Anda di halaman 1dari 17

AUTONOMIC

DISORDERS OF THE
UROGENITAL SYSTEM
Clare J. Fowler
ABSTRACT
The highly distributed nature of the neural control of the bladder and genitalia
means that disorders of these functions are very likely to occur with many different
neurologic diseases, although the range of symptoms is limited. In this chapter the
clinical presentations and recommended management of urogenital symptoms in
three conditions are described: multiple sclerosis, the commonest cause of
neurogenic urogenital dysfunction; multiple system atrophy, a much less common
condition, but one in which urogenital dysfunction occurs early; and a disorder of
voiding, which affects neurologically healthy women, now referred to as Fowlers
syndrome.
Continuum Lifelong Learning Neurol 2007;13(6):165181.
INTRODUCTION
The lower urinary tract is peripherally
innervated by nerves of the autonomic
nervous system, but a hierarchy of
higher centers is involved in the per-
ception of bladder fullness and the
decision about the appropriateness of
when to void. In fact, continence
depends on the integrity of the central
and peripheral nervous systems at many
different levelspossibly more so than
any other bodily function. Thus, dis-
turbances of bladder function can result
from disease or disorders of the neo-
cortex, basal ganglia, pons and brain
stem, spinal cord, and the peripheral
innervation. But because the repertoire
of bladder behavior is limited, the range
of dysfunction is also restricted. There
can be abnormalities of the storage
phase, ie, incontinence, or abnormali-
ties of the voiding phase, ie, retention,
or a combination of both problems,
while the neurologic causes are diverse.
The neurology of sexual function is
less well defined, but it again depends
on innervation of the genitalia by
autonomic system nerves while higher
centers modulate that innervation.
In this chapter three disorders that
cause bladder and or sexual dysfunc-
tion will be reviewed, with a brief
description for each condition of the
neurologic basis for the urogenital
dysfunction, the clinical presentation,
and the recommended management.
MULTIPLE SCLEROSIS
Neurologic Basis of
Urogenital Symptoms
Urogenital symptoms in multiple scle-
rosis (MS) are common and result
mainly from spinal cord involvement,
so that some correlation between
lower limb and bladder dysfunction is
often clinically apparent (Betts et al,
1993). In health, a complex of brain
networks is involved in the two pro-
cesses of bladder storage and voiding,
but the final output of these processes
is either activation or inhibition of a
center in the dorsal tegmentum of the
165
KEY POINTS:
A The highly
distributed
nature of the
neural control of
the bladder and
genitalia means
that disorders of
these functions
are very likely to
occur with many
different
neurologic
diseases,
although the
range of
symptoms
is limited.
A The lower urinary
tract is
peripherally
innervated by
nerves of the
autonomic
nervous system,
but a hierarchy of
higher centers is
involved in the
perception of
bladder fullness
and the decision
about the
appropriateness
of when to void.
A Urogenital
symptoms in MS
are common and
result mainly
from spinal cord
involvement, so
that some
correlation
between lower
limb and bladder
dysfunction is
often clinically
apparent.
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
pons, the pontine micturition center
(PMC) (Figure 7-1).
From the PMC, direct pathways
project to the sacral segments of the
spinal cord (S2-S4) and control para-
sympathetic outflow to the detrusor
and reciprocal activation of the striated
urethral sphincter. During storage, pa-
rasympathetic motor innervation of the
detrusor is inhibited so that the de-
trusor pressure does not rise as the
bladder fills and tonic firing of the
motor units of the striated urethral
sphincter and pelvic floor maintain the
pressure of the urethra higher than
that within the bladder. At the initia-
tion of micturition, a relaxation of the
striated urethral sphincter and pelvic
floor occurs, followed by a coordinated
contraction of the detrusor muscle.
This synergistic activity between the
sphincter and the detrusor depends on
connections with the PMC. If these
connections are damaged or interrup-
ted, sphincter contraction may occur as
the detrusor contracts, causing the
disorder known as detrusor sphincter
dyssynergia. The most marked abnor-
mality, however, which develops fol-
lowing disconnection from the PMC, is
a newly formed segmental reflex that
causes reflex detrusor contractions in
response to bladder distension. Unmy-
elinated C fibers, hitherto quiescent
(and therefore known as silent C
fibers), become mechanosensitive and
respond to bladder stretch (de Groat
et al, 1990). This afferent activity,
through synaptic activity in sacral seg-
ments of the cord, causes detrusor
contractions and is responsible for the
emergence of the condition of neuro-
genic detrusor overactivity (DO) and
complaints of urinary frequency, ur-
gency, and urgency incontinence.
Evidence also points to spinal cord
involvement as the major cause of
erectile dysfunction (ED) in MS (Betts
et al, 1994). Cord involvement in MS
may initially result in a partial deficit, so
that ED is variable but with preserved
penile erections nocturnally and on
morning waking (Kirkeby et al, 1988).
In the last 20 years the error of the
dictum if a man can get an erection
at anytime, impotence is likely to be
psychogenic has been recognized. ED
has been estimated to affect between
50% and 75% of men with MS (Zorzon
et al, 1999), depending on the severity
of disability of the group studied.
Women with MS report sexual dysfunc-
tion less frequently than men (Zorzon
et al, 1999), but nevertheless, it is a
problem that is thought to affect more
than 50% of women, and incidence in-
creases with increasing disability.
Clinical Presentation
Bladder dysfunction. Urinary fre-
quency, urgency, and urgency incon-
tinence, reflecting the underlying DO
166
FIGURE 7-1
Location of pontine micturition
center (PMC). This illustration
highlights the need for spinal
cord integrity for bladder control since it is
parasympathetic and somatic innervation arises
from the sacral segments 2-4.
KEY POINT:
A In the last
20 years the
error of the
dictum if a
man can get
an erection at
anytime,
impotence is
likely to be
psychogenic
has been
recognized.
"
DISORDERS OF THE UROGENITAL SYSTEM
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
and easily demonstrable on cystome-
try, are the most common bladder
complaints in MS. Frequency is due to
the reduced bladder capacity. Urgency
and, if the patient cannot hold on,
urgency incontinence, are due to in-
voluntary detrusor contractions. Symp-
toms of incomplete bladder emptying
may be much less prominent, the
patient only admitting to these if
directly asked, Do you feel empty
after voiding? or Can you void again
soon after just doing so? It was found
that patients who thought they were
not emptying their bladder were often
correct, but half of those who thought
they were emptying their bladder were
likely to be wrong; hence, the im-
portance of measuring the postmictu-
rition residual volume with ultrasound
(Figure 7-2).
