Neurology. 2000 Mar 14;54(5):1166-75.

Current Issues in the Diagnoses and Management of Narcolepsy.
Fry J M.

Introduction.Neurology (suppl. 1)50: p. S1, 1998.

Narcolepsy: preliminary retrospective study of psychiatric and psychosocial aspects.
Krishnan RR, Volow MR, Miller PP, Carwile ST

A review of the charts of 24 ambulatory male veterans with narcolepsy or narcolepsy/cataplexy showed an impressive number of psychiatric and psychosocial difficulties in these patients, such as poor adjustment to the illness, high unemployability, and disturbed intrafamily relationships. Sixteen of the patients had psychiatric disorders according to DSM-III criteria, including adjustment disorder, major depressive episode, alcohol dependence, and personality disorder, but excluding any type of psychotic disorder. The study suggests that narcoleptic/cataplectic patients have more of these difficulties than narcoleptic patients do.

Am J Psychiatry (1984 Mar) 141(3):428-31

The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene [see comments]
Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E

Narcolepsy is a disabling sleep disorder affecting humans and animals. It is characterized by daytime sleepiness, cataplexy, and striking transitions from wakefulness into rapid eye movement (REM) sleep. In this study, we used positional cloning to identify an autosomal recessive mutation responsible for this sleep disorder in a well-established canine model. We have determined that canine narcolepsy is caused by disruption of the hypocretin (orexin) receptor 2 gene (Hcrtr2). This result identifies hypocretins as major sleep-modulating neurotransmitters and opens novel potential therapeutic approaches for narcoleptic patients. Comment in: Cell 1999 Aug 20;98(4):409-12

In: Cell (1999 Aug 6) 98(3):365-76

Vigilance and automobile accidents in patients with sleep apnea or narcolepsy.
Findley L, Unverzagt M, Guchu R, Fabrizio M, Buckner J, Suratt P

Patients with obstructive sleep apnea or narcolepsy report difficulty remaining alert and attentive. To detect impaired vigilance, we designed Steer Clear, a computer program simulating a long and monotonous highway drive that presents 780 obstacles in 30 min. Sixty- two patients with sleep apnea hit a higher percentage of obstacles (4.3 +/- 0.6% [SEM]) than 12 age- and sex-matched subjects without sleep apnea (1.4 +/- 0.3%; p < 0.05) and 10 age- and sex-matched volunteers (1.2 +/- 0.3%; p < 0.05). Ten patients with untreated narcolepsy hit a higher percentage of obstacles while performing on Steer Clear (7.7 +/- 3.2%) than 10 age- and sex-matched subjects without narcolepsy (1.2 +/- 0.3%; p < 0.05). Poor performance on Steer Clear was associated with a higher auto accident rate in the patients with sleep apnea or narcolepsy (p < 0.01). Twenty-one patients who performed normally on Steer Clear had 1 accident in 5 years (0.05 accident/driver/5 yr), and in none of these accidents were they at fault as drivers. Twenty-five patients who performed poorly on Steer Clear had 5 auto accidents in 5 years (0.20 accident/driver/5 yr), and in 20% of these accidents they were at fault as drivers. Twenty-one patients who performed very poorly on Steer Clear had 8 auto accidents in 5 years (0.38 accident/driver/5 yr), and in 38% of these accidents they were at fault as drivers. These 21 patients who performed very poorly on Steer Clear (hitting > 4.5% of obstacles) had a significantly higher auto accident rate than the patients who performed normally (hitting < 1.8%). We conclude: (1) Patients with sleep apnea or narcolepsy performed more poorly on a test of vigilance, Steer Clear, than did control subjects; (2) Impaired vigilance as measured by Steer Clear is associated with a high automobile accident rate in patients with either sleep apnea or narcolepsy.

