anorectal function in fluctuating (on-off) parkinson's disease: evaluation by combined...

Movement Disorders Vol. 10, No. 5 , 1995,. pp. 650-657 0 1995 Movement Disorder Society

Anorectal Function in Fluctuating (On-Off) Parkinson’s Disease: Evaluation by Combined Anorectal Manometry

and Electromyography

Waseem Ashraf, *Zbigniew K. Wszolek, *Ronald F. F‘feiffer, *Marlene Normand, *Kenneth Maurer, Faye Srb, *Loraine L. Edwards, and Eamonn M. M. Quigley

Sections of Gastroenterology and Hepatology and *Section of Neurology, University of Nebraska Medical Center, Omaha, Nebraska, U.S.A.

Summary: Anorectal dysfunction and constipation are well recognized in Par- kinson’s disease and may reflect the direct involvement of the gastrointestinal tract by the primary Parkinson’s disease process. We hypothesized, therefore, that anorectal function would alter in parallel with fluctuations in motor function related to on- and off-periods in Parkinson’s disease, and employed combined anorectal manometry and electromyography to investigate anorectal function during both on- and off-periods in patients with Parkinson’s disease. Manometric recordings revealed a deterioration in voluntary sphincter squeeze during off-periods (squeeze index, on versus off, mean & SEM: 46.4 5 11.1 versus 29.6 f 7.9 mm Hg, p < 0.05); correspondingly, simultaneous electromyographic (EMG) recordings showed poor recruitment of external anal sphincter and puborectalis muscles during off-periods. A hypercontractile (“paradoxical”) rectosphincteric reflex response occurred during both on- and off-periods, and was associated with an increase in EMG activity in the external sphincter and/or the puborectalis muscle. These changes in manometric and EMG parameters paralleled changes in overall motor function. These findings provide further support for the involvement of the pelvic floor musculature in the Parkinson’s disease process and also provide EMG correlates for some of the manometric abnormalities described in Parkinson’s disease. Key Words: Anorectal manometry-Anal sphincter electromyography-Anorectal function-Parkinson’s disease-‘ ‘On-off ’ fluctuations.

In some patients with Parkinson’s disease, therapy may be complicated by a variable response to oral L-Dopa, which features a striking fluctuation between relative mobility and immobility. The tim- ing of these fluctuations usually corresponds with the onset and termination of the therapeutic effects of L-Dopa (1,2), thus giving rise to this phenomenon commonly referred to as on-off periods or fluctua-

Accepted March 27, 1995. Address correspondence to Dr. E. M. M. Quigley at Depart-

ment of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center, 600 South 42nd Street, Box 982000, Omaha, NE 68198-2000, U.S.A.

tions. These fluctuations have also been associated with variable bladder (3,4) and esophageal motor function (5 ) .

Gut dysfunction, which is common in Parkin- son’s disease, is often debilitating and occasionally even life threatening (6,7). Increasing neuropatho- logical and neurophysiological evidence suggests that such gastrointestinal symptoms as dysphagia, constipation, and defecatory dysfunction in Parkin- son’s disease may be an integral component of the primary disease process (6,&11). Thus, in clinical studies an improvement in defecation and anorectal function has been demonstrated in Parkinson’s disease patients in response to the subcutaneous ad-

650

ON-OFF FLUCTUATIONS IN ANORECTAL FUNCTION 651

ministration of the dopamine agonist, apomorphine (12). Similarly, voiding efficiency was shown to im- prove after apomorphine (13). Lewy bodies, the characteristic neuropathologic finding in Parkin- son’s disease, have been identified throughout the gut in both myenteric and submucosal plexi as well as in celiac and paravertebral ganglia (8-10,14,15). Therefore, it seemed reasonable to speculate that dopamine depletion, such as occurs during an off- period, would induce alterations in anorectal function, consistent in a manner analogous to the fluctuations in motor function observed during these periods.

The purpose of this study was to investigate anorectal function, employing combined anorectal manometry and electromyography, in relation to both on- and off-periods in patients with Parkinson’s disease.

METHODS

Subjects Five patients (three male, two female) who had

Parkinson’s disease and who exhibited prominent on-off fluctuations were recruited from the Move- ment Disorders Clinic at the University of Ne- braska Medical Center. Their mean age was 64.2 years (range, 58-70) and the mean duration of Par- kinson’s disease was 18 years (range, 10-26). On-off fluctuations were present for 9.4 years (range, 6- 12). This study was reviewed and approved by the Institutional Review Board of the University of Ne- braska Medical Center.

