[Cerebrovascular complications of immunologically mediated heparin-induced thrombocytopenia]. / Zerebrovaskuläre Komplikationen der Heparininduzierten Thrombozytopenie Typ II (HIT-II).

Immunologically mediated heparin-induced thrombocytopenia (HIT) is a thrombotic disease caused by antibodies occurring after heparin exposure. Thrombocytopenia occurs within a few days after heparin exposure, about half of HIT-patients develop venous or arterial thrombotic complications. Neurological complications of HIT are mainly ischaemic stroke and sinus vein thrombosis. To ensure the primary clinical diagnosis functional and immunological assays for antibody detection are available. The probability for the occurrence of HIT depends on the nature of heparin employed (LMWH vs. UFH) and individual patient characteristics such as gender and primary disease (medical vs. surgical patients). In the case of suspected HIT heparin administration should be discontinued immediately and replaced by an alternative anticoagulation to prevent the expansion or development of further thrombotic complications. Herein we report a case of a patient suffering from HIT-associated embolic cerebral ischaemic stroke.

A complete BAC-based physical map of the Arabidopsis thaliana genome.

Arabidopsis thaliana is a small flowering plant that serves as the major model system in plant molecular genetics. The efforts of many scientists have produced genetic maps that provide extensive coverage of the genome (http://genome-www. stanford.edu/Arabidopsis/maps.html). Recently, detailed YAC, BAC, P1 and cosmid-based physical maps (that is, representations of genomic regions as sets of overlapping clones of corresponding libraries) have been established that extend over wide genomic areas ranging from several hundreds of kilobases to entire chromosomes. These maps provide an entry to gain deeper insight into the A. thaliana genome structure. A. thaliana has been chosen as the subject of the first large-scale project intended to determine the full genome sequence of a plant. This sequencing project, together with the increasing interest in map-based gene cloning, has highlighted the requirement for a complete and accurate physical map of this plant species. To supply the scientific community with a high-quality resource, we present here a complete physical map of A. thaliana using essentially the IGF BAC library. The map consists of 27 contigs that cover the entire genome, except for the presumptive centromeric regions, nucleolar organization regions (NOR) and telomeric areas. This is the first reported map of a complex organism based entirely on BAC clones and it represents the most homogeneous and complete physical map established to date for any plant genome. Furthermore, the analysis performed here serves as a model for an efficient physical mapping procedure using BAC clones that can be applied to other complex genomes.

Sex differences in perihemorrhagic edema evolution after spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Clinical data on sex differences in perihemorrhagic edema (PHE) after intracerebral hemorrhage (ICH) are lacking. METHODS: Patients with spontaneous supratentorial ICH who had received standard conservative treatment were identified retrospectively. PHE development was assessed over a 14-day period on follow-up CT scans (days 1, 2-4, 5-7, 8-11, and 12-14). ICH and PHE volumes were assessed semiautomatically and compared between men and women. RESULTS: A total of 387 patients (233 men) were included. Starting at days 2-4, women showed lower PHE values (P < 0.05; days 2-4, 8-11) or a trend toward significance (P ≤ 0.1; days 5-7, 12-14). CONCLUSIONS: Female sex may predict lower PHE volumes.

Bone subtraction CTA for transcranial arteries: intra-individual comparison with standard CTA without bone subtraction and TOF-MRA.

AIM: To evaluate the impact of bone subtraction computed tomography angiography (BS-CTA) for the assessment of transcranial arteries in comparison with standard CTA (S-CTA) without bone removal and time-of-flight magnetic resonance angiography (TOF-MRA). MATERIALS AND METHODS: Cranial unenhanced CT and S-CTA were performed in 53 patients with suspected cerebrovascular disease. BS-CTA datasets were reconstructed from the S-CTA and unenhanced CT source images. TOF-MRA was performed within 24h after CTA on a 1.5 T MRI system. Two radiologists, in consensus, evaluated the segments of the internal carotid artery (C2-C7), the vertebral artery (V4), and the basilar artery for the degree of stenosis. A five-step scale (0-49, 50-69, 70-89, 90-99% and occlusion) for the degree of stenosis was applied for all segments. Wilcoxon's signed rank test was used for statistical analysis. RESULTS: Seven hundred and fifty vessel segments (ICA:636, VA:106, BA:53) were analysed. The degree of stenosis on S-CTA was consistent with TOF-MRA in all segments. BS-CTA showed a trend towards higher stenosis scores in cases of calcified plaques compared to S-CTA (p=0.11) and TOF-MRA (p=0.09), which was not statistically significant. In transcranial segments, BS-CTA revealed equivalent scores compared to S-CTA and TOF-MRA (p=0.25; p=0.20). CONCLUSION: BS-CTA produced similar results to TOF-MRA and S-CTA and can be applied as a non-invasive imaging method for the transcranial arteries. However, BS-CTA shows a trend towards overestimation of the degree of stenosis.

