Morphometric MRI Analysis: Improved Detection of Focal Cortical Dysplasia Using the MP2RAGE Sequence.

BACKGROUND AND PURPOSE: Focal cortical dysplasias are the most common resected epileptogenic lesions in children and the third most common lesion in adults, but they are often subtle and frequently overlooked on MR imaging. The purpose of this study was to evaluate whether MP2RAGE-based morphometric MR imaging analysis is superior to MPRAGE-based analysis in the detection of focal cortical dysplasia. MATERIALS AND METHODS: MPRAGE and MP2RAGE datasets were acquired in a consecutive series of 640 patients with epilepsy. Datasets were postprocessed using the Morphometric Analysis Program to generate morphometric z score maps such as junction, extension, and thickness images based on both MPRAGE and MP2RAGE images. Focal cortical dysplasia lesions were manually segmented in the junction images, and volumes and mean z scores of the lesions were measured. RESULTS: Of 21 focal cortical dysplasias discovered, all were clearly visible on MP2RAGE junction images, whereas 2 were not visible on MPRAGE junction images. In all except 4 patients, the volume of the focal cortical dysplasia was larger and mean lesion z scores were higher on MP2RAGE junction images compared with the MPRAGE-based images (P = .005, P = .013). CONCLUSIONS: In this study, MP2RAGE-based morphometric analysis created clearer output maps with larger lesion volumes and higher z scores than the MPRAGE-based analysis. This new approach may improve the detection of subtle, otherwise overlooked focal cortical dysplasia.

Critical appraisal of RCTs by 3rd year undergraduates after short courses in EBM compared to expert appraisal.

Introduction: An essential aim of courses in evidence-based medicine (EBM) is to improve the skills for reading and interpreting medical literature adequately. Regarding the conceptual framework, it is important to consider different educational levels. Aim: Our primary aim was to investigate the applicability of different instruments for the assessment of methodological study quality by 3rd grade students after short courses in EBM. Our secondary outcomes were agreement with expert assessments and student's knowledge and competences. Methods: We conducted four short courses in EBM of 90 minutes each for health care management and medical students focused on critical appraisal of the literature. At the end, the students assessed five publications about randomized controlled trials (RCTs) using five different instruments; the results were compared to expert assessments. Results: In total, 167 students participated in our EBM courses. Students' assessments showed a non-systematic over- and underestimation of risk of bias compared to expert assessments with no clear direction. Agreement with expert assessments ranged between 66% to over 80%. Across RCTs, evidence was found that the choice of instrument had an impact on agreement rates between expert and student assessments (p=0.0158). Three RCTs showed an influence of the instrument on the agreement rate (p<0.05 each). Discussion: Our results contrast sharply with those of many other comparable evaluations. Reasons may be a lack of students' motivation due to the compulsory courses, and the comparison to a reference standard in addition to self-ratings causing objectivity. Conclusion: Undergraduates should become familiar with the principles of EBM, including research methods, and the reading of scientific papers as soon as possible. For a deeper understanding, clinical experience seems to be an indispensable precondition. Based on our results, we would recommend an integration of lectures about EBM and critical appraisal at least twice during studies and with greater intensity shortly before graduation.

Factors associated with severity in invasive community-acquired Staphylococcus aureus infections in children: a prospective European multicentre study.

Staphylococcus aureus is the main pathogen responsible for bone and joint infections worldwide and is also capable of causing pneumonia and other invasive severe diseases. Panton-Valentine leukocidin (PVL) and methicillin-resistant S. aureus (MRSA) have been studied as factors related with severity in these infections. The aims of this study were to describe invasive community-acquired S. aureus (CA-SA) infections and to analyse factors related to severity of disease. Paediatric patients (aged 0-16 years) who had a CA-SA invasive infection were prospectively recruited from 13 centres in 7 European countries. Demographic, clinical and microbiological data were collected. Severe infection was defined as invasive infection leading to death or admission to intensive care due to haemodynamic instability or respiratory failure. A total of 152 children (88 boys) were included. The median age was 7.2 years (interquartile range, 1.3-11.9). Twenty-six (17%) of the 152 patients had a severe infection, including 3 deaths (2%). Prevalence of PVL-positive CA-SA infections was 18.6%, and 7.8% of the isolates were MRSA. The multivariate analysis identified pneumonia (adjusted odds ratio (aOR) 13.39 (95% confidence interval (CI) 4.11-43.56); p 0.008), leukopenia at admission (<3000/mm(3)) (aOR 18.3 (95% CI 1.3-259.9); p 0.03) and PVL-positive infections (aOR 4.69 (95% CI 1.39-15.81); p 0.01) as the only factors independently associated with severe outcome. There were no differences in MRSA prevalence between severe and nonsevere cases (aOR 4.30 (95% CI 0.68- 28.95); p 0.13). Our results show that in European children, PVL is associated with more severe infections, regardless of methicillin resistance.

