[Cerebrotendinous xanthomatosis: a multicentric retrospective study of 15 adults, clinical and paraclinical typical and atypical aspects]. / Étude rétrospective multicentrique de 15 cas adultes de xanthomatose cérébrotendineuse : aspects cliniques et paracliniques typiques et atypiques.

INTRODUCTION: Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an autosomal recessive inheritance, is secondary to deficiency of sterol 27-hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms include clinical or infraclinical xanthomas affecting the skin and tendons, early cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of the dentate nuclei and periventricular white matter hyperintensities. The diagnosis is based on an increased cholestanol level in serum, confirmed by the presence of a mutation in the CYP27A1 gene. Treatment is based on chenodeoxycholic acid. METHOD: We report a retrospective multicentric study of 15 cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical, molecular and MRI findings were recorded in all patients. RESULTS: The average age at diagnosis was 39years (range 27-65). Disease onset occurred in childhood in 73% of patients and in adulthood in 27%. All patients with a pediatric onset were diagnosed during adulthood (age range 28-65years). Clinical symptoms variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline, epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8), psychiatric disorders, cataract and xanthomas. One patient had an atypical presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in all: findings consisted in T2-weighted hyperintensity of the dentate nuclei (47%), periventricular leuoencephalopathy (73%) which preferentially involved the posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%), hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients. The most frequent mutation was 1183C>T (n=5/15). Under treatment with chenodeoxycholic acid, eight patients improved initially, followed by stabilization in five of them, and worsening in the others. Four patients died. CONCLUSION: Patients with the xanthoma-neurological disorder association should be tested for cerebrotendinous xanthomatosis. The disease often begins in childhood with a diagnostic delay but also in adulthood. Involvement of the dentate nuclei is specific but not sensitive and the supratentorial leucoencephalopathy is not specific but with an antero-posterior gradient. A vascular distribution and involvement of the corpus callosum are possible. Serum cholestanol assay is very reliable: an elevated level provides the diagnosis, which must nevertheless be confirmed by molecular biology.

Isolated tumefactive demyelinating lesions: diagnosis and long-term evolution of 16 patients in a multicentric study.

Isolated tumefactive demyelinating lesion (TDL) is a rare disease and a challenging entity especially for the differential diagnosis, biopsy indications, and therapeutic decisions. Long-term evolution is not well known. The objective of the study is to describe clinical and MRI characteristics and long-term follow-up of patients with isolated TDL. We performed a retrospective study including patients (1) with one TDL radiologically defined by a ≥20 mm FLAIR hyperintensity involving the white matter associated with T1 hypointensity that enhanced after gadolinium injection and (2) without any other MS lesion on the first MRI. Tumor, abscess, or other inflammatory diseases (ADEM, Baló's concentric sclerosis, systemic disease) were excluded. Sixteen patients (11 females/5 males) were included. The mean age of onset was 35.7 years (range 20-65). MRI disclosed supratentorial lesions with a mean size of 39.4 mm and usually mild edema/mass effect. Peripheral (mainly open-ring pattern) and central (mainly heterogeneous) enhancement were respectively seen in 9/16 and 11/16 patients. CSF study (n = 15) found oligoclonal bands (OCB) in seven. A cerebral biopsy was performed in 11 cases showing acute inflammatory demyelination. Thirteen patients were treated by pulse steroids with marked improvement in ten. At last clinical follow-up (mean 65.8 months, range 6-181), diagnosis was MS in 5 (31 %), isolated TDL in 10 (63 %) and one patient had a second TDL (6 %). Isolated tumefactive demyelinating lesions are a rare diagnostic entity. After a mean follow-up of 5 years, almost one-third became MS whereas most of the patients had no further event.

Is monitoring plasma levels of netilmicin necessary in neonates?

Thirty-two neonates were treated with netilmicin 3 mg/kg every 12 h by IV infusion for 30 min for suspected infections, colonization, or proven infections. Pharmacokinetic studies were performed in order to define the situations in which monitoring of plasma levels would be appropriate. Mean plasma levels were within the therapeutic range and did not differ in fullterms and preterms. In the 4 children who had 2 successive pharmacokinetic studies, plasma levels were increased between H1 and H5 at the second evaluation due to netilmicin accumulation. Plasma half-life was longer in proven infections and seemed to decrease in preterms with increased gestational age. These results suggest that the dosage schedule should be left inchanged, but that administration time should be reduced from 30 to 20 min and that peak and trough plasma levels should be measured only in proven infections, in very premature babies (gestational age less than 33 wk), and during netilmicin treatment longer than 5 d.

[Does the placebo effect exist in newborn infants?]. / L'effet placebo existe-t-il chez le nouveau-né?

