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Cauda equina syndrome: The timing of surgery probably does influence

outcome
N. V. Todd a
a
Department of Neurosurgery, Newcastle General Hospital, UK

Online Publication Date: 01 August 2005

To cite this Article Todd, N. V.(2005)'Cauda equina syndrome: The timing of surgery probably does influence outcome',British Journal
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 British Journal of Neurosurgery, August 2005; 19(4): 301 – 306
REVIEW ARTICLE
Cauda equina syndrome: the timing of surgery probably does influence
outcome
N. V. TODD
Department of Neurosurgery, Regional Neurosciences Centre, Newcastle General Hospital, UK
Introduction
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Patients with cauda equina compression require
decompressive surgery. When that decompressive
surgery should be performed is a matter of con-
troversy. That is because the effect of earlier
decompression upon outcome is controversial. There
are over 100 papers on cauda equina syndrome
(CES) within the literature and that literature can
currently be used to support almost any view with
regard to the timing of surgery. For example:
. decompressive surgery should be carried out as
an emergency;1
. following a complete lesion the timing of surgery
does not influence outcome;2,3
. decompression achieved ‘early’ achieves statisti-
cally better outcomes than ‘late’ decompression;4,5
. decompression achieved within 48 h of CES
achieves better outcomes than decompression
beyond 48 h, but there is no difference in
outcome in patients treated at different times
within the 48-h period.6
Class 1 evidence from a randomized controlled trial
will never be obtained because there will never be a
trial in which patients are randomized to delayed
decompression. The next best evidence (Class 2)
would be meta-analysis of appropriate papers from
the literature. Meta-analysis is an appropriate statis-
tical method for combining the results of a number
of separate studies (w2 analysis of 2 6 2 cells is not
appropriate, as the data represent several separate
studies not one sample randomly selected from the
general population). Treated individuals should only
be compared with control individuals from the same
study, since patient characteristics in different
studies may differ in important respects; combining
patients across many studies is not an appropriate
way to estimate any overall treatment affect.7 The
Correspondence: Mr N. V. Todd, Department of Neurosurgery, Regional Neurosciences Centre, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE,
UK. Tel: 44 191 233 6161 ext 22472.
ISSN 0268-8697 print/ISSN 1360-046X online Ó The Neurosurgical Foundation
DOI: 10.1080/02688690500305324
Ahn et al.6 ‘meta-analysis’ can be criticized on these
bases.
Selection of papers for meta-analysis and
methods
Standard database searches yielded over 100 clinical
papers addressing CES. There are seven pa-
pers,1,4,5,8–11 which report patients operated on
before or after a specific time limit (24 or 48 h after
CES), which test the difference in outcome of ‘early’
and ‘late’ decompression. Two papers4,10 compared
patients treated less than 24 h after the onset of CES
with those treated more than 24 h after the onset of
CES. Four papers1,5,9,11 compared patients treated
less than or more than 48 h after the onset of CES.
One paper8 gives the raw data, which therefore can
be used to compare decompression less than or more
than 24 h and also less than or more than 48 h after
the onset of CES.
There is no a priori reason to think that a decom-
pression should be performed before any specific
time point. However, the literature typically presents
data before and after a specific time point; it is
therefore reasonable to approach the question of
whether earlier surgery is associated with a better
outcome by considering two groups:
. groups treated less than 24 hours;
. groups treated less than 48 h after the onset of
CES;
and their corresponding ‘late’ groups (i) more than
24 h and (ii) more than 48 h after the onset of CES.
The literature is complex and confused, and in order
to simplify the analysis to provide a robust assess-
ment of whether the duration of CES matters, this
review will look at only one input variable (‘early’ v
‘late’ decompression) and only one output variable
(recovery of socially normal bladder function). The
 302 N. V. Todd
null hypothesis is that earlier decompression does not
lead to better bladder function following CES.
Review of selected papers
Dinning & Schaeffer4 reported 39 patients, of whom
14 had bladder paralysis and were catheterized. Of
the 14 patients with bladder paralysis, nine were
operated on within 24 h and five were operated on
more than 24 h after the onset of bladder paralysis.
Early treatment (524 h) was associated with com-
plete recovery of bladder function in eight patients.
