Johannes Treib

Presence of Chlamydia pneumoniae DNA in the cerebral spinal fluid is a common phenomenon in a variety of neurological diseases and not restricted to multiple sclerosis.

Chlamydial DNA and viable organisms have been reported in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. We investigated whether this phenomenon is specific for MS and not occurring in patients with other neurological diseases (OND) or in healthy controls and whether it is caused by infected blood monocytes having crossed the blood–brain barrier. Twelve (21%) of fifty‐eight MS patients and 20 (43%) of 47 OND patients had Chlamydia pneumoniae DNA in the CSF as determined by nested polymerase chain reaction. Viable organisms were cultured from one OND patient. We failed to detect C. pneumoniae in the CSF of 67 neurologically healthy persons. C. pneumoniae was detected in parallel in the blood monocytes of 2 of 6 CSF‐positive MS patients and in 8 of 10 CSF‐positive OND patients. Thus, chlamydial presence cannot exclusively be explained as being caused by contaminating infected monocytes that have crossed the blood–brain barrier. In peripheral blood mononuclear cell‐negative patients, chlamydia have been cleared from the circulation but persist in the central nervous system (CNS), indicating the establishment of a chronic process. In summary, the presence of C. pneumoniae in patients with neurological diseases is a common phenomenon and is not restricted to MS patients. The pathogenetic relevance of a chronic chlamydial CNS infection for neurological diseases remains unclear, but the hypothesis that susceptible patients may be impaired in their ability to clear chlamydiae from the CNS requires further examination.

Highly Substituted Hydroxyethyl Starch (HES 200/0.62) Leads to Type-l von Willebrand Syndrome after Repeated Administration

Hydroxyethyl starch (HES) is a frequently used plasma substitute that is popular due to a high degree of therapeutic safety. However, the administration of large volumes of highly substituted, high-molecular-weight starch often leads to iatrogenic von Willebrand syndrome (vWS) with hemorrhagic complications. In patients with cerebral circulatory disturbances we carried out hemodilution therapy during 9-10 days, infusing HES 200/0.62. A von Willebrand factor (vWF) multimeric analysis was carried out in 6 patients using a modified western blot according to the sodium dodecyl sulfate agarose gel electrophoresis method. The vWF multimeric analysis showed that all multimers decreased to the same degree, corresponding to type-I vWS.