Study Protocol Extrapyramidal function was assessed using the

Unified Parkinson’s Disease Rating Scale (UPDRS) (16). In three patients a combined study of anorectal manometry and electromyography was performed during an on-phase. The patients’ dopaminergic medication was then deliberately withheld until a repeat neurological examination and UPDRS evaluation confirmed the onset of the off-phase, at which time the manometric and electromyographic examinations were repeated. The procedure was re- versed in the other two patients, in whom off-period studies were performed initially, followed by on- period evaluation. For all five subjects, the interval between these two studies was 35 k 15 min; patients remained lying flat and attached to the recording apparatus, with electromyography (EMG) wires remaining in situ during this interval.

ANORECTAL MANOMETRY AND EMG

Figure 1 illustrates the recording system. The manometric assembly (5 lumens radially arrayed at 0.5 cm intervals) straddles the sphincter; bipolar coated wire electrodes (17) record simultaneously from the left and the right sides of the external anal sphincter (EAS) and puborectalis (PR) muscles.

Sphincter pressures and electrical activity were recorded simultaneously for the three muscles at rest, during voluntary squeeze (voluntary contraction of the external sphincter for at least 60 s or until the pressure increments decayed to the level of the basal sphincter pressure), and during testing of the rectosphincteric reflex [(RSR) by rapid balloon inflation with 60 ml of air]. Finally, with the balloon in the rectum, stepwise balloon inflation was performed at 5-ml increments and the threshold for rectal sensation was defined.

icter

‘ W E x t e r n a l Anal Sphincter

Electrode \ EMG

Electrode

FIG. 1. Recording apparatus. Manometric assembly 15-lumen catheter (Arndorfer Inc., Greendale, WI, U.S.A.) with individual side holes radially arrayed at 0.5-cm intervals straddles sphincter (defined by a prior station pull-through procedure)]. A distal inflatable balloon (for rectosphincteric reflex and sensation testing) lies in the rectum. Assembly perfused at 0.1 cc/min by low-compliance perfusion system (Amdorfer Inc.) and pressure changes recorded by Sandhill strain gauges and TDS recorder (Sandhill Inc., Littleton, CO, U.S.A.). Bipolar, coated wire electrodes (their ends offset to avoid electrical contact) have been inserted into the left and right sides of the external anal sphincter and puborectalis muscles through a hypodermic needle that was subsequently withdrawn, leaving the wires in situ. The free ends of the wire attached to a Viking 11 electromyographic (EMG) recorder (Nicolet, Madison, WI, U.S.A.), from which the high- level EMG waveform was coupled through an interphase box that attenuated the signal by 1,OOO:l and provided input to be displayed simultaneously with the manometric recording on three channels of the Sandhill TDS recorder.

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652

DATA ANALYSIS

W. ASHRAF ET AL.

RESULTS

A total motor score was calculated from the UPDRS for both on- and off-periods.

From the manometric trace the following parameters were evaluated: mean basal sphincter pressure, sphincter length, maximal and sustained squeeze pressure, squeeze duration, and squeeze index (area under the squeeze curve). Basal sphincter pressure was defined as a mean of the pressures recorded from each side hole during the pull- through procedure. Sphincter length was defined at each side hole from the point of initial pressure rise above baseline until the pressure again decayed to or below baseline, and a mean value was calculated from all five side holes. The typical squeeze response included a rapid initial rise in pressure that rapidly decayed to a plateau. The maximal squeeze pressure was defined as the mean of the three greatest increments recorded during squeeze and always corresponded to the initial response. The sustained squeeze pressure was defined as the plateau squeeze pressure sustained after the initial increment. Squeeze duration was defined as the time, in seconds, from the onset of squeeze until the pressure had decayed to basal sphincter pressure, or until 60 s had elapsed, a mean value being de- rived from those recording sites that demonstrated the greatest increments. Finally, the squeeze index was defined as the area under the squeeze curve and was calculated by planimetry. All recordings were performed at a chart speed of 2.5 m d s .

EMG recordings were analyzed for any change from the baseline (on-period) activity and for abnormal recruitment of motor units during testing of the rectosphincteric reflex.

All data are expressed as mean 2 SEM. For statistical analysis of the data, x 2 , and Student’s, and paired t tests were used as appropriate.