In: Chest (1995 Sep) 108(3):619-24

A clinical picture of child and adolescent narcolepsy.
Dahl RE, Holttum J, Trubnick L

Although narcolepsy is rarely diagnosed before adulthood, symptoms often begin much earlier and can easily mimic psychiatric disorders in children and adolescents. Clinical experience from a pediatric sleep center is reviewed in 16 consecutive cases of polysomnographically proven narcolepsy with onset of symptoms by age 13 years. Only 1 of the 16 patients presented with the classic clinical tetrad of symptoms (sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis). Behavioral and emotional disturbances were present in 12 of 16 cases, with four patients appearing to have been misdiagnosed with a psychiatric disorder before recognition of the narcolepsy. Obesity appeared as an unexpected association in this case series, with 11 of the 16 narcoleptic patients found to be overweight at the time of diagnosis. The varied clinical presentations, polysomnographic findings, family history, and associated psychiatric symptoms are described. The importance of considering narcolepsy in the differential diagnosis of any child or adolescent with excessive sleepiness is emphasized. Registry Numbers: 113-45-1(Methylphenidate) Registry Numbers: 438-60-8(Protriptyline)

In: J Am Acad Child Adolesc Psychiatry (1994 Jul-Aug) 33(6):834-41

Familial patterns of narcolepsy [see comments]
Guilleminault C, Mignot E, Grumet FC

Familial patterns of narcolepsy were investigated in a clinic population of 334 unrelated narcoleptic patients. 40% of probands had at least 1 family member with an isolated daytime sleepiness complaint and 6% had a positive family history of narcolepsy. Multicase families were rare; only two families were found with 3 or more affected relatives. Family members often shared the same HLA-DR2 haplotype as the proband but did not have narcolepsy. However, the risk of disease for first-degree relatives was six to eighteen times greater than that for unrelated individuals. Although most patients were HLA-DR2+, 2 new HLA-DR2- individuals were found. The data predict that as many as 9% of unrelated North-American white patients with narcolepsy will be DR2-. Analysis of these and other data indicates that although strongly associated with disease, the HLA-DR2 haplotype is neither sufficient nor necessary for the development of narcolepsy. Comment in: Lancet 1990 Feb 17;335(8686):424 Comment in: Lancet 1990 Mar 24;335(8691):726-7 Comment in: Lancet 1990 Apr 14;335(8694):913

In: Lancet (1989 Dec 9) 2(8676):1376-9

Narcolepsy
Aldrich MS ISSN: 0028-4793

[No Abstract Available]

[see comments] In: N Engl J Med (1990 Aug 9) 323(6):389-94

HLA DR15 (DR2) and DQB1*0602 typing studies in 188 narcoleptic patients with cataplexy.
Rogers AE, Meehan J, Guilleminault C, Grumet FC, Mignot E

Narcolepsy is considered a homogeneous clinical entity when excessive daytime sleepiness and cataplexy are present. Cataplexy is a polymorphic symptom that can be very mild and is thus subjectively defined. The Multiple Sleep Latency Test (MSLT) is widely used as a diagnostic test for narcolepsy. A short mean sleep latency and multiple sleep onset REM periods (SOREMPs) are typically observed in narcoleptic patients. The discovery of a tight association of narcolepsy with HLA class II antigens offers a unique opportunity to explore the respective value of the MSLT or of the presence of clear- cut cataplexy in defining an etiologically homogeneous group of narcoleptic patients. In this study, we carried out HLA typing for DR15(DR2) and DQB1*0602 in 188 narcoleptic patients with cataplexy in three ethnic groups (24 Asians, 61 Blacks, and 103 Caucasians). These results confirm the importance of DQB1*0602 typing rather than DR15 (DR2) typing in Black narcoleptic patients and demonstrate that the presence of clear-cut cataplexy is a better predictor for DQB1*0602 positivity than the presence of abnormal MSLT results.

In: Neurology (1997 Jun) 48(6):1550-6

Narcolepsy associated with lesions of the diencephalon.
Aldrich MS, Naylor MW

Although symptomatic narcolepsy, or narcolepsy due to identifiable brain lesions, was once thought to be common, there are few well- documented reported cases since the discovery of the association of REM sleep abnormalities with narcolepsy. Even fewer such reports have been accompanied by human leukocyte antigen (HLA) testing. We report 3 patients who fulfill criteria for symptomatic narcolepsy, 1 with a craniopharyngioma, the 2nd with a hypothalamic syndrome of unknown etiology, and the 3rd with obstructive hydrocephalus and a sarcoid granuloma in the region of the 3rd ventricle. The first 2 were positive for HLA-DR2 while the 3rd was negative for the HLA-DR2 and HLA-DQwl antigens. These findings suggest that diencephalic lesions can be associated with signs and symptoms of narcolepsy that are clinically indistinguishable from those of idiopathic narcolepsy, and that the HLA-DR2 antigen is not required in all cases of symptomatic narcolepsy.

