[Vaccination status in very and extremely preterm infants at the age of 2 years--a nationwide pilot analysis]. / Impfstatus bei Frühgeborenen mit einem Geburtsgewicht unter 1500 g im Alter von 2 Jahren--eine deutschlandweite Piloterhebung.

Preterm infants are at increased risk of suffering from vaccine preventable diseases. Therefore it is recommended to vaccinate them in time at the same chronological age as full term infants. Several reports have shown that vaccinations of very and extreme low birth weight infants are often delayed but till now there are no data for Germany. Our study analysed the vaccination rates and suffered complications of 318 preterm infants with birth weights under 1 500 g at the age of 2 years from all over the country copying their vaccination-record and asking the parents to answer a questionnaire. The preterm infants received the first 3 doses of the pentavalent or hexavalent vaccines consequently (1st dose: 100%, 2nd dose: 100%, 3rd dose: 97.5%), whereas the booster dose was accomplished to a lesser extent (89.0%) during their second year of life. The majority of the vaccinations were administered delayed. Moreover, the preterm infants received the first doses of the pneumococcal conjugate vaccine and the measles-mumps-rubella vaccine quite consequently, but the booster dose was again injected less frequent. According to their parents 17.8% of these preterm infants suffered from non-severe adverse reactions and none of them had an episode of apnoea following the immunisation. In conclusion preterm infants in Germany receive their basic immunisations consequently, but often too late. There is still the need to improve the frequency of the booster dose application especially in the second year of life and to prevent delays of vaccinations.

[Long-term prognosis of former very and extremely preterm babies in adulthood in Germany]. / Langzeitprognose sehr kleiner Frühgeborener in Deutschland.

Previous studies about the prognosis of former very and extremely small preterm babies (birthweight <1500 g, gestational age <32 weeks) in Germany only reached till puberty. Well known are significant increases of cognitive deficits, cerebral palsy and sensory impairments in correlation with gestational age and compared with term newborns. After a pilot project at the Children's University Hospital in Wuerzburg we collected the data of 291 people from 10 different children's Hospitals in Germany who were born between Jan 1st 1979 and Dec 31st 1986. We could recognize a clear increase of surviving babies after 1982. 50 (17%) of them had a birth weight under 1000 g. 27% finished school with the highest grade ("Abitur"), 37% with a high school degree and 22% with a normal degree. Most of them are still in an occupational training. 22% referred about chronic bronchitis, 54% need spectacles, 19% have regular physiotherapy. By a questionnaire about the quality of life (KIDDO KINDL) we recorded criteria in the fields of physical and psychological wellness and the all day functioning which were without significant differences to a normal cohort. In addition there was no difference in the quality of life criteria between former preterm babies born in West-Germany and those born in East-German hospitals. Further analyses of these results are necessary. In conclusion we could find that quality of life in those former very preterm babies in Germany who are now in adulthood and took part in our study is not significantly worse in comparison with people without any risk factors in the perinatal period. For more exact analysis of many influencing factors on the long term prognosis of former very preterm babies a national multicenter study is absolutely necessary, especially for preterms under 1000 g birthweight.

Acute flaccid paralysis as initial symptom in 4 patients with novel E1alpha mutations of the pyruvate dehydrogenase complex.

We report on 4 boys from 3 families presenting initially in infancy with an acute onset of flaccid tetraparesis and areflexia, resembling Guillain-Barré syndrome (GBS). However, the cerebrospinal fluid (CSF) protein was normal, while serum and CSF lactate were elevated. All patients had recurrent similar episodes, usually associated with infections. Brain MRI showed T (2) hyperintensities in the basal ganglia in two boys, in one of them at the first clinical presentation; the other one had a normal brain MRI during the first episode. A third boy had a normal MRI twice but an increased lactate peak in the basal ganglia in (1)H-MR spectroscopy. Motor nerve conduction velocities (NCV) were normal in all patients. Biochemical analyses of muscle tissue, performed in two patients, revealed a deficiency of the pyruvate dehydrogenase (PDH). Molecular genetic analysis of the X-chromosomal E1alpha subunit of PDH showed three new mutations in phylogenetically conserved areas of the protein: Glu358Lys in patient 1; Arg88Lys in patient 2 and 3 (brothers); and Leu216Ser in patient 4. In conclusion, children with "atypical GBS" should be evaluated for a mitochondrial disorder, including pyruvate dehydrogenase deficiency, even after a first episode.

