Impact of an intensive multimodal educative program on behavioral disorders of polyhandicapped patients: A randomized controlled trial.

BACKGROUND: Hospitalized children and young adults with polyhandicap (PLH) often present with behavioral and relational disorders that are mainly related to their difficulties in communicating and interacting with their environments. Educational support is rarely provided to these patients. An intensive multimodal educative program could help in reducing behavioral disorders and in improving the quality of life of healthcare workers, including nurses and auxiliary nurses. METHODS: A multicenter, randomized controlled trial compared the impact of the usual practice of an educative program (1 h a week) to a multimodal intensive educative program (5 h a week) at 12 months. Patients aged 3-25 with PLH defined by the combination of five criteria (motor deficiency, severe-to-profound mental impairment, daily life dependence, restricted mobility, onset of cerebral lesion at younger than 3 years, and at least one behavioral disorder per week [withdrawn behavior, unexplained crying, teeth grinding, self-injury, aggression, stereotypy, or merycism]) were included. The primary outcome was the evolution of the predominant behavioral disorder between study inclusion and 12 months. Healthcare workers completed questionnaires about chronic stress, coping strategies, and quality of life at study inclusion and at 12 months. RESULTS: Overall, 60 patients were included. Despite a tendency toward reduced teeth grinding, withdrawn and self-injury behaviors, the intervention was not significantly effective: The median duration of continuous behavioral disorders (stereotypy, unexplained crying, withdrawn behavior, and teeth grinding) did not differ between groups. The median frequency of the discontinuous behavioral disorders (self-injury) did not differ between groups. Considering each disorder separately, there was a decrease in teeth grinding, self-injury, and autistic-like traits in the intervention group, although it did not reach statistical significance. This study also suggested decreased depersonalization feelings by healthcare workers. CONCLUSION: Although the study did not show a significant reduction in behavioral disorders in patients with PLH, these results encourage further evaluation of educational management, particularly in regard to patients with self-injury and with withdrawn and teeth-grinding behaviors.

Comprehensive cDNA study and quantitative analysis of mutant HADHA and HADHB transcripts in a French cohort of 52 patients with mitochondrial trifunctional protein deficiency.

BACKGROUND: Deficiency of mitochondrial trifunctional protein (MTP) is caused by mutations in the HADHA and HADHB genes, which have been mostly delineated at the genomic DNA level and have not been always elucidated. AIM: To identify mutations in a French cohort of 52 MTP deficient patients and the susceptibility of mutations generating premature termination codons (PTCs) to the nonsense mRNA mediated decay (NMD). METHODS: Mutation screening in fibroblasts was performed at the cDNA level and real-time RT-PCR was used to compare the levels of the different PTC-bearing mRNAs before and after a treatment of fibroblasts by emetine, a translation inhibitor. RESULTS: A mutation detection rate of 100% was achieved. A total of 22 novel mutations were identified, including a large-sized genomic deletion in HADHB gene. A high proportion of all identified mutations were non-sense, frameshift and splicing mutations, generating (PTCs), distributed essentially on HADHA coding regions. We could demonstrate that the majority of mutations resulting in PTCs conform to the established rules governing the susceptibility to NMD. CONCLUSION: Our results emphasize the value of cDNA analysis in the characterization of HADHA and HADHB mutations and further strengthen the model of haploinsufficiency as a major pathomechanism in MTP defects.

Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations.

OBJECTIVE: To determine the spectrum of clinical, neuropsychological, and neuroradiologic features in patients with autosomal recessive primary microcephaly (MCPH) due to ASPM gene mutations. METHODS: ASPM was sequenced in 52 unrelated MCPH probands. In patients with ASPM mutations, we evaluated the clinical phenotype, cognition, behavior, brain MRI, and family. RESULTS: We found homozygous or compound heterozygous ASPM loss-of-function mutations in 11 (22%) probands and 5 siblings. The probands harbored 18 different mutations, of which 16 were new. Microcephaly was severe after 1 year of age in all 16 patients, although in 4 patients the occipital-frontal circumference (OFC) at birth was decreased by only 2 SD. The OFC Z score consistently decreased after birth. Late-onset seizures occurred in 3 patients and significant pyramidal tract involvement in 1 patient. Intellectual quotients ranged from borderline-normal to severe mental retardation. Mild motor delay was noted in 7/16 patients. Language development was delayed in all patients older than 3 years. Brain MRI (n = 12) showed a simplified gyral pattern in 9 patients and several malformations including ventricle enlargement (n = 7), partial corpus callosum agenesis (n = 3), mild cerebellar hypoplasia (n = 1), focal cortical dysplasia (n = 1), and unilateral polymicrogyria (n = 1). Non-neurologic abnormalities consisted of short stature (n = 1), idiopathic premature puberty (n = 1), and renal dysplasia (n = 1). CONCLUSIONS: We provide a detailed description of features associated with ASPM mutations. Borderline microcephaly at birth, borderline-normal intellectual efficiency, and brain malformations can occur in ASPM-related primary hereditary microcephaly.