In: Neurology (1989 Nov) 39(11):1505-8

Investigations into the neurologic basis of narcolepsy.
Guilleminault C, Heinzer R, Mignot E, Black J

The understanding of narcolepsy has been enhanced by neurophysiologic investigations in humans and by pharmacologic and biochemical studies using the canine model of narcolepsy. Repetitive microsleeps have a more deleterious effect on performance than several short complete naps during the day. Under normal living conditions, the nocturnal sleep of narcoleptic patients is disrupted, and the spectral analysis of central EEG leads shows less delta power density per epoch than it does in age-matched controls, who have an absence or decrease of the usual decay in delta power across the night. Cataplexy is associated with a drop in H-reflex, even during partial cataplectic attacks. Monitoring of heart rate and intra-arterial blood pressure during cataplexy in humans shows a decrease in heart rate and an increase in blood pressure with onset of cataplexy, but the change in heart rate is secondary to the change in blood pressure. Investigations of narcoleptic Doberman pinschers have implicated several neurotransmitters in the brainstem and amygdala. In vivo dialysis and in situ injections of carbachol indicate that the pontine reticular formation is not the only muscarinic cholinergic region involved, but data support the existence of a multisynaptic descending pathway involved in the muscle atonia of cataplexy. Carbachol injections into the basal forebrain induce status cataplecticus. Experimental findings suggest a hypersensitivity of the overall muscarinic cholinergic system and that this hypersensitive cholinergic system is linked to the limbic system. An increase in the postsynaptic D2 dopaminergic receptor is observed in the amygdala of narcoleptic dogs compared with controls, with impairment of dopamine release. The associated findings suggest that an abnormal cholinergic-dopaminergic interaction could underlie the pathophysiology of narcolepsy.

In: Neurology (1998 Feb) 50(2 Suppl 1):S8-15

Treatment modalities for narcolepsy. Fry JM

Narcolepsy, a lifelong disorder, requires long-term management of symptoms. Interventions may be nonpharmacologic, such as lifestyle changes, and pharmacologic for relief of daytime sleepiness. Pharmacologic treatment of narcolepsy has depended on the use of CNS stimulants to increase wakefulness, vigilance, and performance. The medications considered effective in the treatment of narcolepsy include dextroamphetamine, pemoline, methylphenidate, methamphetamine, and modafinil; only methylphenidate hydrochloride and dextroamphetamine are approved for use in the United States. The currently available stimulants are associated with sympathomimetic side effects, limitations in efficacy, and negative effects on nighttime sleep. This has led to the development of alternative agents. Modafinil, a new wake-promoting agent, has been shown to be effective in reducing daytime sleepiness in patients with narcolepsy. The results of a United States 18-center randomized, placebo- controlled, 9-week trial of modafinil in the treatment of patients with narcolepsy has recently been reported. Patients receiving modafinil demonstrated significant improvement in all subjective and objective measures of sleepiness. Treatment with modafinil 200 mg and 400 mg daily significantly reduced mean scores on the Epworth Sleepiness Scale compared with baseline and placebo (p < 0.001) and significantly increased mean scores on the Maintenance of Wakefulness Test (p < 0.001) and the Multiple Sleep Latency Test (p < 0.001) compared with baseline and placebo. More improvement, as recorded on the Clinical Global Impression of Change scale, was seen in the modafinil group than in the placebo group at all time points (p < 0.001). Modafinil was well tolerated, with headache the only adverse event to occur significantly more often in the active treatment group (p < 0.05). These results suggest that modafinil is an important new therapeutic option for the treatment of narcolepsy.

In: Neurology (1998 Feb) 50(2 Suppl 1):S43-8

Childhood narcolepsy.
Wise MS

Narcolepsy may present during childhood and is probably underrecognized and underdiagnosed in this population. The core symptoms of narcolepsy in children are similar to those in adults, but the expression may be different because of maturational factors. This report focuses on the presenting features that are unique to childhood narcolepsy and the appropriate diagnostic evaluation for suspected narcolepsy in children. Psychosocial and academic problems are almost universal in children with narcolepsy, and management strategies should address these areas. Although currently available stimulant medications may be helpful to some extent, the cornerstone of management is education, emotional and academic support, and careful follow-up over time. The overall goal for managing childhood narcolepsy is to assist the child and family in achieving optimal quality of life.

