Catheter ablation of coronary sinus accessory pathways in the young.

BACKGROUND: Accessory atrioventricular pathways (APs) are the most common tachycardia substrate for supraventricular tachycardia (SVT) in the young. Endocardial catheter ablation of AP may be unsuccessful in up to 5% of patients because of a coronary sinus location. OBJECTIVE: The purpose of this study was to obtain data on ablation of accessory pathways within the coronary venous system (CVS) in the young. METHODS: Analysis of feasibility, outcome, and safety in patients ≤18 years with coronary sinus accessory pathways (CS-APs) and catheter ablation via CVS in a tertiary pediatric electrophysiological referral center (May 2003 to December 2021) was performed. The control group adjusted for age, weight, and pathway location was established from patients of the prospective European Multicenter Pediatric Ablation Registry who all had undergone endocardial AP ablation. RESULTS: Twenty-four individuals underwent mapping and intended AP ablation within the CVS (age 2.7-17.3 years; body weight 15.0-72.0 kg). Because of proximity to the coronary artery, ablation was withheld in 2 of the patients. Overall procedural success was achieved in 20 of 22 study patients (90.9%) and in 46 of 48 controls (95.8%). Coronary artery injury after radiofrequency ablation was noted in 2 of 22 study patients (9%) and in 1 of 48 controls (2%). In CVS patients, repeat SVT occurred in 5 of 22 patients (23%) during median follow-up of 8.5 years, and 4 of the 5 underwent reablation, resulting in 94.4% overall success. Controls were free from SVT during follow-up of 12 months as defined by the registry protocol. CONCLUSION: Success of CS-AP ablation in the young was comparable to that of endocardial AP ablation. Substantial risk of coronary artery injury should be considered when CS-AP ablation is performed in the young.

Chest X-rays and Lung Ultrasound Are Not Interchangeable in Intensive Care Practice.

PURPOSE: Data comparing lung ultrasound (LUS) and chest X-rays (CXRs) have increased over the past years. However, there still is a lack of knowledge as to how these modalities compare with one another in the critical care setting, and several factors, including artificial study conditions, limit the generalizability of most published studies. Our study aimed to analyze the performance of LUS in comparison with CXRs in real-world critical care practice. MATERIALS AND METHODS: This study presents new data from the prospective FASP-ICU trial. A total of 209 corresponding datasets of LUS and CXR results from 111 consecutive surgical ICU patients were subanalyzed, and categorial findings were compared. Statistical analysis was performed on the rates of agreement between the different imaging modalities. RESULTS: A total of 1162 lung abnormalities were detected by LUS in ICU patients compared with 1228 detected by CXR, a non-significant difference (p = 0.276; 95% CI -0.886 to 0.254). However, the agreement rates varied between the observed abnormalities: the rate of agreement for the presence of interstitial syndrome ranged from 0 to 15%, consolidation from 0 to 56%, basal atelectasis from 33.9 to 49.34%, pleural effusion from 40.65 to 50%, and compression atelectasis from 14.29 to 19.3%. The rate of agreement was 0% for pneumothorax and 20.95% for hypervolemia. CONCLUSIONS: LUS does not detect more lung abnormalities in real-world critical care practice than CXRs, although a higher sensitivity of LUS has been reported in previous studies. Overall, low agreement rates between LUS and CXRs suggest that these diagnostic techniques are not equivalent but instead are complementary and should be used alongside each other.

Clinical Decision-Making in Practice with New Critical Care Ultrasound Methods for Assessing Respiratory Function and Haemodynamics in Critically Ill Patients.

Situations often arise in intensive care units (ICUs) for which only sparse primary evidence or guidelines are applicable or to which existing evidence cannot be applied owing to interactions of multiple disease states. To improve and guide intensive care management in complex scenarios, ultrasonography and echocardiography are invaluable. In five clinical scenarios involving acute deterioration, serial ultrasound examinations of the respiratory system, general critical care ultrasound (GCCUS), and non-invasive haemodynamic critical care echocardiography (CCE) were used routinely. Ultrasonographic results were used to guide further management and initiate experimental therapy or transition from curative to supportive care. The process of initiation of ultrasound examinations to clinical decision-making in these complex scenarios is outlined. These case vignettes highlight the utility of ultrasound and echocardiography. When clinical management is not clear, or evidence is not available, the use of ultrasound for the evaluation of the respiratory system, GCCUS, and non-invasive haemodynamic CCE can help to guide management, reveal newly developed pathologies, lead to clinical management changes, and support the decision for employing experimental therapy approaches in a dynamic way of which few other imaging modalities or monitoring tools are currently capable.

