Ralph Woessner

Influence of a Long-Term, High-Dose Volume Therapy with 6% Hydroxyethyl Starch 130/0.4 or Crystalloid Solution on Hemodynamics, Rheology and Hemostasis in Patients with Acute Ischemic Stroke

Background: This study was performed to investigate the clinical effects of a 4-day volume therapy with a newly developed, 6% hydroxyethyl starch (HES) 130/0.4 versus crystalloid solution, with particular regard to systemic and cerebral hemodynamics, rheology and safety. Methods: In a randomized, double-blind study, 40 patients suffering from an acute ischemic stroke received either 6% HES 130/0.4 or crystalloid solution as continuous infusion over 4 days with a total dose of 6.5 liters. Efficacy parameters studied included hemodynamics (cardiac output, blood pressure, flow velocity with transcranial Doppler) and rheology (hematocrit and plasma viscosity). Safety parameters examined included laboratory, hemostaseology (including factor VIII) and an adverse event questionnaire (including pruritus). Results: In both groups, a small, but not significant increase in cardiac output was observed. There were no significant changes regarding the remaining efficacy or safety parameters, except for the well-known increase in serum alpha-amylase through the infusion of HES. Conclusion: In our study with patients suffering from acute ischemic stroke, continuous infusion (1 ml/min) of HES 130/0.4 or crystalloid solution did not differ regarding safety or hemodynamic efficacy.

Chronic Fatigue Syndrome in Patients with Lyme Borreliosis

Several authors have reported a chronic fatigue-like syndrome in patients that have suffered from Lyme borreliosis in the past. To further investigate this suspicion of an association without sample bias, we carried out a prospective, double-blind study and tested 1,156 healthy young males for Borrelia antibodies. Seropositive subjects who had never suffered from clinically manifest Lyme borreliosis or neuroborreliosis showed significantly more often chronic fatigue (p = 0.02) and malaise (p = 0.01) than seronegative recruits. Therefore we believe it is worth examining whether an antibiotic therapy should be considered in patients with chronic fatigue syndrome and positive Borrelia serology.

Treatment with anticoagulants in cerebral events (TRACE)

90 patients with acute stroke and a concomitant cardiac embolism source or a symptomatic high-grade stenosis of an extra-or intracranial vessel received in a mulitcenter, randomized, controlled study either Enoxaparin 1 mg/kg BW s.c. b.i.d. or i.v. heparin aPTT-adjusted daily for 8 +/- 2 days as secondary prophylaxis. There were no significant differences between the two groups regarding cerebral and systemic embolic events, bleeding complications, length of hospital stay, number of diagnostic and therapeutic measures and outcome after three months. This suggests that Enoxaparin, which is easier to administer and monitor, is a safe drug in patients with acute cerebral events.

Incidence and prevalence of infection with human granulocytic ehrlichiosis agent in Germany. A prospective study in young healthy subjects.

AbstractBackground: Only limited data are available on incidence and prevalence of infection with the human granulocytic ehrlichiosis (HGE) agent in a healthy population. Materials and Methods: In a prospective study, we tested 361 male soldiers (age 18–29 years) from southwestern Germany for the HGE agent immunoglobulin G (IgG) using an indirect immunofluorescence antibody assay and for Borrelia burgdorferi IgG with an ELISA at the beginning and the end of their 10-month military service. Using a standardized questionnaire, the subjects were asked about clinical symptoms at the beginning and the end of the observation period. Results: Of these 361 subjects, 14.9% were HGE agent IgG positive at study entry. 19 participants (5.3%) seroconverted from IgG negative to positive during the observation period resulting in an incidence rate of 6.4% per year. 20 subjects converted from initially HGE agent. IgG positive to negative resulting in a reconversion rate of 6.6% per year. Concurrence of Borrelia IgG and HGE agent IgG was observed in 21.1%, whereas 13.7% were HGE agent IgG positive but Borrelia IgG negative (not significant). Clinical symptoms associated with HGE were not present in seroconverting subjects. Conclusion: Infection with the HGE agent occurs frequently in southwestern Germany but was asymptomatic in these young subjects.

The Erve virus: possible mode of transmission and reservoir.

SummaryThe Erve virus is suspected to cause severe headache in humans, lasting several days (thunderclap headache). Mice are characterized as a probable reservoir for the Erve virus. We tested 396 wild mice for Erve virus using an immunofluorescence test and found Erve virus antibodies in five cases, showing that small mammals form a reservoir for Erve virus. If ticks are the vector for the virus, a coincidence with borreliosis should exist. We were unable to confirm this in a homogeneous cohort of 955 young men, 62 of whom tested positive for borreliosis. This group did not test positive significantly more often in the immunofluorescence test than a gender- and age-matched control group.

