[Bilateral spastic paresis without the ability to walk]. / Bilaterale spastische Paresen ohne Gehfähigkeit.

BACKGROUND: Developmental disorders and severe damage to major parts of the brain cause loss of motor, sensor, cognitive and mental function. These disorders cannot be medically treated in a sufficiently curative manner and are likely to develop into severe disability in children and adults. THERAPY: Medical nursing care and treatment aims to achieve the best possible quality of life by a lack of pain, ability to communicate, autonomy, and activities of daily life. As part of the team neuro-orthopedic surgeons have to analyze the orthostatic effects of motor functional disorders in order to set up a treatment plan that includes preventive and palliative treatment options by movement therapy, orthotic, medicinal, and surgical interventions. CONCLUSION: Pain and severe progressive deformities, such as contracture of extremity joints, hip dislocation, and spinal deformity must be prevented as far as possible. Activities of daily life should be enhanced by balancing and promoting muscle power and stabilizing weak and unstable parts of the body when possible.

[Quality assurance in the orthopaedic management of neuromuscular diseases]. / Qualitätssicherung in der Neuroorthopädie.

Increased interest in quality improvement has been brought about by advances in medical technology, health economics and social attitudes over the past decades. Targeted evaluation of infrastructure as well as therapeutic pathways and outcomes can help both patient and carer to achieve optimal treatment processes and a low error rate by means of continuous improvements. While on the one hand there is an urgent need for quality evaluation of health care in disabled persons, on the other this evaluation is challenging since quality of life has to be evaluated for each individual case. Neuroorthopaedic care involves diagnosis, analysis, treatment and rehabilitation of orthopaedic disorders resulting from cerebral and neuromuscular diseases. The aim of treatment is to achieve the best possible quality of life from infancy through to old age, which is measured according to pain-free movement as well as on the ability to actively participate in a social environment. To measure therapeutic outcome, technical methods such as electronic gait analysis, functional scores, questionnaires on subjective satisfaction, as well as economic evaluation of the cost-benefit ratio. Furthermore, medical treatment and technical and logistical processes are evaluated. Evaluation of structure quality provides information on personnel, time, infrastructure, cooperation and knowledge resources.

The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa.

[Neuromodulation of spasticity in children by intrathecal baclofen]. / Neuromodulation der Spastik bei Kindern durch intrathekal verabreichtes Baclofen.

INTRODUCTION: Treatment with intrathecal baclofen (ITB) is an important part of the complex therapy of patients with cerebral spasticity aiming to improve the motoric functions and to reduce pain intensity. MATERIAL AND METHODS: ITB was started in the Orthopaedic Hospital in Speising in 1999. From 1999 to 2006 a total of 15 children aged 3 to 16 years old were selected for this special treatment. RESULTS: The average degree of spasticity according to Ashworth (scale 1-5) could be reduced by ITB from 4.38 to 3.0, the time spent sitting could be increased from 3.3 to 5.8h per day and the pain intensity (VAS 1-10) could be reduced from 4.2 to 0.6. The time necessary for nursing treatment was shortened from 7.5 to 3.4 (VAS 1-10). Also improved was the emotional situation, the ability to swallow, the posture of the head and the concentration ability. CONCLUSION: ITB provides neuromodulation even in pediatric patients with complex neuromotoric spasticity.

Decrease of Lp(a) during weight reduction in obese children is modified by the apo(a) kringle-IV copy number variation.

