Biological markers of narcolepsy with cataplexy (classical narcolepsy) include sleep-onset REM periods (SOREM) on multiple sleep latency tests (MSLT), HLA-DQB1*0602 positivity, low levels of cerebrospinal fluid (CSF) hypocretin-1 (orexin A), increased body mass index (BMI), and high levels of CSF leptin.
Seventeen young adults with a sole diagnosis of HLA DQB1 0602 positive narcolepsy with cataplexy (25.1 +/- 4.6 years old) and 17 healthy comparison subjects (26.8 +/- 4.8 years old).
This results were comparable with other authors, confirming the utility of using specific biomarkers (HLA-DQB1*0602 allele and Hypocretin-1 CSF level) in narcolepsy with cataplexy.
Sporadic narcolepsy with cataplexy is a disabling disease that is strongly associated with the major histocompatibility class II allele HLA DQB1*0602 and is characterized by profound reduction in the cerebrospinal fluid (CSF) concentration of hypocretin 1 levels.
About three quarters of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy had low CSF hypocretin-1 values, and appear to form a distinct clinical entity.
Across populations, low CSF hcrt-1 and HLA-DQB1*0602-positivity characterized the majority of NC (80% to 100%, P = 0.53; 80% to 100%, P = 0.11) but a minority of NwC patients (11% to 29%, P = 0.75; 29% to 89%, P = 0.043).
These ELISA assay results do not support the hypothesis that HLA DQB1*0602-positive narcolepsy with cataplexy is associated with serum antibodies against preprohypocretin or its cleavage products.
To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects.
Essential hypersomnia (EHS) exhibits excessive daytime sleepiness without cataplexy and is associated with the HLA-DRB1*1501-DQB1*0602 haplotype, similar to narcolepsy with cataplexy.
SNP rs5770917 located between CPT1B and CHKB, and HLA-DRB1*1501-DQB1*0602 haplotype were previously identified as susceptibility loci for narcolepsy with cataplexy.
Exome sequencing in 18 families with at least two affected narcolepsy with cataplexy subjects revealed non-synonymous mutations in the second exon of P2RY11 in two families, and P2RY11 re-sequencing in 250 non-familial cases and 135 healthy control subjects revealed further six different non-synonymous mutations in the second exon of P2RY11 in seven patients.
Acting on a specific genetic background, an autoimmune process targeting hypocretin neurons in response to yet unknown environmental factors is the most probable hypothesis in most cases of human narcolepsy with cataplexy.
The sleep disorder narcolepsy with cataplexy is characterized by a highly specific loss of hypocretin (orexin) neurons, leading to the hypothesis that the condition is caused by an immune or autoimmune mechanism.
Narcolepsy with cataplexy is a lifelong disease resulting from the loss of hypocretin neurons in the hypothalamus; structural changes are not, however, limited only to the hypothalamus.
Impaired neurotransmission of hypocretin/orexin (neuropeptides of the lateral hypothalamus) is involved in the neurobiology of narcolepsy with cataplexy (NT1).
White matter alterations related to hypocretin pathway have been less evaluated in patients who have narcolepsy with cataplexy (NC), as compared to the identified exploration of gray matter and have varied among structural brain magnetic resonance imaging studies.
The gold standard exam of narcolepsy with cataplexy is Hypocretin-1 dosage, but in patients without cataplexy and idiopathic hypersomnia, there are no specific diagnostic lab findings.