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In the treatment of children/adolescents with diabetes medical rehabilitation plays an important role. It was the aim of the survey to analyze trends in the number of patients admitted to rehabilitation, the quality of diabetes care, the incidence of acute complications, risk factors for cardiovascular co-morbidities like lipids and blood pressure and the familial status nationwide and over a period of 13 years. Methods: Currently seven hospitals offer in-patient rehabilitation for children/adolescents with diabetes in Germany. Six hospitals participated in the survey. All children/adolescents (n=7.163) who participated in an in-patient rehabilitation 01/01/2004-31/12/2016 were included. Clinical/familial data were assessed: age, sex, family situation, type/duration of diabetes, insulin dosage, self-monitoring, acute complications, height, body weight, blood pressure and laboratory parameters. For collecting and storage of data the computer software DPV® (Diabetes-Patienten-Verlaufsdokumentation, University of Ulm, Germany) was used. Statistical analyses were performed using the programme SAS (Statistical Analysis Software 9.4, SAS Institute Inc, Cary, North Carolina, USA). Results: During the study period 7.163 patients took part in 10.987 in-patient rehabilitation procedures. The yearly number of patients participating in rehabilitation remained stable. There was no change in the quality of diabetes control (HbA1c: p=0.30, fasting blood glucose: p=0.80). The incidence of severe hypoglycaemia decreased (p

Autoantibodies (AAb), especially antinuclear (ANAs) and anticytoplasmatic antibodies (ACyA), are essential diagnosing markers for several autoimmune diseases. The current gold standard method for ANA detection is manual indirect immunofluorescence (IIF) on human epithelial-2 (HEp-2) cells. However, this technique is cost and time consuming, and characterized by considerable intra- and interlaboratory variability. Thus, an automated IIF-HEp-2 reader has been developed recently. In the current study, we compared the performance of the automated AAb IIF-HEp-2 interpretation to conventional detection methods. Autoantibody detection by IIF on HEp-2 cells was performed in a total of 260 sera of patients, including 34 with systemic lupus erythematosus, 111 with dermatomyositis or polymyositis, 74 with systemic sclerosis, 41 with rare AAb patterns, and 137 healthy individuals. Visual interpretation and routine immunoassays were compared with a novel automated IIF-HEp-2 system using Aklides pattern recognition algorithms. Positive AAbs were detected in 95-100% of rheumatic patients by automated interpretation, in 74-100% with manual reading, and in 64-100% by immunodot assay. Receiver operating characteristic curve analysis of fluorescent intensity revealed a high sensitivity and specificity for automated reading of AAb with an agreement ranging from 90% to 95% between manual and automated interpretation (kappa 0.554-0.69) for systemic sclerosis and myositis, respectively. This study demonstrates a good correlation between manual and automated interpretation of AAb including ANA and ACyA in patients with autoimmune diseases. Full automation of HEp-2 cell assay reading may minimize errors in ANA pattern interpretation and thus help in the standardization of ANA assessment.

Visual system dysfunction has been reported in Parkinson's disease (PD). The objective of the present study was to evaluate a putative association of distorted colour vision and delayed initiation and execution of movement in PD. We performed the Farnsworth-Munsell 100-hue test and estimated the total error score in 30 previously untreated parkinsonian patients and 30 age- and sex-matched controls. We then determined slowness in motor readiness and motor programming in the parkinsonian subjects on the same day. Subjects were asked to press a start button and release it after the randomized appearance of a visual stimulus and to move their right index finger to a reaction button as quickly as possible. Reaction time was considered as elapsed time between onset of the stimulus light and release of the start button, movement time was the time period between release of the start button and the pressing of the reaction button. Significant differences appeared between parkinsonian patients' and controls' reaction times (P = 0.007), movement time (P = 0.001) and total error score (P = 2.23E-08). A significant relation (Spearman R = 0.473, P = 0.008) was found between movement time and total error score, but not between reaction time and total error score (Spearman R = 0.259, P = 0.166). We conclude, that visual dysfunction and execution of movement are more influenced by altered dopaminergic neurotransmission in PD in comparison to the initiation of movement.

