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M Schwaninger

Publications and source records attributed to M Schwaninger.

At least 19 recordsLinked to original sources
PubMed2006

The ICAM-1 E469K gene polymorphism is a risk factor for spontaneous cervical artery dissection.

In a primary study on proinflammatory genetic profiles in stroke, the authors found the E469K polymorphism of the intercellular adhesion molecule 1 (ICAM-1) highly represented in the subgroup with spontaneous cervical artery dissection (sCAD). They further investigated the same genetic variant in a second group of 65 patients with sCAD. An association between sCAD and EE genotype was confirmed (odds ratio 3.16; p < 0.01), indicating that a proinflammatory predisposition is a risk factor for sCAD.

Adult↗
PubMed2006

NF-kappaB signalling in cerebral ischaemia.

In acute stroke, neuronal apoptosis and inflammation are considered to be important mechanisms on the road to tissue loss and neurological deficit. Both apoptosis and inflammation depend on gene transcription. We have identified a signalling pathway that regulates transcription of genes involved in apoptosis and inflammation. In a mouse model of focal cerebral ischaemia, there is an induction of the cytokine TWEAK (tumour necrosis factor-like weak inducer of apoptosis) and its membrane receptor Fn14. TWEAK promotes neuronal cell death and activates the transcription factor NF-kappaB (nuclear factor kappaB) through the upstream kinase IKK [IkappaB (inhibitory kappaB) kinase]. In vivo, IKK is activated in neurons. Neuron-specific deletion of the subunit IKK2 or inhibition of IKK activity reduced the infarct size and neuronal cell loss. A pharmacological inhibitor of IKK also showed neuroprotective properties. IKK-dependent ischaemic brain damage is likely to be mediated by NF-kappaB, because neuron-specific inhibition of NF-kappaB through transgenic expression of the NF-kappaB superrepressor was found to reduce the infarct size. In summary, there is evidence that IKK/NF-kappaB signalling contributes to ischaemic brain damage and may provide suitable drug targets for the treatment of stroke.

Animals↗
PubMed2006

Subarachnoid hemorrhage due to Borrelia burgdorferi-associated vasculitis.

We report the case history of a patient who suffered a subarachnoid hemorrhage (SAH) in association with early Lyme neuroborreliosis. After a tick bite, this patient developed erythema chronicum migrans and complained of stinging radicular pain in both legs. A computed tomography (CT) scan was performed because of acute headache and nuchal rigidity, which revealed an occipital SAH. Cerebrospinal fluid analysis provided further evidence of acute neuroborreliosis. Digital substraction angiography showed irregularities in the right posterior cerebral artery, which might be due to vasculitis, but no aneurysms.

Animals↗
PubMed2005

Cerebrovascular manifestations of Takayasu arteritis in Europe.

OBJECTIVES: Takayasu arteritis is well known as a cause of stroke in Asia but has rarely been described in the Western world. Here we report the clinical and neuroimaging follow-up of a series of patients with Takayasu arteritis from Europe. METHODS: Seventeen consecutive patients who fulfilled the diagnostic criteria for Takayasu arteritis of the American College of Rheumatology were evaluated on follow-up by standardized neurological examination, sonography and MRI. RESULTS: At follow-up almost 20 yr after onset of symptoms, the subclavian artery and the common carotid artery were often affected. In addition, evidence of intracranial pathology was found in seven patients. In contrast to the severe vessel involvement, the neurological state was stable. Two patients had suffered from stroke before the diagnosis was made and therapy was initiated, and one patient had recurrent transient ischaemic attacks. Intermittent dizziness was associated with pathology of the vertebral and basilar arteries. However, clinical symptoms of subclavian steal syndrome were rare. CONCLUSION: This case series shows that the clinical neurological course of Takayasu arteritis on treatment is benign in most cases despite the severe vascular involvement.

Adolescent↗
PubMed2004

[Symptomatic dissection of the internal carotid artery. A rare manifestation of autosome dominant polycystic kidney disease?].

Autosomal dominant polycystic kidney disease (ADPKD) is a frequent, genetically heterogenous disease with renal and extrarenal manifestations. Intracranial aneurysms are found in about 10% of cases. Other vascular manifestations of ADPKD have been described only in small case series. We report a 44-year-old ADPKD patient who developed acute large middle cerebral artery infarction secondary to subpetrous dissection of the internal carotid artery. Six months after the stroke, pseudoaneurysm was demonstrated on magnetic resonance angiography at the site of a previous dissection. Based on this case report, we review the spectrum of neurovascular manifestations and stroke associated with ADPKD and summarize current concepts of the pathogenesis of this disease. Finally, special aspects of the diagnostic evaluation and therapeutic management in patients with ADPKD and cervicocephalic dissection are discussed.

Aneurysm, False↗
PubMed2003

[Fabry's disease: new therapeutic options for this lysosomal storage disorder].