[Validity of care assessment in disabled and mentally retarded children]. / Validität der Pflegebegutachtung bei körperbehinderten und bei geistig behinderten Kindern.

16 children with spastic cerebral palsy and 25 mentally retarded children were assessed via the scales "Self-Care" and "Mobility" of the Pediatric Evaluation of Disability Inventory (PEDI). Age-adjusted PEDI scores were compared with the classification according to the three levels of the German statutory nursing insurance. Good correlations and highly significant dependence were found in children with spastic cerebral palsy but no dependence was seen in mentally retarded children. Apparently, assessment guidelines of the German statutory nursing insurance do not guarantee a valid assessment in all disabled children. In conclusion, future assessments of nursing needs in children should employ standardised assessment methods.

Bilateral deficit during short-term, high-intensity cycle ergometry in girls and boys.

Peak torque during an isokinetic bilateral knee extension or flexion is usually lower than the summed peak torque of two unilateral contractions, and this phenomenon is designated as bilateral deficit (BD). The objectives of this study were to determine whether a BD also exists for more complex, alternating movements (e.g., short-term, high-intensity cycling), and to assess the possible effects of gender and maturity. Forty children and adolescents performed two unilateral (ULWAnT) and one bilateral Wingate anaerobic test (BLWAnT). The highest power reached in any 3-s interval (peak power; PP), and the total mechanical work (TMW) performed during the test was determined. Individual BD for PP (BDpp, %) was calculated by dividing the PP in the BLWAnT by the sum of the PP values of both ULWAnTs. The BD for TMW (BDTMw) was calculated in the same way. The sum of PP generated during the two ULWAnTs was larger than the PP measured in the BLWAnT (P<0.000001). The same difference was observed for TMW (P<0.0001). Maturity did not affect the BDpp or BDTMW (P=0.34). However, the BD was more pronounced in females compared to males (P= 0.03). In conclusion, a BD is evident during cycling exercise.

Effective and safe but forgotten: methsuximide in intractable epilepsies in childhood.

The efficacy and safety of methsuximide (MSM) was evaluated in children with intractable epilepsies in a prospective uncontrolled study. MSM was added to the therapeutic regimen of 112 children with intractable epilepsy under inpatient conditions, all of whom were therapeutically refractory to various first-line antiepileptic drugs (AED) or combinations of other AED. Titration of MSM was performed following a uniform protocol. Administration of MSM resulted in a 50% or greater reduction in seizure frequency in 40 patients after a short-term observation period (mean 9.1 weeks). After a mean of 3.7 years, the rate of seizures and side effects were re-evaluated in 39 patients who were still receiving MSM as part of their antiepileptic regimen. Twenty two of these patients derived long-term benefit from MSM. In patients with good seizure control, fasting plasma levels of N-desmethylmethsuximide, the principal active metabolite of MSM, were 25.3-44.7 mg l(-1)(mean 36.0 mg l(-1)). Thus effective plasma levels of N-desmethylmethsuximide in children were found to be higher than previously described. Forty one of 112 patients (28.9%) developed side effects during MSM treatment. No serious or irreversible side effects were seen. Our study demonstrates the value of MSM as an 'add-on' drug in intractable epilepsies.

Critical illness neuropathy in pediatric intensive care patients.

Critical illness neuropathy is an axonal polyneuropathy recognized more frequently in adult intensive care patients with sepsis and multiple organ dysfunction. In children the diagnosis is rarely made. Within 1 year the authors observed two children with critical illness neuropathy. Both patients, a male 6 years, 6 months of age with a brain contusion and a male 2 years, 6 months of age who underwent craniectomy for Crouzon's disease, required prolonged mechanical ventilation and developed sepsis with multiple organ dysfunction. Three to 4 weeks after successful treatment of the sepsis, a flaccid tetraparesis was noticed in both patients. Laboratory investigations of blood and cerebrospinal fluid and spinal magnetic resonance imaging revealed normal results. Electrophysiologic examinations were indicative of an axonal polyneuropathy. Spontaneous improvement occurred within several months. It is likely that critical illness neuropathy occurs more often in critically ill children than previously thought. Careful neurologic examination and early electrophysiologic investigations are necessary to establish the diagnosis. Important differential diagnoses of acquired lower motor neuron weakness in pediatric intensive care medicine are discussed.