With worsening neurologic disease
and increasing spinal cord lesions such
that mobility deteriorates, bladder con-
trol is likely to become more difficult to
treat. This is a result of worsening of
DO, inefficient emptying of the blad-
der, possibly recurrent urinary tract
infections, spasticity, reduction in gen-
eral mobility, and sometimes, cognitive
impairment. Fortunately, however, in
contrast to urinary tract dysfunction
following traumatic spinal cord injury,
MS rarely causes upper urinary tract
involvement (Sirls et al, 1994). This is
true even when long-standing MS has
resulted in severe disability and spas-
ticity. The reason is not known, but the
implication is that the focus of man-
agement should be on symptomatic
relief.
Sexual dysfunction. A study that
analyzed the type of sexual dysfunc-
tion that affected men with MS who
were still ambulant found that ED was
the most common complaint (63%),
followed by ejaculatory dysfunction
and/or orgasmic dysfunction (50%)
and reduced libido (40%) (Zorzon
et al, 1999). Other nonspecific effects
of MS may also have adverse effects on
sexual function, including fatigue, de-
pression, spasticity, and anxiety about
incontinence.
Although a recent questionnaire
survey of 133 women with mild dis-
ability in the United States, of whom
half reported voiding symptoms, found
that 70% still enjoyed sexual inter-
course, felt aroused, and could expe-
rience orgasm (Borello-France et al,
167
FIGURE 7-2
Algorithm for management of
neurogenic incontinence.
PVR = postvoid residual; CISC = clean
intermittent self-catheterization.
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
2004), in women with advanced
MS, 62% experienced sensory dysfunc-
tion in the genital area (Hulter and
Lundberg, 1995). Loss of orgasmic
capacity is the complaint for which
women seek treatment (Dasgupta et al,
2004).
Management
Bladder dysfunction. The symptoms
of urgency, frequency, and urgency in-
continence are due to detrusor over-
activity and can, therefore, logically be
treated with antimuscarinic agents. A
number of different preparations are
now available (Table 7-1), and long-
acting formulations (extended life
[XL]) have the advantage of once-daily
administration. Patients who have cog-
nitive impairment are best treated by
the medications less likely to cross the
blood-brain barrier, such as trospium
chloride.
Although it might appear appropri-
ate to immediately prescribe an anti-
muscarinic for patients complaining of
urinary urgency, a measurement needs
to be made first. If there is any reason
to suspect that the patient is not em-
ptying completely, the postmicturition
residual volume should be measured
(Fowler, 1996). This can be conve-
niently done using a small portable
ultrasound device, which many special-
ist nurse continence advisors have
available. It is important to recognize
incomplete emptying because any resi-
dual volume in the bladder can trigger
volume-determined reflex detrusor
contractions and thus exacerbate DO.
Figure 7-2 shows a simple algorithm
for managing the common symptoms
of bladder dysfunction in MS. The
place of cystometry and video cysto-
metry in the routine investigation of
these patients is questionable. It has
been argued that it is only through
these investigations that detrusor
sphincter dyssynergia can be recog-
nized, but since no specific treatment is
available for that disorder other than
managing the consequence, ie, incom-
plete emptying and raised detrusor
pressure, a pragmatic approach such
168
TABLE 7-1
Oral Antimuscarinic Agents for Treating Symptoms of
Detrusor Overactivity
Generic
Name
Trade Name in
the United States
Dose
(mg) Frequency
Elimination
Half-life of
Drug (Hours)
Propantheline Pro-Banthine 7.515.0 Tid 30 min
ac and qhs
<2
Tolterodine Detrol 12 bid 2.4
Tolterodine Detrol LA 24 od 8.4
Trospium Sanctura 20 bid 20
Oxybutynin Ditropan 2.55.0 bid to tid 2.3
Oxybutynin XL Ditropan XL 530 od 13.2
Darifenacin Enablex 7.515.0 od 1319
Solifenacin Vesicare 510 od 4068
ac = before meals; bid = 2 times daily; od = daily; tid = 3 times daily; qhs = each bedtime;
qid = 4 times daily.
KEY POINTS:
A It was found
that patients
who thought
they were not
emptying their
bladder were
often correct,
but half those
who thought
they were, were
likely to be
wrong; hence,
the importance
of measuring the
postmicturition
residual volume
with ultrasound.
A Although it
might appear
appropriate to
immediately
prescribe an
antimuscarinic
for patients
complaining of
urinary urgency,
a measurement
needs to be
made first.
"
DISORDERS OF THE UROGENITAL SYSTEM
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
as shown in Figure 7-2 has much to
recommend it.
If a raised postmicturition residual
volume is demonstrated, some means
of reducing this will be necessary to
improve symptoms. This can be done
by having either the patient or some-
times the caregiver perform clean
intermittent catheterization (CIC). CIC
has been advocated if the postmictu-
rition residual volume is greater than
100 mL, a somewhat arbitrary figure,
but one about which there seems to be
general agreement. Teaching the tech-
nique is more likely to be successful if
patients are well motivated and have
good cognitive skills and adequate
manual dexterity. Because patients also
need to have sufficient mobility to be
able to get into a comfortable position
to catheterize efficiently, ideally over
the toilet, severe immobility can pres-
ent a problem (Case 7-1).
Unfortunately, little else improves
bladder emptying; although there
were claims that alpha-blockers could
reduce the postmicturition residual
volume, subsequent studies have not
confirmed this. On theoretical grounds
this is not surprising since it is thought
the defect of bladder emptying in MS
is due to poorly sustained and incoor-
dinated relaxation of the striated
sphincter, a muscle on which alpha-
blockers are thought to be ineffective.
If patients are performing self-
catheterization, urine specimens sent
to the laboratory are likely to grow
microorganisms, although other crite-
ria that indicate a urinary tract infection
are not present. However, if genuine
recurrent urinary tract infections do
occur with the expected clinical symp-
toms of dysuria and change in color
and odor of the urine, investigations
should be carried out to discover if
there is a nidus for infection in the
urinary tract, and a urologic referral is
mandatory. Hematuria is another indi-
cation for prompt urologic referral.