Background —Second harmonic imaging (SHI) is a new ultrasound technique that is able to detect microbubbles in the tissue vascular space. The aim of this pilot study was to prove that this technique may detect focal abnormalities of cerebral echo-contrast enhancement in acute hemispheric stroke. Case Descriptions —Two male patients (aged 72 and 64 years) were included who presented with acute onset of severe hemiparesis and no established demarcation of the ischemic area in CT scans. After bolus application of galactose-based microbubbles, axial SHI examinations in a diencephalic plane of sections were performed using the transtemporal approach. Ultrasound investigations were recorded and evaluated offline. In both individuals demarcated focal abnormalities of cerebral contrast enhancement were detectable: in patient 1 the region of the lentiform nucleus and the adjacent parts of the temporoparietal lobe was affected, and in patient 2 a large region including the lentiform nucleus and cortical white matter was involved for at least 24 hours. Follow-up CT scans demonstrated a striatocapsular infarct in patient 1 and complete MCA infarction in patient 2, correlating with the presumed ischemic area in acute ultrasound examinations. The patient with complete MCA infarction showed missing contrast enhancement in the entire hemisphere of the affected side in follow-up SHI examinations. He died of malignant space-occupying brain edema. In the patient with the striatocapsular infarction, reappearance of echo-contrast enhancement in the ischemic area was assessable after 1 week. Conclusions —SHI may identify focal abnormalities of cerebral echo-contrast enhancement in acute hemispheric stroke. Furthermore, this technique helps to determine size, localization, and prognosis of the ischemic region and could be useful for bedside assessment of echo-contrast agent distribution related to brain tissue perfusion.

Die Encephalomyelitis disseminata (Multiple Sklerose) als haufigste organische, zumeist progredient oder schubformig verlaufende neurologische Erkrankung in unseren Breiten, bietet in ihrer vielfaltigen Auspragung psychopathologische Normabweichungen unterschiedlichsten Ausmases. In die neurologische Rehabilitationsklinik kommen die Patienten zu Lasten verschiedenster Kostentrager nahezu ausnahmslos vordiagnostiziert. Nicht selten sind Wiederholungsbehandlungen, so das Verlauf, Progredienz oder Stillstand gut zu objektivieren sind. Psychopathologische Veranderungen werden haufig beschrieben, wobei die Atiologie von Personlichkeitsstorungen unterschiedlich beurteilt wird. Neben dem Begriff der „organischen Wesensanderung” werden auch reaktive Phanomene diskutiert, wie Probleme der Krankheitsverarbeitung, soziale Konflikte u.a. Anhand einer ausfuhrlichen Kasuistik wird die Komplexitat des Krankheitsbilds im Zusammenspiel mit verschiedenen Personlichkeitsanteilen und ihre Auswirkung auf Befindlichkeit, Verlauf und Therapie dargestellt. Ausgehend von diesem Einzelfall werden Hypothesen erarbeitet mit dem Versuch, die seelischen Grundprobleme dieser Patientengruppe so transparenter darzustellen. Daneben soll die Notwendigkeit einer mehrdimensionalen Diagnostik aufgezeigt werden, wobei im Verlauf einer Behandlung jeweils verschiedene Ebenen im Vordergrund stehen konnen, die sich verzahnen. Ein phanomenologisch ausgerichteter, kontaktorientierter therapeutischer Zugang, der die verschiedenen Diagnoseebenen berucksichtigt, erscheint der individuellen Problemlage der Patienten angemessen.

