Early vibration assisted physiotherapy in toddlers with cerebral palsy - a randomized controlled pilot trial.

OBJECTIVES: to investigate feasibility, safety and efficacy of home-based side-alternating whole body vibration (sWBV) to improve motor function in toddlers with cerebral palsy (CP). METHODS: Randomized controlled trial including 24 toddlers with CP (mean age 19 months (SD±3.1); 13 boys). INTERVENTION: 14 weeks sWBV with ten 9-minute sessions weekly (non-individualized). Group A started with sWBV, followed by 14 weeks without; in group B this order was reversed. Feasibility (≥70% adherence) and adverse events were recorded; efficacy evaluated with the Gross Motor Function Measure (GMFM-66), Pediatric Evaluation of Disability Inventory (PEDI), at baseline (T0), 14 (T1) and 28 weeks (T2). RESULTS: Developmental change between T0 and T1 was similar in both groups; change scores in group A and B: GMFM-66 2.4 (SD±2.1) and 3.3 (SD±2.9) (p=0.412); PEDI mobility 8.4 (SD±6.6) and 3.5 (SD±9.2) (p=0.148), respectively. In two children muscle tone increased post-sWBV. 24 children received between 67 and 140 sWBV sessions, rate of completed sessions ranged from 48 to 100% and no dropouts were observed. CONCLUSION: A 14-week home-based sWBV intervention was feasible and safe in toddlers with CP, but was not associated with improvement in gross motor function.

Clinical and genetic findings in a family with NMNAT1-associated Leber congenital amaurosis: case report and review of the literature.

BACKGROUND: Leber congenital amaurosis (LCA) is a severe retinal dystrophy, typically manifesting in the first year of life. Mutations in more than 18 genes have been reported to date. In recent studies, biallelic mutations in NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 have been found to cause LCA. PURPOSE: To broaden the knowledge regarding the phenotype of NMNAT1-associated LCA. METHODS: Clinical ophthalmologic examinations were performed in two sisters with LCA. Whole exome sequencing was performed in one of the affected girls, with subsequent segregation analysis in the affected sister and unaffected parents. The literature was reviewed for reports of NMNAT1-associated LCA. RESULTS: Exome sequencing revealed the known NMNAT1 mutation c.25G>A (p.Val9Met) in a homozygous state. Segregation analysis showed the same homozygous mutation in the affected younger sister. Both parents were found to be heterozygous carriers of the mutation. The two girls both presented with severe visual impairment, nystagmus, central atrophy of the pigment epithelium, and pigment clumping in the periphery before the age of 6 months. Retinal vessels were attenuated. Both children were hyperopic. In the older sister, differential diagnosis included an inflammatory origin, but electrophysiology in her as well as her sister confirmed a diagnosis of LCA. Pallor of the optic nerve head was not present at birth but developed progressively. CONCLUSIONS: We confirmed a diagnosis of NMNAT1-associated LCA in two siblings through identification of the mutation (c.25G>A [p. Val9Met]) in a homozygous state. In infants with non-detectable electroretinogram (ERG), along with severe congenital visual dysfunction or blindness and central pigment epithelium atrophy with pigment clumping resembling scarring due to chorioretinitis, LCA due to NMNAT1 mutations should be considered.

Angiotensin II receptor blocker induced fetopathy: 7 cases.

BACKGROUND: During a period of 12 months 7 newborns with a partially severe fetopathy caused most probably by maternal sartan-intake in pregnancy were treated in 5 German teaching hospitals. Sartans antagonize the effect of angiotensin II at the AT1-receptor and are used to treat arterial hypertension. METHOD: We presented 2 cases at the yearly GNPI meeting 2010 and we were informed about similar cases in other German teaching hospitals which we brought together in this publication. RESULTS: In the presented cases, maternal sartan intake was noticed at different times in pregnancy and was in part discontinued some weeks before delivery. In all pregnancies oligohydramnios was present and fetal kidneys displayed a hyperechogenic structure on ultrasound. The newborns' postnatal course varied: oligohydramnios sequence with lung hypoplasia, arterial hypotension and renal insufficiency were the predominant problems of the first days of life. The majority (4/7) of infants did not survive this period, in other cases there was a complete (1/7) recovery of renal function whereas others survived with renal impairment (2/7), in part requiring chronic dialysis. Further distinctive features seen frequently were disturbances of cranial ossification and flaccid paralysis of hands and feet with deviations as well as sensorineural hearing loss. CONCLUSION: These case reports again underline the hazardousness of maternal sartan intake with potential fatal outcome for the newborn. Though the use of sartans in pregnancy is contraindicated and several case reports of sartan induced fetopathies exist, the risk of sartan treatment generally seems to be underestimated.

