Urodynamic Study in Multiple System Atrophy: A Retrospective Observational Study

Abstract

This retrospective study aimed to evaluate the characteristics of neurogenic bladder in patients with multiple systemic atrophy and distinguish between cerebellar and parkinsonian-type urodynamic patterns. We reviewed 19 patients diagnosed with multiple systemic atrophy with low urinary tract symptoms who underwent an urodynamic study at Pusan National University Yangsan Hospital between March 2010 and February 2022. This study did not account for the differences observed between the multiple system atrophy subtypes in the voiding phase. Urodynamic study is an effective tool to understand the complicated bladder pattern in patients with multiple system atrophy.

Highlights

• • Urinary symptoms are the most common clinical features of multiple system atrophy.

• • Urodynamic study revealed decreased detrusor contractility in voiding phase.

• • Urodynamic evaluation is necessary for the patients with multiple system atrophy.

INTRODUCTION

Multiple system atrophy (MSA) is a known, fatal, adult-onset neurodegenerative disease characterized by progressive autonomic failure and various combinations of parkinsonian or cerebellar and pyramidal features [1]. There are 2 types of MSA: the parkinsonian subtype (MSA-P), which is characterized by bradykinesia, rigidity, and an increased risk of falls [2], and the cerebellar subtype (MSA-C), which is characterized by a predominant motor presentation, such as cerebellar ataxia [2,3]. Over the course of the disease, patients with MSA commonly experience lower urinary tract symptoms (LUTS), such as urinary frequency, incontinence, urinary urgency, or nocturia, with an estimated prevalence of over 90% [4,5]. Urinary dysfunction is a differential diagnostic indicator, and urinary incontinence is considered a diagnostic criterion in the second consensus statement on the diagnosis of MSA [6].

Few studies are available regarding the patterns of the urodynamic findings of MSA, urinary symptoms, and bladder contractility between the MSA subtypes [7,8]. Therefore, this retrospective study aimed to evaluate the characteristics of neurogenic bladder in patients with MSA and distinguish between the urodynamic patterns in the subtypes of MSA through a urodynamic study, the gold standard for neurogenic bladder assessment.

MATERIALS AND METHODS

Participants

We reviewed patients diagnosed with probable or possible MSA according to clinical criteria [6]. MSA subtypes were classified by neurologists according to consensus criteria [9]. All patients had LUTS and underwent an urodynamic study at our clinic between March 2010 and February 2022. Data on patient age, sex, LUTS, medication history, and time from symptom onset were obtained from the medical records. Symptom onset was defined as the onset of any urological symptoms regardless of their type, including frequency (≥ 8 micturition episodes per day), urgency, nocturia (≥ 2 micturition episodes per night), incontinence, or residual sensations. Disease progression was assessed using the Unified Multiple System Atrophy Rating (UMSARS) part IV score at the time of examination (Table 1). A total of 44 patients were reviewed; however, 25 were excluded due to incomplete medical records (Fig. 1). The study protocol was approved by the Institutional Review Board of Pusan National University Yangsan Hospital (IRB reference number: 05-2023-052), and the requirement for informed consent was waived due to the retrospective study design.

Table 1. Clinical characteristics and demographics of patients.

Characteristics		Overall (n = 19)	MSA-P (n = 7)	MSA-C (n = 12)	p value
Sex
	Male	8 (42.1)	3 (42.9)	5 (41.7)	0.663
Age at symptom onset (yr)		58.6 (55.4–62.1)	58.0 (56.1–59.2)	60.0 (55.7–63.9)	0.384
Age at examination (yr)		62.9 (58.9–65.6)	59.5 (56.9–63.1)	64.3 (60.3–66.8)	0.164
Disease duration (mon)		25.9 (19.6–44.9)	24.7 (16.7–29.7)	29.2 (19.7–61.7)	0.592
UMSARS part IV		2 (2–3)	2 (1–3)	2 (2–3)	0.432
Clinical features
	Orthostatic hypotension	12 (63.2)	4 (57.1)	8 (66.7)	0.526
	Frequency	14 (73.7)	5 (71.4)	9 (75.0)	0.634
	Nocturia	14 (73.7)	5 (71.4)	9 (75.0)	0.634
	Urgency	7 (36.8)	3 (42.9)	4 (33.3)	0.526
	Residual sensation	15 (78.9)	6 (85.7)	9 (75.0)	0.525
	Incontinence	16 (84.2)	7 (100.0)	9 (75.0)	0.227
Medication
	Levodopa	7 (36.8)	6 (85.7)	1 (8.3)	0.002*
	Carbidopa	1 (5.3)	1 (14.3)	0 (0)	0.368
	Amantadine	4 (21.1)	1 (14.3)	3 (25.0)	0.525
	MAO-B inhibitor	2 (10.5)	1 (14.3)	1 (8.3)	0.614
	Alpha-blocker	8 (42.1)	3 (42.9)	5 (47.0)	0.663

