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International Parkinson and Movement Disorder Society
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Autonomic Issues in Parkinson's Disease

Autonomic Issues in Parkinson's DiseaseDate: April 2017
Authors: Nestor Galvez-Jimenez, MD, MSc, MHA; Ramon Lugo-Sanchez, MD; Tarannum Khan, MD
Editors: Michael S. Okun, MD, and Stella M. Papa, MD

What do you really need to know about autonomic issues in Parkinson’s disease?

Recent advances as well as experience accrued when caring for patients with Parkinson’s’ disease (PD) has revealed that autonomic disturbances are an integral component of the evaluation of patients and that their symptoms have often become a source of disability. Autonomic symptoms in PD include but are not limited to sweat, cardiovascular dysfunction, and gastrointestinal urogenital system failure, which together or in various combinations may affect quality of life (QOL) and also therapeutic outcomes. Three experts from the Cleveland Clinic address the common questions on autonomic PD dysfunction.

Dr. Nestor Galvez-Jimenez: How should orthostatic hypotension be defined? Current consensus by the American Autonomic Society defines changes in orthostatic blood pressure as a drop of 20 points systolic or of 10 points diastolic (measure in mm of Hg) pressure within three minutes of standing. Other symptoms that may accompany such BP changes include an excessive and inappropriate heart rate response to standing, which when greater than 130 beats per minute, defines the presence of postural tachycardia. The diagnosis is also possible when the heart rate is below 130, but above the normal expected value for that individual’s age and gender. It is important to keep in mind that other factors including medication related effects and dehydration as well as intravascular volume depletion may affect PD patients. When suspicious of one of these issues, a spot urine sodium excretion may be obtained.

Are there other 'orphan' or nonspecific symptoms that may suggest the presence of cardiovascular or hemodynamic autonomic dysfunction?

Dr. Ramon Lugo-Sanchez: Some patients may complain of feeling fatigue with a sense of generalized weakness, neck and shoulder pain or heaviness (so called coat hanger sign), mental fogginess and at times frank intermittent confusion. These commonly heard complaints may be a manifestation of a smoldering orthostatic hypotension, orthostatic intolerance, or abnormal cardiovagal/baroreflex control.

Is treatment with levodopa the cause of orthostatic hypotension?

Dr. Tarannum Khan: Over the past decade, studies have shown that the long held view of orthostatic hypotension resulting from levodopa treatment is not completely correct.  Studies by the Clinical Neurocardiology Section at the National Institutes of Health (NIH) have demonstrated that orthostatic hypotension can be present in patients with Parkinson disease with and also in those without exposure to levodopa therapy.  This group has shown that plasma norepinephrine levels, which may represent a marker for peripheral sympathetic denervation, are partially affected in PD patients when compared to controls and to those with pure autonomic failure.  In this group’s experience, orthostatic hypotension in PD reflects sympathetic neurocirculatory failure as part of a generalized sympathetic denervation. Further, cardiac sympathetic denervation has been demonstrated by the same group in PD patients when using 6-[18F]fluorodopamine-derived cardiac PET scanning. Recent evidence also suggests that orthostatic hypotension may specifically affect cognition in those PD patients with the PDOH complex.

Which other dysautonomias may be observed in Parkinson's disease patients?

Dr. Nestor Galvez-Jimenez: Heat or cold abnormalities may be an associated complaint in some PD patients.  The cold hands/cold feet symptom complex may be a manifestation of such dysautonomic complaints. Using sweat studies, the function of post ganglionic sympathetic sudomotor cholinergic axon may be assessed and found abnormal in some patients with a small fiber neuropathy, or as part of a more widespread neurodegenerative autonomic failure disorder, such as Parkinson’s disease, Parkinsonism (Multiple system atrophy) or other conditions such as diabetic neuropathies.  In patients with multiple system atrophy, sweat disturbances have been shown to be of central origin affecting the presynaptic component of a reflex arc.

Are there any gender differences in autonomic symptoms affecting PD patients?

Dr. Tarannum Khan: There appear to be no significant gender differences among Parkinson’s disease patients involving both the central and peripheral autonomic nervous system, although the literature on the topic is sparse for women sufferers.  Nonetheless, the manifestations may differ in some cases, as women with MSA have preferential bladder involvement at onset, and/or preceding the onset of motor symptoms as compare to men who usually present with erectile dysfunction.

How do you assess erectile dysfunction in the patient with PD?

