Category Archives: Clinical presentation

Clinical presentation of patients with aseptic meningitis: Discussion (part 3)

Diagnostic PCR

Adult patients who received antibiotics were likely to have relatively low glucose levels, a sign associated with bacterial meningitis. Surprisingly, one-fourth of patients who were empirically treated remained on the anti-infectives after the positive PCR test result was available. This proportion was not significantly different than that of patients who were negative for EV, suggesting that the EV PCR test result did not impact anti-infective use in aseptic meningitis. More than one-third of EV-positive patients who were given only antibiotics remained on the drugs 24 h post-result. Clearly, this use of antibiotics is inappropriate, because a positive EV result essentially eliminates the possibility of a bacterial cause.

Clinical presentation of patients with aseptic meningitis: Discussion (part 2)

The difference in length of stay between the EV-positive and EV- negative patients was not surprising, because a positive result is very strong evidence for a self-limited disease. In spite of the clear association between a positive result and a shortened hospital stay, it is difficult to determine the extent to which a positive PCR test enabled clinicians to discharge the patient. Because EV meningitis is typically mild, many patients may have been promptly discharged by virtue of their improving clinical condition, had the test not been performed or had it been negative. Conversely, a negative EV PCR test may lead the physician to be tentative about releasing the patient, or the EV-negative patients may have had complicated illnesses that naturally led them to remain in hospital longer (EV-negative diagnoses in the present study included encephalitis, temporal lobe tumour, septicemia, seizure disorders, mononucleosis, central nervous system lymphoma, transient ischemic attack and others). EV PCR testing appeared to influence isolation precautions especially in patients who were previously not isolated.

Clinical presentation of patients with aseptic meningitis: Discussion (part 1)

EV meningitis
There was a considerable overlap in the clinical and laboratory features of patients with and without EV meningitis. Patients with EV meningitis were frequently admitted and were treated empirically with antibiotics and acyclovir. EV meningitis was more common in younger patients and those with fever, rash, photophobia, sudden onset and a history of exposure to someone unwell. The prevalence of headache, fever, stiff neck and seizure are consistent with other studies of viral meningitis. The oldest EV-positive patient in the present study was 34-years-old. Although statistically significant, the small difference in temperature (0.8 °C) is unlikely to be clinically useful. The higher rate of exposure to sick contacts in the EV-positive group may reflect the large pediatric representation (and therefore may include school/ daycare exposures or perhaps parents being over-inclusive in recalling sick person contacts).

Clinical presentation of patients with aseptic meningitis: Results — The decision to admit (part 3)

The overall length of stay in hospital was shorter in the group whose CSF was positive for EV. The EV-positive group had a mean stay of 5.44±1.07 days (n=27), significantly fewer days than the EV-negative group (14.31±2.36 days [n=70], P=0.024). A positive EV PCR test result, however, did not significantly shorten the time between the test result and discharge (Table 4).

Table 4. Experience in hospital based on CSF EV PCR test result

EV PCR test result
Positive Negative P
Lenght of stay, day 5.44±1.07 (27) 14.31±2.36 (70) 0.024
Lenght of stay, day 2.45±0.74 (27) 8.73±2.04 (66) 0.055

Data presented as mean ± SEM (n) unless otherwise indicated. CSF Cerebrospinal fluid; EV Enteroviral; PCR Polymerase chain reaction

Clinical presentation of patients with aseptic meningitis: Results — The decision to admit (part 2)

CSF properties, such as glucose or protein concentration, WBC count, or cell differential did not predict which patients would be admitted to the hospital (Table 3). Glucose levels were within the normal range (2.2 mmol/L to 3.9 mmol/L) in all patients. Children not admitted had a mean CSF protein level within the normal range (0.15 g/L to 0.45 g/L), whereas protein levels were elevated in admitted children and both admitted and discharged adults. The mean CSF WBC counts were elevated in all groups; however, nonadmitted children had a more modest WBC increase than the other groups. Fischer’s exact test found no association between the proportion of patients admitted and the season in which they presented (September to November versus all other months, P=0.465).

