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Drug-induced aseptic meningitis.

Aseptic meningitis is a rare but well-recognized complication of drug therapy. The clinical presentation of drug-induced aseptic meningitis (DIAM) is distinct. Symptoms typically include fever, neck stiffness, headache, confusion, nausea and vomiting. The major categories of causative agents are non-steroidal anti-inflammatory drugs, antimicrobials and also intravenous immunoglobulins, monoclonal antibodies and vaccines. These drugs most commonly implicated as causes of aseptic meningitis act more likely through an immunological mechanisms. However, the exact pathogenetic mechanism of DIAM is still unknown. The diagnosis of drug-induced aseptic meningitis is difficult and infectious etiologies must be excluded. In some cases the diagnosis has been confirmed by rechallenging the patient with the suspected agent. In this case, informed written consent is necessary and rechallenge must be medically supervised both to document the response and to offer medical care and advice, if required. The outcome of DIAM is generally good, usually without long term sequelae.

Adjuvants, Immunologic↗

Naproxen-induced recurrent aseptic meningitis.

Aseptic meningitis has been linked to treatment with several nonsteroidal antiinflammatory drugs (e.g., ibuprofen, tolmetin, sulindac), particularly in patients with disturbed immunity. Naproxen, however, has only once been reported to cause meningitis. We report a case of recurrent aseptic meningitis related to prolonged naproxen usage in a 38-year-old woman with longstanding, minimally symptomatic systemic lupus erythematosus (SLE). Two years after starting naproxen, she experienced three separate episodes of meningitis within a period of 10 months; each episode was preceded by resumption of naproxen administration or an increase in drug dosage. There was no clinical or serologic evidence for the flare-ups of her SLE. Discontinuation of naproxen was followed by prompt recovery once the relationship of the drug to her symptoms was realized. Off the drug, the patient has remained free of meningeal symptoms for more than 18 months. Nonsteroidal antiinflammatory agents should be considered as possible causal agents in evaluating meningitis of obscure etiology.

Adult↗

Relapsing polychondritis and aseptic meningitis.

Aseptic meningitis is a rare complication of relapsing polychondritis. We describe a 60-year-old man who developed a prolonged episode of aseptic meningitis for which no cause could be determined and, that resolved spontaneously. He then developed classic relapsing polychondritis 14 months later. He subsequently had another episode of prolonged meningitis complicated by hydrocephalus. No infectious cause for the meningitis could be determined after extensive investigation including meningeal biopsy. The patient responded to corticosteroids and antituberculous therapy.

Biopsy↗

Sensorineural hearing loss caused by NSAID-induced aseptic meningitis.

Aseptic meningitis is a rare complication of nonsteroidal anti-inflammatory drug (NSAID) use. Otologic symptoms may include sensorineural hearing loss and tinnitus. A 66-year-old woman sought the care of an otologist for sudden bilateral sensorineural hearing loss and a substantial increase in baseline tinnitus. The patient had previously undergone a left tympanoplasty secondary to cholesteatoma and had been treated for atypical face pain with ibuprofen taken every six hours for three months. Magnetic resonance imaging (MRI) with gadolinium demonstrated abnormal enhancement of the dura mater and the surrounding basal cisterns, with extension of enhancing dura mater into the internal auditory canals. Cerebrospinal fluid examination revealed evidence of aseptic meningitis. An audiogram confirmed new bilateral sensorineural hearing loss. Hearing loss and tinnitus resolved and no abnormalities were observed with MRI when nonsteroidal anti-inflammatory medication was discontinued. Otolaryngologists are well aware of the otologic sequelae in patients with meningitis. However, NSAIDs need to be considered as possible causal agents in the evaluation of meningitis with otologic symptoms.

Aged↗

[Drug-induced aseptic meningitis].

Aseptic meningitis is a very rare drug reaction involving non-steroidal antiinflammatory agents (ibuprofen and sulindac), antibiotics (cotrimoxazole, trimethoprim, ciprofloxacin) and miscellaneous drugs such as carbamazepine, human immune globulin and muromonab CD3. Meningeal symptoms occur a few hours after drug intake and resolve without sequelae within one or two days after drug withdrawal, mainly in young females with systemic lupus erythematosus or mixed connective tissue disease. Biological findings and radiological investigations are not suggestive of an infectious etiology or rheumatological/neurological disturbances. Diagnosis is simple when recurrent episodes coincide with drug ingestion.

Anti-Bacterial Agents↗

Clinical data and cerebrospinal fluid findings in Lyme meningitis versus aseptic meningitis.