Parkinson’s Disease Rating: Total Motor Score The characteristics of the Parkinson’s disease

subjects are summarized in Table 1. All had constipation, all but one being laxative dependent. The total motor score (UPDRS) was 10.0 f 1.7 for the on-period and 42.8 * 8.7 for the off-period (p < 0.05). Individual motor scores for each period and for each patient and their relationship with the duration of Parkinson’s disease and on-off fluctuations are shown in Table 1.

Anorectal Manometry and EMG Figure 2 compares manometric and EMG record-

ings during voluntary sphincter squeeze from the same patient during on-periods (Fig. 2A) and off- periods (Fig. 2B). Both the initial and sustained squeeze increments are clearly impaired during the off-period. Correspondingly, the simultaneous EMG recording shows poor recruitment of both EAS and PR during the off-period. In comparing EMG activity between on- and off-periods for all five subjects at rest, activity in the EAS was de- creased in four patients when off; activity in the PR appeared unchanged between the two periods. Dur- ing voluntary squeeze, EMG activity in both EAS and PR was seen to decrease in all five patients when off, during both the initial and sustained phases of squeeze.

Figure 3 compares various manometric parameters during on- and off-periods for each patient and demonstrates a consistent deterioration in maximum squeeze pressure (on- versus off-period: 3 1.7 f 5.4 versus 20.2 k 4.2 mm Hg, p < 0.05), and squeeze index (on- versus off-period: 46.4 ? 11.1 versus 29.6 & 7.9 mm Hg, p < 0.05), during the off-period. Maximum squeeze pressure and squeeze duration also declined during the off-period

TABLE 1. Subject characteristics

Pt. Age

UPDRS motor PD On-off (Total score)

duration fluctuations Swallowing no. (yrs) Sex (yrs) duration (yrs) On period Off period Constipation“ difficulty Laxatives

1 65 M 10 8 13 64 Yes Yes Yes 2 65 F 12 8 8 44 Yes No Yes 3 I0 F 26 10 15 29 Yes Yes Yes 4 63 M 12 7 8 59 Yes No Yes 5 58 M 20 14 6 18 Yes No No

UPDRS, Unified Parkinson’s Disease Rating Scale; PD, Parkinson’s disease. Subjective complaint of infrequent bowel movement ( ~ 3 stools/week) and/or difficult defecation.

Movement Disorders, Vol. 10, No. 5 , 1995


FIG. 2. Examples of on-period (A) and off-period (B) voluntary squeeze from a single patient. Both maximal, initial, and sustained squeeze pressures deterio- rate during the off-period. These pressure changes are accompa- nied by a simultaneous decrease in external anal sphincter (EAS) and puborectalis (PR) electromyographic (EMG) activity during the off-period. Note also the close relationship between pressure fluctuation and EMG activity during squeeze (A).

ON-Mod A

but these changes did not achieve statistical signif- icance: maximum squeeze (on- versus off-period 82.4 * 12.7 versus 68.7 f 14.7 mm Hg, p: NS), squeeze duration (on- versus off-period, 53.4 * 6.6 versus 46.5 f 10.2 s, p: NS). Basal sphincter pressure (on- versus off-period: 34.1 -+ 1.3 versus 39.3 ? 5.5 mm Hg, p: NS) and the volume of initial rectal sensation (65.0 ? 21.6 versus 70.0 ? 20.3 mi, p: NS) did not change.

Linear regression analysis revealed significant

correlation between changes in total motor score and various parameters of voluntary squeeze: R = 0.44 for maximal squeeze, 0.51 for sustained squeeze and 0.43 for squeeze index.

Rectosphincteric Reflex Two patients demonstrated a hypercontractile or

paradoxical response on testing of the RSR during both on- and off-periods (Fig. 4). In a third patient this abnormal response was evident only during the

Movement Disorders, Vol. 10, No. 5 , 1995

W. ASHRAF ET AL. 6.54

80 -

60 - X 0 TI c - 8 40- P) P) J U v)

20 -

20/

0’ On Period

Off Period

I2O! 100

‘“1 0’ On

Period Off

Period O J On

Period Off

Period

FIG. 3. Comparisons of maximal (A), and sustained (B) squeeze pressures and squeeze index (C) between on- and off-periods. Both the sustained squeeze pressure and squeeze index deteriorated significantly during the off-period. Horizontal bars indicate mean values. *p < 0.05, on versus off-period.

