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Preventing Labyrinthitis Ossificans
The Role of Steroids
Christopher J. Hartnick, MD;
Hank Y. Kim, MD;
Patricia M. Chute, EdD;
Simon C. Parisier, MD
Arch Otolaryngol Head Neck Surg. 2001;127:180-183.
ABSTRACT
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Objective To identify a possible relationship between the administration of steroids
at the time of diagnosis of bacterial meningitis and the development of labyrinthitis
ossificans.
Design Retrospective analysis of the charts of 38 children requiring cochlear
implantation who presented with bacterial meningitis and then developed bilateral
profound deafness. The patients' charts were reviewed for age at diagnosis,
the type of antibiotic administered, and the administration, dosage, and duration
of steroid (dexamethasone) therapy. Labyrinthitis ossificans was established
by preoperative computed tomographic and/or magnetic resonance imaging and
by the intraoperative findings as described in the operative report.
Patients and Methods Patients were 38 children who received cochlear implantation by a single
senior otolaryngologist for bacterial meningitis–related deafness. Ten
patients' charts (26%) were available for full review; 9 of these 10 patients
had documented pneumococcal meningitis and the other patient had Haemophilus influenzae–type meningitis.
Results One of the 6 patients who received steroid therapy at the time of initial
illness had documented evidence of labyrinthitis ossificans either radiographically
or at the time of surgery. All 4 patients who failed to receive steroid therapy
developed labyrinthitis ossificans. The results achieve statistical significance
by  2 analysis and a t test (P<.01).
Conclusion The results of this retrospective study are highly suggestive of a role
for steroids in preventing the development of labyrinthitis ossificans in
children with pneumococcal meningitis.
INTRODUCTION
HEARING LOSS following an episode of bacterial meningitis is a well-documented
phenomenon, with an incidence ranging from 5% to 35%.1, 2, 3, 4
A subset of patients who develop such hearing loss have profound bilateral
loss for which cochlear implantation becomes a surgical option. In one prospective
series that reported a 10.3% (19 of 185 patients) incidence of hearing loss
following an episode of bacterial meningitis, 7 (37%) of the 19 affected patients
were deafened bilaterally.2 By performing these
implantations, surgeons realized that one particular aspect of the disease
process was that there is a high incidence of labyrinthitis ossificans following
bacterial meningitis that complicates the surgical procedure and may affect
the long-term outcome.5 Eisenberg et al6 reported that 80% of children who became profoundly
deaf following a bout of meningitis had some level of labyrinthitis ossificans.
It is conceivable that any factor that might affect the development of labyrinthitis
ossificans might improve the surgical exercise of implantation as well as
the long-term results.
In the hopes of discovering treatment strategies that would decrease
the incidence of developing hearing loss following an episode of bacterial
meningitis, much work has been done to identify the 5% to 35% of patients
at risk. Less work has been done to characterize patients who develop labyrinthitis
ossificans and to identify treatment strategies. One treatment strategy that
has been examined with regard to hearing loss following meningitis is the
use of steroids. In 1988, Lebel et al7 reported
that there is a statistically significant effect in using steroids to prevent
hearing loss for children who have Haemophilus influenzae–type meningitis. There were not enough patients with non–H influenzae–type meningitis in this series to comment
on the efficacy of steroids in these situations. With the American Academy
of Pediatrics' official declaration in 1991 that H influenzae type b vaccine be universally administered, the incidence of H influenzae–type meningitis has dropped dramatically
and the role of steroids in non–H influenzae–type
meningitis has since assumed a greater importance. Controversy persists as
to whether to administer steroids universally to children with non–H influenzae–type meningitis. Various avenues of
research have been pursued to dispel this controversy. One of these avenues
is to examine the role of steroids not on hearing itself, but rather on the
long-term outcome of patients who became deaf as a result of meningitis and
who seek cochlear implantation. Since one of the major factors that influences
the long-term outcome of cochlear implantation is labyrinthitis ossificans,
it is arguable that if steroids inhibit the development of labyrinthitis ossificans,
then steroids should be given universally for the treatment of non–H influenzae–type meningitis.
