A Prospective Study of Higher Neural Control Changes Following Intra-detrusor Injection of Onabotulinumtoxin-A in Patients With Multiple Sclerosis and Lower Urinary Tract Symptoms.
Conditions: Multiple Sclerosis, Lower Urinary Tract Symptoms, Neurogenic Bladder, Detrusor, Overactive, Urge Incontinence
Sponsor: The Methodist Hospital Research Institute

Brain Control of Voiding 
 
1 
 
The parent IRB protocol is PRO0010110 (titled: Brian control of voiding in women) which includes 
fMRI and UDS in neurogenic bladder individuals. Then there were several amendments (new uploaded 
version 6, please see pages 2-3) for a subset of individuals that underwent onabotulinumtoxinA 
injection as part of their neurogenic bladder management (routine clinical management) and had a 
repeat fMRI/UDS. Thus, this new analysis is entitled “Central Nervous System Changes Following 
BotulinumtoxinA Injection in the Bladder” as is this clincialtrials.gov registry. 
 
 
CLINICAL PROTOCOL: BRAIN CONTROL OF VOIDING IN WOMEN 
 
Version 6 dated 7/20/2015 
 
 
PI: 
Rose Khavari, MD 
 
Co-Investigators: 
Timothy Boone, MD 
Christof Karmonik, PhD 
Steve Fung, MD 
 
Funding Source: 
Rose Khavari is a scholar supported in part by NIH grant K12 DK0083014, the Multidisciplinary K12 
Urologic Research (KURe) Career Development Program to DJL from the National Institute of Diabetes 
and Digestive and Kidney Diseases (NIDDK), National Institutes of Health. 
 
 

Brain Control of Voiding 
 
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Background 
 
The lower urinary tract has two functions: storage and voluntary elimination of urine. Normal voluntary 
voiding in neurologically intact patients is triggered by the release of tonic inhibition from suprapontine 
centers, allowing the pontine micturition center to trigger the voiding reflex. Mediated through spinal 
centers, this reflex initiates the relaxation of the pelvic floor musculature and the urethral sphincter. The 
bladder then contracts and empties.  
 
In the last two decades, the evolution of neuroimaging modalities in the field of neurourology has 
provided a new frontier of research.  In 1998, Blok et al. studied normal female micturition in 10 subjects 
with CNS PET imaging. Increased blood flow was demonstrated in the right dorsal pontine tegmentum 
and the right inferior frontal gyrus. (1) Other investigators have incorporated the use of fMRI to examine 
brain region activation during bladder filling (2), and voluntary pelvic floor muscle contractions (3, 4). 
Furthermore, others have published fMRI evidence of cortical neuroplastic changes after pelvic floor 
muscle training and biofeedback therapy for stress urinary incontinence (5). Krhut et al. used fMRI to 
preliminarily examine brain activity during bladder emptying, localizing areas in the parahippocampal 
gyrus, anterior cingulate gyrus, inferior temporal gyrus and inferior frontal gyrus during micturition (6).  
Our project to evaluate the normal healthy female subjects with concurrent urodynamics and fMRI has 
yielded valuable information regarding anatomical locations neuronal control in micturition. We 
completed the first part of current project (IRB Pro00005508) in July of 2013 and have reported our 
results at multiple scientific meetings. The manuscript is in progress currently. This would be second 
report in the literature on micturition with simultaneous UDS and fMRI and higher number of subjects. In 
summary all of our ten subjects were able to void while supine.  Each patient was able to void at least 
three complete voiding cycles within the fMRI scanning phase, with time to initiate voiding and 
cystometric capacity as factors in total number of voiding cycles.  
Group analysis of the patients (since all were able to void) yielded consistent areas of activation during 
the initiation of voiding (asterisks, Figure 1).  These included regions for motor control (cerebellum, 
thalamus, caudate, lentiform nucleus, red nucleus, supplementary motor area, postcentral gyrus), emotion 
(anterior and posterior cingulate gyrus and insula), executive function (left superior frontal gyrus), as well 
as the parahippocampal gyrus, precuneus, cuneus, occipital lobe (visual stimulus), and a focal region in 
the midbrain.  
 
