Cerebellar cleft: confirmation of the neuroimaging pattern.

We recently described the neuroimaging and clinical findings in 6 children with cerebellar clefts and proposed that they result from disruptive changes following prenatal cerebellar hemorrhage. We now report an additional series of 9 patients analyzing the clinical and neuroimaging findings. The clefts were located in the left cerebellar hemisphere in 5 cases, in the right in 3, and bilaterally in one child who had bilateral cerebellar hemorrhages as a preterm infant at 30 weeks gestation. In one patient born at 24 weeks of gestation a unilateral cerebellar hemorrhage has been found at the age of 4 months. Other findings included disordered alignment of the folia and fissures, an irregular gray/white matter junction, and abnormal arborization of the white matter in all cases. Supratentorial abnormalities were found in 4 cases. All but 2 patients were born at term. We confirm the distinct neuroimaging pattern of cerebellar clefts. Considering the documented fetal cerebellar hemorrhage in our first series, we postulate that cerebellar clefts usually represent residual disruptive changes after a prenatal cerebellar hemorrhage. Exceptionally, as now documented in 2 patients, cerebellar clefts can be found after neonatal cerebellar hemorrhages in preterm infants. The short-term outcome in these children was variable.

[Pediatrics]. / Pédiatrie.

This year we present three papers on recent advances in paediatrics from the fields of neonatology, adolescent medicine and Duchenne muscular dystrophy. 1. Recent studies question the application of pure oxygen for neonatal reanimation and suggest that lower concentrations or even air may be more adequate for the reanimation of most newborns. 2. Bullying is an aggressive, repetitive and intentionally blessing behaviour. It is observed mainly at school and the victims are usually children with a weak personality or children suffering from chronic diseases. The doctor's role is to detect this behaviour and to help protect the victims. 3. The respiratory surveillance of patients with Duchenne muscular dystrophy is the corner-stone of their management. An algorithm allows to time correctly the initiation of non-invasive ventilation and to insure as long as possible a good life quality.

[Pediatrics]. / Pédiatrie.

This article summarizes the medical progress achieved in 2 frequent and 2 rare pathologies: 1. Cryptorchidism should be operated around 12 months of age and hormonal treatment abandoned in order to maintain fertility and avoid development of testicular tumors. 2. For the treatment of streptococcal pharyngitis oral cephalosporins for 4 to 5 days are equivalent to a Penicillin treatment of 10 days. 3. Thanks to carvedilol (a beta-blocker agent), levosimendan (a calcium sensibiliser) and nesiritide (an analog to the natriuretic peptide) a new hormonal approach to cardiac failure is possible. 4. Corticosteroids allow to improve quality of live and life expectancy in Duchenne muscular dystrophy, provided treatment starts early and a multidisciplinary approach is assured.

Autosomal dominant nemaline myopathy: a new phenotype unlinked to previously known genetic loci.

We report a large family with a mild form of autosomal dominant nemaline myopathy and a new phenotype. Onset of symptoms was in infancy with hypotonia and motor delay. Weakness involved neck flexors, abdominal and proximal limb muscles. There was no bulbar, respiratory or foot dorsiflexion weakness and no slowness in movement. Patients had remarkably good physical endurance and no limitation in daily activities, but were slow runners since childhood. Nemaline rods were seen in less than 5% of muscle fibres. No linkage to the five known nemaline myopathy genes (alpha-tropomyosin-3, nebulin, alpha-actin, troponin T1 and beta-tropomyosin), to the ryanodine receptor gene (associated with core-rod myopathy) or to the 15q21-23 locus was found.

Morphological, clinical and genetic aspects in a family with a novel LAMP-2 gene mutation (Danon disease).

A family with several cases of severe cardiomyopathy and moderate myopathy is described, affecting two brothers and their cousin as well as their mothers. One boy died of sudden cardiac arrest at 17 years of age. The two brothers were treated with an implantable defibrillator and their mother died suddenly at 40 years of age. Muscle biopsy in males showed vacuolar myopathy in two cases, and no abnormality on standard staining in the third case. Cardiac biopsies showed hypertrophic and vacuolated fibres. Complete absence of LAMP-2 was demonstrated by immunohistochemistry on the vacuolated skeletal and cardiac muscle, but also on the morphologically normal skeletal muscle. Sequencing of LAMP-2 gene showed a novel S157X mutation in exon 4. Danon disease is a rare and potentially lethal cause of hypertrophic cardiomyopathy. Diagnosis can be made by immunohistochemistry performed on cardiac or muscle biopsy, and confirmed by genetic analysis, which also allows for easy family screening and counselling.

Craniofacial and cutaneous findings expand the phenotype of hereditary neuralgic amyotrophy.

BACKGROUND: Hereditary neuralgic amyotrophy (HNA) is an autosomal-dominant disorder associated with recurrent, episodic, painful, brachial neuropathy. The gene for HNA has been mapped to chromosome 17q25. Characteristic features including hypotelorism, short stature, and cleft palate occur in some patients. OBJECTIVE: To further characterize the clinical, neurologic, and craniofacial features in 27 patients from seven families with HNA. METHODS: Medical history, physical examination, and facial measurements were obtained. Facial measurements were also made on 60 healthy controls. RESULTS: Twenty-five patients had an average of three attacks of brachial neuritis. The right arm was involved more frequently. Cleft palate was present in four individuals. Facial measurements showed significant hypotelorism in HNA patients versus controls. Unusual skin folds and creases were observed on the necks of several individuals as well as on the scalp of one man: cutis verticis gyrata. In three families, deep skin creases were present on the limbs of infants and toddlers who were subsequently affected with HNA. CONCLUSIONS: The phenotypic consequences of the mutant hereditary neuralgic atrophy gene may include a wider spectrum than previously appreciated and involve nonneural tissue.