This study was designed as a retrospective review of the charts of children
who received cochlear implantation by one surgeon for bacterial meningitis–related
hearing loss. The aim was to ascertain whether the use of steroids affected
the development of labyrinthitis ossificans.
PATIENTS AND METHODS
A retrospective chart review was performed on all patients who received
cochlear implantation by one senior otolaryngologist at either the Lenox Hill
Hospital or the Manhattan Eye, Ear, and Throat Hospital, New York, NY, for
postmeningitic hearing loss. The patients and their families were contacted
and signed an informed consent form allowing the release of information from
the hospital at which the patient was initially treated. Thirty-eight procedures
were performed between 1983 and 1997. Twenty-eight patients (74%) could not
be contacted for release of medical records; inpatient medical records from
the acute illness were obtained from 10 patients (26%).
These records were reviewed, and the age at time of illness; the etiologic
agent; the use, dosage, and duration of steroids; and the antibiotic used
were elucidated. Preoperative temporal bone studies were reviewed and correlated
with intraoperative findings to determine the presence of labyrinthitis ossificans.
The null hypothesis for this study was that steroids do not affect the
development of labyrinthitis ossificans. A 2 analysis and
a t test were used to analyze the data.
RESULTS
The mean age at the time of acute illness was 13.7 months, ranging from
4 months to 30 months of age. Streptococcus pneumoniae
was the etiologic agent in 9 of 10 patients. H influenzae was the agent in the other case. Antibiotics were initiated immediately
after the diagnosis of meningitis, and ceftriaxone sodium was the antibiotic
used most often. Five patients received ceftriaxone alone and 2 received it
in combination with vancomycin hydrochloride. One patient received a combination
of ampicillin sodium and gentamicin sulfate. The exact antibiotic regimen
could not be ascertained from the charts of 2 patients.
Six patients received dexamethasone for 4 days, and 4 patients did not
receive steroids throughout their entire clinical course. Five of the 6 patients
began receiving steroids at the same time as the initiation of antibiotics.
The other patient began receiving steroids 3 days later after culture confirmation
of bacterial meningitis. The exact dosage of dexamethasone ranged from 0.5
to 1.0 mg/kg daily, with a mean of 0.6 mg/kg daily. The patients who were
treated with steroids were, as a group, older than the patients who were not,
although the difference was not statistically significant. Five of 6 patients
treated with steroids during the acute illness were not found to have cochlear
ossification either radiographically or at the time of surgery. By contrast,
the 4 patients who did not receive steroid therapy developed labyrinthitis
ossificans intraoperatively (Table 1).
A 2 analysis and a t test demonstrated
a statistical significance (P<.01). The average
time from acute illness to implantation in those who developed labyrinthitis
ossificans was 42.5 months compared with an average of 11 months for those
who did not develop labyrinthitis ossificans.
COMMENT
The goal of this study was to determine the role that steroids might
have in preventing the development of labyrinthitis ossificans. To this end,
the results are statistically significant in positing such a role. The importance
of this study stems from the controversy surrounding the use of steroids in
the scenario of bacterial meningitis. The 1994 Report of
the Committee on Infectious Diseases recommends steroid use for H influenzae–type meningitis but cautions that the
use of steroids for pneumococcal meningitis, although recommended, has not
been proven to be effective.8 This has left
an unresolved question where there is no treatment algorithm for patients
with non– H influenzae–type meningitis.
This lack of resolution is further accentuated in light of the decline of H influenzae–type meningitis since 1991 and the relative
rise of pneumococcal and neisserial meningitis. To add to this dilemma, there
are data showing that pneumococcal and meningococcal meningitis produce a
higher incidence of hearing loss than does H influenzae meningitis. Dodge et al2 reported in
1984 on a prospective series of 185 children who had bacterial meningitis;
31% of those with streptococcal pneumonia–type meningitis had hearing
loss compared with 10.5% of the Neisseria-type population
and 6% of the H influenzae–type population.