Figure 1. 

Brain Control of Voiding 
 
3 
 
Preliminary correlation-interaction network analysis of 5 representative subjects were performed with the 
voxel-intensity time courses for a subject depicted (Figure 2A). This yielded spring-embedded network 
layouts that for each subject exhibited a small-world structure of focal clusters with short-range 
interactions connected by long-range edges (Figure 2B). A 3-D representation of cluster connectivity 
(Figure 2C) showed various clusters in the cerebellum connected to clusters in parietal, frontal and 
temporal lobes and to clusters in the limbic system mainly via the medial posterior brain regions (e.g. 
posterior cingulate).   
#2
#3
#4
#5
A. Voxel-intensity 
time courses
(#3)
C. Computed Network-Clusters (#3)
B. Spring-embedded
Correlation networks
#1
 
Figure 2 
Now that we have a better understanding of normal healthy micturition we plan to study brain activity in 
patients with neurogenic bladder (such as patients with multiple sclerosis) and voiding dysfunction. There 
is no similar report in the literature. In patients with multiple sclerosis, urinary symptoms are common 
sequel: urgency, urge incontinence, frequency, urinary retention (7, 8). These patients often undergo 
urodynamic testing and abnormalities are seen in almost all symptomatic cases.  Common findings 
include neurogenic detrusor over-activity, detrusor sphincter dyssynergia and detrusor hypocontractility.   
Clinical correlation between women with these chronic urologic problems and new discoveries at the 
level of CNS activity will give a better understanding of this disorder, leading to the development of more 
effective diagnostic and treatment modalities.  
 
In addition the literature lacks any data regarding sensory effects of bladder medications used for 
neurogenic detrusor overactivity(NDO) or overactive bladder(OAB). A common and FDA approved 
treatment for these patients include use of Botulinum toxin A injected in the bladder. This is a routine 

Brain Control of Voiding 
 
4 
 
management for urinary symptom control in these patients. Despite having knowledge and data that 
Botulinum toxin A decreases the bladder contractility we have no human data how it affects the sensory 
efferent fibers to the brain and decreasing urgency and frequency. Our platform is a perfect model to 
study the effects of botulinum toxin A on sensory efferent fibers of the bladder and correlate that to the 
centers in the brain that respond to urgency and frequency. Thus we propose that patients who based on 
their clinical needs and exams are candidates for intravesical botulinum toxin A and have been a 
candidate in our study to have another fMRI with concurrent UDS about 8 weeks following their 
intravesical botulinum toxin A injection. 
 
Purpose and Objectives 
 
To perform functional MRI neuroimaging and data analysis on female subjects diagnosed with voiding 
dysfunction or neurogenic bladder during the act of micturition. Our goal with this pilot study is to 
determine whether BOLD signal changes on fMRI during voiding are substantial for data analysis. If so, 
data analysis will yield specific regions of the brain that are activated and/or deactivated during voiding. 
The second objective of this study is to determine whether concurrent urodynamics data gathered in the 
scanner can be correlated to fMRI data in order to elucidate simultaneous bladder function measurements 
with BOLD signal measurements. 
 
Second objective of this study is to evaluate the sensory effects of intravesical injection of botulinum 
toxin A used for neurogenic detrusor activity. 
 
Risk Category 
 
(45 CFR 46.406) Category 3: Research involving greater than minimal risk and no prospect of direct 
benefit to the individual subject, but likely to yield generalizable knowledge about the subject's disorder 
or condition. 
 