An additional therapy that may
sometimes be of value is the synthetic
169
Case 7-1
A 42-year-old woman, diagnosed with MS 6 years ago when she presented
with sensory symptoms followed by optic neuritis, has suffered a
deterioration of mobility over the last year, such that she now needs a cane
for walking. She reports poor bladder control, which has been present for
the past 2 to 3 years but has noticeably worsened in the last year. Her
problems are of urinary frequency, such that she has been restricting fluid
intake, but her most troublesome symptom is urinary urgency. With her
reduced mobility she finds it difficult to reach a toilet in time and notices
urgency is particularly likely to come on as she rises from a sitting position.
On questioning as to whether she empties her bladder, she answers not
all the time, saying that she can often void again having just emptied her
bladder 30 minutes before.
Using abdominal ultrasound, she is shown to have a postmicturition
residual volume of 160 mL. She is therefore started on clean intermittent
self-catheterization (CISC) and given oral long-acting tolterodine 4 mg once
a day. Taking this medication and using CISC twice a day, she stops having
episodes of urgency incontinence and feels it safe to drink more liquids.
Comment. This womans case history illustrates the importance of
measuring the postmicturition residual volume if effective treatment is to
be achieved.
KEY POINT:
A If genuine
recurrent urinary
tract infections
do occur with the
expected clinical
symptoms of
dysuria and
change in color
and odor of
the urine,
investigations
should be carried
out to discover
if there is a nidus
for infection in
the urinary tract,
and a urologic
referral is
mandatory.
Hematuria is
another
indication
for prompt
urologic referral.
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
antidiuretic hormone desmopressin.
Its use in children to treat nocturnal
enuresis is well established, and stud-
ies have also demonstrated its efficacy
in women with MS and nighttime
frequency. It was shown to be effective
if taken during the day in providing
the patients with a period up to 6
hours during which they were not
troubled by urinary frequency and
were without any rebound nighttime
frequency (Hoverd and Fowler, 1998).
However, patients must be cautioned
to use desmopressin only once in 24
hours despite the convenience of its
effect, and it should not be given to
those with dependent leg edema
caused by immobility who have night-
time frequency. Nor should desmo-
pressin be prescribed for patients over
the age of 65 years as there is a risk of
its inducing cardiac failure.
There is, however, a point in the
progression of MS where first-line
treatment may be insufficient to con-
tain urinary symptoms and yet the
patient does not want to have a long-
term indwelling catheter. This point in
decline is often reached as the neuro-
logic disability, particularly mobility, is
deteriorating and the patient there-
fore is not in a robust state of health to
undergo bladder augmentation sur-
gery, such as a clam cystoplasty. A
very promising treatment that can
then be used at this stage is detrusor
injection of botulinum A toxin. The
discovery that injection of botulinum
toxin A directly into the smooth
muscle of the detrusor resulted in a
significant alleviation of neurogenic
bladder dysfunction (Schurch et al,
2000) is having far-reaching conse-
quences. Originally proposed on the
basis that botulinum toxin A would
block the presynaptic release of para-
sympathetic acetylcholine-mediating
detrusor contraction, the benefits of
this treatment appear to exceed those
expected from an agent that merely
paralyzes the detrusor muscle. It
seems likely that botulinum toxin A is
also affecting the vesicular release
of neurotransmitters involved in the
afferent arm of abnormal reflex blad-
der contractions (Apostolidis et al,
2006).
Many hundreds of patients world-
wide have nowbeen successfully treated
by injections of 200-mU to 300-mU
botulinum toxin A (Botox) injected in
20 to 30 equally spaced points in the
bladder wall. In our department we have
used a minimally invasive technique,
performed in 20 minutes as a clinic
procedure under local anesthetic, to
treat 43 patients with MS. All benefited,
with their voiding diaries showing
remarkable improvements in the re-
duction of urinary urgency, frequency,
and incontinence. However, they then
all needed to perform CISC, even
the 30% who had not been doing
so prior to treatment. Fortunately, this
did not appear to affect their quality
of life, which showed highly signifi-
cant improvements, with the benefit
lasting for a mean of 9.7 months. Cen-
ters with the longest experience of
this treatment have been able to
show that subsequent reinjections are
as effective as the initial one and
of comparable duration (Grosse et al,
2005).
With further neurologic progression,
there may become a stage when a long-
term indwelling catheter becomes nec-
essary. A suprapubic catheter is the
preferred management option. This
should be sited by a urologic surgeon
who may want the patient to have a
general anesthetic so that the bladder
can be distended, facilitating the supra-
pubic puncture into the otherwise
shrunken organ.
Sexual dysfunction. Prior to the ad-
vent of the oral erectogenic medications,
men with MS were successfully treated
with intracavernosal injection therapy
(Kirkeby et al, 1988). Subsequently, a
170
KEY POINT:
A The discovery
that injection of
botulinum toxin
A directly into
the smooth
muscle of the
detrusor resulted
in a significant
alleviation of
neurogenic
bladder
dysfunction
is having
far-reaching
consequences.
"
DISORDERS OF THE UROGENITAL SYSTEM
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
multicenter placebo-controlledtrial dem-
onstrated an excellent response to sil-
denafil citrate in men with MS (Fowler
et al, 2005). Although in that study
orgasmic capacity was also increased, a
fact that was attributed to the men
being able to sustain an erection longer,
it is known that a significant proportion
of men continue to have difficulty with
ejaculation, for which, as yet, no effec-
tive medication is available, although
yohimbine may be tried. Probably the
best recourse is to use a vibrating sex
aid.
Following the success of sildenafil
citrate in the treatment of sexual
function with men, a small placebo-
controlled trial in women with sexual
dysfunction and MS was carried out. A
questionnaire was used to measure
sexual response, and although there
was a significant improvement in lu-
brication and some improvement in
sensation, there was no overall change
in orgasmic response in the active-
treatment group compared with those
in the placebo-treated group (Dasgupta
et al, 2004). Although disappointing,
this was not perhaps surprising.
The pharmaceutical industry con-
tinues research to discover agents that
might be effective in the treatment of
female sexual dysfunction, but despite
the current lack of specific treatment,
women with MS found the oppor-
tunity to discuss their problem with
a health care professional beneficial
(Hulter and Lundberg, 1995).
