[Predictive factors of seclusion duration in patients hospitalized in psychiatry settings. A prospective multisite study in the DTRF Paris-Sud]. / Facteurs prédictifs de la durée d'isolement chez les patients hospitalisés en psychiatrie. Une étude prospective multicentrique au sein du DTRF Paris-Sud.

INTRODUCTION: In psychiatric inpatient settings seclusion is a last resort to ensure the safety of the patient, other patients, and staff from disturbed behaviors. Despite its major interest for patients, seclusion could negatively impact treatment adherence and patient/staff relationships. Indeed, some secluded patients report a feeling of guilt during the measure and do not consider seclusion to be a healthcare intervention. To be more beneficial and to reduce the feeling by patients of being forced, seclusions should be as short and rare as possible. In other words, measures to reduce seclusion are available and have been clearly identified. Such measures could be applied, in the first instance, in patients with longer duration. In this way, the aim of this study was to investigate predictive factors of a seclusion of long duration. METHODS: Our study was based on the dataset of the EPIC study, an observational prospective French multicenter study of seclusion and restraint. The EPIC study occurred in seven French psychiatric hospitals in the southern region of Paris. Inclusions were realized for 73days and allowed a data collection of 302 seclusion measures. Of these measures 236 were effectively a seclusion in a standardized room. Because the median duration was 7days, we defined two groups of patients: duration<7days and duration ≥ 7 days. Our variable to be explicated was duration ≥ 7 days. Explicative variables available in EPIC study were age, sex, forced hospitalization, autoagressivity, heteroagressivity, use of sedative treatment (oral or intramuscular), history of seclusion and patient diagnoses. We used bivariate and multivariate analyses to explore the association between a seclusion duration ≥ 7 days and explicative variables. Diagnoses were classified as psychotic disorders, mood disorders and others diagnoses. To be included in multivariate logistic regressions, diagnoses were treated as dummy variables (mood disorder vs psychotic disorders; psychotic disorders vs others; mood disorders vs others). Statistical analyses were performed using SPSS software 20.0 and R 3.4.0. RESULTS: Of the 236 measures of seclusion the mean age was 38.2 (±12.8), 196 (83%) patients were forcibly hospitalized prior to their seclusion, 147 (62%) had a diagnosis of psychotic disorder, 43 (18%) a diagnosis of mood disorder and 33 (14%) an "other diagnosis". Mean duration was 10.2 (1.5) days and median was 7.1 days. One hundred and thirty-five (47%) patients were in the group of duration ≥ 7 days. In bivariate analyses, variables associated with a duration ≥ 7 days were: being in forced hospitalization prior to the seclusion (P=0.04), administration of a sedative treatment (P=0.01) and against the group of others diagnoses the diagnosis of mood disorders (P<0.0005) and psychotic disorders (P=0.001). Multivariate analyses showed that, against the group of other diagnoses, the group of psychotic disorders [OR=3.3, CI 95% (1.3-8.4), P=0.01], the group of mood disorder [OR=2.7, CI 95% (1.4-4.9), P=0.002] and administration of sedative treatment [OR=8.1, CI 95% (2.0-32.5), P=0.003] were significantly associated with a duration ≥ 7 days. These results were independent from other confusion variables. Considering the hospitalization status, psychotic disorders was the only diagnosis which showed an association between duration ≥ 7 days and forced hospitalization [OR=2.9 CI 95% (1.1-7.8), P=0.03]. CONCLUSION: Our study highlighted two profiles of higher risk to remain ≥ 7days in seclusion. The first one is patients with a diagnosis of mood disorder who needed sedative treatment. The second one is patients with a diagnosis of psychotic disorder who needed sedative treatment and forced hospitalized before seclusion. Thus, these two profiles could be a good target to practice, in the first instance, measures to reduce seclusion duration in psychiatry settings.

[Niemann-Pick type C disease and psychosis: Two siblings]. / Maladie de Niemann-Pick de type C et troubles psychiatriques : le cas d'une fratrie.