Research Design 
 
This is a pilot observational study in which brain activity will be observed via fMRI during simultaneous 
urodynamics testing. This study will examine the blood-oxygen-level-dependent (BOLD) signals during 
fMRI of the brain of subjects diagnosed with neurogenic bladder or dysfunctional voiding. BOLD signals 
are an indirect measure of neural activity that can be identified on fMRI. There are no known risks to a 
subject's fetus. There is no known teratogenic risk associated with urodynamics or fMRI. Patients will be 
screened with a urine pregnancy test at enrollment. Patients with a positive pregnancy test will be 
excluded from the study. As a pilot study, 50 subjects will be recruited to investigate the feasibility of the 
study. There is no control group because this study involving human subjects with both urodynamic and 
fMRI testing is complex, time-consuming, and expensive. In addition we can already use our data for the 
past two years on normal healthy females as our control. Furthermore, no investigator has published 
previously regarding simultaneous urodynamics and fMRI in patients with neurogenic bladder and 
dysfunctional voiding. Subjects diagnosed with neurogenic bladder (e.g. MS) and dysfunctional voiding 
would have already undergone baseline urodynamic studies as part of their routine care and will proceed 
to concurrent fMRI and urodynamics testing. 
 
 
 

Brain Control of Voiding 
 
5 
 
Inclusion Criteria for subjects with voiding dysfunction and neurogenic bladder: 
• 
Women ages 18 years or older 
• 
Primary language is English 
• 
Presence of lower urinary tract symptoms (urinary frequency, urgency, urge incontinence or 
difficulty emptying) 
• 
Presence or history of neurologic illness or injury (spinal cord injury, spina bifida, Parkinson’s, 
major spine surgery, multiple sclerosis, or other neurological disorders) and dysfunctional voiding. 
• 
Performed baseline clinic urodynamics testing as part of routine urologic evaluation of voiding 
dysfunction within 24 months of scanning (if not done, will be performed as part of the study). 
 
Exclusion Criteria for subjects with voiding dysfunction: 
• 
Male 
• 
Patients without lower urinary tract symptoms (urinary frequency, urgency, urge incontinence or 
difficulty emptying, etc) 
• 
Positive urine pregnancy test at enrollment (There are no known risks to a subject's fetus. There is no 
known teratogenic risk associated with urodynamics or fMRI) 
• 
Presence of active and symptomatic urinary tract infection 
• 
Exclusive use of indwelling urethral or suprapubic catheter or other methods of urinary diversion 
• 
Severity of neurologic illness: severe immobility, severe dyscoordination, cognitive impairment   
 
STUDY PROCEDURE 
Subjects will be recruited via bulletin board advertisement, web site and word of mouth.  
 
All procedures are investigational. None of the following are part of standard clinical care. 
 
There are no known risks to a subject's fetus. There is no known teratogenic risk associated with 
urodynamics or fMRI. Patients will be screened with a urine pregnancy test at enrollment and before 
fMRI scanning.  Patients with a positive pregnancy test will be excluded from the study.  
 
Procedure Visits: 
 
1) Informed Consent and Enrollment 
Patients will be screened with a history and physical, urinalysis and urine culture, and urine pregnancy 
test. Subjects will also be asked to fill out the following questionnaires: Urogenital Distress Inventory 
(UDI-6), Incontinence Impact Questionnaire (IIQ-7), and the Hamilton Anxiety Rating Scale (HAM-A).  
Patients will also be asked to fill out an fMRI safety screening questionnaire and demographics form. 
 
After informed consent and enrollment, subjects will be scheduled for one or two visits: 
 
2) Clinic Urodynamics Visit 
Subjects diagnosed with neurogenic bladder or dysfunctional voiding have already undergone clinic 
urodynamics based on routine clinical care and will proceed to step 3. If there is a patient that would need 
a urodynamic study they will be instructed to arrive at The Methodist Hospital Department of Urology. 
This visit will consist of multichannel urodynamics in the clinic setting, so subjects can acclimate to the 

Brain Control of Voiding 
 
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catheters and the testing situation. This visit will be 100% research.  However, the test performed is one 
used by the urology clinic in daily clinical care.  While the data collected will be for study use only, there 
is nothing experimental about the urodynamics procedure.  Prior to catheter insertion, a dip stick 
urinalysis is performed to exclude bacteriuria. 
 