Treatment more than 24 h after the onset of bladder
paralysis was associated with complete recovery of
bladder function in one patient. Fishers exact test
gives p ¼ 0.023, which suggests statistically signifi-
cant benefit to decompression within 24 h.
Kennedy10 reported 19 patients decompressed less
or more than 24 h after the onset of CES. All patients
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had ‘symptoms of urinary dysfunction and saddle
hypoaesthesia’. Twelve patients had complete loss of
bladder control and were catheterized. Seven pa-
tients had ‘partial sphincter loss as they were able to
control micturition by manual compression or breath
holding’. Fifteen patients had reduced anal tone and/
or peri-anal wink. Eleven patients were decom-
pressed within 24 h ‘of the full syndrome’, eight
patients were decompressed after 24 h. All 11
patients in the early group achieved normal or
reasonable bladder control. Only three of the eight
patients treated from 24 to 72 h achieved normal or
reasonable bladder control. Fishers exact test gives
p ¼ 0.0048. This also suggests a statistically signifi-
cant benefit to decompression within 24 h.
Hellstrom reported 17 patients, 16 of whom
underwent surgery.8 The inclusion criteria included
‘sphincter involvement in the form of disturbed
micturition, retention of urine and loss of urethral
sensation as well as constipation, lack of rectal
distension and impotence’. The raw data are listed
so that we can consider decompression achieved less
than or more than 24 h and less than 48 h compared
with more than 48 h. A total of nine patients were
operated on less than 24 h after the onset of CES, five
had normal bladder function, four had persistent
urinary symptoms. Seven patients were operated on
more than 24 h after the onset of CES, five had
normal bladder function, two had persistent urinary
symptoms. Recalculating these data, we find that 12
patients were operated on less than 48 h after the
onset of CES, eight had normal bladder function,
four had persistent urinary symptoms. Four were
operated on later than 48 h after the onset of CES,
two had normal bladder function and two had
persistent bladder symptoms.
Shapiro published two papers, one in 199311 and
one in 2000.5 The 1993 paper reported 14 patients
treated between 1986 and 1991. The 2000 paper
reported 44 patients treated since 1987. Although the
Shapiro 2000 paper does not specifically state this, it
is highly likely that the 2000 paper includes the
previously reported 1993 data. On that basis data
from the 1993 paper have not been included in this
analysis. Shapiro5 reported 44 patients, of whom all
had retention of urine or incontinence of urine, or
both with saddle sensation that was either reduced or
completely absent. Twenty patients were treated
within 48 h, of whom 19 regained continence with
normal bladder function. Twenty-four patients were
treated more than 48 h after the onset of the cauda
equina syndrome, 15 had persistent impairment of
bladder function and nine were grossly incontinent of
stool and urine. w2 analysis of these data gives a total
w2 of 15.17 (df ¼ 1) p 5 0.001 (minimum threshold
frequencies were achieved). This paper suggests, at a
high level of probability, that decompression less
than 48 h after the onset of the CES is associated with
a greater likelihood of recovery of bladder function
than a decompression achieved more than 48 h after
the onset of the syndrome.
O’Laoire1 reported 29 patients with bladder
dysfunction. Thirteen were catheterized. Sixteen
were able to pass urine by abdominal bladder
compression or breath holding. Perineal sensory
disturbance was present in 27 of the 29 patients.
Three patients were operated on within 48 h of the
first onset of urinary symptoms and two regained
normal bladder function. Twenty-six were operated
on more than 48 h after the first onset of urinary
symptoms, of whom 16 achieved normal bladder
function. A direct comparison of the two groups
cannot be made for two reasons: first, the study is
unbalanced, it is mainly a study of delayed surgery;
secondly, the minimum frequency threshold for w2
was not achieved.
Chang9 reported four patients with urinary reten-
tion or incontinence, one of whom was said to have
‘incomplete retention with reduced bladder and
bowel sensation’. All four had bilateral saddle
hypaesthesia or anaesthesia. One patient was oper-
ated on within 12 h of the onset of urinary
incontinence and recovery of bladder function was
incomplete. Three patients were operated on at 5
days, 14 days and 5 months; two regained normal
bladder function and one did not.