It is possible to view the decision as to whether to give steroids to
children with non–H influenzae–type meningitis
(in hopes of preventing labyrinthitis ossificans) in the context of a decision
to which there seems to be a resolution, namely, the decision to give steroids
to prevent hearing loss in children with H influenzae–type
meningitis. In analyzing this recommendation, one can infer the thresholds
that were drawn as far as concerned the relative risks of steroid administration
compared with their benefits. In the article by Lebel and colleagues,7 15.5% of patients who did not receive dexamethasone
had some form of hearing loss as opposed to only 3.3% of patients who received
dexamethasone. To decrease the incidence of hearing loss by 12%, they advocated
giving dexamethasone to every child with bacterial meningitis. They justified
this claim by noting the low incidence of adverse effects (in their series,
namely, gastrointestinal bleeding) attributable to the steroid administration.
In their series, 2 (1%) of 200 patients had gastrointestinal bleeding and
needed transfusion therapy. One of these 2 had a bout of gastroenteritis just
prior to admission. Another 2 patients had heme-positive stools without frank
bleeding. The Committee on Infectious Diseases reviewed the study by Lebel
and colleagues7 among others and weighed the
risks and benefits of steroid administration. They set the benchmark by noting
that, for the sake of that small fraction of children who would face the sequelae
of meningitis, it is worthwhile to administer steroids universally to children
with H influenzae–type meningitis.
The data of Lebel and colleagues7 and
the risks-benefits analysis used to analyze the use of steroids to prevent
hearing loss in H influenzae–type meningitis
lead one to address the issue of steroid administration in the contemporary
era where pneumococcal and neisserial meningitis predominate. While the issue
of steroids affecting the development of hearing loss in these strains of
meningitis remains controversial, other issues have not been explored. What
about the population of children who do in fact develop hearing loss and present
for possible cochlear implantation? The question arises as to whether the
use of steroids would help this population. At this point, the question of
labyrinthitis ossificans arises. By examining data such as that published
by Rauch et al5 from the Massachusetts Eye
and Ear Infirmary, Boston, and by Eisenberg et al,6
one can infer that 70% to 80% of patients who became deaf as a result of meningitis
will develop labyrinthitis ossificans. Following this logic, 5 of the 7 patients
in the series by Dodge and coworkers2 are at
risk for developing labyrinthitis ossificans. If steroids were to ameliorate
the problem of cochlear ossification, then, using the relative risk thresholds
established here for steroid administration to prevent long-term hearing loss,
the logical conclusion would argue for the administration of steroids to all
patients with bacterial meningitis. These data for and the conclusions drawn
from this present study are framed by this argument and derive importance
from it.
To draw widespread conclusions from this study, it is important to address
its limitations. First, it was a retrospective study designed to identify
potential causal relationships. Its weakness is that of any retrospective
study—there are no careful designs to eliminate other potential confounders.
To establish without doubt one-to-one causal relationship, a prospective study
would be required; animal studies would help provide corroborating evidence.
The second problem that these data do not directly address but that
would need clarification prior to the universal administration of steroids
is the question of timing, duration of administration, and dosage. In the
article by Lebel and coworkers,7 dexamethasone
was administered at a daily dose of 0.6 mg/kg in 4 divided doses for 4 days
beginning as soon as a diagnosis of menignitis was made. Rasmussen et al9 published data on 94 patients followed up for sequelae
of pneumococcal meningitis and found that steroid treatment did not significantly
alter the development of hearing loss. In the series by Rasmussen and coworkers,9 steroids were given in the form of prednisone, 40
mg orally, beginning for at least 1 week, starting after the etiologic diagnosis
was made. Because the time to identify the exact etiologic organism may take
2 to 3 days, the delay between diagnosis of meningitis and administration
of steroids was a matter of days in many cases. The take-home message may
well be that for steroids to be effective, they may have to be administered
as soon as a diagnosis is made. As concerns the present study, the only patient
who developed labyrinthitis ossificans after the administration of steroids
was given steroids 3 days after admission when the etiologic diagnosis of
bacterial meningitis was made.
This article describes a small series of patients for whom the administration
of steroids appears beneficial in preventing the development of labyrinthitis
ossificans. It remains difficult to explain this clinical finding because
of the paucity of data regarding the development of labyrinthitis ossificans.
