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Sleep–Wake Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Margaret Kay-Stacey, Eunice Torres-Rivera, Phyllis C. Zee
Multiple factors are thought to contribute to the developed of narcolepsy, including:37A genetic predisposition.Environmental factors.Triggering events that lead to selective, immune-mediated destruction, and/or dysfunction of the orexin-producing neurons in the lateral hypothalamus.
Types of Sleep Disturbances in Women
Published in Zippi Dolev, Mordechai Zalesch, Judy Kupferman, Sleep and Women's Health, 2019
Zippi Dolev, Mordechai Zalesch, Judy Kupferman
In 2000, the brains of narcolepsy sufferers were examined postmortem. Researchers found that cells related to the production of hypocretin had disappeared. This is an autoimmune disease, in which the body attacks itself and kills only those cells. Scientists have yet to discover why this happens. The disease does have a genetic aspect—if one family member suffers from narcolepsy, the chance of another family member to suffer from it is slightly higher; however, it is not a classic hereditary disease.
Physiology of Sleep and Sleep Disorders
Published in John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford, Head & Neck Surgery Plastic Surgery, 2018
Narcolepsy is a condition in which subjects develop severe, often unavoidable chronic sleepiness, with fragmented sleep and frequent awakenings at night, often beginning in early adolescence or adult life. Its prevalence is 1 in 2500, but most are undiagnosed. Consequent problems include avoidance of social or emotional situations, exam failures, few work opportunities, marital difficulties, low self-esteem and depression.
Narcolepsy Treatment: Voices of Adolescents
Published in Behavioral Sleep Medicine, 2022
Lena Xiao, Anna Chen, Arpita Parmar, Lucy Frankel, Alene Toulany, Brian J. Murray, Indra Narang
The main treatment for narcolepsy is pharmacotherapy addressing excessive daytime sleepiness and cataplexy. Excessive daytime sleepiness is often treated with stimulants such as amphetamine, dextroamphetamine, and methylphenidate, as well as wake-promoting agents including modafinil (Thorpy & Bogan, 2020). However, these medications may cause common side effects such as palpitations, anorexia, headache, nervousness, nausea, and insomnia (Black & Hirshkowitz, 2005; Clavenna & Bonati, 2017; Kingshott et al., 2001; Rammohan, 2002). Cataplexy is treated with sodium oxybate, selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, and tricyclic antidepressants (Wise et al., 2007). Common adverse effects include headache, nausea, epigastric discomfort, weight gain, and dry mouth (Babiker & Prasad, 2015; Kotagal, 2018). Specifically, sodium oxybate is a powerful sedative with the potential for misuse and has an inconvenient dosing regimen requiring a dose in the middle of the night. Tricyclic antidepressants may also cause serious adverse events such as arrhythmias, parkinsonism, neuroleptic malignant syndrome or seizures (Houghton et al., 2004). Overall, the disadvantages of pharmacotherapy in narcolepsy are inconsistent efficacy, development of tolerance, dependence, and nonadherence (Houghton et al., 2004; Pérez-Carbonell et al., 2020). Although there are medications or combinations of medications that are efficacious for narcolepsy, these have to be balanced with side effects, which may negatively impact the adherence with daily treatment over the long-term (Taddeo et al., 2008).
Pitolisant for the treatment of cataplexy in adults with narcolepsy
Published in Expert Opinion on Orphan Drugs, 2021
Gerard J. Meskill, Ulf Kallweit, Donna Zarycranski, Christian Caussé, Olivier Finance, Xavier Ligneau, Craig W. Davis
The symptoms of narcolepsy include not only EDS but also manifestations of REM sleep dysregulation (e.g. cataplexy, sleep paralysis, hypnagogic hallucinations) [1,2]. There is a need for increased awareness of cataplexy and other REM-associated features when treating patients with narcolepsy. Patients with cataplexy often alter their behavior to prevent potential cataplexy attacks, which may severely limit their social and interpersonal interactions. Consider, for example, the mother of the groom who refuses to sit at the head table at her son’s wedding reception because she is concerned that the joy and laughter associated with the occasion might trigger an embarrassing episode of cataplexy. Such self-imposed restrictions may successfully regulate emotions to reduce cataplexy, but the use of such strategies to improve symptom control comes at the expense of social, familial, educational, and occupational opportunities for patients. These limitations may ultimately render life less fulfilling, both personally and professionally, for affected patients. Effective treatment of cataplexy can help patients toward a fuller range of emotional expression and life experiences.
Emerging therapeutic targets for narcolepsy
Published in Expert Opinion on Therapeutic Targets, 2021
Marieke Vringer, Birgitte Rahbek Kornum
Narcolepsy is a rare and chronic sleep disorder that is primarily characterized by excessive daytime sleepiness (EDS) and disturbed sleep-wake regulation. Narcolepsy is one of the best studied sleep disorders. There is a large literature on the topic and several recent reviews regarding the etiology [1–4], neurobiology [5–9], and clinical management of the disease [10–17]. Symptomatic treatment has been available for many years but the increased knowledge about the etiology and neurobiology of the disease has given rise to continuous efforts to explore new treatment targets and better treatment options (Table 1). The focus of this review is on these emerging treatment targets. Chapter 1 is a short introduction to the disease, its neurobiology and current treatments. For readers interested in an in-depth review of these topics, we refer to the reviews mentioned above. Chapters 2–5 describe different treatment targets and summarizes the ongoing drug development efforts for each target. The last two chapters give a conclusion and some future directions.