The purpose of this study was to evaluate the potential of contrast-enhanced three-dimensional (3-D) power Doppler (CE3DPD) in the assessment of intracranial vascular structures, and to compare the results with unenhanced 3-D power Doppler (3DPD) and magnetic resonance angiography (MRA) findings. We insonated 25 patients without cerebrovascular diseases through the temporal bone window using 3DPD and CE3DPD; for comparison, 13 patients underwent MRA. Identification rates of vascular segments and of small branches of intracranial vessels were evaluated by two independent investigators blinded to MRA results. In 21 patients with adequate insonation conditions, CE3DPD significantly improved identification rates compared to 3DPD for the complete visualization of the P1 segment (80.9 vs. 19.0%, p < 0.005, P2 segment (80.9 vs. 42.8%, p < 0.05 and A1 segment (85.7 vs. 38.1%, p < 0.005). Furthermore, CE3DPD depicted, in significantly more examinations, branches of the middle (MCA) and posterior cerebral artery (PCA). Interobserver agreement was higher than 95% for the main intracranial segments and branches of the MCA, but relatively low (80.1-85.7%) for branches of the PCA. In comparison to CE3DPD, MRA identified only parieto-occipital branches of the PCA, temporal branches of the MCA, frontal branches of the anterior cerebral artery and the MCA bifurcation more frequently and accurately. In 4 patients with inadequate acoustic temporal bone windows, the application of a galactose-based microbubble suspension allowed clear 3-D visualization of almost all major intracranial vascular segments and some branches of the large arteries. In conclusion, CE3DPD is a more sensitive ultrasonic tool compared to unenhanced 3-D reconstructions. It makes 3-D ultrasound imaging of the basal cerebral circulation easier to perform and interpret, by providing an improved spatially oriented display of image position. As such, this method may increase operator diagnostic confidence level under pathologic conditions.

To the Editor: Baumgartner et al1 recently reported on the diagnostic value of contrast-enhanced transcranial color-coded duplex sonography (CE-TCCS) in ischemic cerebrovascular disease. In this study, 33 patients with insufficient temporal insonation conditions (21 patients had ischemic stroke and 12 suffered from transient ischemic attack) were investigated after application of a galactose-based echo contrast agent. The presence of an insufficient temporal bone window was indicated when two sonographers estimated that they were unable to evaluate the basal cerebral arteries by means of color and spectral Doppler imaging in unenhanced examinations. After application of a galactose-based echo contrast agent, 66% of the CE-TCCS examinations were considered conclusive. Cross-flow through the anterior and posterior communicating arteries due to extracranial occlusive disease could be demonstrated in 3 and 2 patients, respectively. No stenoses or occlusions of intracranial arteries could be visualized. We would like to add our CE-TCCS experiences in severely affected stroke individuals with insufficient acoustic bone windows (IABW). 30 patients (17 women and 13 men; mean age, 75.2 [range, 59 to 86] years) with IABW and severe cerebrovascular event (European Stroke Scale score of

Transcranial color-coded real-time sonography (TCCS) is an emerging diagnostic technique that allows noninvasive imaging of intracranial vessels within parenchymal structures. However, in some patients, transcranial ultrasound is particularly hindered by insufficient ultrasound penetration through the temporal bone. The present study evaluates whether or not application of an echo-contrast agent in ultrasound-refractory patients with middle cerebral artery (MCA) trunk occlusion enhances image acquisition enough to yield accurate diagnoses. Contrast-enhanced (CE) TCCS examinations, computed tomography scans and angiographic studies were performed in 20 patients with clinical symptoms suggestive of MCA occlusion within 12 h of the onset of symptoms. For comparison, 20 control persons without history or clinical signs for cerebrovascular diseases were examined using CE-TCCS. In none of the patients or control subjects did unenhanced TCCS investigations depict any color-coded vascular signal of an intracranial vessel. After application of 9 mL of 400 mg/mL galactose-based microbubbles, CE-TCCS was performed. In subjects with MCA occlusion, CE-TCCS examinations were repeated within 24 h, 48 h and 5 days after stroke. In stroke patients (n = 20), CE-TCCS showed an occluded MCA main stem in 11 patients, and this vessel was clearly demonstrable on the unaffected side. On the affected side, the posterior cerebral artery (PCA) and anterior cerebral artery (ACA) could be visualized in 8 of 11 subjects; in 3 patients, at least 1 of these vessels was detectable. Angiographic studies confirmed the diagnosis of MCA trunk occlusion in all 11 individuals. In follow-up investigations, 3 stroke patients had angiographic and CE-TCCS examinations consistent with vessel reperfusion. Nine stroke patients had a patent MCA shown in angiographic and CE-TCCS examinations. In the control group, the MCA trunk could be visualized in all subjects by CE-TCCS. CE-TCCS is a sensitive and specific ultrasound method for the diagnosis of MCA trunk occlusion that overcomes the anatomical hindrance of inadequate acoustic bone window. This technique may help to identify patients suitable for thrombolytic therapies and monitor their response.

