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Background: Superficial siderosis (SS) is a rare finding on T2*-weighted magnetic resonance imaging (MRI), regarded as a radiological marker of cerebral amyloid angiopathy (CAA). The present study investigates with 7.0-tesla MRI the prevalence of SS and its underlying pathological substrate in a consecutive series of post-mortem brains of elderly patients with various neurodegenerative and cerebrovascular lesions., Materials and Methods: The prevalence of SS and associated lesions was screened using 7.0-tesla MRI and their neuropathological correlates in 120 post-mortem brains of patients with various neurodegenerative and cerebrovascular diseases., Results: Eighty-three separate zones of SS were detected in 45 brains (37.5%), including 25 areas of disseminated SS (dSS) and 58 areas of focal SS (fSS), restricted to less than 3 sulci. dSS was spatially related to sequels of 14 lobar haematomas and 11 cerebral infarcts, while fSS was connected to 19 microbleeds and 39 micro-infarcts (p < 0.001). Comparison of the 15 CAA to the 30 non-CAA brains showed that dSS was due to an old lobar haematoma in 53% of the former group compared to 3% of the latter group (p = 0.003). fSS was due to a microbleed in 7% of the CAA brains and to 40% of the non-CAA brains (p = 0.03)., Conclusions: SS is associated with both haemorrhagic and ischaemic underlying lesions. It is frequently observed on T2*-weighted 7.0-tesla MRI, and two types of SS may be described. Clinicians should keep in mind that SS may be found in other settings than CAA.

Congenital glucose-galactose malabsorption (CGGM) is a rare autosomal recessive disorder, which presents as a protracted diarrhea in early neonatal life. We describe the clinical history, diagnostic evaluation, and management of 7 children with CGGM in western France. There were 4 girls and 3 boys from 5 families, born between 1984 and 2010. The principal complaint was a neonatal onset of watery and acidic severe diarrhea complicated by hypertonic dehydration. The diarrhea stopped with fasting. In 2 cases, the family history supported the diagnosis. In the other cases, elimination of glucose and galactose (lactose) from the diet resulted in the complete resolution of diarrhea symptoms. In 2 cases, the H2 breath tests were positive. In 2 cases, the HGPO or oral glucose tolerance test (OGTT) demonstrated an abnormal curve with glucose and a normal curve with fructose. DNA sequencing was not used. When glucose and galactose were eliminated from the diet, the infants had normal growth and development. In conclusion, CGGM is a rare etiology of neonatal diarrhea; however, the diagnosis is easy to make and the prognosis is excellent., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Microbleeds (MBs) are frequently detected in brains of patients with Alzheimer dementia and rare in those with frontotemporal lobar degeneration (FTLD). This study investigates for the first time the topographic distribution of MBs on a T2*-weighted gradient-echo 7.0-T magnetic resonance imaging (MRI) in post-mortem FTLD brains., Patients and Methods: The neuropathological and MRI findings in 12 FTLD brains were compared with eight age-matched controls. The presence of cerebrovascular lesions was evaluated on a coronal section of a cerebral hemisphere at the level of the mamillary body and on a horizontal section through pons and cerebellum. On MRI, the distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central and the occipital level of a cerebral hemisphere., Results: Overall, cerebrovascular lesions were rare. Only white matter damage was significantly more severe in FTLD brains compared with controls (P = 0.03). On MRI, MBs were only significantly prevalent in the deep cortical layers (P < 0.01) and borderline increased in the middle cortical layers (P = 0.07) of the frontal section., Conclusions: Cerebrovascular lesions are rare in FTLD. The white matter damage has to be considered as part of the neurodegenerative process. MBs prevail in the frontal regions with the most severe neuronal damage and probably represent associated disruption of the blood-brain barrier., (© 2012 The Author(s) European Journal of Neurology © 2012 EFNS.)

Background: Capsule endoscopy is recommended for children with Peutz-Jeghers syndrome as young as 8 years of age. Aim of our study was to evaluate the contribution of capsule endoscopy in managing risk of further obstructive complications., Methods: A retrospective analysis of 27 children who received at least 1 capsule endoscopy was conducted. Peutz-Jeghers syndrome was diagnosed based on the presence of an STK11 gene mutation or on the association of a hamartoma with 2 of 3 criteria (family history, mucocutaneous pigmentation, small bowel polyposis)., Results: Thirty-seven capsule endoscopies were performed in 27 patients. The median age at first endoscopy was 11.4 years (range, 5.4-20.9). Jejunal polyps were found in 72% and ileal polyps in 55% of capsules. The original recommendations were followed 20/30 times. Three gastroscopies, 4 colonoscopies, 7 double balloon enteroscopies and 1 intra-operative enteroscopy were performed after the capsules. These procedures revealed jejunal polyps in 9/9 cases (8/9 resected) and ileal polyps in 3/5 (all resected). One intussusception occurred 8.4 months after the capsule endoscopy and required surgical resection., Conclusion: Capsule endoscopy is easily feasible in Peutz Jeghers syndrome, but the practice of systematic and repeated procedures needs to be validated prospectively., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Cerebrovascular lesions are frequently observed in Alzheimer brains. Not all of them are due to cerebral amyloid angiopathy. Some of them are related to the severity of the degenerative process itself, implying additional vascular factors in the pathogenesis of Alzheimer's dementia. The aim of the study was to investigate the impact of cerebrovascular pathology on brains with frontotemporal lobar degeneration (FTLD)., Patients and Methods: Twenty-two brains with autopsy-proven FTLD were compared to 15 brains of age-matched patients without evident cognitive decline, who died from an illness not related to a brain disease. The prevalence and the severity of small ischaemic and haemorrhagic lesions were determined. Vascular risk factors and the use of antithrombotic agents were also recorded., Results: The patients with FTLD were heterogeneous concerning age of onset, disease duration, clinical presentation, genetic background and neuropathological typing. Cerebrovascular risk factors and lesions were overall rare in FTLD brains without differences in their prevalence and severity compared to the controls. Only white matter changes were more prevalent in the FTLD group (p = 0.04) and showed a trend to greater severity (p = 0.08)., Conclusions: Cerebrovascular pathology is not contributing to the evolution of the disease process of patients with FTLD. The isolated prevalence of white matter changes should not be considered as a vascular indicator., (Copyright © 2012 S. Karger AG, Basel.)