The purpose of this study was to characterise Lyme meningitis (LM) in a Belgian paediatric population and to suggest findings that could allow early distinction from aseptic meningitis (AM). The medical records of patients hospitalised between 1993 and 2000 and with a discharge diagnosis of LM (n=14) or AM (n=16) were retrospectively reviewed. The Kruskal-Wallis test was used to compare data. Of the patients, 16 were identified with AM and 14 with LM, amongst which 7 presented with isolated LM and 7 with associated peripheral facial palsy (PFP). Patients with AM, when compared with LM, complained of more pronounced signs and symptoms of meningitis (fever, headaches, and neck stiffness); they statistically displayed a shorter period of symptoms before admission (1.6 vs 15 days), higher neutrophilic component (mean 56% vs 2.4%), and lower protein levels (mean 0.39 vs 1.12 g/l) on cerebrospinal fluid analysis. In the neuroborreliosis group, the duration of symptoms was shorter and the cerebrospinal protein level was lower in cases of LM associated with PFP compared to isolated LM (mean 1.3 vs 15 days; mean 0.55 g/l vs 1.12 g/l). Conclusions. Our results suggest that some clinical data and laboratory findings may help the physician to diagnose aseptic or Lyme meningitis before completion of serologic testing. LM should be suspected in cases of meningitis with very low CSF neutrophilic counts and high protein levels associated with prolonged duration of symptoms, low grade fever, and absence of pronounced signs of meningitis.

Adolescent↗

Cerebrospinal fluid and serum immunoglobulins and antibody titers in mumps meningitis and aseptic meningitis of other etiology.

Cerebrospinal fluid (CSF) and serum from 19 patients with mumps meningitis and 19 patients with meningitis of other etiology were investigated on two or more occasions for at least 1 month after onset. Intrathecal synthesis of immunoglobulin (Ig) G was found in 55%, of IgA in 26%, and of IgM in 24% of the patients. Oligoclonal Ig was demonstrable by agarose gel electrophoresis in 37% of the patients, mostly already during the first week after onset, and could persist for years. Mumps virus antibody synthesis within the central nervous system occurred in 37% of the mumps meningitis patients. The inflammatory reaction within the central nervous system as reflected by mononuclear pleocytosis, Ig synthesis, and oligoclonal Ig was not correlated to the clinical course. The blood-brain barrier was evaluated by determination of the CSF total protein, CSF/serum albumin ratio, and CSF/serum alpha2-macroglobulin ratio. A significant correlation was found among these three parameters. Persistence of the elevated CSF/serum albumin ratio seems to influence prognosis, and this parameter is recommended for evaluation of the blood-brain barrier function.

Antibodies, Viral↗

Sudden death in a 35-year-old man with occult malformation of the brain and aseptic meningitis.

A 35-year-old man was found dead by his wife. He was reported to have had symptoms of a common cold the week preceding his death. The medicolegal autopsy yielded signs of central dysregulation (ectasia of the urinary bladder and rectum, dystelectasis of the lungs) together with marked brain edema and fresh bite marks on the tongue. The cause of death was presumed to be lethal epileptic seizure. Neuropathologic examination revealed neuronal nodular heterotopia as well as discrete lymphocytic meningitis (aseptic meningitis). The death was most probably caused by the combination of the meningitis with the occult malformation, leading to a lowered seizure threshold and subsequent lethal seizure. The morphologic findings of this case are presented, and the probable mechanisms of death are discussed.

Adult↗

Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post-Haemophilus influenzae era.

CONTEXT: Children with meningitis are routinely admitted to the hospital and administered broad-spectrum antibiotics pending culture results because distinguishing bacterial meningitis from aseptic meningitis is often difficult. OBJECTIVE: To develop and validate a simple multivariable model to distinguish bacterial meningitis from aseptic meningitis in children using objective parameters available at the time of patient presentation. DESIGN: Retrospective cohort study of all children with meningitis admitted to 1 urban children's hospital from July 1992 through June 2000, randomly divided into derivation (66%) and validation sets (34%). PATIENTS: Six hundred ninety-six previously healthy children aged 29 days to 19 years, of whom 125 (18%) had bacterial meningitis and 571 (82%) had aseptic meningitis. INTERVENTION: Multivariable logistic regression and recursive partitioning analyses identified the following predictors of bacterial meningitis from the derivation set: Gram stain of cerebrospinal fluid (CSF) showing bacteria, CSF protein > or =80 mg/dL, peripheral absolute neutrophil count > or =10 000 cells/mm3, seizure before or at time of presentation, and CSF absolute neutrophil count > or =1000 cells/mm3. A Bacterial Meningitis Score (BMS) was developed on the derivation set by attributing 2 points for a positive Gram stain and 1 point for each of the other variables. MAIN OUTCOME MEASURE: The accuracy of the BMS when applied to the validation set. RESULTS: A BMS of 0 accurately identified patients with aseptic meningitis without misclassifying any child with bacterial meningitis in the validation set. The negative predictive value of a score of 0 for bacterial meningitis was 100% (95% confidence interval: 97%-100%). A BMS > or =2 predicted bacterial meningitis with a sensitivity of 87% (95% confidence interval: 72%-96%). CONCLUSIONS: The BMS accurately identifies children at low (BMS = 0) or high (BMS > or =2) risk of bacterial meningitis. Outpatient management may be considered for children in the low-risk group.

