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Recurrent Meningitis


Recurrent meningitis typically is defined as two or more separate episodes of meningitis and associated cerebrospinal fluid (CSF) pleocytosis that occur weeks to months apart with full recovery between events. In contrast, recrudescence or relapsed meningitis represents the persistence of the original infection due to treatment failure. Recurrent meningitis is uncommon. Bacterial infection is the most common cause of recurrent meningitis, although recurrent episodes can be characterized by negative CSF cultures. Rarely, a virus such as herpes simplex virus (HSV) can be causative.

Etiologic Agents

Recurrent meningitis appears to have decreased in the era of conjugate vaccines against the three most common causes. The pathogen in >50% of patients with recurrent bacterial meningitis has been Streptococcus pneumoniae , most often associated with an underlying anatomic abnormality or immunodeficiency. Neisseria meningitidis is the second most common bacterial pathogen (approximately 25% of recurrent bacterial meningitis), most often associated with complement deficiency. Recurrent meningitis due to Haemophilus influenzae type b (Hib) is now rare. Staphylococcus aureus and gram-negative bacilli such as Escherichia coli can be associated with recurrent meningitis; the recurrent detection of any of these organisms suggests a communication between the subarachnoid space and the paranasal sinuses, skin (such as a dermal sinus), or intestine if gram-negative organisms are isolated (such as posterior neuroenteric fistula or anterior meningomyelocele). Other bacteria, such as oral streptococci, Proteus spp., enterococci, Klebsiella spp., and group B Streptococcus have been sporadically reported to cause recurrent meningitis. In cases in which bacteria cannot be detected, the differential diagnosis of recurrent aseptic meningitis should be considered, particularly if molecular testing is unrewarding ( Box 42.1 ).

BOX 42.1
Conditions Associated With Recurrent Aseptic Meningitis

  • Mollaret syndrome

  • Familial Mediterranean fever (FMF)

  • Intracranial or intraspinal cyst

  • Dermoid or epidermoid tumor

  • Behçet disease

  • Sarcoidosis

  • Systemic lupus erythematosus

  • Intracranial tumor

  • Drug-induced (e.g., penicillins, cephalosporins, trimethoprim-sulfamethoxazole, nonsteroidal anti-inflammatory drugs, intravenous immune globulin, OKT3, tumor necrosis factor [TNF] inhibitors, antiepileptic agents, chemotherapeutic agents) , ,

  • Herpes simplex virus type 1 or 2 infection

  • Enterovirus infection

  • Migraine syndrome

  • Vogt-Koyanagi-Harada syndrome

  • Kikuchi Fujimoto disease

Epidemiology

In two studies of adult bacterial meningitis, recurrence occurred in 5%–6% of patients. , Rates are even lower in children. A 1999 review of 463 cases of pediatric bacterial meningitis identified 6 confirmed recurrent episodes, representing 1.3% of cases.

Anatomic Defects

The most common predisposing condition is a communication between the subarachnoid space and the base of the skull (CSF leak or fistula) resulting from head trauma, surgery, or a congenital defect; immunologic defects are less common. CSF rhinorrhea or otorrhea occurs after approximately 1%–2% of all head injuries, but either condition is more frequent following certain fractures, that is, 11% of basilar skull fractures and 25% of fractures involving the paranasal sinuses. Most CSF leaks resolve spontaneously within a few days. Persistent CSF leaks are associated with an increased risk for meningitis.

The risk for development of meningitis by time since the injury. About one-fifth of cases of posttraumatic meningitis occur within 1–2 weeks after head trauma, one-third within the first month, and one-half within 6 months. However, almost 50% of patients have the first episode of meningitis ≥7 months after the traumatic event causing a CSF leak, and a delay of as long as 34 years has been reported. Procedures such as intracranial surgery, nasal and paranasal sinus surgery, and otologic surgery also can predispose to recurrent meningitis. On average, meningitis related to neurosurgery develops within 10 days of the procedure, with an incidence of 0.3%–10%. S. aureus is the major pathogen although gram-negative bacteria frequently are isolated.

Various congenital defects in the bony structure of the skull contribute to the development of CSF fistulas and thus predispose to recurrent meningitis ( Box 42.2 ). Although skull defects themselves are not uncommon, the rate of complicating recurrent meningitis probably is low. For example, in children with idiopathic sensorineural hearing loss, computed tomography (CT) of the temporal bone revealed that 21% had an inner-ear malformation. Mondini dysplasia (a developmental arrest at the seventh week of gestation characterized by hypoplasia of the cochlear labyrinth resulting in 1–1.5 turns instead of the normal 2.5 turns and occasionally associated with intrauterine CMV infection) is commonly cited as contributing to recurrent meningitis ( Fig. 42.1 ). Although deafness frequently is associated with Mondini dysplasia, it is unilateral and therefore often unrecognized. Additionally, trauma can precipitate a fistulous connection in milder congenital defects and lead to meningitis. Epidermoid and dermoid cysts with dermal sinus tract are well-known causes of recurrent meningitis, with many cases coming to attention because of a new-onset neurologic deficit, infection, or both. Lymphangiomatosis of the skull is a rare cause of CSF leak and recurrent meningitis.

BOX 42.2
Congenital Anomalies Associated With Recurrent Bacterial Meningitis

Anomalies of the Anterior Fossa

  • Encephalocele

  • Meningocele

  • Meningoencephalocele

  • Defects of the cribriform plate

  • Enlarged subarachnoid space

  • Intracranial cyst

Anomalies of the Temporal Bone

  • Mondini dysplasia

  • Stapedial anomalies

  • Klippel-Feil syndrome

  • Pendred syndrome

  • Petromastoid fistula

  • Widened cochlear aqueduct

  • Hyrtl fissure

Spinal Defects

  • Dermoid or epidermoid cyst

  • Neuroenteric fistula

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