3) fMRI Scanning Visit 
The second visit will be the fMRI scanning session at the Methodist Hospital. Subjects will be instructed 
to arrive 30 minutes prior to scanning. Subjects will have a dip stick urinalysis performed and a urine 
pregnancy test to confirm that they are not pregnant prior to the insertion of the catheters and the MRI.  
Urodynamics catheters will be inserted. After task instruction, subjects will be placed in the scanner. Task 
instruction consists of giving subjects directions to hold their urine, relax their pelvic muscles, and void 
will be conveyed to them via instructions printed on a screen they will see while in the scanner. Patients 
will also be instructed to squeeze a bulb in their hand if they experience claustrophobia or discomfort, and 
want to be removed from the scanner. Scanning will then begin.  
 
After standard localizer and structural scans, the functional sequence and urodynamics will start. The 
bladder will be filled with sterile saline, as per urodynamics procedure. Subjects will be instructed 
(visually using a projection screen and mirror, standard procedure for the HNL) to hold their bladder, and 
then view a fixation cross for 30 seconds. They will be asked to indicate, via finger button, when their 
bladder is full. Subjects will then be instructed (again using a projection screen and mirror) to relax their 
pelvic floor muscles, and then to urinate. The experiment will conclude with the subject pressing the 
finger button to indicate they are finished urinating. At that point an instruction to relax will appear and 
then be replaced by a fixation cross that the subject will view it for 30 seconds and the experiment will be 
complete. The urodynamic and scanning cycle may be repeated up to 5 cycles. 
 
4) repeat fMRI scanning visit: 
This visit would only apply to the patients that clinically were a candidate for intravesical injection of 
botulinum toxin A and went on receiving it as a part of their routine care. If they agree, we would recruit 
them for a repeat fMRI scan just as detailed above about 8weeks (+/- 4 weeks) following their botox 
injection. Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7), and the 
Hamilton Anxiety Rating Scale (HAM-A) will be re-obtained at this visit. 
 
Sample Size 
 
How many subjects (or specimens, or charts) will be used in this study? 
Local: 50  Worldwide: 50 
 
Please indicate why you chose the sample size proposed: 
This is a pilot study. These experiments are novel, as there is currently no similar study in the literature. 
There is no way to predict numbers required in order to find statistically variations between arms of each 
experiment. Pilot data from this study will aid in powering future studies on the same topic. This study 
involving human subjects with both urodynamic and fMRI testing is complex, time-consuming, and 
expensive. Furthermore, no investigator has published previously regarding simultaneous urodynamics 

Brain Control of Voiding 
 
7 
 
and fMRI. This protocol is for a feasibility study. Once the feasibility of our model is established, we can 
work on studying control groups. 
 
Data Analysis 
Provide a description of your plan for data analysis. State the types of comparisons you plan (e.g. 
comparison of means, comparison of proportions, regressions, analysis of variance). Which is the 
PRIMARY comparison/analysis? How will the analyses proposed relate to the primary purposes of your 
study? 
 
The data analysis will be similar to other data analytic strategies carried out in the laboratory. It requires 
fairly complex analysis techniques and is thus difficult to summarize without going into lengthy details. 
Briefly, our data analysis will be as follows: We have made extensive use of a general linear model in 
analyzing and designing our fMRI experiments. To compare data from different subjects, the scan data 
from each subject must be transformed into a standard anatomical framework. We follow the approach of 
Frackowiak et al (1997), which analyzes the brain into small local volumes or “voxels”. The fMRI signal 
from each voxell is then subjected to the following transformation steps: 
 
Analysis Step 1: Spatio-temporal normalization to a standard brain map, and smoothing to improve the 
signal-to-noise ratio. 
 
