Erich Schmutzhard

European Lyme borreliosis.

Lyme borreliosis is a term introduced to designate a new nosologic entity describing the various disease states of the infection with tickor insect-borne borrelia. At least part of the Lyme borreliosis spectrum, e.g., erythema chronicum migrans’,* and acrodermatitis chronica atrophicans, has been known in Europe for many years although demonstration of the causative infectious agent was made only recently.

Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933]

BackgroundThe treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question.DesignGACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage.Conclusion372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients.Trial RegistrationCurrent Controlled TrialsISRCTN45122933

Attenuated Corticomedullary Contrast: An Early Cerebral Computed Tomography Sign Indicating Malignant Middle Cerebral Artery Infarction: A Case-Control Study

BACKGROUND AND PURPOSE No neuroradiological markers have been characterized that support a timely decision for decompressive surgery in malignant middle cerebral artery (MCA) infarction (mMCAI). This case-control study was designed to analyze whether early cerebral CT (CCT) scanning provides reliable information for the prospective selection of stroke patients at risk of developing mMCAI. METHODS Thirty-one pairs (n=62) were formed with cases (mMCAI) and controls (acute but not malignant MCA infarction) closely matched in terms of age, sex, and stroke etiology. CCT was performed within 18 hours of stroke onset and analyzed by a blinded neuroradiologist according to a defined panel of 12 CCT criteria. RESULTS In terms of predicting mMCAI, the criteria of extended MCA territory hypodensities >67% and >50%, hemispheric brain swelling, midline shift, and hyperdense MCA sign exhibited high specificity (100%, 93. 5%, 100%, 96.7%, and 83.9%, respectively) but low sensitivity (45.2%, 58.1%, 12.9%, 19.4%, and 70.9%, respectively). Two criteria yielded high sensitivity (subarachnoid space compressed, 100%; cella media compressed, 80.6%) but low specificity (29% and 74.2%, respectively). The criterion of attenuated corticomedullary contrast yielded both high specificity (96.8%) and sensitivity (87.1%). The latter remained as the crucial criterion [Exp(B)=90.8; 95% CI, 5.8 to 1427. 5] in a 2-tailed logistic regression analysis with the strongest correlating parameters (Spearman correlation factor >/=0.6 or </=-0.6). CONCLUSIONS The analysis of CCT scans within 18 hours of stroke onset revealed an attenuated corticomedullary contrast as the crucial CCT criterion, which, with both sufficient sensitivity and specificity, predicted mMCAI with 95% certainty.

Computed Tomographic Parameters Predicting Fatal Outcome in Large Middle Cerebral Artery Infarction

Background: Large middle cerebral artery (MCA) ischaemic stroke when associated with extensive mass effect can result in brain herniation and neurological death. As yet there are few guidelines to aid the selection of patients for aggressive interventional therapies, such as decompression hemicraniectomy and/or hypothermia. Methods: We studied a cohort of patients from seven centres with large MCA infarction requiring neurocritical care. The purpose of this analysis was to assess the use of early radiological signs on follow-up computed tomographic (CT) signs performed within 48 h of stroke onset for predicting mortality at 30 days. The CT parameters assessed included horizontal displacement of the septum pellucidum, pineal shift, complete or partial infarction of the temporal lobe, involvement of additional vascular territories, and the presence of hydrocephalus. The primary outcome measure was in-hospital death within 30 days. Results: One hundred and thirty-five patients who had follow-up CT scans within 48 h were identified from a total of 201 patients with large MCA infarction that received conventional medical therapy alone. The median age was 68 (range 29–99), 56% were female, and the median NIHSS category was 26–30 at 48 h. Among CT variables in univariable analysis, anteroseptal shift ≧5 mm, pineal shift ≧2 mm, complete temporal lobe infarction, involvement beyond the MCA territory, and moderate or severe hydrocephalus were equally predictive of death. Multivariable analysis adjusting for time to CT scan revealed the following predictors of fatal outcome: anteroseptal shift ≧5 mm (OR 10.9; 95% CI 3.2–37.6), NIHSS within 48 h >20 (OR 6.6; 95% CI 2.3–19.3), and infarction beyond the MCA territory (OR 4.9; 95% CI 1.6–15.0). Conclusions: We identified the role of early CT signs in predicting death following massive MCA infarction. The CT parameters anteroseptal shift (>5 versus ≤5 mm), pineal shift ≧2 mm, hydrocephalus, temporal lobe infarction, and other vascular territory infarction if present were predictive of fatal outcome. These CT parameters require prospective validation before they should be considered reliable markers for decision-making.