MULTIPLE SYSTEM ATROPHY
Neurologic Basis of
Urogenital Symptoms
The explanation for the multiple types
of bladder dysfunction that can oc-
cur in multiple system atrophy (MSA)
probably reflects the neuronal atro-
phy in the CNS that occurs at many
different sites involved in bladder
control (Kirby et al, 1986). It has been
proposed that cells situated in the
dorsal tegmentum of the pons, possi-
bly those of the PMC, are involved in
the atrophying process. It may be that
their decline results in loss of in-
hibition and thus DO. Involvement of
the intermediolateral cell columns of
the spinal cord, which convey the
descending sympathetic and parasym-
pathetic innervation of the sacral re-
gion, may account for the observed
open bladder neck and impairment
of bladder emptying. Neuronal atrophy
of cells in the Onuf nucleus leads to
chronic denervation of the striated
sphincters (Sakuta et al, 1978), both
anal and urethral. It is the combi-
nation of DO, incomplete emptying,
and sphincter weakness that accounts
for the early and severe incontinence
that so often characterizes the onset
of MSA.
Much less is known about the
neuropathologic substrate of sexual
dysfunction in MSA, but whereas ED
was formerly thought to be secondary
to hypotension, the dissociation of
these disorders (Kirchhof et al, 2003)
and the observation that erectile re-
sponses can be restored in men with
MSA and hypotension by treatment
with sildenafil citrate argue for a
different pathophysiology. Erection is
known to result from stimulation of
dopamine receptors in the medial
preoptic area of the hypothalamus,
and it has been hypothesized that ED
could result either from impairment
of sacral autonomic innervation or
impairment of dopaminergic-mediated
pathways in the CNS (Kirchhof et al,
2003).
Clinical History
The earliest studies of MSA drew at-
tention to the premonitory nature of
urogenital symptoms in the condition.
The explanation for this remains to
be discovered, but after initial stud-
ies that highlighted the fact that
171
KEY POINTS:
A The
pharmaceutical
industry
continues
research to
discover agents
that might be
effective in the
treatment of
female sexual
dysfunction,
but despite the
current lack of
specific
treatment,
women with
MS found that
the opportunity
to discuss their
problem with a
health care
professional
was beneficial.
A The explanation
for the multiple
types of bladder
dysfunction that
can occur in
multiple system
atrophy (MSA)
probably reflects
the neuronal
atrophy in the
CNS that occurs
at many different
sites involved in
bladder control.
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
urogenital symptoms were early and
almost invariable in the disease (Beck
et al, 1994), recent studies have exam-
ined the chronology of evolution of
postural hypotension compared with
disorders of bladder and sexual func-
tion. It was clearly shown that, at onset,
the incidence of urinary symptoms was
more than twice that of orthostatic
symptoms (96% compared with 43%)
and that no patients had orthostatic
symptoms only, but 53% had urinary
symptoms alone (Sakakibara et al,
2000). There were 43% with both uri-
nary and orthostatic symptoms, and
in 21% urinary symptoms appeared
first (Figure 7-3).
A study that looked retrospectively
at a group of 71 men with a diagnosis
of probable MSA who had bladder
complaints noted that ED was a
complaint in all men who were que-
ried. The onset of ED had preceded
the onset of bladder symptoms in 58%
and the onset of orthostatic hypoten-
sion symptoms in 91%. Bladder symp-
toms also preceded symptoms of
orthostatic hypotension in 76% of
patients (Kirchhof et al, 2003).
Female sexual dysfunction in MSA
has been little studied, but a single pa-
per reported that, when women with
MSA-parkinsonian type or Parkinsons
disease and healthy controls were
questioned, 47% of the patients with
MSA-parkinsonian type, but only 4% of
the patients with Parkinsons disease
and 4% of the control group, admitted
to reduced genital sensitivity. Further-
more, the appearance of this complaint
in female patients with MSA showed a
close temporal relation to the onset of
the disease (Oertel et al, 2003).
Erectile dysfunction is common in
the general population, and its inci-
dence is known to increase with age.
Likewise, bladder symptoms are also
common and often due to under-
lying urologic disorders. However,
the evidence points to the fact that
urogenital complaints are an early and
almost inevitable component of MSA,
be it MSA-parkinsonian type or MSA-
cerebellar type, and an absence of
these symptoms makes the diagno-
sis unlikely. Furthermore, urogenital
symptoms may be valuable in distin-
guishing cases of MSA from other
forms of parkinsonism and idiopathic
Parkinsons disease because in those
conditions urogenital symptoms occur
late, often in the context of marked
neurologic disability.
Clinical Presentation
Urinary incontinence or a fear of im-
minent incontinence is the most com-
mon presenting bladder complaint,
although other urinary symptoms may
precedethis (Kirby et al, 1986; Sakakibara
et al, 2000). Although urinary symp-
toms in either men or women are com-
mon, the onset of incontinence in the
preceding 4 to 5 years, together with
an appropriate neurologic profile, is
an ominous portent for a diagnosis of
MSA. Detailed studies of patients us-
ingvideourodynamics, cystometry, and
sphincter EMG (Kirby et al, 1986) have
172
FIGURE 7-3
Timing of urinary and orthostatic symptoms
in patients with multiple system atrophy.
Sakakibara R, Hattori T, Uchiyama T, et al. Urinary
dysfunction and orthostatic hypotension in multiple
system atrophy: which is the more common and earlier
manifestation? J Neurol Neurosurg Psychiatry
2000;68(1):6569. Reprinted with permission from
BMJ Publishing Group Ltd.
KEY POINT:
A A recent study
has clearly shown
that, at onset,
the incidence of
urinary symptoms
was more than
twice that of
orthostatic
symptoms (96%
compared to 43%)
and that no
patients had
orthostatic
symptoms only,
but 53% had
urinary symptoms
alone.
"
DISORDERS OF THE UROGENITAL SYSTEM
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
shown that often a combination of
DO and sphincter weakness is pres-
ent. The finding of an open bladder
neck, generally an unusual feature in
a man, is quite specific in men with
MSA. Occasionally a patient may pres-
ent with complete urinary retention,
but difficulty voiding is much more
common and the likelihood of raised
postmicturition residual volume seems
to increase as the disease progresses
(Ito et al, 2006). A raised postmictu-
rition residual volume is much more
common in MSA than Parkinsons dis-
ease and may even be of diagnostic
value in the differential diagnosis of the
two conditions (Hahn and Ebersbach,
2005).
Management
Some while ago men with MSA and
incontinence were often considered
for prostatectomy, but in recent years
this seems to be occurring less often,
presumably due to urologists increas-
ing awareness of MSA and the more
widespread use of pressure-flow stud-
ies to demonstrate obstructed outflow
before surgery. Men with MSA who
have had transurethral prostatectomy
seldom report that surgery improves
their bladder symptoms.