Discussion
If we combine the data from the three clinical
papers4,8,10 in whom an internal comparison of
treatment 524 and 424 h after the onset of CES
can be made we get an observed frequency distribu-
tion as seen in Table I. Four papers1,5,8,9 contain
data that allow an internal comparison of patients
treated less than and more than 48 h after the onset of
CES (Table II). Forest plots for these data can be
seen in Fig. 1. The odds ratio (OR) of there being
a positive benefit to decompression within 24 h
is 3.89 (confidence interval, CI, 1.17–12.95). The
probability of there being a statistically significant
 Cauda equina syndrome 303

benefit to decompression within 24 h compared with
decompression thereafter is p ¼ 0.03. This appears to
disprove the null hypothesis that there is no benefit
to earlier decompression. The OR of there being a
benefit to decompression less than 48 h compared
with more than 48 h after the onset of CES is 4.41
(CI 1.55 – 12.55). This is a statistically significant
affect at the p ¼ 0.005 level. This appears to
disprove the null hypothesis that there is no benefit
to decompression within 48 h, cf. beyond 48 h after
CES.
TABLE I. Decompression 524 cf 424 hours after CES
Timing of surgery
Outcome Less than 24 h More than 24 h
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Recalculating the data in Tables I and II suggests
that treatment less than 24 h after the onset of CES is
approximately five times more likely to be associated
with recovery of bladder function than treatment
after 24 h; it is approximately four times more likely
than treatment less than 48 h after the onset of CES
will be associated with normal bladder function than
treatment later than 48 h.
Meta-analysis is an appropriate method for
comparing the results of several different rando-
mized controlled trials after excluding trials where
there is a possibility of severe bias.7 Meta-analysis
has specific rules. Meta-analysis was initially
designed, in part, to allow the comparison of
different randomized controlled trials in a similar
area, for example, different trials addressing the
treatment of hypertension. The important issue is
that, within the paper itself, must be the comparison
that one is looking for. For example, a paper should

Normal bladder function
Bladder function not normal
References 4, 8, 10.
TABLE II. Decompression 524 cf 424 hours after CES
Outcome
Normal bladder function
Bladder function not normal
References 1, 5, 8, 9.
24 9 contain both the placebo group and the active group
5 11 (or the old treatment compared with the new
treatment). Meta-analysis is not appropriate for
comparing different papers, for example, one paper
that reports the natural history of untreated hyper-
tension and a second paper that looks at an active
Timing of surgery
treatment. A randomized controlled trial will never
Less than 48 h More than 48 h be performed in patients with CES. Meta-analysis is
appropriate for systematic review provided the
29 29
studies are sufficiently similar to make it reasonable
7 28
to consider combining their results. The six
studies1,4,5,8–10 reported patients:

FIG. 1. Forest plots of data from papers.

 304 N. V. Todd
. who had a severe cauda equina lesion;
. where one outcome measure, socially normal
bladder function, could be identified;
. contained an internal comparison of early (524
or 548) vs late (424 or 448 h) after the onset of
CES.
There is a risk of bias in meta-analysis of observa-
tional studies which include biases of poor patient
control, publication bias and control of confounding
factors; however the data strongly suggest that
treatment 524 cf 424 or 548 cf 448 h after the
onset of severe CES is associated with a statistically
significantly greater likelihood of recovery of bladder
function.
Ahn et al.6 performed what they called meta-
analysis, but what was, in fact, logistic regression
analysis on 322 patients from 42 papers. This paper6
suggested benefit to surgery less than 48 h compared
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with more than 48 h after CES, but no evidence for
benefit for earlier surgery performed within the 48 h
window. Although this paper is called a meta-analysis
it simply put together many different papers from the
literature and it does not obey the rules of meta-
analysis. The paper has been severely criticized
because of errors of both methodology and data
interpretation.12 The inclusion of different popula-
tions of patients from different studies creates
artefacts of unknown type and magnitude; both
input and output variables lack comparability be-
tween the papers. There is little statistical power and
there is insufficient sample size to detect a change of
risk in the 524 compared with the 24 – 48 h groups.