[Neuro-ophthalmological and ophthalmological findings in Joubert syndrome]. / Neuroophthalmologische und ophthalmologische Befunde beim Joubert-Syndrom.

BACKGROUND: Joubert syndrome (JS) belongs to the ciliopathies and is a mostly autosomal recessively inherited disease (in the case of OFD1 mutations, JS is an X-linked trait). It is characterised by midbrain-hindbrain malformations with developmental delay, hypotonia and ataxia and a broad spectrum of other facultative findings. The aim of our study was to examine the ophthalmological and neuro-ophthalmological features of JS in our patients and to compare our findings to those of other studies. METHODS: In a retrospective study we evaluated the ophthalmological and neuro-ophthalmological findings of 9 consecutive patients who met the diagnostic criteria of JS. RESULTS: All patients had abnormalities of ocular motility, 4/9 used head thrusts to shift gaze (oculomotor apraxia OMA). In 6/8 patients, the optokinetic reflex (OKN) was absent. Furthermore, 8/9 children showed nystagmus, mostly see-saw nystagmus. Manifest strabismus was found in 8/9 while 3/9 had a retinopathy with either abnormal ERG and/or fundus appearance with or without visual impairment. Chorioretinal colobomata were present in 5/9 cases. Two patients showed a unilateral congenital ptosis, one a facial nerve paresis. CONCLUSIONS: The early neuro-ophthalmological findings in JS are not pathognonomic, but may lead to the diagnosis of JS. The syndrome should be suspected in patients with nystagmus, especially see-saw nystagmus, and abnormal OKN and/or OMA, and/or colobomata of the fundus, and further paediatric examinations should be initiated.

[Strabologic and neuro-ophthamologic aspects of childhood cancer]. / Strabologische und neuroophthalmologische Aspekte kindlicher Tumorerkrankungen.

Pediatric oncology has achieved major progress by continuous optimization of diagnostic and therapeutic approaches. In the interdisciplinary team, the ophthalmologist plays an important role. In the field of strabismus and neuro-ophthalmology clinical symptoms as strabismus, visual loss, anisocoria, visual field defects, and involuntary eye movements may be key indicators of childhood cancer. The appropriate diagnostic workup as well as the diagnostic and therapeutic steps during the course of the disease are important often requiring individually tailored approaches.

Analysis of cancellous bone turnover by multiple slice analysis at distal radius: a study using peripheral quantitative computed tomography.

We compared the results of peripheral quantitative computed tomography (pQCT) measurements (XCT-900; Stratec) at the 4% site of the distal radius (section 1; slice thickness of 2 mm) and in two proximally adjacent sections (sections 2 and 3). The study population consisted of 138 ambulatory patients (age 16.4 +/- 5.6 yr; mean +/- SD; 71 female) who were referred to a pediatric densitometry unit. Total volumetric bone mineral density (BMD) increased, whereas the area of the radial cross-section decreased in a proximal direction. There was a decrease in bone mineral content between sections 1 and 3, which was more pronounced in subjects under age 16. Cancellous BMD significantly decreased from section 1 to 3 only under the age of 16. In 12 patients under age 17 who suffered from increased bone fragility, cancellous BMD decreased about 2.5 times more between sections 1 and 3 than in age-matched patients who received anticonvulsant therapy but had a normal neurologic and musculoskeletal status (-21.4% +/- 16.9 vs -8.1% +/- 6.3; p = 0.02). This suggests that in the bone fragility group, trabeculae were removed faster during longitudinal growth of the radius. In conclusion, multiple slice analysis may provide information on the dynamic turnover of metaphyseal trabeculae during growth.

Right sternoclavicular dislocation after traumatic delivery: a case report.

Sternoclavicular (SC) dislocation is an injury that is very rare in the newborn. Thus far there have been no reports describing this in neonates after a traumatic birth injury. This condition can be difficult to differentiate from epiphyseal separation, which occurs more often in older children. For successful treatment, early diagnosis is essential. Timely surgical reposition and fixation with following immobilization is recommended in instances of complete (SC) dislocation. We report a trauma-induced case of SC dislocation in a neonate successfully managed by polydioxanon cord fixation.