Analysis Step 2: Statistical analysis to determine the significance of the activity measured at each voxel. 
We use an established statistical framework [K.J. Friston, et al., Human Brain Mapping 2, 189-210 
(1995); K.J. Friston, A.P. Holmes, K.J. Worsely, Neuroimage 10, 1-5 (1999)] in terms of a general linear 
model, which incorporates and formalizes the independent explanatory variables in our experiment. Given 
the variance of each parameter, we can construct a t-statistic as a measure of the significance of 
differences in the parameters estimated from the different experiments, at different voxels, or in different 
subjects. In practice, we construct a statistic out of a particular linear combination of the parameters that 
describes a quantity of interest. To express this mathematically, we define a contrast vector that specifies 
a linear combination of parameters. Then the t-statistic is the quantity of interest divided by its standard 
error. When we calculate a t-statistic at each voxel in an imaged brain, measuring the significance 
of a difference between parameters from different subjects or different experimental conditions, the 
resulting set is  called a statistical parametric map. We use such maps to determine areas of significant 
activation in the brain during presentation of stimuli or performance of the task.  
 
A linear regression analysis will also be employed to look for covariance of behavioral variables with 
observed brain activity. For instance, the degree of preference for an image or the amount of prior 
exposure to the stimulus can be entered into the analysis as explanatory variables for the brain activation. 
In this case, the degree to which behavioral variables cause linear changes in brain activity can be 
illustrated by fitting the estimated response to the observed time series of dynamic blood flow in the 
brain. The regions identified in this type of analysis will be used to generate “regions of interest”, smaller 
areas of voxels that can be analyzed without making assumptions regarding the underlying 
hemodynamics. In this analysis, the raw change in magnetic signal can be read out and compared across 
any variable of interest. 
 

Brain Control of Voiding 
 
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Potential Risks/Discomforts 
Risks with Pregnancy:  
There are no known risks to a fetus associated with urodynamics or fMRI. Regardless, pregnancy is an 
exclusion criterion. Every subject will be screened with a urine pregnancy test at enrollment. Subjects 
with a positive pregnancy test will be excluded from the study. 
 
Urodynamics Testing:  
Urodynamics studies involve invasive catheterization of the urethra and the rectum. The risks and 
discomforts of urodynamics testing include: discomfort in the bladder, urethra and rectum at the time of 
testing. The subject may also experience dysuria for 12 hours after testing. Another risk is that of urinary 
tract infection (UTI). All subjects undergoing urodynamic testing will be screened for UTI prior to 
testing. Patients will be given information regarding the symptoms and signs of UTI and asked to call the 
urology investigator’s office if they have any of the symptoms after testing. If a UTI is present, it will be 
treated. 
 
fMRI:  
Movement or heating of metallic implants is a potential risk, and so subjects will be screened to exclude 
people with metallic implants. Some individuals experience claustrophobic reactions in the scanner. 
Subjects will be informed of this prior to the study, but because it is difficult to predict who will have 
such a reaction, this is not a specific exclusion criterion. Any subject experiencing claustrophobia will be 
removed from the scanner immediately. There is no invasive component to this study, such as IV 
catheters. Therefore, bruising or infection are not risks.. The Siemens 3 T scanner has been approved by 
the FDA. However, there may be additional risks associated with scanning at 3 T compared to the 
conventional clinical scanners in the 1.5-2.0 T range. These include: 1) Effect of the static field. There is 
no conclusive evidence for irreversible or hazardous bioeffects to acute, short term exposures of humans 
up to 2.0 T (Shellock and Kanal, 1996). Studies have indicated some side-effects at 4.0 T, namely unusual 
sensations including nausea, vertigo, and metallic taste (Schenk 1991). However, there is no evidence that 
this is either irreversible or harmful. If subjects experience unusual sensations, they will be withdrawn. 2) 
Effect of the gradient field. MRI operates by rapidly changing small additional fields, called gradients. 
This will induce small electrical currents in any conductor, and this could theoretically induce mild 
peripheral nerve stimulation. However, this is not substantially different at higher magnetic fields since 
the gradients are separate from the main magnet. There is no evidence that the effect of the gradients is 
any different at 3 T than at 1.5 T. However, if subjects experience peripheral nerve stimulation, e.g. 
tingling or twitching, they will be withdrawn. 3) Effect of the RF electromagnetic field. The higher 
magnetic field strength requires that higher RF frequency pulses are used to excite the protons in the 
subject’s brain.  
 