BACKGROUND: Lipoprotein(a) [Lp(a)] is considered an independent risk factor for cardiovascular disease. Its concentration is mainly determined by the kringle-IV repeat copy number variation (CNV) at the apolipoprotein(a) [apo(a)] locus. OBJECTIVE: We aimed to investigate the immediate effect of weight reduction on plasma Lp(a) levels and its dependency on the apo(a) CNV in obese children. DESIGN: We performed a prospective longitudinal intervention study of a low-fat hypocaloric diet conducted in a 3-week dietary camp for obese children. In all, 140 obese participants (54 boys and 86 girls) with a mean age of 12.5+/-1.6 years and a mean relative body mass index (BMI) before treatment of 165.6+/-24.7% were included. Body weight and plasma levels of Lp(a), lipids, apolipoproteins A-I and B, insulin, and C-reactive protein were determined before the onset and after the end of the intervention. In addition, the number of apo(a) kringle-IV repeats were determined using sodium dodecyl sulfate agarose gel electrophoresis. RESULTS: The mean loss of body weight was 5.0+/-1.3 kg (-6.6%), resulting in a mean decrease of the relative BMI of 6.6%. Blood chemistry revealed significant changes in all parameters, especially in Lp(a), with a decrease from 24.4+/-30.6 to 17.9+/-22.6 mg per 100 ml or -19% (P<0.001). The decrease of Lp(a) levels was higher in the group with low compared with high molecular weight apo(a) phenotypes (-23.9 vs -16.6%). CONCLUSIONS: Weight reduction in obese children is associated with significant changes in Lp(a) levels, especially in subjects with high pre-treatment Lp(a) concentrations. This effect is markedly influenced by the molecular phenotype at the copy-number variable apo(a) locus.

[The hip joint in neuromuscular disorders]. / Hüftgelenk bei neuromuskulären Erkrankungen.

Physiologic motor and biomechanical parameters are prerequisites for normal hip development and hip function. Disorders of muscle activity and lack of weight bearing due to neuromuscular diseases may cause clinical symptoms such as an unstable hip or reduced range of motion. Disability and handicap because of pain, hip dislocation, osteoarthritis, gait disorders, or problems in seating and positioning are dependent on the severity of the disease, the time of occurrence, and the means of prevention and treatment. Preservation of pain-free and stable hip joints should be gained by balancing muscular forces and by preventing progressive dislocation. Most important is the exact indication of therapeutic options such as movement and standing therapy as well as drugs and surgery.

Determinants of plasma apolipoprotein A-V and APOA5 gene transcripts in humans.

OBJECTIVE: Apolipoprotein A-V (apoAV) contributes to the regulation of triglyceride metabolism, which plays a role in the pathogenesis of atherosclerotic diseases. We therefore ascertained determinants of hepatic APOA5 transcript and apoAV plasma levels in humans. DESIGN: We determined influences of anthropometric variables, biochemical factors related to lipid and glucose metabolism, hepatic mRNA levels transcribed from the APOA1/C3/A4/A5 cluster and transcription factor genes implicated in the regulation of APOA5 as well as common single nucleotide polymorphisms (SNPs) at the APOA5 locus on APOA5 expression in 89 obese patients and 22 non-obese controls. RESULTS: Mean, age and sex adjusted, hepatic APOA5 mRNA or apoAV plasma levels did not differ by obesity status, homoeostasis model assessment insulin resistance or inflammatory markers. In multivariate regression models, the c56C > G SNP, plasma apoCIII, plasma nonesterified fatty acids, hepatic APOA5 transcripts, sex and a weak association with obesity status explained 61% of the variance in apoAV plasma levels. Hepatic transcript levels of carnitine palmitoyltransferase 1 (CPT1A1) and peroxisome proliferator-activated receptor alpha (PPARA), plasma nonesterified fatty acids and the c56C > G SNP explained 48% of the variance in hepatic APOA5 transcript levels. CONCLUSION: Apolipoprotein A-V plasma levels are independently associated with plasma free fatty acid and hepatic APOA5 mRNA levels. Associations of APOA5 transcripts with PPARA and CPT1A1 transcripts suggest that APOA5 expression is intimately linked to hepatic lipid metabolism.

Apolipoprotein AV does not contribute to hypertriglyceridaemia or triglyceride lowering by dietary fish oil and rosiglitazone in obese Zucker rats.