Although comparison with a placebo is necessary to demonstrate the "true" effect of a drug, neonatologists are usually reluctant to use a placebo. The reason given is the lack of placebo effect in neonates. We studied heart and respiration rates and behaviour in normal neonates during heelstick for diagnosis of phenylketonuria. In this open randomized study we compared no treatment with an "analgesic" treatment consisting of water and sucrose. There was no difference in heart and respiration rates and behaviour between the two groups. These results do not demonstrate a "suggested" placebo effect and can in part be explained by the model and tools used to measure pain. The results do not support the non-use of placebo in drug evaluation trials in children.

[Drug utilization at the end of pregnancy]. / Consommation médicamenteuse en fin de grossesse.

To evaluate drug utilization during the last 15 days of pregnancy, one hundred six women were interviewed post-delivery in the CHU Bretonneau in Tours. Eighty-three percent received at least one drug during the 15 days preceding delivery and 27% more than 3 different drugs. Treatments for venous disorders (31% of patients), iron (31%), analgesics (25%), antacids (11%), magnesium (11%) and laxatives (11%) were most frequently used. In 92% of cases the drug was prescribed. Five women received a drug with potential risk for the neonate. However only one infant developed and adverse effect, possibly due to benzodiazepine (hypotonia).

[Medical and psychological status of one-year-old premature babies without severe disability. Case-control prospective study]. / Devenir médical, psychologique et affectif à l'âge d'un an des prématurés indemnes de handicap sévère. Etude prospective cas-témoins.

BACKGROUND: This case-control prospective study was conducted to determine whether and how medical, psychological and affective development differs from premature to full-term newborns without severe disability. POPULATION AND METHODS: Newborns under or at 33 weeks gestation (W) were included from December 1992 to January 1994 and were matched with two controls. The same examiners evaluated each infant at the effective postnatal age of nine to ten months. RESULTS: Fifty premature babies (average gestational age [GA] = 30.7 W) were compared to 100 controls. The main problems were bronchopulmonary (P = 0.03) and sleep (P = 0.027) disorders. Motor disability was suspected in 9% of the cases and none control (P = 0.00003, OR = 3.44). By multivariate analysis, cases differed from the controls by infant-mother relation disturbances (OR = 13.3), motherhood anxiety (OR = 13.3), poor expressiveness (OR = 5.6), peripheral tonus anomalies (OR = 39.5) and sleep troubles (OR = 5.8). CONCLUSION: Premature newborns had risks for the child-mother relation but not for psychoaffective development disturbances.

[Newborn resuscitation in the delivery room: evaluation of a regional training program conducted in 1990 in the Centre region]. / Réanimation du nouveau-né en salle de naissance: évaluation de l'action régionale de formation conduite en 1990 dans la région Centre.

OBJECTIVE: To evaluate the regional programme designed to train personnel for resuscitation of the neonate in the delivery room and organized in the district of Centre, France in 1990. STUDY: Transversal study. SITE: The different maternities of the district. POPULATION: 31 maternities, 156 persons in charge of neonates in the delivery room including medical personnel (doctors, mid-wives) and paramedics, with or without any special training in 1990. METHOD: A single evaluator visited each maternity and met the personnel involved. The modalities of the evaluation were not given in advance and included a census of the personnel who had participated in the training programme and changes in material. The success of the training programme was evaluated on a theoretical and practical basis for the personnel and on the number of severe meconium aspirations observed. RESULTS: The training programme had reached 53% of the personnel involved. It had a wide impact both in terms of changed material and in neonatal resuscitation rates compared with untrained personnel. The number of severe meconium aspirations fell from 3 in 1989 to 0 in 1990.

[Fetal cerebral accident due to massive fetomaternal hemorrhage. A case report]. / Accident cérébral foetal par hémorragie foetomaternelle massive. Un cas.

Massive fetomaternal haemorrhage (FMH) occurs in 0.12 to 0.5% of pregnancies. It is most often spontaneous and involves uncomplicated near-term pregnancies. It causes fetal anaemia, with or without fetal distress and hydrops fetalis. To our knowledge only one paper has reported a neurological complication (hemiplegia). We describe one case of FMH (maximal Kleihauer test = 6.5%) at 28 weeks gestation, which was spontaneous, reversible, associated with sinusoidal fetal heart rare (FHR) and hydrops fetalis; and complicated by an intraventricular antenatal haemorrhage at 30 weeks gestation. Echographic abnormalities decreased. The infant was born at 40 weeks gestation. Clinical examination was normal during the first week of life. At the age of 4 1/2 months, examination showed axial hypotonia and moderated dilatation of intracerebral lateral ventricules without any other brain damage. At the age of 24 months, the child had retarded walking and hypotonia. The outcome was spontaneously favourable with disappearance in utero of the intraventricular haemorrhage (HIV), without hydrocephalia or ischaemic lesions. Three cases of similar FMH have been reported but none of them described cerebral complications. Intrauterine intravascular transfusion should be proposed early. No single pathophysiological mechanism of FMH has been universally accepted and there is no aetiological treatment. The risk of recurrence of FMH in later pregnancies requires careful follow-up.