Single-leg Wingate Test in children: reliability and optimal braking force.

PURPOSE: Single-leg cycle ergometry employing the protocol of the Wingate Test (WAnT) has been used to assess unilateral muscle power and leg-dominance. The objectives of this study were to determine the reliability of the single-leg WAnT (SLWAnT) and to establish optimal braking force for the SLWAnT. METHODS: Twenty female and 19 male subjects (prepubertals: 6.0-9.9 yr, 7 female and 6 male; midpubertals: 11.0-14.9 yr, 7 female and 7 male; and postpubertals: 17.0-20.9 yr, 6 female and 6 male) came to the laboratory on three occasions. On each visit, they first performed two SLWAnT after a standardized warm-up, one with each leg. Braking force for these tests was kept constant throughout all visits. On each of the following visits, subjects performed four additional SLWAnT, two with each leg, with braking force varying from test to test to determine the braking force associated with the highest performance over 30 s. RESULTS: Although a significant increase in performance was observed from visit to visit in some groups, intraclass correlation coefficients (which included trial-to-trial differences) of peak power and total work generated during the first two SLWAnT of each visit ranged from 0.89 to 0.98. Optimal braking force (J x rev(-1)) could be estimated from 0.4052 x body mass(1.4662) for all subjects irrespective of gender or maturity. The standard error of estimate was lowest in the prepubertals and highest in postpubertals (8.3-31.4 J x rev(-1)). CONCLUSIONS: SLWAnT is a highly reliable method to measure single-leg power. The above equation provides good estimates of optimal braking force. The SLWAnT can, therefore, be used to monitor changes in single-leg power and to assess leg-dominance.

[Current diagnosis in muscular dystrophies. New developments, methods of examination and case examples]. / Aktuelle Diagnostik bei Muskeldystrophien. Neue Entwicklungen, Untersuchungsmethoden und Fallbeispiele.

Recent progress in the field of molecular genetics revealed a broader spectrum of dystrophin-related disorders than previously assumed. In addition, the pathogenetic basis of other types of muscular dystrophies could be identified: some autosomal-recessive limb girdle dystrophies are caused by mutations of sarcoglycan genes, others are caused by deficiency of the sarcoplasmatic enzyme calpain-3. Emery-Dreifuss muscular dystrophy is due to the deficiency of the nuclear membrane protein emerin. About 50% of congenital muscular dystrophies are related to mutations of a extracellular matrix protein merosin (alpha-laminin). A series of monoclonal antibodies for immunohistochemistry is now available recognizing many cytoskeletal muscle proteins. In combination with molecular genetics a diagnostic flow chart can be developed which allows a definite diagnosis in most cases. In this review disease entities are illustrated by case reports. We discuss the significance of immunohistochemical and molecular methods for diagnosis.

Acute transverse myelitis in childhood: nine cases and review of the literature.

Acute transverse myelitis (ATM) is a rare disease in childhood and adolescence. It is characterized by paraplegia with or without sensory symptoms and bladder dysfunction, and typically manifests itself over a period of hours to 1 week. This is a report of nine patients who were treated between 1993 and 1996. To exclude treatable conditions, spinal and cranial MRI with and without contrast medium, electrophysiologic tests, and CSF examinations are performed as soon as possible after onset. At present post- or parainfectious inflammation is thought to be the most frequent cause of ATM. Some causes of ATM can be proved only by follow-up examination. The most important differential diagnoses are multiple sclerosis and Guillain-Barré syndrome with its variants. After exclusion of spinal cord compression, and if specific antibiotic treatment is not possible, a 3-day high-dose i.v. steroid pulse therapy is the most promising treatment. Prognosis is variable and residual symptoms are common. A controlled multicenter study is suggested to assess epidemiology, etiology, and prognosis of ATM.

Terminal deletion of the long arm of chromosome 10: a new case with breakpoint in q25.3.

Since the first patient with partial deletion of the long arm of chromosome 10 was described in 1978, another 23 cases have been reported, with the breakpoint ranging from 10q23.3-26.2. To contribute further to the delineation of the monosomy 10qter syndrome, we describe a female child who, at age 3 6/12 years, was diagnosed with a de novo deletion of the long arm of chromosome 10, with a breakpoint in 10q25.3. The phenotypic manifestations in this child are compatible with those of previously reported cases. However, in contrast to most other patients, we found a moderate expression of the syndrome, with no genitourinary or cardiac malformations and with only mild retardation. Based on our observations and those of others, we conclude that a typical craniofacial appearance and varying degrees of psychomotor retardation are always found in patients with 10q- syndrome.