Background and Purpose Elevations of protein S-100 (S-100) in cerebrospinal fluid and serum have been reported after cerebral infarctions. The aim of our study was to evaluate the time course of serum S-100 concentrations after territorial middle cerebral artery (MCA) infarctions in correlation with clinical data and prognosis. Methods S-100 serum levels were serially determined in 26 patients with an acute infarction in the territory of the MCA at day 0 (within 12 hours after onset of symptoms), day 1 (24 hours after stroke onset), and days 2, 3, 4, 5, 7 or 8, and 10 after stroke and in 26 age- and sex-matched control subjects. S-100 assays were performed using a two-site radioimmunoassay technique. The clinical status was documented using the Scandinavian Stroke Scale. The functional deficit 4 weeks after stroke onset was scored by use of the modified Rankin scale. A cranial computed tomography (CCT) was performed initially and at day 4 or 5. Results Elevated concentrations of S-100 (>0.2 μg/L) were observed in 21 of 26 patients with MCA infarction but in none of the control subjects. S-100 levels peaked at days 2 and 3 after stroke. The S-100 concentrations in serum were significantly higher in patients with severe neurological deficits at admission, with extensive infarctions and a space-occupying effect of ischemic edema as compared with the rest of the population. S-100 values were not significantly correlated with the functional prognosis. Conclusions Presence of S-100 in serum after ischemic stroke may be due to combined leakage out of necrotic glial cells and passage through an impaired brain-blood barrier, indicating severe ischemic cell injury. Therefore, S-100 in serum can be used as a peripheral marker of ischemic focal brain damage and may be helpful for therapeutic decisions in acute ischemic stroke.

Power Doppler (PD) is a new ultrasonic technique that allows improved visualization of vascular structures. The aim of our study was to compare the ability of power-based transcranial color-coded duplex sonography (p-TCCS) to conventional transcranial color-coded duplex sonography (TCCS) and contrast-enhanced transcranial color-coded duplex sonography (CE-TCCS) in the visualization of the vertebrobasilar system.In 41 patients without cerebrovascular diseases, we evaluated and compared identification rates of major vessels of the vertebrobasilar system and branches using both ultrasound (US) techniques. In 9 patients we performed additional CE-TCCS studies. Furthermore, the possibility of visualization of the basilar artery (BA) and the vertebral arteries (VA) over the long course was investigated.TCCS and p-TCCS were equally effective at showing the VAs (74 of 82 v 80 of 82), proximal segments of the BA (37 of 41 v 41 of 41) and P1 segments of the posterior cerebral artery (PCA) (72 of 82 v 82 of 82). However, the diagnostic sensitivity of p-TCCS was significantly better for peripheral segments of the PCA (34 of 82 v 68 of 82 for P2 and 2 of 82 v 24 of 82 for P3 segments, P.001), distal parts of the BA (25 of 41 v 38 of 41, P.01), the anterior inferior cerebellar artery (AICA) (0 of 82 v 8 of 82, P.0001) and the posterior inferior cerebellar artery (PICA) (13 of 82 v 34 of 82, P.001). Furthermore, using transtemporal coronal sections, p-TCCS allowed visualization of the BA over the complete course in connection with one or both VAs in half of the patients. Except P2 and P3 segments, CE-TCCS did not increase resolution compared with p-TCCS.PD offers significant advantages over color-coded sonography in imaging the BA and small-calibre vessels like the PICA, AICA, and peripheral segments of the PCA. P-TCCS in combination with TCCS increases the diagnostic sensitivity to identify vascular structures of the vertebrobasilar system.