Acid maltase deficiency (AMD) is a metabolic myopathy which may be revealed at adulthood by respiratory muscle weakness, resulting in reduced vital capacity, alveolar hypoventilation and sleep apnoea. We observed two men, 39 and 42 years old respectively, suffering from asthenia and exertional dyspnoea for several months. After a stay in the intensive care unit, as a result of respiratory failure associated with pneumonia, these patients were referred to the respiratory medicine unit on account of persistent hypercapnia during the day and a fall in oxygen saturation at night. The investigations revealed proximal muscle weakness, a reduced vital capacity, alveolar hypoventilation (PaCO2: 67 and 49 mmHg), reduced maximum static inspiratory and expiratory pressures, carbon dioxide hyporesponsiveness and sleep apnoea on overnight polysomnography. Electromyography showed a myopathic pattern. Muscle biopsy confirmed the diagnosis of AMD. Non-invasive ventilation overnight partially corrected the clinical symptoms and the resting hypercapnia in both patients. The adulthood form of AMD is a rare disease that should be considered in a large number of clinical situations, particularly in unexplained respiratory failure. Our observations suggest that non invasive ventilation together with enzyme supplementation (Myozyme®) is effective in correcting alveolar hypoventilation., (Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Individual rupture risk assessment of intracranial aneurysms is a major issue in the clinical management of asymptomatic aneurysms. Aneurysm rupture occurs when wall tension exceeds the strength limit of the wall tissue. At present, aneurysmal wall mechanics are poorly understood and thus, risk assessment involving mechanical properties is inexistent. Aneurysm computational hemodynamics studies make the assumption of rigid walls, an arguable simplification. We therefore aim to assess mechanical properties of ruptured and unruptured intracranial aneurysms in order to provide the foundation for future patient-specific aneurysmal risk assessment. This work also challenges some of the currently held hypotheses in computational flow hemodynamics research., Methods: A specific conservation protocol was applied to aneurysmal tissues following clipping and resection in order to preserve their mechanical properties. Sixteen intracranial aneurysms (11 female, 5 male) underwent mechanical uniaxial stress tests under physiological conditions, temperature, and saline isotonic solution. These represented 11 unruptured and 5 ruptured aneurysms. Stress/strain curves were then obtained for each sample, and a fitting algorithm was applied following a 3-parameter (C(10), C(01), C(11)) Mooney-Rivlin hyperelastic model. Each aneurysm was classified according to its biomechanical properties and (un)rupture status., Results: Tissue testing demonstrated three main tissue classes: Soft, Rigid, and Intermediate. All unruptured aneurysms presented a more Rigid tissue than ruptured or pre-ruptured aneurysms within each gender subgroup. Wall thickness was not correlated to aneurysmal status (ruptured/unruptured). An Intermediate subgroup of unruptured aneurysms with softer tissue characteristic was identified and correlated with multiple documented risk factors of rupture., Conclusion: There is a significant modification in biomechanical properties between ruptured aneurysm, presenting a soft tissue and unruptured aneurysms, presenting a rigid material. This finding strongly supports the idea that a biomechanical risk factor based assessment should be utilized in the to improve the therapeutic decision making., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Typing a tumor of the lateral ventricle is often an issue, even for an experienced Neuropathologist. In this location are encountered specific entities, such as neurocytoma and subependymal giant cell astrocytoma, as well as more usual tumors, displaying a common misleading morphology, for instance a main clear cell component. The panel of diagnostic tools given to the pathologists has been increasing for a few years, enriched by immunohistochemical and molecular probes., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Tau is the proteinaceous component of intraneuronal aggregates common to neurodegenerative diseases called Tauopathies, including myotonic dystrophy type 1. In myotonic dystrophy type 1, the presence of microtubule-associated protein Tau aggregates is associated with a mis-splicing of Tau. A toxic gain-of-function at the ribonucleic acid level is a major etiological factor responsible for the mis-splicing of several transcripts in myotonic dystrophy type 1. These are probably the consequence of a loss of muscleblind-like 1 (MBNL1) function or gain of CUGBP1 and ETR3-like factor 1 (CELF1) splicing function. Whether these two dysfunctions occur together or separately and whether all mis-splicing events in myotonic dystrophy type 1 brain result from one or both of these dysfunctions remains unknown. Here, we analyzed the splicing of Tau exons 2 and 10 in the brain of myotonic dystrophy type 1 patients. Two myotonic dystrophy type 1 patients showed a mis-splicing of exon 10 whereas exon 2-inclusion was reduced in all myotonic dystrophy type 1 patients. In order to determine the potential factors responsible for exon 10 mis-splicing, we studied the effect of the splicing factors muscleblind-like 1 (MBNL1), CUGBP1 and ETR3-like factor 1 (CELF1), CUGBP1 and ETR3-like factor 2 (CELF2), and CUGBP1 and ETR3-like factor 4 (CELF4) or a dominant-negative CUGBP1 and ETR-3 like factor (CELF) factor on Tau exon 10 splicing by ectopic expression or siRNA. Interestingly, the inclusion of Tau exon 10 is reduced by CUGBP1 and ETR3-like factor 2 (CELF2) whereas it is insensitive to the loss-of-function of muscleblind-like 1 (MBNL1), CUGBP1 and ETR3-like factor 1 (CELF1) gain-of-function, or a dominant-negative of CUGBP1 and ETR-3 like factor (CELF) factor. Moreover, we observed an increased expression of CUGBP1 and ETR3-like factor 2 (CELF2) only in the brain of myotonic dystrophy type 1 patients with a mis-splicing of exon 10. Taken together, our results indicate the occurrence of a mis-splicing event in myotonic dystrophy type 1 that is induced neither by a loss of muscleblind-like 1 (MBNL1) function nor by a gain of CUGBP1 and ETR3-like factor 1 (CELF1) function but is rather associated to CUGBP1 and ETR3-like factor 2 (CELF2) gain-of-function., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Unlabelled: Thoracic actinomycosis is a rare disease, with high morbidity related to delayed diagnosis., Objectives: To identify and analyse paediatric thoracic actinomycosis to promote earlier diagnosis., Design: A 10-year descriptive retrospective review (1999-2008). Clinical, biological, and radiological data were collected and compared to identify common signs., Results: Three patients were identified. The time to diagnosis varied from 4 months to 3 years. Fever, asthenia, pain, weight loss, and sweats were the most common complaints. A predisposing factor was systematically observed. Irregular subpleural nodules were revealed with an infiltrative aspect. Definitive diagnosis was always histological., Conclusion: Actinomycosis should be sought in patients with asthenia and weight loss, local pain, when chest radiological evidence of distal nodules is observed with a non-specific biologic inflammatory syndrome. At this time, anaerobic bacteriological tests and histology should be performed., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: In view of the increasing recognition of cerebral microbleeds (MCBs) with MRI, there is a need to validate their detection in post-mortem brains in patients with cerebrovascular diseases and dementia., Materials and Methods: Out of 20 post-mortem brains of patients with Alzheimer dementia and with different cerebrovascular lesions, 45 large sections of the cerebral hemispheres, brainstem and cerebellum were submitted to a 7.0-T T₂*-weighted MRI, and afterwards compared to the histological detection of haematomas, MCBs and mini-bleeds (MNBs)., Results: The sensitivity, specificity, predictive positive value and predictive negative value of the T₂* imaging to detect MCBs and MNBs were excellent for those in the cortico-subcortical regions. There was a significant overestimation of MNBs in the striatum due to iron deposits unrelated to old haemorrhages. Also in the deep white matter, 42% of MNBs were not detected, while 31% of T₂* hyposignals were not due to MNBs but to vessels filled with post-mortem thrombi., Conclusions: When evaluating the 'bleeding load' with 7.0-T T₂*-weighted MRI in post-mortem brain sections of patients with dementia and vascular risk factors, only quantification of small cerebral bleeds in the cortico-subcortical regions is reliable., (Copyright © 2011 S. Karger AG, Basel.)