Preferably, urologic surgery should
be avoided, using instead medical
means to manage incontinence or
incomplete bladder emptying. The
management algorithm outlined in
Figure 7-2 has also proved highly
effective in patients with MSA, and
many who had been incontinent at an
early stage of the disease manage to
maintain continence until they become
severely disabled (Beck et al, 1994),
when a suprapubic indwelling catheter
is the preferred option. Synthetic anti-
diuretic hormone (desmopressin) can
be highly effective in reducing night-
time frequency and may also have a
beneficial effect on postural hypoten-
sion (Case 7-2).
In some patients detrusor overactiv-
ity predominates and does not re-
spond adequately to anticholinergics.
It will be interesting to see if the re-
cently introduced intervention of de-
trusor injections of botulinum toxin
(Schurch et al, 2000) proves to have
173
Case 7-2
A 57-year-old man was first seen by a urologist 3 years ago, and although
no urologic abnormality could be found, he was demonstrated on a
number of occasions not to be emptying his bladder fully. He was started
on long-acting tolterodine 4 mg daily and shown how to do CISC. He
had been taking sildenafil for ED for 5 years.
Two years ago a neurologist made a diagnosis of parkinsonism, and
1 year ago a diagnosis of MSA was made on clinical grounds based on his
neurologic deterioration. He was complaining then that his incontinence,
particularly at night, was very distressing, so he was advised to do CISC
before going to bed and to use desmopressin spray at night. When next
seen, he was no longer experiencing nocturnal enuresis and with CISC
at eight hourly intervals, his bladder control during the day had greatly
improved. However, at his most recent examination he was noted to have
developed hypophonic slurring dysarthria, akinesia, and rigidity.
Comment. The bladder symptoms of MSA can be significantly alleviated
by appropriate treatment despite continuing deterioration of the
underlying neurologic condition.
A Although urinary
symptoms in
either men or
women are
common, the
onset of
incontinence in
the preceding 4
to 5 years,
together with an
appropriate
neurologic
profile, is an
ominous portent
for a diagnosis
of MSA.
A Men with MSA
who have had
transurethral
prostatectomy
seldom report
that surgery
improves
their bladder
symptoms.
KEY POINTS:
A The evidence
points to the fact
that urogenital
complaints are an
early and almost
inevitable
component of
MSA, be it MSA-
parkinsonian type
or MSA-
cerebellar type,
and an absence
of these
symptoms makes
the diagnosis
unlikely.
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
a role in the management of these
patients.
The majority of men in the general
population with ED are successfully
treated by oral phosphodiesterase in-
hibitors, but a small study of six men
with MSA showed that, in those with
preexisting postural hypotension, sil-
denafil citrate exacerbated the blood
pressure fall to a potentially dangerous
degree, whereas those without pos-
tural hypotension did not show
changes (Hussain et al, 2001). From
this, the recommendation has been
made that lying and standing blood
pressure should be checked in men
with parkinsonism before prescrib-
ing oral phosphodiesterase inhibitors.
Furthermore, it would seem prefer-
able to use the shorter-acting phospho-
diesterase inhibitors such as silden-
afil or vardenafil rather than the
popular tadalafil, with its half-life of
18 hours.
URINARY RETENTION IN
YOUNG WOMEN
(FOWLERS SYNDROME)
Neurologic Basis
Until the latter part of the 20th cen-
tury, urinary retention in women was
commonly considered to be psycho-
genic. Urologic or gynecologic causes
of retention are rare and can be ex-
cluded by cystoscopy, leaving a signifi-
cant number of women in whom
retention is said to have a functional
basis. Past teaching was that urinary
retention was either the presenting
symptom of MS or that it was due to
hysteria. However, in 1985 this
author recorded an unusual type of
EMG activity from the striated urethral
sphincter using a concentric needle
electrode in a series of young women
with urinary retention. The EMG activ-
ity consisted of complex repetitive
discharges and a myotonic-like sound-
ing component, decelerating bursts,
which was proposed to indicate im-
paired urethral relaxation. Detailed anal-
ysis of the EMG activity using single-
fiber electrode techniques showed that
the jitter of the constituent complexes
was so low that the activity was the
result of ephaptic transmission of im-
pulses between muscle fibers. A pro-
portion of these young women also
had a history or clinical features of
polycystic ovaries (Fowler et al, 1988).
It was hypothesized that the hor-
monally sensitive striated sphincter
had developed a local muscle mem-
brane instability, allowing direct spread
of excitatory impulses and, thus, the
inappropriate and involuntary sustained
contraction of the sphincter (Fowler
andDasgupta, 2002). Inthe last 20 years,
this condition has been increasingly
referred to as Fowlers syndrome.
In a group of somewhat older
women with urinary retention who
otherwise have the characteristic fea-
tures of Fowlers syndrome, altera-
tions of cardiovascular autonomic
function were discovered. It was then
proposed that the condition is due to
an occult dysautonomia (Amarenco
et al, 2006). In the authors experi-
ence, however, if all possible urologic
or neurologic disorders are eliminated
and an abnormally high urethral pres-
sure is demonstrated (see below), the
condition does not evolve but remains
an isolated disorder of voiding, benign
though highly inconvenient.
A retrospective study of 247 women
with urinary retention referred to uro-
neurology at Queen Square over a
4-year period showed that Fowlers
syndrome was the most common
diagnosis, accounting for 58%. No
diagnosis to explain the urinary reten-
tion could be made in 32% of the
women, but in only two of that large
series of women was urinary retention
the presenting symptom of a neuro-
logic disease (Kavia et al, 2006). If
urinary retention is due to either
174
KEY POINTS:
A The
recommendation
has been made
that lying and
standing blood
pressure should
be checked in
men with
parkinsonism
before
prescribing oral
phosphodiesterase
inhibitors.
A Urologic or
gynecologic
causes of
retention are
rare and can
be excluded by
cystoscopy,
leaving a
significant
number of
women in
whom retention
is said to have
a functional
basis.
A It was
hypothesized
that the
hormonally
sensitive striated
sphincter had
developed a local
muscle
membrane
instability,
allowing direct
spread of
excitatory
impulses and,
thus, the
inappropriate
and involuntary
sustained
contraction of
the sphincter.
