P.8.b.003 Therapist's role of primary health care in the management of patients with mental disorders

Abstract

La maladie de Niemann-Pick de type C (NPC) est une maladie neuro-viscérale rare, de transmission autosomique récessive, ayant une présentation clinique extrêmement hétérogène. La forme adulte de la maladie est habituellement d’expression neurologique. On peut alors retrouver un syndrome cérébelleux (ataxie, troubles de la marche, dysarthrie), des mouvements anormaux, une cataplexie, des crises d’épilepsie, une dysphagie, une paralysie verticale du regard, ainsi qu’une détérioration cognitive évoluant vers une démence. Des symptômes psychiatriques non spécifiques (manifestations psychotiques de type schizophrénique, syndromes dépressifs, troubles bipolaires, troubles obsessionnels compulsifs, troubles du comportement) y sont souvent associés. Cependant, la maladie de NPC peut également se manifester sous la forme de troubles psychiatriques isolés. Ce tableau psychiatrique est le plus souvent atypique, s’associant à des hallucinations visuelles, une confusion mentale, une fluctuation des symptômes, une réponse inhabituelle ou paradoxale au traitement, une catatonie, une altération cognitive progressive, ou encore à des crises d’épilepsies. La découverte récente d’un traitement, le miglustat, permettant d’en améliorer l’évolution, doit amener les psychiatres à la rechercher devant tout tableau psychotique atypique. Cette revue complète de la littérature internationale vise à porter la maladie de NPC à leur connaissance.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.To achieve this literature review, we used the “PubMed” search engine, looking for the following keywords: Niemann-Pick type C AND (schizophrenia OR psychosis).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.