The exact mechanism of the development of labyrinthitis ossificans is controversial.
Its existence was noted as far back as the 1890s when Scheibe10
and Steinbrugge11 described the association
between suppurative labyrinthitis and labyrinthine ossification. Wittmaack12 separated labyrinthine inflammations into those arising
from tympanic, hematologic, and meningogenic sources. Paparella and Sugiura13 outlined the pathologic stages where an initial inflammatory
phase was followed by a fibrosis and then ossification. They posited that
the cell responsible for fibrosis and ossification was the undifferentiated
mesenchymal cell. Exactly how and where the focus of infection spreads from
the meninges to the cochlea remain debated. It has been noted that the most
frequent area of ossification is at the scala tympani in the basal turn of
the cochlea.14 This finding lends support to
the theory that infection spreads from the meninges to the inner ear by way
of the cochlear aqueduct. This finding is also of surgical relevance because
it is at this area of the cochlea where the implant will be inserted. Others
have posited that infection spreads to the labyrinth from the meninges by
way of the internal auditory canal.15
Understanding the pathophysiology of labyrinthitis ossificans would
allow for a greater understanding of how steroids might exert their effects.
The current theory as to the mechanism of steroids' action on preventing hearing
loss after meningitis stems from the knowledge that with brain edema and increased
intracranial pressure found in the scenario of meningitis, there can be resulting
reduction of cerebral perfusion with resultant hypoxia of regional tissues.16 The local hyopxia and ischemia are associated with
elevations of arachidonic acid metabolites.17
Steroids seem to have some role in inhibiting the production of these arachidonic
acid metabolites by pathways that involve interleukin 1 and cachectin.
Mechanistic studies involving the role of steroids in preventing the
development of labyrinthitis ossificans require some animal model. A review
of the literature shows both animal models for bacterial meningitis and subsequent
labyrinthitis18 as well as an animal model
for labyrinthitis ossificans after pneumococcal meningitis.19
Brodie et al19 used the Mongolian gerbil as
an animal model and found that 14 of 15 gerbils injected intrathecally with
live S pneumoniae organisms had cochlear fibrosis,
ossification, or both. In a recent article, Nabili et al20
used this animal model to delineate the chronology of labyrinthitis ossification
following bacterial meningitis. They used fluorochromes that are incorporated
into osteoid as it is mineralized to follow the development of labyrinthitis
ossificans. Ossification began as early as 3 weeks following initial infection
and calcification, and remodeling was complete by 1 year. The authors write
of the importance of knowing the chronology of the development of labyrinthitis
ossificans to gain experience in the proper timing of early implantation.
The present study was designed to examine the question posed from a
clinical context. Although the number of patients is small, the results argue
for the administration of steroids in particular dosages given at the time
of diagnosis to children with bacterial meningitis. The suggestion that steroids
be given to all children with bacterial meningitis to help facilitate the
surgical insertion and long-term outcome of cochlear implantation for those
few children who, first, will become profoundly deaf and receive implantation
and, second, will develop labyrinthitis ossificans without the administration
of steroids is not lightly asserted. The results of our preliminary clinical
study warrant further prospective studies to isolate a possible causal relationship
and further clarification by means of animal studies where the influence of
steroid administration can be carefully examined.
AUTHOR INFORMATION
Accepted for publication July 13, 2000.
Presented as a poster at the meeting of the American Society of Pediatric
Otolaryngology, Orlando, Fla, May 17-18, 2000.
From the Department of Pediatric Otolaryngology, Children's Hospital
Medical Center, Cincinnati, Ohio (Dr Hartnick); Department of Otolaryngology,
Montefiore Medical Center, Bronx, NY (Dr Kim); and the Cochlear Implant Center,
New York, NY (Drs Chute and Parisier).
Corresponding author: Christopher J. Hartnick, MD, Department of
Pediatric Otolaryngology, Children's Hospital Medical Center, 3333 Burnet
Ave, Cincinnati, OH 45229 (e-mail: harq4k{at}chmcc.org).
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