"
DISORDERS OF THE UROGENITAL SYSTEM
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
central or peripheral nervous system
disease, neurologic features with ab-
normalities on imaging and CSF exam-
ination are almost invariably present
and often prominent (Sakakibara et al,
2006). This is not the case in Fowlers
syndrome.
Clinical Presentation
A retrospective questionnaire survey
of 91 women with Fowlers syndrome
showed that the common clinical
features are painless urinary retention,
with a demonstrated bladder capacity
at some stage of the history in excess
of 1 L and difficulty in removing
catheters used for self-catheterization
(Swinn et al, 2002). Abdominal strain-
ing does not help voiding. A striking
aspect of these womens history is an
absence of the sense of bladder
fullness that would be expected with
such large bladder capacities and
general decrease in bladder sensation.
Animal studies indicate that contrac-
tion of the striated sphincter has an
inhibitory effect on detrusor contrac-
tion and on bladder afferent activity
(de Groat et al, 2001), and the
activation of comparable neural path-
ways in these women could account
for the observed clinical features.
In many of the patients a clinical
incident, such as a surgical procedure
under general anesthesia, a urinary
tract infection, or childbirth, may have
triggered the onset of retention. In
younger women in particular, the
onset is often apparently spontaneous
(Swinn et al, 2002). Sometimes after
acute catheterization voiding ability
may recover, but retention then recurs
some months or even years later. A
young woman with retention may
admit on direct questioning to having
had an interrupted urinary stream for
many years, although this was unrec-
ognized as being abnormal, or recur-
rent urinary tract infections, probably
resulting from incomplete emptying.
Intermittent self-catheterization is un-
doubtedly more difficult for these
young women than for women with
MS, and it is not uncommon for them
to describe difficulty with removing
the catheter, as if something is grip-
ping it as it is withdrawn. This is
thought to be due to contraction of
the normally innervated but patholog-
ically overactive striated sphincter
around the catheter.
Although the syndrome was origi-
nally described on the basis of needle
EMG of the striated urethral sphincter
(the abnormality is not found in the
anal sphincter), urethral sphincter
EMG is not an easy test to perform,
and despite the use of local anes-
thetic, it is uncomfortable for the
patient. Furthermore, although EMG
sampling gives some indication as to
whether or not the abnormality is
present, the result gives no quanti-
tative estimate of dysfunction, unlike
the urethral pressure profile. Using
a pull-through catheter, urethral
pressure can be measured at rest with
the expected value derived from the
following equation: expected value
(cm H
2
O) = 92 age (in years).
Women with Fowlers syndrome
commonly have values in excess of
100 cm H
2
O (Kavia et al, 2006). The
volume of the sphincter muscle esti-
mated by a vaginal ultrasound probe
may show enlargement, so if there is a
typical history and both the urethral
pressure profile and the sphincter
volume are abnormally raised, EMG
is now less commonly required to
confirm the diagnosis (Kavia et al,
2006).
Management
The mainstay of management is CISC,
but many women find this uncomfort-
able; it is not unusual for a suprapubic
catheter to be required. Psychologi-
cally, the prospect of indefinite self-
catheterization for a young woman
175
KEY POINTS:
A A retrospective
study of 247
women with
urinary retention
referred to
uro-neurology at
Queen Square
over a 4-year
period showed
that Fowlers
syndrome was
the most
common
diagnosis,
accounting
for 58%.
A The common
clinical features
of Fowlers
syndrome are
painless urinary
retention with a
demonstrated
bladder capacity
at some stage
of the history
in excess of 1 L
and difficulty
in removing
catheters used
for self-
catheterization.
A Intermittent self-
catheterization
is undoubtedly
more difficult
for young
women with
Fowlers
syndrome than
for women with
MS, and it is not
uncommon for
them to describe
difficulty with
removing the
catheter, as if
something is
gripping it as
it is withdrawn.
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
is understandably distressing. The only
intervention that has been found to
restore voiding is sacral nerve stimu-
lation (SNS), also called sacral neuro-
modulation (Swinn et al, 2002). This
involves inserting a unilateral stimu-
lating lead into the presacral plexus
through the third sacral foramen
and connecting it to an external bat-
tery with its settings adjusted so that
the patient senses pelvic sensations.
The stimulation is then set to sub-
threshold intensity so that the sub-
ject rapidly adapts to the continuous
stimuli.
Exactly the same intervention is
used to treat intractable urinary fre-
quency and urgency, and the paradox
of the same treatment being used to
treat clinically opposite conditions is
probably best understood by consider-
ing the underlying pathophysiology
of each disorder: in overactive blad-
der conditions it seems likely the sti-
mulation of afferents is having an
inhibitory effect, whereas in Fowlers
176
Case 7-3
A 37-year-old nurse was first seen at age 22 after she had undergone
an ear, nose, and throat procedure under general anesthetic. Following
this she was unable to urinate. She had some feeling of pressure when
her bladder was full but had lost normal sensation. In addition, she
was complaining of vague sensory symptoms in her left leg. Clinical
examination was essentially normal except for some inconsistent sensory
disturbance on the left. However, neurologic investigations, including
a myelogram, MRI of the brain, and visual evoked potentials, were normal.
A neurologist suggested her urinary retention might have been of
psychogenic origin.
A year later, urethral sphincter EMG was highly abnormal. Profuse
complex repetitive discharges and decelerating bursts were recorded,
consistent with the diagnosis of Fowlers syndrome.
She remained in complete urinary retention and for 7 years managed
to empty her bladder by intermittent self-catheterization. This did not
prevent her from working full time, and she spent 1 year backpacking
in the Far East. Then 8 years ago an SNS was implanted, and although she
passed urine postoperatively, within 24 hours she developed symptoms
and signs of an infection at the stimulator site. The stimulator had to
be removed, and the infective microorganism was the nosocomial
multiresistant Staphylococcus aureus. She was required to avoid contact
with patients and was off work for many months. She remained reluctant
to consider a repeat attempt at SNS and continued with intermittent
self-catheterization for another 6 years until she accepted the offer of
a stimulator implant using the new 2-stage technique. Fortunately,
this was successful, and she was able to urinate spontaneously for the first
time in 15 years. She no longer needs to self-catheterize.
Comment. The young woman was initially the victim of then prevailing
medical prejudice some 20 years ago, which asserted urinary retention
in women was commonly psychogenic. It is particularly important
that neurologists are aware of this condition because urologists often refer
these patients when their investigations fail to reveal an abnormality.
