Treatment for narcolepsy without cataplexy

IVIg was administered three times, but clinical improvement was not revealed. One out of 11 patients was 52 years old and disease duration was not mentioned. However, the structure binding to MHC class II binding groove is similar to peptide fragments from infectious agents and hypocretin cell autoantigens, therefore the host binds and cross-reacts with CD4 + T cells instead of infectious agents, resulting in autoimmune response to hypocretin neurons. The TCR recognizes the presented peptide with specific amino acid sequence and activates CD4 + T cells. MHC class II binding groove selects peptide fragments with specific amino acids in the context of DQ1A *01:02вЂ“DQB1 *06:02. At MHC/TCR synapse level, this is caused by structural similarities between infectious agents (e.g., H1N1 and/or Streptococcus pyogenes) and hypocretin neuron autoantigen. Subsequently, autoimmune disease persists from uptake by self-tissue antigen and APC. Activation of the cross-reactive TH1 of the microbial epitope and auto-antigen releases cytokines and chemokines and recruit activated monocytes and macrophages, leading to self-tissue damage. This mechanism may occur at the cross reactive by helper T cells and MHC II/TCR synapse level. The fourth mechanism is molecular mimicry, that is characterized by structural similarity of pathogen and antigenic determinants of the host. Specific deletion is a basis for the autoimmune process. Hypocretin-producing cell damage is selective and the melanin-concentrating neuron is not impaired in narcolepsy patients. Decreased hypocretin in CSF suggests that more than 90 percent of hypocretin producing neurons are lost, and this process has begun at narcolepsy onset. The association between hypocretin and narcolepsy has been validated by the reduction of hypocretin peptide in CSF and hypothalamus in narcolepsy patients. Hypocretin has a long-lasting effect on the target neuron, that helps to maintain daytime wakefulness, suppression of REM sleep, and therefore paralysis or dream-like hallucination, that is a REM sleep characteristic manifested during the day when it is deficient. Hypocretin producing neuron is active during wakefulness and stimulates cortex, basal forebrain, brain stem and hypothalamus producing norepinephrine, serotonin, dopamine, and histamine. There are two coned hypocretin receptors, HCRTR1 and HCRTR2, that are serpentine G-protein-coupled receptors. Prepro-hypocretin is enzymatically cleaved into two peptides, divided into hypocretin 1 and 2, and consists of 33 and 28 amino acids, respectively. Hypocretin is synthesized in the lateral hypothalamus and is derived from a protein precursor called prepro-hypocretin. Quality of life studies suggest the impact of narcolepsy is equal to ParkinsonвЂ™s disease. In many patients with narcolepsy, sleepiness is severe, resulting in difficulty focusing and staying awake at school, work and during periods of inactivity. Hypnagogic hallucinations or sleep paralysis are mostly transient. Cataplexy may disappear spontaneously in some patients and it is presumed the patient adapts to his or her illness and avoids situations in which cataplexy can occur.

Symptomatic fluctuations may appear in the clinical course and in general, EDS is the initial symptom and cataplexy occurs slowly over several months after onset and persists for life.

Narcolepsy patients exhibit EDS, cataplexy (decreased muscle tone triggered by emotions) and abnormal transition to rapid eye movement (REM) sleep. Narcolepsy is characterized by decreased cerebrospinal fluid (CSF) hypocretin concentration associated with arousal, wakefulness and sleep regulation.

Treatment for narcolepsy without cataplexy