Treatment of narcolepsy: A rare disease of unknown etiology

2021 ◽  
Vol 19 ◽  
Author(s):  
Joaquín M. Campos ◽  
Claudia Molina
Keyword(s):  
Excessive Daytime Sleepiness ◽  
Neurological Disease ◽  
Short Review ◽  
European Population ◽  
Sodium Oxybate ◽  
Unknown Etiology ◽  
Sleep Paralysis ◽  
Main Symptom ◽  
Diagnostic Difficulties ◽  
Hypnagogic Hallucinations

Background: Narcolepsy, also known as Gélineau syndrome, is a chronic and neurological disease that affects 0.05% of the European population, though that percentage could be higher due to the diagnostic difficulties. The main symptom is excessive daytime sleepiness, although it may be accompanied by cataplexy, sleep paralysis and hypnagogic hallucinations. Objective: Nowadays, there is no cure for narcolepsy and the treatment is symptomatic: psychostimulants for the sleepiness by means of amphetamines, methylphenidate or modafinil, and antidepressants and sodium oxybate for treating cataplexy. Method: This is a short review regarding pharmacotherapy for narcolepsy. Result: Hypocretins were discovered in 1998. They are neuropeptides whose deficit is responsible for this symptomatology, has opened up a new field of investigation. Conclusion: Agonists of hypocretins could be a promising therapy against this disease.

scholarly journals 0427 Bicuculine Increased the Cataplexy in the Male Taiep Rats: An Animal Model of Narcolepsy with an Inherent Tubulopathy

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A163-A164
Author(s):  
C Cortes ◽  
J R Eguibar ◽  
J M Ibarra-Hernandez
Keyword(s):  
Theta Rhythm ◽  
Sodium Oxybate ◽  
Male Rats ◽  
Control Group ◽  
Sleep Paralysis ◽  
Dark Cycle ◽  
Gaba Antagonist ◽  
Eeg Recordings ◽  
Hypnagogic Hallucinations

Abstract Introduction Narcolepsy is a hypersomnolence that is characterized by sleep fragmentation, sleep paralysis, hypnagogic hallucinations and cataplexy that is characterized by atonia induced by strong emotions. The amygdala is the trigger for cataplexy through GABAergic mechanisms. Taiep is a myelin mutant with TUBB4A tubulopathy which showed spontaneous episodes of atonia or induced by manipulations from the tail or the thorax. EEG recordings during immobility episodes (IE′s) had a cerebral cortex desynchronized associated to theta rhythm in the hippocampus. The aim of this sturdy was to analyze the effects of bicuculine administration on IE′s and sleep-wake pattern on adult male taiep rats. Methods We used 6 taiep male rats at 9 months of age. The subjects (Ss) lived in individual acrylic cages with water and food pellets available ad libitum, under a 12:12 light-dark cycle (lights on at 0700), with controlled temperature and humidity recording room. All Ss were implanted to record EEG, EMG and EOG to characterize EI′s. We evaluated a basal 24 h EEG recording and then after bicuculine i.p. administration of 0.5, 1 y 1.5 mg/Kg every 48h. We measured the number, mean duration and latency to the first IE′s. Results The duration of IE′s increased 527% with 1 mg/Kg and reach 700% with 1.5 mg/Kg of bicuculine (P<0.01) with respect to saline-treated control group. Importantly, the frequency of IEs did not differ among the groups and did not affect the number of awake, slow wave or rapid eye movements sleep phases. Conclusion Bicuculine, a specific GABA antagonist, modify the duration of IES but not their frequency supporting a role of GABAergic mechanism on IE′s. It is relevant because sodium oxybate, an indirect GABA agonist, reduced cataplexy and improved sleep quality on narcoleptic patients. Support CONACYT grants 243333 and 243247 to CC and JRE, respectively and from VIEP-BUAP 2019 to CA in Neuroendocrinología BUAP-CA-288.

scholarly journals 0756 A One Year Observational Early Access Pitolisant Study of Excessive Daytime Sleepiness in Narcolepsy

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A287-A288
Author(s):  
D J Stultz ◽  
S Osburn ◽  
T Burns ◽  
N Stanley ◽  
R Walton ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Excessive Daytime Sleepiness ◽  
Daytime Sleepiness ◽  
Sodium Oxybate ◽  
Average Score ◽  
Sleep Paralysis ◽  
Nocturnal Sleep ◽  
Early Access ◽  
History Of ◽  
One Year