Obliterating intracranial vasculopathy mimicking multiple sclerosis.

BACKGROUND: The first ever diagnosis of multiple sclerosis (MS) requires consideration of both diagnostic criteria and differential diagnosis. Clinicians are particularly challenged by rare conditions which may mimic MS symptoms and relapses. CASE REPORT: We report the case of a young female patient who presented with relapsing left hemispheric symptoms that were highly suspicious of MS but were caused by an idiopathic occlusive angiopathy of the circle of Willis. CONCLUSION: Occlusive disease of the great cerebral arteries in young patients is a rare but important differential diagnosis of MS. It has to be considered in patients presenting with the first symptoms suspicious of MS as substantial treatment consequences will arise.

Accuracy of perfusion-CT in predicting malignant middle cerebral artery brain infarction.

BACKGROUND: We performed a prospective study on patients with middle cerebral artery(MCA) ischemic stroke to evaluate the accuracy of perfusion-CT imaging(PCT) to predict the development of malignant brain infarction (MBI). METHODS: 106 patients(women 37 %, mean age 65 years)underwent native cranial computed tomography (CCT), CT angiography(CTA) and PCT after a median of 2 h after stroke onset. We assessed the patency of the MCA and the area of tissue ischemia (AIT)according to cerebral blood flow(CBF), cerebral blood volume (CBV) and time-to-peak (TTP)maps. Optimum sensitivity, specificity,positive (PPV) and negative predictive values (NPV) were calculated for the end-point MBI (= midline shift > 5 mm or decompressive surgery) by means of receiver operating characteristics(ROC). RESULTS: 20 patients (19 %)developed a MBI. In these patients,a larger AIT was found in all perfusion maps as compared to the remaining patients (p < 0.001). All perfusion maps had a very high NPV (95.4-98.4 %), a high sensitivity (85-95 %) and specificity (71.6-77.9 %) and only a moderate PPV (44-47.4 %). Best prediction was found for CBF maps with AIT of > 27.9 % of the hemisphere. CONCLUSION: PCT allows the discrimination of patients without a relevant risk for MBI from those having a 50 % risk of MBI development. Due to the high sensitivity and specificity, PCT is a reliable tool in detecting MBI. Because of PCT's better availability, it is the method of choice at present for an early risk stratification of acute stroke patients.

[Magnetic resonance imaging findings of the brain in adult HIV and AIDS patients]. / Magnetresonanztomografische Befunde des Gehirns bei adulten Patienten mit HIV und AIDS.

The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) includes not only the human immunodeficiency virus (HIV) infection itself but also opportunistic infections and tumors secondary to AIDS. Despite progress in antiretroviral therapy and the subsequent decrease in the incidence of associated diseases, opportunistic infections and tumors secondary to the HIV infection continue to be the limiting factor in terms of survival with AIDS. Therefore, the therapeutic aim is permanent antiretroviral therapy as well as early diagnosis and treatment of opportunistic infections. Magnetic resonance imaging is often the diagnostic method of choice in suspected CNS pathology of HIV patients. In the following, the typical clinical and radiological features of several AIDS-related pathologies are presented and discussed.

FLAIRfusion Processing with Contrast Inversion : Improving Detection and Reading Time of New Cerebral MS Lesions.

