White Matter Lesions and Encephalopathy in Patients Treated For Primary Central Nervous System Lymphoma

A retrospective analysis of the clinical presentations and neuroimaging characteristics of 33 patients with a primary central nervous system lymphoma (PCNL) who received cranial radiotherapy was performed to assess incidence of and risk factors for radiation-induced encephalopathy. CT and MRI scans were revised by a neurologist and a radiologist in conference. White matter abnormalities before and after radiotherapy on the last scan before recurrence were quantified according to a semi-quantitative scale. All available medical records were retrieved and reviewed with respect to demographic and tumor-related variables, treatment modalities, disease-free and overall survival and clinical symptoms and signs of encephalopathy. CT and MRI scans showed severe white matter lesions in 75% of 20 patients and in 86% of patients aged more than 60 years. Forty percent of patients presented with new clinical signs of cognitive impairment a median of 14.5 months after initial diagnosis (8.5 months after radiotherapy). The risk of white matter lesions appeared greater in patients aged > 60 (RR 1.2, 95% CI = 0.8–2.0), in patients with prior white matter lesions (RR 1.3, 95% CI = 0.8–2.1) and in patients with multifocal cerebral lymphoma (RR 1.5, 95% CI = 1.0–2.1). In conclusion, the risk of white matter lesions and clinical symptoms and signs of encephalopathy is high in patients treated by radiotherapy for PCNL. The risk appears to be greatest in older patients, patients with multifocal tumor and in those with prior white matter lesions on CT or MRI.     

Neurodevelopmental outcome in full-term newborns with refractory neonatal seizures

Aim: This retrospective study describes the prognosis of full‐term newborns with refractory neonatal seizures, comparing the need for treatment with two versus three or more antiepileptic drugs. Methods: We reviewed our database (January 2002–December 2007) to include newborns with refractory neonatal seizures and abnormal electroencephalogram. Group A consisted of 17 newborns with two antiepileptic drugs. Group B consisted of 29 newborns with three or more antiepileptic drugs. Outcome was determined at 2 years of age using the Dutch Bayley Scales of Infant Development or a neurodevelopmental classification scheme. Results: Group A and group B were comparable regarding to a variety of demographic and aetiologic factors. Thirteen newborns died before 2 years of age and one was lost to follow‐up. Normal development at 2 years of age was found in 50% and 5% for group A and B, respectively. Severe neurodevelopmental delay at 2 years of age was found in 30% and 68% for group A and B, respectively. Conclusion: The number of antiepileptic drugs probably reflects increased seizure burden and is – in that way – related to poor outcome. This may be useful information for early prediction of adverse neurological outcome in the first days of life.     

German guidelines for the sequential medical treatment of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs

The German Society of Rheumatology approved new German guidelines for the sequential medical treatment of rheumatoid arthritis (RA) based on the European League Against Rheumatism (EULAR) recommendations for the management of RA published in 2010. An update of the EULAR systematic literature research was performed in Medline, Embase, and Cochrane databases. Meta-analyses, controlled trials, cohort studies, and registry data addressing traditional and biologic disease-modifying antirheumatic drugs, glucocorticoids, and treatment strategies published between January 2009 and August 2011 were included. Two reviewers independently evaluated and compared the additional data that had been published after the time limit set by the EULAR recommendations. A national guideline working group developed an adapted set of recommendations. The new German guidelines were accepted by vote using an informal Delphi approach. Twelve recommendations and the resulting updated treatment algorithm were developed and approved as a practical orientation for rheumatologists. These recommendations are based on a successive treatment with traditional and biologic disease-modifying drugs depending on the individual progress of the disease and distinct patient characteristics. The German guidelines have been developed on the basis of the internationally well-recognized EULAR recommendations. In addition, more recent evidence from a systematic literature research was considered. They have been developed and approved by a group of national experts aiming at guidance for rheumatologists to reach best medical practice.     

Lupine-induced anaphylaxis in a child without known food allergy.

BACKGROUND: Lupine allergy is caused by ingestion of the flour of a plant called Lupinus albus, a member of the Leguminosae family. Lupine allergy has been described in adult patients previously known to have peanut allergy (cross-reactivity). OBJECTIVE: To describe the first case of an anaphylactic reaction caused by ingestion of lupine flour in a pediatric patient without a known peanut allergy. METHODS: Symptom assessment, nutritional history, and skin and blood tests. RESULTS: An otherwise healthy 8-year-old boy had nose and eye discharge followed by facial edema and difficulty breathing 30 minutes after eating an industrially prepared waffle containing eggs, sugar, and lupine flour. He had no history of food allergy and was eating a normal diet, including peanuts and other legumes. Results of skin prick tests using commercial extracts were positive to peanuts and negative to eggs, soy, and nuts; results of a prick-to-prick test using lupine flour were strongly positive (+ + + +). His total IgE level was 1,237 UI/mL. Specific IgE antibodies were positive to lupine seeds (20.8 kU/L) and peanuts (> 100 kU/L). CONCLUSIONS: To our knowledge, we describe the first case of an anaphylactic reaction after ingestion of lupine flour in a child without known allergy. In the case of peanut allergy or any anaphylactic reaction without evident cause, especially after industrially prepared food ingestion, lupine should be considered in the list of allergens tested. Lupine is increasingly used in industrially prepared food but is not regularly declared in the composition, leading to difficulties in allergen avoidance.     

