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Interview to Dr. Soňa Nevšímalová, 1st European narcolepsy day

18/03/2010 ● Lecturas 41.902


Dra. Soňa Nevšímalová President of the nEUroped project for the study of narcolepsy in children. Professor of Neurology. Faculty of Medicine, Department of Neurology. Charles University. Prague, Czech Republic
Question. Do you believe that narcolepsy in children is commonly under-recognized or misdiagnosed?
Answer. According to some clinicians and epidemiologists, only 1 out of 10 narcoleptic patients is correctly diagnosed and treated. The diagnosis certainly depends on the level of pediatric, neurological and psychiatric knowledge in different countries. Thanks to Prof. Roth and the long tradition of clinical and scientific research in this field, I believe, most of the patients in the Czech Republic –including children– are diagnosed correctly. However, just recently, I came across the opinion –even among respected European pediatric neurologists– that narcolepsy, if it does exist in children, is extremely rare. This idea documents that a great many pediatric cases are missed even in EU countries.

Q. The spectrum of narcolepsy is quite broad in childhood; therefore, the delay between the onset of symptoms and accurate diagnosis is long. Treatment of the condition at onset could ameliorate the long-term effects and improve quality of life, even if treatment of narcolepsy remains limited and understudied in the pediatric population. What is your opinion?
A. Excessive daytime sleepiness (EDS) is usually the first symptom of narcolepsy in pediatric cases and, in the absence of cataplexy in the clinical picture, the diagnosis can sometimes be difficult. Doubt is justifiable mainly in those patients whose MSLT shows no convincing proof at the beginning of the disease and/or when the child is too young for classical MSLT examination. In such cases, polysomnographic monitoring, HLA examination and, particularly, hypocretin estimation in the cerebrospinal fluid (CSF) are really helpful. However, there are still cases of narcolepsy without cataplexy with negative HLA and hypocretin findings, where SOREMs in MSLT can appear with a delay. In my opinion, to start with modafinil treatment in such ‘unclear cases’ is a lesser mistake than the ‘wait-and-see’ approach. Treatment should start as early as possible. Sleepiness hampers progress at school and untreated narcolepsy and /or sleepiness of other etiology (e.g. idiopathic hypersomnia) can have a negative impact on further educational achievements.

Q. On the other hand, it seems that the clinical severity of narcolepsy does not depend on the age at onset (Nevsimalova S, Sleep Med 2009; 10: 967-72) and it evolves as a non progressive disease. Altogether this could suggest rather limited benefits of early treatment. In your view, would this be a right conclusion?
A. I am afraid not. According to our study, the maximum severity of the disease (excessive daytime sleepiness as well as cataplexy) appears at the beginning of the disease, and the first and most important peak of age at onset comes in adolescence. Children and particularly adolescents are, therefore, the most distressed population group. Epidemiological studies have shown that narcolepsy has a major negative impact on the quality of life (greater than epilepsy or sleep disorders such as sleep apnea). I believe the prognosis will improve in the future thanks to earlier diagnosis and better treatment (modafinil, sodium oxybate).

Q. You have participated in a recently published study (Hallmayer et al, Nature Genetics 2009; 41: 708-11) where you stated that narcolepsy is strongly associated with the T-cell receptor alpha locus. Could you hypothesize on the connection between this finding and the pathophysiology of the disease?
A. An autoimmune etiology of narcolepsy has long been suspected but never proved. Prof. Mignot with co-workers collected 807 HLA-DQB1*0602 positive cases of narcolepsy-cataplexy and 1,074 HLA-DQB1*0602 positive controls from 3 ethnic groups of the United States, Canada and Europe and, using genome-wide association (GWA), found a link between narcolepsy and polymorphism in the T-cell receptor alpha locus. This is the first documented genetic involvement of T-cell receptor (TCR); therefore, narcolepsy can provide new insights into how HLA-TCR interaction contributes to organ-specific autoimmune targeting and may serve as a model for other HLA-associated disorders.

In another important paper (Aran et al, Sleep 2009; 32: 879-983) Prof. Mignot’s group found that streptococcal infections are probably a significant environmental trigger for narcolepsy that can launch the autoimmune response.

Q. Could you tell us the goals of the nEUroped Project?
A. nEUroped (http://www.neuroped.eu/) is a project currently co-funded by the European Union Public Health Program (April 2008-2011) and devoted to three rare pediatric neurological diseases: alternating hemiplegia in childhood (AHC), rare surgically treatable epileptic syndromes (RSTES) and narcolepsy. 13 different organizations from 10 EU countries participate in this project with the aim to create registries, to improve awareness of these conditions within professional and social life (families, teachers, public), to facilitate research (pathogenesis, diagnosis, management and treatment), to improve services, and to provide insight into a number of rare nervous system disorders in children generally. The outcome of the project should cover data analysis and review designed to develop and disseminate relevant recommendations (Guidelines). The Network should bring benefit to patients and their families, patient organizations, research groups, and other interested parties across Europe.

Q. We know that the first step is focused on creating a European database of narcolepsy in children. Do you think is it convenient to have two separate databases for adults and for children?
A. You are right, surely not. But the decision depends on the nEUroped Steering Board Committee (SBC). It was decided to establish only one IT provider running a database with a common part for three different diseases (AHC, RSTES and narcolepsy), and with separate parts for each specific diagnosis. The common database should be focused on clinical history, medical needs, behavioral problems and education needs, social relations, quality of life and social support. The whole Registry should be simple and centered –as you can see– more on social needs. The still existing EU Narcolepsy Network is focused more specifically on scientific research and on the establishment of international research and cooperation.
Dra. Rosa Peraita-Adrados
Unidad de Sueño-Neurofisiología Clínica
Hospital General Universitario Gregorio Marañón


Prof. Dr. Juan V. Sánchez-Andrés
Depto. Médico, Viguera eds.
Sueño
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