Infections following tickbites. Tick-borne encephalitis and lyme borreliosis — A prospective epidemiological study from tyrol

SummaryWe present here a prospective study on infections following tickbites in military recruits in the province of Tyrol (Austria). 84 recruits experienced tickbites and underwent clinical and serological examination twice at four-week intervals for signs of tick borne encephalitis (TBE)-virus orBorrelia burgdorferi infections. 56 and 50 recruits could be evaluated for TBE-virus and Borrelia infection, respectively. Whereas no recruit was found with clinical or laboratory evidence of TBE-virus infection, two (4%) recruits showed an erythema chronicum migrans as primary manifestation of aBorrelia burgdorferi infection and 11 (20%) recruits had a significant increase in the titer of anti-Borrelia burgdorferi antibodies. Our results support the predominance of a subclinical course of a tick-transmitted borrelia infection in the population under observation, and shed some light on the epidemiological situation of tick-transmitted diseases in Tyrol.ZusammenfassungDie Ergebnisse einer prospektiven Studie über Infektionen nach Zeckenbiß bei Rekruten des österreichischen Bundesheeres im Bundesland Tirol (Österreich) werden hier vorgelegt. Insgesamt 84 Rekruten wurden nach einem Zeckenbiß zweimal innerhalb von vier Wochen klinisch und serologisch auf Zeichen einer Frühsommer-Meningo-Enzephalitis(FSME)-Virusinfektion und einerBorrelia burgdorferi-Infektion untersucht. Endgültig konnten 56 und 50 Rekruten für die Analyse von FSME-Virus- bzw. Borrelia-Infektionen herangezogen werden. Während bei keinem Rekruten eine FSME-Virusinfektion nachgewiesen werden konnte, zeigten zwei (4%) ein Erythema chronicum migrans als Primärmanifestation der Lyme-Borreliose und bei 11 (20%) Rekruten wurde ein signifikanter Anstieg von Anti-Borrelia burgdorferi-Antikörpern festgestellt. Diese Ergebnisse zeigen ein Überwiegen von subklinischen Verläufen der von Zecken übertragenen Borrelien-Infektion und erhellen die epidemiologische Situation der Zecken-vermittelten Erkrankungen in Tirol.

Borrelia burgdorferi antibodies in patients with relapsing/remitting form and chronic progressive form of multiple sclerosis.

Sera of 106 multiple sclerosis patients and 103 closely matched controls were examined for Borrelia burgdorferi antibodies. The prevalence rate in multiple sclerosis patients was 14.2%, in controls 25.2%. Overall prevalence was 20.1%. Mean IgG antibody level was insignificantly higher in controls than in multiple sclerosis patients. Patients with a chronic progressive course of multiple sclerosis had an insignificantly higher mean borrelia antibody level, when compared with those suffering from relapsing/remitting form of disease.