Introduction: Leptomeningitis and pachymeningitis are known to occur consecutive to many causes., Observation: We report the case of a 24-year-old woman with symptoms of raised intracranial pressure and repeated switching transient hemiparesis. The magnetic resonance imaging (MRI) showed a pachyleptomeningitis. Search for a cause was negative. The pathology examination of meningeal tissue revealed a malignant melanoma, without any sign of cutaneous melanoma, leading to the diagnosis of primary leptomeningeal malignant melanoma., Conclusion: A meningeal biopsy can enable the rare diagnosis of primary leptomeningeal malignant melanoma in a patient with unexplained pachyleptomeningitis., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Biopsies of brain stem lesions are useful for histopathological analysis, which guide appropriate treatment. The frame-based stereotactic procedure is the gold standard technique for biopsies of the brain stem. For the past few years, a frameless stereotactic robot, the NeuroMate robot (Renishaw, UK) has also been used for brain biopsies. We report a retrospective study of 15 patients who underwent NeuroMate robot-guided biopsies of brain stem lesions to evaluate the efficiency and safety of the system., Methods: From January 2004 to March 2006, 15 patients (five children and ten adults) underwent 17 biopsies of brain stem lesions. The lesions were located in the mesencephalon in two cases, in the pons in seven cases, in the pons and the medulla oblongata in five cases, and in the whole midbrain in one case. The biopsy procedure comprised four stages: image acquisition, preoperative planning, patient-to-image registration, and operative procedure. A transcerebellar approach was used in 12 cases and a double oblique anterior frontal approach in five cases., Results: Two adults underwent a second procedure because the first biopsy was not contributive. There was no operative mortality. We observed two cases of transient morbidity and one case of permanent morbidity., Conclusions: The frameless NeuroMate robot is an efficient and safe instrument for biopsies of brain stem lesions. We believe that the use of frameless stereotactic techniques for brain stem biopsies could increase the number of biopsies and therefore improve the diagnostic yield and accuracy of the technique., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Background: Limb-girdle muscular dystrophy 2I (LGMD2I) is caused by mutations in the fukutin-related protein gene FKRP, which is also involved in congenital muscular dystrophy (MDC1C)., Objective: To evaluate the clinical, biological, radiological and mutational characteristics of LGMD2I patients with FKRP mutation., Methods: Eleven patients from nine families from the north of France were studied. Demographical data, muscular testing results, cardiac and respiratory examinations, muscle histological features and a genetic analysis of the FKRP gene for each patient are reported. Eight patients underwent brain MRI and seven neuropsychological tests., Results: The patients included six women and five men. The mean age at onset was 9 years (range 1.5 to 23 years). Five patients remained self-ambulatory, whereas the other six were confined to a wheelchair by a mean age of 19 years, after a mean disease duration of 10 years. Nine patients suffered from restrictive respiratory insufficiency, and two male patients had severe dilated cardiomyopathy. Neuropsychological tests revealed memory impairment in four cases. Brain MRI revealed cerebral abnormalities in four patients (4/8). Ten patients were carriers of the common L276I mutation, which was either homozygous (four patients) or heteroallelic with another mutation (six patients). Among the mutations found, three were novel: L322V, L489R and R275G., Conclusions: This study reveals inter- and intrafamilial phenotypic variability in LGMD2I, with a preponderance of myocardiopathy and restrictive respiratory insufficiency. It also demonstrates central nervous involvement, probably associated with changes in alpha-dystroglycan expression in the brain.

Transplant recipients are very susceptible to invasive aspergillosis, which increases mortality rate. Disseminated aspergillosis in the liver transplant recipient can affect virtually any organ and endocarditis is often lethal despite cardiac surgery and antifungal therapy. We report the case of a eight-month-old girl who presented with Aspergillus fumigatus endocarditis 18 days after liver transplantation that was successfully treated by a combination of antifungal drugs associated to a low dosage of immunosuppressive therapy.

Meningiomas infrequently develop in children, and their clinical picture is somewhat different than in adults. We describe here a case of a meningioma in a 9-year-old girl unusual in two aspects. Firstly, it arose from the cavernous sinus what is exceptional in children. Secondly, despite the big tumor mass the child was almost asymptomatic. The only symptoms at presentation were a slight facial asymmetry and minimal laterodeviation of her mandible. Those symptoms had not been noticed by her parents and were detected during careful routine dental examination. The clinical course was quite aggressive and several neurosurgical interventions were necessary. This case underlines the importance of careful medical and dental examination during routine checkup consultations and undertaking necessary diagnostic procedures aimed at elucidating of all detected, even minimal abnormalities.

