Long-term antibiotic treatment with roxithromycin in patients with multiple sclerosis.

BACKGROUND: There are conflicting results concerning an association between Chlamydia pneumoniae and MS (multiple sclerosis). In the present study, we investigated a possible therapeutic option with antibiotics. PATIENTS AND METHODS: In our randomized, placebo-controlled double-blind study, 28 patients with the confirmed diagnosis of MS [61% relapsing-remitting MS (RR-MS), 32% secondary chronic-progressive MS (SP-MS) and 7% primary chronic progressive MS (PP-MS)] were treated over a time period of 12 months with three cycles of a 6-week oral antibiotic therapy with roxithromycin (300 mg per day) or placebo. RESULTS: No significant differences were observed in patients with RR-MS regarding the expanded disability status scale (EDSS) and the relapse rate when comparing treatment with roxithromycin and placebo. CONCLUSION: Our study shows that the patients with MS do not profit from a long-term antibiotic treatment with roxithromycin compared to placebo treatment. A causative connection between bacterial infections with C. pneumonia and MS therefore does seem very unlikely.

[Pain, fatigue, depression after borreliosis. Antibiotics used up--what next?]. / Schmerzen, Müdigkeit, Depressionen nach Borrelieninfektion. Antibiotika ausgereizt--was jetzt?

Antibiotic treatment--usually stage-dependent in terms of the active agent, duration and form of application--is the central pillar in the management of Lyme disease. In the late stages of borreliosis, symptoms may persist despite extensive and repeated antibiotic treatment. In this phase, borreliosis-typical neuropathy and neuralgia, chronic fatigue and neuropsychological deficits predominate. Irrespective of whether renewed antibiotic treatment is indicated or not, symptomatic treatment must be continued.

[Differential diagnosis of Lyme borreliosis]. / Die wichtigsten Differenzialdiagnosen: Wanderröte oder Arzneimittelexanthem--Neuroborreliose oder MS?

In all three stages, Lyme borreliosis offers a wide range of possible differential diagnoses: even the "typical" erythema chronicum migrans may present as erysipelas, erysipeloid, erythema annulare centrifugum or a drug-induced exanthema. In the advanced stages II and III, neuroborreliosis in particular may be mimicked by various other conditions of both infectious and noninfectious etiology. Major examples are CEE (Central European Encephalitis), ehrlichiosis, chlamydial infections and multiple sclerosis. Currently, the biggest diagnostic problem is the non-standardized laboratory diagnostic work-up. For this reason, even in the presence of a positive or borderline IgG antibody result, unclear symptoms should prompt a differential diagnostic investigation.

[Studies on the importance of tick-borne encephalitis in Rhineland-Pfalz]. / Untersuchungen zur Bedeutung der Frühsommer-Meningoenzephalitis in Rheinland-Pfalz.

Within the scope of a prospective clinical study during 2001 in Rhineland-Palatinate specimen from sera and cerebrospinal fluids of 163 patients with suspected meningitis were controlled in an enzyme immunoassay concerning a TBE infection. Questionable results were checked via a neutralisation test. In no case such an infection was confirmed. No virus specific nucleic acids could be detected in 998 nymphs and adults of Ixodes ricinus in an additional investigation in 2000. Therefore Rhineland-Palatinate has to be considered as a region with low virus prevalence. A general recommendation for vaccination is not necessary.

[Stroke therapy. What is established, what is new?]. / Schlaganfalltherapie. Was hat sich bewährt, was ist neu?

Early treatment of a stroke, for example, on a stroke unit reduces neurological deficits and decisively improves survival. Of initial importance is an optimal supply of oxygen. Fever should be rapidly reduced, and blood sugar within the normal range also improves the prognosis. Only when blood pressure is very high is--moderate--lowering recommended. On the contrary, raising the blood pressure and cardiac output may have a positive effect on cerebral bloodflow with fewer neurological deficits resulting. In the case of immobile patients or patients with higher-grade paralysis, antithrombotic measures--increasingly utilizing low molecular-weight heparins--are indicated. Last but not least, early physiotherapy and logopedic treatment have an important role to play. Special forms of therapy such as thrombolysis can be carried out only in well equipped centers with experienced personnel. The use of oxygen-binding plasma substitutes and hypervolemic hemodilution are highly promising future therapeutic options.