[A Pair of Siblings with a rare R5H-Mutation in Exon 1 of the MAPT-Gene]. / Ein Geschwisterpaar mit einer seltenen Tau-Gen-Mutation (MAPT R5H).

We report on a female patient presenting with primary progressive aphasia (PPA) and her brother presenting with psychosis. Both siblings had an R5H-mutation in exon 1 of the MAPT-gene. The PPA patient presented for the first time at the age of 72 years with a 4-year-history of language impairment. After a progressive course the patient died at the age of 76 years. The R5H-MAPT-gene mutation detected in the siblings has been described only once in 2002 by Hayashi et al. [1]. In this previous case from Japan, a 75-year-old patient initially displayed amnesia and disorientation. He became bedridden, with progressive mutism and rigidity of the upper extremities. Noteworthy are the manifold signs and symptoms in R5H-mutations and the late age of onset. For future trials, the detection of biomarkers for frontotemporal lobar degeneration in presymptomatic cohorts like the genetic frontotemporal dementia initiative (GENFI) is of help for stratifying subjects at risk.

[Immunization in children and adolescents with rheumatic and musculoskeletal diseases]. / Sinnvolle Impfprävention bei Kindern und Jugendlichen mit rheumatischen und muskuloskelettalen Erkrankungen.

BACKGROUND: Children and adolescents with inflammatory rheumatic diseases have a disease and treatment-related increased risk of infections. This risk includes vaccine-preventable diseases; therefore, vaccinations represent an important preventive measure against infection in these patients. However, approximately one in three patients with a juvenile rheumatic disease is nowadays still inadequately vaccinated, mostly due to uncertainty regarding the efficacy and safety of vaccination in these patients. OBJECTIVES: This paper summarizes the available evidence regarding the efficacy and safety of vaccinations in children and adolescents with rheumatic diseases and gives recommendations for the clinical practice. RESULTS AND PERSPECTIVES: Almost 2000 children and adolescents with rheumatic diseases were examined in the more than 30 previously published vaccination studies, comprising nearly all standard vaccinations in the immunization schedule. The immunogenicity was usually sufficient and there was no evidence of a relevant aggravation of the underlying disease. Recommendations for the clinical practice are given also considering data beyond pediatric rheumatology; however, a final benefit-risk assessment is not yet possible.

[Evidence of treatment of chronic inflammation in childhood and adolescence with biologics]. / Evidenz der Therapie chronisch-entzündlicher Erkrankungen in Kindheit und Adoleszenz mit Biologika.

BACKGROUND: Biologics, usually monoclonal antibodies or fusion proteins, are thought to specifically interfere with immunopathogenesis of chronic inflammatory diseases. In order to test these substances also in children and adolescents, financial incentives for manufacturers were created and classification of chronic inflammatory diseases and definition of disease activity, improvement, relapse and remission were established and large international research cooperation projects were founded. METHODS: A selective literature search was carried out for treatment of chronic inflammatory diseases in children and adolescents with biologics including current guidelines. RESULTS: Only 7 out of 18 prescribed biologics have been approved for children and mostly within narrow limits. The evidence for efficacy is based on four randomized double blind placebo-controlled studies, seven withdrawal studies and seven observational studies. In spite of the limited evidence in comparison to their use in adult patients these substances are broadly used worldwide and have enlarged and substantially improved the therapeutic choices in children when conventional treatment failed or proved to be toxic. Severe adverse events including infections occasionally occur (0.01-0.03 events per patient year) but the rate of malignancies is not obviously increased; however, only two thirds of patients respond to treatment. Improvement is often incomplete, some patients deteriorate and definite termination of drug treatment is possible in only a few patients. CONCLUSION: As the prescription of biologics has become an important issue of treatment but is based on insufficient evidence data, further studies are necessary in children and adolescents with diseases, such as juvenile idiopathic arthritis, Crohn's disease, ulcerative colitis and inherited fever syndromes. As many drugs are available these studies can be conducted against verum.

[Assessment of risk of bias in controlled studies]. / Bewertung des Risikos für Bias in kontrollierten Studien.

BACKGROUND: Practicing physicians are faced with many medical decisions daily. These are mainly influenced by personal experience but should also consider patient preferences and the scientific evidence reflected by a constantly increasing number of medical publications and guidelines. With the objective of optimal medical treatment, the concept of evidence-based medicine is founded on these three aspects. It should be considered that there is a high risk of misinterpreting evidence, leading to medical errors and adverse effects without knowledge of the methodological background. OBJECTIVES: This article explains the concept of systematic error (bias) and its importance. Causes and effects as well as methods to minimize bias are discussed. This information should impart a deeper understanding, leading to a better assessment of studies and implementation of its recommendations in daily medical practice. CONCLUSION: Developed by the Cochrane Collaboration, the risk of bias (RoB) tool is an assessment instrument for the potential of bias in controlled trials. Good handling, short processing time, high transparency of judgements and a graphical presentation of findings that is easily comprehensible are among its strengths. Attached to this article the German translation of the RoB tool is published. This should facilitate the applicability for non-experts and moreover, support evidence-based medical decision-making.