We report on four patients with a histologically proven diagnosis of arteritis temporalis and clinical and/or neuroradiological evidence of severe focal cerebral ischemia due to intracranial vasculitis. While one patient suffered from a transient ischemic attack, CCT and MRI scans of the other patients showed multiple lacunar infarctions, combined with territorial infarctions in two cases. Necropsy in one patient demonstrated generalized giant cell vasculitis in large and small cerebral vessels. We suppose that the cerebral involvement was provoked by insufficient steroid therapy of arteritis temporalis in two patients. In one case, remission could be achieved by a combination of high-dose steroids and cyclophosphamide; one further patient remitted under lower steroid dosage. Steroid therapy was ineffective in two patients, one of whom died due to secondary complications. We conclude that central nervous system affection is a rare but dangerous complication of arteritis temporalis and may present as cerebral micro- and macroangiopathy.

Early pre-motor symptoms (also frequently termed "non-motor" symptoms) in Parkinson's disease (PD), which precede the onset of motor symptoms, are being increasingly recognized by clinicians. Non-motor symptoms in the pre-motor phase of PD include impaired olfaction (hyposmia), sleep disturbances (i.e., radid eye movement sleep behavior disorder, daytime sleepiness), behavioral/emotional dysfunction (i.e., change of personality or change of core personal characteristics), dysautonomia (i.e., constipation, urinary dysfunction, orthostatic hypotension), depressive symptoms (i.e., fatigue, apathy, anxiety), and chronic pain (joint and muscle). The pre-motor phase of PD is based on current pathophysiological concepts that relate these symptoms to early structural changes within lower brainstem nuclei and the peripheral nervous system including the autonomic and enteric ganglia. The perspective to identify these symptoms as early as possible will enable neurologists to make a diagnosis at the pre-motor stage of PD. Thus, the development of a PD risk score will be the first means to identify individuals at risk who are most likely to develop the prototypical motor symptoms of PD later in life. More importantly, these individuals at risk will be the first to benefit from disease-modifying strategies. In this workshop report, the elements of a PD risk score are proposed, including the stepwise sequence of escalating diagnostic measures to diagnose the pre-motor stage in PD.

Syringomyelia classically presents with slowly progressing dissociated sensory and upper and lower motor deficits. Atypical and acute manifestations have rarely been described. We report here on 3 patients with syringomyelia, who had acute and atypical brainstem symptoms with regard to the underlying disease. These symptoms occurred after acute elevation of the intrathoracic and intra-abdominal pressure, respectively, and remitted subsequently. Vertebrobasilar ischemia was initially suspected.

A 67-year-old woman who developed acute secondary mania immediately after a mixed (perforating and cortical) embolic brain infarction in the territory of the right middle cerebral artery is described. According to neuroradiological findings ischemic lesions involving the basal and medial areas of the temporal lobe and the head of the caudate as well as the putamen were evident. In the pathogenesis of secondary mania due to cerebrovascular disease, the pattern of involved structures is unique and underlines the significance of lesion location after damage of the minor hemisphere.

We report the case of a 54-year-old male patient, who developed the symptoms of Kleine-Levin syndrome (KLS) at the age of fifty. Four years later Parkinsonian symptoms (PS) appeared. The possible relationship between both KLS and PS, e.g. regarding neuroendocrinological similarities, will be discussed to explain the subsequent onset of PS after the manifestation of KLS in this patient.

Features of Parkinson's disease (PD) include oxidative stress, nigral mitochondrial complex I deficiency and visual dysfunction, all of which are also associated with coenzyme Q(10) (CoQ(10)) deficiency. The objective of this monocenter, parallel group, placebo controlled, double-blind trial was to determine the symptomatic response of daily oral application of 360 mg CoQ(10) lasting 4 weeks on scored PD symptoms and visual function, measured with the Farnsworth-Munsell 100 Hue test (FMT), in 28 treated and stable PD patients. CoQ(10) supplementation provided a significant (P=0.01) mild symptomatic benefit on PD symptoms and a significantly (F((1,24))=8.48, P=0.008) better improvement of FMT performance compared with placebo. Our results indicate a moderate beneficial effect of oral CoQ(10) supplementation in PD patients.

