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Narcolepsy (and Cataplexy)
Published in Alexander R. Toftness, Incredible Consequences of Brain Injury, 2023
If somnolence is like a switch that turns a person's consciousness off and forces them to sleep, then cataplexy is like a switch for a person's muscles that forces them to relax. During an attack of cataplexy, the person loses the ability to move or tone their muscles, resulting in a drooping face, sagging jaw, tongue protrusion, and may cause the person to fall down due to the loss of motor control in the legs (Bassetti et al., 2019). These difficulties in moving muscles are similar to what happens in sleep paralysis, and it has been theorized that cataplexy is similar to REM sleep occurring while you are fully awake (Gauci et al., 2017). Cataplexy doesn't occur during the transition between sleeping and wakefulness like sleep paralysis does—cataplexy happens throughout the course of the person's waking day. Cataplexy attacks can be complete and affect all muscles in the body, or partial, in which they affect only a part of the body such as the face or neck. These attacks usually last for seconds—or a minute or two—and, importantly, the person remains fully awake and conscious the whole time (Adamantidis et al., 2020).
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
This phenomenon is thought to be caused by intrusion of the atonia of REM sleep into the wakeful state. Extraocular muscles and muscles of respiration are not affected. Attacks are often triggered by positive emotions, such as amusement, surprise, and elation, but may also occur with negative emotions such as anger or fear, though this is less common. The distribution of weakness from the atonia is variable, ranging from total postural collapse to minor forms involving focal muscle groups: buckling of the knees, dropping of the head, sagging of the face or jaw, or merely slurred speech. Consciousness is preserved and the duration is short, ranging from a few seconds to a few minutes. Recovery is rapid and complete. Cataplexy can be quite severe around the onset of the disease.
Parasomnias
Published in Stanley R. Resor, Henn Kutt, The Medical Treatment of Epilepsy, 2020
Cataplexy is a flaccid paralysis of the large skeletal muscles which represents an intrusion of the atonia of REM sleep into wakefulness. Most often the paralysis is partial and manifested only by a transient weakness in the arms, legs, or neck. In some instances however, postural atonia is more complete and the patient falls dramatically to the ground. The attacks have a sudden onset often triggered by strong emotion such as laughter, excitement, or anger. Cataplexy is invariably symptomatic of narcolepsy of which it is occasionally the presenting complaint.
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
In the absence of adequate hypocretin activity, patients with NT1 experience not only EDS but also REM sleep dysregulation, which manifests as elements of REM sleep occurring during wakefulness or sleep-wake transitions (i.e. cataplexy, sleep paralysis, hypnagogic hallucinations) [2,9,10]. Muscle atonia is a normal characteristic of REM sleep [18]. During wakefulness, muscle tone is maintained by activity in several neural pathways, including REM sleep-suppressing neurons in the ventrolateral periaqueductal gray and lateral pontine tegmentum (vlPAG/LPT), norepinephrine neurons of the locus coeruleus, serotonin neurons of the dorsal raphe nucleus, and acetylcholine neurons in the lateral dorsal tegmental/pedunculopontine tegmental (LDT/PPT) nuclei [10,12,18–20]. Cataplexy is thought to result from the intermittent activation of REM sleep atonia circuitry, which allows the intrusion of this REM sleep manifestation (i.e. muscle atonia) into wakefulness [9,10,18,21]. Strong emotions activate neural pathways in the prefrontal cortex and amygdala, and hypocretin functions to suppress atonia during normal wakefulness [12,20,21]. Due to the lack of adequate hypocretin activity in patients with NT1, the experience of strong emotions can lead to disinhibition of neurons in the REM sleep atonia circuit and reduced activity in neural pathways that maintain normal muscle tone, which results in the occurrence of muscle atonia during wakefulness (i.e. cataplexy; Figure 1) [9,10,12,18,20,21].
Emerging therapeutic targets for narcolepsy
Published in Expert Opinion on Therapeutic Targets, 2021
Marieke Vringer, Birgitte Rahbek Kornum
Another interesting avenue for treatment of narcolepsy is immunotherapy. In the ideal world, NT1 would be detected very early in the disease process, while the immune system is still active and there still are Hcrt neurons to rescue. Today, with increased disease awareness and better diagnostic tools, such as advanced electroencephalography (EEG) data analysis, patients are diagnosed closer and closer to disease onset. However, there is currently no biomarker available that tracks the immunological disease process, and it is unknown how well (and if at all) occurrence of symptoms correlate with the progression of the underlying pathology. There is a great need for a biomarker that can distinguish patients with an ongoing Hcrt neuron destruction from those where the immune attack is no longer active. The next big question is then what treatment target to choose. Unfortunately, there is no clear and consistent effect of any of the treatment attempts reported mainly as case studies. It could be that the cases included in these studies had progressed too far in their disease course. We know from mouse studies that cataplexy only occurs when a quite severe loss of Hcrt neurons is already present. In other words: immunosuppressive treatment might be wasted on patients with full-blown cataplexy. NT2 patients sometimes progress to NT1, but this is not the typical picture. If such patients could be identified with more certainty, these would be an obvious choice for future investigations into immune system drug targets in narcolepsy.