[Ischemic or hemorrhagic stroke? Rapid diagnosis improves prognosis for the patient]. / Ischämischer oder hämorrhagischer Schlaganfall? Schnelle Diagnostik verbessert die Prognose des Patienten.

In industrialized countries, stroke is the third most common cause of death, and often leads to permanent disability. When clinical suspicion is raised, a thorough diagnostic work-up and treatment must be initiated without delay. In recent years, decisive advances have been made in this area, and the pathophysiological categorization of ischemic cerebral infarction has become accepted, with the modern imaging procedures having played a significant role. Reliable differentiation from intracerebral hemorrhage is enabled in particular by CCT and MRI, and is of great importance both for acute treatment and secondary prevention. Stroke units make available the necessary equipment and personnel. Patients who receive initial treatment on a stroke unit are already benefiting from a 31% reduction in mortality and severe disability.

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

BACKGROUND: 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.

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.

[Autochthonous cases of tick-borne encephalitis in Rhineland-Palatinate]. / Autochthone Fälle der Frühsommer-Meningoenzephalitis in Rheinland-Pfalz.

Tick-borne encephalitis (TBE) is a neurotrophic viral disease which is endemic to certain regions. Such areas in Germany include Bavaria, Baden-Württemberg, and the Odenwald region in Hessen. So far, it has not been endemic to Rhineland-Palatinate. There, only two single cases of TBE occurred in the years 1992 and 1997, near the town of Idar-Oberstein. We report two new cases of TBE which appeared in 1999 and two current cases from the Idar-Oberstein region which have been verified clinically and serologically. At admission, the patients suffered from headache, muscle pains, and high fever, in one case meningitis was suspected. In all four patients, serology for borrelia was negative in serum and CSF. The described cases indicate that it is possible to acquire TBE in Rhineland-Palatinate, although only two cases have been reported in this area over the previous 10 years. Particularly in regions with a low incidence of TBE, the disease should be taken into consideration as a differential diagnosis. Studies of tick populations in regions with a low incidence can help in evaluating the benefit of possible vaccine recommendations by local public health authorities.

The Erve virus: possible mode of transmission and reservoir.

The 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.

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 of stroke on an intensive stroke unit: a novel concept.

In industrialised nations stroke ranks as number three among causes of death and is the most frequent cause of disability in old age. Demographic changes will result in stroke gaining increasing importance for individuals as well as for society as a whole. Stroke is already a major cost factor for healthcare and social security systems because of its high long-term costs. Therapeutic nihilism, although still widespread among patients and some physicians, is no longer justified. Long-term outcome after stroke can be significantly improved by providing therapy in wards specialised in early rehabilitation, so-called 'stroke units'. Recent magnetic resonance imaging (MRI) and positron emission tomography (PET) studies, as well as lysis therapy studies have shown that the first 3-6 h are crucially important. For this reason, the concept of "intensive stroke units" also called "intensive care stroke units" has been implemented in Germany. The goal of an intensive stroke unit is the optimal care of stroke patients under intensive care conditions for the first 3-4 days with the aim of improving outcome, long-term morbidity, and reducing long-term healthcare costs. Another important objective is the development and research of new therapeutic concepts and approaches that are based on pathophysiological considerations. A further goal is the initiation of specific therapies depending on the suspected underlying pathophysiology, for example, local or systemic thrombolysis, full-dose heparinisation, platelet aggregation inhibitors, oral anticoagulants, neuroprotective agents, decompression craniotomy, sympathomimetically supported volume therapy and hypothermia. A final objective is to minimise the number of complications through intensive monitoring. Basic acute management includes optimal oxygen supply, rapid normalisation of blood glucose and body temperature, volume therapy, maintaining a high blood pressure and cardiac output to improve remaining cerebral perfusion in the presence of ischaemically impaired autoregulation, treating cerebral oedema, prophylaxis of thrombosis, and early mobilisation. Rapid and easy access to computerised tomography (CT), MRI, Doppler and duplex scanning of the brain-supplying blood vessels, and echocardiography is essential. The ready availability of intensive care monitoring (blood pressure, electrocardiography, central venous pressure, transcranial Doppler (TCD), TCD embolism detection, cerebral pressure, electroencephalography and cardiac output is also imperative. We would like to stress at this point that this manuscript is a personal view describing stroke care in Germany. Many of the principles described have not been widely adopted elsewhere, perhaps in part due to a lack of available facilities. However, many of our recommendations are based on logical principles and thus, we feel, bear further scrutiny.

