[Evaluation of stroke units as medical technology].
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Emergency Medical Services↗
Biomedical subjects
E B Ringelstein
Publications and source records attributed to E B Ringelstein.
Temporal hypometabolism at the onset of cryptogenic temporal lobe epilepsy.
Most patients with intractable temporal lobe epilepsy (TLE) exhibit temporal glucose hypometabolism. The reasons for the development of this abnormality are as yet unclear. The current notion is that an initial injury causes seizures, which in turn give rise to hypometabolism. The aim of this study was to assess whether temporal reductions in glucose metabolism in non-lesional TLE are the result of repeated seizures or whether hypometabolism represents an initial disturbance at the onset of disease. Glucose consumption was assessed with fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in 62 patients with cryptogenic non-refractory TLE in different stages of disease. Twelve subjects without neurological illness served as controls. Patients with onset of epilepsy at least 3 years prior to the PET scan were defined as having chronic TLE. Using this criterion, the whole patient cohort included 27 patients with de novo TLE and 35 patients with chronic TLE. The groups were matched for age and sex. The appearance of high-resolution magnetic resonance images of the brain was unremarkable in all patients. In the total cohort, number, duration and frequency of seizures had a significant relation to the magnitude of hypometabolism. Temporal hypometabolism was exhibited by 26 of the 62 patients (42%), including 8 out of 27 (30%) with newly diagnosed TLE and 18 out of 35 (51%) with chronic TLE. The disturbances were more extensive and more severe in patients with chronic TLE. It is concluded that temporal hypometabolism may already be present at the onset of TLE, but is less frequent and less severe in newly diagnosed than in chronic TLE. The metabolic disturbance correlates with the number of seizures. These findings suggest that an initial dysfunction is present in a considerable number of patients and that hypometabolism is worsened by continuing epileptic activity.
Adolescent↗
[Detection of circulating cerebral microemboli by transcranial Doppler ultrasonography].
Thromboembolic events represent a major complication of cardiovascular diseases and interventions. Although general risk factors and predictors for thromboembolic events are well known from population-based studies, hardly any therapeutic consequences for the individual patient can be drawn, e.g. for a well-balanced therapy with anticoagulants. A new approach towards an optimised therapy adapted to the individual risk of each patient may be based on the detection of circulating microemboli by transcranial Doppler sonography. With this technique, gaseous or solid microparticles circulating in the blood can noninvasively be detected. Due to their small size, they do not induce thromboembolic events themselves. However, several studies demonstrate that they indicate an increased thromboembolic activity and correlate directly with manifest stroke or emboli. From a transcranial Doppler probe positioned on the temporal plane at the patient's skull, the middle cerebral artery's blood flow is recorded and is analysed acoustically and optically for circulating microemboli. This technique has already been used for risk stratification of high-risk patients and therapeutic decision-making in neurologic routine, e.g. for the indication to anticoagulate the patient or for carotis surgery. Data to evaluate its value in cardiology are limited and based on few clinical studies. In this review, the basic principles and the methodological and technical background for the detection of microemboli, as well as current limitations, are discussed. Furthermore, clinical studies and their results evaluating this technique in patients with cardiological diseases and during cardiovascular interventions are reviewed.
Angioplasty, Balloon, Coronary↗
Disturbed benzodiazepine receptor function at the onset of temporal lobe epilepsy--lomanzenil-binding in de-novo TLE.
PURPOSE: Epileptogenic foci exhibit disturbed function at the level of the benzodiazepine receptor. The aim of our study was to investigate the incidence of focal reductions of temporal benzodiazepine receptor binding (BRB) as assessed by scintigraphy with 123I-iomazenil in patients with denovo temporal lobe epilepsy (TLE). METHODS: Forty adult patients (age: 34+/-12 years) with cryptogenic denovo TLE underwent scintigraphy with 123I-iomazenil. In all patients, symptomatic epilepsy was excluded by clinical investigation and MRI. The median duration of TLE was seven months, and the patients had a median of three documented seizures in their history of disease. BRB was quantified in four temporal regions covering the whole temporal lobe. Temporal asymmetry values (ASY) were compared with data determined in 13 age-matched controls yielding Z-scores for global and regional temporal BRB. RESULTS: A significant reduction of temporal BRB was found in 19 of the 40 patients (48 %), mainly in mesial temporal regions; temporal BRB asymmetries were also found in patients with a short history of seizures and low seizure frequency (< or = 1 year; n = 32, 13/32 (41 %)). Only in the entire cohort did the magnitude of temporal reduction of BRB correlate with the duration of TLE as well as with the number of previous partial seizures (r = 0.40 and r = 0.36; p < 0.03, respectively). CONCLUSIONS: Foci of decreased BRB can already be detected at the onset of TLE; their magnitude is related to ongoing epileptic activity.