Hemodynamic profiling by critical care echocardiography could be more accurate than invasive techniques and help identify targets for treatment.

In this prospective observational study, non-invasive critical care echocardiography (CCE) was used to obtain quantitative hemodynamic parameters in 107 intensive care unit (ICU) patients; the parameters were then visualized in a novel web graph approach to increase the understanding and impact of CCE abnormalities, as an alternative to thermodilution techniques. Visualizing the CCE hemodynamic data in six-dimensional web graph plots was feasible in almost all ICU patients. In 23.1% of patients, significant tricuspid regurgitation prevented correlation between thermodilution techniques and echocardiographic hemodynamics. Two parameters of longitudinal right ventricular function (TAPSE and S') did not correlate in ICU patients. Clinical surrogate parameters of hemodynamic compromise did not correlate with measured hemodynamics. 26.2% of the patients with mean arterial pressures above 60 mmHg had cardiac indices (CI) below 2.5 L min-1·m-2. A CI below 2.2 L·min-1·m-2 was associated with a significant ICU survival disadvantage. CCE was feasible in addition or as an alternative to thermodilution techniques for the hemodynamic evaluation of ICU patients. Six-dimensional web graph plots visualized the hemodynamic states and were especially useful in conditions in which thermodilution methods were not reliable. Hemodynamic CCE identified patients with previously unknown low CI, which correlated with a higher ICU mortality.

Stereophotogrammetry can feasibly assess 'physiological' longitudinal three-dimensional head development of very preterm infants from birth to term.

Head development is a surrogate for brain development in infants and is related to neurocognitive outcome. There is only limited knowledge on early extra-uterine head shape and size assessment in very preterm infants. Here, 26 very preterm infants with a mean gestational age of 29.1 ± 2.2 weeks and a mean birth weight of 1273.8 ± 427.7 g underwent serial stereophotogrammetric 3D head imaging in weekly intervals from birth to term-equivalent age. The main outcome was the longitudinal assessment of the 'physiological' preterm head development with cephalometric size (head circumference, cranial volume) and shape parameters (cranial index, cranial vault asymmetry index) according to chronological and postmenstrual age (PMA). Potential clinical risk factors for the development of an abnormal low cranial index (dolichocephaly) were analysed. In serial measurements of 26 infants, the estimated head volume (95% confidence interval) increased from 244 (226-263) cm3 at 28 weeks PMA to 705 (688-721) cm3 at 40 weeks PMA. Moderate or severe dolichocephaly occurred in 21/26 infants (80.8%). Cranial index decreased over time (72.4%; 70.7-74 95% confidence interval). Brachycephaly and plagiocephaly were uncommon. No risk factors for severe dolichocephaly were identified. Our study shows that early detection of head shape and size anomalies utilizing 3D stereophotogrammetry is feasible and safe even in very preterm infants < 1500 g and/or < 32 weeks. 3D stereophotogrammetry could be used for timely identification of infants at risk for head shape anomalies. No specific risk factors for head shape anomalies were identified, especially not mode and duration of respiratory support.

The hazardous (mis)perception of Self-estimated Alcohol intoxication and Fitness to drivE-an avoidable health risk: the SAFE randomised trial.

