Narcolepsy is a term that comes from the French coined

Narcolepsy is a term that comes from the French , coined in the 19th century by the French physician Gélineau from the combined form of the Greek words (“numbness”, “stupor”) and (“an attack”, “seizure”). Since its description, narcolepsy has gained increased attention, being a sleep disorder that presents a great impact upon an individual׳s life and that leads to an important daytime impairment. Reflecting concern on the consequences of this disorder, drivers with narcolepsy in United Kingdom, for instance, are required to inform authorities of their condition and must have 3–6 months of satisfactory control of symptoms in order to get licensed. Prevalence may vary from place to place, but studies made in North America, Western Europe and Asia show that, on average, 1 in every 3000 people have narcolepsy . Interestingly, this disorder is more common in men and its onset occurs typically in adolescence, from 15 to 30 years . Despite of researchers׳ efforts in understanding its pathophysiology and finding objective measures for this disease, some aspects of narcolepsy remain a mystery because it buy Cyanine3.5 carboxylic acid most likely represents a heterogeneous disorder. However, some complaints are as diagnostic criteria for narcolepsy. Since the 1st edition of the International Classification of Sleep Disorders (ICSD 1 revised, 2001) , excessive daytime sleepiness is presented as the first diagnostic criteria for narcolepsy, associated with irrepressible need to sleep, or sudden muscle weaknesses, and recurrent daytime lapses into sleep occurring almost daily for at least 3 months. Of note, these criteria were maintained in the 2nd edition of the ICSD, updated in 2005 , and are still part of the current diagnosis of narcolepsy described on the 3rd edition of the ICSD, updated in the present year . In addition, the essential associated features of narcolepsy: sleep paralysis, hypnagogic hallucinations, automatic behaviors and disrupted major sleep episode also remain unchanged. Although some similarities can be found across the ICSD updates regarding the classification of narcolepsy, several changes occurred in this field, especially because of advances in understanding the pathophysiology of this disease. The 1st revised edition of the ICSD reports a single type or narcolepsy, described as a disorder of unknown etiology, with lack of information regarding the pathology and the familial pattern of the disorder. The ICSD 2, already mention 4 subtypes of narcolepsy, referred in the 5th and last edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V, 2013) : narcolepsy with cataplexy; narcolepsy without cataplexy; narcolepsy due to medical condition; unspecified narcolepsy . From this description, the cataplexic property of narcolepsy started to be seen as a differential pattern of the disease, being more specifically related to its genetic specificities. At the genetic level, since ICSD 1 narcolepsy is closely associated with the human leukocyte antigen (HLA) gene, with the HLA DBQ1⁎0602 allele already cited as a potential specific HLA marker associated with narcolepsy . On the 2nd edition of ICSD, the familial pattern of narcolepsy is more deeply specified, with the presence of the HLA DBQ1⁎0602 subtype being more specific to narcolepsy, and restricted to narcolepsy with cataplexy. In the pathophysiological level, cataplexic narcolepsy is described as a disorder associated with the loss of approximately 50,000 to 100,000 hypothalamic neurons containing the neuropeptide hypocretin (orexin). Thus, measuring cerebrospinal fluid (CSF) levels of hypocretin-1, with findings of hypocretin-1 levels ≤110pg/mL or ⅓ of mean control values, is suggested as an alternative diagnostic criterion of narcolepsy with cataplexy in ICSD 2 . However, it is only on the 3rd and more recent edition of the ICSD that the objective measure of CSF hypocretin levels is actually included as a diagnostic criteria of narcolepsy under the statement that it has now been firmly established that narcolepsy with cataplexy is caused by a deficiency in hypocretin signaling, most likely due to a selective loss of hypothalamic hypocretin producing neurons . Thus, cataplexic narcolepsy becomes essentially defined as a hypocretin deficiency syndrome, which is reflected in the need for objective measurements in the clinical criteria. In this scenario, the ICSD 3 describes 2 types of narcolepsy: type 1, with cataplexy and 2 or more sleep onset REM periods (SOREMs) and sleep latency of ≤8min on a multiple sleep latency test (MSLT) and/or CSF hypocretin-1 concentration of ≤110pg/mL or <⅓ of mean control values; type 2, with absence of cataplexy, CSF hypocretin-1 concentration not measured or >110pg/mL or >⅓ of mean control values and the hypersomnolence and/or MSLT findings not better explained by other causes. Of note, each sort brings the specific description of type 1 or 2 narcolepsy due to medical conditions .