An international view of hydroxyethyl starches.

Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. A variety of different HES solutions exist worldwide, which differ greatly in their pharmacological properties. HES is classified according to its manufactured or in vitro molecular weight (MW) into high MW (450-480 kDa), medium MW (200 kDa), and low MW (70 kDa) starch preparations. However, this is not sufficient, because as HES is metabolized in vivo, its MW changes, and it is the in vivo MW which is responsible for the therapeutic and adverse effects of each HES. The rate of metabolization depends mainly on the degree of hydroxyethyl substitution (ranging from 0.4 to 0.7), and the C2/C6 ratio of hydroxyethylation. A high degree of substitution and a high C2/C6 ratio lead to a slow metabolization of HES, resulting in a large in vivo MW. Slowly degradable high MW HES 450/0.7 and medium MW HES 200/0.62 have a high in vivo MW and are eliminated slowly via the kidneys. As a result, these starches have a relatively long-lasting volume effect. When infusing higher volumes (>1500 ml) are infused, large molecules accumulate in the plasma. This can result in bleeding complications due to decreased factor VIII/von Willebrand factor, platelet function defects, incorporation into fibrin clots, and an unfavorable effect on rheological parameters. Rapidly degradable medium MW HES 200/0.5 or low MW HES 70/0.5 are quickly split in vivo into smaller, more favorable molecule sizes, resulting in faster renal elimination, shorter volume effect, and fewer adverse effects on coagulation and rheological parameters. For historical and marketing reasons, only slowly degradable, high MW HES (480/0.7) is available in the United States. In Europe, a large variety of HES solutions are available, dominated by medium MW, easily degradable HES (200/0.5). Because of increasing international competition and the availability of newly developed starches, it is important to be aware of the pharmacological properties of HES and the advantages and disadvantages of the individual preparations.

Effects of multiple sclerosis and other inflammatory CNS disorders on tick-borne encephalitis serology.

The goal of the present study was to investigate whether a direct association exists between false-positive recognition of IgG antibodies and inflammatory changes in the central nervous system (CNS) and whether inflammatory diseases of the CNS affect the specificity of the enzyme-linked immunosorbent assay (ELISA) of tick-borne encephalitis (TBE) virus. A group of patients (1,815), treated in the Department of Neurology, University Hospital of the Saarland, Homburg/Saar, Germany, were tested forTBE IgG antibodies by ELISA. Several subgroups of patients with and without inflammatory changes in the CSF as well as patients with and without confirmed multiple sclerosis (MS) were investigated. Overall, 4.5% of all the 1,815 patients and 4.8% of the patients with inflammatory changes in the CSF but without MS had TBE IgG antibodies. In the subgroup with inflammatory changes in the CSF and MS, 4.4% of the patients were TBE IgG-positive. In the subgroup without inflammatory changes in the CSF, 3.8% of the patients without MS were TBE IgG-positive and 4.9% of the patients with MS were TBE IgG-positive. The rate of TBE IgG positivity was not significantly different in the subgroups with and without inflammatory changes in the CSF (P = 0.45). The comparison of the subgroups with and without MS showed no significant difference in the TBE IgG titer (P = 0.83) as well. This indicates that the specificity of the ELISA was affected neither by inflammatory changes in the CSF nor by MS.

Clinical and serologic follow-up in patients with neuroborreliosis.

The authors performed a clinical and serologic follow-up study after 4.2 +/- 1.2 years in 44 patients with clinical signs of neuroborreliosis and specific intrathecal antibody production. All patients had been treated with ceftriaxone 2 g/day for 10 days. Although neurologic deficits decreased significantly, more than half the patients had unspecific complaints resembling a chronic fatigue syndrome and showed persisting positive immunoglobulin M serum titers for Borrelia in the Western blot analysis.

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.

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 patient's 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.