In: Neurology (1998 Feb) 50(2 Suppl 1):S37-42 ISSN: 0028-3878

The influence of clinical symptoms on quality of life in patients with narcolepsy.
Goswami M

Quality of life is a multidimensional construct involving subjective well-being, health, and welfare. For the patient with narcolepsy, as for any patient with a chronic illness, clinical symptoms have a major impact on physical and psychosocial function and hence on quality of life. This article briefly reviews selected effects of narcolepsy and describes the results of studies undertaken by researchers at the Sleep-Wake Disorders Center of Montefiore Medical Center in New York City. The goal of these studies was to determine the social characteristics and perceived needs of patients and to document the prevalence of the clinical features of narcolepsy and their impact on quality of life. Using a combination of methodologies- -mail survey, record review, and personal interviews--the researchers found that clinical symptoms of narcolepsy have a profound impact on the physical, mental, and social health of those affected with the disorder.

In: Neurology (1998 Feb) 50(2 Suppl 1):S31-6 ISSN: 0028-3878

The psychosocial aspects of narcolepsy.
Douglas NJ

Although referrals for narcolepsy are increasing, physicians continue to confront obstacles in diagnosing and treating this condition. Patients with narcolepsy also face challenges at work, at school, and at home. One of the more disturbing problems is the lack of public awareness of the disorder and its potential therapy. As a result, patients with narcolepsy are often viewed in the school or work setting as being "lazy." In addition, the psychological and sexual side effects of the medications currently available to treat narcolepsy can lead to marital, family, and work-related problems. Irritability, anxiety, and impotence are common. Of particular concern are the risk for a serious automobile accident when the person with narcolepsy remains untreated and the reluctance of narcoleptic patients to seek treatment for fear of losing their driver's license. This article addresses the health system factors that influence the identification and care of patients with narcolepsy and focuses on the psychosocial impact of the disease.

In: Neurology (1998 Feb) 50(2 Suppl 1):S27-30

Proton spectroscopy in the narcoleptic syndrome. Is there evidence of a brainstem lesion?
Ellis CM, Simmons A, Lemmens G, Williams SC, Parkes JD

There is controversy regarding the relationship of structural or biochemical brainstem lesions to "idiopathic" narcolepsy. Most cases of the narcoleptic syndrome are considered to be idiopathic because no structural lesion is detectable, although some cases of secondary narcolepsy are known to be associated with no structural brainstem lesions. Using proton spectroscopy, we determined levels of ventral pontine metabolite pools in 12 normal subjects and 12 subjects with idiopathic narcolepsy. REM sleep is generated in ventral pontine areas. Proton spectroscopy was used to study levels of N-acetyl aspartate (NAA) as a marker of cell mass, creatine and phosphocreatine (Cr + PCr), and choline (Cho). The intensity of the peaks, as determined by the area under the peak (AUP), was measured. The AUP correlates with the quantity of chemical present. In this study, the ratios of NAA to Cr + PCr were similar in normal subjects and in narcoleptic subjects with idiopathic narcolepsy. No differences in measured metabolic ratio were observed in subjects who slept during the scan procedure compared with those who remained awake. Subjects with "symptomatic" narcolepsy accompanied by an obvious structural brain lesion were not studied. Proton spectroscopy of the brain initiates a new kind of neurochemistry, allowing the noninvasive study of metabolic pools in the living human brain without the use of any kind of tracer or radioactive molecule. In this study, there was no evidence of cell loss in the ventral pontine areas of subjects with the narcoleptic syndrome. Registry Numbers: 56-84-8(Aspartic Acid) Registry Numbers: 57-00-1(Creatine) Registry Numbers: 67-07-2(Phosphocreatine) Registry Numbers: 997-55-7(N-acetylaspartate)