Values are presented as median (interquartile range) or number (%).

MSA-P, multiple system atrophy-parkinsonian type; MSA-C, multiple system atrophy-cerebellar type; UMSARS, unified multiple system atrophy rating scale; MAO-B, monoamine oxidase type b.

^*Asterisk indicates statistical significance (p < 0.05).

Fig. 1. Flowchart showing the patient selection process.

Urodynamic study

The urodynamic study (Medical Measurement System, Amsterdam, Netherlands; MMSTM) was conducted according to the International Continence Society urodynamic guidelines [10]. To record vesical pressure (P_ves), we inserted a 6-Fr double lumen catheter into the bladder and measured the abdominal pressure (P_abd) using a 10-Fr balloon catheter inserted into the rectum, which was then filled with 20 mL of distilled water. For the procedure, patients were placed in a supine position, and warmed normal saline was infused into the bladder at a speed of 24 mL/min; up to 600 mL saline was infused unless the patient experienced a strong urge to void or 2 consecutive spontaneous leakages occurred. The detrusor pressure was obtained indirectly by subtracting the P_abd from the P_ves.

The intra-vesical and intra-abdominal pressures were continuously measured, and sphincter activity was measured using surface electrodes. Primary outcome data were cystometric bladder capacity, compliance, detrusor sphincter dyssynergia (DSD) assessed via surface electromyography, and post-void residual volume (PVR). For data analysis in the urodynamic study, we defined normal bladder sensitivity as the feeling of the first sensation when the bladder was filled with 252.9 ± 124 and 153.5 ± 91.6 mL in males and females, respectively [11]. Patients with a PVR less than 100 mL and compliance less than 20 cmH₂O/mL were defined as normal, whereas those with a PVR greater than 100 mL and compliance less than 20 cmH₂O/mL were considered to exhibit incomplete bladder emptying.

Statistics

Quantitative data were analyzed using SPSS version 27.0 (IBM Corp., Armonk, NY, USA). The Kolmogorov–Smirnov test was used to prove the non-normality of the data, Fisher’s exact test was used to analyze categorical data, and the Mann–Whitney U test was used for distributional data. A p value of 0.05 indicated statistical significance.

RESULTS

Demographic data

A total of 178 patients were diagnosed with probable or possible MSA; however, only 44 underwent a urodynamic study at our institution. Of the 44 patients, 25 were excluded due to incomplete medical records. At the first urodynamic examination, the median age was 62.9 years, with a disease duration of 25.9 months. Regarding the clinical features, 16 (84.2%), 15 (78.9%), 14 (73.7%), 12 (63.2%), and 7 (36.8%) patients complained of urinary incontinence, residual sensation, urinary frequency and nocturia, orthostatic hypertension, and urinary urgency, respectively (Table 1).

Of the 19 patients, 7 were diagnosed with MSA-P and 12 with MSA-C. There were no significant differences between the subgroups regarding age at urodynamic examination, disease duration, or disease progression, as assessed using the UMSARS part IV score. In addition, clinical symptoms, including orthostatic hypotension or LUTS, such as frequency, nocturia, urgency, residual sensation, and incontinence, showed no statistically significant differences between the subgroups. Medical history, including the use of alpha-blockers, amantadine, or carbidopa, showed no significant differences, except for the proportion of patients using levodopa (Table 1).

