Leukotrienes in patients with clinically active multiple sclerosis.

OBJECTIVES: The role of leukotrienes (LTs) in the pathophysiology of multiple sclerosis (MS) has been controversially discussed in the past. Studies of LTs in the cerebrospinal fluid (CSF) revealed different results mainly because of analytical difficulties. MATERIAL AND METHODS: In the present study we used highly sensitive and specific analytical methods for measuring LTs in the CSF as well as in urine samples from 20 patients with active MS and 20 control patients with noninflammatory neurological disorders. RESULTS: LTB4 concentrations in CSF were almost twice as high in MS patients compared with controls (P < 0.001). CSF concentrations of the cysteinyl-LTs (LTC4, LTD4 and LTE4) as well as urinary LTE4 showed no significant differences compared with controls (P > 0.05). In addition, there was no significant association between CSF pleocytosis, clinical severity or time of disease onset. CONCLUSIONS: The increased concentration of LTB4 in the CSF of MS patients may indicate a biological importance for this mediator in MS.

[Differential diagnosis and therapy of headache in general practice. Anamnesis is the alpha and omega]. / Differenzialdiagnose und Therapie des Kopfschmerzes in der Praxis. Die Anamnese ist das A und O.

Headache is one of the most common reasons for a patient to consult the doctor. Of prime importance are the correct differential diagnosis and effective treatment. A differentiation is made between primary and secondary headache. In the international classification, the primary headache syndromes include migraine with and without an aura, tension type headache, headache associated with misuse of analgesics, cluster headache, and a number of rare forms of headache with no structural lesion. The secondary headache syndromes occur symptomatically as sequelae of underlying disease, the spectrum of causes covering more than 300 different disorders. In patients with headache of unclear genesis, careful history-taking and thorough physical examination should be followed by a further diagnostic work-up.

Effects of boswellic acids extracted from a herbal medicine on the biosynthesis of leukotrienes and the course of experimental autoimmune encephalomyelitis.

Mixed acetylboswellic acids, pentacyclic triterpenes extracted from the gum resin of Boswellia serrata Roxb., significantly inhibited the ionophore-stimulated release of the leukotrienes (LT) B4 and C4 from intact human polymorphonuclear neutrophil leukocytes (PMNLs), with IC50 values of 8.48 micrograms/ml and 8.43 micrograms/ml, respectively. Purified acetyl-11-keto-beta-boswellic acid was about three times more potent as inhibitor of the formation of both LTB4 (IC50 = 2.53 micrograms/ml) and LTC4 (IC50 = 2.26 micrograms/ml) from human PMNLs in the same assay. The comparative agent MK 886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]- 2,2-dimethylpropanoic acid, L-663,536, CAS 118, 414-82-7) was about 10 to 100-fold more active than the boswellic acids in inhibiting the formation of 5-lipoxygenase products in human PMNLs, with IC50 values of 0.0068 microgram/ml (LTB4) and 0.49 microgram/ml (LTC4). After daily intraperitoneal dosage the extract of mixed acetylboswellic acids (20 mg/kg) significantly reduced the clinical symptoms in guinea pigs with experimental autoimmune encephalomyelitis (EAE) between days 11 and 21. However, the inflammatory infiltrates in the brain and the spinal cord were not significantly less extensive in the treated animals than in the respective control group. The multiple intraperitoneal application of boswellic acids did not inhibit the ionophore-challenged ex vivo release of leukotrienes B4 and C4 from PMNLs separated from the blood of guinea pigs with EAE. The boswellic acids have thus been characterized as selective, non-redox and potent inhibitors of the biosynthesis of leukotrienes in vitro.

[Intraspinal manifestation of cysticercosis--Cysticercus racemosus. A case report and review of the literature]. / Intraspinale Manifestation der Zystizerkose--Cysticercus racemosus. Kasuistik und Literaturübersicht.

Neurocysticercosis is one of the most common, world-wide parasitic diseases of the central nervous system. On the basis of a case report and a review of the literature, the present paper describes the rare course of an intraspinal cysticercus racemosus infection. In conjunction with magnetic resonance imaging and computed tomography it is necessary to consider conventional myelography occupies an important position in the diagnosis of spinal manifestations of cysticercosis, cross-reactions, especially with Echinococcus antigens, by means of serological tests. In addition to the desirable surgical removal of the cysts, drug therapy with praziquantel and albendazole may be employed. Albendazole has recently been authorized for use in Germany.