INTRODUCTION: Niemann-Pick type C disease (NPC) is a rare, neurovisceral, autosomal recessive disease, with an extremely heterogeneous clinical presentation. The adult form of the disease is usually expressed as a neurological form. Non-specific psychiatric symptoms are often associated with NPC. For some cases, it can also be expressed as an isolated psychiatric disorder form. Since 2009, the launching of a medicine called miglustat has helped to improve the disease evolution. CASE HISTORIES: We report two siblings followed-up in the same department of psychiatry and with an atypical psychotic symptomatology. Case 1 is a 27-year-old French male. He was hospitalised several times due to disordered behaviour, psychomotor excitation, mood instability and wandering. He was originally diagnosed with schizophrenia. However, the patient's psychosis proved refractory to treatment. He also exhibited a number of neurological signs (pyramidal signs and abnormal movements of the hands, head and limbs), which were considered related to his antipsychotic medication. Three years later, a full physical, neurological and neuropsychological examination revealed various neurological and visceral symptoms. He was diagnosed with NPC based on a classical biochemical NPC-phenotype following filipin staining in cultured skin fibroblasts. NPC1 gene sequencing revealed that he was a compound heterozygote for the p.S954L and p.N1156S mutations. The patient's psychiatric and neurological symptoms are currently stabilized by miglustat, allowing the patient to cease antipsychotic medication. Case 2 is the elder sister of Case 1. She was hospitalised several times due to acute delirium, hallucinations and suicidal tendencies. She was diagnosed with paranoid schizophrenia at 22 years of age. She has received a variety of typical and atypical antipsychotics. Many of these drugs proved initially effective but the patient's symptoms repeatedly returned. The patient shows persistent and worsening gait disorder and abnormal arm movements. A follow-up neurological examination at age 29 did not detect any ataxia, cataplexy or vertical supra-nuclear gaze palsy. Direct NPC1 gene sequencing detected a mutant NPC1 allele held in common with her brother, but full sequencing of both the NPC1 and NPC2 genes and multiplex ligation-dependent probe amplification (MLPA) did not detect any other pathogenic mutation or other anomalies. DISCUSSION: Because NPC is an autosomal recessive condition, heterozygous individuals carrying only one causal gene mutation are usually asymptomatic. Thus, while the accepted wisdom would suggest that patient 2 is not affected by the disease, it is interesting to consider why she has developed neurological and psychiatric disorders like her brother. Several hypotheses are discussed: mental expression in heterozygous genetic factor predisposing to schizophrenia, comorbidity or fortuitous association. It is not currently known whether a patient with a single NPC gene mutation can express NPC in full, partially, or perhaps just to a minimal degree. This case of a patient with a heterozygous "carrier" NPC genotype and neuropsychiatric disorders suggestive of the disease raises the possibility that symptomatic heterozygous NPC patients may exist. On the other hand, if the heterozygous genotype of patient 2 does not give rise to symptomatic disease, it is pertinent to question whether it could be a predisposing factor for the development of psychiatric pathologies. There are currently no published data on the occurrence of heterozygous NPC1 or NPC2 mutations among patients with atypical psychiatric presentations combined with neurological symptoms. Conversely, there are no published data demonstrating an increased frequency of psychiatric disorders in families affected by NPC. Finally, in view of the history of psychiatric disorders in this family, it is possible that psychosis simply occurred concomitantly with symptomatic NPC in patient 1 by chance, and that schizophrenia occurred simultaneously with an asymptomatic NPC carrier genotype in patient 2. To investigate this further, NPC patients' carrier family members (parents and siblings) should be fully screened for signs suggestive of the disease.

[Adult onset Niemann-Pick type C disease and psychosis: literature review]. / Maladie de Niemann-Pick de type C chez l'adulte et troubles psychiatriques : revue de littérature.

INTRODUCTION: Niemann-Pick type C disease (NPC) is a rare hereditary disease, which psychiatrists do not face often in France. Indeed, only a couple of articles specifically describing the psychiatric-disorders in the adult form have been published. And for the most part, they were not written by psychiatrists. This comprehensive international literature review aims at providing knowledge on this disease to French psychiatrists. METHODS: To achieve this literature review, we used the "PubMed" search engine, looking for the following keywords: Niemann-Pick type C AND (schizophrenia OR psychosis). RESULTS: Niemann-Pick type C disease (NPC) is a rare, neurovisceral, autosomal recessive disease, with an extremely heterogeneous clinical presentation. It is characterized by a wide range of symptoms that are not specific, such as neurological, systemic or psychiatric symptoms. The adult form of the disease concerns a small proportion (5 %) of the people affected and is usually expressed as a neurological form. A variety of progressive and disabling symptoms are encountered, mainly cerebellar signs (cerebellar ataxia, impaired gait, dysarthria), but also movement disorders, cataplexy, seizures and dysphagia. Patients face constant cognitive deterioration, which can result in severe dementia. Abnormal saccadic eye movement is often the first manifestation of the disease. Supranuclear gaze palsy is considered to be a specific sign and should be systematically searched for. In terms of systemic signs, the usual infantile hepatosplenomegaly is very fickle in the adult form; if present, it is usually asymptomatic. Non-specific psychiatric symptoms are often associated with NPC disease. For one third of cases, it can also express as an isolated psychiatric-disorder form, such as schizophrenia-like psychosis (paranoid delusions, auditory hallucinations, interpretative thoughts, and disorganization), depression, bipolar disorder, obsessive-compulsive behaviour and behavioural problems (sleep disorders, hyperactivity, agitation, aggressiveness or self-mutilations). This psychiatric overview is mostly atypical and is accompanied by visual hallucinations, confusion, symptom fluctuations, treatment resistance or aggravation with neuroleptic drugs, catatonia, progressive cognitive decline, but also seizures. The late appearance of neurological manifestations is often wrongfully attributed to the effects of antipsychotic medication, which generates tardy diagnosis. Most of NPC affected patients die prematurely. NPC diagnosis is based on a filipin test on a fibroblast culture from a skin biopsy and also on a sequencing of the NPC1 and NPC2 genes. Routine laboratory biochemistry profiles are generally normal. The early diagnosis is fundamental to deploy the best follow-up care. The patient should therefore be in contact with a reference centre. Until recently, NPC treatment consisted in supportive therapies and symptomatic drugs, useful, however, with variable efficacy. The recent discovery of a medicine called Miglustat (N-butyldeoxynojirimycin; NB-DJN; Zavesca(®), Actelion Pharmaceuticals Ltd.) which improves the disease evolution, should encourage psychiatrists to look for it in every atypical psychosis.