Adolescent↗
Mutation analysis in Chariot-Marie Tooth disease type 1: point mutations in the MPZ gene and the GJB1 gene cause comparable phenotypic heterogeneity.
Charcot-Marie-Tooth disease type 1 (CMT1) is a demyelinating peripheral neuropathy most commonly caused by a DNA duplication on chromosome 17p11.2 including the peripheral myelin protein 22 (PMP22). Point mutations in the myelin protein zero gene (MPZ) and gap junction protein, beta-1 gene (GJB1) are also found in association with CMT1 or the subclass of CMT type X (CMTX), respectively. Recently point mutations in these genes have been found in patients showing the axonal variant of CMT, CMT type 2 (CMT2). We here describe the clinical and electro-physiological findings caused by two novel and two recently described MPZ mutations and six GJB1 mutations. Different MPZ and GJB1 mutations were associated with different grades of severity in CMT1 and CMTX. The novel MPZ Glu141st op mutation was associated with the axonal CMT2. We conclude that the clinical and electrophysiological heterogeneity among CMT patients carrying point mutations in MPZ and GJB1 is similar. Thus for clinical purposes CMT1 and CMT2 patients should be screened for mutations in these two genes after duplication on chromosome 17p11.2 has been excluded as the disease causing mutation.
Adolescent↗
Thirty-seven CAG repeats in the androgen receptor gene in two healthy individuals.
X-linked recessive spinobulbar muscular atrophy (SBMA) is an adult-onset X-linked neurodegenerative disease, characterised by muscular atrophy, bulbar symptoms and endocrinological disturbances. SBMA is caused by the expansion of a CAG repeat in the androgen receptor gene. The maximum number of CAG repeats found in a healthy person is 35 while the minimum number of repeats found in SBMA patients is 38. We have identified a 46-year-old man from an SBMA family with 37 CAG repeats who until now is clinically unaffected. Interestingly, his 85-year-old mother who has the genotype 37/51 CAG repeats is clinically unaffected as well. These results suggest an exactly defined border between normal and disease alleles.
Aged↗
Mutation analysis of 4 candidate genes for hereditary neuralgic amyotrophy (HNA).
Hereditary neuralgic amyotrophy (HNA) is a rare autosomal dominant disorder. It is characterised by recurrent episodes of focal neuropathy involving the brachial plexus. Genetic linkage analysis has mapped HNA to chromosome 17q25 within a 3.5-cM interval flanked by the short tandem repeat markers D17S785 and D17S802. Here, we report the mutation analysis of four candidate genes. Mutation analysis was performed on the complete coding regions of these genes. Several exonic and intronic single nucleotide polymorphisms were detected. However, no disease-causing mutations were found, indicating that these genes are most probably not involved in the pathogenesis of HNA. In addition, we have characterised and localised a putative pseudogene of the SEC14-like 1 gene.
Brachial Plexus Neuritis↗
Rapid response of identified resident endoneurial macrophages to nerve injury.
Macrophages play a central role in the pathogenesis of peripheral neuropathy but the role of resident endoneurial macrophages is undefined because no discriminating markers exist to distinguish them from infiltrating hematogenous macrophages. We identified and characterized resident endoneurial macrophages during Wallerian degeneration in radiation bone marrow chimeric rats created by transplanting wild-type Lewis rat bone marrow into irradiated TK-tsa transgenic Lewis rats. In such animals, resident cells carry the transgene, whereas hematogenous cells do not. As early as 2 days after sciatic nerve crush and before the influx of hematogenous macrophages, resident transgene-positive endoneurial macrophages underwent morphological and immunophenotypic signs of activation. At the same time, resident macrophages phagocytosing myelin were found, and proliferation was detected by bromodeoxyuridine incorporation. Continuous bromodeoxyuridine feeding revealed that resident endoneurial macrophages sequentially retracted their processes, proliferated, and expressed the ED1 antigen, rendering them morphologically indistinguishable from hematogenous macrophages. Resident endoneurial macrophages thus play an early and active role in the cellular events after nerve lesion before hematogenous macrophages enter the nerve. They may thus be critically involved in the pathogenesis of peripheral neuropathy particularly at early stages of the disease and may act as sensors of pathology much like their central nervous system counterparts, the microglial cells.
