[Aspects of post-tramatic stress disorder after a traffic acident]. / Aspekte posttraumatischer Symptombildung nach einem Autoverkehrsunfall.

Post-traumatic stress disorder (PTSD) occurs most frequently in the general population after traffic accidents and affects up to 15 % of those involved. Mental and physical comorbidity, preliminary damage or injury can herald the development of PTSD, but the scope of social support after the accident plays a crucial role in whether and to what extent potential PTSD develops. Against this background, preventive and injury reduction aspects of the interaction between insurance companies and their customers are conceivable, which could also positively affect health economic and aspects of job or customer satisfaction.

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.

Intrathecal IgA synthesis in neurosyphilis.

Neurosyphilis can develop during any stage of syphilis. It has recently been reported that cerebrospinal fluid (CSF) data from patients with parenchymal or meningovascular neurosyphilis all show the absence of IgA synthesis and occasionally a concomitant IgM synthesis. In this context, it has been stated that intrathecal IgA synthesis contradicts the diagnosis of neurosyphilis. In our CSF analysis of four patients with definite neurosyphilis we observed an intrathecal synthesis of IgA, IgG and IgM in two patients. Our data are consistent with data of other studies suggesting that about 50% of patients with neurosyphilis show intrathecal synthesis of IgA. Therefore, intrathecal synthesis of IgA does not necessarily contradict the diagnosis of neurosyphilis. We hypothesize that intrathecal synthesis of IgA does not necessarily serve as a discriminating feature between neurosyphilis and other inflammatory central nervous system (CNS) disorders and that other laboratory parameters and the clinical picture have to be taken into account as well.

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.

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.

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.

Increased haemorrhagic risk after repeated infusion of highly substituted medium molecular weight hydroxyethyl starch.

Infusion of the large volumes of high molecular weight hydroxyethyl starch (HES) has been know to lead to coagulation disorders. Medium molecular starch is considered a safe alternative, even after repeated administration. In 10 patients with cerebrovascular diseases, a 10-day hemodilution was carried out using 10% HES 200/0.62. Initially, a loading dose of 500 ml was administered once over 45-60 min, followed by 500 ml maintenance dose per day for 10 days. Its high intravascular molecular weight (120,000 D) showed that cleavage of the starch is slowed due to the higher degree of substitution. The continuous increase of HES-serum concentration to 27.7 mg/ml gave evidence of a cumulation of poorly degradable molecules. Although this caused a prolonged volume effect, plasma viscosity and erythrocyte aggregation were influenced in an unfavourable way. The negative effects were not evident in their influence on the coagulation system. Under therapy, a significant 42.8% increase (p < 0.01) in activated partial thromboplastin time occurred. Factor VIII:C, von Willebrand ristocetin co-factor and von Willebrand factor antigen dropped during the therapy below the hemostasiological limit of 30% (p < 0.01), and in some patients below 10%. A high degree of substitution, particularly after repeated infusion, leads to a cumulation of large molecules that are difficult to break down and which unfavourably affect rheological and hemostasiological parameters.

Neurochemical differences in the CSF between Binswanger's and Alzheimer's disease.

In 21 patients suffering from Binswanger's disease (BD) and in 53 patients suffering from Alzheimer's disease, we measured cerebrospinal fluid (CSF) concentrations of somatostatin-like immunoreactivity (SLI), high molecular weight form somatostatin (HMV-SST), somatostatin-25/28 (SST-25/28), somatostatin-14 (SST-14), Des-ala-somatostatin (Des-ala-SST), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). The patients were classified into three stages of intellectual deterioration according to the global deterioration scale (GDS). Levels of SLI were significantly decreased in BD in general and in SDAT patients with severe dementia (GDS 7), compared to a control group (BD overall 19.7 +/- 11.6 fmol/ml, SDAT 18.6 +/- 7.9 vs. 30.5 +/- 8.6 fmol/ml in controls, p < 0.01 for both). In SDAT patients, SLI levels correlated with dementia scores (r = -0.65, p < 0.05), but not in BD. HVA levels were decreased significantly in SDAT and BD patients with severe dementia (SDAT 273.5 +/- 138.7, BD 224.3 +/- 69.9 vs. 364.9 +/- 103.8 nmol/ml, p < 0.01 in controls, p < 0.05 for both). In BD patients with light dementia (GDS 2-4), HVA levels were significantly elevated (p < 0.05). In BD, HVA levels correlated with dementia (r = -0.59, p < 0.01). 5-HIAA was significantly elevated in BD patients with light dementia (p < 0.05). Qualitative and quantitative changes in the molecular forms of SLI are compatible with a dysregulated posttranslational processing SDAT and BD. We also observed significant correlations between SLI, 5-HIAA and HVA in BD indicating a neurochemical heterogeneous and generalized process affecting several transmitter systems and functions. In summary, our study shows that despite their quite different neuropathology, SDAT and BD do not differ fundamentally in their neurochemical profile.

Somatostatin, its molecular forms and monoaminergic transmitter metabolites in Binswanger's disease. Neurochemical-neuropathological considerations.

Cerebrospinal fluid (CSF) concentrations of somatostatin-like immunoreactivity (SLI), high molecular weight form somatostatin (HMV-SST), somatostatin-25/28 (SST-25/28), somatostatin-14 (SST-14), Des-ala-somatostatin (Des-ala-SST), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in 21 patients with Binswanger's dementia (BD). Patients were classed into three stages of intellectual deterioration according to the Global deterioration scale (GDS). Levels of SLI were significantly decreased in patients suffering from BD, compared to a control group (19.7 +/- 11.6 fmol/ml vs. 30.5 +/- 8.6 fmol/ml, P < 0.01). There was no correlation with dementia scores (r = 0.34, P = 0.51). The observed qualitative and quantitative changes in the molecular pattern of SLI suggest that occurrence of a dysregulated posttranslational processing in patients with BD. Whereas 5-HIAA levels were not significantly changed in patients with BD, HVA was significantly increased in mild to moderate dementia (GDS 2-4) and significantly decreased in severe cases (GDS 7) (224.3 +/- 69.9 nmol/ml vs. 364.9 +/- 103.8 nmol/ml, P < 0.01); this correlated with dementia scores (r = -0.59, P < 0.01). The existence of significant correlations between SLI, 5-HIAA and HVA in BD point to a heterogeneous and generalized neurochemical process affecting several transmitter systems and functions.