Abstract Introduction Pitolisant is a H3 receptor antagonist/inverse agonist that has been FDA approved for excessive daytime sleepiness in narcolepsy at doses of either 17.8 mg or 35.6 mg per day. Methods 13 patients (3 males and 10 females) were studied having an average age of 46.8 years, with the majority receiving a dose of 35.6 mg Pitolisant. One patient received 17.8 mg throughout the year, and another advanced after 6 months to the 35.6 mg dose due to hepatic issues. 12 of the patients were Caucasian and one was Asian. 100% of the patients had co-existing sleep and psychiatric disorders. 46% had co-existing sleep apnea and were on CPAP/BIPAP. 38.5% had a history of a head injury. 84.6% of the patients had associated cataplexy, 38% had sleep paralysis, 92% had disrupted nocturnal sleep, and 46% had hypnogogic hallucinations. Throughout the year the patients were monitored using the Epworth Sleepiness Scale (ESS). Nine patients completed the 12-month ESS scales. 12/13 were on other medications to treat narcolepsy prior to starting Pitolisant. 6/13 were on sodium oxybate, 7/13 were on an antidepressant, and 11/13 were on either a stimulant, modafanil, or armodafanil. Only one patient was on Pitolisant alone. Results The patient’s average ESS score at onset was 16.2 Statistically significant findings using paired t-tests were documented. After one-month ESS scores decreased to an average of 13.2 (t=2.38, 9df, P=.04). At 3 months it was 12.4 (t=2.81, 10df, P=.02), at 6 months it was 12.75 (t=4.69, 11df, P<.001) and at 12 months the average score was 13.11 (t=2.55, 8df, P=.03) documenting clinically meaningful decrease of ESS by >/= 3 points. Three patients had ESS scores </=10 at 12 months. Conclusion Improvement on ESS was documented at one month and sustained for one year in patients diagnosed with having narcolepsy both with and without cataplexy. Support **No support was given for this study. Dr. Stultz is a speaker for Harmony Biosciences and has served on their advisory committee. She is also a speaker for Jazz Pharmaceuticals.

Narcolepsy: Differential Diagnosis or Etiology in Some Cases of Bipolar Disorder and Schizophrenia?

CNS Spectrums ◽  
2003 ◽  
Vol 8 (2) ◽  
pp. 120-126 ◽  
Author(s):  
Alan B. Douglass
Keyword(s):  
Bipolar Disorder ◽  
Differential Diagnosis ◽  
Psychiatric Patients ◽  
Human Leukocyte ◽  
Sleep Paralysis ◽  
Leukocyte Antigen ◽  
Psychotic Features ◽  
Hypnagogic Hallucinations ◽  
Rule Out

AbstractDoes narcolepsy, a neurological disease, need to be considered when diagnosing major mental illness? Clinicians have reported cases of narcolepsy with prominent hypnagogic hallucinations that were mistakenly diagnosed as schizophrenia. In some bipolar disorder patients with narcolepsy, the HH resulted in their receiving a more severe diagnosis (ie, bipolar disorder with psychotic features or schizoaffective disorder). The role of narcolepsy in psychiatric patients has remained obscure and problematic, and it may be more prevalent than commonly believed. Classical narcolepsy patients display the clinical “tetrad”—cataplexy, hypnagogic hallucinations, daytime sleep attacks, and sleep paralysis. Over 85% also display the human leukocyte antigen marker DQB10602 (subset of DQ6). Since 1998, discoveries in neuroanatomy and neurophysiology have greatly advanced the understanding of narcolepsy, which involves a nearly total loss of the recently discovered orexin/hypocretin (hypocretin) neurons of the hypothalamus, likely by an autoimmune mechanism. Hypocretin neurons normally supply excitatory signals to brainstem nuclei producing norepinephrine, serotonin, histamine, and dopamine, with resultant suppression of sleep. They also project to basal forebrain areas and cortex. A literature review regarding the differential diagnosis of narcolepsy, affective disorder, and schizophrenia is presented. Furthermore, it is now possible to rule out classical narcolepsy in difficult psychiatric cases. Surprisingly, psychotic patients with narcolepsy will likely require stimulants to fully recover. Many conventional antipsychotic drugs would worsen their symptoms and make them appear to become a “chronic psychotic,” while in fact they can now be properly diagnosed and treated.

Hypnagogic Hallucinations and Sleep Paralysis

Narcolepsy ◽  
2008 ◽  
pp. 87-97 ◽  
Author(s):  
Armando D’Agostino ◽  
Ivan Limosani
Keyword(s):  
Sleep Paralysis ◽  
Hypnagogic Hallucinations

Narcolepsy with cataplexy

2017 ◽  
Author(s):  
Gert Jan Lammers
Keyword(s):  
Excessive Daytime Sleepiness ◽  
Pharmacological Treatment ◽  
Clinical Symptoms ◽  
Sleep Latency ◽  
Daily Life ◽  
Sleep Stages ◽  
Nocturnal Sleep ◽  
Practical Guidelines ◽  
Multiple Sleep Latency ◽  
Hypnagogic Hallucinations

