. In
our study, the patients unanimously voted for pain as being the most
bothersome symptom that they encounter.

(Enlarge Slide)
In summary, nonmotor symptoms need to become recognized as part of
the symptom complex of Parkinson's disease by patients and their
healthcare providers. We will need to develop valid and reliable methods
of measuring and evaluating nonmotor symptoms in Parkinson's disease

http://www.medscape.org/viewarticle/527867_5

3/7

11/11/2015

Nonmotor Symptoms of Parkinson's Disease: Recognition, Diagnosis, and Treatment

in order to design clinical trials that can establish the efficacy and safety
of interventions to facilitate clinical decision-making.
Discussion

(Enlarge Slide)
Speaker: Is there some association between sleep disorders prior to the
actual onset of the motor symptoms in Parkinson's disease?

(Enlarge Slide)
Galit Kleiner-Fisman, MD: Given the fact that there are problems with
sleep in the general population, it is very difficult, without motor
symptoms, to necessarily predict the onset of Parkinson's disease just by
virtue of sleep complaints. However, if primary care physicians and other
healthcare providers are cognizant of the fact that there may be a
relationship, they may be able to note the sleep disturbance and then
monitor patients carefully over time for onset of motor symptoms of
Parkinson's disease. Although currently we do not yet have any
treatments that may modify the course or the natural history of the
disease, in the future, if we do have some way to modify the disease,

(Enlarge Slide)

then early diagnosis will be crucial and sleep disturbances may help alert
us to when we need to intervene. In addition, as I mentioned, there are
some conditions that are more correlated with Parkinson's disease than
others, such as REM-behavior disorder. Certainly if a patient has
complaints of REM-behavior disorder, it is important to keep in mind that
Parkinson's disease may occur in the future.
Speaker: It may be that several of these phenomena actually are
preclinical markers of Parkinson's disease.

(Enlarge Slide)
Dr. Kleiner-Fisman: Until recently, when patients came to physicians
and mentioned these nonspecific complaints of pain or sleep
disturbances, patients were often perceived to be malingering or to have
symptoms of depression. It is only now becoming clear that, in fact, these
are part of the Parkinson's disease symptom complex, and we really
need to listen carefully to patients when they tell us these complaints. A
lot of pain complaints may also be mistaken for arthritis problems or

http://www.medscape.org/viewarticle/527867_5

4/7

11/11/2015

Nonmotor Symptoms of Parkinson's Disease: Recognition, Diagnosis, and Treatment

pains that the elderly population commonly have. Many patients tell us
that they have knee, hip, or back problems and subsequently, especially
in our nonmotor fluctuation survey of patients, we found that even these
joint complaints could fluctuate between "on" and "off" states. As such,
these can be attributed to their Parkinson's disease, not just to
degenerative arthritic problems.

(Enlarge Slide)
Speaker: Sometimes the terminology can get a little confusing for the
symptomatology.

(Enlarge Slide)
Dr. Kleiner-Fisman: I think that is, again, a very good point, and one of
the reasons why in our study we pursued focus groups with patients
specifically, because the terminology may vary amongst them and may
not necessarily reflect the symptoms that we, as healthcare providers,
are trying to pursue. It is a question of what words mean to different
people. It is very difficult to use just 1 word to describe a phenomenon,
and often times I ask patients to describe to me specifically what they are
feeling. One of the things I ask them is whether or not their symptoms
change during the course of the day or if symptoms respond to
medications and so forth. Oftentimes we know that dystonia is

(Enlarge Slide)

"medication responsive," and it is an "off" feature. So, that helps

sometimes to get at the underlying symptom.
Discussion (cont'd)
Speaker: For sleep disorders, how do you decide when to just go with a
clinical evaluation vs referring for one of the sleep studies you
mentioned?

(Enlarge Slide)
Dr. Kleiner-Fisman: Some symptoms, especially in a cognitively intact
and articulate patient, can easily be distinguished. Patients may tell you
that they have violent thrashings at night and their partner, for example,
may have some injury as a result of the thrashing suggesting REMbehavior disorder. However, in some cases patients just do not know why
it is that they are not sleeping well. In that case, it may be useful to have
a sleep assessment. This is an all-night videotape monitoring and
electrical recordings of brain and respiratory activity, so that features or
sleep may be further elucidated.

http://www.medscape.org/viewarticle/527867_5

(Enlarge Slide)

5/7

11/11/2015

Nonmotor Symptoms of Parkinson's Disease: Recognition, Diagnosis, and Treatment

Speaker: I think, if there was a definition of "off" states and fluctuations it

might be helpful for a 10-second description of what those are.

(Enlarge Slide)
Dr. Kleiner-Fisman: Symptoms may vary, depending on the "on" or "off"

(Enlarge Slide)

state. When patients take their medications and they alleviate symptoms,
we refer to this as the "on" state. Their function may return to normal.
They may be mobile. They generally feel good during this period of time.
However, as dopaminergic levels may fall prior to taking their next dose
of dopaminergic medication, their symptoms of Parkinson's disease may
return; we refer to this as the "off" state.
Summary
(Enlarge Slide)
In summary, nonmotor symptoms are common and menacing problems
for patients with Parkinson's disease. These are now becoming more
recognized as part of the Parkinson's disease symptom complex by
healthcare providers. Sleep disturbances in Parkinson's disease are
widespread and occur in at least half of all patients and appear to be
correlated to disease severity. Both Parkinson's disease-related and
non-Parkinson's disease-related medications may interfere with sleep. All
patients with Parkinson's disease should be screened for a sleep
disorder, given its high prevalence.

(Enlarge Slide)

In many cases, treatment begins with adequate sleep hygiene. Then

various medications can be manipulated, depending on the specific
etiology of the sleep disorder. Another common nonmotor symptom
complex affecting Parkinson's patients is sensory symptoms that include
pain, which in some cases may be one of the most bothersome
symptoms that patients complain of. Further work needs to be done,
elucidating the mechanism of pain and sensory processing in
Parkinson's disease. In the future, as nonmotor symptoms become more
widely recognized and accepted as part of the Parkinson's disease
symptom complex, new tools that are valid and reliable will need to be
developed to evaluate nonmotor symptoms in order to design clinical
trials establishing the efficacy and safety of new interventions.

Previous

Page 5 of 6

Next Page

Print

About Medscape Education

Priv acy Policy

Terms of Use

WebMD

Medscape France

Medscape Deutschland

WebMD Corporate

Help

All material on this website is protected by copyright, Copyright 1994-2015 by Medscape, LLC. This website also contains material copyrighted by 3rd parties.

MORE

We have updated the Medscape Terms of Use which you may access HERE. By using Medscape, you agree to the Medscape Terms of Use.
close

http://www.medscape.org/viewarticle/527867_5

6/7

11/11/2015

Nonmotor Symptoms of Parkinson's Disease: Recognition, Diagnosis, and Treatment

This website uses cookies to deliver its services as described in our Cookie Policy. By using this website, you agree to the use of cookies.
close

http://www.medscape.org/viewarticle/527867_5

7/7