Animals↗
Kinetic parameters of 3-[(123)I]iodo-L-alpha-methyl tyrosine ([(123)I]IMT) transport in human GOS3 glioma cells.
The radiolabelled amino acid 3-[(123)I]iodo-L-alpha-methyl tyrosine ([(123)I]IMT) is a promising tool for the diagnosis and monitoring of brain tumors using single-photon emission tomography (SPECT). However, little is known about the precise kinetics of [(123)I]IMT uptake in human glioma cells. The kinetic analysis of [(123)I]IMT transport in human GOS3 glioma cells yielded a high-affinity apparent Michaelis constant (K(m) = 20.1 +/- 1.5 microM). The maximum transport velocity (V(max)) amounted to 34.8 +/- 1.9 nmol/mg protein/10 min. Competitive inhibition experiments revealed that [(123)I]IMT transport is mediated principally by the sodium-independent system L.
Biological Transport↗
Characterization of 3-[(123)I]iodo-L-alpha-methyl tyrosine transport in astrocytes of neonatal rats.
3-[(123)I]Iodo-L-alpha-methyl tyrosine ((123)I-IMT) is used for diagnosis and monitoring of brain tumours by means of single-photon emission tomography. As recently shown, (123)I-IMT is predominantly mediated into rat C6 glioma cells by sodium-independent system L for large neutral amino acids. Until now, (123)I-IMT transport in non-neoplastic glial cells has not been examined. Therefore, the aim of this study was to examine the cellular pathways and precise transport kinetics of (123)I-IMT uptake into astrocytes of neonatal rats. In particular sodium-independent (123)I-IMT transport into neonatal astrocytes was compared with sodium-independent (123)I-IMT uptake into neoplastic rat C6 glioma cells. Competitive inhibition experiments showed that (123)I-IMT is exclusively transported via sodium-independent system L into the neonatal astrocytes (92%). Kinetic analysis of sodium-independent (123)I-IMT uptake into neonatal astrocytes and into C6 glioma cells revealed apparent Michaelis constants K(M) = 13.9 +/- 0.5 microM and K(M) = 33.9 +/- 4.1 microM, respectively, which are in the same range of K(M) values as those recently determined for amino acid transport into neoplastic and non-neoplastic glial cells. Indeed, the K(M) values in the micromolar range correspond to the expression of the LAT-1 subunit of system L both in the neonatal astrocytes and in C6 glioma cells. However, sodium-independent maximum transport velocities (V(max)) differed significantly between neonatal astrocytes and C6 glioma cells (11.1 +/- 0.3 and 39.9 +/- 3.3 nmol/mg protein/10 min, respectively).
Amino Acid Transport Systems↗
Complete inhibition of in vivo glioma growth by oncostatin M.
We describe here the oncostatin M (OSM)-dependent inhibition of in vivo tumour formation after intracerebral inoculation of glioblastoma cells in mice. We generated human glioblastoma cells transfected with the OSM gene under the control of a tetracycline-response promoter. Upon removal of tetracycline from the medium, cells exhibited a differentiated cell morphology, while proliferation was significantly inhibited. After implantation of these cells into nude mice brains, large tumours developed in animals lacking OSM expression, whereas no tumour formation was observed in mice with induced OSM expression. Our results suggest that OSM exerts pronounced antitumorigenic effects on glioblastoma cells in vivo and provide arguments for a therapeutic application of OSM in humans.
Animals↗
Behavioural relevance of atypical language lateralization in healthy subjects.
In most humans, language is lateralized to the left side of the brain. It has been speculated that this hemispheric specialization is a prerequisite for the full realization of linguistic potential. Using standardized questionnaires and performance measures, we attempted to determine if there are behavioural correlates of atypical, i.e. right-hemispheric and bilateral, language lateralization. The side and degree of language lateralization were determined by measuring the hemispheric perfusion differences by functional transcranial Doppler ultrasonography during a word generation task in healthy volunteers. Subjects with left (n = 264), bilateral (n = 31) or right (n = 31) hemisphere language representation did not differ significantly with respect to mastery of foreign languages, academic achievement, artistic talents, verbal fluency or (as assessed in a representative subgroup) in intelligence or speed of linguistic processing. These findings suggest that atypical hemispheric specialization for language, i.e. right-hemisphere or bilateral specialization, is not associated with major impairments of linguistic faculties in otherwise healthy subjects.