Background: Infliximab (IFX) is efficacious in inducing remission in severe forms of pediatric Crohn's disease (CD). Adult studies indicate that IFX is also safe and well tolerated as maintenance therapy. The present study aimed to evaluate in a prospective manner the efficacy and safety of IFX as maintenance therapy of severe pediatric CD comparing scheduled and "on demand" treatment strategies., Methods: Forty children with CD (nonpenetrating, nonstricturing as well as penetrating forms, mean age: 13.9 +/- 2.2 years) with a severe flare-up (Harvey-Bradshaw Index [HBI] > or =5, erythrocyte sedimentation rate [ESR] >20 mm/h) despite well-conducted immunomodulator therapy (n = 36 azathioprine, n = 1 mercaptopurine, n = 3 methotrexate) combined with steroids were included in this randomized, multicenter, open-label study. Three IFX infusions (5 mg/kg) were administered at week (W)0/W2/W6. At W10, clinical remission (HBI <5) and steroid withdrawal were analyzed and IFX responders were randomized to maintenance therapy over 1 year: group A, scheduled every 2 months; group B, "on demand" on relapse., Results: In all, 34/40 children came into remission during IFX induction therapy (HBI: 6.7 +/- 2.5 (WO) vs. 1.1 +/- 1.5 (W10); P < 0.001). At the end of phase 2, 15/18 (83%) patients were in remission in group A compared to 8/13 (61%) children in group B (P < 0.01), with a mean HBI of 0.5 versus 3.2 points (group A versus B, P = 0.011). In group A, 3/13 (23.1%) children experienced a relapse compared to 11/12 (92%) children in group B. No severe adverse event occurred during this trial., Conclusions: IFX is well tolerated and safe as maintenance therapy for pediatric CD, with a clear advantage when used on a scheduled 2-month basis compared to an "on demand" basis.

Objective: Vascular dementia (VaD) and Alzheimer disease with cerebrovascular disease (AD+CVD) are the leading causes of dementia after Alzheimer disease alone (AD). Little is known about the progression of either VaD or AD+CVD. The aim of this study was to compare demographic features, cognitive decline and survival of patients with VaD, AD+CVD and AD alone attending a memory clinic., Methods: This study included 970 patients who were followed at the Lille-Bailleul memory clinic, France. Cognitive functions were measured with the Mini Mental State Examination (MMSE) and the Dementia Rating Scale (DRS). Survival rate was analysed with a left-truncated Cox model. Analyses were adjusted for age, sex, education, hypertension, diabetes and baseline MMSE and DRS., Results: Of 970 patients, 141 had VaD, 663 AD alone and 166 AD+CVD. The latter were significantly older than AD or VaD patients at onset (71 (SD 7) vs 69 (9) and 68 (9) years, p = 0.01) and at first visit (75 (6) vs 73 (8) and 72 (8) years, p = 0.0002). Baseline MMSE and DRS evaluations were highest for VaD compared with AD alone or AD+CVD patients (p<0.006). Cognitive decline during follow-up was slowest for VaD, intermediate for AD+CVD and fastest for AD alone (p = 0.03). After adjustment, compared with AD patients, mortality risk was similar for those with VaD (relative mortality risk (RR) = 0.7 (0.5 to 1.1)) and tended to be lower for AD+CVD (RR = 0.7 (0.5 to 1.0)). The shorter the delay between first symptoms and first visit, the longer patients survived., Conclusion: This clinical cohort study shows that patients with VaD, AD+CVD and AD present different characteristics at baseline and during follow-up, and underlines the need to distinguish between them.

Introduction: Starting from a recent clinical case, we present the different causes of rectal prolapse and their specific treatments. In this case, the relation to infectious colitis was questionable., Observation: This 3-year-8-month-old boy had repetitive rectal prolapses with phlegmy and bloody diarrhea, with reduction increasingly difficult. Stool analysis was negative but pseudomembranous colitis was found with coloscopy and was confirmed by biopsy., Discussion: Hygienic and dietary measures are the first steps in the treatment rectal prolapse. Pseudomembranous colitis, often related to Clostridium difficile toxins; is a severe form of postantibiotic diarrhea. Its treatment is based on oral antibiotic therapy with metronidazole or vancomycin for 10 days. Rectal prolapsus in children is cured without recurrence in 98% of cases., Conclusion: In the case reported herein, rectal prolapse did not recur after diarrhea recovery with antibiotic therapy, suggesting a causative link with pseudomembranous colitis.

Scientific and medical studies report that the environment, and particularly physical activity and the diet, changes the metabolic programming. A systematic review of size and growth during infancy supports conclusions with regard to preventing later obesity. Moreover, the correlation has been established between birth weight, arterial blood pressure, plasmatic lipid level, and cardiovascular mortality. The European Nutrition Committee has written new recommendations with lower protein levels. A lot of data support the application of blocking sensibilisation through intervention in pregnancy and lactation. Primary prevention is possible with breastfeeding for the first 4-6 months of life, particularly for high-risk allergic families. This is a priority for the national health program in France for controlling the increasing obesity.

Neurofibrillary degeneration is often observed in the brain of patients with type 1 myotonic dystrophy (DM1). It consists principally of the aggregation of Tau isoforms that lack exon 2/3 encoded sequences, and is the consequence of the modified splicing of Tau pre-mRNA. In experimental models of DM1, the splicing of several transcripts is modified due to the loss of Muscleblind-like 1 (MBNL1) function. In the present study, we demonstrate that the MBNL1 protein is also present in the human brain, and consists of several isoforms, as shown by RT-PCR and sequencing. In comparison with controls, we show that the adult DM1 brain exhibits modifications in the splicing of MBNL1, with the preferential expression of long MBNL1 isoforms--a splicing pattern similar to that seen in the fetal human brain. In cultured HeLa cells, the presence of long CUG repeats, such as those found in the DM1 mutation, leads to similar changes in the splicing pattern of MBNL1, and the localization of MBNL1 in nuclear RNA foci. Long CUG repeats also reproduce the repression of Tau exon 2/3 inclusion, as in the human disease, suggesting that their effect on MBNL1 expression may lead to changes in Tau splicing. However, while an overall reduction in the expression of MBNL1 mimics the effect of the DM1 mutation, none of the MBNL1 isoforms tested so far modulates the endogenous splicing of Tau. The modified splicing of Tau thus results from a possibly CUG-mediated loss of function of MBNL1, but not from changes in the MBNL1 expression pattern.

Study Objectives: The objectives of the study were to present our institutional experience of idiopathic chylothorax in children and to propose therapeutic strategies., Design: This was a retrospective, single-center study., Patients: Patients were 6 children (4 boys, 2 girls) presenting with an idiopathic chylothorax diagnosed from the presence of a chylous pleural effusion with triglycerides greater than 1.2 mmol/L and a cellularity greater than 1000 cells/mL with a predominance of lymphocytes., Results: Median age of onset was 7 years (range, 2-14 years). Initial symptoms included cough (n = 4), tachypnea (n = 4), asthenia (n = 5), abdominal pain (n = 2), and bronchitis (n = 1). Chest radiography showed 2 left, 2 right, and 2 bilateral pleural effusions. Serum biology assessment was normal in all children. Respiratory function assessment at diagnosis revealed a decrease in functional residual capacity in 3 children and a decrease in lung diffusing capacity in 2 children. Initially, all patients received a medium-chain triglyceride diet for 29 months (range, 10-50 months). Total parenteral nutrition was required for 4 patients (for 1-4 months), and somatostatin was tried in one child. Two children required pleuroperitoneal shunting, bilateral in one case. During the follow-up (median duration, 6 years; range, 2-16 years), chylothorax stabilized in all patients and 5 patients were able to return to a normal diet., Conclusion: A medium-chain triglyceride diet associated in some cases with total parenteral nutrition may stabilize idiopathic chylothorax in children. In cases where conservative treatment has failed, pleuroperitoneal shunting may be useful.

