Lykke Larsen

Results of a Multinational Study Suggest the Need for Rapid Diagnosis and Early Antiviral Treatment at the Onset of Herpetic Meningoencephalitis

ABSTRACT Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.

Use of intracranial pressure monitoring in bacterial meningitis: a 10-year follow up on outcome and intracranial pressure versus head CT scans

Abstract Background: The aim of this study was to evaluate the clinical outcome of patients with severe bacterial meningitis where intracranial pressure (ICP) monitoring has been performed. Methods: A retrospective observational study including patients admitted 1st. January 2005 to 31st. December 2014. Thirty nine patients age 18–89 years were included. All the patients received intensive care with mechanical ventilation, ICP monitoring, sedation, antibiotics and corticosteroids according to current guidelines. Clinical outcome was defined as death during hospitalization or survival at hospital discharge. Results: The most common pathogen was Streptococcus pneumoniae (26; 67%). Thirteen patients died (33%) and neurologic impairment was noted in twenty two (84.6%) surviving patients. In S. pneumoniae cases patients with adverse outcome were significantly older (p = 0.0024) and immunosuppressed (p = 0.034). Lower mean-cerebral perfusion pressure (CPP) was found to correlate with adverse outcome (p = 0.005). Cerebrospinal fluid (CSF) was drained in fourteen patients. Increased ICP (>20 mmHg) was observed in twenty four patients. No significant correlation was found between measured ICP and head CT scans with signs of elevated ICP. Conclusions: Patients with severe meningitis should be admitted to intensive care units and evaluated for ICP monitoring regardless of head CT findings.

Managing atypical and typical herpetic central nervous system infections: results of a multinational study

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection.

Cerebrospinal fluid lactate as a marker to differentiate between community-acquired acute bacterial meningitis and aseptic meningitis/encephalitis in adults: a Danish prospective observational cohort study

Abstract Background: The ability of cerebrospinal fluid (CSF) lactate to distinguish between acute bacterial meningitis (ABM) and aseptic meningitis/encephalitis (AME) is debated. We assessed the diagnostic value of CSF lactate to discriminate between ABM and AME. Methods: We included 176 patients from a prospective adult cohort with neuroinfections. In total, 51 ABM and 125 AME patients with clinically and/or microbiologically diagnosed acute meningitis were examined with CSF-lactate and traditional markers for infection. Receiver operating characteristic (ROC) curves were used to assess diagnostic performance. Results: In CSF, lactate, leukocytes, fraction of neutrophils, protein and glucose ratio, were significantly different between the ABM and AME groups. CSF lactate had the best diagnostic value, with an area under the curve (AUC) of 0.976 (95%CI 0.966–0.997) and using a cut-off of 3.5 mmol/L a sensitivity of 96% and specificity of 85%. Antibiotic treatment before lumbar puncture had no significant effect on the AUC of CSF lactate. Conclusions: Compared to traditional CSF-markers, CSF lactate is more accurate to distinguish between ABM and AME.

Patterns of cerebral tissue oxygen tension and cytoplasmic redox state in bacterial meningitis

Compromised cerebral energy metabolism is common in patients with bacterial meningitis. In this study, simultaneous measurements of cerebral oxygen tension and lactate/pyruvate ratio were compared to explore whether disturbed energy metabolism was usually caused by insufficient tissue oxygenation or compromised oxidative metabolism of pyruvate indicating mitochondrial dysfunction.