The ORs are very wide and the statement that there
is no difference between the 524 and 24 – 48-h
groups is not reasonable as the CI includes the
possibility of a large increase in the risk of delayed
surgery. Lack of statistical significance ( p4 0.05) is
not equivalent to no increase in risk, i.e. lack of proof
of benefit is not the same as proof of lack of benefit.
There are a number of papers within the literature
which suggest that surgical delays do not adversely
affect the final outcome following CES.2,3,13,14 In a
recent article, Gleave & MacFarlane3 reviewed a
number of experimental and clinical papers, and
came to the conclusion that, where CES appears to
be ‘complete’ at the time of presentation emergency
or urgent, decompression of the cauda equina is
not required. Gleave & McFarlane came to this
conclusion partly on the basis of an experimental
literature, which suggested to them that cauda equina
compression needs to be relieved within 4 – 6 h if it is
to be effective and partly upon their analysis of the
clinical literature.
Gleave and MacFarlane3 reviewed a total of 13
clinical papers.1,2,4–6,8–11,13–16 Some of the papers
either contain no primary data or the patients were all
decompressed late (more than 48 h after the onset of
the syndrome).12,15,16 Two studies2,14 grouped
patients on the basis of the speed of onset of
symptoms; neither of these two papers reports the
time lapse from the onset of complete CES to
decompressive surgery. Although the authors3 state
that there is no correlation between the timing of
surgery and outcome, it is impossible to substantiate
or refute that view from the data in these papers.2,14
Gleave & McFarlane3 conclude that ‘surgical delays
do not affect final outcome adversely’. Statistical
analysis of the data contained in the papers that they
quoted was not performed.
The relevance of experimental studies17,18 to the
clinical situation is unclear. For example, the studies
by Delamarter et al.17 used a model where the cauda
equina nerve roots were compressed to 75%. Yet a
central disc prolapse in man that occupied 75% of
the spinal canal would very commonly be associated
with no CES symptoms. The experimental literature
can legitimately be used to inform the design of
human studies, but one must be cautious about
applying the results of such experimental studies
directly to the human condition. Moreover, even if
an experiment in animals demonstrated an irrever-
sible lesion after some hours of CES, this would not
preclude a benefit to decompression after that time
point in man.
The cauda equina syndrome (CES) is a syndrome
of clinical findings that imply significant compression
of the cauda equina nerve roots. That syndrome
might include some or all of the following:
. impaired urethral or bladder sensation;
. impaired rectal sensation;
. difficulty in initiating micturition;
. retention of urine;
. incontinence of urine and/or bowel incontinence
together with objective evidence of impaired or
absent perineal/genital/saddle sensation;
. a palpable bladder;
. dribbling incontinence and/or a patulous anus.
There may also be symptoms and/or signs of lateral
nerve root compression (unilateral or bilateral).
Gleave & MacFarlane3 distinguish patients who have
urinary difficulties of neurogenic origin ‘including
altered urinary sensation, loss of desire to void, poor
urinary stream and the need to strain in order to
micturate’ [an incomplete cauda equina syndrome
(CESI)]; from painless urinary retention and over-
flow incontinence where the bladder is no longer
under executive control, complete CES cauda equina
syndrome with retention [CESR].
It would be generally agreed that the outcome
following decompression of an incomplete cauda
equina lesion is usually favourable with over 90% of
patients recovering neurological function specifically
recovering socially normal bladder function.
Gleave & MacFarlane3 believe that the literature
fails adequately to distinguish between patients who
have an incomplete or complete cauda equina lesion.