Toscana virus infection in german travellers returning from the mediterranean

Toscana virus is a member of the sandfly fever group, genus Phlebovirus of the family Bunyaviridae [1]. It is a well-known cause of meningitis in humans in several regions of the Mediterranean (the Tuscany region of Italy [2], Portugal [3]. In recent years increasing numbers of Toscana virus infections have been observed in tourists returning from Italy and Portugal. We report on two human cases of acute Toscana virus infection in tourists returning from southern France and Greece, respectively. The cases were detected during a retrospective serological study on the prevalence of arbovirus antibodies in 140 patients with central nervous system (CNS) disorders in the Saarland in Germany. Indirect immunofluorescence was used for detection of antibodies. In this test system IgM-titers > 1:10 and IgG-titers > 1:40 indicate an acute infection with Toscana virus. Case 1: On August 12, 1994, a 19-year-old man was admitted to a neurological department with typical symptoms of meningitis (fever, weakness, severe headache, nausea, vomiting, and neck stiffness) with increasing intensity for about 1 day. Neurological examination including electroencephalography and computed tomography revealed no abnormalities, with the exception of symptoms of meningeal irritation. Cerebrospinal fluid showed signs of aseptic meningitis with 82/3 cells, predominantly lymphocytes. Microbiological and serological testing did not reveal any positive results. The symptoms improved during the next days and the patient was discharged from the hospital 7 days after admission with all symptoms resolved and without any neurological sequelae. Our retrospective serological testing using indirect immunofluorescence found positive IgM (1: 40) and IgG (1: 80) against Toscana virus. On retrospective contact the patient remembered a stay of 2 weeks near Marseille, southern France, and returning to Germany 12 days before the onset of symptoms. On his return trip he did not enter any known endemic area of Toscana virus. Case 2: A 73-year-old woman was admitted to a neurological department on June 30, 1993. The patient complained of fever, severe headache, nausea, and vomiting for about 1 day. Neurological examination (including electroencephalography and computed tomography) revealed no abnormal results with the exception of meningeal symptoms. In CSF 73/3 cells (predominantly lymphocytic cells) were found, which led to the diagnosis of aseptic meningitis. The intensity of symptoms decreased slowly during the following days without any therapy and the patient could be discharged from the hospital 11 days after admission without any neurological sequelae. Our retrospective serological testing revealed IgM (1:20) and IgG (1:80) antibodies against Toscana virus. When contacting the patient, she reported that she had been visiting Lavrion (60 km south of Athens, Greece) from May 30 to June 18, 1993. Anamnestically she remembered many insect bites during her stay. On her return journey she did not enter any other known endemic area of Toscana virus. These two cases of acute Toscana virus infection in travellers to the Mediterranean, detected only by chance, indicate, that Toscana virus infection in travellers is not a rare event. E.g. Schwarz [4] reported on 13 cases of Toscana virus meningitis in travellers mainly to Italy. The two cases also show the importance of asking patients about their travel history, possibly connected with the acute symptoms. The two cases in southern France and Greece also indicate that Toscana virus is not restricted to the known endemic areas (Italy, Portugal), but probably has larger areas of occurrence, at least in the European part of the Mediterranean. Acute Toscana virus infection mostly presents as mild disease with meningeal irritation or aseptic meningitis. The symptoms last about 4 to 7 days and resolve without any neurological sequelae. The diagnosis can be made by detection of antibodies in the blood. Invasive diagnostic procedures are unnecessary. The two cases presented above show that Toscana virus infections are not rare in travellers. Physicians and neurologists should be aware of these sandtly-transmitted infections causing neurological symptoms. It also shows the importance of asking the patient for his putative travel history and to think of imported infections in those patients. G. Dobler, J. Treib, A. Haass, G. FrOsner, R. Woesner, K. Schimrigk

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.

Transcranial Doppler Monitoring of Intracranial Pressure Therapy with Mannitol, Sorbitol and Glycerol in Patients with Acute Stroke

Introduction: The noninvasive management of the conservative therapy for intracranial pressure (ICP) with hyperosmolar substances is a central problem in the treatment of brain edema. Using transcranial Doppler (TCD), a continuous monitoring of ICP is now possible, because the TCD pulsatility index (PI) intraindividually closely correlates with the level of ICP. Patients and Methods: We administered an ICP-lowering treatment 113 times in 10 patients with intracranial bleeding or ischemic stroke who also had signs of elevated ICP in the computer tomogram. The treatment was carried out over a period of 9 days, using 50 g each of intravenous sorbitol (n = 38) and mannitol (n = 32) or oral glycerol (n = 43). Results: PI was significantly lowered between 20.0 and 23.9% (p < 0.01) by all substances in the affected and unaffected sides. The differences between the three substances and the differences between the affected and unaffected sides were not significant. The duration of the therapeutic effect of glycerol (190 ± 41 min) was significantly longer (p < 0.01) than that of sorbitol (150 ± 28 min) or mannitol (130 ± 20 min). The duration of the therapeutic effect was also significantly shorter (p < 0.01) in patients with a high PI (> 1.5). All three substances led to a significant increase (p < 0.01) in minimal (= diastolic) flow velocity (Vmin). The increase was highest for glycerol (56.3 ±72.6%). Summary: The decrease in PI under therapy was caused by an increase in Vmin. This indicates that ICP therapy with hyperosmolar substances improves brain edema and does not suggest a therapy-induced vasoconstriction.

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.

Thunderclap headache caused by Erve virus

Systematic studies of a possible human neuropathogenicity of the Erve virus have not yet been carried out. In a randomized, blind study 166 patients with viral encephalitis, 46 patients with cerebral hemorrhage, 72 patients with “thunderclap” headache, and 205 healthy blood donors were examined by indirect immunofluorescence for Erve virus antibodies. None of the patients with encephalitis, two patients with cerebral hemorrhage (4.3%), 10 patients with thunderclap headache (13.9%; p < 0.0001), and two blood donors (1.0%) exhibited antibodies against the Erve virus. These results suggest a human pathogenicity of the Erve virus for the first time.