Is the type and extent of hippocampal sclerosis measurable on high-resolution MRI?

INTRODUCTION: The purpose of this study is to relate hippocampal volume and FLAIR signal intensity to Wyler grading of hippocampal sclerosis (HS). METHODS: Of 100 consecutive patients with temporal lobe epilepsy and HS as histopathological diagnosis, 32 had high-resolution 3 Tesla MRI and anatomically well-preserved hippocampi following amygdalo-hippocampectomy. Hippocampal volume on 3D T1-weighted gradient echo and signal intensity on coronal FLAIR sequences were determined using FreeSurfer and SPM tools and related to Wyler grading. Seizure outcome was determined after 1 year. RESULTS: Histopathology showed four Wyler II, 19 Wyler III, and 9 Wyler IV HS. Hippocampal volumes were 3.08 ml for Wyler II (Wyler II/contralateral side: p > 0.05), 2.19 ml for Wyler III (p < 0.01), 2.62 ml for Wyler IV (p = 0.01), and 3.08 ml for the contralateral side. Normalized FLAIR signals were 1,354 (p = 0.0004), 1,408 (p < 0.0001), 1,371 (p < 0.04), and 1,296, respectively. Wyler II hippocampi were visually normal. Two of four (50%) Wyler II, 16/19 (84%) Wyler III, and 6/9 (66%) Wyler IV patients achieved Engel I outcome. CONCLUSIONS: Combined volumetry and quantitative FLAIR signal analysis clearly identifies Wyler III and IV HS. Quantitative FLAIR signal analysis may be helpful to identify Wyler II HS.

[Diagnosis and treatment of Lyme arthritis. Recommendations of the Pharmacotherapy Commission of the Deutsche Gesellschaft für Rheumatologie (German Society for Rheumatology)]. / Diagnostik und Therapie der Lyme-Arthritis. Empfehlungen der Kommission Pharmakotherapie der DGRh.

These guidelines summarize the current evidence for diagnosis and treatment of Lyme arthritis and the most frequent skin manifestations of Borrelia burgdorferi infections. Lyme arthritis is a monoarticular or oligoarticular form of arthritis that typically involves the knee. A positive enzyme-linked immunosorbent assay (ELISA) for IgG antibodies should be followed by an IgG immunoblot. A positive PCR test from synovial fluid adds increased diagnostic certainty. Serum positivity for antibodies to Borrelia burgdorferi without typical symptoms does not justify antibiotic treatment. Oral antibiotic treatment for erythema migrans is recommended using doxycycline, 200 mg once per day for 10-21 days, alternative choices are amoxicillin, cefuroxime and azithromycin. For children below 8 years of age, amoxicillin is recommended.Lyme arthritis can usually be successfully treated with orally administered antimicrobial agents. Doxycycline, 1 × 200 or 2 × 100 mg for 30 days is the antibiotic agent of choice. Amoxicillin (3 × 500-1000 mg) can be alternatively chosen. Patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy should be treated intravenously. In this situation, ceftriaxone at 2 g per day for 14-21 days is recommended. There is no evidence to recommend long-term and combined treatments.

[Quality guidelines for presurgical epilepsy diagnosis and operative epilepsy therapy: 1st revised version]. / Qualitätsleitlinien für prächirurgische Epilepsiediagnostik und operative Epilepsietherapie : 1. Neufassung.

In patients with pharmacorefractory epilepsy, preoperative epilepsy evaluation and subsequent epilepsy surgery lead to a significant improvement of seizure control, proportion of seizure-free patients, quality of life and social participation. The aims of preoperative epilepsy evaluation are to define the chance of complete seizure freedom and the likelihood of inducing new neurological deficits in a given patient. As epilepsy surgery is an elective procedure quality standards are particularly high. As detailed in the first edition of these practice guidelines, quality control relates to seven different domains: (1) establishing centres with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuing medical education of employees, (4) surveillance by trained personnel during the video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures and (7) cooperation of epilepsy centres. In the first edition of these practice guidelines published in 2000 it was defined which standards were desirable and that their implementation should be aimed for. These standards related especially to the certification required for different groups of medical doctors involved and to the minimum numbers of procedures required. In the subsequent decade quite a number of colleagues have been certified by the trinational Working Group (Arbeitsgemeinschaft, AG) for Presurgical Epilepsy Diagnosis and Operative Epilepsy Treatment (http://www.ag-epilepsiechirurgie.de) and therefore, on 8 May 2013 the executive board of the AG decided to now make these standards obligatory.