Home and hospital treatment of acute seizures in children with nasal midazolam.

Rectal diazepam is widely used in the treatment of acute seizures in children but has some disadvantages. Nasal/sublingual midazolam administration has been recently investigated for this purpose but never at home or in a general paediatric hospital. The aim of this open study was to determine the efficacy, the tolerance and the applicability of nasal midazolam during acute seizures in children both in hospital and at home. We included known epileptic children for treatment at home and all children with acute seizures in the hospital. In all, 26 children were enrolled, 11 at home and 17 in the hospital (including two treated in both locations); only one had simple febrile seizure. They had a total of 125 seizures; 122 seizures (98%) stopped within 10 minutes (average 3.6 minutes). Two patients in the hospital did not respond and in three, seizures recurred within 3 hours. None had serious adverse effects. Parents had no difficulties administering the drug at home. Most of those who were using rectal diazepam found that nasal midazolam was easier to use and that postictal recovery was faster. Among 15 children who received the drug under electroencephalogram monitoring (six without clinical seizures), the paroxysmal activity disappeared in ten and decreased in three. Nasal midazolam is efficient in the treatment of acute seizures. It appears to be safe and most useful outside the hospital in severe epilepsies, particularly in older children because it is easy for parents to use. These data should be confirmed in a larger sample of children. Its usefulness in febrile convulsions also remains to be evaluated.

Atypical presentation of Prader-Willi syndrome with cerebral venous thrombosis: association or fortuity?

A newborn female born at term was admitted at 28 hours for seizures and generalized hypotonia. Cerebral ultrasound showed a right temporal echogenic lesion confirmed on MRI and thought to be secondary to thrombosis of the vein of Labbé. The EEG showed epileptic discharges over the right temporal region. Extensive thrombotic studies revealed a transiently decreased PTT consistent with a prothrombotic state. The hypotonia did not resolve after the acute phase as expected, raising the possibility of another underlying cause. Because of a peculiar phenotype with almond-shaped eyes and bitemporal depression, Prader-Willi syndrome (PWS) was suspected. Methylation analysis confirmed PWS, FISH analysis excluded a deletion in 15q11-q13, maternal uniparental disomy (UPD) was confirmed. To our knowledge, this is the first report of the association of a neonatal venous thrombosis and a PW Syndrome.

The role of posterior fossa decompression in acute cerebellitis.

BACKGROUND: We present two cases of children who were diagnosed with cerebellitis with acute cerebellar swelling. This rare pathology is potentially fatal, and no clear treatment guidelines are described in the literature. DISCUSSION: Considering our experience, we discuss the different therapeutic strategies and propose aggressive surgical measures consisting of external ventricular drainage and posterior fossa decompression in case of failure of early response to medical treatment to limit secondary cerebellar and brainstem lesions.

Clinical and histologic findings in autosomal centronuclear myopathy.

Centronuclear myopathy (CNM) is a congenital myopathy characterized by chains of centrally located nuclei in a large number of muscle fibers. Clinically, an early-onset form was reported in several autosomal-recessive (AR) families and many sporadic patients, whereas a late-onset form was found in most autosomal-dominant (AD) families. The boundary between these two forms remains unclear, and the molecular basis of autosomal CNM is still unresolved. To better define the clinical and morphologic characteristics of autosomal CNM, the authors analyzed a series of 29 patients from 12 families. Two subgroups were identified in three AD families: two families had a relatively late onset of disease and a slow progression of diffuse weakness, whereas the third family, who had a similar clinical course, also presented a unique diffuse muscle hypertrophy. Two presumed AR families and seven sporadic patients were analyzed together, and three subgroups were identified: 1) an early-onset form with ophthalmoparesis; 2) an early-onset form without ophthalmoparesis; and 3) a late-onset form without ophthalmoparesis. Overall, 23 muscle biopsies were reviewed; a majority of patients had >20% central nuclei, fiber type 1 predominance, and a radial distribution of sarcoplasmic strands on oxidative stains. A marked endomysial fibrosis was observed in three sporadic patients with a relatively severe clinical course. The classification reported in this study will be useful for the diagnosis and the follow-up evaluation of patients with autosomal CNM and for the research into the molecular defects underlying the condition.

Local variability in respiratory syncytial virus disease severity.

Respiratory syncytial virus (RSV) lower respiratory tract infections are considered to be a serious disease in centres such as the Sophia Children's Hospital (Rotterdam, the Netherlands), but as more benign infections in others such as the Geneva Children's Hospital (Switzerland). To assess the clinical severity of RSV infections at the two sites, 151 infants primarily admitted with a virologically confirmed RSV infection were studied prospectively (1994-5) and retrospectively (1993-4) (55 infants in Geneva and 96 in Rotterdam). Parameters of RSV morbidity which were more severe in Rotterdam during the two winter seasons were apnoea (1.8 v 23.9%), the rate of admission to the intensive care unit (3.6 v 28.1%), mechanical ventilation (0 v 7.3%), and length of stay in hospital (6.8 v 9.1 days). In Geneva higher respiratory rates (59.2 v 51.2), more wheezing (65.5 v 28.8%), and more retractions (81.8 v 63.3%) were recorded. Fewer infants younger than 4 months (54.9 v 68.7%), but more breast fed infants (94.1 v 38.5%), were admitted in Geneva, although the morbidity parameters remained different after correction for these two variables in multivariate analyses. Thus unidentified local factors influence the pattern and severity of RSV infection and may affect the results of multicentre prophylactic and therapeutic studies.