BACKGROUND: Worldwide, alcohol-related road traffic accidents represent a major avoidable health risk. The aim of this study was to evaluate the accuracy of self-estimating the degree of acute alcohol intoxication regarding the legal driving limit, and to identify risk factors for misjudgement. METHODS: In this prospective randomised controlled crossover trial, 90 social drinkers (mean age 23.9 ± 3.5 years, 50% female) consumed either beer or wine. Study group subjects were made aware when exceeding the legal driving limit (BrAC = 0.05%). Controls received no information about their BrAC. For crossover, beer or wine were consumed in the opposite order. RESULTS: 39-53% of all participants exceeded the legal driving limit whilst under the impression to be still permitted to drive. Self-estimation was significantly more accurate on study day 2 (p = 0.009). Increasing BrAC positively correlated with self-estimation inaccuracy, which was reproducible during crossover. Multiple regression analysis revealed fast drinking and higher alcohol levels as independent risk factors for inaccurate self-estimation. CONCLUSIONS: Social drinkers are commonly unaware of exceeding the legal driving limit when consuming alcohol. Self-estimating alcohol intoxication can be improved through awareness. Dedicated awareness programs, social media campaigns and government advice communications should be utilised to address this avoidable hazard. Trial registration The trial was registered prospectively at the Witten/Herdecke University Ethics Committee (trial registration number 140/2016 on 04/11/2016) and at the DRKS-German Clinical Trials Register (trial registration number DRKS00015285 on 08/22/2018-Retrospectively registered). Trial protocol can be accessed online.

Development and evaluation of the focused assessment of sonographic pathologies in the intensive care unit (FASP-ICU) protocol.

BACKGROUND: The use of ultrasonography in the intensive care unit (ICU) is steadily increasing but is usually restricted to examinations of single organs or organ systems. In this study, we combine the ultrasound approaches the most relevant to ICU to design a whole-body ultrasound (WBU) protocol. Recommendations and training schemes for WBU are sparse and lack conclusive evidence. Our aim was therefore to define the range and prevalence of abnormalities detectable by WBU to develop a simple and fast bedside examination protocol, and to evaluate the value of routine surveillance WBU in ICU patients. METHODS: A protocol for focused assessments of sonographic abnormalities of the ocular, vascular, pulmonary, cardiac and abdominal systems was developed to evaluate 99 predefined sonographic entities on the day of admission and on days 3, 6, 10 and 15 of the ICU admission. The study was a clinical prospective single-center trial in 111 consecutive patients admitted to the surgical ICUs of a tertiary university hospital. RESULTS: A total of 3003 abnormalities demonstrable by sonography were detected in 1275 individual scans of organ systems and 4395 individual single-organ examinations. The rate of previously undetected abnormalities ranged from 6.4 ± 4.2 on the day of admission to 2.9 ± 1.8 on day 15. Based on the sonographic findings, intensive care therapy was altered following 45.1% of examinations. Mean examination time was 18.7 ± 3.2 min, or 1.6 invested minutes per detected abnormality. CONCLUSIONS: Performing the WBU protocol led to therapy changes in 45.1% of the time. Detected sonographic abnormalities showed a high rate of change in the course of the serial assessments, underlining the value of routine ultrasound examinations in the ICU. Trial registration The study was registered in the German Clinical Trials Register (DRKS, 7 April 2017; retrospectively registered) under the identifier DRKS00010428.

Stereophotogrammetric head shape assessment in neonates is feasible and can identify distinct differences between term-born and very preterm infants at term equivalent age.

The development of head shape and volume may reflect neurodevelopmental outcome and therefore is of paramount importance in neonatal care. Here, we compare head morphology in 25 very preterm infants with a birth weight of below 1500 g and / or a gestational age (GA) before 32 completed weeks to 25 term infants with a GA of 37-42 weeks at term equivalent age (TEA) and identify possible risk factors for non-synostotic head shape deformities. For three-dimensional head assessments, a portable stereophotogrammetric device was used. The most common and distinct head shape deformity in preterm infants was dolichocephaly. Severity of dolichocephaly correlated with GA and body weight at TEA but not with other factors such as neonatal morbidity, sex or total duration of respiratory support. Head circumference (HC) and cranial volume (CV) were not significantly different between the preterm and term infant group. Digitally measured HC and the CV significantly correlated even in infants with head shape deformities. Our study shows that stereophotogrammetric head assessment is feasible in all preterm and term infants and provides valuable information on volumetry and comprehensive head shape characteristics. In a small sample of preterm infants, body weight at TEA was identified as a specific risk factor for the development of dolichocephaly.

