Recurrent meningitis in childhood should always
prompt a search for an underlying cause. Meningitis is usually acquired
by the spread of blood-borne bacteria into the cerebrospinal fluid (CSF).
However, if more than one episode has occurred, other possible routes of
entry should be considered. Bacteria can gain entrance to the
subarachnoid space by migration along congenital tissue planes or
acquired anatomical pathways(1,2). Alternatively, the usual hematogenous
spread may be facilitated by an immunological deficiency, which makes
the host defences inadequate barriers against potential bacterial
pathogens(1). We describe a child with recurrent episodes of bacterial
meningitis who was investigated for both immunodeficiency and an
anatomical defect.
Case Report
An 8-year-old boy presented with pneumococcal
meningitis. He responded to intravenous ceftriaxone and vancomycin. The
previous year he had been treated for pneumococcal meningitis as well.
He had made a good recovery from this illness and there had been no
apparent sequelae. He had previously suffered from frequent ear
infections with chronic discharge, and upper respiratory tract
infections. He also had occasional bouts of diarrhea. He had chickenpox
with severe scarring at 6 years of age. There was no significant family
history, and his 3-year-old sibling was well.
Investigations were carried out for an underlying
cause during his convalescence. A CT scan of the sinuses and mastoids
demonstrated a persistent collection in the left mastoid antrum,
representing chronic mastoiditis. In addition, the posterior wall of the
antrum, separating the mastoid from the central nervous system, was very
thin. Abdominal ultrasound scan showed normal splenic size.
Measurement of total immunoglobulins (Ig) revealed
pan-hypogammaglobulinemia with IgG 1.5 g/L (normal range 5-15), IgM <0.1
g/L (0.5-2), IgA < 0.1 g/L (0.2-2.5), IgE < 2.0 IU/mL (<52). He also had
abnormal specific antibody responses (Measles IgG-Negative, Mumps IgG–Negative,
Rubella IgG-positive, Tetanus IgG-negative, and Varicella Zoster virus
IgG-positive). T lymphocyte subsets were normal. Complement studies were
normal, an HIV antibody test was negative, and a nitroblue tetrazolium
test was normal.
Genetic immune defects, such as X linked
hypogammaglobulinemia were ruled out by molecular immunological studies,
and a diagnosis of common variable immune deficiency was made. He was
commenced on regular, 3-weekly courses of intravenous immunoglobulin,
and penicillin prophylaxis. He has made a full recovery and is now
making good progress.
Discussion
The incidence of recurrent meningitis has not been
well studied. Kline reviewed the world literature from 1978-1988 and
found 47 patients with recurrent meningitis(3). Of these patients,
33(70%) are <18 years old at the time of diagnosis. Predisposing factors
included a congenital CSF fistula in 55% of cases, traumatic or surgical
CSF fistula in 17%, immunodeficiency in 21% and unknown cause in 6%(3).
Drummond, et al.(4) reported 6 (1.3%) children with recurrent
meningitis over an 11-year period after reviewing 463 cases of
meningitis. Of these, two were diagnosed with temporal anatomical
abnormalities, 2 with immunological deficiencies and no underlying
etiology for recurrent meningitis was identified in the remaining 2
patients(4).
Children with immunodeficiencies are at increased
risk from hematogenous spread of bacteria to the meninges. Although a
number of immunodeficiency conditions may be associated with recurrent
meningitis, the most common causes are immunoglobulin deficiency,
complement deficiency and hyposplenia(1).
Recurrent meningitis has been reported in the
immunoglobulin-deficient condition X-linked agammaglobulinemia as well
as in selective deficiencies of IgG, IgA, and IgG2(5,6). Common variable
immune deficiency (CVID) represents a hetero-geneous group of disorders,
which usually present in the 2nd or 3rd decades of life. Recurrent
meningitis in association with CVID has not been reported before.
Patients with CVID may have normal or decreased numbers of B cells. In
contrast to X-linked agammaglobulinemia the immunoglobulin levels are
low rather than absent. Clinical presentations are typical of humoral
immune deficiencies, with poor responsiveness to antigens. Associated
T-cell dysfunction has been reported, but nevertheless patients usually
benefit from intravenous immuno-globulin replacement therapy.
Links between recurrent meningitis and deficiencies
of both the classical and alternative complement pathways are
well-described(1,5,7) In these deficiencies the most common pathogen is
N. meningitidis. Splenic hypofunction is also associated with an
increased risk of septicemia and meningitis with encapsulated bacterial
pathogens. However, minor immunodeficiencies like selective IgA
deficiency and IgG2 subclass deficiency are not rare, but not commonly
associated with recurrent meningitis. The presence of minor antibody
deficiency should not preclude the search for anatomical defect(8).
When CSF communicates with the middle ear cavity, the
nose or the nasopharynx, there is potential for CSF bacterial
contamina-tion and meningitis. Acquired traumatic temporal bone
fractures are the most common cause of a CSF leak into the middle ear. A
fracture of the temporal bone may result in a disruption of the tegmen
with a concomitant tear in the middle fossa dura, resulting in CSF leak.
Although a chronic CSF fistula can result from temporal bone fracture,
the majority of CSF leaks heal spontaneously(9).
Congenital temporal bone anomalies like the Mondini
malformation can also predispose to CSF fistulae(10). The Mondini
malformation is a consequence of a disruption in the embryonic
development of the inner ear during the 7th week of gestation. This
results in a shortened cochlea, an enlarged vestibule, and sensorineural
hearing loss, with a CSF leak at the modeolus. CSF may leak into the
middle ear at the deficient oval window. Congenital CSF leak may also
occur within the bony labyrinth. A child with recurrent meningitis and
congenital sensorineural hearing loss should be strongly suspected of
having a translabyrinthine CSF fistula(4).
CSF fistulae can originate from the anterior skull
base. CSF rhinorrhea in children is more commonly due to developmental
defects than trauma. Such defects include ethmoidal encephaloceles,
dysplasia of the cribiform plate and CSF leakage via an empty sella.
Recurrent meningitis has also been reported in children with dermal
sinus tract associated with a dermoid cyst within the lumbosacral spinal
canal(2).
Conclusion
It is important to assess the etiology of recurrent
meningitis to provide optimal management to prevent further recurrences.
All children with more than one episode of meningitis should undergo a
thorough evaluation by appropriate neuroimaging and immune function
studies.
Contributors: All the authors were involved in
management and diagnosis of the case, review of literature and drafting
of the manuscript.
Funding: None.
Competing interests: None stated.