Adolescent↗
Absence of circulating microemboli in patients with atrial fibrillation undergoing electric cardioversion.
Electrical cardioversion (CV) of atrial fibrillation (AF) is associated with an increased risk of stroke, and its appropriate prevention is still a matter of debate. It is known that, besides dislodgement of pre-existing intra-atrial thrombi, the "stunned" atrium after CV is an important cause of thrombus formation and subsequent embolism. We investigated whether CV of AF is associated with occurrence of circulating microemboli (ME) representing a sensitive marker of the actual thromboembolic activity. Twenty-nine patients (22 men) aged 54 +/- 13 years suffering from valvular (n = 5) or nonvalvular (n = 24) AF were studied. All but 1 patient (with recent-onset AF) had been put on oral anticoagulation (INR >2.0) for at least 3 weeks before and 4 weeks after successful CV. In all patients, exclusion of internal carotid artery stenosis and atrial thrombus was performed prior to CV. Five unilateral 1-hour transcranial Doppler ME monitorings over the middle cerebral artery were performed (1) before CV, and (2) immediately, (3) 4-6 h, (4) 24 h, and (5) 2-4 weeks after CV. Total absence of circulating ME was found before CV as well as during a cumulative monitoring time of 115 h after successful CV. Electrical CV of AF after at least 3 weeks of effective anticoagulation is not associated with occurrence of cerebral circulating ME. This finding requires further investigation including high-risk patients with AF undergoing CV based on different treatment protocols.
Aged↗
Clinically silent circulating microemboli in 20 patients with carotid or vertebral artery dissection.
BACKGROUND AND PURPOSE: Carotid and vertebral artery dissections are frequently complicated by cerebral embolism. Detection of clinically silent circulating microemboli by transcranial Doppler sonography (TCD) is now widely investigated in patients with carotid artery disease in the hope to identify patients at increased risk for stroke. METHODS: In 20 patients with carotid (n = 17) or vertebral (n = 2) artery dissection, or both (n = 1), we performed a 1-hour microembolus detection downstream to the dissection in the middle or in the posterior cerebral artery, respectively. RESULTS: Five patients with a carotid artery stenosis of > or = 90% or with carotid artery occlusion showed microembolic signals at a rate of up to 15 events/h. In all these patients, the onset of the dissection was within the last 58 days. Patients with lower degrees of stenosis or onset of symptoms beyond 58 days did not show microembolic signals at all. Three patients who had presented with recurrent ischaemic events prior to TCD monitoring unexceptionally had microembolic signals. CONCLUSION: Microembolic signals occur in patients with high-grade stenosis or occlusion due to acute cervical artery dissection. Patients with microemboli seem to be at increased macroembolic risk, i.e. stroke recurrence, and may require close-meshed clinical follow-up and possibly stronger antithrombotic treatment.
Adult↗
Treatment of acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the TOPAS trial. Therapy of Patients With Acute Stroke (TOPAS) Investigators.
BACKGROUND AND PURPOSE: To study the safety and efficacy of the low-molecular-weight heparin certoparin, we performed a randomized, double-blind, dose-finding multicenter trial in patients with acute ischemic stroke (Therapy of Patients With Acute Stroke [TOPAS]). METHODS: We randomized 404 patients to 4 treatment groups within 12 hours of stroke onset: 3000 U anti-factor Xa (aXa) certoparin once daily (treatment group 1); 3000 U aXa twice daily (group 2); 5000 U aXa twice daily (group 3); and 8000 U aXa twice daily (group 4). The primary efficacy variable was the proportion of patients reaching a favorable functional outcome (Barthel Index >/=90 points) at 3 months. CT was performed at trial entry, after 7 days, and on clinical deterioration. RESULTS: The proportion of patients with Barthel Index >/=90 was not different between treatment arms (61.5%, 60.8%, 63.3%, and 56.3% in the 4 groups, respectively; intent-to-treat population). European Stroke Scale scores improved in all treatment groups within the first 14 days to a similar extent. During the follow-up of 6 months, percentages of patients with recurrent stroke/transient ischemic attack were 11.0%, 5.9%, 9.7%, and 13.0% in the 4 groups, respectively. Overall mortality was only 7.4%. Two parenchymal cerebral hematomas and 1 extracranial bleeding episode occurred in treatment group 1 versus 1 and 0 in group 2, 2 and 0 in group 3, and 4 and 5 in group 4, respectively. During certoparin treatment, 1 deep vein thrombosis but no pulmonary embolism was observed. CONCLUSIONS: Dose increase of certoparin up to 8000 U aXa twice daily did not improve the functional outcome of patients with ischemic stroke. Severe bleeding tended to be more frequent in the highest dose group only.
