| 1. |
- Gnann, J. W., et al.
(författare)
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Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy
- 2015
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 61:5, s. 683-691
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Grände, Per-Olof, et al.
(författare)
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Lund strikes again - Reply
- 2002
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 46:10, s. 1281-1283
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Grände, Per-Olof, et al.
(författare)
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Treatment of intracranial hypertension and aspects on lumbar dural puncture in severe bacterial meningitis.
- 2002
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 46:3, s. 264-270
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Tidskriftsartikel (refereegranskat)abstract
- 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. METHODS: During a four-year period, an ICP-monitoring device was implanted in patients admitted to our hospital with severe bacterial meningitis and suspected intracranial hypertension. ICP above 20 mmHg was treated using the Lund Concept, which includes antihypertensive therapy (beta1-antagonist,alpha2-agonist), normalization of the plasma colloid osmotic pressure and the blood volume, and antistress therapy. RESULTS: ICP above 20 mmHg was found in all 12 patients studied. It was effectively reduced in all but two patients, who died. Both patients had a low cerebral perfusion pressure (<10 mmHg), dilated pupils at start of therapy and were beyond recovery. Radiological signs of brain swelling were present in only five patients. Seven patients recovered fully, while mild audiological impairment was observed in two and minor neurological sequelae in one patient. Eight patients showed signs suggesting imminent brain stem herniation before start of ICP-reducing treatment, seven of whom had been subjected to diagnostic lumbar dural puncture shortly before development of the brain stem symptoms. These symptoms gradually regressed after initiation of therapy, and in one patient reversal of brain stem herniation was documented by MRI. CONCLUSIONS: Severe bacterial meningitis can be associated with increased ICP, which can be reduced using the Lund Concept. The high survival rate, the low frequency of sequelae and the reversal of signs of imminent brain stem herniation in these high-risk patients indicated beneficial effects of the intervention. The study confirms earlier observations that lumbar dural puncture is potentially hazardous in patients with intracranial hypertension, because it may trigger brain stem herniation. A normal CT brain scan does not rule out intracranial hypertension.
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| 4. |
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| 5. |
- Melhus, Åsa, et al.
(författare)
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Vibrio vulnificus : Havsbakterie med dödlig potential
- 2001
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 98:32-33, s. 3400-3402
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Tidskriftsartikel (refereegranskat)abstract
- Vibrio vulnificus is a halophilic gram-negative rod widespread in the aquatic environment and associated with primary septicemia and severe wound infections. The first Swedish case was reported in 1994. Ever since, sporadic cases have occurred in the south of Sweden whenever the coastal water temperature has exceeded 20 degrees C. Critical for a successful outcome in these infections has been early diagnosis with appropriate antibiotic and surgical treatment. A review of this subject was prompted by two cases of fulminant septicemia, which both presented themselves as atypical erysipelas.
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| 6. |
- Nääs, Anja, et al.
(författare)
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Temporal pathway analysis of cerebrospinal fluid proteome in herpes simplex encephalitis
- 2023
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Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 55:10, s. 694-705
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesWe examined the temporal changes of the CSF proteome in patients with herpes simplex encephalitis (HSE) during the course of the disease, in relation to anti-N-methyl-D-aspartate receptor (NMDAR) serostatus, corticosteroid treatment, brain MRI and neurocognitive performance.MethodsPatients were retrospectively included from a previous prospective trial with a pre-specified CSF sampling protocol. Mass spectrometry data of the CSF proteome were processed using pathway analysis.ResultsWe included 48 patients (110 CSF samples). Samples were grouped based on time of collection relative to hospital admission - T1: & LE; 9 d, T2: 13-28 d, T3: & GE; 68 d. At T1, a strong multi-pathway response was seen including acute phase response, antimicrobial pattern recognition, glycolysis and gluconeogenesis. At T2, most pathways activated at T1 were no longer significantly different from T3. After correction for multiplicity and considering the effect size threshold, 6 proteins were significantly less abundant in anti-NMDAR seropositive patients compared to seronegative: procathepsin H, heparin cofactor 2, complement factor I, protein AMBP, apolipoprotein A1 and polymeric immunoglobulin receptor. No significant differences in individual protein levels were found in relation to corticosteroid treatment, size of brain MRI lesion or neurocognitive performance.ConclusionsWe show a temporal change in the CSF proteome in HSE patients during the course of the disease. This study provides insight into quantitative and qualitative aspects of the dynamic pathophysiology and pathway activation patterns in HSE and prompts for future studies on the role of apolipoprotein A1 in HSE, which has previously been associated with NMDAR encephalitis.
