Robert C. Flanigan, MD, FACS
Sam J. Brancato, MD
BASICS
DESCRIPTION
• Parkinson disease (PD), also called paralysis agitans is a neurodegenerative disorder associated with loss of dopaminergic neurons.
• Three cardinal features are rest tremor, rigidity, and bradykinesia.
• Postural instability, sometimes deemed a cardinal feature, is nonspecific and usually absent in early disease.
• Autonomic dysfunction is manifested by urinary urgency and frequency, constipation, and orthostatic hypotension. Retention can also be seen.
EPIDEMIOLOGY
Incidence
• PD incidence increases with age, from 17.4 cases per 100,000 persons per year between 50–59 yr of age to 93.1 in 100,000 persons per year between 70–79 yr of age.
• Life risk of developing PD is 1.5%
• Voiding dysfunction occurs in 40–70% of patients with PD.
Prevalence
N/A
RISK FACTORS
• Men are about 1.5 times more likely than women to develop PD
• The median age of onset is 60 yr and the mean duration of the disease from diagnosis to death is 15 yr.
• Young-onset PD affects 5–10% of patients with the initial symptom arising before the age of 50 yr.
Genetics
• About 15% of patients with PD have a 1st-degree relative with the disease, typically without a clear mode of inheritance
• Mutations in two genes cause autosomal dominant forms of PD
– α-Syn gene (SNCA): Located on chromosome 4q
– Leucine-rich repeat kinase 2 (LRRK2): located on chromosome 12q
• To date, approximately 16 risk loci have been identified, some of which overlap with the genes known to contain disease-causing mutations
PATHOPHYSIOLOGY (1)
• Selective loss of dopaminergic projections from the substantia nigra pars compacta (a component of the basal ganglia) to the caudate nucleus and putamen
• Dopamine deficiency in the nigrostriatal pathways accounts for most of the clinical motor features of the disease
• The net effect of the basal ganglia on micturition is inhibitory, which is abolished due to cell loss in the substantia nigra
– The bladder detrusor can thus become unstable and result in urgency and frequency with urge incontinence
• The smooth sphincter is synergic, however pseudodyssynergia, as well as delay in striated sphincter relaxation (bradykinesia) leading to urinary retention (2)
– Impaired detrusor contractility may also occur
• PD can also be associated with bowel dysfunction (constipation) and sexual dysfunction
• Urinary symptoms tend to become worse in the course of the disease. Early on other correctable causes such as benign prostatic enlargement in men can cause similar symptoms
• Centrally acting anticholinergic drugs such as trihexyphenidyl and benztropine have been used to treat PD and can cause urinary retention
ASSOCIATED CONDITIONS
• Autonomic dysfunction
– Constipation
– Orthostatic hypotension
– Urinary urgency/frequency/urge incontinence
• BPH
• Dementia
• Depression
• Sleep disturbance
• Erectile dysfunction
• Hyposmia
• Visual hallucination
GENERAL PREVENTION
N/A
DIAGNOSIS
HISTORY
• Urinary symptoms usually appear after the onset of neurologic symptoms
• Assess for LUTS:
– Storage symptoms: Most common, include nocturia, urgency, frequency, and incontinence
– Voiding symptoms: Difficulty initiating stream, weak FOS/prolonged urination, and straining
• Elevated PVRs are uncommon in PD patients
• Assess for concurrent urologic conditions:
– BPH in men and SUI in women
• Assess for polypharmacy
– Central acting anticholinergics listed below can be used in younger patients in whom tremor is the major symptom but may exacerbate incomplete emptying and urinary retention
– Benztropine mesylate (Cogentin), trihexyphenidyl (Artane), biperiden (Akineton), orphenadrine (Norflex, Flexon)
PHYSICAL EXAM
• Cardinal features are rest tremor, rigidity, and bradykinesia.
• Slow, pill-rolling tremor of the hands (4–6 cycles/s) seen primarily at rest
– Abolished by use of the affected hand
– Aggravated by stress and cold weather
• Facial expressions can be immobile or rigid and speech slowed
• Slow, shuffling gait with loss of normal arm swing (rarely prominent early in the course of PD)
• Assessment of pelvic floor reflexes, motor and sensory
• Digital rectal exam
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• No diagnostic test exists for PD as the diagnosis is clinical.
• Standard urologic evaluation (U/A, C&S) based on initial symptoms
Imaging
• Brain MRI is reserved for patients suspected of having PD who fail to respond to therapeutic doses of L-dopa administered for 12 wk, to exclude rare secondary causes and subcortical vascular pathology.
• Routine urologic imaging is not required.
Diagnostic Procedures/Surgery
• PD is a clinical diagnosis, although the definition of PD is a postmortem finding based on the neuropathologic examination.
• Urodynamics:
– Detrusor overactivity is the most common cystometric abnormality.
– Sporadic involuntary activity in the striated sphincter during involuntary bladder contraction is common, however, this does not cause obstruction.
– Pseudodyssynergia may occur, as well as delay in striated sphincter (bradykinesia) relaxation at the onset of voluntary micturition, both of which can be misinterpreted as true dyskinesia.