Adolescent↗

The aseptic meningitis syndrome.

The diagnosis and treatment of acute meningitis is a challenge for the primary care physician. Differentiating between bacterial meningitis and aseptic meningitis is not always straightforward. The aseptic meningitis syndrome is usually viral in origin, and enteroviruses account for most cases. The aseptic syndrome also may be caused by unusual bacterial organisms such as Mycobacterium tuberculosis, Leptospira species, Brucella species, Borrelia burgdorferi and others. The classic presentation consists of the acute onset of meningismus, headache, fever, malaise with pleocytosis and normal glucose and slightly elevated protein in the cerebrospinal fluid. Cerebrospinal fluid lactate and serum C-reactive protein measurements may be helpful in differentiating aseptic meningitis from treatable bacterial meningitis. Aseptic meningitis of viral origin usually responds to expectant care. Other causes of aseptic meningitis must be searched for and treated if present.

Clinical Protocols↗

Cytokine elevations in infants with bacterial and aseptic meningitis.

We sought to determine whether the detection of cytokines, produced during the inflammatory response, would aid in the diagnosis of meningitis in young infants. We measured cerebrospinal fluid (CSF) and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) in 62 infants less than 6 months of age whose condition was evaluated for meningitis. Twenty infants had culture-proved meningitis, 22 had aseptic meningitis, and 20 control infants had no evidence of meningitis. The CSF IL-6 levels were elevated in all 20 infants with bacterial meningitis and in 9 of 22 infants with aseptic meningitis but were undetectable in all control subjects. Furthermore, CSF IL-6 levels were 10 times greater in infants with bacterial versus aseptic meningitis (p < 0.001). Levels of TNF in CSF were detected in 12 of 20 infants with bacterial meningitis and were undetectable in infants with aseptic meningitis and in control infants (p < 0.02). Plasma IL-6 and TNF levels were unreliable for the detection of meningitis in this patient population. We conclude that the presence of IL-6 in the CSF reliably identifies infants with meningitis and that the presence of CSF TNF is a highly specific indicator of bacterial meningeal inflammation.

Humans↗

The clinical evaluation of an outbreak of aseptic meningitis in children.

BACKGROUND: Aseptic meningitis is a common disease in children; The present report describes the clinical and laboratory studies of 62 children involved in an outbreak of aseptic meningitis. METHODS: Sixty-two children with aseptic meningitis having been hospitalized from February to June 1993 were evaluated. The clinical data were obtained by review of the medical records. Initial cerebrospinal fluid (CSF) laboratory values were recorded, and CSF specimens were submitted to determine the viral etiology. RESULTS: Thirty-three percent of the cases were aged 2-5 years. Echovirus 30 was isolated from CSF specimens in 17 children, this is the only virus isolated from CSF during this period. The illness was characterized by transient fever, headache and vomiting. There was wide variation in the number of leukocyte from 14 to 2333 cell/mm3 in the spinal fluid. CSF protein ranged from 19 mg/dL to 114 mg/dL, and CSF sugar was normal in all specimens. Virus isolation was related to the cell count in CSF. There was no significant relationship between CSF cell count and protein content (r = 0.162, p = 0.2237). Hospital stay ranged from 1 to 14 days with an average of 3.9 days. CONCLUSIONS. The disease was mild and self-limiting without death or complication. Enterovirus isolation from CSF can substantially establish the diagnosis and the subsequent management, therefore, early discharge is expectable.

Adolescent↗

Active and total T cells in blood and cerebrospinal fluid during the course of aseptic meningitis.

Patients with aseptic meningitis (AM) were examined with the active T cell rosette test, which has been claimed to reflect cell-mediated immunocompetence more accurately than determination of total T cells. Higher percentages of active T cells were demonstrated in CSF compared to blood regardless if specimens were obtained on days 1-4, days 5-10, or later than 20 days after onset of symptoms, Active T cell percentages in CSF decreased when values for specimens obtained on days 5-10 were compared with those taken later than 20 days after onset, while no significant variations of active T cell percentages in blood were observed. The percentages of total T cells were higher in CSF than blood in specimens from days 5-10, and later than 20 days after onset, but no significant fluctuations of total T cells occurred in either CSF or blood over the course of AM.

Adolescent↗

Aseptic meningitis in children.

Aseptic meningitis is an acute inflammation of the meninges that can be caused by a number of different etiological agents. During the acute phase of the illness, the child demonstrates major neurological symptoms. Nursing interventions are mainly supportive and based not only on the child's presenting symptoms, but also on the child's developmental needs. Parent teaching and support by nurses during the child's hospitalization is essential.

Child↗