Table 3. ANOVA of cerebrospinal fluid (CSF) characteristics based on admission status

CSF characteristic Age 0-16 years Age >16 years
Admitted Not admitted P Admitted Not admitted P
Glucose, mmol/L 2.85±0.13 (43) 2.91±0.21 (4) 0.890 3.58±0.18 (47) 3.22±0.29 (15) 0.321
Protein, g/L 1.41±0.39 (43) 0.43±0.09 (4) 0.448 0.86±0.08 (47) 0.82±0.11 (15) 0.798
White blood cell count, 109/L 220.72±103.89 (47) 21.25±12.26 (4) 0.581 177.70±53.71 (47) 330.00±129.54 (15) 0.208
Neutrophils, % 36.50±6.31 (20) 23.00±23.00 (2) 0.529 6.12±3.26 (26) 11.14±4.97 (14) 0.387
Mononuclear cells, %) 57.80±6.94 (20) 76.50±23.50 (2) 0.428 93.62±3.25 (26) 83.07±6.67 (14) 0.117

Data presented as mean ± SEM (n), unless otherwise indicated

Clinical presentation of patients with aseptic meningitis: Results — The decision to admit (part 1)

In all, 83.6% of patients were admitted for treatment or observation (n=116, one patient left against medical advice). A linear regression analysis was conducted on the following variables to determine the most important factors in patient admission: sex, age older than 16 years, headache, fever, stiff neck, rash, photophobia, onset of less than 48 h, exposure to a sick person, the presence of seizure, focal neurological symptoms, GCS <15, nausea or vomiting, and admitted to hospital (14.13±0.23 [n=47] versus 15.00±0.00 in the nonadmitted group [n=15], P=0.040). CSF properties, such as glucose or protein concentration, WBC count, or cell differential did not predict which patients would be admitted to the hospital (Table 3). 

Clinical presentation of patients with aseptic meningitis: Results — Initial presentation (part 2)

Aseptic

EV-positive patients were less likely than EV-negative patients to report seizure (2.9% versus 18.1%, P=0.037) or to demonstrate focal neurological findings (6.3% versus 36.1%, P=0.001). However, the average Glasgow Coma Scores (GCS), where recorded, were near normal (GCS=15) and were statistically similar in both groups of patients. Recorded temperatures were significantly higher in EV-positive patients as calculated by t test (38.0±0.2°C versus 37.2±0.1°C, P<0.001).

Clinical presentation of patients with aseptic meningitis: Results — Initial presentation (part 1)

The records of 34 EV-positive patients (nine adults, 25 children) and 83 control patients (57 adults, 26 children) were consulted for differences in signs, symptoms and characteristics using Fisher’s exact test (Table 1). The EV-positive group was significantly younger (mean [±SD] 7.9±2.0 years) than the EV-negative group (mean 30.2±2.6 years, P<0.001). There were no EV-positive patients older than 34 years of age.

Clinical presentation of patients with aseptic meningitis: Results — Anti-infective use

Meningitis

Further analysis (linear regression using the same characteristics as above) of the empirically treated group demonstrated that age older than 16 years was a determinant in the provision of acyclovir, accounting for 22.6% (n=38) of the variability between the administered and the nonadministered groups. By linear regression, those receiving both antibiotics and acyclovir were also more likely to be adults. An age older than 16 years was responsible for 14.5% of the variance within the group who received both anti-infectives, headache for those receiving only acyclovir (20.6 % variance explained), and age older than 16 years and nausea (22.6 % and 10.0 % variance, respectively) for those receiving antibiotics alone (n=38). In the adult population, ANOVA demonstrated that a higher CSF glucose level was associated with acyclovir use (P=0.008, n=37), while a lower CSF glucose level was associated with antibiotic use (P=0.015, n=37). The presence of headache also played a role in the prescription of antibiotics, accounting for 20.6% of the variance between the treated group and the untreated group (n=38), by linear regression.

Clinical presentation of patients with aseptic meningitis: Methods

Subsequent to appropriate ethics approval from both institutions, patients seen at Capital District Health Authority (CDHA) (Halifax, Nova Scotia) hospitals or the Izaak Walton Killam (IWK) Hospital (Halifax, Nova Scotia) whose CSF samples were tested for the presence of enterovirus by means of PCR from January 2006 to December 2008 were identified from the laboratory information systems. All adults from CDHA with either positive or negative EV PCR test results were reviewed. Due to the large volume of pediatric charts, all EV-positive children were reviewed and date-matched to an equal number of EV-negative pediatric patients. For the examination of the seasonality of EV meningitis all 372 Nova Scotian EV PCR-tested patients were included.

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