They believe that early treatment groups contain an

excess of patients who have an incomplete cauda
equina lesion and who would be expected to do well
with decompressive surgery. The group treated after
a delay contains patients who initially had an
incomplete cauda equina lesion that became com-
plete because of the delay in treatment. Comparison
of such early and late groups appears to favour early
treatment because the early group contains greater
numbers of incomplete CES patients. It is difficult to
support such a criticism for the six papers that have
been analysed here.1,4,5,8–10 These papers are largely
patients with loss of central control of bladder
function. In the Dinning paper, all 14 had bladder
paralysis and were catheterized. In the Kennedy
paper 12 patients were catheterized and the remain-
ing five were only able to control micturition by
abdominal compression. Hellstrom had 16 patients,
all of whom had retention of urine with loss of
urethral sensation and altered micturition. Shapiro
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had 44 patients all of whom had retention of urine or
incontinence. O’Leary had 29 patients, 13 were
catheterized and 16 were able to pass urine only by
abdominal compression, and Chang had four
patients, of whom one was said to have ‘incomplete
retention’. I think any ordinary reading of these
papers would suggest that all but one of these
patients had loss of neurogenic control of bladder
function. It is possible that there are a small number
of patients who had a severe, but perhaps not
ultimately ‘complete’ cauda equina lesion, but there
is no suggestion that such patients were over-
represented in either an early or late treatment
group, and the presence of small numbers of
‘incomplete’ patients randomly distributed would
be unlikely to effect the overall conclusion. It is
important to recall that the patients were selected by
experienced spinal surgeons as representing the small
proportion of all of their symptomatic disc prolapses
who had what they believed to be a severe (complete)
cauda equina lesion. If it is accepted that the patients
in the six papers that permit meta-analysis do
represent patients with severe (complete) CES (the
sort of patients in whom we struggle to decide
whether to operate upon urgently or not) the
conclusion must be that at a statistically significant
level of probability early surgery is better than
delayed surgery.
Clinical guidelines
The literature puts patients into different groups (e.g.
524, 548 h after CES), but it is not necessarily
logical to base clinical decisions about the timing of
decompressive surgery on that basis. If we do then
the assumption must be that the patients within a
group, e.g. 524 h are similar and the likelihood of
recovery of neurological function is the same for all
members of the group provided they are decom-
pressed within 24 h. This would imply that in a
patient with CES, persistent and/or further nerve
Cauda equina syndrome 305
root compression, swelling and/or ischaemia (con-
sequent upon surgical delay) does not reduce the
likelihood of functional recovery (e.g. recovery of
bladder function). There is no a priori reason to think
that specific time points have a logical basis. The
524- or 548-h (or other) time points are simply
those reported in the literature. The logical inter-
pretation is that earlier is better (e.g. 10 h is better
than 20 h).
It is likely that a time-dependant effect represents a
continuum of progressive benefit/disbenefit in which
case prompt decompression is probably better.
Biological relationships are not typically abrupt
(square wave function); rather are they continuous.
Where compliance is a relevant issue (as is likely to
be the case with CES) then a logarhythmic relation-
ship is likely. If there is a continuous (probably
logarhythmic) relationship to the likelihood of
recovery of neurological function following CES
then the earliest possible decompression is likely to
offer the greatest likelihood of recovery of function.
Even if a surgeon was not entirely convinced that
earlier decompression was proven to be of benefit, it
must be accepted that there is a range of opinion,
which includes a possibility that earlier decompres-
sion is better. In this case, it would be prudent for the
surgeon to adopt a precautionary principle and
operate early, rather than late. There may be practical
difficulties in arranging for such patients to be
operated on very rapidly by the most experienced
surgeon with an appropriate ‘team’. On a practical
basis, it might be that, if surgery was deliberately
delayed for a few hours so that an experienced
surgeon was operating fresh after a night’s sleep (in
comparison to a potentially tired and/or inexper-
ienced junior surgeon), then that might be a
justifiable compromise, but it is probably in the
patients best interests that the service is so organized
that such surgery can be carried out promptly by
surgeons of appropriate seniority and experience.
Conclusion
Six clinical studies report the effect of ‘early’/‘late’
decompression following CES upon the likelihood of
recovery of bladder function.1,4,5,8–10 Meta-analysis
demonstrates that patients treated earlier than 24 h
after the onset of CES are more likely to recover
bladder function than those treated beyond 24 h
( p ¼ 0.03); patients treated within 48 h after the onset
of CES are more likely to recover bladder function
than those treated beyond 48 h (p ¼ 0.005). The
timing of surgery following CES probably does
influence outcome.
Acknowledgements
I am grateful to Professors Mendelow and Wright,
Messrs Jenkins and Crossman, and Dr Gregson for
their helpful criticism of drafts of this paper.
 306 N. V. Todd
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