AIMS/HYPOTHESIS: Apolipoprotein AV (apoAV) is a recently discovered apolipoprotein with a triglyceride-lowering effect in genetically modified mice. Transcription of the human gene encoding apoAV (APOA5) is suppressed by insulin and stimulated by fibrates. Our goal was to study the expression of Apoa5, in comparison with Apoa4 and Apoc3, in hypertriglyceridaemic, obese and insulin-resistant Zucker rats receiving the insulin sensitiser rosiglitazone and/or a fish oil diet to lower triglycerides. METHODS: Hepatic Apoa5, Apoa4 and Apo3 mRNA and liver and plasma apoAV were measured in lean and obese Zucker rats receiving rosiglitazone while on a coconut oil or fish oil diet. RESULTS: Basal hepatic Apoa5 expression was similar in obese and lean Zucker rats. Unexpectedly, obese Zucker rats tended to have higher plasma apoAV levels despite their hypertriglyceridaemic state. Both rosiglitazone and the fish oil diet significantly increased Apoa5 mRNA, by about 70%, but tended to lower liver and plasma apoAV. Rosiglitazone had no effect on Apoa5 mRNA in cultured rat hepatocytes. No intact PPAR (peroxisome proliferator-activated receptor) response element was identified in the rat Apoa5 promoter. CONCLUSIONS/INTERPRETATION: Our data indicate that apoAV does not contribute to the hypertriglyceridaemia of obese Zucker rats or to the hypolipidaemic effect of rosiglitazone or a fish oil diet. The divergent changes of Apoa5 mRNA and apoAV levels suggest co- or post-translational regulation. The increase in Apoa5 mRNA induced by rosiglitazone is not directly mediated by peroxisome proliferator-activated receptor gamma.

Decrease of plasma apolipoprotein A-IV during weight reduction in obese adolescents on a low fat diet.

OBJECTIVE: Apolipoprotein (apo) A-IV is an antiatherogenic apolipoprotein, which may be involved in the regulation of food intake. Plasma apoA-IV is elevated in human obesity and apoA-IV polymorphisms have been associated with the extent of obesity. Our aim was to determine the effects of weight loss on plasma apo-IV in obese adolescents and to examine the relation of apoA-IV with the degree of obesity. DESIGN: Longitudinal intervention study of a low fat hypocaloric diet conducted in a dietary camp. SUBJECTS: Two groups of obese adolescents (n=47 and n=29), age: 12.7+/-1.7 and 11.7+/-2.6 y, relative body mass index (RBMI): 168+/-24 and 175+/-34%, respectively. MEASUREMENTS: Plasma total apoA-IV, apoA-I, apoB, plasma distribution of apoA-IV, leptin, lipids, and lipoproteins before and after 3 weeks of weight reduction. RESULTS: Plasma apoA-IV decreased from 11.5+/-4.1 mg/dl before to 6.7+/-2.2 mg/dl after weight reduction in the first group (P<0.001) and to a similar extent in the second group. The relative amount of lipid-free apoA-IV and apoA-IV associated with apoA-I increased slightly, whereas apoA-IV associated with lipoproteins devoid of apoA-I decreased. ApoA-IV levels before and after weight reduction and the changes in plasma apoA-IV did not independently correlate with RBMI, weight loss, or plasma leptin. CONCLUSION: Plasma apoA-IV decreases markedly in overweight adolescents undergoing short-term weight reduction. The decrease is not directly related to the degree of weight loss and the mechanisms underlying this reduction remain to be clarified.

[Neurogenic spinal deformities. II. Sitting and seating devices: principles and indications]. / Neurogene Wirbelsäulendeformitäten. Teil 2: Sitzen und Sitzhilfen--Prinzipien der Anpassung.

Sitting is a dynamic process regulated by motor reactions due to endogenic and exogenic influences. Patients with neuromuscular disorders may not continuously adapt their sitting posture but seating devices may improve their quality of life. Prerequisites for the indication of high quality and cost effective seating devices are guidelines for planning and fitting which consider both pathomorphologic mechanisms and the patient's personality. In order to avoid functional problems and pain caused by an insufficient seating device it is necessary to pay attention to the exact indication, time, and combination of technical options. Planning within a seating clinic needs teamwork. First the goal of treatment is defined; it depends on the functional deficit, on the daily living activities of the patient, and on the social environmental factors. Second fitting of the devices follows defined treatment guidelines. By examination of the sensoric and statomotoric system it is possible to classify the patient's sitting or seating ability for simplifying indication: three groups of active sitters who are able to change position of trunk and pelvis actively are differentiated from three groups of passive sitters who have to be seated.

Patient safety technology for microadsorbent systems in extracorporeal blood purification.