In idiopathic Parkinson's disease (IPD) approximately 60 % of the nigrostriatal neurons of the substantia nigra (SN) are degenerated before neurologists can establish the diagnosis according to the widely accepted clinical diagnostic criteria. It is conceivable that neuroprotective therapy starting at such an ‘advanced stage’ of the disease will fail to stop the degenerative process. Therefore, the identification of patients at risk and at earlier stages of the disease appears to be essential for any successful neuroprotection. The discovery of several genetic mutations associated with IPD raises the possibility that these, or other biomarkers, of the disease may help to identify persons at risk of IPD. Transcranial ultrasound have shown susceptibility factors for IPD related to an increased iron load of the substantia nigra. In the early clinical phase, a number of motor and particularly non-motor signs emerge, which can be identified by the patients and physicians years before the diagnosis is made, notably olfactory dysfunction, depression, or ‘soft’ motor signs such as changes in handwriting, speech or reduced ambulatory arm motion. These signs of the early, prediagnostic phase of IPD can be detected by inexpensive and easy-to-administer tests. As one single instrument will not be sensitive enough, a battery of tests has to be composed measuring independent parameters of the incipient disease. Subjects with abnormal findings in this test battery should than be submitted to nuclear medicine examinations to quantify the extent of dopaminergic injury and to reach the goal of a reliable, early diagnosis.

People with brain injuries involving the amygdala are often poor at recognizing facial expressions of fear, but the extent to which this impairment compromises other signals of the emotion of fear has not been clearly established. We investigated N.M., a person with bilateral amygdala damage and a left thalamic lesion, who was impaired at recognizing fear from facial expressions. N.M. showed an equivalent deficit affecting fear recognition from body postures and emotional sounds. His deficit of fear recognition was not linked to evidence of any problem in recognizing anger (a common feature in other reports), but for his everyday experience of emotion N.M. reported reduced anger and fear compared with neurologically normal controls. These findings show a specific deficit compromising the recognition of the emotion of fear from a wide range of social signals, and suggest a possible relationship of this type of impairment with alterations of emotional experience.

Power-based transcranial color-coded sonography and contrast-enhanced transcranial color-coded sonography are ultrasonographic techniques that allow improved visualization of vascular structures. The present study was designed to investigate and compare the diagnostic capacity and applicability of both methods in the assessment of intracranial vessels of the circle of Willis (33 patients) and the vertebrobasilar system (21 patients). Compared to conventional transcranial color-coded sonography, both power-based and contrast-enhanced transcranial color-coded sonography improved the diagnostic sensitivity in identifying peripheral segments and small vessels of the circle of Willis. Contrast-enhanced transcranial color-coded sonography was significantly superior to power-based transcranial color-coded ultrasonography in the depiction of the second segment of the middle cerebral artery (66 of 66 versus 60 of 66, P0.005), both segments of the anterior cerebral artery (66 of 66 versus 56 of 66 for the A1 segment, P0.005; 61 of 66 versus 44 of 66 for the A2 segment, P0.005), the first segment of the posterior cerebral artery (66 of 66 versus 55 of 66, P0.005), and the basilar artery using the transtemporal approach (21 of 21 versus 15 of 21, P0.05). Using the transforaminal approach contrast-enhanced transcranial color-coded real-time sonography did not increase fine resolution of the vertebrobasilar system compared to power Doppler sonography. In conclusion, contrast-enhanced transcranial color-coded real-time sonography further improves the diagnostic potential of power Doppler sonography in the identification of vascular structures of the circle of Willis. Contrast-enhanced transcranial color-coded sonography and power Doppler sonography are equally effective in visualizing the vertebrobasilar system with branches.