Safety of Transseptal Puncture for Access to the Left Atrium in Infants and Children.

Transseptal puncture (TSP) is a standard procedure to obtain access to the left heart. However, data on TSP in infants and children particularly with congenital heart defects (CHD) is sparse. Safety and efficacy of TSP in infants and children < 18 years with normal cardiac anatomy and with CHD were assessed. 327 TSP were performed in a total of 300 individuals < 18 years from 10/2002 to 09/2018 in our tertiary pediatric referral center. Median age at TSP was 11.9 years (IQR 7.8-15; range: first day of life to 17.9 years). 13 subjects were < 1 year. Median body weight was 43.8 kg (IQR 26.9-60; range: 1.8-121 kg). CHD was present in 28/327 (8.6%) procedures. TSP could be successfully performed in 323/327 (98.8%) procedures and was abandoned in 4 procedures due to imminent or incurred complications. Major complications occurred in 4 patients. 3 of these 4 subjects were ≤ 1 year of age and required TSP for enlargement of a restrictive atrial septal defect in complex CHD. Two of these babies deceased within 48 h after TSP attempt. The third baby needed urgent surgery in the cath lab. Pericardial effusion requiring drainage was noted in the forth patient (> 1 year) who was discharged well later. Minor complications emerged in 5 patients. The youngest of these individuals (0.3 years, 5.8 kg) developed small pericardial effusion after anterograde ballon valvuloplasty for critical aortic stenosis. The remaining 4/5 patients developed small pericardial effusion after ablation of a left-sided accessory atrioventricular pathway (6.1-12.2 years, 15.6-34.0 kg). TSP for access to the left heart was safe and effective in children and adolescents > 1 year of age. However, TSP was a high-risk procedure in small infants with a restrictive interatrial septum with need for enlargement of interatrial communication.

Lone Atrial Flutter in Children and Adolescents: Is It Really "Lone"?

Atrial flutter (AFL) in children and adolescents beyond the neonatal period in the absence of any underlying myocardial disease ("lone AFL") is rare and data is limited. Our study aims to present clinical and electrophysiological data of presumed "lone AFL" in pediatric patients and discuss the role of endomyocardial biopsy (EMB) and further follow-up. Since July 2005, eight consecutive patients at a median age of 12.7 (range 10.4-16.7) years presenting with presumed "lone AFL" after negative non-invasive diagnostic work-up had electrophysiological study (EPS) and induction of cavotricuspid isthmus (CTI) conduction block by radiofrequency (RF) current application. In 6/8 patients EMB could be taken. Induction of CTI conduction block was achieved in all patients. Histopathological examination of EMB from the right ventricular septum exhibited myocarditis or cardiomyopathy in 4/6 patients, respectively. During follow-up, 4/8 patients had recurrent arrhythmia (AFL n = 2, wide QRS complex tachycardia n = 1, monomorphic premature ventricular contractions n = 1) after the ablation procedure. 3/4 patients with recurrent arrhythmia had pathological EMB results. The remaining patient with recurrent arrhythmia had a negative EMB but was diagnosed with Brugada syndrome during further follow-up. Taking together results of EMB and further clinical course, only 3/8 patients finally turned out to have true "lone AFL". Our study demonstrates that true "lone AFL" in children and adolescents is rare. EMB and clinical course revealed an underlying cardiac pathology in the majority of the individuals studied. EMB was very helpful in order to timely establish the diagnosis of myocarditis or cardiomyopathy.

Critical Care Echocardiography as a Routine Procedure for the Detection and Early Treatment of Cardiac Pathologies.

