[Multicentric study of medical care and practices in spinal muscular atrophy type 1 over two 10-year periods]. / Amyotrophie spinale type 1 : enquête multicentrique des pratiques de soins et d'accompagnement palliatif sur deux périodes successives de 10ans.

AIM: Questions about care practices and the role of palliative care in pediatric neurodegenerative diseases have led the Neuromuscular Committee of the French Society of Neurology to conduct a retrospective study in spinal muscular atrophy type 1, a genetic disease most often leading to death before the age of 1 year. MATERIAL AND METHODS: A retrospective multicenter study from pediatricians included in the reference centers of pediatric neuromuscular diseases was carried out on two 10-year periods (1989-1998 and 1999-2009). RESULTS: The 1989-1998 period included 12 centers with 106 patients, the 1999-2009 period 13 centers with 116 children. The mean age of onset of clinical signs was 2.1 months (range, 0-5.5 months), the median age at diagnosis was 4 months (range, 0-9 months) vs 3 months. The median age of death was 7.5 months (range, 0-24 months) vs 6 months. The care modalities included physiotherapy (90 %), motor support (61 % vs 26 % for the previous period), enteral nutrition by nasogastric tube (52 % vs 24 %), and 3.4 % of children had a gastrostomy (vs 1.8 %). At home, pharyngeal aspiration was used in 64 % (vs 41 %), oxygen therapy in 8 %, noninvasive ventilatory support in 7 %. The mean age at death was 8.1 months (range, 0-24 months) vs 7 months, the time from diagnosis to death was 4 months vs 3 months. Death occurred at home in 23 % vs 17 %, in a pediatric unit in 62 % vs 41 %. The use of analgesics and sedative drugs was reported in 60 % of cases: 40 % morphine (vs 18 %) and benzodiazepines in 48 % (vs 29 %). Respiratory support was limited mostly to oxygen by nasal tube (55 % vs 54 %), noninvasive ventilation in 9 % of the cases, and intubation and assisted mechanical ventilation (2 %). DISCUSSION AND CONCLUSION: These results confirm a change in practices and the development of palliative care in children with a French consensus of practices quite different from the standard care in North-America and closer to the thinking of English medical teams. A prospective study within the 2011 national hospital clinical research program (PHRC 2011) is beginning in order to evaluate practices and the role of families and caregivers.

Unusual consequences of status epilepticus in Dravet syndrome.

Although status epilepticus (SE) affects the course of Dravet syndrome (DS), it rarely alters dramatically psychomotor outcome. We report an unusual pattern in 3 patients who following refractory SE lasting respectively 2, 7 and 12h experienced persistent and severe cognitive and motor deterioration. We compared these patients to published data and to personal experience in Necker hospital, to find links between severe outcome and clinical features such as treatment or duration of refractory SE. The key point was that anoxoischemic-like lesions appeared on MRI although cardiovascular function had remained stable. Therefore, neither hemodynamic failure, nor abnormalities of cardiac rhythm could explain the lesions and neurological worsening. For theoretical reasons the responsibility of therapy common for the 3 patients, e.g., barbiturates was suspected.

[Management of the first nonfebrile seizure in infants and children]. / Conduite à tenir devant une première crise épileptique du nourrisson et de l'enfant.

Seizures are the most common pediatric neurologic disorder. This article describes the guidelines of the French Pediatric Neurology Society, highlighting the importance of a thorough history and examination. Paroxysmal nonepileptic events should be excluded. The role of biological and neuroradiological investigations is discussed. An electroencephalographic recording and advice from a pediatric neurologist are suggested.

[Ifosfamide induced encephalopathy: 15 observations]. / Encéphalopathie induite par l'ifosfamide: 15 observations.

INTRODUCTION: Ifosfamide is an alkylating agent used in the treatment of germ-cell tumors, sarcomas and lymphomas. One of its main side effects is the encephalopathy of which the incidence may reach 30% in the literature, in adults and children just as well. OBJECTIVES: Based on both our experience and a review of the literature, we propose some recommendations for the management of this complication. PATIENTS AND METHODS: We report 15 encephalopathy cases in non-brain tumor patients, which occurred between January 1987 and March 2002 in children from 2 to 17 years old, treated for solid tumors at the Institut Gustave Roussy. Ifosfamide was administered at a posology between 5.4 and 15 g/m(2)/course, associated with other antimitotics such as actinomycin D, etoposide or vincristine. RESULTS: Six patients experienced a grade III neurological toxicity according to the NCI classification, which developed as excess drowsiness lasting up to 36 hours. Six other patients developed grade IV neurotoxicity, including two comas resolving within 4 days and four short generalized convulsions. Three other children experienced grade II drowsiness. Brain MRIs were normal and EEG showed an aspecific encephalopathy tracing. This early central neurotoxicity appeared right from the first administration, and occurred immediately after the first injection or during the second or third day of treatment. It was most often reversible, usually 3 to 5 days after the last ifosfamide administration. Five patients were administered a treatment with Methylene Blue with a demonstrable efficacy in only one case. No death or neurological sequelae have been noted. Ifosfamide has been renewed after the neurological accident in 7 of those patients. Only 1 of those 7 patients developed grade IV neurotoxicity during the next course of treatment. In 2 of those 7 children, Methylene Blue was used in a prophylactic way. No neurological disorders have been noted during the next courses of treatment. DISCUSSION: In the literature, the following are described as risk factors for ifosfamide encephalopathy: advanced pelvic disease, previous cisplatyl treatment and renal failure. We have not found any of these predisposing factors in our series, but three of the fifteen patients had severe neurotoxicity associated with Vincristin during previous treatments. CONCLUSION: Facing a clinical diagnosis of ifosfamide encephalopathy, it is recommended to discontinue administration of ifosfamide and inject by intravenous route 50 mg Methylene Blue every 4 hours until the symptomatology recedes. The re-challenge of Ifosfamide is not contra-indicated and should be performed under prophylactic treatment with Methylene Blue by intravenous route at the dose of 50 mg every 6 hours.