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| 7. |
- Schliamser, Silvia E., 1953-
(författare)
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Neurotoxicity of β-lactam antibiotics : experimental kinetic and neurophysiological studies
- 1988
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The neurotoxic potential of intravenous administered benzylpenicillin (BPC) was studied in rabbits with intact blood-CNS barriers and rabbits with experimental E. coli meningitis. At onset of epileptogenic EEG activity or seizures, serum, CSF and brain tissue were collected for assay of BPC. Based on the fact that, in tissues, BPC seems to remain extracellularly, brain concentrations of BPC were expressed as brain tissue fluid (BTF) levels, calculated as lOx the concentration in whole brain tissue. Neurotoxicity could be precipitated in all rabbits. In normal rabbits BTF levels of BPC were considerably higher than those in CSF indicating a better penetration across the blood-brain barrier (BBB). BPC penetrated better to CSF and BTF in meningitic rabbits than in normal controls, suggesting some degree of damage of the BBB concomitant with meningeal inflammation. E. coli meningitis did not increase the neurotoxicity of BPC. In control rabbits the intracistemal injection of saline resulted in some degree of pleocytosis. Unmanipulated animals are therefore preferable as controls. Epileptogenic EEG-changes was the most precise of the two variables used for demonstration of neurotoxicity. EEG-changes were therefore used as neurotoxicity criterion in the following rabbit experiments. To evaluate the effect of uraemia alone and uraemia plus meningitis on the neurotoxity of BPC in rabbits, cephaloridine was used to induce uraemia. Meningitis was induced by intracistemal inoculation of a cephalosporinresistant strain of E. cloacae. Untreated rabbits were used as controls. Uraemia resulted in increased BTF penetration of BPC, possibly explained by permeability changes in the BBB and/or decreased binding of BPC to albumin. Uraemia did not result in increased penetration of BPC into the CSF of non-meningitic rabbits. Uraemic non-meningitic rabbits had the highest BTF levels of BPC at the criterion, indicating that cephaloridine-induced renal failure increased the epileptogenic threshold in these rabbits. The combination of uraemia and meningitis increased the neurotoxicity of BPC since the criterion was reached at considerably lower BTF levels of BPC. Meningitis, either alone or together with uraemia, did not increase the neurotoxicity in comparison to control rabbits. Higher BTF levels of BPC were found in meningitic rabbits than in controls with intact blood-CNS barriers at onset of EEG-changes. In all groups of rabbits there was a pronounced variability of BPC levels in the CSF while the intra-group variations in BTF levels were much smaller. Thus, BTF and not CSF levels were decisive for the neurotoxicity of BPC. Using the same EEG-model, the neurotoxic potential of imipenem/cilastatin (I) and a new penem derivative, FCE 22101 were compared in a cross-over study. Both I and FCE 22101 were significantly more neurotoxic than BPC. While BTF levels of the three antibiotics could be detected in all tested rabbits, detectable CSF levels were only found in one of twelve rabbits treated with I or FCE 22101, indicating that BTF concentrations rather than CSF ones are decisive for neurotoxicity of ß-lactam antibiotics. The EEG-model used was found to be a suitable model for cross-over studies of intravenously administered antibiotics. Using the "silent-second" as EEG-threshold, a CNS interaction between intraperitoneally administered BPC and intravenous thiopental was demonstrated in rats. The most probably site for this interaction is the organic acid transport system out of the CNS. Thiopental distribution in the rat brain seemed to depend not only on its lipid solubility.
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| 8. |
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| 9. |
- Westman, Gabriel, 1977-, et al.
(författare)
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Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis.
- 2021
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Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 27:8, s. 1131-1136
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim was to investigate the correlation between biomarkers of brain injury and long-term neurocognitive outcome, and the interplay with intrathecal inflammation and neuronal autoimmunity, in patients with herpes simplex encephalitis (HSE).METHODS: A total of 53 adult/adolescent HSE patients were included from a prospective cohort in a randomized placebo-controlled trial investigating the effect of a 3-month follow-up treatment with valaciclovir. Study subjects underwent repeated serum/cerebrospinal fluid (CSF) sampling and brain magnetic resonance imaging in the first 3 months along with cognitive assessment using the Mattis Dementia Rating Scale (MDRS) at 24 months. CSF samples were analysed for biomarkers of brain injury, inflammation and synaptic autoimmunity. The predefined primary analysis was the correlation between peak CSF neurofilament protein (NFL), a biomarker of neuronal damage, and MDRS at 24 months.RESULTS: Impaired cognitive performance significantly correlated with NFL levels (rho = -0.36, p = 0.020). Development of IgG anti-N-methyl-D-aspartate receptor (NDMAR) antibodies was associated with a broad and prolonged proinflammatory CSF response. In a linear regression model, lower MDRS at 24 months was associated with previous development of IgG anti-N-methyl-D-aspartate receptor (NMDAR) (beta = -0.6249, p = 0.024) and age (z-score beta = -0.2784, p = 0.024), but not CSF NFL, which however significantly correlated with subsequent NMDAR autoimmunization (p = 0.006).DISCUSSION: Our findings show that NFL levels are predictive of long-term neurocognitive outcome in HSE, and suggest a causative chain of events where brain tissue damage increases the risk of NMDAR autoimmunisation and subsequent prolongation of CSF inflammation. The data provides guidance for a future intervention study of immunosuppressive therapy administered in the recovery phase of HSE.
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| 10. |
- Westman, Gabriel, 1977-, et al.
(författare)
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Clinical significance of IgM and IgA class anti-NMDAR antibodies in herpes simplex encephalitis
- 2018
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 103, s. 75-80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Herpes simplex encephalitis (HSE) is a devastating disease, often leaving patients with severe disabilities. It has been shown that IgG anti-N-methyl-o-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.
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