In: Neurology (1998 Feb) 50(2 Suppl 1):S23-6

Diagnostic aspects of narcolepsy.
Aldrich MS

The diagnostic criteria for narcolepsy continue to evolve as more is learned about the features of this and other sleep disorders. A variety of symptoms have been said to distinguish narcolepsy from other sleep disorders, including cataplexy, character of daytime sleepiness, sleep paralysis, hypnagogic hallucinations, and automatic behavior. Other diagnostic assessments, such as determination of human leukocyte antigen (HLA) haplotype and findings of sleep laboratory assessments, also contribute to the differential diagnosis. As diagnostic and analytic techniques have become more sophisticated, however, it has become apparent that many of the characteristic features of narcolepsy--including the HLA-DR2 haplotype, sleep-onset REM sleep, and short sleep latency--may also be present in other sleep disorders. Although unambiguous cataplexy does not occur with other sleep disorders and is therefore a valuable symptom for diagnosis, it may occur with a few other neurologic disorders. Furthermore, the clinical assessment of cataplexy-like symptoms is not always straightforward. Current evidence suggests there is a fairly well-defined syndrome of narcolepsy-cataplexy that is highly associated with specific HLA markers and REM sleep abnormalities. On the other hand, there is substantial clinical overlap between narcolepsy without cataplexy and idiopathic hypersomnia. Patients with features of narcolepsy who do not have definite cataplexy and patients with features of idiopathic hypersomnia must be assessed thoroughly because of the possibility that other sleep disorders are the cause of the symptoms.

In: Neurology (1998 Feb) 50(2 Suppl 1):S2-7

Genetic and familial aspects of narcolepsy.
Mignot E

Narcolepsy-cataplexy is a disabling sleep disorder characterized by excessive daytime sleepiness and abnormal REM sleep. The development of human narcolepsy involves environmental factors acting on a specific genetic background. The importance of environmental factors is evidenced by the reported 25 to 31% of monozygotic twins who are concordant for narcolepsy. One of the predisposing genetic factors is located in the MHC DQ region. More than 85% of all narcoleptic patients with definite cataplexy share a specific HLA allele, HLA DQB1*0602 (most often in combination with HLA DR2), compared with 12 to 38% of the general population, as evaluated in various ethnic groups. Genetic factors other than HLA are also likely to be involved. Even if genuine multiplex families are rare, 1 to 2% of the first-degree relatives of narcolepsy patients manifest the disorder, compared with 0.02 to 0.18% in the general population. Studies using a canine model of narcolepsy illustrate the importance of non-MHC genes in disease predisposition. In this model, narcolepsy is transmitted as a single autosomal recessive trait, canarc-1. In spite of an association with immune-related polymorphisms, narcolepsy does not appear to be a classic autoimmune disease. Other pathophysiologic models involving the microglia and the release of specific cytokines in the CNS may be involved and are being explored. This approach, together with positional cloning studies in humans and canines, should reveal the cause of narcolepsy and open new therapeutic avenues.

In: Neurology (1998 Feb) 50(2 Suppl 1):S16-22

Narcolepsy in children.
Kotagal S

Childhood narcolepsy is frequently under-diagnosed. Hypersomnolence may not always be accompanied by cataplexy, sleep paralysis, or hypnagogic hallucinations in the early stages. Pathophysiologic considerations revolve around an altered central nervous system catecholamine-acetylcholine balance. Both idiopathic and symptomatic forms have been described. Serial polysomnography and multiple sleep latency tests may be required to establish a definitive diagnosis. The long-term management requires the provision of both pharmacological and non-pharmacological forms of therapy.

In: Semin Pediatr Neurol (1996 Mar) 3(1):36-43

Health-related quality of life effects of modafinil for treatment of narcolepsy.
Beusterien KM, Rogers AE, Walsleben JA, Emsellem HA, Reblando JA, Wang L, Goswami M, Steinwald B

OBJECTIVE: To evaluate the burden of illness of narcolepsy and assess the health-related quality-of-life (HQL) effects of oral modafinil, a wake-promoting therapy for excessive daytime sleepiness associated with narcolepsy. METHODS: Subjects with narcolepsy enrolled in a nine- week, placebo-controlled, double-blind study and were randomized to placebo, modafinil 200 mg, or modafinil 400 mg. After the study, consenting subjects received modafinil in a 40-week open-label extension. A self-administered HQL questionnaire consisting of the 36- Item Short Form Health Survey (SF-36) and supplemental narcolepsy- specific scales was given to subjects at baseline, study endpoint, and several open-label timepoints. RESULTS: 481 subjects completed a baseline and double-blind endpoint HQL assessment. Compared to population norms, baseline HQL scores reflected substantial burden in vitality, social functioning, and performing usual activities. At study endpoint, subjects in the 400 mg modafinil group had significantly higher scores than placebo for 10 of the 17 HQL scales. The 400 mg modafinil group had more energy, fewer difficulties performing usual activities, fewer interferences with social activities, improved psychological well-being and higher productivity, attention and self-esteem compared to placebo subjects (p<.05). The positive treatment effects were sustained over the open- label extension. CONCLUSION: Modafinil significantly improves health- related quality of life in narcolepsy. Registry Numbers: 68693-11-8(modafinil)