Alternative technologies for extracorporeal blood purification systems based on microadsorbents in suspension are discussed. Principally, microadsorbents offer higher efficiency and flexibility when compared to conventional column-based adsorption systems. Systems already clinically employed (e.g., BioLogic DT) or close to clinical application (e.g., the microspheres-based detoxification system, MDS) are described. The MDS technology, in particular, is characterized by efficiency and a high degree of flexibility with respect to both the use of different adsorbents as well as the combination with hemodialysis/hemofiltration therapy. It was designed for continuous use in intensive-care units, but enables also the removal of low-density lipoprotein, fibrinogen, autoimmune antibodies, immune complexes, and other pathophysiologically relevant substances. Alternative anticoagulation regimes and safety systems on fluorescence sensor technology have recently been developed for the MDS and are presented in this paper.

[Single event multilevel surgery to improve gait in diplegic cerebral palsy - a prospective controlled trial]. / Operative Mehretageneingriffe zur Gangverbesserung bei spastischer Diplegie - Eine prospektive kontrollierte Untersuchung1.

AIM: To evaluate prospectively the outcome of gait-improvement surgery in children with spastic diplegia. METHOD: Three-dimensional gait analysis was performed in twenty children with spastic diplegia. Ten children underwent single event multilevel surgery for gait improvement. Indications for individual procedures followed a fixed set of selection criteria. The other ten children continued with their physiotherapy programme and served as a control group. A second gait analysis was performed in all children after 1.5 years. Time-distance parameters and kinematics of the pelvis, hip, knee and ankle joints in the sagittal plane served as main outcome measures RESULTS: The patients walked faster with an increased stride length after surgery in comparison to the conservatively treated controls. The average pelvic tilt increased slightly and the range of motion of the knee joint increased considerably after multilevel surgery. The motion at the ankle remained unchanged over the study period in both the groups. An improved knee extension during the stance phase of gait served to improve stance limb stability and facilitated an unhindered swing phase of the opposite limb. CONCLUSION: This prospective trial showed favourable changes in gait function after multilevel surgery in spastic diplegic children.

Clinical and neuropsychological outcome in 33 patients with biotinidase deficiency ascertained by nationwide newborn screening and family studies in Austria.

UNLABELLED: Newborn screening for biotinidase deficiency (BD) provides prevention of neurological sequelae in patients with low residual enzyme activity by early treatment with oral biotin substitution. Screening 1.1 million newborns in Austria and consecutive family studies led to the identification of 21 patients with profound BD (residual activity <10%) (incidence: 1:59,800) and to 12 patients with partial BD (residual activity 10%-30%) (incidence 1:89,700). Application of an HPLC assay using the natural substrate biocytin allowed exact quantification of extremely low residual biotinidase activities and thus subdivision of patients with profound BD into a group with a residual activity 0%-1% of normal activity (n = 5) and >1%-<10% (n = 16) respectively. Evaluation of clinical and neuropsychological outcome showed that only patients with a biotinidase activity < 1% (n = 3/5) exhibited characteristic clinical symptoms within the first weeks of life, while five patients with a residual activity of 1.2%-4.6% did not develop clinical symptoms even when not treated until 3.5 21 years. In all patients with residual activity <10% and biotin substitution within the first weeks of life, neuropsychological outcome was normal, while abnormal in three out of five patients tested for IQ and treated after the age of 3.5 years. In five out of nine patients with poor compliance or delayed or no treatment, visual and brainstem auditory evoked potentials were measured and were within age-related normal values. All patients with partial BD available for follow-up remained clinically and neuropsychologically asymptomatic without treatment at ages 2.5 10 years. CONCLUSION: The incidence of biotinidase deficiency in Austria is comparable to other European countries. Subdivision of the group of patients with profound biotinidase deficiency suggests that only patients with residual activities < 1% are prone to develop clinical symptoms early in life, while patients with residual activities >1% may remain asymptomatic even without treatment, as do patients with partial deficiency. Moderate mental retardation might represent a possible manifestation of cerebral dysfunction in patients with profound biotinidase deficiency.

[Botulinum toxin type A in the treatment plan for cerebral palsy]. / Botulinumtoxin Typ A bei Spastizität im Kindesalter.