Transthoracic and transesophageal echocardiography are important investigations in the intensive care unit (ICU) to diagnose acute cardiac pathologies and assess the haemodynamic status. Recommendations for critical care echocardiography (CCE) have been published recently, but these still lack an evidence-based foundation. It is not known if performing transthoracic echocardiography (TTE) on a routine basis instead of only when required in acute cases is feasible or clinically useful. In this single-centre prospective observational study, we routinely performed TTE on 111 consecutive non-cardiological, non-cardiothoracic surgical ICU patients in two surgical ICUs in a tertiary care facility. Significant cardiac pathologies were detected in 82 (76.6%) and critical cardiac pathologies in 33 (30.8%) of the 107 patients. The most common critical cardiac pathologies were sPAP > 50 mmHg (19.63%), tricuspid annular plane systolic excursion ≤ 13 mm (9.4%), grade III diastolic dysfunction (8.4%), severe tricuspid valve insufficiency (5.6%) and left ventricular ejection fraction (LV-EF) ˂ 30% (4.7%). Some of the most commonly found cardiac pathologies are not well emphasised in current recommendations and training programs. We observed a progression of the cardiac pathologies previously described in 41 of the patients (91.1%). Patients with echocardiographic abnormalities had a significant survival disadvantage in the ICU. By performing CCE routinely, we observed the range and prevalence of cardiac pathologies that can be detected by echocardiography in critically ill patients. We recommend routine transthoracic CCE in ICU patients for early detection of cardiac pathologies and to help inform early intervention regimens, since cardiac conditions carry a significant survival disadvantage for the ICU patient.

Efficacy and safety of non-transvenous cardioverter defibrillators in infants and young children.

BACKGROUND: Implantable cardioverter defibrillators (ICD) protect from sudden cardiac death (SCD). In infants and young children, ICD implantation and programming is challenging due to small body size, elevated heart rates, and high physical activity. PURPOSE: We report our experience applying a non-transvenous ICD (NT-ICD) system to infants and children < 12 years of age and < 45-kg body weight. METHODS: Between 07/2004 and 07/2016, NT-ICD had been implanted in 36 patients. Nine out of 36 patients (25%) had NT-ICD implantation for primary and 27/36 (75%) for secondary prevention. Underlying diseases included inherited primary electrical arrhythmogenic diseases (n = 26; 72%), cardiomyopathies (n = 8; 22%), and congenital heart defects (n = 2; 6%). The median (interquartile range) age at implantation was 6 (1.9-8.4) years, and the median body weight was 21.7 (11.2-26.8) kg. Three different NT-ICD implantation techniques had been applied over time: (1) abdominal device/subcutaneous shock coil, (2) abdominal device/pleural shock coil, and (3) subcardiac device/pleural shock coil. RESULTS: During median follow-up of 5.2 (2.7-7.2) years, appropriate ICD discharges were documented in 12 (33.3%) and inappropriate shocks in 4 patients (11.1%). In 12/36 individuals (33.3%), a total of 25 surgical revisions were required due to NT-ICD malfunction. Eighteen out of 25 (72%) surgical revisions were necessary in patients with subcutaneous shock coil/abdominal device position. Surgical revisions (3/25, 12%) were significantly reduced (p < 0.001) after modifying the implantation technique to subcardiac device/pleural shock coil. CONCLUSIONS: NT-ICD was safe and effective in infants and young children. Appropriate ICD discharges occurred in a considerable number of patients. After modifying the implantation technique, the need for surgical revision could significantly be decreased.

Long-Term Follow-Up After Radiofrequency Catheter Ablation of Accessory Atrioventricular Pathways in Children.