Suppression of experimental autoimmune encephalomyelitis by a new specific inhibitor of leukotriene biosynthesis.

The actions of the specific inhibitor of leukotriene synthesis, 3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2- dimethylpropanoic acid (L-663, 536, CAS 118414-82-7) were investigated in groups of guinea pigs that had been given both low and high doses of the encephalitogenic stimulant to induce experimental autoimmune encephalomyelitis (EAE). After daily intraperitoneal application over a period of 2 to 3 weeks the substance L-663, 536 (5 mg/kg) largely suppressed the clinical symptoms of EAE in some of the animals. The difference in the clinical symptoms between those animals that had been treated with L-663, 536 and those that had not was observed primarily in the experiment with a high encephalitogenic dose. The onset of progressive paralysis of the hind limbs that was observed in approximately 80% of the control animals only occurred in 40% of the guinea pigs that were treated with L-663, 536. No paresis at all was observed in about 25% of the treated animals. In both laboratory animals studies the CNS inflammatory infiltrates were significantly less extensive in the treated animals than in the respective control groups. The release of leukotrienes B4 and C4 by circulating neutrophil granulocytes in guinea pigs under treatment with L-663, 536 was also significantly reduced--in contrast to the untreated control animals. On the basis of the present results, it may be assumed that the L-663, 536-induced suppression of EAE in guinea pigs is attributable to the inhibition of leukotriene biosynthesis.

[Herpes simplex encephalitis with cerebral hemorrhage]. / Herpes-simplex-Enzephalitis mit intrazerebraler Blutung.

In a 20-year-old woman with herpes simplex encephalitis the dominant feature was an intracerebral bleeding which was diagnosed by computed tomography in the initial stages of the disease. Since lesions in herpes simplex encephalitis typically present in the CT as hypodense zones in which petechial bleedings may occur, it is likely that the bleeding in this patient was caused by an inflammation in the area of an histologically confirmed arteriovenous angioma.

[Metabolic aspects of multiple sclerosis]. / Stoffwechselaspekte der Multiplen Sklerose.

According to the present opinion multiple sclerosis (MS) is caused by a concurreance of various factors. This predisposing factor seem to be related to a disturbance of the lipid- and fatty acid metabolism, characterized by decreased concentrations of polyunsaturated fatty acids (PUFA) and essential fatty acids (EFA) in the plasma, the blood cells, the cerebrospinal fluid (CSF) and white matter of the brain in patients with MS. A disturbed absorption of EFA could be excluded. Now the question arises whether there is a disturbed utilisation of EFA with the consequence of biochemical changes in myelin and blood cells. According to lipid-chemical and lipolytic enzymological studies a disturbance of the fatty acid elongation system as well as primary increased activation of the phospholipase A1 is conceivable. According to the demonstrated results the conception of a metabolic immunological caused generalised defect of the biological membranes - especially those of the myelin sheath and platelets - as predisposing factor for the increased platelet aggregation is possible. Even though these ideas do not yet allow a concrete pathogenetic conclusion, the prostaglandins (PG) might be of importance because their precursors are fatty acids and influence the immune mechanisms. Possibly, new approaches follow from the synopsis of present working hypotheses for an extended biochemical-immunological model of multiple sclerosis. Further immunological and laboratory methods should concentrate on differentiating MS from other diseases of the central nervous system and on diagnosing the disease in its early stage. The results of this work are fully discussed in other publications. Separate prints can be requested from the author.

Investigation of the blood-brain barrier for IgG in inflammatory syndromes of the central nervous system.

To investigate whether an intravenously administered compound of the IgG class is able to penetrate the CSF barrier despite its high molecular weight, 12 hepatitis B surface antibody (anti-HBs)-negative patients received 20 ml each of a beta-propiolactone-treated IgG compound with a high anti-HBs titer (1:115,000) as a marker. 8 had an inflammatory CSF syndrome. In cases of inflammatory CSF syndromes, significantly more marked IgG crossed the blood-brain barrier, this could be of considerable clinical importance.

Multivariate analysis of the serum-cerebrospinal fluid-protein-relation for the diagnosis of neurological diseases of the central nervous systems.