In: Sleep (1999 Sep 15) 22(6):757-65

DQB1*0602 and DQA1*0102 (DQ1) are better markers than DR2 for narcolepsy in Caucasian and black Americans.
Mignot E, Lin X, Arrigoni J, Macaubas C, Olive F, Hallmayer J, Underhill P, Guilleminault C, Dement WC, Grumet FC

In the present study, we tested 19 Caucasian and 28 Black American narcoleptics for the presence of the human leucocyte antigen (HLA) DQB1*0602 and DQA1*0102 (DQ1) genes using a specific polymerase chain reaction (PCR)-oligotyping technique. A similar technique was also used to identify DRB1*1501 and DRB1*1503 (DR2). Results indicate that all but one Caucasian patient (previously identified) were DRB1*1501 (DR2) and DQB1*0602/DQA1*102 (DQ1) positive. In Black Americans, however, DRB1*1501 (DR2) was a poor marker for narcolepsy. Only 75% of patients were DR2 positive, most of them being DRB1*1503, but not DRB1*1501 positive. DQB1*0602 was found in all but one Black narcoleptic patient. The clinical and polygraphic results for this patient were typical, thus confirming the existence of a rare, but genuine form of DQB1*0602 negative narcolepsy. These results demonstrate that DQB1*0602/DQA1*0102 is the best marker for narcolepsy across all ethnic groups.

In: Sleep (1994 Dec) 17(8 Suppl):S60-7

Modafinil: a double-blind multicentric study.
Billiard M, Besset A, Montplaisir J, Laffont F, Goldenberg F, Weill JS, Lubin S

Modafinil is a central putative alpha-1 postsynaptic agonist with vigilance-promoting properties. Fifty narcoleptics (33 male and 17 female) participated in a multicentric study aimed at assessing the effects of the compound on night sleep, feeling on awakening, excessive daytime sleepiness and cataplexy. Modafinil was administered in a double-blind cross-over design at a daily dosage of 300 mg versus placebo. The duration of the study was 12 weeks, including a 2-week "run in" period with placebo, a first 4-week treatment period with either modafinil or placebo, a 2-week wash-out period with placebo and a second 4-week treatment period with either placebo or modafinil. Daily evaluation was based on a sleep log, visual analog scales, a sleep questionnaire and a clinical global index. Sleep laboratory evaluation took place on nights 1, 28, 42 and 70. It included 1 night of polysomnography preceded by a questionnaire on therapeutic and side effects, and a maintenance of wakefulness test (MWT). Sleep logs did not show any modification of night sleep, but a reduction of daytime sleepiness and sleep. Feeling on awakening was not modified. An overall benefit was noted by physicians as well as by patients. MWT disclosed a positive effect of modafinil on excessive daytime sleepiness. Cataplexy was not modified. Registry Numbers: 68693-11-8(modafinil)

In: Sleep (1994 Dec) 17(8 Suppl):S107-12

Narcolepsy and its treatment with stimulants. ASDA standards of practice.
Mitler MM, Aldrich MS, Koob GF, Zarcone VP

This review is part of the standards of practice recommendations. It has been commended and reviewed by the Board of the ASDA. It reflects recommendations of the Board for the practice of sleep medicine in North America. The subcommittee is responsible for the presented write-up. Institutional address: Sleep Disorders Center Scripps Clinic Research Foundation La Jolla CA 92038. (REFERENCE 22 OF 25) 98012407 Aldrich MS, Chervin RD, Malow BA Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy. In: Sleep (1997 Aug) 20(8):620-9 ISSN: 0161-8105 Since its introduction, the multiple sleep latency test (MSLT) has played a major role in the diagnosis of narcolepsy. We assessed its diagnostic value in a series of 2,083 subjects of whom 170 (8.2%) were diagnosed with narcolepsy. The sensitivity of the combination of two or more sleep onset rapid eye movement (REM) periods (SOREMPs) with a mean sleep latency of < 5 minutes on an initial MSLT was 70% with a specificity of 97%, but 30% of all subjects with this combination of findings did not have narcolepsy. In some narcoleptics who had more than one MSLT, the proportion of naps with SOREMPs varied substantially from the initial MSLT to the follow-up test. The highest specificity (99.2%) and positive predictive value (PPV) (87%) for MSLT findings was obtained with the criteria of three or more SOREMPs combined with a mean sleep latency of < 5 minutes, but the sensitivity of this combination was only 46%. The combination of a SOREMP with a sleep latency < 10 minutes on polysomnography yielded a specificity (98.9%) and PPV (73%) almost equal to those obtained from combinations of MSLT findings, but the sensitivity was much lower. Our results suggest that the MSLT cannot be used in isolation to confirm or exclude narcolepsy, is indicated only in selected patients with excessive daytime sleepiness, and is most valuable when interpreted in conjunction with clinical findings.