If the diagnosis is recognized, sacral neuromodulation can restore
voiding ability.
KEY POINT:
A The only
intervention
which has been
found to restore
voiding is
sacral nerve
stimulation,
also called sacral
neuromodulation.
"
DISORDERS OF THE UROGENITAL SYSTEM
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
syndrome the stimuli may counteract
the inhibition that results from the
overactive sphincter. Studies of wom-
en with retention due to Fowlers
syndrome suggest that SNS does not
restore voiding by a direct sphincter
relaxant effect since urethral pres-
sure profiles remain abnormally raised
and abnormal EMG activity continues
(DasGupta and Fowler, 2004). PET
functional brain imaging of women
in whom neuromodulation had re-
stored the ability to void showed res-
toration of activity associated with
brain stem autoregulation and atte-
nuation of cingulate activity (Dasgupta
et al, 2005).
The surgical techniques for SNS have
evolved and improved in recent years,
but the reoperation rate either to adjust
the site of the stimulating lead, to
alleviate discomfort from the stimulat-
ing box, or to try to restore lost
effectiveness remains high, at about
50%. However, long-term studies of
the efficacy of SNS have shown that
higher percentages of patients with
retention continue to respond than
those withurinary frequency or urgency
incontinence, and a recent retrospec-
tive study of the long-term efficacy in
retention showed this was greater in
women with Fowlers syndrome than
in those who had had a normal sphinc-
ter EMG (De Ridder et al, 2007). At
Queen Square our experience has been
comparable, with two thirds of patients
continuing to void without need for
catheterization at 5-year follow-up
(Kavia et al, 2006) (Case 7-3).
Although SNS provides an alterna-
tive to lifelong self-catheterization, an
oral medication that restores sphinc-
ter relaxation would be preferable.
Attempts to enhance available nitric
oxide, the neurotransmitter shown to
effect striated sphincter relaxation,
have not been successful so far (Datta
et al, 2007), although this is clearly the
direction of research that is most likely
to lead to the discovery of a treatment
in the future.
REFERENCES
" Amarenco G, Raibaut P, Ismael SS, et al. Evidence of occult dysautonomia
in Fowlers syndrome: alteration of cardiovascular autonomic function
tests in female patients presenting with urinary retention. BJU Int
2006;97(2):288291.
A study suggesting that urinary retention is part of a generalized autonomic dysfunction.
" Apostolidis A, Dasgupta P, Fowler CJ. Proposed mechanism for the
efficacy of injected botulinum toxin in the treatment of human detrusor
overactivity. Eur Urol 2006;49(4):644650.
Hypothesis to explain why detrusor botulinum toxin A injections work so well.
" Beck RO, Betts CD, Fowler CJ. Genitourinary dysfunction in multiple
system atrophy: clinical features and treatment in 62 cases. J Urol 1994;
151(5):13361341.
Retrospective study highlighting the early occurrence of urogenital symptoms in
multiple system atrophy (MSA).
177
KEY POINTS:
A PET functional
brain imaging of
women in whom
neuromodulation
had restored
the ability to
void showed
restoration of
activity
associated with
brain stem
autoregulation
and attenuation
of cingulate
activity.
A Although sacral
nerve stimulation
provides an
alternative to
lifelong self-
catheterization,
an oral
medication that
restores sphincter
relaxation would
be preferable.
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
" Betts CD, DMellow MT, Fowler CJ. Urinary symptoms and the neurological
features of bladder dysfunction in multiple sclerosis. J Neurol Neurosurg
Psychiatry 1993;56(3):245250.
Clinical study that showed a clear association between the extent of spinal cord
dysfunction and urinary symptoms in multiple sclerosis (MS).
" Betts CD, Jones SJ, Fowler CG, Fowler CJ. Erectile dysfunction in multiple
sclerosis. Associated neurological and neurophysiological deficits, and
treatment of the condition. Brain 1994;117(pt 6):13031310.
The neurologic context of erectile dysfunction in MS.
" Borello-France D, Leng W, OLeary M, et al. Bladder and sexual function
among women with multiple sclerosis. Mult Scler 2004;10(4):455461.
Women mildly affected by MS are still mostly able to enjoy sexual intercourse.
" Dasgupta R, Critchley HD, Dolan RJ. Fowler CJ. Changes in brain activity
following sacral neuromodulation for urinary retention. J Urol
2005;174(6):22682272.
A PET study of women examining the central mechanisms of response to sacral
neuromodulation.
" DasGupta R, Fowler CJ. Urodynamic study of women in urinary retention
treated with sacral neuromodulation. J Urol 2004;171(3):11611164.
Sacral neuromodulation in urinary retention does not work by reversing the sphincter
abnormality.
" Dasgupta R, Wiseman OJ, Kanabar G, et al. Efficacy of sildenafil in the
treatment of female sexual dysfunction due to multiple sclerosis. J Urol
2004;171(3):11891193.
Sildenafil citrate had little effect on sexual function in women with MSa
placebo-controlled trial.
" Datta SN, Kavia RB, Gonzales G, Fowler CJ. Results of double-blind
placebo-controlled crossover study of sildenafil citrate (Viagra) in women
suffering from obstructed voiding or retention associated with the
primary disorder of sphincter relaxation (Fowlers Syndrome). Eur Urol
2007;51(2):489497.
Sphincter relaxation, which is under nitric oxide control, did not improve with
sildenafil citrate in women with voiding dysfunction.
" de Groat W, Kawatani T, Hisamitsu T, et al. Mechanisms underlying the
recovery of urinary bladder function following spinal cord injury. J Auton
Nerv Syst 1990;30(suppl):7177.
An important basic science paper that showed the emergence of an unmyelinated
fiber reflex causes detrusor overactivity following spinal injury.
" de Groat WC, Fraser MO, Yoshiyama M, et al. Neural control of the urethra.
Scand J Urol Nephrol Suppl 2001;35(207):3543.
Review of the experimental evidence showing the effect of sphincter contraction on
detrusor activity.
178
"
DISORDERS OF THE UROGENITAL SYSTEM
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
" De Ridder D, Ost D, Bruyninckx F. The presence of Fowlers syndrome
predicts successful long-term outcome of sacral nerve stimulation
in women with urinary retention. Eur Urol 2007;51(1):229233.
A study that shows that among all women with retention treated with sacral
neuromodulation, those with Fowlers syndrome do better in the long term.