In a population comprising 197 patients, serum and CSF proteins were assayed using the radial immunodiffusion technique devised by Mancini. Multiple discriminants analysis was applied to investigate whether the measured CSF/serum protein relations and their ratios could be regarded as an indicator of specific neurological diseases. One significant finding was that the slope angle alpha of the regression line between the serum/CSF relation and molecular weight may represent an important indicative parameter. A small angle is suggestive of enhanced permeability of the BBB, a large angle of a correspondingly lowered permeability. Further, the analyses demonstrated that the combined use of several predictors can markedly improve differential diagnosis. The study also demonstrates the potential of a statistical analytic technique that is still rarely applied in medicine.

[Diagnosis of central nervous system diseases. Multivariate analysis of the serum-cerebrospinal fluid- protein relation]. / Zur Diagnose von Erkrankungen des zentralen Nervensystems. Multivariate Analyse der Serum-Liquor-Protein-Relation.

In a population comprising 197 patients serum and CSF proteins were assayed using the radial immunodiffusion technique devised by Mancini. Multiple discriminant analysis was applied to investigate whether the measured CSF/serum protein relations and their ratios could be regarded as an indicator of specific neurologic diseases. One significant finding was that the slope angle alpha of the regression line between the serum/CSF relation and molecular weight may represent an important indicative parameter. A small angle is suggestive of enhanced permeability of the blood-brain barrier, a large angle of a correspondingly lowered permeability. Further, the analyses demonstrated that the combined use several predictors can markedly improve differential diagnosis. The study also demonstrates the potential of a statistical analytic technique that is still rarely applied in medicine.

Essential fatty acids in the serum and cerebrospinal fluid of multiple sclerosis patients.

Statistical evaluation of essential fatty acids (determined by gas chromatography) in the serum and cerebrospinal fluid of patients with definite MS and acute CCT showed marked differences as compared to healthy subjects. It was also evident that the decrease of essential fatty acids in MS patients differed from that of CCT patients. Whereas the fatty acid levels in the serum of MS patients revealed only minor differences as compared to the controls and CCT patients, MS patients did show a clear decrease, especially of linoleic and arachidonic acids, in the CSF. This difference was most pronounced in cholesterol esters in the CSF. One absorption study with safflower oil demonstrated normal enteral absorption of essential fatty acids and the ability to cross the blood-CSF barrier.

Influence of human allergic encephalitogenic peptide on platelet aggregation in multiple sclerosis.

After addition of encephalitogenic peptide to the blood of multiple sclerosis patients a factor X with platelet aggregation activating property could be demonstrated in the supernatant serum. Factor X was able to induce a platelet aggregation or to enhance an ADP-induced platelet aggregation. These findings suggest an explanation for the well-known platelet alterations found in multiple sclerosis.

Platelet aggregation and multiple sclerosis.

Measurements of blood platelet aggregation were carried out in 30 patients suffering from multiple sclerosis (MS) and in 15 healthy individuals. Compared with the control group, the MS patients showed an increase in both spontaneous and induced (ADP and serotonin) platelet aggregation. The possible pathogenetic significance of these results is discussed.

[Immunoglobulins in bacterial and viral meningitis. Results of a controlled randomized clinical study of intravenous and intrathecal application]. / Immunglobuline bei bakteriellen und viralen Meningitiden. Ergebnisse einer kontrollierten randomisierten klinischen Studie intravenöser und intrathekaler Applikation.

The efficacy of additional intravenous and intrathecal immunoglobulin (Ig) therapy was investigated in a randomized clinical trial with 68 patients divided with the aid of a list of random numbers into two groups according to their infection. The group of bacterial infections of the CNS included 29 patients and the group of virus infections of the CNS 39 patients. The statistical evaluation of patients with bacterial infections and of those with virus infections was done separately. Group 1 received 10 g Ig each as a short infusion on two consecutive days. Patients with bacterial infections received in addition on every second day and patients with viral infections on every fifth day 500 mg of the same preparation by intrathecal injection. In contrast to this, a control group received the usual therapy only, principally antibiotics for purulent meningitis. The following characteristics were investigated and compared as variable criteria of the course of the disease and consequently of the efficacy of the additional therapy with Ig: CSF cell count, CSF protein, pyrexia, general condition, paralyses, neuropsychological defects, vigilance and EEG recording. As overall criteria of the course of the disease the length of stay in hospital and the rise in temperature were considered. The results of the statistical analysis showed a statistically significant superiority for the Ig-treatment which was most marked in the regression of the CSF pleocytosis, total CSF protein and pyrexia. For the subjectively graded clinical evaluations such as general condition, disturbances of vigilance, transient paralyses, neuropsychological defects and EEG tracings the statistical significance still applied, even if not so pronounced as for the previously mentioned criteria.