Objective: We tested the hypothesis that a higher education level is associated with faster cognitive decline and lower survival in a cohort of 670 Alzheimer's disease patients, followed for 3.5 years at the Lille-Bailleul memory centre., Methods: The patients were categorized in 3 groups according to educational levels: low (12 years). Cognitive function was measured with the Mini Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (DRS). Survival was analyzed with a Cox model. Analyses were adjusted for age, sex, cholinesterase inhibitor treatment, diabetes, hypertension, visible vascular lesions on MRI, baseline DRS and MMSE., Results: The adjusted mixed random model showed that MMSE declined faster for patients with high and intermediate educational levels compared with those with a low educational level (p < 0.0001). The mean annually adjusted DRS decline was highest for the groups with the most education (p = 0.05). The mortality risk was not higher in the better-educated groups (high vs. low: RR = 0.84; 95% CI = 0.35-1.99, intermediate vs. low: RR = 0.82; 95% CI = 0.41-1.63)., Conclusion: In our cohort, highly educated patients had a faster cognitive decline than less educated patients but similar mortality rates. Our findings support the cognitive reserve hypothesis., ((c) 2007 S. Karger AG, Basel.)

Background: Polymyositis with cranial neuropathy has been rarely reported., Case Reports: We describe here three cases of polymyositis with trigeminal or facial neuropathy. Patients had muscular weakness, myalgia, rhabdomyolysis, endomysial infiltration with necrosis and regeneration at biopsy of muscle and, for two of them, a myopathic pattern at electromyogram. Two patients had also a Sjögren's syndrome and anti-nuclear antibodies. Anti-JO1 antibodies were presents in only one case. The outcome for one patient was good with corticosteroids alone. One other improved with the adjunction of immunoglobulin. The third one had a macrocheilia, a facial diplegia, antibodies against voltage-gated potassium channels and a neuromyotonia secondary to a paraneoplastic syndrome. He died after one year despite a treatment by corticosteroids and immunoglobulin. Patients fulfilled the diagnosis of polymyositis according to clinical, electromyographic, biological and histopathologic criteria. For the two patients with Sjögren's syndrome, the question of a primitive or a secondary Sjögren's syndrome remains unknown., Conclusion: The occurrence of a cranial neuropathy in polymyositis should make us looking for an association with paraneoplastic syndrome or connective tissue disease.

Unlabelled: Pediatric non hypertrophic pyloric stenosis (NHPS) are uncommon. Their causes and treatments are debated., Material and Method: Retrospective review of all cases of NHPS from 3 pediatric surgery services during the period 1984-2002., Results: Six children, aged 17 months to 15 years, underwent surgery for NHPS. Clinical symptoms, food vomiting and loss of weight, were present for several weeks before the diagnosis of NHPS was made. The diagnosis was peptic stenosis in 3 cases and has not been established in 3 cases. Search for Helicobacter pylori was negative in all cases. Failure of specific medical treatment and endoscopic dilatations led to pyloric resection in 3 cases and pyloroplasty in 3 cases. Post operative course was uneventful with normal oral feeding and normalisation of weight status. Histologic data were aspecific. No recurrence was observed., Discussion: We discuss the origin of the pyloric stenosis, regarding clinical, operative and pathological data: were the stenosis the cause or consequence of peptic ulcer? Peptic disease is always advocated, but difficult to prove and may be excessively incriminated. Late symptomatic congenital and acquired idiopathic pyloric stenosis should be recalled. In all cases of proved pyloric stenosis, after failure of medical and endoscopic treatment, a simple surgical procedure (pyloroplasty) associated with medical treatment seems to be effective., Conclusion: The diagnosis of NHPS should be suspected in a child with food vomiting and loss of weight if his age is not concordant with hypertrophic pyloric stenosis. Upper gastro-intestinal series and endoscopy are diagnostic. The precise cause of the stenosis is more difficult to asses. When the medical treatment fails, a pyloroplasty is usually curative.

Objective: To analyse serious upper gastrointestinal (UGI) complications associated with non-salicylate non-steroidal anti-inflammatory drugs (NSAIDs) in children., Methods: All serious UGI complications associated with non-salicylate NSAIDs approved in France to treat moderate pain or fever in children, spontaneously reported to the French Pharmacovigilance system or to the companies, between the launching of each study drug in France to December 31, 2000., Results: Serious UGI complications were reported in 61 children aged from 11 months to 15 years during treatment with niflumic acid (27), ibuprofen (23) and tiaprofenic acid (11). No case was reported with ketoprofen. UGI manifestations were UGI bleeding (15) and 46 gastrointestinal symptoms with endoscopic lesions i.e. gastritis (18), gastric ulcer (13), duodenal ulcer (7), duodenitis (4) and oesophageal ulcer (4). NSAID was combined with a salicylate in 36% of cases, given by the parents in self medication in 6.6% of cases and used outside its product licence in 33.8% of cases., Conclusion: NSAIDs used in children for fever or moderate pain are associated with a risk of serious UGI complications which increases with length, dose and association with a salicylate.

Introduction: Limb-girdle muscular dystrophy type 2I (LGMD2I) is caused by mutations in the fukutin related protein gene (FKRP gene). This study tries to evaluate clinical, biological and mutational characteristics of LGMD2I., Patients and Methods: Eleven patients belonging to 9 families from the North of France were selected. We reported demographic data, and results of muscular testing, cardiac, and respiratory examination, as well as the histopathological features of muscle tissue and a genetic analysis of FKRP gene for each patient., Results: There were 6 females and 5 males. Mean age at onset was 9.7 years old. Six had Duchenne like phenotype, 5 Becker like phenotype. Nine patients suffered from restrictive respiratory failure, two males had severe dilated cardiomyopathy. Ten patients had the common L276I mutation. Three mutations had not been previously identified: L322V, L489R and R275G heterozygous mutations associated with the L276I mutation., Conclusion: This study underlines inter and intra familial phenotypic variability in LGMD2I, preponderance of cardiomyopathy in males and restrictive respiratory insufficiency in female.