The dependence of cell-mediated immune activation in malaria on age and endemicity

In vitro, neopterin, a pyrazino-[2, 3-d]-pyrimidine compound, is produced by human monocytes-macrophages following induction by either supernatants from activated T lymphocytes or by recombinant gamma interferon. In vivo, its determination in urine or serum provides a sensitive and specific test for the activation grade of cell-mediated immune reactions. Urinary neopterin levels were measured in 128 Tanzanian individuals (age 6 months to 54 years) with parasitologically proven malaria. Levels in a subgroup of 117 previously untreated patients were compared with those previously reported from 19 untreated malarial patients from Bangkok, Thailand (age 7 to 62 years). The influence of concomitant variables such as age, fever, parasitaemia, duration of symptoms and local endemicity of malaria upon neopterin excretion levels was analysed. In the Thai patients, levels were considerably higher than in Tanzanian subjects of similar age. Among the Tanzanian patients, an overwhelming influence of age was detected, children showing extremely high neopterin excretion levels. The other variables did not influence neopterin levels significantly. Our findings are in accord with recent data on the prevalence and mean titres of antibodies to the circumsporozoite protein of Plasmodium falciparum, which indicate that in endemic areas acquired humoral immunity develops slowly with increasing age, while prevalence and severity of disease decline.

Acute polyneuropathy in critically ill patients.

We studied five patients in the intensive care unit (ICU) with acute polyneuropathy. All had previously presented severe infectious processes, accompanied by diverse organ failure accompanied by the Adult Respiratory Distress Syndrome (ARDS) in all cases. Two patients died and the three survivors suffered severe motor deficiencies. Electromyographic studies revealed axonal damage which predominately affected motor neurons. Cerebrospinal fluid was normal in all the patients except one, who showed a moderate increase of lymphocytes. The common causes of polyneuropathy were excluded, but in all cases a nutritional disorder was detected, based on laboratory values of proteins, serum albumin and transferrin. We conclude that polyneuropathy is relatively frequent among critically ill patients and must be closely monitored because of diagnostic difficulties and the repercussions on the progress of these patients. In spite of uncertainties about its cause, it appears to be related to severe infectious processes, ARDS, and nutritional disorders.

Epidemiology of borrelia infections in Austria.

From April 1984 to July 1985 873 cases of Borrelia infections were registered at the Hygiene Institute of the University of Vienna. 2609 serum samples of these patients were investigated for antibodies against B. burgdorferi by means of IFA- and ELISA-tests. Erythema chronicum migrans (ECM) was recognized in 60.9% of patients, neurological abnormalities were recorded in 23.4% of which the majority manifested themselves as polyradiculitis and meningopolyneuritis (MPN). Acrodermatitis chronica atrophicans (ACA) was recognized in 11.5%. A small number of patients suffered from Lymphadenosis cutis benigna (LCB), arthritis and cardiac abnormalities. Sixty percent of patients were females and 40% males. Infections were found in all age groups ranging from 2-83 years in females and 1-85 years in males. Tick- or insect-bites prior to the onset of illness were reported by 47.2% and 15.6% of patients, respectively. The main vector is the hard tick Ixodes ricinus. Flying insects from the family tabanidae, i.e. Chrysops caecutiens and Haematopota species, must also be considered as transmitters. Antibodies to B. burgdorferi were found in 22.3%, 93.6% and 100% of sera from patients with ECM, MPN and ACA, respectively. Six of 11 patients with LCB and all with arthritis and cardiac abnormalities showed serologic reactivity. Geographically, Borrelia infections are distributed in all states of Austria. The seasonal distribution of cases show a peak in July and August, but the onset of clinical manifestation could be observed throughout the year. These results present Austria as an area where tick- or insect-borne Borrelia infections are very frequent and endemic in all Austrian states.

Polyneuritis cranialis associated with Borrelia burgdorferi.

Three patients with classical idiopathic polyneuritis cranialis, in whom no other aetiology could be detected, were examined serologically, by means of indirect immunofluorescence test, for antibodies (IgM and IgG) against Borrelia burgdorferi, the aetiologic agent of Lyme disease. In each case polyneuritis cranialis was caused by infection with Borrelia burgdorferi. Therapy with penicillin proved to be effective.