off-period of the study. Among the patients who exhibited a hypercontractile response on RSR testing, two demonstrated an inappropriate simultaneous increase in EMG activity in both EAS and PR (Fig. 4); in the third patient, activity increased during RSR testing in the PR alone (Fig. 5).

subjects (1 I ,18,20). Simultaneous recordings of electrical and pressure activity in this study clearly showed abnormal recruitment of both EAS and PR muscles in relation to this response, thereby con- firming that this response originates in the EAS-PR complex. In one patient who showed this abnormal response only when in an off-period, the sphincter

DISCUSSION

Both the manometric and EMG findings of a poor squeeze profile, paradoxical anal sphincter response during simulated defecation, and a synchro- nous increase in EMG activity in the EAS and PR muscles are similar to those reported previously in Parkinson’s disease (1 1 J8-20). In this study we have, for the first time, demonstrated parallel changes in anorectal manometry and EMG during the off-period in subjects who have significant on- off fluctuations. During the off-period, we noted a further decrease in squeeze that corresponded with a decrease in the recruitment of motor units from the EAS and PR muscles. This deterioration also paralleled changes in overall motor function as mea- sured by the UPDRS-total motor score, supporting the hypothesis that changes in anorectal function are reflective of the parkinsonian process.

This study also provides insights into the previously described abnormal sphincter response to rectal distension in Parkinson’s disease, which fea- tured a prolonged and prominent contraction with- out any evidence of the relaxation seen in normal

relaxed appropriately when in an on-period, per- haps indicating a less severe and reversible abnormality. This finding, taken together with the deterioration noted in other parameters during the off-period, further supports the concept of the involvement of the external sphincter and pelvic floor musculature, in a manner analogous to that observed in other muscle groups, by the Parkinson’s disease process. Further evidence for this hypothesis is provided by the prior demonstration of improvement in both sphincter pressures and EMG activity by the administration of the dopaminergic agent, apomorphine (12,19). Other visceral symptoms such as belching and urinary retention have also been correlated with on-off fluctuations in Par- kinson’s disease and have been ameliorated by apomorphine administration (4,5). The pathophysiol- ogy of this dysfunction is unclear but its characteristics are reminiscent of those observed in the axial musculature and are considered to result from stri- atal dopamine depletion.

The abnormal sphincter response, which is vari- ably identified among nonparkinsonian patients with outlet-type constipation or anismus, is a well-

Movemenr Disorders. Val. 10, No. 5. 1995


FIG. 4. Example of an abnormal or “paradoxical” rectosphincteric reflex response recorded during both on- (A) and off- (B) periods in the same patient. Note the dominant contractile response after inflation of the rectal balloon. In this example, the paradoxical reflex is shown to be associated with an abnormal increase in EMG activity in both the external anal sphincter (EAS) (left and right) and the puborectalis (PR).

A

recognized cause of constipation (21,22), and has come to be regarded as an indication of a general- ized abnormality of dysfunction of the external sphincter, PR, and levator ani muscle complex. These muscles appear to be an integrated, dynamic

unit and may show patterns of complete or partial relaxation, nonrelaxation, or even paradoxical contraction in the same patient, depending on the po- sition of pressure channels (23,24).

In conclusion, off-period fluctuations were asso-

Movement Disorders, Vol. 10, No. 5 , 199s

656 W. ASHRAF ET AL.

A 0 N - P e ri od

EAS (Left)

. .. .. .. . . -

. ..

wtnl ballon inflates

B OF”-Period

EAS (Left)

I

rectal ballon inflates

FIG. 5. “Paradoxical” rectosphincteric reflex related to inappropriate contraction of the puborectalis alone. In this instance the hypercontractile response is identified during both on (A) and off (B) periods. EAS, external anal sphincter; PR, puborectalis.

ciated with a deterioration in anorectal manometric pressures and EMG activity in the EAS and PR muscles. Constipation in Parkinson’s disease may reflect colonic inertia, pelvic floor (or “outlet”) dysfunction, or both (11). For some patients, ob- structed or difficult defecation is the major prob- lem. Our findings suggest that a relationship between defecatory dysfunction and on-off fluctuations should be sought in Parkinson’s disease patients with symptomatic constipation and if confirmed, apomorphine administration should be considered.

1 .

2.

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5.

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