The aim of this study was to investigate the diagnostic potential of contrast-enhanced transcranial color-coded sonography (CE-TCCS) and contrast-enhanced transcranial power-based sonography (CE-TPS) in patients with insufficient or absent acoustic bone windows (IABW). Due to temporal bone thickness, the basal cerebral circulation could not be insonated in 21 of 172 patients using unenhanced transcranial color-coded real-time sonography (TCCS) and transcranial power-based sonography. Additional CE-TCCS and CE-TPS were performed after application of 400 mg/ml galactose microbubble suspension. In both modalities, the use of echo-contrast agents allowed visualisation of the first segment of the middle cerebral artery (MCA) in all patients. The A1 segment of the anterior cerebral artery (67% in CE-TCCS; 81% in CE-TPS), P1 segment of the posterior cerebral artery (71% in CE-TCCS; 76% in CE-TPS) and the basilar artery (48% in CE-TCCS; 67% in CE-TPS) were depictable in the majority of the examinations. The M3 (5% in CE-TCCS; 33% in CE-TPS; p < 0.05), P2 (24% in CE-TCCS; 71% in CE-TPS; p < 0.005), P3 segments (0% in CE-TCCS; 43% in CE-TPS; p < 0.005) and the posterior communicating artery (5% in CE-TCCS; 33% in CE-TPS; p < 0.05) were detected in a significantly greater proportion of subjects using power Doppler. In conclusion, CE-TCCS and CE-TPS appear to be sensitive ultrasonic tools that provide reliable data regarding the basal cerebral circulation in patients with IABW. Furthermore, CE-TPS offers advantages over CE-TSSC in the identification of small-caliber arteries and vessels that run at unfavorable angels to the ultrasound beam. Both methods can overcome hyperostosis of the skull that is a major hindrance in transcranial ultrasonography, and may be helpful in the diagnosis of occlusive diseases of intracranial vessels.

Background Indirect immunofluorescence (IIF), utilizing ethanol-fixed neutrophils as substrate, is still the method of choice for detecting antineutrophil cytoplasmic antibodies (ANCA) in vasculitis. The conventional immunofluorescence microscopy for detection of ANCA is subjective and interlaboratory tests showed occasionally large variances in ANCA determination. Objectives Aim of this study was to develop a novel ANCA module for the automated immunofluorescence reading system AKLIDES® for detection of ANCA and to assess its diagnostic value. Methods Samples were analyzed by IIF with ethanol- and formalin-fixed neutrophils (ethN and formN). Seventy ANCA positive samples with defined antigen specificities (myeloperoxidase, n=20 and proteinase 3, n=50) were used as a “training set” for the development of the new ANCA module of AKLIDES®. Sera from 291 patients (“test set”) with ANCA associated vasculitis and other systemic rheumatic diseases were tested for ANCA using the novel ANCA module and conventional fluorescence microscopy. Results For the analysis of IIF patterns of the nucleus and cytoplasm new algorithms of image processing were developed by using the training set. The module is divided into two profiles for the recognition of ANCA patterns of ethN and formN. Furthermore, a differentiation between positive and negative samples and a detailed separation into the different basic patterns C-ANCA (cytoplasmic pattern) and P-ANCA (perinuclear pattern) were implemented. The ANCA module was evaluated with the test set of 291 sera with ethN and formN slides regarding to the differentiation between positive and negative samples and compared with the manual interpretation of the slides. The Cohen’s kappa values for this comparison were 0.871 for ethN and 0.866 for formN. Furthermore, the analysis of the “test set” with regard to the differentiation of the C-ANCA and P-ANCA pattern showed a high agreement for ethN (kappa =0.739), formN (kappa =0.742), and for the combined result (kappa =0.901). The resulting sensitivities/specificities and negative/positive likelihood ratios for the comparison between manual and automatic reading (ethN, formN and combined result) showed medium to high agreement. Conclusions In summary, a novel ANCA fluorescence pattern recognition algorithm could be implemented successfully into AKLIDES®. The preliminary investigation of the automatic reading of ethanol- and formalin-fixed neutrophils demonstrated a high diagnostic performance for the detection of ANCA. Further studies are needed to evaluate this novel fully automated method for initial screening of suspected vasculitis patients. Disclosure of Interest None Declared

