MORT NEURONALE PROGRAMMEE (RELATIONS ENTRE EMBRYOGENESE ET MALADES NEURODEGENERATIVES)

PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Osteonecrosis after Allogeneic Bone Marrow Transplantation

Osteonecrosis after bone marrow transplantation is usually severe. Most patients develop acute and chronic graft-versus-host disease requiring a high dose of steroids for a long period of time. Generally ineffective nonoperative treatment in the past has resulted in treatment primarily with total hip arthroplasty (THA). We asked whether THA (1) reliably improved functional status, (2) led to more complications, and (3) THA after bone marrow transplantation was as durable as THA for idiopathic ON. We retrospectively reviewed 77 patients (123 hips) with osteonecrosis. The mean age at surgery was 33 years (range, 15.7–56 years). We performed all arthroplasties with an alumina ceramic bearing coupled with an alumina head 32 mm in diameter. The minimum followup was 2 years (mean, 9.2 years; range, 2–26 years). We documented seven revisions: three for late septic loosening, four for late aseptic loosening. Considering loosening of any component as the end point, the survivorship was 74.8% (range, 58.7%–90.9%) at 10 years. In this difficult situation, we believe the results acceptable. Septic loosening affecting this specific population has to be considered a serious event

On the complementarities of different techniques for the assessment of severity and evolution of dysarthria associated with lysosomal storage diseases

International audienc

On the complementarities of different techniques for the assessment of severity and evolution of dysarthria associated with lysosomal storage diseases

International audienc

Evaluation perceptive longitudinale de la dysarthrie dans des maladies lysosomales avant et après traitement

International audienc

Recommendations for the diagnosis and management of Niemann-Pick disease type C: An update

Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease caused by mutations in either the NPC1 (in 95% of cases) or the NPC2 gene (in around 5% of cases), which lead to impaired intracellular lipid trafficking and accumulation of cholesterol and glycosphingolipids in the brain and other tissues. Characteristic neurological manifestations of NP-C include saccadic eye movement (SEM) abnormalities or vertical supranuclear gaze palsy (VSGP), cerebellar signs (ataxia, dystonia/dysmetria, dysarthria and dysphagia) and gelastic cataplexy. Epileptic seizures are also common in affected patients. Typically, neurological disease onset occurs during childhood, although an increasing number of cases are being detected and diagnosed during adulthood based on late-onset neurological signs and psychiatric manifestations. Categorization of patients according to age at onset of neurological manifestations (i.e. early-infantile, late-infantile, juvenile and adolescent/adult-onset) can be useful for the evaluation of disease course and treatment responses. The first international guidelines for the clinical management of NP-C in children and adults were published in 2009. Since that time a significant amount of data regarding the epidemiology, detection/diagnosis, and treatment of NP-C has been published. Here, we report points of consensus among experts in the diagnosis and treatment of NP-C based on a follow-up meeting in Paris, France in September 2011. This article serves as an update to the original guidelines providing, among other things, further information on detection/diagnostic methods, potential new methods of monitoring disease progression, and therapy. Treatment goals and the application of disease-specific therapy with miglustat are also re-evaluated. (C) 2012 Elsevier Inc. All rights reserve

РЕКОМЕНДАЦИИ ПО ДИАГНОСТИКЕ И ЛЕЧЕНИЮ БОЛЕЗНИ НИМАННА-ПИКА ТИП С

(Pediatric Pharmacology. – 2010; 7(1):16-24)(Педиатрическая фармакология. – 2010; 7(1):16-24

A diagnostic flow chart for POLG-related diseases based on signs sensitivity and specificity.

International audienceOBJECTIVE: Diseases due to mutations of POLG gene, encoding the mitochondrial DNA polymerase, are reputed to have very diverse clinical presentations and have been proposed to cause up to 25% adult mitochondrial diseases. Our objective was the evaluation of the specificity and sensitivity of the signs encountered with POLG mutations. DESIGN: Forty-four patients out of 154 with sequenced POLG gene had mutations affecting either one (POLG(+/-) group) or two POLG alleles (POLG(+/+) group). Phenotyping included clinical signs, electroneuromyography and brain imaging while mitochondrial investigations encompassed muscle histochemistry, respiratory chain assays and search for multiple mitochondrial deletions. The specificity and sensitivity of the signs associated with POLG mutations were analysed by comparison between POLG(+/+) and patients without POLG mutation. RESULTS: High sensitivity but low specificity was observed with single signs such as axonal sensory neuropathy, cerebellar syndrome, movement disorders and weakness involving ocular, pharyngeal, axial and/or limb muscles. Specificity was increased with combination of previous signs plus psychiatric symptoms, cognitive impairment and epilepsy. High specificity and sensitivity was only obtained with sensory neuronopathy associated with one of the following signs: weakness of ocular, pharyngeal, axial and/or limb muscles. Mitochondrial investigations did not suffice for diagnosis. The widespread neuromuscular signs were often present since disease onset and were the rule above 50 years of age leading to a very low probability of POLG mutations in patients with less than three signs and absent sensory neuropathy. CONCLUSIONS: Phenotypes associated with POLG mutations follow a reproducible pattern, which allows establishing a diagnostic flow chart

Urinary sulphatoxymelatonin as a biomarker of serotonin status in biogenic amine-deficient patients

Abstract Melatonin is synthesized from serotonin and it is excreted as sulphatoxymelatonin in urine. We aim to evaluate urinary sulphatoxymelatonin as a biomarker of brain serotonin status in a cohort of patients with mutations in genes related to serotonin biosynthesis. We analized urinary sulphatoxymelatonin from 65 healthy subjects and from 28 patients with genetic defects. A total of 18 patients were studied: 14 with autosomal dominant and recessive guanosine triphosphate cyclohydrolase-I deficiency; 3 with sepiapterin reductase deficiency; and 1 with aromatic L-amino acid decarboxylase deficiency. Further 11 patients were studied after receiving serotoninergic treatment (serotonin precursors, monoamine oxidase inhibitors, selective serotonin re-uptake inhibitors): 5 with aromatic L-amino acid decarboxylase deficiency; 1 with sepiapterin reductase deficiency; 3 with dihydropteridine reductase deficiency; and 2 with 6-pyruvoyltetrahydropterin synthase deficiency. Among the patients without therapy, 6 presented low urinary sulphatoxymelatonin values, while most of the patients with guanosine triphosphate cyclohydrolase-I deficiency showed normal values. 5 of 11 patients under treatment presented low urine sulphatoxymelatonin values. Thus, decreased excretion of sulphatoxymelatonin is frequently observed in cases with severe genetic disorders affecting serotonin biosynthesis. In conclusion, sulphatoxymelatonin can be a good biomarker to estimate serotonin status in the brain, especially for treatment monitoring purposes