Prenatal ultrasonographic diagnosis of polymicrogyria.

We report a rare case of polymicrogyria diagnosed at 27 weeks' gestation on ultrasound examination and associated with cytomegalovirus (CMV) infection. The ultrasound finding suggesting this diagnosis was the direct visibility of the overfolded cortical ribbon. The cerebral surface was clearly visible because of a markedly enlarged pericerebral space associated with micrencephaly secondary to CMV infection. Bilateral opercular dysplasia was also present. Very few sonographic markers of infectious fetopathy were observed other than periventricular cysts located behind both ventricular horns. Magnetic resonance imaging (MRI) of the fetal brain confirmed the ultrasound findings and also showed the presence of marked micrencephaly, whereas cephalic measurements acquired on ultrasound examination (biparietal diameter and head circumference) were within the normal range. This case emphasizes the complementary roles of sonography and MRI in the prenatal diagnosis of cerebral abnormalities. Moreover, it illustrates the fact that polymicrogyria is easier to diagnose on ultrasound examination during the second trimester, before the development of secondary sulci.

[Organization of Gaucher disease management in France]. / Organisation de la prise en charge de la maladie de Gaucher en France.

Gaucher disease management in France is facilitated by CETG (Comitee of Evaluation and Treatment of Gaucher disease). Four hundred and fifty-six patients are enrolled in 2006 in the French Gaucher registry of CETG. Two hundred and thirty patients had treatment. Eighty five % are type 1, 10.5% type 2 and 5.5% type 3. Only 1 patient had a saposin C deficiency. Information on CETG is available on www.cetl.net.

[Management of acute visual loss in children]. / Conduite à tenir devant une baisse aiguë de l'acuité visuelle chez l'enfant.

Acute or rapidly progressive visual loss in children needs urgent attention and treatment. It may be unilateral orbilateral. Etiology depends upon the involved areas: eye ball, optic nerve, retro-chiasmatic pathways. Psychogenic origin is quite common in school-age children, however, it has to be considered last. Unilateral visual loss may be overlooked. Acute total transitory visual loss may be due to epilepsy or to migraine. Rapidly progressive visual loss may be due to retinal disease, optic neuritis or cortical blindness. Management of visual loss depends on clinical features, associated symptoms, and aspect of the optic disc. It needs collaboration between ophthalmologist,pediatrician and neuropediatrician. Retinal hemorrhages first call to mind a traumatic origin. Swelling of the optic disc may be due to increased intracranial pressure or due to optic neuritis. When the optic disc is normal it is necessary to rule out organic diseases before establishing the diagnosis of a psychogenic vision disturbance. In emergency, brain neuroimaging is the best way to diagnose intracranial mass and visualize optic pathways.

Classical West "syndrome" phenotype with a subtelomeric 4p trisomy.

We report a girl with mild mental retardation with onset of infantile spasms at age of 9 months. Treatment with a short course of adrenocorticotropic hormone (ACTH) was successful. Initially, a diagnosis of idiopathic West syndrome, with good neurological outcome and disappearance of epilepsy after treatment, was made. Conventional karyotype was normal. Reinvestigations were done at age 8 years, because of a new pregnancy. Karyotyping of both parents was done because of mild dysmorphic features in the proband, and to eliminate other causes than early age epilepsy as the etiology of her mental retardation. Parental karyotypes showed a balanced paternal translocation (4p;17q) resulting in partial 4p trisomy, without significant 17q monosomy in the proband. Chromosomal abnormalities usually lead to a severe West syndrome with poor prognosis of neurological outcome (persistent severe epilepsy, mental retardation, and behavioral disturbances). The presence of an undetected cytogenetic anomaly in our proband with transient hypsarythmia is unusual and led us to propose systematic telomeric screening in apparently "idiopathic" West syndrome patients with mild mental retardation and subtle dysmorphic features.