QUESTIONNAIRES:  
Completing the questionnaires may cause you to have or to experience some level of emotional 
discomfort due to the personal nature of the questions. The study doctor and staff will maintain a 
professional and caring attitude while administering the questionnaires. 
 
 

Brain Control of Voiding 
 
9 
 
REFERNCES 
 
1. Blok BF, Sturms LM and Holstege G: Brain activation during micturition in women. Brain. 121 ( 
Pt 11): 2033-42, 1998.  
2. Kuhtz-Buschbeck JP, Gilster R, van der Horst C, Hamann M, Wolff S and Jansen O: Control of 
bladder sensations: an fMRI study of brain activity and effective connectivity. Neuroimage. 47: 
18-27, 2009.  
3. Kuhtz-Buschbeck JP, vander Horst C, Wolff S, Filippow N, Nabavi A, Jansen O and Braun PM: 
Activation of the supplementary motor area (SMA) during voluntary pelvic floor muscle 
contractions--an fMRI study. Neuroimage. 35: 449-57, 2007.  
4. Seseke S, Baudewig J, Kallenberg K, Ringert RH, Seseke F and Dechent P: Voluntary pelvic 
floor muscle control--an fMRI study. Neuroimage. 31: 1399-407, 2006.  
5. Di Gangi Herms AM VR, Reisenauer C, Herms A, Grodd W, Enck P, Stenzl A and Birbaumer N: 
Functional imaging of stress urinary incontinence. Neuroimage 2006, 29:276-275. 
6. Krhut J TJ, Holy P, Zachoval R, and Zvara P: A Preliminary Report on the Use of Functional 
Magnetic Resonance Imaging with Simultaneous Urodynamics to Record Brain Activity During 
Micturition. Journal of Urology 2012, 188:474-479. 
7. De Seze M, Ruffion A, Denys P, Joseph PA, Perrouin-Verbe B: The neurogenic bladder in 
multiple sclerosis: review of the literature and proposal of management guidelines. Mult Scler. 
13: 915-928, 2007. 
8. Hennessey A, Robertson NP, Swingler R, Compston DA: Urinary, faecal and sexual dysfunction 
in patients with multiple sclerosis. J Neurol. 246: 1027-1032, 1999. 
 
 

Brain Control of Voiding 
 
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APPENDICIES 
 
 
Appendix A:  UDI-6 Questionnaire 
Appendix B:  IIQ-7 Questionnaire 
Appendix C:  HAM-A rating scale 
Appendix D:  Schedule of Events 
Appendix E:  Patient Demographics Questionnaire 
 
 
 

Brain Control of Voiding 
 
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Appendix A:  UDI-6 Questionnaire 
BRAIN CONTROL OF NORMAL VOIDING IN WOMEN                             PI:  Rose Khavari, MD 
SUBJECT INITIALS/ID#: 
 
DATE: 
 
Urogenital Distress Inventory UDI-6 
Does not 
happen 
(0) 
Present, but not 
at all bothersome 
 (1) 
Somewhat 
bothersome  
(2) 
Moderately 
bothersome  
(3) 
Quite a bit 
bothersome  
(4) 
1. Do you usually experience frequent urination? 
 
 
 
 
 
2. Do you usually experience urine leakage 
associated with a feeling of urgency; that is, a strong 
sense of needing to go to the bathroom? 
 