Diagnosis of tick-borne encephalitis: Evaluation of sera with borderline titers with the TBE-ELISA

SummaryTick-borne encephalitis (TBE) is a member of the Flaviviridae family. Strong cross-reactions can occur between members of this family, so that it may be difficult to diagnose specific flavivirus infections, especially when tests with frequent cross-reactions e. g. ELISA tests are used. We tested 238 sera with borderline titers for TBE using the indirect immunofluorescence or neutralization test for other flaviviruses (yellow fever, dengue, West Nile) to detect cross-reactions due to other flavivirus infections or flavivirus vaccination. Only one serum reacted against all the flaviviruses tested, indicating cross-reactivity due to infection with any of the flaviviruses. Two other sera exhibited low antibody titers against yellow fever, which could be confirmed by the neutralization test, indicating recent yellow fever vaccination. None of the other sera reacted at all against any of the flaviviruses tested in the tests used, which indicates false positive reactions with the TBE-ELISA. Sera with borderline titers in the TBE-ELISA in particular should be retested using other test systems (preferably neutralization) and for other flaviviruses (yellow fever, dengue, West Nile) to detect cross-reactions and to confirm positive results.ZusammenfassungDas Virus der Frühsommer-Meningoenzephalitis (FSME) zählt zur Familie der Flaviviridae. Verschiedene Viren dieser Familie zeigen untereinander starke serologische Kreuzreaktionen. Die Diagnostik von Flavivirus-Infektionen wird dadurch sehr erschwert, insbesondere bei Verwendung kreuzreagierender Teste, wie z. B. des ELISA. Wir testeten 238 im FSME-ELISA grenzwertig oder schwach positiv reagierende Seren mittles Indirekter Immunofluoreszenz oder Neutralisationstest gegen weitere Flaviviren (Gelbfieber-, Dengue-, West Nil Virus). Damit sollten mögliche kreuzreagierende Antikörper aufgrund vorangegangener Flavivirus-Infektionen oder Flavivirus-Impfungen ermittelt werden. Dabei reagierte eines der getesteten Seren mit allen Flavivirus-Antigenen positiv, ein Reaktionsmuster, das auf eine Flavivirus-Infektion (z. B. Dengue-Fieber) schließen läßt. Zwei weitere Seren reagierten schwach positiv nur gegen Gelbfieber, ein Hinweis auf eine zurückliegende Gelbfieber-Impfung. Alle anderen Seren zeigten keine Reaktivität in den von uns verwendeten Testen, ein Hinweis auf falsch positive Reaktionen im FSME-ELISA. Insbesondere Seren, die im FSME-ELISA niedrigtitrig reagieren, sollten in einem anderen Testsystem (vorzugsweise im Neutralisationstest) getestet werden zum Ausschluß von Kreuzreaktionen mit anderen Flaviviren und zur Bestätigung der Spezifität der nachgewiesenen Antikörper.

Influence of Low Molecular Weight Hydroxyethyl Starch (HES 40/0.5-0.55) on Hemostasis and Hemorheology

Hydroxyethyl starch (HES) with a high or medium molecular weight (MW) and a high degree of substitution is difficult to degrade and leads to an accumulation of large molecules. These molecules have a negative effect on hemostasiological parameters. In 10 patients with cerebrovascular diseases, a hemodilution therapy was carried out with low MW HES for 10 days. Due to the low MW of the HES used (56-61 kD), the rheological parameters erythrocyte aggregation and plasma viscosity were significantly lowered (p < 0.01). No coagulation parameters studied were affected beyond the dilution effect, which was measured using the decline in hematocrit. Low MW starch is a volume substitute that is well-suited for repeated infusion or hemodilution therapy, particularly for patients with increased hemorrhagic diathesis, because it does not affect hemostasis. The disadvantage of a relatively short volume effect can be compensated through a continuous infusion of a larger volume.