Section 7 Hypersomnia
7.1 Narcolepsy
There are three main forms of narcolepsy
Secondary narcolepsy, which is found in a variety of conditions including:
2 The patient has a 30-minute nap every day, right after lunch. Which statement about the naps is likely to be true?
7 Why was the fluoxetine not effective in reducing cataplexy?
B Inhibition of adrenergic uptake is effective; fluoxetine is a serotonin reuptake inhibitor with little effect on adrenergic reuptake.
9 The patient is started on modafinil 200 mg in the morning. After a week, he reports little improvement in the sleepiness and no effect on the cataplexy. What is the next step?
A Increase the dose of modafinil to 400 mg, either as one dose in the morning or 200 mg in the morning and 200 mg at noon.
10 With the adjustment of his stimulant medication, the patient has some but not complete improvement in his sleepiness, but the cataplexy is still severe. What is the next step in therapy?
1 D. Narcolepsy with cataplexy. An important clue that makes the first three answers unlikely is that she never lost consciousness. The features that suggest the diagnosis are at the end of the vignette. She has severe sleepiness that began in the teenage years and recurrent episodes of buckling of the knees, a classic description for narcolepsy. One important lesson in this question is to read the entire question and answer. The important information might come at the end. What happened to this patient is that she developed cataplexy while watching a comedy program on television, lost tone of the strap muscles of her neck, and the ensuing anatomical position of her head and neck led to an obstructed upper airway. It is important to remember that the correct name of the disease is “narcolepsy with cataplexy” to distinguish it from “narcolepsy without cataplexy,” emphasizing that only in the former is hypocretin deficiency believed to be pathogenetic. PPSM5, p 957; ICSD2, p 81
2 A. Naps have a very refreshing quality in patients with narcolepsy, and prescription of strategically timed naps is an important aspect of treatment. Patients become more alert and energetic for up to several hours. That is in contrast to patients with sleep apnea or idiopathic hypersomnia, in whom the sleepiness generally does not improve that much with napping. PPSM5, p 962
3 D. Enuresis is not a feature of narcolepsy. The classic tetrad includes sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Other common symptoms include disrupted nocturnal sleep and automatic behavior. PPSM5, p 957
4 D. Sleep disruption and the complaint of insomnia are common and often not elicited during history taking in these patients. Sleep paralysis has been reported to occur in 40% to 80% of narcoleptics. Rapid eye movement sleep can occur much earlier that the typical 90 minutes after sleep onset, and it can occur at sleep onset. This finding, although common in this population, is not considered diagnostic. Early REM sleep also occurs in depressed patients. ICSD2, p 81
5 A. Once symptoms of narcolepsy are present, which often begins during the teenage years, the condition becomes lifelong. Cataplexy is found in at least 60% of cases and is a necessary component of the entity “narcolepsy with cataplexy.” Although it is hypothesized that in some patients an autoimmune process may be responsible for the loss of hypocretin neurons, there has been no rigorous association with any specific autoimmune disorder. Knowledge of narcolepsy and its symptoms, pathophysiology, and treatment will be tested in several sections of the exam. Atlas, p 108
6 C. In the context of a supporting clinical history, the finding during the MSLT of a mean sleep latency of 8 minutes or less and two or more SOREMPs is considered diagnostic of narcolepsy. The finding of early REM is not considered specific enough to be diagnostic. Low hypocretin (less than 110 ng/L) in the CSF is diagnostic of narcolepsy with cataplexy and may be used instead of the MSLT to confirm the diagnosis. ICSD2, p 84
7 B. In both animal models of narcolepsy and humans with narcolepsy, inhibition of adrenergic uptake improves cataplexy. Dopamine and serotonin uptake inhibition is not very effective. Fluoxetine is a serotonin uptake inhibitor. PPSM5, p 940
8 A. Drugs that inhibit adrenergic uptake (protriptyline, desipramine, viloxazine, atomoxetime) are often effective in improving cataplexy. Atomoxetine is a selective norepinephrine reuptake inhibitor approved for use in ADHD. Modafinil has no effect on cataplexy. Prazosin, an alpha 1 antagonist, dramatically aggravates canine narcolepsy-cataplexy. PPSM5, pp 940-941
9 A. The dose of modafinil could be increased to 400 mg, before treating him with either methylphenidate or dextroamphetamine; armodafinil being the R-isomer of modafinil, a dose of 100 mg would be no more effective than 200 mg modafinil. Initial treatment regimens for the treatment of narcolepsy are given in PPSM5. PPSM5, p 962
10 D. Sodium oxybate (gamma-hydroxybutyric acid, GHB) is highly effective in treating cataplexy in narcolepsy and it also improves daytime sleepiness. Before the availability of sodium oxybate, antidepressants such as clomipramine were widely used for this indication. The reader must know the treatment of narcolepsy cold. PPSM5, ch 85
11 A. Hypocretin (also called orexin) is produced by a small number of cells in the lateral hypothalamus. The hypocretin-producing cells are markedly decreased or absent in patients with narcolepsy with cataplexy. The cells may be damaged as part of an autoimmune process. Hypocretin levels in the CSF are reduced (less than 110 ng/L) or absent in narcolepsy with cataplexy patients. Low histamine levels have been reported in patients with hypersomnia. PPSM5, p 942
12 D. This is a classic description of isolated sleep paralysis. The episodes are generally uncommon, and treatment is usually reassurance. They usually do not indicate that other features of narcolepsy will emerge.
13 B. Sodium oxybate in high or toxic doses can lead to respiratory failure. GHB, the “street” version of the medication, can lead to death. Abuse of sodium oxybate is actually unusual because a great deal of salt (sodium) is added to the liquid product, giving it a very noticeable unpleasant taste.
14 C. Sodium oxybate increases slow-wave sleep, and slow-wave sleep is associated with increased growth hormone secretion. Some athletes, such as the weightlifter brother, use illicit GHB for this purpose as a performance-enhancing product. Kava as a “natural” sleep aid has been removed from many markets because it can cause liver failure. Van Cauter et al, 2004
Summary
Forms of Narcolepsy
There are three main forms of narcolepsy
Secondary narcolepsy, which is found in a variety of conditions including:• Genetic disorders
♦ That cause mainly CNS abnormalities: Niemann Pick type C, autosomal dominant cerebellar ataxia, Norrie’s disease (blindness and hearing loss), Coffin-Lowry syndrome (mental retardation and cardiovascular defects)