 
 
 
 
3. Do you usually experience urine leakage 
associated with coughing, sneezing, laughing? 
 
 
 
 
 
4. Do you experience small amounts of leakage (that 
is, drops)?? 
 
 
 
 
 
5. Do you experience difficulty emptying your 
bladder? 
 
 
 
 
 
6. Do you experience pain or discomfort in the 
lower abdomen or genital region? 
 
 
 
 
 
TOTAL  
 
 
 
 
 

Brain Control of Voiding 
 
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Appendix B:  IIQ-7 Questionnaire 
BRAIN CONTROL OF NORMAL VOIDING IN WOMEN                   PI:  Rose Khavari, MD 
SUBJECT INITIALS/ID#: 
 
DATE: 
 
 
 
 
 
Incontinence Impact Questionnaire (IIQ-7) 
Not at all 
 (0) 
Slightly  
(1) 
Moderately  
(2) 
Greatly  
(3) 
Has urine leakage affected your: 
 
 
 
 
1. Household chores? 
 
 
 
 
2. Physical recreation activities? 
 
 
 
 
3. Entertainment activities? 
 
 
 
 
4. Travel for distances greater than 30 minutes away from home? 
 
 
 
 
5. Social activities? 
 
 
 
 
6. Emotional health (nervousness, depression, etc)? 
 
 
 
 
7. Feeling frustrated? 
 
 
 
 
TOTAL  
 
 
 
 

Brain Control of Voiding 
 
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Appendix C:  HAM-A Rating Scale 
 
 
 

Brain Control of Voiding 
 
14 
 
 
 
 
 
 
 
 

Brain Control of Voiding 
 
15 
 
Appendix D:  Schedule of Events 
 
 **NOTE:  All activities are RESEARCH Related. 
 
                1 – The urine analysis done at visit 2 and visit 3 are dipstick analysis only and no culture is performed 
                2 – The urine pregnancy test done at visit 3 is a kit that shows immediate results of positive or negative 
                3 -- Only for the patients who have not had a UDS in the preceding 24 months 
 
 
Activity** 
Screening Phase 
Study Phase 
Only if indicated 
8 weeks after BOTOX inj. 
Screen and Enroll 
Visit 1 
Visit 2 
 
Visit 3 
 
Visit 4 
Patient History 
X 
 
 
 
Physical Exam 
X 
 
 
 
Medication Review 
X 
 
 
 
Consent for Study 
X 
 
 
X 
UA and UC+S 
X 
X¹ 
X¹ 
X 
Urine Pregnancy Test 
X 
 
X² 
X 
UDI-6 questionnaire* 
X 
 
 
X 
IIQ-7 questionnaire† 
X 
 
 
X 
HAM-A rating scale‡ 
X 
 
 
X 
fMRI Screening Form 
X 
 
 
 
Urodynamics Testing 
(part of routine care in 
this population) 
 
X3 
X 
X 
fMRI Scanning 
 
 
X 
X 
UA: urine analysis. UC: Urine culture & Sensitivity. *UDI-6: Urogenital Distress Inventory questionnaire. † IIQ-7: Incontinence Impact questionnaire. ‡HAM-A : Hamilton Anxiety rating scale.  

Brain Control of Voiding 
 
16 
 
Appendix E:  Patient Demographic Form 
Demographics Form 
 
Brain Control of Normal Voiding in Women       
Dear Subject: 
Please take a few minutes to complete this form.  This information is completely confidential.  The information is needed for 
the study, Brain Control of Normal Voiding in Women, in order to match your data with other subjects.       
Subject ID Number: ____________________________________ 
Date: ___________________________ 
Age:   
 
Date of Birth   
/ 
/ 
 
Occupation: __________________________________________ 
 
 
List any medical illnesses you have had and the approximate year of treatment: 
 
__________ 
___________________________________________________ 
 
___________________________________________________ 
 
__ 
 
___________________________________________________ 
 
 
__ 
 
 
List all surgical procedures you have had and the approximate year of treatment: 
 
___ 
 
 
__ 
 
 
__ 
 
 
__ 
 
 
 
 
 
 
__ 
_ 
 
 
 