OBJECTIVES: The purpose of this study was to evaluate long-term safety and efficacy of catheter ablation of accessory atrioventricular pathways (AP) in a pediatric cohort. BACKGROUND: Radiofrequency catheter ablation of accessory AP is the recommended treatment for patients with atrioventricular re-entrant tachycardia. Data on long-term results ≥1 year after AP ablation in pediatric patients is sparse. METHODS: A total of 296 patients <18 years of age who had undergone radiofrequency-AP ablation between October 2002 and June 2015 were included into the study. Follow-up was >1 year in all patients. Median age at ablation had been 11.6 years, and median follow-up was 5.6 years. Recurrence of AP conduction after ablation was defined as documentation of pre-excitation, supraventricular tachycardia attributable to AP, or proof of AP conduction during repeat electrophysiological study. RESULTS: AP ablation succeeded in 268 of 296 individuals (91%). After successful ablation, recurrence of AP conduction was observed in 29 of 268 individuals (10.8%). Of those 29, 23 (79%) had AP recurrence within the first year after ablation, whereas 13 (45%) had recurrence of AP conduction already within the first month. Six patients had late recurrence of AP conduction >1 year post-ablation. Procedural success and freedom from AP conduction after a single ablation procedure was 86% at 1 month, 83% at 1 year, and 81% at 5 years after ablation. CONCLUSIONS: After radiofrequency ablation of AP in children, recurrence of AP conduction occurred in 23 subjects (8% of the study cohort) within the first year after ablation. Late recurrences >1 year after ablation were noticed in 6 children (2% of the study group), highlighting the need for longer follow-up >1 year. Results of the present study on late AP recurrence should be taken into account whenever families are counselled for pediatric AP ablation.

Adjunctive ivabradine in combination with amiodarone: A novel therapy for pediatric congenital junctional ectopic tachycardia.

BACKGROUND: Treatment of congenital junctional ectopic tachycardia (JET) is often challenging. In the majority of patients affected, a combination of ≥2 antiarrhythmic drugs is required for JET control. OBJECTIVE: The purpose of this study was to assess the efficacy and safety of adjunctive ivabradine therapy for pediatric congenital JET. METHODS: Since January 2015, 5 consecutive patients aged 10 days to 3.5 years (median 8 weeks) were treated with adjunctive ivabradine for congenital JET. All patients had previously undergone antiarrhythmic therapy with unsatisfactory control of JET. Ivabradine was administered orally at an initial dosage of 0.05-0.1 mg/kg/d divided into 2 single doses and was increased up to 0.28 mg/kg/d if necessary. RESULTS: In all 5 patients, ivabradine proved to be successful in controlling JET. Complete suppression of JET and conversion into sinus rhythm were achieved in 4 of 5 patients. The remaining patient had effective heart rate control with persistent slow JET. Mean heart rate was reduced by 31% compared to pre-ivabradine (P = .03) as assessed by 24-hour Holter monitoring. Echocardiography revealed improvement of left ventricular function in all 3 patients with previously impaired left ventricular function. No significant side effects of ivabradine were encountered during median follow-up of 135 days (range 37-203 days). CONCLUSION: In our group of patients with congenital JET, adjunctive treatment with ivabradine resulted in effective and safe rhythm/heart rate control and therefore may be recommended early in the course of this rare inborn tachyarrhythmia.

Catheter Ablation of Pediatric Focal Atrial Tachycardia: Ten-Year Experience Using Modern Mapping Systems.

Experience of catheter ablation of pediatric focal atrial tachycardia (FAT) is still limited. There are data which were gathered prior to the introduction of modern 3D mapping and navigation systems into the clinical routine. Accordingly, procedures were associated with significant fluoroscopy and low success rates. The aim of this study was to present clinical and electrophysiological details of catheter ablation of pediatric FAT using modern mapping systems. Since March 2003, 17 consecutive patients <20 years underwent electrophysiological study (EPS) for FAT using the NavX(®) system (n = 7), the non-contact mapping system (n = 6) or the LocaLisa(®) system (n = 4), respectively. Radiofrequency was the primary energy source; cryoablation was performed in selected patients with a focus close to the AV node. In 16 patients, a total number of 19 atrial foci (right-sided n = 13, left-sided n = 6) could be targeted. In the remaining patient, FAT was not present/inducible during EPS. On an intention-to-treat basis, acute success was achieved in 14/16 patients (87.5 %) with a median number of 11 (1-31) energy applications. Ablation was unsuccessful in two patients due to an epicardial location of a right atrial focus (n = 1) and a focus close to the His bundle (n = 1), respectively. Median procedure time was 210 (84-332) min, and median fluoroscopy time was 13.1 (4.5-22.5) min. In pediatric patients with FAT, 3D mapping and catheter ablation provided improved clinical quality of care. Catheter ablation may be considered early in the course of treatment of this tachyarrhythmia in symptomatic patients.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) with multiple vascular complications misdiagnosed as Dubowitz syndrome.