Prevalence of antibodies to tick-borne encephalitis virus and Borrelia burgdorferi sensu lato in samples from patients with abnormalities in the cerebrospinal fluid

Within the last few years, an increase in cases of tick-borne encephalitis (TBE) as well as an expansion of TBE-endemic regions have been noted in southern Germany. In 1994, a patient was diagnosed for the first time with TBE that had been acquired in Saarland. Up to this point, the Saarland had been considered TBE-free. In a retrospective study, we tested serum samples from 904 patients with abnormalities in the cerebrospinal fluid (CSF) for TBE antibodies. The IgG ELISA used (Immunozym-FSME-IgG, Immuno GmbH, Heidelberg, Germany) yielded 47 positive and 134 borderline sera. The percentage of positive sera showed a significant increase during the time period studied (1989-1994): One IgG-positive serum sample was also IgM-positive. Of the CSF samples, 2 were IgG-positive and 7 were borderline for IgG. In three patients, a positive intrathecal antibody index (IAI) was found, indicating an incrathecal antibody production. An analysis of the vaccination history of the patients showed that only 19% of the patients with a positive TBE IgG titre and only 5.9% of the borderline patients had been vaccinated against TBE. We compared 98 patients that tested positive or borderline for TBE IgG with 98 sex-and-age-matched patients that tested negative. The parameters studied included the patients complaints upon discharge, the average duration of stationary treatment and 16 different neurological symptoms. We did not observe any significant differences between the two groups. We also tested the sera of 704 of the 904 patients for antibodies to Borrelia burgdorferi (Borrelia burgdorferi ELISA, Genzyme Virotech GmbH, Rüsselsheim, Germany). 155 (22.0%) of the sera were IgG-positive, 136 (19.3%) were borderline, 32 patients (4.6%) had a positive intrathecal antibody index (IAI). The fact that no patient with a clinically manifest case of TBE had acquired the disease in the Saarland indicates that the actual risk of acquiring an acute TBE in the Saarland is very low, despite the high percentage of samples that tested positive for IgG in the ELISA. The increase in the number of serum samples that tested positive for TBE IgG during the last years could be explained by an expansion of TBE regions into the Saarland, increasing vaccination of the population or more travel to endemic regions. The proportion of patients with IgG antibodies to Borrelia was 22%. Because only part of the patients suffered from an acute, clinically manifest borreliosis, and since the serum IgG titre had remained positive for many years after contact with the microorganisms, we suspected that a large percentage of the population would show signs of a clinically silent infection in their sera. 4.6% of the patients had a positive IAI quotient, a clear indication of neuroborreliosis.

Tick-borne encephalitis in the Saarland and the Rhineland-Palatinate

SummaryThe Saarland and the Rhineland-Palatinate are not considered endemic regions for tick-borne encephalitis (TBE), and patients in this region have not been routinely advised to undergo vaccination or serologic testing for TBE. In 1994, a significantly increased incidence of TBE cases was noted in the neighbouring state of Baden-Württemberg. In the same year, the first TBE acquired in the Saarland was diagnosed. To investigate the infection risk for TBE in the Saarland and Rhineland-Palatinate, the records of 2,123 serologic tests for TBE collected since 1989 were systematically examined. In addition, 904 frozen sera of patients displaying inflammatory changes in the cerebrospinal fluid (CSF) were analyzed. IgG and IgM antibodies against TBE virus were found in 15 patients, four of which were verified clinically and serologically as TBE. One of these four cases was certainly and another was probably acquired in the Saarland. Three other patients displayed serologic signs of a TBE virus contact. The results of this study suggest that the occurrence of single cases in the Saarland has to be considered, but the risk is very small.ZusammenfassungDas Saarland und Rheinland-Pfalz gelten nicht als Frühsommer-Meningoenzephalitis (FSME)-Endemiegebiete. Daher wurde in dieser Region nicht zu einer Impfung gegen FSME geraten und es wurde auch nur selten serologisch auf diese Krankheit untersucht. 1994 wurde in Baden-Württemberg eine deutliche Zunahme der Erkrankungsfälle registriert. Ferner wurde in diesem Jahr die erste im Saarland erworbene FSME dokumentiert. Zur Klärung der Frage, wie hoch das Infektionsrisiko für TBE im Saarland und Rheinland-Pfalz ist, wurden seit 1989 durchgeführte 2123 serologische FSME-Untersuchungen aufgearbeitet und 904 tiefgefrorene Seren von Patienten mit entzündlichen Liquorveränderungen serologisch nachuntersucht. Bei insgesamt 15 Patienten fanden wir IgG- und IgM-Antikörper gegen den Erreger der FSME. 4 Fälle wurden klinisch und serologisch als FSME gesichert, wobei eine Erkrankung sicher und eine weitere wahrscheinlich im Saarland erworben wurden. Bei drei weiteren Patienten fanden wir serologische Hinweise auf einen FSME-Virus Kontakt. Die Untersuchungsergebnisse legen den Verdacht nahe, daß im Saarland mit vereinzelten Erkrankungsfällen gerechnet werden muß. Das Infektionsrisiko ist jedoch sehr gering.