" Fowler CJ. Investigation of the neurogenic bladder. J Neurol Neurosurg
Psychiatry 1996;60(1):613.
A review stressing the importance of measurement of the postvoid residual volume in
the management of neurogenic incontinence.
" Fowler CJ, Christmas TJ, Chapple CR, et al. Abnormal electromyographic
activity of the urethral sphincter, voiding dysfunction, and polycystic
ovaries: a new syndrome? BMJ 1988;297(6661):14361438.
The original proposal of Fowlers syndrome.
" Fowler CJ, Dasgupta R. Electromyography in urinary retention and
obstructed voiding in women. Scand J Urol Nephrol Suppl 2002;(210):
5558.
A review explaining more recent thinking about the pathophysiology of urinary
retention in women with Fowlers syndrome.
" Fowler CJ, Miller JR, Sharief MK, et al. A double blind, randomised study
of sildenafil citrate for erectile dysfunction in men with multiple sclerosis.
J Neurol Neurosurg Psychiatry 2005;76(5):700705.
Sildenafil citrate was highly effective in treating erectile dysfunction in men with
MSplacebo-controlled trial.
" Grosse J, Kramer G, Sto hrer M. Success of repeat detrusor injections of
botulinum a toxin in patients with severe neurogenic detrusor
overactivity and incontinence. Eur Urol 2005;47(5):653659.
The first paper to review the long-term benefits of repeated injections of botulinum
toxin.
" Hahn K, Ebersbach G. Sonographic assessment of urinary retention in
multiple system atrophy and idiopathic Parkinsons disease. Mov Disord
2005;20(11):14991502.
Raised postmicturition residual volume may have diagnostic value for the diagnosis of
MSA.
" Hoverd PA, Fowler CJ. Desmopressin in the treatment of daytime urinary
frequency in patients with multiple sclerosis. J Neurol Neurosurg
Psychiatry 1998;65(5):778780.
Desmopressin in patients with MS taken during the day did not result in rebound
nighttime frequency.
" Hulter BM, Lundberg PO. Sexual function in women with advanced
multiple sclerosis. J Neurol Neurosurg Psychiatry 1995;59(1):8386.
An important early study of sexual dysfunction in women with MS.
179
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
" Hussain IF, Brady CM, Swinn MJ, et al. Treatment of erectile dysfunction
with sildenafil citrate (Viagra) in parkinsonism due to Parkinsons disease
or multiple system atrophy with observations on orthostatic hypotension.
J Neurol Neurosurg Psychiatry 2001;71(3):371374.
Small placebo-controlled study that stressed the importance of measuring blood
pressure in patients with parkinsonism before prescribing sildenafil citrate.
" Ito T, Sakakibara R, Yasuda K, et al. Incomplete emptying and urinary
retention in multiple-system atrophy: when does it occur and how do we
manage it? Mov Disord 2006;21(6):816823.
Repeated measures of postvoid residual volume show that this increased with the
progression of MSA.
" Kavia RB, Datta SN, Dasgupta R, et al. Urinary retention in women: its
causes and management. BJU Int 2006;97(2):281287.
Outcome of investigation of management of a large number of women with urinary
retention referred to a UK tertiary center.
" Kirby R, Fowler C, Gosling J, Bannister R. Urethro-vesical dysfunction in
progressive autonomic failure with multiple system atrophy. J Neurol
Neurosurg Psychiatry 1986;49(5):554562.
Early study highlighting the many different types of bladder dysfunction that can occur
in MSA.
" Kirchhof K, Apostolidis AN, Mathias CJ, Fowler CJ. Erectile and urinary
dysfunction may be the presenting features in patients with multiple
system atrophy: a retrospective study. Int J Impot Res 2003;15(4):293298.
A retrospective study.
" Kirkeby HJ, Poulsen EU, Petersen T, Drup J. Erectile dysfunction in
multiple sclerosis. Neurology 1988;38(9):13661371.
Before the advent of sildenafil citrate men with erectile dysfunction and MS were
successfully treated with intracavernosal injections.
" Oertel WH, Wa chter T, Quinn NP, et al. Reduced genital sensitivity in female
patients with multiple system atrophy of parkinsonian type. Mov Disord
2003;18(4):430432.
The only report of female sexual dysfunction in MSA.
" Sakakibara R, Hattori T, Uchiyama T, et al. Urinary dysfunction and
orthostatic hypotension in multiple system atrophy: which is the more
common and earlier manifestation? J Neurol Neurosurg Psychiatry
2000;68(1):6569.
An important study that shows urinary dysfunction occurs earlier than orthostatic
hypotension in MSA.
" Sakakibara R, Yamanishi T, Uchiyama T, Hattori T. Acute urinary retention
due to benign inflammatory nervous diseases. J Neurol 2006;253(8):
11031110.
A helpful review of the central and peripheral neurologic causes of urinary retention and
the associated neurologic features.
180
"
DISORDERS OF THE UROGENITAL SYSTEM
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
" Sakuta M, Nakanishi T, Toyokura Y. Anal muscle electromyograms differ
in amyotrophic lateral sclerosis and Shy-Drager syndrome. Neurology
1978;28(12):12891293.
Remarkably early study giving the basis for sphincter EMG in the diagnosis of MSA.
" Schurch B, Sto hrer M, Kramer G, et al. Botulinum-A toxin for treating
detrusor hyperreflexia in spinal cord injured patients: a new alternative
to anticholinergic drugs? Preliminary results. J Urol 2000;164(3 pt 1):692697.
Much-cited paper, the first report of the benefits of botulinum toxin A treatment for
intractable detrusor overactivity.
" Sirls LT, Zimmern PE, Leach GE. Role of limited evaluation and aggressive
medical management in multiple sclerosis: a review of 113 patients. J Urol
1994;151(4):946950.
Postvoid residual volume measurement only, the recommended management in
patients with MS.
" Swinn MJ, Wiseman OJ, Lowe E, Fowler CJ. The cause and natural history
of isolated urinary retention in young women. J Urol 2002;167(1):151156.
A retrospective review of women with Fowlers syndrome, which defined the
clinical history.
" Zorzon M, Zivadinov R, Bosco A, et al. Sexual dysfunction in multiple
sclerosis: a case-control study. I. Frequency and comparison of groups.
Mult Scler 1999;5(6):418427.
Clinical features of patients with sexual dysfunction due to MS.
181
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.