PURPOSE: To evaluate the performance of an innovative image processing approach for detection of T2-weighted hyperintense multiple sclerosis (MS) lesions. METHODS: In this study 20 consecutive patients with inflammatory demyelinating lesions were retrospectively evaluated of whom 10 patients featured progressive disease and 10 a stable lesion load. 3 mm transversal FLAIRfusion imaging was processed and archived. Image processing was performed through landmark-based 3D co-registration of the previous and current isotropic FLAIR examination followed by inversion of image contrast. Thereby, the hyperintense signals of the unchanged MS plaques extinguish each other, while newly developed lesions appear bright on FLAIRfusion. Diagnostic performance was evaluated by 4 experienced readers. Consensus reading supplied the reference standard. Sensitivity, specificity, NPV (negative predictive value), PPV (positive predictive value), interreader agreement and reading time were the outcome measures analyzed. RESULTS: Combined sensitivity was 100% at a specificity of 88.2%, with PPV ranging from 83.3% to 90.1% and NPV at 100%. Reading time was nearly 5­fold faster than conventional side by side comparison (35.6 s vs. 163.7 s, p < 0.001). Cohen's kappa was excellent (>0.75; p < 0.001) and Cronbach's alpha was 0.994. CONCLUSION: FLAIRfusion provides reliable detection of newly developed MS lesions along with strong interreader agreement across all levels of expertise in 35 s of reading time.

Low rate of contrast-induced Nephropathy after CT perfusion and CT angiography in acute stroke patients.

BACKGROUND: The aim of the study was to assess (i) the rate of contrast-induced nephropathy (CIN), (ii) the amount and time course of renal dysfunction, (iii) the identification of risk factors and calculation of a risk score for CIN in acute stroke patients after CT perfusion (CTP) and CT angiography (CTA). METHODS: 162 patients were investigated,who had received 140 ml of non-ionic low osmolar contrast agent (300 mg iodine per ml, Ultravist 300, Schering AG) for CTA and CTP. We assessed electrolytes, creatinine, and creatinine clearance before and up to 7 days after administration of contrast agent. In addition, the risk factors for CIN were recorded and a previously validated risk score for CIN was calculated. We also assessed the amount of crystalloid fluid substitution and newly prescribed drugs. CIN was defined as an increase of the serum creatinine-level of > 0.5 mg/dl or > 25% above baseline within 48 hours after contrast agent administration. RESULTS: 154 patients (94 %) received crystalloid fluid substitution (mean 6.1 l) within 48 h after contrast agent administration. During follow-up the creatinine values and the creatinine clearance remained stable while sodium and potassium increased significantly (p < 0.0001) after contrast agent administration. In patients with a pathological creatinine value on admission (n = 40), the creatinine clearance did not decrease significantly (p = 0.18). The risk score for developing a CIN was low in the majority of stroke patients. A manifest CIN occurred in 3 patients (2 %). No patient had to be hemodialysed. CONCLUSION: CIN is a rare complication in acute stroke patients examined by multimodal contrast-based CT due to the low prevalence of risk factors associated with CIN. In conjunction with appropriate fluid substitution, low osmolar nonionic contrast agents seem to be safe in clinical routine.

Comparison of Intracranial Aneurysms Treated by 2-D Versus 3-D Coils: A Matched-Pairs Analysis.

OBJECTIVE: Knowledge on the influence of 2D and 3D coils to occlude intracranial aneurysms is poor. Therefore, aim of our analysis was to evaluate whether the use of 3-D versus 2-D coils alone may improve the efficacy of endovascular aneurysm treatment. PATIENTS AND METHODS: We performed a matched pair analysis comparing aneurysms treated by 3-D coils as initial "framing" coils to aneurysms treated exclusively by 2-D coils. Number of coils, implanted coil length/volume, and associated packing density were calculated. Aneurysmal occlusion was assessed and monitored 6 months (DSA; magnetic resonance angiography (MRA)) and 18 months (MRA) after embolization. Periprocedural complications and retreatment rate of each group were analyzed. RESULTS: Our retrospective analysis revealed 50 pairs. Concerning the 3-D group, number of coils (353 in total, median 7; p = 0.002), implanted coil length (55.69 ± 48.4 cm), implanted coil length per volume (5.92 mm/mm3), and packing density (30 %; p = 0.017) was higher than in the 2-D group (259 in total, median 5 coils; 38.52 ± 43.13 cm; 4.54 mm/mm3; 23 %). Occlusion was not significantly different immediately after treatment but at 6 and 18 months follow-up in favor of 3-D coils. Retreatment was performed in 2 cases of the 3-D group and in 3 cases of the 2-D group and therefore in a similar range (p = 0.564). CONCLUSION: Initial use of 3-D coils revealed a higher packing density and a higher long-term occlusion. Therefore, we recommend initial use of 3-D coils.