Urodynamic data

In the filling phase, the patients’ bladder sensitivity was reported to be normal (26.3%), hypersensitive (36.8%), or hyposensitive (36.8%); the median cystometric bladder capacity was 433 mL (interquartile range [IQR], 325–500), and the median compliance was 28 mL/cmH₂O (IQR, 13.6–58.5). In the filling phase, 3 patients (15.8%) reported detrusor overactivity (DO), 2 reported terminal DO, 1 reported sustained DO, and 16 (84.2%) reported normal detrusor. In contrast, in the voiding phase 15.8% reported normal, 31.6% reported underactive, and 52.6% reported acontractile bladder. The median PVR was 338 mL (IQR, 227–464.5), and 16 patients (84.2%) complained of incomplete bladder emptying. In addition, 31.6% of the patients reported DSD.

The MSA subtypes showed no significant differences in bladder sensitivity, PVR, maximum detrusor pressure in the voiding phase, or bladder type in the filling and voiding phases. The MSA-C group showed lower cystometric bladder capacity (median, 350 mL), lower compliance (median, 15.8 mL/cmH₂O), and higher incidence of DSD (50%) than the MSA-P group (433 mL, 74.8 mL/cmH₂O, and 0.0%, respectively) (p < 0.05) (Table 2).

Table 2. Urodynamic study results and comparison between subtypes.

Variables		Overall (n = 19)	MSA-P (n = 7)	MSA-C (n = 12)	p value
Bladder sensitivity					0.165
	Normal	12 (63.1)	3 (42.9)	9 (75.0)	-
	Hypersensitivity	1 (5.3)	0 (0.0)	1 (8.3)	-
	Hyposensitivity	6 (31.6)	4 (57.1)	2 (16.7)	-
Cystometric bladder capacity (mL)		433.0 (325.0–500.0)	533.0 (485.0–551.0)	350.0 (289.5–437.3)	0.004*
PVR (mL)		338.0 (227.0–464.5)	479.0 (263.5–512.0)	319.0 (220.3–359.5)	0.260
Incomplete bladder emptying		16 (84.2)	6 (85.7)	10 (83.3)	0.704
Bladder compliance (mL/cmH2O)		28.0 (13.6–58.5)	71.8 (48.6–107.5)	15.8 (7.1–28.4)	0.001*
Abnormal compliance		7 (36.8)	0 (0.0)	7 (58.3)	0.016*
Bladder type in filling					0.223
	Normal	16 (84.2)	7 (100.0)	9 (75.0)	-
	Terminal DO	2 (10.5)	0 (0.0)	2 (16.7)	-
	Sustained DO	1 (5.3)	0 (0.0)	1 (8.3)	-
Bladder type in voiding					0.536
	Normal	3 (15.8)	1 (14.3)	1 (8.3)	-
	Underactivity	6 (31.6)	1 (14.3)	5 (41.7)	-
	Acontractile	10 (52.6)	5 (71.4)	6 (50.0)	-
Maximal Pdet in voiding phase (cmH2O)		19 (14–41)	15 (6–28)	25 (16–44)	0.167
DSD		6 (31.6)	0 (0.0)	6 (50.0)	0.034*

Values are presented as median (interquartile range) or number (%).

MSA-P, multiple system atrophy-parkinsonian type; MSA-C, multiple system atrophy-cerebellar type; PVR, post-void residual volume; DO, detrusor overactivity; P_det, detrusor pressure; DSD, detrusor sphincter dyssynergia.

^*Asterisk indicates statistically significant (p < 0.05).

DISCUSSION

Patients with MSA are known to develop LUTS, which include urinary urgency and frequency, urge incontinence, and nocturia [1]. The most frequent initial symptom of MSA is bladder dysfunction, as mentioned in the second consensus statement of the Movement Disorder Society [5]. However, previous urodynamic studies have demonstrated that patients with MSA show characteristics of impaired bladder sensation, decreased bladder compliance, detrusor overactivity in the filling phase, acontractile or underactive bladder in the voiding phase, and increased PVR (Table 3) [4,5,7,8,12,13,14].

Table 3. Typical urodynamic findings of patients with MSA.

Phase	Urodynamic findings
Filling phase	Impaired bladder sensation
	Decreased compliance
	Uninhibited external sphincter relaxation (Urine leakage)
Voiding phase	Weak detrusor contraction (Underactive/Acontractile detrusor)
	Detrusor sphincter dyssnergia
	Incomplete bladder emptying (Increased post-void volume)
	Lower maximal flow rate

MSA, multiple system atrophy.