UNLABELLED: To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. In microcephalic osteodysplastic primordial dwarfism type II (MOPD II; disproportionate short statue, microcephaly, facial abnormalities), however, cerebral aneurysms and other vascular abnormalities are frequent complications. MOPD II is a genetic disorder caused by mutations in the pericentrin (PCNT) gene (21q22). We report on a patient who came to our attention as a 22-year-old with subarachnoid bleeding due to a ruptured cranial aneurysm. Until then, the patient was thought and published to have Dubowitz syndrome; previously, he was treated with coronary bypass surgery for extensive coronary angiopathy. Consecutive genetic testing revealed MOPD II. After clinical stabilization, the patient was discharged to a specialized rehabilitation center where he died due to re-rupture of a cranial aneurysm. CONCLUSION: In patients with short stature-especially when clinical features are accompanied by vascular complications-MOPD II should be considered as a differential diagnosis leading to consecutive genetic testing. After detection of mutations in the PCNT gene, a full vascular status including cerebral imaging and cardiac evaluation needs to be determined in order to analyze vascular abnormalities and initiate prophylactic treatment.

Low-abundant cerebrospinal fluid proteome alterations in dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is one of the most common neurodegenerative diseases and shares multiple clinical and neuropathological parallels with Alzheimer's (AD) and Parkinson's disease (PD). A variety of clinical signs are suggestive for the diagnosis, and imaging (ßCIT SPECT) contributes substantially to the diagnosis. The study reported here was performed in search for a biomarker in the cerebrospinal fluid (CSF) of these patients. We applied 2D fluorescence difference gel electrophoresis and mass spectrometry to analyze the CSF proteome pattern of DLB patients after depleting twelve high-abundant proteins. The densitometric analysis of 2D gels showed the up- or down-regulation of 44 protein spots. Subsequently, 23 different proteins were identified. The majority is involved in acute phase and immune response. Many of these proteins were previously reported before as being associated with AD or PD, which strongly suggests a molecular cross-talk and may explain clinical and pathological overlap of these disease entities. Among the identified proteins are two highly upregulated proteins-inter alpha trypsin inhibitor heavy chain (ITIH4) and calsyntenin 1-that may have the potential to serve as molecular biomarkers specific for DLB. The identification of DLB-associated proteome changes will help to further understand pathological processes occurring in DLB and may provide future prospects to diagnostic and therapeutic options.

Codon 129 polymorphism specific cerebrospinal fluid proteome pattern in sporadic Creutzfeldt-Jakob disease and the implication of glycolytic enzymes in prion-induced pathology.

Cerebrospinal fluid (CSF) contains a dynamic and complex mixture of proteins, which can reflect a physiological and pathological state of the central nervous system. In our present study, we show CSF protein patterns from patients with the two most frequent subtypes of sporadic Creutzfeldt-Jakob disease (sCJD) defined by the codon 129 genotype (MM, MV, and VV) and the protease-resistant form of prion protein (type 1 and type 2). The densitometric analysis of 2D gels showed up-regulation of 27 and down-regulation of 3 proteins in the MM-sCJD as well as the up-regulation of 24 proteins in the VV-sCJD as compared to nondemented control. Almost 40% of sCJD specific regulated proteins in CSF are involved in glucose metabolism, regardless of the codon 129 polymorphism. The increase in CSF levels of lactate dehydrogenase (LDH), glucose-6-phosphate isomerase (G6PI), and fructose-bisphosphate aldolase A (ALDOA) were validated on a larger group of sCJD patients including three possible codon 129 polymorphism carriers and three control groups consisting of nondemented, neurological cases as well as patients suffering from Alzheimer's disease or vascular dementia. Subsequently, the abundance of these glycolytic enzymes in the brain as well as their cellular localization were determined. This study demonstrates for the first time the implication of G6PI in prion-induced pathology as well as its cellular translocalization in sCJD. The identification of sCJD-regulated proteins in CSF of living symptomatic patients in our study can broaden our knowledge about pathological processes occurring in sCJD, as they are still not fully understood.