Tick-borne encephalitis diagnosis in patients with inflammatory changes in the cerebrospinal fluid in a region with very low prevalence

SummaryTick-borne encephalitis (TBE)-IgG antibodies are used for the serologic detection of antigen contact caused by TBE infection or immunization. In the present study, enzyme-linked immune sorbent assay (ELISA) results from a group of patients with inflammatory changes in the cerebrospinal fluid (CSF) were re-examined using Western blot technology. The result of the TBE-IgG-ELISA was positive in 47 of the 904 sera samples tested. Retesting the sera with a Western blot confirmed this result in only 31.8% of the positive cases. In 134 of the 904 sera, the ELISA result was borderline. In 5.5% of these sera, the Western blot reacted specifically. The remaining 723 sera samples tested negative with the ELISA. Of these sera, 15 were selected randomly and retested with the Western blot; none of them tested positive. The high number of false positive ELISA results can be explained by the highly selected group of patients and the low prevalence of TBE in the region studied. In patients with meningitis or encephalitis with positive ELISA results and uncharacteristic clinical symptoms, the treating physician should consider the possibility of nonspecific reactions involving inflammatory mediators or cross-reactivity with other flaviviruses. The ELISA-mediated diagnosis of TBE should therefore be verified by means of the patients history and clinical symptoms, as well as further serologic tests including the Western blot, the hemagglutination test and the neutralization test.ZusammenfassungFSME-IgG-Antikörper werden zum serologischen Nachweis eines Antigen-Kontaktes infolge einer Infektion oder einer Immunisierung verwendet. In dieser Untersuchung wurde der ELISA bei einer Risikogruppe von Patienten mit entzündlichen Liquorveränderungen mit Hilfe eines Western Blot verifiziert. Ein FSME-IgG-ELISA ergab bei 47 der 904 untersuchten Seren einen positiven Befund. Eine Western-Blot-Untersuchung bestätigte dieses Ergebnis in nur 31,8% der Fällen. Bei 134 der 904 Untersuchten ergab die ELISA-Testung ein grenzwertiges Ergebnis. Bei 5,5% dieser Seren reagierte der Western-Blot spezifisch. 723 Seren waren im ELISA negativ. Von 15 zufällig aus diesen 723 ausgewählten Proben war keine im Western-Blot positiv. Die hohe Zahl falsch positiver ELISA-Ergebnisse kann durch die hochselektionierte Patientengruppe und die niedrige FSME-Prävalenz in der untersuchten Region erklärt werden. Bei Patienten mit einer Meningitis oder Enzephalitis sollte bei positiven ELISA-Testergebnissen und uncharakteristischer klinischer Symptomatik an die Möglichkeit von unspezifischen Reaktionen mit Entzündungsmediatoren oder an Kreuzreaktionen mit anderen Flaviviridae gedacht werden. Die “ELISA-Diagnose” einer FSME sollte daher sowohl anamnestisch und klinisch als auch mit weiterführenden serologischen Untersuchungen (Western-Blot, Hämagglutinationstest, Neutralisationstest) überprüft werden.

Authors' Reply to: C.W. Stratton, D.B. Wheldon. Antimicrobial Treatment of Multiple Sclerosis. Infection 2007; 35: 383-385

We have acknowledged with great interest the letter by Drs. Wheldon and Stratton. The role of Chlamydia pneumoniae in the pathogenesis of multiple sclerosis has been the subject of debate for several years. Various studies tried to elucidate whether C. pneumoniae plays a role at all and if, to what extent. For this reason, we decided to carry out a double-blind, placebo-controlled study with a monotherapy of roxithromycin. Roxithromycin is a state-of-the-art macrolid antibiotic. Its efficacy in the treatment of C. pneumoniae is well studied. Since we aimed in our study to influence an existing MS through eradication of a possible C. pneumoniae infection, roxithromycin was a suitable antibiotic. In addition, clinical studies in adults have shown that roxithromycin is tolerated well with little side effects even when given for several weeks or months. In our study, patients with multiple sclerosis did not profit from an antibiotic therapy with roxithromycin. The strategy of Wheldon to use several antibiotics is very interesting and has greater potential to eradicate pathogens due to a broader spectrum of efficacy. However, antibiotic polypharmacy increases the risk for side effects and negative pharmacological interactions. The positive results in individual patients with multiple sclerosis treated with a combination of antibiotics are interesting and encouraging. However, these results need further study and reproduction in a double-blind, randomized, placebo-controlled study with a larger number of subjects, before the antibiotic combination therapy suggested by Wheldon can be judged fairly.