Narcolepsy with cataplexy is caused by disturbed cerebral hypocretin (also called orexin) transmission. It results in impaired physiological boundaries of wake and sleep stages and their specific components, leading to clinical symptoms such as excessive daytime sleepiness (EDS), impaired sustained attention, disturbed nocturnal sleep, cataplexy, and hypnagogic hallucinations. This chapter discusses the consequences for daily life of the disorder, the diagnostic challenges, particularly the interpretation of the results of the multiple sleep latency test (MSLT), the presumed cause and pathophysiology, the frequent comorbidities such as obesity, and practical guidelines for optimal nonpharmacological as well as pharmacological treatment.

scholarly journals Sodium Oxybate for Excessive Daytime Sleepiness in Narcolepsy-Cataplexy

SLEEP ◽  
2004 ◽  
Vol 27 (7) ◽  
pp. 1242-1243 ◽  
Author(s):  
Isabelle Arnulf ◽  
Emmanuel Mignot
Keyword(s):  
Excessive Daytime Sleepiness ◽  
Daytime Sleepiness ◽  
Sodium Oxybate

Neurology and Sleep Research

1971 ◽  
Vol 16 (4) ◽  
pp. 283-293 ◽  
Author(s):  
Roger Broughton
Keyword(s):  
Sleep Deprivation ◽  
Rem Sleep ◽  
Epileptic Seizures ◽  
Sleep Paralysis ◽  
Sleep Research ◽  
Cerebrovascular Accidents ◽  
Therapeutic Relevance ◽  
New Knowledge ◽  
Neurological Conditions ◽  
Hypnagogic Hallucinations

This brief review documents some of the important contributions of recent sleep research to the understanding of a number of neurological conditions. Narcoleptic attacks have been shown to be either episodes of NREM or REM sleep; and cataplexy, sleep paralysis and vivid hypnagogic hallucinations consist of dissociated or inappropriate REM sleep. Important relationships of the hypersomnias and various comas to sleep mechanisms are being increasingly elucidated. Various types of epileptic seizures have been found to be affected differentially by the two types of sleep and by arousal from them; and sleep deprivation may activate or perpetuate epilepsy. Finally, some miscellaneous conditions, such as dyskinesias, cerebrovascular accidents, migraine, and memory and repair functions have been considered. As well as being of pathophysiological interest, much of this new knowledge has a direct diagnostic and therapeutic relevance.

scholarly journals What do we know about sleep paralysis?

2018 ◽  
Vol 19 (3) ◽  
pp. 174-184
Author(s):  
Paulina Wróbel-Knybel ◽  
Michał Flis ◽  
Rafał Dubiel ◽  
Hanna Karakuła-Juchnowicz
Keyword(s):  
Mental Disorders ◽  
Rem Sleep ◽  
Cultural Context ◽  
Somatic Symptoms ◽  
The Body ◽  
Somatic Complaints ◽  
Bibliographic Databases ◽  
Sleep Paralysis ◽  
Somatic Disorders ◽  
Hypnagogic Hallucinations

Summary Introduction: Sleep paralysis (SP) is a condition that widely occurs among people all over the world. It has been known for thousands of years and is rooted in the culture of many countries. It arouses strong emotions, though still little is known about it. The clinical picture of the disorder can be very diverse. It is often accompanied by hypnopompic and hypnagogic hallucinations, somatic complaints and the feeling of intense anxiety. A feeling of paralysis in the body with inhibited consciousness is always observed with the experience. SP pathophysiology is not fully understood, however, most theories explaining this phenomenon are based on the assumption that it results from dysfunctional overlap of REM sleep and wakefulness. It is experienced by healthy people, but it is more often associated with somatic and mental disorders, which is why it is becoming an object of interest for researchers. Aim: The aim of this work is to present the most important information about the disorder known as sleep paralysis - its history, cultural context, pathophysiology, prevalence, symptomatology, coexistence with other somatic and mental disorders as well as diagnostics and available forms of prevention and treatment. Materials and methodology: The available literature was reviewed using the Google Scholar bibliographic databases searching the following keywords: sleep paralysis, REM sleep parasomnias, sleep disorder, night terrors and time descriptors: 1980-2018. Results 1. Sleep paralysis has already been described in antiquity, and interpretations related to its occurrence are largely dependent on culture and beliefs. 2. Symptomatology of the disorder is very diverse: both mental and somatic symptoms are present. 3. The pathophysiology of the disorder has not been fully explained. The basis of most theories regarding sleep paralysis is the assumption that it results from the dysfunctional overlap of REM sleep and wakefulness. 4. The prevalence of SP at least once in a lifetime is 7.6% in the general population, although it is estimated that it is much more frequent in people with various mental and somatic disorders. 5. Treatment of SP is associated with a change in lifestyle and the use of pharmacotherapy and psychotherapy.

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