List all medications you are taking (Include non-prescription drugs): 
 
___ 
 
 
__ 
 
 
__ 
 
 
__ 
 
 
__ 
 
 
___ 
 
 
__ 
 
 
__ 
 
 
__ 
 
 
__ 
 
List all medication allergies: 
Medication 
 
Type of Reaction 
 
___ 
 
 
__ 
 
Medication 
 
Type of Reaction 
 
___ 
 
 
__ 
 
 
 
 
 

Brain Control of Voiding 
 
17 
 
 
OB/GYN HISTORY 
How many times have you been pregnant?   _____ 
Number of vaginal deliveries   ______    C-sections   _____ 
Weight of largest child at birth   _______  
Any deliveries with an episiotomy or tear into the rectum? 
Yes   ___   No   ___ 
 Date of last menstrual period  _______________ 
How many days does period last   ________ 
Do you have severe menstrual cramping?  Yes   ___   No   ____ 
Date of last PAP smear _______________ 
Was last PAP normal?  Yes   ___   No   ____ 
 
Subject ID Number: _____________________________________ 
SOCIAL HISTORY 
Do you smoke now or in the past?  
   No  
__    Yes  ______ 
Packs per day?  
__ 
Years smoked?  ________ 
If you have quit, please indicate year   ________ 
Do you drink alcoholic beverages?        No   
___   Yes   
___ 
Explain:  
 
How much coffee, tea and/or soda do you drink in one day? 
Explain:  ______________________________________________ 
________________________________________ 
 
REVIEW OF SYSTEMS 
Do you now or have you had problems with any of the following? 
 
Y 
N 
Please explain any Yes answers. 
GENERAL: Recent weight changes, fever, weakness, fatigue, 
headaches 
 
 
 
INTEGUMENTARY: Rashes, eruptions, dryness, jaundice, changes 
in skin, hair or nails, discoloration of skin 
 
 
 
EYES: Blurred vision, double vision, pain 
 
 
 
EARS, NOSE, MOUTH & THROAT: 
Soreness and/or redness of 
gums, hoarseness, difficulty in 
swallowing, head colds, 
discharges, obstruction, 
postnasal drip, sinus pain, 
earaches 
 
 
 
MUSCULOSKELETAL: Joint pain, neck pain, back pain 
 
 
 
RESPIRATORY: Chest pain, wheezing, cough, difficulty breathing, 
asthma, bronchitis, pneumonia, tuberculosis, 
shortness of breath, emphysema 
 
 
 
NEUROLOGIC: Fainting, blackouts, seizures, paralysis, tingling, 
tremors, memory loss, dizzy spells, stroke 
 
 
 

Brain Control of Voiding 
 
18 
 
CARDIOVASCULAR: 
Chest pain, rheumatic fever, rapid heart 
beat, high blood pressure, swelling, 
dizziness, faintness, varicose veins, heart 
valve problems 
 
 
 
ENDOCRINE: 
Thyroid trouble, fatigue, heat or cold intolerance, 
excessive sweating, thirst, hunger 
 
 
 
GASTROINTESTINAL: 
Appetite, nausea, vomiting, diarrhea, 
constipation, indigestion, food intolerance, 
hemorrhoids, jaundice, heartburn, diabetes, 
hepatitis 
 
 
 
GENITOURINARY – MALE: 
Hernias, testicular or penile problems, impotency, (erectile 
dysfunction), infertility, frequency or painful urination, blood in 
urine, urinary retention 
 
 
 
GENITOURINARY –  FEMALE: 
Vaginal pain, pain with sexual intercourse, low sexual desire, 
frequency or painful urination, blood in urine, urinary retention 
 
 
 
HEMATOLOGIC/LYMPHATIC: Anemia, easy bruising or bleeding, 
past transfusions, swollen glands, blood clotting problems 
 
 
 
PSYCHOLOGIC: Nervousness, insomnia, headache, depression 
 
 
 
ALLERGIES:   Plant, food, environmental