Europäische Versorgungsstandards für Menschen mit rheumatoider Arthritis

In a joint initiative by the boards of the German Society for Rheumatology (DGRh) and the Association of Rheumatology Clinics (VRA) the European ?standards of care“ for rheumatoid arthritis, recently suggested by the European Musculoskeletal Conditions Surveillance and Information Network (eumusc.net) and supported by the European League Against Rheumatism (EULAR), were translated and annotated. The recommendations include aspects of the management of the disease, actual medical care, and access to information – this includes all types of support people with RA need, and, last but not least communication of the necessary knowledge. Furthermore, health care structures such as the availability of medical staff with relevant expertise are also important.     

Brauchen wir noch klinische Studien in der Rheumatologie?

Despite a large number of approved therapies demonstrating efficacy in the treatment of rheumatic diseases, only 60–85?% of patients with the indications for rheumatoid arthritis are adequately treated in Germany. Additionally, approved therapies for other immune-mediated diseases are often entirely lacking, indicating the great medical need for the development of new innovative therapies in this specialized field. The development of new drugs is expensive due to the high costs of conducting clinical trials in all phases of development up to obtaining approval; therefore, pharmaceutical companies are looking for ways to save costs in the particular developmental stages. Although the classical regions for drug development (i.e. western Europe, the USA and Japan) offer both a high level of data quality and a good infrastructure to conduct clinical trials due to high standards of education and quality, clinical trials are expensive in these regions. Beside high costs, the comparatively low recruitment rates in these regions are one of the main reasons for the shifting of drug developmental stages from classical regions to eastern European, Latin American and Asian countries, which provide services for drug development and high recruitment rates for comparatively less money. However, there are many strong arguments for the participation of regions in western Europe, especially German sites in clinical trials. In this article these arguments are discussed and possible solutions and strategies for conducting and compensation of study centers in Germany for clinical trials in the field of rheumatology are provided.     

CAPN1 mutations: Expanding the CAPN1-related phenotype: From hereditary spastic paraparesis to spastic ataxia

Aims and objectiveTo characterize the phenotype of CAPN1 (SPG76) mutations in patients diagnosed with hereditary spastic paraplegia (HSP).BackgroundThe CAPN1 gene, located on chromosome 11q13.1, is a protein-coding gene involved in neuronal plasticity, migration, microtubular regulation and cerebellar development. Several families with CAPN1 mutations have recently been reported to present with autosomal recessive (AR) HSP and/or ataxia.MethodPatients with HSP were identified through neurological and genetic clinics with detailed phenotyping. Whole exome sequencing revealed novel pathogenic CAPN1 mutations in four patients from 3 families.ResultsAffected families were of Turkish, Japanese, and Punjabi descent and all were consanguineous. Onset of spastic paraplegia in the four patients was between 20 and 37 years. Two also had mild ataxia. Three different novel, homozygous mutations in CAPN1 were found: c.2118+1G > T, c.397C > T, c.843+1G > C. The patient with the earliest onset also manifested profound muscle weakness, likely related to a second homozygous mutation in DYSF (dysferlinopathy).ConclusionsThe phenotype of AR CAPN1 mutations appears to be spastic paraplegia with or without ataxia; onset is most commonly in adulthood. Eye movement abnormalities, skeletal defects, peripheral neuropathy and amyotrophy can sometimes be seen. Occasionally, patients can present with ataxia, illustrating the genotypic and phenotypic overlap between HSP and spastic ataxia. With the advent of exome sequencing, mutations in more than one gene can be identified, which may contribute to the phenotypic variation, even within a family.     

Sustained attention in children and adolescents after traumatic brain injury: relation to severity of injury, adaptive functioning, ADHD and social background

Primary objective: To examine the relationship of child and family psychosocial variables and traumatic brain injury (TBI) severity as it relates to sustained attention (the Paediatric Assessment of Cognitive Efficiency, PACE).

Research design: Forty-two children and adolescents were recruited and participated in a 2 year longitudinal study to evaluate sustained attention using the computerized testing metric, PACE. More specifically, errors of omission (inattention) and commission (impulsiveness) were measured.

Main outcomes and results: Significant improvement on inattention and impulsiveness were observed over time. High pre-injury psychosocial adversity and low pre-injury adaptive functioning significantly predicted a greater number of inattention errors. Severity of injury predicted the reduction of impulsiveness. Moreover, omission errors immediately after TBI predicted later secondary attention-deficit/hyperactivity disorder (SADHD, ADHD that emerges after TBI).

Conclusions: Based on these findings, it is important to consider pre-injury child and family psychosocial characteristics in addition to severity of injury when predicting outcome of TBI in children.