G/A polymorphism at -258 of the hepatic glucokinase promoter is not associated with decreased birth weight in preterm neonates.

BACKGROUND: A high percentage of preterm neonates are born small for gestational age (SGA). These children show a high morbidity and mortality after birth and often develop insulin resistance with ensuing impaired glucose metabolism in adulthood. Since insulin is important for intrauterine growth, fetal insulin resistance might also influence birth weight of preterm neonates. OBJECTIVES: A common polymorphism in the promoter region of the human hepatic glucokinase (-258) is associated with a decreased promoter activity, an enhanced insulin secretion, and hypertension and hepatic insulin resistance in adults. In this pilot study we wanted to investigate whether the G/A polymorphism at -258 of the hepatic glucokinase promoter has an effect on birth weight of preterm neonates and therefore might constitute a genotype leading to low birth weight and metabolic defects. METHODS: We enrolled 106 preterm neonates in our study. 44 of them were SGA and 62 AGA neonates. We extracted DNA from a buccal swab and identified the polymorphism by PCR-ARMS. RESULTS: We found no difference in the prevalence of the polymorphism in either groups. CONCLUSION: The polymorphism at -258 of the fetal hepatic glucokinase promoter is most probably not of a major relevance in the pathophysiology of low birth weight in preterm neonates.

Nifedipine in hypertensive crises of infants and children.

Nifedipine given by the sublingual route has been used in the treatment of 30 hypertensive emergencies in 20 children suffering from renal disease. The mean dosage of nifedipine was 0.33 mg/kg body weight. In 20 hypertensive crises occurring in 16 patients a single dose of nifedipine was sufficient to lower systolic as well as diastolic blood pressure significantly within 90 min. for a period of 4 to 12 hours. No side effects were noted with the exception of a transient flush in one patient. Nifedipine proved to be suitable for the primary treatment of hypertensive emergencies in children suffering from renal hypertension. The advantages of nifedipine compared to other drugs used for treating hypertensive crises is the rapid onset of the antihypertensive action without need for an intravenous form of administration.

[Mathematical models in hematology]. / Mathematische Modelle in der Hämatologie.

The use of mathematical models in haematology is shown by some examples concerning stem cell kinetics, erythropoiesis and thrombopoiesis. At first, model assumptions are formulated which include the biological knowledge and some regulatory hypotheses. Then, the reaction of the model on stimulation and suppression is calculated. Finally, by comparison with experimental or clinical data one can evaluate how far the model assumptions are sufficient to understand the measurements. Thus one can exclude wrong hypotheses and identify the important regulatory influences.

The kinetics of hematopoietic stem cells during and after hypoxia. A model analysis.

A previously described mathematical model of the hematopoietic stem cell system has been extended to permit a detailed understanding of the data during and after hypoxia. The model includes stem cells, erythroid and granuloid progenitors and precursors. Concerning the intramedullary feedback mechanisms two basic assumptions are made: 1) The fraction "a" of CFU-S in active cell cycle is regulated. Reduced cell densities of CFU-S, progenitors or precursors lead to an accelerated stem cell cycling. Enlarged cell densities suppress cycling. 2) The self renewal probability "p" of CFU-S is also regulated. The normal steady state is described by p = 0.5, indicating that on statistical average each dividing mother stem cell is replaced by one daughter stem cell, while the second differentiates. Diminished cell densities of CFU-S or enlarged densities of progenitors and precursors induce a more intensive self renewal (p greater than 0.5), such that the stem cell number increases. The self renewal probability declines (p less than 0.5) if too many CFU-S or too few progenitors and precursors are present. The model reproduces bone marrow data for CFU-S, BFU-E, CFU-C, CFU-E, 59 Fe-uptake and nucleated cells in hypoxia and posthypoxia. Although the ratio of differentiation into the erythroid and granuloid cell lines is kept constant in the model, a changing ratio of CFU-E and CFU-C results. The model suggests that stem cells and progenitor cells are regulated by a regulatory interference of erythropoiesis and granulopoiesis.

Cerebral complications in Schimke immuno-osseous dysplasia.