In this study, the patients complained of LUTS: frequency (73.7%), nocturia (73.7%), urgency (36.8%), residual sensation (78.9%), and incontinence (84.2%). Every patient (100%) had at least one of the described symptoms. Urinary dysfunction is one of the most common clinical manifestations of MSA. In some previous studies, patients with MSA showed a higher prevalence of frequency (43%–45%), nocturia (65%–69%), urinary urgency (64%), and incontinence (66%–75%) than healthy controls [11,15]. However, urinary symptoms are descriptive, and it is difficult to reflect the pathophysiology of dysfunctional voiding in patients with MSA.

In the urodynamic studies, our subjects showed a larger PVR with decreased bladder sensitivity, decreased compliance, impaired contractility, and DSD. In contrast, DO and associated leakage were less prominent in this study. These results were similar to those of previous studies and the characteristic urodynamic findings of MSA [4,7,8,12,13,14]. Currently, urodynamic study is the gold standard for determining the etiology of voiding dysfunction and LUTS [16]; it is useful not only to obtain the objective results of bladder function but also to accurately diagnose and determine the treatment or compensation methods. As urinary symptoms are one of the diagnostic criteria for probable MSA [6], urodynamic studies can provide important diagnostic clues for differentiating MSA from Parkinson’s disease (PD) [17]. Through the frontal-striatal loop, the denervated striatum of patients with PD exhibits frontal dysfunction [18] and a consequent overactive bladder. In contrast, MSA pathology involves the pontine micturition center, sacral preganglionic neurons, and neuronal cell loss, including the Onuf nucleus [19], and MSA patients exhibit incomplete bladder emptying and an underactive bladder [17].

Urodynamic study can provide standardized parameters for storage and voiding function of bladder in neurological diseases, which can assist healthcare providers to make decisions on interventions such as indwelling or clean intermittent catheterization. These interventions can help improve the quality of life for individuals with urinary dysfunction by managing their symptoms and reducing the risk of complications, such as urinary tract infections. Additionally, some studies have suggested criteria to distinguish MSA from PD using urodynamic studies [17]. A study has proposed that incomplete bladder emptying may serve as a predictive marker for shorter survival [20]. Therefore, urodynamic studies should be strongly recommended in patients with MSA with LUTS.

The results of the subtype analysis for MSA showed no difference in the voiding phase by bladder type; however, the prevalence of acontractile detrusor was higher in MSA-P patients (71.4%) than in MSA-C patients (41.7%). This result is supported by recent studies that show that detrusor underactivity is significantly higher in MSA-P than in MSA-C [12,17,21]. In addition, this study showed a statistically higher prevalence of DSD in patients with MSA-C than in those with MSA-P in the voiding phase. DSD has also been described as a critical feature of MSA [13,22]; however, few studies have compared the prevalence of these subtypes. A previous cohort study with a larger sample size showed equivalent DSD prevalence between subtypes. Several mechanisms can cause DSD, including the pontine micturition complex, spinal cord, and Onuf nucleus. However, precise anatomic-functional correlations cannot be made in MSA [13]. Previous studies suggested that the cerebellum was responsible for bladder overactivity and sphincter relaxation; cerebellar vermis activation was significantly lower in patients with MSA than in control subjects, as shown on a single-photon emission computed tomography [5,23]. This finding may support the higher prevalence of DSD in patients with MSA-C.

This study had several limitations. First, this was a single-center study with a small sample size. Second, it was based on the first urodynamic study after onset of the patients’ symptoms. Thus, in some cases, the study was delayed depending on the patients’ circumstances; conversely, there were cases where the symptoms were mild and urodynamic findings were normal. Our study was only conducted on MSA patients with LUTS, which have resulted in a selection bias. Urinary dysfunction is one of the most common symptoms of MSA; however, the result of this study does not represent all patients with MSA. Statistically, the period from symptom onset to the test period did not differ significantly between the two subgroups, but the period was widely distributed from 4 months to 11 years.

In conclusion, urodynamic findings in MSA revealed a larger PVR with decreased compliance, detrusor contractility, and DSD. These findings can assist in the diagnosis of urinary symptoms and understanding of the pathophysiology of LUTS in patients with MSA. Therefore, urodynamic studies can help manage LUTS and prevent complications in patients with MSA. In addition, further studies are required to understand the pathophysiology of the urodynamic differences between the subtypes of MSA.