Fabry's disease is an x-linked, recessive, lysosomal storage disorder that results from deficient alpha-galactosidase A activity with pathological sphingolipid deposition mainly in endothelium, smooth muscle cells, kidneys, central and peripheral nervous system, and myocardium. Clinical manifestation mostly occurs during childhood and adolescence with severe pain attacks or chronic pain mainly in hands and feet, hypohydrosis, and skin lesions (angiokeratoma). In more advanced disease stages, renal and cerebrovascular complications develop with proteinuria and later renal failure and cerebral ischemia caused by cerebral microangiopathy, dilatative arteriopathy, or cardiac embolism. Heterozygote female carriers are severely affected more often than was previously considered. The diagnosis is based on the detection of deficient alpha-galactosidase A activity in leukocytes, fibroblasts, or tissue biopsies. Two randomised placebo-controlled studies showed that enzyme replacement is effective by demonstrating either reduced pain or reduced tissue sphingolipid deposition. Early diagnosis of Fabry's disease is important in view of these new causal therapeutic options.

Adult↗
PubMed2003

Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia.

BACKGROUND AND PURPOSE: The potential neuroprotective effect of the granulocyte colony-stimulating factor (G-CSF) after glutamate-induced excitotoxicity in cell culture and after focal cerebral ischemia in rats was studied. We hypothesized the existence of the G-CSF receptor (G-CSFR) as a main G-CSF effector on neurons, and immunohistochemistry, immunoblotting, and polymerase chain reaction were performed. The G-CSFR-mediated action was studied by activation of signal transducer(s) and activator(s) of transcription-3 (STAT3) in the periphery of the infarction. METHODS: Neuroprotection of various G-CSF concentrations on glutamate-induced excitotoxicity was studied in cell culture. In vivo, ischemia was induced by use of a suture occlusion model of the middle cerebral artery (90-minute occlusion) in the rat. Thirty minutes after the induction of ischemia, the animals (n=12 per group) received G-CSF at 60 microg/kg body wt IV for 90 minutes or vehicle (saline). Infarct volume was calculated on the basis of 2,3,5-triphenyltetrazolium chloride staining 24 hours after ischemia. Expression of the G-CSFR was studied by immunohistochemistry and verified by reverse transcription-polymerase chain reaction and immunoblotting. Expression of STAT3 was determined by immunohistochemistry. RESULTS: In cell culture, G-CSF exhibited a significant neuroprotective effect after glutamate-induced excitotoxicity (P<0.05). A G-CSF concentration of 10 ng/mL was maximally effective, resulting in a nearly complete protection. In vivo, G-CSF reduced infarct volume to 47% (132.0+/-112.7 mm3 versus 278.9+/-91.6 mm3 [P<0.05] in the control group). Immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction revealed the existence of G-CSFRs in neurons and glial cells. Animals treated with G-CSF significantly upregulated STAT3 in the periphery of the infarction compared with control animals (P<0.05). CONCLUSIONS: G-CSF achieved a significant neuroprotective effect in cell culture and after intravenous administration after stroke. Increased STAT3 expression in the penumbra of G-CSF-treated rats suggests mediation by G-CSFR.

Animals↗
PubMed2003

[Acute meningitis after transrectal prostate biopsy].

Acute meningitis caused by Escherichia coli is a rare disease in adulthood. Medical procedures, e.g. surgical interventions, have been described as a cause. Infection by blood transmission of fecal E. coli is also known. We report a case of acute meningitis after transrectal prostate biopsy. E. coli could be identified both in the cerebrospinal fluid and in the blood culture. A broad initial antibiotic therapy was administered. After cultural isolation of E. coli the therapy was switched to cefotaxime. The initially comatose patient recovered swiftly.

Acute Disease↗
PubMed2002

[Myxedema coma as a rare differential diagnosis of severe consciousness disturbance].

Myxedema coma is a rare and life-threatening complication of untreated hypothyroidism. Therefore, it must be part of the differential diagnosis in comatose patients. We report one patient who presented with CO(2) narcosis,hypothermia, bradycardia,hyporeflexia, tetraparesis, ascitis, pleural effusions, and heart insufficiency. Examination of the CSF, cranial CT, MRI, and MR angiography were normal. In suspicion of myxedema coma,the patient was treated with high dose L-thyroxine and hydrocortisone for preventing secondary adrenal insufficiency. A fast clinical recovery, decreased T4 (7.2 ng/l) and T3 (0.93 ng/l), and increased TSH (20.19 mU/l) together with the following anamnesis of radio iodine therapy and insufficient thyroxine intake confirmed the diagnosis. In conclusion, treatment of the myxedema coma must be started as soon as the laboratory results are confirmatory, since its course depends on the time of initiation of treatment.

Adrenal Insufficiency↗
PubMed2002

[Cerebrotendinous xanthomatosis, a treatable metabolic disorder].

