CASPR2 autoimmunity in children expanding to mild encephalopathy with hypertension.

OBJECTIVE: To delineate autoimmune disease in association with contactin-associated protein 2 (CASPR2) antibodies in childhood, we reviewed the clinical phenotype of children with CASPR2 antibodies. METHODS: Retrospective assessment of patients recruited through laboratories specialized in autoimmune CNS disease. RESULTS: Ten children with serum CASPR2 antibodies were identified (age at manifestation 18 months to 17 years). Eight children with CASPR2 antibody titers from ≥1:160 to 1:5,120 had complex autoimmune diseases with an age-dependent clinical phenotype. Two children with structural epilepsy due to CNS malformations harbored nonspecific low-titer CASPR2 antibodies (serum titers 1:80). The clinical symptoms of the 8 children with high-titer CASPR2 antibodies were general weakness (8/8), sleep dysregulation (8/8), dysautonomia (8/8) encephalopathy (7/8), neuropathic pain (7/8), neuromyotonia (3/8), and flaccid paresis (3/8). Adolescents (3/8) showed pain, neuromyotonia, and encephalopathy, whereas younger children (5/8) displayed severe hypertension, encephalopathy, and hormonal dysfunction mimicking a systemic disease. No tumors were identified. Motor symptoms remitted with immunotherapy. Mild behavioral changes persisted in 1 child, and autism spectrum disorder was diagnosed during follow-up in a young boy. CONCLUSION: High-titer CASPR2 antibodies are associated with Morvan syndrome in children as young as 2 years. However, CASPR2 autoimmunity mimics systemic disease and hypertensive encephalopathy in children younger than 7 years. The outcome following immunotherapy was mostly favorable; long-term behavioral impairment may occur in younger children.

Transient severe non-proliferative retinopathy in an adolescent with type 1 diabetes and chronic myeloid leukemia.

The onset of diabetic retinopathy correlates with the long-term quality of glycemic control. A 17-yr-old adolescent with type 1 diabetes presented unexpectedly with acute non-proliferative retinopathy despite good glycemic control. Two months later chronic myeloid leukemia (CML) was diagnosed. Chemotherapy was initiated and within a few weeks the patient was in full remission concerning leukemia. Retinopathy completely resolved within 8 months. The patient was in good metabolic control throughout the course. To our knowledge, this is the first report of CML-triggered retinopathy in a well-controlled diabetic adolescent. In case of unexpected retinopathy in patients with type 1 diabetes, other potential causes of retinopathy should be considered.

The Mth60 fimbriae of Methanothermobacter thermoautotrophicus are functional adhesins.

The ability to adhere onto surfaces is of very high importance for microorganisms, enabling them to stay in a favourable habitat for life. In the case of Bacteria cell surface organelles called fimbriae/pili have been shown to be used for adhesion; corresponding cell surface appendages of Archaea have not yet been defined. The first detailed characterization of archaeal fimbriae, namely those of Methanothermobacter thermoautotrophicus, allowed us to identify mth60 as the main structural fimbrin gene. Recombinant expression of mth60 in Escherichia coli was used to generate sufficient amounts of Mth60 to induce antibodies in rabbits. The antiserum reacted specifically with the 16 kDa fimbrial glycoprotein and could specifically detach adhering M. thermoautotrophicus cells from various surfaces. In addition we proved that cells adhering to solid surfaces - organic and inorganic ones - express many more fimbriae than cells growing in liquid cultures. The Mth60 fimbriae therefore are used by M. thermoautotrophicus as adhesins.

A daily comprehensive muscle training programme increases lean mass and spontaneous activity in children with Prader-Willi syndrome after 6 months.

UNLABELLED: The reduction of spontaneous physical activity (PA) and of muscle tissue are thought to be major causes of fat accretion and metabolic deterioration in Prader-Labhart-Willi syndrome (PWS). We investigated whether a generalized physical training programme in a home setting improves these parameters. The prospective study included 11 prepubertal children (mean age 8.7 years, range 5.9-11.8) with documented PWS and under continuous growth hormone treatment for at least 2.8 years. Seven children were enrolled in a training programme for several muscle groups during 4-10 minutes daily. Twelve matched children with PWS served as controls (average age 8.8 years, 6.1-11.3). Before and after training, at 6 months, PA was assessed by measuring walking distance by pedometer registration and by an activity score, and body composition by DEXA expressed as standard deviation scores (SDS) related to height. After training, lean mass (LM) increased from -1.83 to -1.48 SDS, p <0.05, whereas the controls showed no change. In the training group, walking distance and PA increased from 4.2 to 4.7 km/d and from 255 to 266 points, respectively, and these rises significantly exceeded those observed in controls. CONCLUSION: Children with PWS can be motivated by their families to follow a short daily training, which has general effects on PA and does increase, but not normalize LM.

Improving body composition and physical activity in Prader-Willi Syndrome.

OBJECTIVE: To determine if muscle training in Prader-Willi Syndrome (PWS) can improve local body composition, physical capacity, and activity. STUDY DESIGN: Seventeen children and adolescents with PWS and 18 control children were enrolled in a daily short calf muscle training program for 3 months. Before (t(0)) and after 3 months of training (t(3m)), spontaneous physical activity and exercise capacity were assessed by pedometer registrations and activity protocols. Local body composition was determined by calf circumference and skinfold measurements at t(0), t(3m), and 3 months after t(3m) (t(6m)). RESULTS: During training, calf skinfold decreased from 1.1 to 0.8 SD (P <.01) and calf circumference in PWS increased from 1.4 to 1.9 SD (P <.05), reflecting improved muscle mass. At t(3m), a significant increase in spontaneous physical activity (from 45% to 71%, compared with baseline data of control children, P <.05) and physical capacity (from 31%-78%, P <.01) was found. CONCLUSIONS: In persons with PWS, a well-defined and easy-to-accomplish training program improves local body composition and has generalized effects on physical activity and capacity, opening up a new therapeutic option to improve metabolic conditions.