Unlabelled: "Air swallowing" described as being part of functional gastrointestinal disorders in "Rome criteria" in 1999 is often misdiagnosed, particularly in non-mentally deficient children., Aims: To recognize "air swallowing" child and to describe any progress according to the treatment., Population and Methods: This retrospective study reports 13 cases of children without mental deficiency or neuromuscular disease. Clinical elements and precise histories are detailed and we have contacted consulting doctors or families for news., Results: Ten boys and 3 girls, from 2,5 years to 10 years old, were referred for long lasting pain or abdominal distension. Numerous laboratory investigations were always normal. Diagnosis relied upon the observation of air swallowing and X-Rays views of gastric distension. Air swallowing was observed 7 times, 9 children had twitches and 3 language troubles. In 10 cases, X-rays showed gastric and colic distension. Three children have Chilaïditi syndrome. Favourable results followed in 12 cases after an average of 28 months of treatment. One case was lost for follow-up. Treatment was long, often disappointing and required the intervention of a psychiatrist, a paediatrician and (temporarily) a speech therapist., Conclusion: Pathological childhood aerophagia is often underdiagnosed and deserves to be better known by paediatricians, psychiatrists and surgeons. A late diagnosis leads to many negative results and causes anxiety. An early diagnosis should lead to a multidisciplinary care.

Background: Inflammatory bowel disease (IBD) is recognized in young children, however, only rare data on onset and evolution are available in children younger than 1 year. In the present clinical study, we aimed to analyze characteristics and clinical course of children with very early onset IBD. We were particularly interested in the relationship between bacterial infections and the use of antibiotics before the onset of IBD., Patients and Methods: The IBD database of Necker-Enfants-Malades-Hospital was screened for patients with IBD with disease onset during the first year of life and a follow-up of at least 2.5 years. Ten patients were identified during the period 1996-2002., Results: All patients presented with rectal bleeding and had colonic involvement. Four patients had definitive diagnosis of Crohn disease; ulcerative or indeterminate colitis was seen in 2 and 4 children, respectively. Five of the patients had a positive history of neonatal or early-onset bacterial infection with use of antibiotics before onset of IBD, 4 patients were still breastfed and 3 just weaned when GI symptoms started. Seven patients had a severe onset of disease requiring bowel rest, parenteral nutrition and steroid medication, followed by azathioprine or cyclosporine medication. Surgery was necessary in 3 of 10 patients. Disease relapses were frequent and observed in 8 of 10 children., Discussion: Very early onset IBD may reflect a subgroup of patients characterized by a particular sensitivity to modifications of the intestinal flora. Neonatal IBD was most often severe in presentation and evolution.

Background: Camptocormia, characterised by extreme forward flexion of the thoracolumbar spine and severe stooping in the supine position, seems to be prevalent in Parkinson's disease., Objective: The aim of this study was to identify features of parkinsonian camptocormia and to describe the main clinical characteristics of patients with Parkinson's disease who develop the condition., Methods: An extensive range of clinical, biochemical and imaging data were gathered for 23 patients with Parkinson's disease with camptocormia, notably including magnetic resonance imaging (MRI) of the brain and spine, electromyographic recordings of the paravertebral muscles and muscle biopsies., Results: Camptocormia occurred in severe Parkinson's disease with axial predominance, motor fluctuations and dysautonomic symptoms. The condition was often associated with spondyloarthritic changes and pain. MRI showed paraspinal muscle signal abnormalities in five patients and fatty involution in seven patients. The seven patients had motor unit reductions on the spinal erector electromyogram. The MRI results for the girdle muscles were normal. Cranial MRI showed signal abnormalities for the basal ganglia in three patients., Discussion: Various mechanisms may contribute to the development of parkinsonian camptocormia: dopaminergic depletion in Parkinson's disease induces functional changes in the organisation of the corticospinal and reticulospinal tracts, where dysfunction could contribute to axial rigidity. Furthermore, rigidity of the spinal flexion muscles could lead to under-use of the spinal extension muscles, which become progressively atrophic. Rigidity may also induce spinal deformations, leading to a neurogenic syndrome via compression of the spinal nerves., Conclusion: The screening and early management of camptocormia in Parkinson's disease is likely to be important for preventing axial disorders and spinal deformations.

We report the observation of an 18-year-old girl, whose clinical presentation was very suggestive of a congenital myopathy with neonatal onset. A congenital myopathy had been already diagnosed in her brother and in addition her half-cousin died diagnosed with a severe nemaline myopathy at age 4 years. A muscle biopsy performed on both siblings revealed histological and ultrastructural features of 'cap myopathy'. This case report suggests that 'cap myopathy' and some cases of nemaline myopathy with neonatal onset might be two phenotypic expressions of the same genetic disorder. These two entities could therefore, perhaps, be regarded as 'Z-line disorders' possibly caused by defective myofibrillogenesis.

The primary feature of dementia with Lewy bodies (DLB) is the aggregation of alpha-synuclein into characteristic lesions: Lewy bodies (LBs) and Lewy neurites. However, in most of DLB cases, LBs are associated with neurofibrillary tangles and amyloid plaques (both Alzheimer disease [AD]-related lesions). We wanted to determine if this overlap of lesions is statistical, as a result of the late onset of both diseases, or results from a specific physiopathological synergy between synucleinopathy and either tauopathy or amyloid pathology. All patients with DLB from our prospective and multidisciplinary study were analyzed. These cases were compared with cases with pure AD and patients with Parkinson disease and controls. All cases were analyzed thoroughly at the neuropathologic and biochemical levels with a biochemical staging of aggregated alpha-synuclein, tau, and Abeta species. All sporadic cases of DLB were associated with abundant deposits of Abeta x-42 that were similar in quality and quantity to those of AD. Amyloid precursor protein (APP) dysfunction is a risk factor for AD as demonstrated by pathogenic mutations and Abeta accumulation. The constant and abundant Abeta x-42 deposition in sporadic DLB suggests that synucleinopathy is also promoted by APP dysfunction. Therefore, we conclude that APP is a therapeutic target for both AD and DLB.

Introduction: The camptocormia (bent spine) is characterized by a severe forward flexion of the thoracolumbar spine which disappears in the supine position. Clinical case. We describe a typical case observed in a parkinsonian patient. The MRI, electromyogram and biopsy of the paraspinal muscles revealed a typical myositis pattern., Discussion: This case, the sixth published to our knowledge, confirms that focal myositis is associated with the camptocormia in Parkinson's disease. Typically it is observed in male subjects, appearing 4 to 6 years after the onset of Parkinson's disease, in fluctuating patients treated by an association of L-Dopa and agonist. It appears quickly and becomes the most important symptom. Antiparkinsonian drugs are useless., Conclusion: This exceptional picture raises original pathophysiological and therapeutic questions. Systematic studies should be performed in order to detail the pathophysiological link between these 3 entities: Parkinson's disease, focal myositis and camptocormia.