Dr. Ramon Lugo-Sanchez: One of the most specific autonomic problem affecting men with PD is erectile dysfunction (ED).  Infrequently, patients will not volunteer this information because of embarrassment, fear of being judged, feeling “less of a man” or simply not appreciating that symptom can be part of a Parkinsonian syndrome.  Hence, quite frequently these issues are underecognized complaints.  The three most common causes of sexual dysfunction are drugs, medical comorbidities and psychological issues.  Once the issue of ED is brought to the attention of an expert provider, the next step is to find common conditions that may affect erectile function and are not directly related to PD.   Conditions such as hyperlipidemia, diabetes mellitus, trauma or psychogenic dysfunction all should be evaluated and addressed. We must remember to exclude medication related side effects when assessing ED complaints.

Additionally, we always recommend a urological evaluation for a more detailed assessment and management plan.  A PD patient may desire to schedule sexual activity during the time of the day when medications are optimally working (i.e. on periods without dyskinesia).  Advice to patients and their sexual partners should also be directed to find sexual activities and/or positions that are comfortable.  Regarding treatment, ED in some patients may respond to sildenafil or apomorphine.  However, these medications may render orthostatic hypotension worse. Educating about medications and the possibility for worsening is critical.  Referral to a sex therapist may be rewarding for a couple.

Are there other urological complaints in men besides ED?

Dr. Nestor Galvez-Jimenez: Urinary incontinence may be present and is likely related to dysfunction of the parasympathetic or sympathetic component of the autonomic nervous system.  It is important to recognize other non-PD causes, particularly prostate gland hypertrophy as this may lead to incomplete bladder emptying and to increasing the risk for urinary tract infection (UTI).  Treatment can include antibiotics for UTI, special underwear for motor limitations or special considerations for those who cannot tolerate medications. Tamsulosin for patients with prostate hyperplasia may be helpful.  Anticholinergic medications can be rarely and selectively tried, however they may lead to confusion and other side effects.                      

What are the chief manifestations of autonomic dysfunction specific to female Parkinson’s patients?                       

Dr. Tarannum Khan: Although there is substantial evidence supporting sexual dysfunction in PD, there are a paucity of studies on sexual dysfunction in women. In one study published in 1997 by Welsh et. al 27 women with a diagnosis of PD were compared with community controls without PD. There was an increased prevalence of sexual dysfunction in the PD affected women. In a prior study by Osborn et. al regarding sexual dysfunction in women drawn from a community population, 66% had complaints about sexual dysfunction.  In this study, the most commonly affected sexual dysfunction was decreased sexual interest (lack of desire), vaginal dryness (lack of arousal), infrequent orgasm and sexual pain. Other possible contributory factors were vaginal tightness (affecting the 4th phase of sexual intercourse: resolution in the sexual cycle of females, the first 3 being desire, arousal and orgasm). In addition, other factors have been reported such as involuntary urination, and general muscle tightness. Another important contributory factor was depression, which could have been present in a third or more of PD affected patients. Depression can contribute to or be the root cause of sexual dysfunction.

Bladder dysfunction is also common in PD and seems to be related to autonomic dysfunction. Specific studies in woman are again lacking. The most common symptoms are increased frequency, urgency and nocturia. These symptoms are due to detrusor muscle hyperactivity. Hypoactive detrusor muscle has been less commonly observed and can lead to urinary retention.

What’s  is the best approach to sexual issues?

Dr. Tarannum Khan:To adequately address the sexual issues in PD women, a general medical examination, an overall assessment of medication therapy, an assessment of other underlying psychological issues, and a possible assessment of any underlying hormonal issues may all be possibly required. The management approach usually begins with treating underlying possible depression with psychotherapy/medications, treating underlying urinary incontinence, and using pelvic physical therapy (if needed). For vaginal dryness and painful intercourse, vaginal estrogen therapies (creams, vaginal tablets and rings) and vaginal moisturizers or lubricants can be used. Many of these therapies will require a consultation with a gynecologist with expertise or interest in sexual dysfunction. Further, a sex therapist may help to provide insights into psychological issues and may provide counseling on marital issues. The usual approach for bladder related symptoms may include urodynamic studies and urological consultation as well as a general medical evaluation. All patients should also undergo a detailed medication review.  Once the cause of sexual dysfunction has been identified, the treatment may include the use of oxybutynin or tolterodine. Occasionally botulinum toxin injections used for bladder wall relaxation in hyperactive detrusor may be helpful in addressing urinary incontinence. An evaluation by an expert is always a great idea as there are also less common causes of sexual dysfunction, many of which are treatable.

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