Adolescent↗
Accuracy of in vivo carotid B-mode ultrasound compared with pathological analysis: intima-media thickening, lumen diameter, and cross-sectional area.
BACKGROUND AND PURPOSE: This study aimed to determine the correlation of in vivo ultrasound measurements of intima-media thickening (IMT), lumen diameter, and cross-sectional area of the common carotid artery (CCA) with corresponding measurements obtained by gross pathology and histology. METHODS: Sixty-six moribund neurological patients (mean age 71 years) underwent B-mode ultrasound of the CCA a few days before death. During autopsy, carotid specimens were removed in toto. Carotid arteries were ligated and cannulated for injection of a hydrophilic embedding material under standardized conditions. The carotid bifurcation was frozen and cut manually in 3-mm cross slices. Digital image analysis was carried out to determine the diameter and the cross-sectional area of the frozen slices of the CCA. IMT was assessed by light microscope. Ultrasonic and planimetric data were compared. RESULTS: Mean measurements of lumen diameter and cross-sectional area were 7.13+/-1.27 mm and 0.496+/-0.167 cm(2), respectively, by ultrasound, and 7.81+/-1.45 mm and 0.516+/-0.194 cm(2), respectively, by planimetric analysis of the unfixed redistended carotid arteries (R(2)=0.389 and 0.497). The mean IMT was 1.005+/-0.267 mm by ultrasound and 0.67+/-0.141 mm histologically, resulting in a mean difference of -31%. CONCLUSIONS: Transcutaneous B-mode ultrasound provides a reliable approach for in vivo measurements of the cross-sectional area and, less exactly, of the lumen diameter of the CCA. Compared with histological results, in vivo ultrasound measurements of the IMT are systematically larger.
Adult↗
Cerebrovascular ischemic events in wind instrument players.
Two cases of ischemic stroke due to carotid artery dissection occurring during wind instrument playing, probably caused by increased intrathoracic and subsequent intrapharyngeal pressure, are presented. A review of the literature revealed three similar patients with other types of cerebrovascular events, such as paradoxical cerebral embolism due to a patent foramen ovale and spinal epidural hematoma during trumpet playing.
Adult↗
Activation of the Jak-Stat- and MAPK-pathways by oncostatin M is not sufficient to cause growth inhibition of human glioma cells.
We have recently described that oncostatin M (OSM), a member of the IL-6 family of cytokines, induces the differentiation of human glioma cells in culture. In order to extend this studies, we analyzed the effect of OSM on other human glioma cell lines including A172, U343-MG and T98G. All of these cell lines express the receptor components of OSM and leukemia inhibitory factor (LIF) gp130, LIFR and the OSM specific OSMRbeta. Therefore, we expected these cell lines to respond to OSM and LIF. Using specific antibodies recognizing proteins of the janus kinase (Jak-)/signal transducers and activator of transcription (Stat-) signaling cascade that has been shown to transduce the signals of the IL-6 cytokines to the nucleus, we could show that Jak1, Jak2 and Tyk2, as well as the Stat proteins Stat1, Stat3 and Stat5b were phosphorylated in all three cell lines by OSM and, at least in part, by LIF. Activation of the Stat proteins was also detected by EMSA which revealed complex formation on the Stat3 DNA-binding element and on a Stat5 binding site. Consistent with our recent findings, OSM treatment also induced the activation of the MAPK erk2 and the tyrosine phosphatase SHP-2 in cells of the A172, T98G and U343-MG cell lines. Although this activation pattern was very close to what we had observed in the GOS3 glioma cells, only T98G showed a growth inhibition in response to OSM while the A172 and the U343-MG cell lines did not respond to OSM treatment in terms of growth inhibition.
Antigens, CD↗