Introduction: Castleman's disease is a lympho-proliferative disease of unknown cause. This rare disease, usually localized, is benign and develops in the young adult. The predominant localization is mediastinal., Observation: A 15 month-old infant was referred for a left latero-cervical mass that had developed since the age of 3 months. Other than this, the clinical examination was normal. Sonography, x-ray and tomodensitometry confirmed the unique nature of the lesion and the absence of loco-regional invasion. Histology following surgical exeresis found a nodule with multiple pseudo-follicular structures. These mitosis-rich structures were arranged concentrically around a vessel and were bordered by small lymphocytes forming a crown. This histological aspect corresponded to Castleman's disease in its vascular hyaline form. Local recurrence was reported twice, 2 and 8 years later and was treated each time with surgical exeresis. Histological examination was always similar to the first., Discussion: Castleman's disease has rarely been reported in infants. The cervical location, at whatever age, is far rarer than the mediastinal form. Supplementary examinations are not always of interest and basically provide information on the isolated or multicentric nature. Surgical exeresis was justified because of the diagnostic doubts and the risk of compression. Diagnosis is based on anatomopathology. Relapses have rarely been described in the literature and raise the question of the potential malignant transformation after several relapses.

Sporadic inclusion body myositis (s-IBM) is the most frequent progressive acquired inflammatory myopathy in people older than 50 years. Abnormal aggregates of 'Alzheimer's proteins', including tau proteins, have been previously demonstrated in s-IBM. In the present study, we have investigated by immunohistochemistry and immunoblotting analysis the presence of tau proteins in muscle biopsy samples from patients with s-IBM and other myopathies with rimmed vacuoles, using newly developed antibodies raised against tau protein epitopes found in Alzheimer's disease brain. Tau immunoreactivity was shown in rimmed vacuoles or inclusions, preferentially with antibodies directed against phosphorylated carboxy-terminal epitopes of tau proteins. Cytoplasmic reactivity was also demonstrated in atrophic, nonvacuolated fibres, as well as in non-necrotic fibres invaded by inflammatory cells. Abnormally phosphorylated tau aggregates were also found in other compartments of the muscle fibre in s-IBM and other myopathies. Tau immunoblotting showed an electrophorectic profile of a doublet within the range of 60-62 kDa isovariants, which was different from tauopathies of the central nervous system. Finally, the unique pattern of immunoreactivity of s-IBM samples towards anti-tau antibodies is a new clue to a possible distinct subclass of peripheral tauopathy, different from the tauopathies of the central nervous system.

Diseases due to mutations in the lamin A/C gene (LMNA) are highly heterogeneous, including neuromuscular and cardiac dystrophies, lipodystrophies, and premature ageing syndromes. In this study we characterized the neuromuscular and cardiac phenotypes of patients bearing the heterozygous LMNA R482W mutation, which is the most frequent genotype associated with the familial partial lipodystrophy of the Dunnigan type (FPLD). Fourteen patients from two unrelated families, including 10 affected subjects, were studied. The two probands had been referred for lipoatrophy and/or diabetes. Lipodystrophy, exclusively observed in LMNA-mutated patients, was of variable severity and limited to postpubertal subjects. Lipodystrophy and metabolic disturbances were more severe in women, even if an enlarged neck was a constant finding. The severity of hypertriglyceridemia and hirsutism in females was related to that of insulin resistance. Clinical muscular alterations were only present in LMNA-mutated patients. Clinical and histological examination showed an invalidating, progressive limb-girdle muscular dystrophy in a 42-yr-old woman that had been present since childhood, associated with a typical postpubertal FPLD phenotype. Six of eight adults presented the association of calf hypertrophy, perihumeral muscular atrophy, and a rolling gait due to proximal lower limb weakness. Muscular histology was compatible with muscular dystrophy in one of them and/or showed a nonspecific excess of lipid droplets (in three cases). Immunostaining of lamin A/C was normal in the six muscular biopsies. Surprisingly, calpain 3 expression was undetectable in the patient with the severe limb-girdle muscular dystrophy, although the gene did not reveal any molecular alterations. At the cardiac level, cardiac septal hypertrophy and atherosclerosis were frequent in FPLD patients. In addition, a 24-yr-old FPLD patient had a symptomatic second degree atrioventricular block. In conclusion, we showed that most lipodystrophic patients affected by the FPLD-linked LMNA R482W mutation show muscular and cardiac abnormalities. The occurrence and severity of the myopathic and lipoatrophic phenotypes varied and were not related. The muscular phenotype was evocative of limb girdle muscular dystrophy. Cardiac hypertrophy and advanced atherosclerosis were frequent. FPLD patients should receive careful neuromuscular and cardiac examination whatever the underlying LMNA mutation.

Infliximab, a monoclonal antibody against tumor necrosis factor-alpha, has been shown to be effective for the treatment of refractory Crohn's disease in adult patients, but experience in pediatrics is limited. This retrospective study included 88 children and adolescents, 39 girls and 49 boys, with a median age of 14 years (range 3.3-17.9). Infliximab was indicated for active disease (66%) and/or fistulas (42%) that were refractory to corticosteroids (70%), and/or other immunosuppressive (82%) agents, and/or parenteral nutrition (20%). Patients received 1 to 17 infusions (median 4) of 5 mg/kg (range 3.8-7.3) of infliximab during a median time period of 4 months (1-17 months). Infusion reaction was noted in 13 patients (15%), with a total of 16 reactions in 450 infusions (4%). At Day 90 after the first infusion of infliximab, symptoms improved in 49% of patients, whereas 29% of patients were in remission and 13% of patients relapsed. From Day 0 to Day 90, Harvey-Bradshaw score decreased from 7.5 to 2.8 (P < 0.001), C-reactive protein from 36 to 16 mg/L (P < 0.01), and 1-hour erythrocyte sedimentation rate from 35 to 17 mm (P < 0.01). Dosage of corticosteroids decreased from to 0.59 to 0.17 mg/kg/d (P < 0.001); 53% of patients could be weaned of corticosteroids and 92% of parenteral nutrition. Treatment with infliximab is well tolerated and effective in most children and adolescents with Crohn's disease that is refractory to conventional immunosuppressive therapy. Nevertheless, long-term efficacy remains to be shown, and further studies are urgently needed to precisely determine the best modality of continuing treatment.