[Bilateral frontal polymicrogyria and Ehlers-Danlos syndrome]. / Polymicrogyrie bifrontale et syndrome d'Ehlers-Danlos.

The authors describe the case of a six-year-old girl with Ehlers-Danlos syndrome associated to bilateral symmetrical frontal polymicrogyria. Several extracellular matrix components, including collagen, are directly implicated in the neuronal migration. We think that a defect in collagen or in another extracellular matrix protein during fetal development could result in this association.

Economic impact of healthcare-associated rotavirus infection in a paediatric hospital.

The aim of this prospective study was to determine the extra-length of stay and the average cost for rotavirus healthcare-associated infection (HAI). Children admitted to the paediatric ward of the Reims University Hospital between the 1 December 2001 and 31 March 2002, were included in a pairwise matched (1:1) case-control study. Cases were defined as patients with rotavirus HAI. Controls were selected according to matching variables in a stepwise fashion. The costs measured in this study included all expenses sustained by the hospital. Information on costs was obtained from medical records and the hospital economic department. The attack rate and the incidence of healthcare-associated acquired rotavirus infection were 6.6% and 15.8 per 1000 hospital days, respectively, during a winter outbreak. Fifteen percent of HAI were identified after discharge. The average cost per case was 1930 and the mean excess length of stay was 4.9 days. Our findings clearly demonstrate the substantial expense incurred as a result of HAI caused by rotavirus in children. To prevent these costly infections, several cost-effective measures such as standard precautions should be reinforced in the education of the healthcare workers.

[How to evaluate a child following a first seizure?]. / Conduite à tenir devant une première crise d'èpilepsie.

Following a first epileptic phenomenon in a child, detailed history-taking, age at onset and complete clinical examination are essential. Previously experienced paroxysmal episodes may correspond to undiagnosed seizures. It is important to inquire about the existence of subjective sensations preceding or initiating attacks, about postictal phenomena such as confusion or drowsiness and about the circumstances of occurrence of the seizures. Clinical examination should look for any neurological signs, cutaneous stigmata or dysmorphic features. Parents should be asked about any recent changes in behaviour or school performances. Interictal, and eventually ictal, EEG data must be interpreted within the general neurological context. In the majority of cases, careful analysis of all the above mentioned data leads to a diagnostic hypothesis on the type(s) of seizures and, sometimes, on the epilepsy syndrome. Indications for further investigations, including MRI, will be discussed on the basis of a precise hypothesis. Treatment with antiepileptic drugs should not usually be started at the first seizure, with the exception of some epilepsy syndromes characterized by regular seizure relapse.

Use of chromosome painting for marker chromosome identification in two children with congenital disorders.

Identification of supernumerary de novo marker chromosomes was considered up to now as difficult and sometimes impossible with classical cytogenetical banding methods. The determination of their chromosomal origin is now easier with fluorescent in situ hybridisation techniques and enables an exact correlation between chromosomal aberration and phenotypic features to be established. The authors describe the use of chromosome painting with chromosome 13 and 18 Whole library DNA probe for identification of supernumerary markers in tow patients with congenital disorders. Cytogenetic examination in the first cave revealed a mosaicism with a ring chromosome 13 but clinical findings were different from the classical "ring 13 syndrome', and chromosome painting revealed in an extra--dicentric 13 chromosome (mos : 47, XX, -13, +r (13) +dic (13) / 46, XX, r (13) / 45, XX, -13 / 48, XX, -13, +r (13), (12) dic (13) / 47, XX, -13, + (2) r (13), R-banding pattern on prometaphases and chromosome painting in the second case confirmed the marker to be a 18 p isochromosome (47, XX, +i (18p)). The feasibility and the usefulness of chromosome painting in ascertainment of the possible genetic significance of markers is discussed.

Utility of short-latency evoked potentials in the classification of progressive, early onset cerebellar ataxias.

In recent years, several authors have proposed new classifications of inherited ataxias, some of them being based on systematic clinical studies of large groups of patients. This methodic approach has led to the identification of new types of ataxias and helped the development of molecular biology research in these diseases. Up to now, nerve conduction velocity and evoked potential studies have not been considered in the classification of hereditary ataxias. We have studied the results of short latency evoked potentials in 102 patients affected by a early onset, progressive cerebellar ataxia. Based on the results of this study and a review of the literature on this subject, we will evaluate the utility of nerve conduction velocity and evoked potential recordings in the classification of this group of diseases.

[Cerebellar ataxia preceding cutaneous symptoms in chickenpox]. / Ataxie cérébelleuse précédant les signes cutanés au cours d'une varicelle.

The authors describe a case of cerebellar ataxia developing 8 days before the exanthema of varicella. Evolution was quickly favorable. On the occasion of this rare observation, the pathophysiology of the neurological complications of varicella are discussed.