UNLABELLED: Schimke immuno-osseous dysplasia is a multisystem disorder consisting of spondylo-epiphysial dysplasia, progressive renal insufficiency due to focal segmental glomerulosclerosis, and immunodeficiency. Cerebrovascular complications have only been described in five patients. Here we report a patient with prominent neurological symptoms most likely caused by transient ischaemic attacks. CONCLUSION: Neurological symptoms consisted of repeated brief spells of hemiparaesthesia, motoric aphasia and diplopia. MRI studies of the CNS revealed progressive white matter lesions. Morphological changes as well as neurological deficits are compatible with cerebral ischaemia.

Analysis of the musculoskeletal system in children and adolescents receiving anticonvulsant monotherapy with valproic acid or carbamazepine.

OBJECTIVE: To examine bone development in children and adolescents who have uncomplicated idiopathic epilepsy and had received monotherapy with carbamazepine or valproic acid for at least 1 year. METHODS: Thirty-nine patients from 6 to 19 years of age (18 girls) were studied. Total bone mineral content (BMC) and trabecular volumetric bone mineral density were measured at the distal radius using peripheral quantitative computed tomography. Maximum isometric grip force was determined with a standard dynamometer. Alkaline phosphatase activity and deoxypyridinoline (a marker of bone resorption) were assessed in serum and urine, respectively. RESULTS: Trabecular volumetric bone mineral density was significantly decreased in the entire group (z score mean +/- standard deviation: -0.62 +/- 1.04) and in the subgroup using valproic acid (-0.75 +/- 1.18). In the carbamazepine subgroup, there was a similar but nonsignificant trend (-0.50 +/- 0.90). Total BMC and isometric maximum grip force were normal in the entire study population (0.10 +/- 1.22) and in the 2 subgroups. The relationship between BMC and grip force was similar between patients and healthy participants. Urinary levels of deoxypyridinoline were significantly elevated above normal in the whole study population (1.35 +/- 2.00) and in both the valproic acid and the carbamazepine subgroups. CONCLUSIONS: Bone turnover can be increased, but bone mass is adequate in children and adolescents who have uncomplicated idiopathic epilepsy and who receive monotherapy with carbamazepine or valproic acid.

Di-(2-ethylhexyl)-phthalate as plasticizer in PVC respiratory tubing systems: indications of hazardous effects on pulmonary function in mechanically ventilated, preterm infants.

Several PVC medical devices contain the plasticizer Di-(2-ethylhexyl)-phthalate (DEHP) in high concentration. Taken systematically DEHP only has minor toxic effects in the human organism. In three preterm infants artificially ventilated with PVC respiratory tubes unusual lung disorders resembling those observed in hyaline membrane disease, verified both clinically and radiologically, were observed during the fourth week of life. It was assumed that these lung disorders were causally related to the exposure to high doses of DEHP, which was released from the walls of the respiratory tubes. DEHP was found in the lung tissue of one patient who died of pneumothorax soon after birth after being artificially ventilated. It is strongly recommended that for disposable PVC respiratory devices the plasticizer DEHP should be used with more restrictions.

[Transient neonatal myasthenia gravis]. / Transiente neonatale Myasthenia gravis.

Ten to twenty percent of the offspring of mothers suffering from myasthenia gravis (MG) also develop transient neonatal MG, since maternal antibodies are able to cross the placenta. We report the course of two newborns of a mother with MG and a healthy father. The first pregnancy was complicated during the 3rd trimester by a hydramnion. The newborn presented with generalized muscle weakness, respiratory distress, weak sounding, anaemia, and poor sucking. Mechanical ventilation was necessary. Confirmation of the diagnosis was achieved by the result of repetitive muscle stimulation, showing a typical decrement in the EMG, and measurement of serum antiacetylcholin receptor antibodies. For 3 months, the infant was treated with neostigmin (cholinesterase inhibitor). After 26 days of hospitalization, the patient was released and followed up regularly. Myasthenic symptoms completely resolved. Side effects of the treatment were not observed. The course of the second pregnancy was normal. This second newborn was healthy. Our case report is remarkable for the very different presentation of two children of the same mother with MG during pregnancy and after delivery, with one child developing severe transient neonatal MG, initially requiring intensive care unit (ICU) treatment followed by quick recovery, and one child being healthy. We also present a score for monitoring the clinical course and adjusting anticholinesterase therapy accordingly.