Silvia E. Schliamser

Treatment of intracranial hypertension and aspects on lumbar dural puncture in severe bacterial meningitis

Background: Brain stem herniation due to raised intracranial pressure (ICP) is a common cause of mortality in severe bacterial meningitis, but continuous measurements of ICP and the effects of ICP‐reducing therapy in these patients have, to our knowledge, not been described.

Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy

BACKGROUND Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority. METHODS Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint. RESULTS The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group. CONCLUSIONS Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors. CLINICAL TRIALS REGISTRATION NCT00031486.

A premature infant with fulminant meningococcal septicaemia

The case is described of a 10-week-old preterm infant, a twin boy born at 34 weeks of gestational age. The day after a hernia operation he had a rapidly progressive fulminant Neisseria meningitidis serogroup B septicaemia, of which he died despite immediate and adequate treatment. No secondary cases occurred among other infants on the neonatal intensive care unit. Epidemiological investigation revealed that of 185 bacterial throat cultures performed on 17 infants on the ward, 37 close relatives to the infants and 131 medical personnel in contact with the deceased patient, 4 (2.2%) were asymptomatic carriers of N. meningitidis. Serotyping and pulsed-field gel electrophoresis of the genomic DNA of the N. meningitidis isolates revealed that the infant and his father had closely related strains.

Clinical significance of IgM and IgA class anti-NMDAR antibodies in herpes simplex encephalitis

BACKGROUND Herpes simplex encephalitis (HSE) is a devastating disease, often leaving patients with severe disabilities. It has been shown that IgG anti-N-methyl-d-aspartate receptor (NMDAR) antibodies appear in approximately 25% of HSE patients and could be associated with impaired recovery of cognitive performance. OBJECTIVES To characterize the prevalence of IgM and IgA anti-NMDAR antibodies in HSE patients, in relation to subsequent development of IgG anti-NMDAR and correlation to cognitive performance. STUDY DESIGN A total of 48 subjects were included from a previously described cohort of patients with HSE verified by HSV-1 PCR. Cerebrospinal fluid (CSF) and serum samples drawn close to onset of disease, after 14-21 days of iv aciclovir treatment and after 90 days of follow-up, were analyzed for the presence of IgM and IgA anti-NMDAR, and related to IgG anti-NMDAR. Antibody levels were correlated to the recovery of cognitive performance, as estimated by the Mattis Dementia Rating Scale (MDRS), for a total of 24 months. RESULTS In total, 27 of 48 (56%) study subjects were anti-NMDAR positive, defined as the presence of IgG (12/48, 25%), IgM (14/48, 29%) or IgA (13/48, 27%) antibodies in CSF and/or serum. IgM or IgA anti-NMDAR did not predict subsequent IgG autoimmunization and did not correlate to cognitive outcome. IgG anti-NMDAR serostatus, but not antibody titers, correlated to impaired recovery of cognitive performance. CONCLUSIONS A majority of HSE patients develop IgG, IgM or IgA anti-NMDAR antibodies. However, the predictive value and clinical relevance of non-IgG isotypes remains to be shown in this setting.

Lund strikes again - Reply

Sir, Our good colleagues in Lund have done it again. Published a paper with a lot of smoke, but severe lack of hard facts (1). The Lund group has not yet demonstrated in a scientific indisputable way that the theoretical foundation for the treatment algorithm is true. On the other hand Bundgaard et al. has raised questions, which cast a shadow of doubt on the theory, even given the fact that the subjects in the latter study is tumor patients under isoflurane anesthesia (2). One of the theoretical foundations of the Lund therapy is a dysfunctional blood brain barrier (BBB). In a recent publication from the Marmarous group it was shown that BBB breakdown is transitional and it was stated that ‘Edema formation clearly does not correspond with BBB opening and an open BBB is clearly not required for edema formation’ (3). In the selected subpopulation of patients with bacterial meningitis and intracranial hypertension in the present publication, the BBB is leaking, but to what extent and for how long a period? All the patients had decreasing ICP during the treatment period, but what about their temperature and, more importantly, what about the PaCO2? To credit the specifics of the Lund therapy for the fall in ICP is only possible if temperature and PaCO2 remained constant. What was the outcome of the patients who did not receive the Lund therapy? What was the time window from onset of the infection to initiation of the therapy? What is RLS? We were told that four patients (1, 4, 5 and 10) were given dihydroergothamine, but how many patients received other medications (please specify), and for how long a period? There might be a beneficial effect of the Lund treatment in selected subgroups of patients but not in the general population of patients with a severe head injury. Questions about the Lund concept have recently been raised in an editorial in this journal (4). I call on our colleagues in Lund to set up a randomized (placebo controlled) multicenter study, which will enable us to answer the question: is the Lund therapy beneficial for patients with intracranial hypertension? Niels Juul