Epilepsy in shunt-treated hydrocephalus.

Although epilepsy is commonly associated with shunt-treated hydrocephalus, its relation to the shunting procedure and the criteria identifying postoperative epilepsy remain controversial. Of 283 patients shunted at Würzburg University Hospital over a 24-year period (1970 to 1994), 182 were followed up for a minimum of 1 year after shunt insertion and entered the study. The data were analyzed retrospectively in 1995 and 1996. Epilepsy was analyzed in relation to the etiology of hydrocephalus, functional status, time and site of shunt insertion, onset of seizures and seizure type, EEG changes, sex, shunt systems, and shunt revisions. Of the 182 patients studied, 37 (20%) developed epilepsy. The incidence of epilepsy varied according to the etiology of hydrocephalus: posthemorrhagic (5%), postinfectious (4%), connatal/miscellaneous/unknown (3%), myelomeningocele (2%), tumor/arachnoidal cyst/aqueduct stenosis (0%). Early shunting and poor functional status was associated with a higher risk for epilepsy. Epilepsy was not influenced by sex, shunt systems, or number of shunt revisions. Twenty-two (12%) of 182 patients developed epilepsy (generalized N=13, focal N=9) after intracranial shunting. Focal EEG abnormalities (N=16) were located mainly at the anatomical site of the shunt (N=14), but only three patients (2%) presented with focal seizures contralateral and focal EEG abnormalities ipsilateral to the site of the shunt. The presence of epilepsy was determined by the etiology of hydrocephalus rather than by surgical intervention. The incidence of postoperative epilepsy (12%) was low. Onset of epilepsy, clinical presentation of seizures, and EEG changes did not appear to be valid criteria for identifying shunt-related epilepsy. Thus, epilepsy as a complication of intracranial shunting might be overestimated in the literature.

Neurophysiological findings in long-term survivors of acute lymphoblastic leukaemia in childhood treated with the BFM protocol 81 SR-A/B.

UNLABELLED: Monitoring of therapy-related late effects after acute lymphoblastic leukaemia (ALL) therapy in childhood has become an increasingly important field in posttherapeutic patient surveillance. The usefulness of neurophysiological investigations (e.g. EEG, evoked potentials (EP)) as part of these attempts is controversial. The present report focuses on this problem and the question whether and to what extent routinely performed EEG recordings and visual evoked potentials (VEP) were correlated with further measures of CNS integrity. EEGs and VEPs were recorded in 163 asymptomatic long-term survivors of ALL in childhood during a large retrospective multicentre study evaluating CNS late sequelae following antileukaemic therapy. Fifty-two ALL long-term survivors (4.5-10.6 years after end of therapy, median: 8.8 years), who had been treated according to BFM-81 SR-A (n = 30) or SR-B (n = 22) were selected for this analysis focusing on therapy-related CNS late effects. Therapy protocols differed with regard to the mode for CNS prophylaxis: SR-A, cranial irradiation with intrathecal methotrexate; SR-B, intrathecal and iv methotrexate. Neurophysiological findings were correlated with illness- and treatment-related parameters, as well as with data on the morphological, neurological and psychological status of the CNS. At the time of follow-up neurophysiological measures were abnormal in 28/52 cases (53.8%). Neither illness- nor therapy-specific differences in CNS prophylaxis showed any relationship to EEG/VEP outcome any relationship to EEG/VEP outcome in this reduced group of the whole study population. Children with EEG/VEP abnormalities showed a significantly higher incidence of structural CNS disturbances compared to those with inconspicuous neurophysiological recordings (60.9% vs 31.8%). However, in this special subject group there was no specific neurophysiological finding for a specific morphological substrate, neurological or psychological deficiency and vice versa. CONCLUSION: Routinely performed EEG/VEP investigations are not very helpful measures to predict the presence or degree of behavioural deficiencies, neurological disturbances, or morphological CNS abnormalities. Patients who received cranial irradiation or systemic methotrexate applications showed the same incidence of neurophysiological disturbances without evidence for specific neurotoxic correlates.