Over the past decade a number of placebo-controlled studies have confirmed that intramuscular injections of botulinum toxin A (BTX A) has antispastic effects. Cerebral palsy is among the most frequent disorders of the growing locomotor apparatus during childhood. Weakness as well as spasticity due to lack of selective neuronal control causes functional impairment and additional mechanisms of compensation, retardation of motor development, secondary deformities of muscles and soft tissues due to a failure of muscle growth, subluxation/dislocation of joints, early osteoarthritis, and pain. Prevention of this vicious circle has to be the main goal of caring for children with spasticity. Quality of life in children with cerebral palsy can be improved by support of their daily living motor activities. Increased muscle tone can be reduced by physical exercises, by individually adapted orthoses, walkers, and wheelchairs, by manual therapy, serial casting and in certain cases by systemic drugs or by multiple-stage surgical procedures. BTX A can be used to enable these treatment possibilities or to increase their effect. In our clinical study (BTX A in 114 patients in 19952/2000) we found no major side effects. Weakness, pain or swelling occurred temporarily. Indications for the use of BTX A are pain, functional impairment, severe cosmetic problems, as well as prevention of secondary contractures, deformities, and dislocations caused by increased muscle tone. We consider the selection of patients for the use of BTX A and the development of a goal-orientated treatment plan by multidisciplinary team approach as the most important steps. Prerequisites are exact statomotoric and dynamic physical examinations, and standardised movement analysis. 3-D-gait analysis and dynamic electromyography is used in cases where functional improvement of gait is the goal of BTX A-treatment.

Blood purification by a membrane technique--a new method for the effective removal of low-density lipoprotein cholesterol.

A membrane plasma fractionation (MPS) technique is applied in order to obtain selective removal of pathological plasma components from the extracorporeal circuit. An effective plasma fractionation procedure should be characterized by the highest possible removal of the pathological plasma components and, equally as important, the lowest unwanted protein losses caused mainly by adsorption to the membrane structure. In order to obtain a higher efficiency of the MPS procedure (high selectivity between removal of pathological plasma components and unwanted losses mainly represented by albumin) several methods such as thermofiltration, application of pulsate flow at the end of secondary filter, etc. have been developed. Clinical verification of these methods led to some improvement in MPS procedure but these results did not seem to be optimal. The main objective of this paper is to present a new two-stage membrane system utilizing a high flow recirculation circuit developed particularly, but not only, for effective removal of low-density lipoprotein cholesterol. The designed and developed system has been tested in vitro using several different plasma fractionation membranes. The results obtained indicated the importance of the membrane structure and membrane material on the efficiency of the tested plasma fractionation procedure. It was also found that it is possible to obtain negligible protein losses for some selected membrane structures applied in the assessed system. Based on preliminary results, it seems that the new two-stage membrane system proposed could be characterized by a very low range of unwanted protein losses leading to high effectiveness of the plasma fractionation procedure.

The genetic background modifies the effects of the obesity mutation, 'fatty', on apolipoprotein gene regulation in rat liver.

BACKGROUND: Obesity is associated with disorders of plasma lipid transport in many, but not in all obese subjects. The effects of obesity on the regulation of genes involved in plasma lipid transport may depend on specific mutations causing or contributing to obesity and/or on interactions of a specific obesity mutation with the genetic background. The 'fatty' (Glu269Pro) leptin receptor mutation causes severe obesity associated with hypertriglyceridaemia and altered hepatic apolipoprotein gene regulation in Zucker fatty rats. OBJECTIVE: To determine whether the effects of the obesity mutation 'fatty' on apolipoprotein gene regulation in rat liver depend on the genetic background. METHODS: We studied hepatic apolipoprotein (apo) A-IV, A-I, and C-III gene expression in obese rats carrying the 'fatty' mutation on the background of the Zucker or Wistar strain. RESULTS: Basal apoA-IV gene expression was increased in fatty rats of both strains, whereas apoA-I and apoC-III gene expression differed between Wistar and Zucker fatty rats: apoA-I gene transcription was reduced to half and apoC-III mRNA was increased two-fold in Wistar fatty, but not in Zucker fatty rats vs lean controls. A fish oil diet suppressed apoA-IV, but not apoA-I gene transcription in Wistar fatty rats, whereas in Zucker fatty rats apoA-IV transcription was unaffected, but apoA-I transcription was suppressed. CONCLUSIONS: Interactions of the 'fatty' leptin receptor mutation with the genetic background significantly affect the basal and diet-induced regulation of the apoA-IV, C-III and A-I genes in rat liver. The genetic background may therefore be a major determinant of the consequences of a specific obesity mutation for plasma lipid transport.