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis which can be clinically diagnosed and specifically treated. It is an underdiagnosed disorder worldwide.Here,we describe two women who were diagnosed with CTX during their forties after symptoms had already developed 15 years earlier. Both patients showed gait ataxia, spastic paraparesis, polyneuropathy, bilateral premature cataracts, tendon xanthomas, and cognitive deficits. One of the patients had also chronic diarrhea. The deficiency of the mitochondrial enzyme sterol 27-hydroxylase results in a virtual absence of chenodeoxycholic acid. This leads to excessive production of cholestanol and cholesterol and accumulation of these sterols in many tissues, especially the eye lens, central nervous system,and tendons. The determination of a high cholestanol serum level allows the diagnosis,which can be confirmed through genetic analysis. Early diagnosis of CTX is important, since an effective therapy is available. Long-term therapy with chenodeoxycholic acid is effective for CTX, mainly in prevention of further deterioration.

Adult↗
PubMed2001

Nuclear factor-kappaB activation is not involved in a MPTP model of Parkinson's disease.

In the present study the involvement of hydroxyl free radicals and nuclear factor-kappaB (NF-kappaB) activation was investigated in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease. MPTP (30 mg/kg, s.c.) produced a significant 2-fold increase in hydroxyl free radicals in the striatum of C57BL/6 mice determined by microdialysis in combination with the salicylate hydroxylation assay. Electrophoretic mobility shift assays did not detect NF-kappaB activation after MPTP treatment. Furthermore, p50-deficient mice showed only minor differences in striatal dopamine and metabolite levels as well as tyrosine hydroxylase immunoreactivity after MPTP administration in comparison to wildtype mice. We postulate that, although hydroxyl radical production was enhanced, NF-kappaB plays only a minor role in the MPTP model because neither neurochemical nor immunocytochemical parameters were altered in p50-deficient mice in comparison to controls.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB.

Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short and transient activation of NF-kappaB in vitro, we observed a long-lasting sustained activation of NF-kappaB in the absence of decreased IkappaBalpha in mononuclear cells from patients with type 1 diabetes. This was associated with increased transcription of NF-kappaBp65. A comparable increase in NF-kappaBp65 antigen and mRNA was also observed in vascular endothelial cells of diabetic rats. As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-beta peptide (Abeta) to the transmembrane receptor for AGE (RAGE) results in protein synthesis-dependent sustained activation of NF-kappaB both in vitro and in vivo. Infusion of AGE-albumin into mice bearing a beta-globin reporter transgene under control of NF-kappaB also resulted in prolonged expression of the reporter transgene. In vitro studies showed that RAGE-expressing cells induced sustained translocation of NF-kappaB (p50/p65) from the cytoplasm into the nucleus for >1 week. Sustained NF-kappaB activation by ligands of RAGE was mediated by initial degradation of IkappaB proteins followed by new synthesis of NF-kappaBp65 mRNA and protein in the presence of newly synthesized IkappaBalpha and IkappaBbeta. These data demonstrate that ligands of RAGE can induce sustained activation of NF-kappaB as a result of increased levels of de novo synthesized NF-kappaBp65 overriding endogenous negative feedback mechanisms and thus might contribute to the persistent NF-kappaB activation observed in hyperglycemia and possibly other chronic diseases.

Adult↗
PubMed2000

Induction of interleukin-6 by depolarization of neurons.

Interleukin-6 (IL-6) has neuromodulatory and neuroprotective effects in vivo. It is expressed in glial cells and neurons both under physiological conditions and in various neurological diseases. Although the expression of IL-6 in glia has been intensely investigated, little is known about the regulation of IL-6 production by neurons. Therefore, we investigated the regulation of IL-6 expression in neurons. Membrane depolarization raised IL-6 mRNA accumulation in primary cortical cells and the PC-12 cell line. In vivo, IL-6 mRNA in the brain increased significantly after epileptic seizures. To investigate IL-6 gene transcription, PC-12 cells were transfected with reporter gene constructs containing the human IL-6 promoter. Membrane depolarization raised IL-6 transcription twofold to fourfold. This increase could be blocked by lowering extracellular Ca(2+) levels or by inhibiting L-type Ca(2+) channels or Ca(2+)/calmodulin-dependent protein kinases. Internal mutations in various elements of the IL-6 promoter revealed the glucocorticoid response element (GRE) 2 to be a depolarization-responsive element. Although the GRE2 bound the glucocorticoid receptor (GR) and was stimulated by dexamethasone, the GR was not responsible for the effect of membrane depolarization because a consensus GRE did not mediate stimulation by membrane depolarization. Instead, another yet undefined factor that binds to the IL-6 GRE2 may mediate the response to membrane depolarization. These data demonstrate that the expression of IL-6 in neurons is regulated by membrane depolarization and suggest a novel Ca(2+)-responsive promoter element. Through this mechanism, IL-6 may function as a neuromodulator induced by neuronal activity.

Animals↗