[Use of supplementation for breast-fed neonates in the maternity ward]. / Recours aux compléments à la maternité chez les nouveau-nés allaités.

OBJECTIVES: The aim of this study was to evaluate our practices regarding the use of supplementation for breast-fed neonates. METHODS: A descriptive and prospective study conducted between 22/05/2010 and 23/03/2010 comprising breast-fed, healthy, singleton infants at the Maternity University Hospital of Tours. Indications for supplementation were collected prospectively by paramedics. RESULTS: The study included 281 breast-fed neonates, of whom 99 (35 %) received supplementation. Supplemented neonates were more often children of primiparae (61.6 % versus 44%; P=0.005), or born to mothers without experience of breast-feeding (69.7% versus 48.9%; P=0.001), born by cesarean section (21.2% versus 10.4%; P=0.01), or were small for gestational age (10.1 % versus 6.6%; P=0.003). The main indications were: to prevent additional weight loss, hunger of the newborn, hypoglycemia, and difficulty to breast-feed. Twenty-nine percent of the neonates were given supplements without medical indication. CONCLUSION: One third of breast-fed infants receive supplementation, not always medically justified. A better understanding of medical indications would avoid supplementation being given to breast-fed infants.

Phenotype and genotype analysis in amyotrophic lateral sclerosis with TARDBP gene mutations.

OBJECTIVE: To describe the phenotype and phenotype-genotype correlations in patients with amyotrophic lateral sclerosis (ALS) with TARDBP gene mutations. METHODS: French TARDBP+ patients with ALS (n = 28) were compared first to 3 cohorts: 737 sporadic ALS (SALS), 192 nonmutated familial ALS (FALS), and 58 SOD1 + FALS, and then to 117 TARDBP+ cases from the literature. Genotype-phenotype correlations were studied for the most frequent TARDBP mutations. RESULTS: In TARDBP+ patients, onset was earlier (p = 0.0003), upper limb (UL) onset was predominant (p = 0.002), and duration was longer (p = 0.0001) than in patients with SALS. TARDBP+ and SOD1+ groups had the longest duration but diverged for site of onset: 64.3% UL onset for TARDBP+ and 74.1% on lower limbs for SOD1+ (p < 0.0001). The clinical characteristics of our 28 patients were similar to the 117 cases from the literature. In Caucasians, 51.3% of had UL onset, while 58.8% of Asians had bulbar onset (p = 0.02). The type of mutation influenced survival (p < 0.0001), and the G298S1, lying in the TARDBP super rich glycine-residue domain, was associated with the worst survival (27 months). CONCLUSION: Differences in phenotype between the groups as well as the differential influence of TARBDP mutations on survival may help physicians in ALS management and allow refining the strategy of genetic diagnosis.

[Current aspects of the fecal flora of the newborn without antibiotherapy during the first 7 days of life: Enterobacteriaceae, enterococci, staphylococci]. / Aspects actuels de la flore fécale du nouveau-né sans antibiotheérapie les sept premiers jours: entérobactéries, entérocoques, staphylocoques.

Last years, il became obvious that the colonization pattern described in 1976-1978 was no more valid: early colonization by Enterobacteriaceae at the 2-3 rd day of life in all newborns, with constant presence of antibioresistant strainseven in non treated newborns. To establish the new pattern of colonization, the same quantitative method of dilution and culture on selective media was used daily from day 1 to day 7 (5 days only for M). The number of Enterobacteriaceae, enterococci and staphylococci was determined in the stools of 10 newborns in the Maternity unit (= M) (term 40 weeks +/- 1, birth weight 3,356 g +/- 383), 10 in the Premature nursery (= P) (term 34.9 weeks +/- 1, birth weight 2,457 g +/- 676), and 14 in the Neonatal intensive care unit (= R) (term 35.2 weeks +/- 3.8, birth weight 2,457 g +/- 763). The results establish that colonization by Enterobacteriaceae is no more constant at D3. It could be demonstrated only in 8/10 M, 1/10 P, and 6/14 R (statistically different - p < 0.01 - between M and P). At D5, 9/10 M, 5/10 P, 10/14 R, and at D7, 6/10 P and 10/14 R were colonized. Resistant Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae) could be found in only 3/10 M, 4/10 P and 6/14 R. Enterococci could be found in 1 newborn M, 2 P and 7 newborns R. Staphylococci appeared earlier: all newborns M, P and R were colonized at D2, 4 and 5 respectively. These bacteria were coagulase negative, associated with Staphylococcus aureus in 3 P. Our hypothesis is that late colonization with Enterobacteriaceae and enterococci is due to the improvement of hygiene procedures and due to the decontaminating effect of antibiotics in other treated newborns (Enterobacteriaceae by 3 rd generation cephalosporin and enterococci by pharyngeal vancomycin).