Saúde mental infanto-juvenil: uma reflexão sobre políticas públicas a partir do dispositivo intercessor como meio de produção de conhecimento na práxis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Unravelling Molecular and Cellular Disease Mechanisms in Infantile Neuronal Ceroid Lipofuscinosis (INCL)

Studying neurodegeneration provides an opportunity to gain insights into normal cell physiology, and not just pathophysiology. In this thesis work the focus is on Infantile Neuronal Ceroid Lipofuscinosis (INCL). It is a recessively inherited lysosomal storage disorder. The disease belongs to the neuronal ceroid lipofuscinoses (NCLs), a group of common progressive neurodegenerative diseases of the childhood. Characteristic accumulation of autofluorescent storage material is seen in most tissues but only neurons of the central nervous system are damaged and eventually lost during the course of the disease leaving most other cell types unaffected. The disease is caused by mutations in the CLN1 gene, but the physiological function of the corresponding protein the palmitoyl protein thioesterase (PPT1) has remained elusive. The aim of this thesis work was to shed light on the molecular and cell biological mechanisms behind INCL. This study pinpointed the localization of PPT1 in axonal presynapses of neurons. It also established the role of PPT1 in early neuronal maturation as well as importance in mature neuronal synapses. This study revealed an endocytic defect in INCL patient cells manifesting itself as delayed trafficking of receptor and non-receptor mediated endocytic markers. Furthermore, this study was the first to connect the INCL storage proteins the sphingolipid activator proteins (SAPs) A and D to pathological events on the cellular level. Abnormal endocytic processing and intracellular re-localization was demonstrated in patient cells and disease model knock-out mouse neurons. To identify early affected cellular and metabolic pathways in INCL, knock-out mouse neurons were studied by global transcript profiling and functional analysis. The gene expression analysis revealed changes in neuronal maturation and cell communication strongly associated with the regulated secretory system. Furthermore, cholesterol metabolic pathways were found to be affected. Functional studies with the knock-out mouse model revealed abnormalities in neuronal maturation as well as key neuronal functions including abnormalities in intracellular calcium homeostasis and cholesterol metabolism. Together the findings, introduced in this thesis work, support the essential role of PPT1 in developing neurons as well as synaptic sites of mature neurons. Results of this thesis also elucidate early events in INCL pathogenesis revealing defective pathways ultimately leading to the neurodegenerative process. These results contribute to the understanding of the vital physiological function of PPT1 and broader knowledge of common cellular mechanisms behind neurodegeneration. These results add to the knowledge of these severe diseases offering basis for new approaches in treatment strategies.

Phenotypic overlap between infantile systemic lupus erythematosus and Aicardi-Goutières syndrome.

Case Reports

Ultrasound biomicroscopy in infantile glaucoma

Background: Glaucoma in infants has many causes. Evaluation of the anatomy of the anterior segment of eyes with infantile glaucoma may help to determine the pathogenesis of an infant's disease and influence therapeutic decisions. Methods: Eleven eyes of six infants with glaucoma were evaluated with ultrasound biomicroscopy (UBM) to evaluate the anatomic characteristics and relationships of the anterior segment structures. Results: The anterior chamber angle, iris, lens, ciliary body, and posterior chamber angle could be imaged in detail. Elongated and anteriorly placed ciliary processes were noted in all eight eyes with trabeculodysgenesis. There were no apparent anomalies in the trabecular meshwork, or anterior chamber. In three eyes with dense corneal opacities, ultrasound biomicroscopy showed severe anterior segment disorganization and thin central corneas with posterior corneal excavation. Conclusions: Ultrasound biomicroscopy is a useful non-invasive method for evaluating infants with glaucoma in cases with corneal opacities. This information can help in surgical planning for glaucoma management.

Insertion dans les soins après une première hospitalisation dans un secteur pour psychose [Linkage to care after first hospitalisation for psychosis]