FRED Flow Diverter: A Study on Safety and Efficacy in a Consecutive Group of 50 Patients.

BACKGROUND AND PURPOSE: Endovascular flow diverters are increasingly used for the treatment of cerebral aneurysms. We assessed the safety and efficacy of the Flow-Redirection Endoluminal Device (FRED) in a consecutive series of 50 patients. MATERIALS AND METHODS: Inclusion criteria were wide-neck, blister-like, or fusiform/dissecting aneurysms independent of size, treated with the FRED between February 2014 and May 2015. Assessment criteria were aneurysm occlusion, manifest ischemic stroke, bleeding, or death. The occlusion rate was assessed at 3 months with flat panel CT and at 6 months with DSA by using the Raymond classification and the O'Kelly-Marotta grading scale. RESULTS: Fifty patients with 52 aneurysms were treated with 54 FREDs; 20 patients were treated with the FRED and coils. Aneurysm size ranged from 2.0 to 18.5 mm. Deployment of the FRED was successful in all cases. There were no device-associated complications. One patient developed mild stroke symptoms that fully receded within days. There have been no late-term complications so far and no treatment-related mortality. Initial follow-up at 3 months showed complete occlusion in 72.3% of the overall study group, Six-month follow-up showed total and remnant-neck occlusion in 87.2% of patients, distributed over 81.5% of the FRED-only cases and 95.0% of the cases with combined treatment. CONCLUSIONS: The FRED flow diverter is a safe device for the treatment of cerebral aneurysms of various types. Our data reveal high occlusion rates at 3 and 6 months, comparable with those in other flow diverters. Long-term occlusion rates are expected.

Negative ultrasound findings in patients with cervical artery dissection. Negative ultrasound in CAD.

BACKGROUND: Cervical artery dissection (CAD) is a common cause of ischemic stroke in the younger age group. Modern imaging techniques allow the depiction of the mural hematoma, even in CADs with only subtle vessel alterations. The aim of this retrospective study was (1) to characterize the angiological features in CAD and (2) to determine the frequency of initially normal ultrasonography (US) findings. METHODS: 86 patients aged 44 +/- 11 years with CAD of the internal carotid (ICA), (n = 55) or the vertebral artery (VA), (n = 31), admitted to our hospital within 8 days (mean 1.6 days) of symptom onset, were included. CAD was confirmed either by CT-angiography, MRI of the neck, MR-angiography or digital substraction angiography (DSA) and was compared with the results of the initial as well as repeated US examinations of the arteries supplying the brain. RESULTS: In 75 patients (81.2 %) signs of vessel stenosis or occlusion were found while 11 patients (12.8%) with CAD of the ICA (n = 9) and the VA (n = 2) had normal US findings. The site of dissection in the US negative patients was highly variable without a predilection site. In 2 of 7 patients with repeated US examinations, complete vessel occlusion was found on follow-up, while in 5 patients again normal results were found. In four patients, there were changing findings in two alternative confirming imaging methods (MRI/DSA, CT/MRI) and in one patient conflicting findings (CT/MRI). Brain infarctions had occurred in 7 of the initially sonographically normal patients while the other 4 had suffered from transient (n = 2) or local (n = 2) symptoms only. CONCLUSION: Approximately 1 out of 8 patients with subsequently proven CAD has negative initial neurovascular US findings despite comprehensive examination. In patients with suspected CAD and negative US examination, repeated US examinations and further diagnostic imaging, especially MRI is necessary.