Transpupillary thermotherapy (TTT) has been proposed over the last a few years for the treatment of subfoveal occult choroidal neovessels resulting from age-related degeneration (AMD) when they are symptomatic and associated with exudation. Several pilot studies have shown how this technique can decrease or slow down the progression of exudation related to choroidal neovessels. Based on these pilot studies, a randomized study (TTT4CNV) is in progress to evaluate the efficacy of TTT. While the inclusion of the patients in this study has come to an end, the therapeutic context of AMD has recently been changed with a permit to market Visudyn for photodynamic therapy (PDT) for some types of subfoveal occult choroidal neovessels. Moreover, the clinical studies in progress on photodynamic therapy and antiangiogenic drugs now make it possible to consider combined treatments possibly including TTT. This paper aims to provide a report on the current place and potential of TTT within the therapeutics available or soon available for subfoveal occult choroidal neovessels of AMD.

We report a 42-year-old woman with a hemangiopericytoma tumor located in nasal fossae, revealed by acute dacryocystitis. Clinical rhinoscopic examination and orbitofacial tomodensitometry showed tumefaction of the lacrimal sac and nasolacrimal duct. We removed the tumor by endonasal surgery. The anatomopathology examination confirmed the diagnosis of hemangiopericytoma. The internal canthus area and the maxillary sinus roof were treated with complementary irradiation.

Introduction: Patients suffering from sarcoidosis sometimes report dyspnoea of effort. The restrictive or obstructive ventilatory problems contribute to this disability, but the systemic manifestations of sarcoidosis should be considered as other possible causes of the dyspnoea., Case Report: We report a case of systemic sarcoidosis in a 29 year old man from the Ivory Coast. The disorder presented in December 1999 with generalised symptoms and grade II dyspnoea (Sadoul). Investigations confirmed pulmonary, mediastinal, hepatic, lachrymal and salivary involvement. Lung function tests at rest showed a combined restrictive and obstructive ventilatory defect. The initial exercise test showed evidence of severe limitation of aerobic metabolism with impaired oxygen uptake without limitation of ventilation. The absence of cardiac involvement, confirmed by echocardiography and myocardial isotope scanning, suggested that the dyspnoea was, at least in part, secondary to a "peripheral" muscular abnormality. After 3 months treatment with oral corticosteroids, the clinical and physiological parameters improved. Exercise testing confirmed an improvement in maximum work rate and oxygen uptake. The relative stability of the functional measurements and the subsequent development of myalgia prompted a biopsy of the quadriceps that showed granulomata within the muscle tissue, confirming a sarcoid myopathy. A combination of steroids and methotrexate allowed the patient to increase his exercise capacity without any major change in the resting lung function tests., Conclusions: This case report underlines the role of exercise testing in determining the cause of dyspnoea. In this patient it contributed to the diagnosis of sarcoid myopathy and lead to modification of his treatment.

We report two cases of nontuberculous mycobacterial keratitis, occurring after corneal trauma with superficial foreign body and after perforating keratoplasty for alkali burn, respectively. Patients initially presented with indolent white corneal infiltrates, which did not respond to topical treatment. Both secondarily developed infectious crystalline keratopathy with unequal intensity. In the first case, the excised flap of lamellar keratectomy was cultured, allowing identification of Mycobacterium abscessus. Mycobacterium chelonae was isolated from a corneal biopsy in the second case. The clinical course showed poor response to antibiotic therapy consisting of ciprofloxacin and amikacin drops in conjunction with a new-generation oral macrolide. Corneal infection recurred after lamellar keratectomy in the first patient. Topical corticosteroid interruption burst corneal inflammation and induced stromal necrosis in the other patient. These intractable mycobacterial infections were finally controlled with penetrating keratoplasty. Our data suggest that a rapidly growing mycobacteria culture is required when clinical presentation consists of chronic bacterial keratitis or infectious crystalline keratopathy.

We report a case of a cerebellar large-cell medulloblastoma in a 12-year-old patient. Despite a gross-total resection followed by a radiation therapy and then a chemotherapy, the death occurred 6 months later. The cyogenetic analysis showed an isochromosome 17q. Immunoreactivity for synaptophysin, neurofilaments, chromogranin and arrestin-like proteins was detected, whereas rhodopsin, vimentin, EMA and PAX-6 were negative. In this study, we demonstrate that large-cell medulloblastoma with translocation in chromosome 17q is a neuronal differentiated medulloblastoma with non-photoreceptor characterization. By reverse transcription and polymerase chain reaction (RT-PCR) method, using primers for beta1, beta2 and visual arrestin, we demonstrate corresponding mRNA for beta1, beta2 arrestin but not for visual arrestin. These results suggest that arrestin immunoreactivity in this tumor corresponds to non-visual arrestin. This case corresponds to a new entity of large-cell medulloblastoma. The potential role of a new marker linked to a beta2 adrenergic receptor needs further molecular characterization to be useful.

Background: Four cases of Crohn disease (CD) were diagnosed between 1990 and 1997 in children living in the same area in the Indre-et-Loire district (county A). The local population raised the hypothesis that an environmental source could be responsible for these cases. An investigation was carried out to assess the excess of cases and to identify their possible determinants., Methods: A case was defined as any new case of CD (European definition) that occurred between 1989 and 1998 in county A or in the adjacent county of the Vienne district. Case finding was done by contacting all hospital services, pediatricians and gastro-enterologists in the 2 districts. A Standardized Incidence Rate (SIR) was calculated for sex and age in adults and children using data from the Inflammatory Bowel Registry of northern France. Statistical significance was assessed by a test taking into account small samples. A descriptive study was carried out among pediatric cases., Results: Four pediatric cases and four adults were identified, all from county A. The SIR in adults was 0,45 (95% Confidence Interval [95% CI: 0.12-1.15). In children, the global SIR was 8,51 (95% CI: 2.29-21.79) and 19,05 (95% CI: 5.12-48.70) in county A. The descriptive study did not identify any exposure leading to a possible hypothesis concerning the origin of the cases., Conclusion: This study has shown that the incidence of CD among children of the area was greater than observed in France and has permitted to establish a close relationship with the affected families, to implement a social approach to the problem and to limit rumors. It illustrates the interest of a systematic stepwise approach, which takes into consideration the anxiety of the local community. Cluster investigation should be integrated as part of the public health agencies activities. However, in most cases, despite an excess risk, results do not allow to conclude in terms of etiology.