BACKGROUND: First hospitalisation for a psychotic episode causes intense distress to patients and families, but offers an opportunity to make a diagnosis and start treatment. However, linkage to outpatient psychiatric care remains a notoriously difficult step for young psychotic patients, who frequently interrupt treatment after hospitalisation. Persistence of symptoms, and untreated psychosis may therefore remain a problem despite hospitalisation and proper diagnosis. With persisting psychotic symptoms, numerous complications may arise: breakdown in relationships, loss of family and social support, loss of employment or study interruption, denial of disease, depression, suicide, substance abuse and violence. Understanding mechanisms that might promote linkage to outpatient psychiatric care is therefore a critical issue, especially in early intervention in psychotic disorders. OBJECTIVE: To study which factors hinder or promote linkage of young psychotic patients to outpatient psychiatric care after a first hospitalisation, in the absence of a vertically integrated program for early psychosis. Method. File audit study of all patients aged 18 to 30 who were admitted for the first time to the psychiatric University Hospital of Lausanne in the year 2000. For statistical analysis, chi2 tests were used for categorical variables and t-test for dimensional variables; p<0.05 was considered as statistically significant. RESULTS: 230 patients aged 18 to 30 were admitted to the Lausanne University psychiatric hospital for the first time during the year 2000, 52 of them with a diagnosis of psychosis (23%). Patients with psychosis were mostly male (83%) when compared with non-psychosis patients (49%). Furthermore, they had (1) 10 days longer mean duration of stay (24 vs 14 days), (2) a higher rate of compulsory admissions (53% vs 22%) and (3) were more often hospitalised by a psychiatrist rather than by a general practitioner (83% vs 53%). Other socio-demographic and clinical features at admission were similar in the two groups. Among the 52 psychotic patients, 10 did not stay in the catchment area for subsequent treatment. Among the 42 psychotic patients who remained in the catchment area after discharge, 20 (48%) did not attend the scheduled or rescheduled outpatient appointment. None of the socio demographic characteristics were associated with attendance to outpatient appointments. On the other hand, voluntary admission and suicidal ideation before admission were significantly related to attending the initial appointment. Moreover, some elements of treatment seemed to be associated with higher likelihood to attend outpatient treatment: (1) provision of information to the patient regarding diagnosis, (2) discussion about the treatment plan between in- and outpatient staff, (3) involvement of outpatient team during hospitalisation, and (4) elaboration of concrete strategies to face basic needs, organise daily activities or education and reach for help in case of need. CONCLUSION: As in other studies, half of the patients admitted for a first psychotic episode failed to link to outpatient psychiatric care. Our study suggests that treatment rather than patient's characteristics play a critical role in this phenomenon. Development of a partnership and involvement of patients in the decision process, provision of good information regarding the illness, clear definition of the treatment plan, development of concrete strategies to cope with the illness and its potential complications, and involvement of the outpatient treating team already during hospitalisation, all came out as critical strategies to facilitate adherence to outpatient care. While the current rate of disengagement after admission is highly concerning, our finding are encouraging since they constitute strategies that can easily be implemented. An open approach to psychosis, the development of partnership with patients and a better coordination between inpatient and outpatient teams should therefore be among the targets of early intervention programs. These observations might help setting up priorities when conceptualising new programs and facilitate the implementation of services that facilitate engagement of patients in treatment during the critical initial phase of psychotic disorders.

Propranolol in infantile haemangioma: simplifying pretreatment monitoring.

BACKGROUND: Infantile haemangiomas (IHs) are very common vascular tumours. Propranolol is at present the first-line treatment for problematic and complicated haemangioma. In accordance with a Swiss protocol, children are monitored for 2 days at the start of the treatment to detect possible side effects of this drug. Our study advocates a simplification of the pretreatment monitoring process. METHODS: All children with a problematic and complicated haemangioma treated with propranolol between September 2009 and September 2012 were included in the study. All patients were hospitalised under constant nurse supervision for 48 hours at the start of the treatment and subjected to cardiac and blood measurements. The dosage of propranolol was 1 mg/kg/day on the first day and 2 mg/kg/day from the second day. Demographic data, clinical features, treatment outcome and complications were analysed. RESULTS: Twenty-nine infants were included in our study. Of these, 86.2% responded immediately to the treatment. There were no severe adverse reactions. Six patients presented transient side effects such as bradycardia, hypotension after the first dose and hypoglycaemia later. No side effects occurred after the second dose. Treatment was never interrupted. CONCLUSION: Propranolol (a β-blocker) is a safe treatment for problematic IH. Side effects may occur after the first dose. A strict 48 hour monitoring in hospital is expensive and may be unnecessary as long as the contraindications for the drug are respected.

Les troubles mentaux de l'enfance : précis de psychiatrie infantile avec les applications pédagogiques et médico-légales / par le Dr Marcel Manheimer,... ; préface de M. le Pr Joffroy

Mécénat texte imprimé : Cet ouvrage a été numérisé grâce au fonds « Docteur Jean-Paul Sichel », dédié à l'histoire de la psychiatrie

Précis de chirurgie infantile

UANL