– Detrusor areflexia relatively rare in PD and when present may often be due to anticholinergic medications.
• Urodynamics is a useful tool for investigating concomitant obstruction secondary to BPH.
Pathologic Findings
Intraneuronal Lewy bodies and Lewy neurites are the pathologic hallmarks of PD.
DIFFERENTIAL DIAGNOSIS
• Parkinson
– Multiple system atrophy
– Normal aging
– Vascular parkinsonism (multiple infarcts within the basal ganglia and subcortical white matter)
– Parkinson plus syndromes
• Voiding dysfunction
TREATMENT
GENERAL MEASURES
• PD is a progressive neurodegenerative disorder despite treatment.
• Levodopa is the mainstay of therapy for PD and the gold standard against which new therapies are compared.
– In the United States, levodopa is combined with the decarboxylase inhibitor carbidopa (Sinemet).
– Levodopa has been shown to have unpredictable effects on bladder function.
• Clinicians should offer behavioral therapies (eg, fluid management, clean intermittent catherization) as 1st-line therapy.
• Evaluate medications that may result in urinary symptoms (such as retention/hesitancy) with anticholinergic drugs such as trihexyphenidyl and benztropine used to treat some patients with PD.
MEDICATION
First Line
• For urologic symptoms of frequency, urgency, and urge incontinence, anticholinergics are commonly used but should be monitored closely in elderly as they may contribute to cognitive decline (3):
– Oxybutynin 5 mg PO TID
– Tolterodine LA 4 mg PO daily
– Others (solifenacin, fesoterodine, darifenacin, trospium)
• β3-Adrenergic agonist agent: Promotes detrusor muscle relaxation and can also be considered for overactive bladder symptoms
– Mirabegron (25–50 mg)
Second Line
• OnabotulinumtoxinA
– While not specifically approved for PD, it is approved for the treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition in adults who have an inadequate response to or are intolerant of an anticholinergic medication
• The following are used but currently not FDA approved for urinary incontinence
– Tricyclic antidepressants (TCA): Imipramine 10–25 mg PO BID–TID
– Selective serotonin norepinephrine reuptake inhibitors (SSNRIs): Duloxetine 20–40 mg PO BID
• Nocturnal polyuria can be treated with desmopressin
SURGERY/OTHER PROCEDURES
Bladder outlet procedure: Consider if coexisting obstruction is found on urodynamic testing
ADDITIONAL TREATMENT
• PDE5 inhibitors for treatment of erectile dysfunction:
– Sildenafil, tadalafil, vardenafil
• Deep brain stimulation of the subthalamic nucleus may decrease urinary symptoms
Additional Therapies
Incontinence aids may be necessary and are primarily chosen by the degree of absorbency required and the ease of use. During the night, high absorbency pads are usually required.
Complementary & Alternative Therapies
Dietary fiber, laxatives, and prokinetic drugs (such as serotonergic agonists) are used to treat PD-related bowel dysfunction.
ONGOING CARE
PROGNOSIS
• PD is a progressive neurodegenerative disorder.
• Despite a variable disease course, the overall prognosis is poor with a mean duration of the disease from diagnosis to death of 15 yr.
COMPLICATIONS
• Urinary incontinence
– Skin breakdown secondary to incontinence
• Urinary retention (often related to anticholinergics)
FOLLOW-UP
Patient Monitoring
Assess for elevated PVRs, specifically if taking anticholinergics
Patient Resources
National Parkinson Foundation: Urinary Problems in PD. http://www.parkinson.org/NationalParkinsonFoundation/files/6c/6c980d82-f158-481c-97a9-0649ea6ba020.pdf
REFERENCES
1. Yeo L, Singh R, Gundeti M, et al. Urinary tract dysfunction in Parkinson’s disease: A review. Int Urol Nephrol. 2012;44(2):415–424.
2. Sakakibara R, Tateno F, Kishi M, et al. Pathophysiology of bladder dysfunction in Parkinson’s disease. Neurobio Dis. 2012;46(3):565–571.
3. Campeau L, Soler R, Andersson KE. Bladder dysfunction and parkinsonism: Current pathophysiological understanding and management strategies. Curr Urol Rep. 2011;12(6):396–403.
ADDITIONAL READING
• Lees AJ, Hardy J, Revesz T. Parkinson’s disease. Lancet. 2009;373(9691):2055–2066.
• Wyndaele JJ, Kovindha A, Madersbacher H. Neurologic urinary incontinence. Neurourol Urodyn. 2010;29(1):159–164.
See Also (Topic, Algorithm, Media)
• Incontinence, Adult Female
• Incontinence, Adult Male
• Neurogenic Bladder, General
CODES
ICD9
• 332.0 Paralysis agitans
• 788.41 Urinary frequency
• 788.63 Urgency of urination
ICD10
• G20 Parkinson’s disease
• N39.41 Urge incontinence
• R35.0 Frequency of micturition
CLINICAL/SURGICAL PEARLS
• Cardinal features are rest tremor, rigidity, and bradykinesia.
• Urinary incontinence is a common feature of PD due to symptoms of overactive bladder.