Evidence of familial syringomyelia in discordant association with Chiari type I malformation.

We report a sister and two half brothers who presented with magnetic resonance imaging (MRI)-proven syringomyelia and associated Chiari type I malformation in two cases. The individuals have the same mother but two different fathers. The mother shows no clinical signs of syringomyelia. The two fathers died through unknown causes. In a third healthy son of the mother by a relationship with a third father syringomyelia was excluded by MRI. We believe that an autosomal-dominant predisposition is the primary factor in the appearance of syringomyelia in these cases.

Clot Burden and Collaterals in Anterior Circulation Stroke: Differences Between Single-Phase CTA and Multi-phase 4D-CTA.

PURPOSE: It has been reported that the extent of intravascular thrombi and the quality of collateral filling in computed tomography (CT) angiography are predictive for the clinical outcome in patients with acute stroke. We hypothesized that multi-phase four-dimensional CTA (4D-CTA) allows better assessment of clot burden and collateral flow compared with arterial single-phase CTA (CTA). METHODS: In 49 patients (33 female; age: 77 ± 12 years) with acute anterior circulation stroke, CTA and 4D-CTA reconstructed from dynamic perfusion CT data were analyzed for absolute thrombus length (TL), clot burden score (CBS), and collateral score (CS). The length of the filling defect was also defined on thin-slice nonenhanced CT as corresponding hyperdense middle cerebral artery sign (HMCAS) when present. RESULTS: There was good correlation (r = 0.62, p < 0.01) between the length of HMCAS (1.29 ± 0.62 cm) and TL in 4D-CTA (1.22 ± 0.51 cm). 4D-CTA and CTA significantly varied (p < 0.01) in TL (1.42 ± 0.73 cm (CTA) versus 1.11 ± 0.62 cm (4D-CTA)), CBS (median: 5, interquartile range: 4-7 (CTA) versus median: 6, interquartile range: 5-8 (4D-CTA); p < 0.001), and CS (median: 2, interquartile range: 1-2 (CTA) versus median: 3, interquartile range: 2-3 (4D-CTA); p < 0.001). Accordingly, CTA significantly overrated clot burden and underestimated collateral flow. CONCLUSIONS: 4D-CTA more closely defines clot burden and collateral supply in anterior circulation stroke than CTA, implicating an additional diagnostic benefit.

An adenine nucleotide translocator gene from Arabidopsis thaliana.

The sequence of an adenine nucleotide translocator (ANT) gene of Arabidopsis contains three introns, the first of which is located upstream of the assumed initiation codon. The presequence characteristic for plant ANTs is processed also in Arabidopsis as suggested by Western blot analysis, most likely at the conserved cleavage site.

On the identification of group II introns in nucleotide sequence data.

Four different consensus sequences (GTI, group II identifiers) have been derived from domains V of known group II introns and are used as query input sequences for sensitive database screenings with the FASTA and LFASTA programs. The set of four GTI sequences can identify all domains V of the 96 known group II introns in the completely sequenced chloroplast genomes of Marchantia polymorpha, Epifagus virginiana, Oryza sativa, Nicotiana tabacum and the completely sequenced mitochondrial genomes of Saccharomyces cerevisiae, Podospora anserina, Schizosaccharomyces pombe and Marchantia polymorpha. Seven moderately high-scoring hits can easily be rejected as false-positives since they do not fulfil secondary structure requirements. Large FASTA outputs obtained after screening the entire nucleotide sequence database are evaluated in a second step by a program (D5SCAN) that allows the assignment of variable selection criteria for potential domain V secondary structures. Database searches with these routines yield evidence for several group II intron sequences previously unrecognized. These include novel intron structures in the cyanobacterium Synechocystis and in the mitochondrial genomes of Marchantia, soybean, pea, broad bean, sugar beet and a heterobasidiomycete. Potential intron remnants are found contributing to the secondary structure of rRNAs in several trypanosome species. At a given sensitivity of 95% positively identified true domains V, the search routine produces one false positive hit per 10,000 kb.

Integrated studies on plant biology using multiparallel techniques.

