AANEM MONOGRAPH ABSTRACT: The bladder has only two essential functions. It stores and periodically empties liquid waste. Yet it is unique as a visceral organ, allowing integrated volitional and autonomous control of continence and voiding. Normal function tests the integrity of the nervous system at all levels, extending from the neuroepithelium of the bladder wall to the frontal cortex of the brain. Thus, dysfunction is common with impairment of either the central or peripheral nervous system. This monograph presents an overview of the neural control of the bladder as it is currently understood. A description of pertinent peripheral anatomy and neuroanatomy is provided, followed by an explanation of common neurophysiological tests of the lower urinary tract and associated structures, including both urodynamic and electrodiagnostic approaches. Clinical applications are included to illustrate the impact of nervous system dysfunction on the bladder and to provide indications for testing. Muscle Nerve 38: 815–836, 2008 NEUROPHYSIOLOGY IN NEUROUROLOGY MARGARET M. ROBERTS, MD, PhD AANEM, Illinois Urogynecology, LTD, Oak Lawn, Illinois, USA Accepted 29 January 2008 The bladder has two essential functions: the storage than 26 billion dollars.1,63,154 This is similar to the and periodic elimination of liquid waste. It has a prevalence of diabetes in the United States6,140 and capacity in the range of 400–500 ml1,2,44,56 in an the total cost of health care for the entire country of average adult but is typically emptied 5–7 times a Switzerland.86 Urinary retention, though less preva- day,3,24 often at much smaller volumes. With an av- lent in the general population, is a common condi- erage urine flow time of less than 30 s,91 the bladder tion in patients with neurologic disorders. It has is actively emptying less than 1% of the time. Thus, been identified in more than 27% of patients admit- the predominant role of the bladder is that of a ted for rehabilitation, with 20% of cases both asymp- reservoir, storing urine at low pressures even during tomatic and unsuspected at presentation.160 Reten- filling to capacity. When necessary, the bladder is tion may be equally burdensome to the individual, also dynamic, responding to increased filling, infec- and untreated; it may result in devastating complica- tion, or even emotional stimuli with elimination at tions including renal failure and death. Until the essentially any volume, any time, as many times as 1970s, upper urinary tract disease was the leading necessary. cause of death in patients with spinal cord injury The significance of normal bladder function may (SCI) and myelomeningocele.57,75,128 be more readily apparent if one considers the impact While impressive for the sheer size of the num- of dysfunction. Urinary incontinence is readily ap- bers, statistics tend to be sterile and dry, failing to preciated as a prevalent and costly problem, affect- capture the human aspect of disease and impair- ing 17 million Americans at an annual cost of more ment. Consider the stigmatization, isolation, loss of self esteem, depression, and risk of institutionaliza- tion that occurs in those with bladder dysfunc- Abbreviations: ASIA, American Spinal Injury Association; BC, bulbocavern- tion.1,43 Failure to maintain continence is a major osus; CAR, clitoroanal reflex; DLPP, detrusor leak point pressure; DSD, de- 141 trusor sphincter dyssynergia; EAS, external anal sphincter; EDX, electro- factor for institutionalization, with more than half diagnostic; EMG, electromyographic; EUS, external urethral sphincter; IC, of those in nursing homes suffering from urinary ischiocavernosus; MUAP, motor unit action potential; NCS, nerve conduction 1,3,43 study; PAG, periaqueductal gray; PAR, peniloanal reflex; PMC, pontine mic- incontinence. Following hemispheric stroke, turition center; SCI, spinal cord injury; SEP, somatosensory evoked potential; urinary continence is the main determinant of dis- VLPP, Valsalva leak point pressure Key words: needle electromyography; nerve conduction study; urinary in- charge home within 6 months, independent of se- continence; urodynamic study; voiding dysfunction verity of hemiparesis.9 Correspondence to: M. Roberts; e-mail: [email protected]. The causes of storage and voiding dysfunction © 2008 Wiley Periodicals, Inc. Published online 14 June 2008 in Wiley InterScience (www.interscience.wiley. are myriad, diverse, and often multifactorial ranging com). DOI 10.1002/mus.21001 from a simple and reversible urinary tract infection AANEM Monograph MUSCLE & NERVE July 2008 815 Table 1. Urinary incontinence. Symptoms and associated cough, laugh, sneeze, or other exertion which ele- conditions1 vates the intraabdominal pressure); urge inconti- Stress nence (which is