Introduction Indirect immunofluorescence (IIF) employing ethanol-fixed neutrophils (ethN) is still the method of choice for assessing antineutrophil cytoplasmic antibodies (ANCA) in ANCA-associated vasculitides (AAV). However, conventional fluorescence microscopy is subjective and prone to high variability. The objective of this study was to evaluate novel pattern recognition algorithms for the standardized automated interpretation of ANCA patterns. Methods Seventy ANCA-positive samples (20 antimyeloperoxidase ANCA, 50 antiproteinase3 ANCA) and 100 controls from healthy individuals analyzed on ethN and formalin-fixed neutrophils (formN) by IIF were used as a 'training set' for the development of pattern recognition algorithms. Sera from 342 patients ('test set') with AAV and other systemic rheumatic and infectious diseases were tested for ANCA patterns using the novel pattern recognition algorithms and conventional fluorescence microscopy. Results Interpretation software employing pattern recognition algorithms was developed enabling positive/negative discrimination and classification of cytoplasmic ANCA (C-ANCA) and perinuclear ANCA (P-ANCA). Comparison of visual reading of the 'test set' samples with automated interpretation revealed Cohen's kappa (κ) values of 0.955 on ethN and 0.929 on formN for positive/negative discrimination. Analysis of the 'test set' with regard to the discrimination between C-ANCA and P-ANCA patterns showed a high agreement for ethN (κ = 0.746) and formN (κ = 0.847). There was no significant difference between visual and automated interpretation regarding positive/negative discrimination on ethN and formN, as well as ANCA pattern recognition (P > 0.05, respectively). Conclusions Pattern recognition algorithms can assist in the automated interpretation of ANCA IIF. Automated reading of ethN and formN IIF patterns demonstrated high consistency with visual ANCA assessment.

Introduction Analysis of autoantibodies (AAB) by indirect immunofluorescence (IIF) is a basic tool for the serological diagnosis of systemic rheumatic disorders. Automation of autoantibody IIF reading including pattern recognition may improve intra- and inter-laboratory variability and meet the demand for cost-effective assessment of large numbers of samples. Comparing automated and visual interpretation, the usefulness for routine laboratory diagnostics was investigated. Methods Autoantibody detection by IIF on human epithelial-2 (HEp-2) cells was conducted in a total of 1222 consecutive sera of patients with suspected systemic rheumatic diseases from a university routine laboratory (n = 924) and a private referral laboratory (n = 298). IIF results from routine diagnostics were compared with a novel automated interpretation system. Results Both diagnostic procedures showed a very good agreement in detecting AAB (kappa = 0.828) and differentiating respective immunofluorescence patterns. Only 98 (8.0%) of 1222 sera demonstrated discrepant results in the differentiation of positive from negative samples. The contingency coefficients of chi-square statistics were 0.646 for the university laboratory cohort with an agreement of 93.0% and 0.695 for the private laboratory cohort with an agreement of 90.6%, P < 0.0001, respectively. Comparing immunofluorescence patterns, 111 (15.3%) sera yielded differing results. Conclusions Automated assessment of AAB by IIF on HEp-2 cells using an automated interpretation system is a reliable and robust method for positive/negative differentiation. Employing novel mathematical algorithms, automated interpretation provides reproducible detection of specific immunofluorescence patterns on HEp-2 cells. Automated interpretation can reduce drawbacks of IIF for AAB detection in routine diagnostics providing more reliable data for clinicians.

Contrast agents enable the visualization of bigger blood vessels in the brain, e.g. the circle of Willis, in color- or power mode, which is a challenging task due to the high attenuation of the transtemporal bone window. Moreover, contrast agent specific imaging mode show potential to visualize microcirculation. Such imaging modes, three of which were investigated, mostly exploit non-linear scattering from microbubbles and the destruction of microbubbles by ultrasound. Functional images are formed from image sequences by locally analyzing the time-intensity-curves after a bolus injection of contrast agent.