Plant biology, especially the fields of molecular genetics and molecular physiology, is currently undergoing a change in paradigm from 'vertical' analysis of the role(s) of one or a few genes to 'horizontal' holistic approaches, studying the function of many or even all of the genes of an organism simultaneously. This change is leading us beyond genomes to transcriptomes, proteomes and metabalomes, and to an understanding of life at an entirely new level. Profiling strategies are putting this change into effect through the generation of large amounts of data, requiring that current bioinformatic approaches adapt and grow in order to make the most of these data.

[Is the Canadian CT head rule for minor head injury applicable for patients in Germany?]. / Lässt sich die Canadian CT Head Rule für das leichte Schädel-Hirn-Trauma auf Deutschland übertragen?

PURPOSE: To evaluate the applicability of the Canadian CT Head Rule (CCHR) on head trauma patients in a German university hospital. METHODS: 122 patients (m = 74; f = 48; 40 +/- 19 years) were examined with cranial CT due to minor head trauma. The need for cranial CT according to the CCHR was evaluated retrospectively. RESULTS: With a sensitivity of 98.9 % and a specificity of 46.6 % all patients with the need for neurosurgical intervention were detected by applying the major criteria of the CCHR. Also, every patient with severe brain injury was detected by the extended criteria with a sensitivity of 99.6 % and a specificity of 34.1 %. This would have led to a reduction in the rate of cranial CT examinations by 45.1 % for the major and 22.1 % for the extended criteria. No patient with severe brain injury would have been missed by application of the criteria. CONCLUSION: The Canadian CT Head Rule for patients with minor head trauma is applicable with a very high sensitivity and the potential of significantly reducing the rate of cranial CT examinations in these patients.

[Clinical value of amino acid imaging in paediatric brain tumours. Comparison with MRI]. / Der klinische Wert der Darstellung kindlicher Hirntumore mit Aminosäuren: Vergleich mit MRT.

PURPOSE: To evaluate single photon emission computed tomography (SPECT) using the amino acid l-3-[123I]-alpha-methyl tyrosine (IMT) and contrast enhanced magnetic resonance imaging (MRI) as diagnostic tools in primary paediatric brain tumours in respect of non-invasive tumour grading. Patients, materials, methods: 45 children with primary brain tumours were retrospectively evaluated. IMT uptake was quantified as tumour/nontumour-ratio, a 4-value-scale was used to measure gadolinium enhancement on contrast enhanced MRI. Statistical analyses were performed to evaluate IMT uptake and gadolinium enhancement in low (WHO I/II) and high (WHO III/IV) grade tumours and to disclose a potential relationship of IMT uptake to disruption of blood brain barrier as measured in corresponding MRI scans. RESULTS: IMT uptake above background level was observed in 35 of 45 patients. IMT uptake was slightly higher in high grade tumours but the difference failed to attain statistical significance. Grading of individual tumours was neither possible by IMT SPECT nor by gadolinium enhanced MRI. CONCLUSION: IMT is accumulated in most brain tumours in children. Tumour grading was not possible using IMT or contrast enhancement as determined by MRI. Neither morphological nor functional imaging can replace histology in paediatric brain tumours.

Flat-Panel Computed Tomography (DYNA-CT) in Neuroradiology. From High-Resolution Imaging of Implants to One-Stop-Shopping for Acute Stroke.

Originally aimed at improving standard radiography by providing higher absorption efficiency and a wider dynamic range, flat-panel detector technology has meanwhile got widely accepted in the neuroradiological community. Especially flat-panel detector computed tomography (FD-CT) using rotational C-arm mounted flat-panel detector technology is capable of volumetric imaging with a high spatial resolution. By providing CT-like images of the brain within the angio suite, FD-CT is able to rapidly visualize hemorrhage and may thus improve complication management without the need of patient transfer. As "Angiographic CT" FD-CT may be helpful during many diagnostic and neurointerventional procedures and for noninvasive monitoring and follow-up. In addition, spinal interventions and high-resolution imaging of the temporal bone might also benefit from FD-CT. Finally, using novel dynamic perfusion and angiographic protocols, FD-CT may provide functional information on brain perfusion and vasculature with the potential to replace standard imaging in selected acute stroke patients.