accompanied by or immediately Inadequate pelvic support with urethral hypermobility preceded by urgency); or continuous leakage. Mixed Inadequate sphincter closure due to anatomic defect or urinary incontinence has features of both stress and functional impairment urge incontinence. While more descriptive, these Lower motor neuron injury categories still fail to define the underlying cause Retention (See text) Low compliance and any combination of these conditions may coex- Pharmacologic agents (adrenergic antagonists, e.g.) ist. In addition, leakage may be insensible and pa- Urge tients may not be able to characterize their urine Detrusor overactivity loss. Common conditions associated with these pre- Idiopathic sentations are indicated in Table 1. Voiding dysfunc- Neurogenic (upper motor neuron involvement) Continuous tion may result from impaired bladder contractility Fistula (due to sensory or motor defects), elevated outlet Ectopic ureter resistance, or a combination of the two. It is often Severe stress incontinence identified after a patient presents with urinary reten- Unrecognized detrusor overactivity tion and complaints of recurrent urinary tract infec- Retention (See below) Low compliance tion, urinary frequency, nocturia, or even inconti- nence, but patients with chronic urinary retention may be asymptomatic in spite of large volume reten- tion (1,000 ml) and associated upper urinary tract injury.53,160 Some causes of urinary retention are to prostatic hypertrophy or cancer, urethral hyper- listed in Table 2. mobility with or without associated pelvic organ pro- lapse, pharmacologic effects, and neurologic dys- function, anywhere along the neuraxis from the OVERVIEW OF NEURAL CONTROL brain to the spinal cord, or in the peripheral nerves Normal bladder function requires the integrity of or ganglia.36 extensive neurologic circuitry of the central and pe- Fortunately, neurourology, the study of the func- ripheral nervous systems supplied by the somatic and tion of the bladder, is a rapidly expanding field. autonomic nervous systems under both voluntary Since this monograph was originally written in and involuntary control.30 While many of the details 1977,35 more than 60,000 publications have ap- have not yet been elucidated, a sophisticated model peared on human bladder function/dysfunction in has been developed over the past eight decades with the English language. The explosion of interest and research with the concomitant emergence of tech- nology has provided new information on bladder function from the molecular level of the neuroepi- Table 2. Causes of urinary retention.1,53 thelium of the bladder wall to the cellular interac- Decreased contractility tion in the frontal cortex of the brain. It is the role of Lower motor neuron injury (cauda equina, radiculopathy neurophysiologists to elicit symptoms and clinical including herpes zoster or simplex, neuropathy) findings which are sometimes nonspecific or silent; Rapid overdistention such as with diuresis. Pharmacologic agents (e.g., anticholinergic) identify those patients in which neurological disease Decreased afferent function is potentially altering bladder function; and exam- Lower motor neuron injury (cauda equina, radiculopathy ine, diagnose, and ultimately ensure implementa- including herpes zoster or simplex, neuropathy) tion of optimal treatment. Analgesics (including alcohol) Outlet obstruction Prostatic hypertrophy (benign or malignant) BLADDER DYSFUNCTION Pelvic organ prolapse Stricture, stenosis, post-operative changes Urinary incontinence is defined by the International Stones Continence Society as “the complaint of any invol- Detrusor sphincter dyssynergia (upper motor neuron untary leakage of urine.”4 It may be a symptom, a dysfunction) sign, or a condition,1 but it is a nonspecific diagnosis Non-neurogenic neurogenic bladder (Hinman syndrome) or and fails to identify the underlying pathophysiologic pseudodyssynergia Pharmacologic agents (e.g., adrenergic agonists) process. It is sometimes categorized by the clinical Combined factors (e.g., diuresis and analgesia such as alcohol) presentation as stress incontinence (occurring with 816 AANEM Monograph MUSCLE & NERVE July 2008 supporting evidence drawn from experimentation in junction with the vascular supply of the area. Perti- animals, monitoring of normal human function, and nent effects of sympathetic stimulation include con- evidence drawn from clinical observation of patients traction of sphincter muscles, relaxation of smooth with neurologic lesions.7 muscle in the wall of hollow viscera, and constriction It is generally accepted that afferent information of blood vessels. The parasympathetic system has a regarding bladder filling is conveyed via the visceral more limited distribution,