In: Sleep (1994 Jun) 17(4):352-71

Narcolepsy is a rare disease in Israel [letter]
Lavie P, Peled R

[No Abstract Available]

In: Sleep (1987 Dec) 10(6):608-9

Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness.
Carskadon MA, Dement WC, Mitler MM, Roth T, Westbrook PR, Keenan S

[No Abstract Available]

In: Sleep (1986 Dec) 9(4):519-24

Treatment of narcolepsy with methamphetamine.
Mitler MM, Hajdukovic R, Erman MK

Eight pairs of subjects (each consisting of a narcoleptic and a control matched on the basis of age, sex, educational background and job) were evaluated under the following double-blind, randomized treatment conditions: baseline, placebo, low dose and high dose methamphetamine. Subjects were drug-free for 2 weeks prior to beginning the protocol. Methamphetamine was the only drug taken during the protocol and was given in a single morning dose of 0, 20 or 40-60 mg to narcoleptics and 0, 5 or 10 mg to controls. The protocol was 28 days long, with each of the four treatment conditions lasting 4 days followed by 3 days of washout. Nighttime polysomnography and daytime testing were done during the last 24 hours of each treatment condition. Daytime sleep tendency was assessed with the multiple sleep latency test (MSLT). Daytime performance was assessed with performance tests including a simple, computer-based driving task. Narcoleptics' mean MSLT sleep latency increased from 4.3 minutes on placebo to 9.3 minutes on high dose, compared with an increase from 10.4 to 17.1 minutes for controls. Narcoleptics' error rate on the driving task decreased from 2.53% on placebo to 0.33% on high dose, compared with a decrease from 0.22% to 0.16% for controls. The effects of methamphetamine on nocturnal sleep were generally dose-dependent and affected sleep continuity and rapid eye movement (REM) sleep. Elimination half life was estimated to be between 15.9 and 22.0 hours. Mild side effects emerged in a dose- dependent fashion and most often involved the central nervous system and gastrointestinal tract. We concluded that methamphetamine caused a dose-dependent decrease in daytime sleep tendency and improvement in performance in both narcoleptics and controls. Methamphetamine at doses of 40-60 mg allowed narcoleptics to function at levels comparable to those of unmedicated controls. Registry Numbers: 537-46-2(Methamphetamine)

In: Sleep (1993 Jun) 16(4):306-17

The action of tricyclics (alone or in combination with methylphenidate) upon several symptoms of narcolepsy.
Takahashi S.

In: Guilleminault C, Dement WC, Passouant P, eds. Narcolepsy. New York: Spectrum 625-641, 1976.

Psychosocial aspects of narcolepsy.
Goswami M, Pollak CP, Cohen FL, Thorpy MJ, Kavey NB, Kutscher AH, eds. New York: Haworth Press, 1992.

Reported accidents in narcolepsy.
Cohen FL, Ferrans CE, Eshler B.

In: Goswai M, Pollak CP, Cohen FL, Thorpy MJ, Kavey NB, Kutscher Ah, eds. Psychosocial aspects of narcolepsy. New York: Haworth Press,71-80, 1992.

Long-term tratment of narcolepsy with methylphidate (RitalinTM)
Honda Y, Hishakawa Y, Takahashi Y.

Curr Ther Res 25:288-298, 1979.

A long-term treatment of narcolepsy and excessive daytime sleepiness with pemoline (BetanaminTM).
Honda Y, Hishikawa Y.

Curr Res 27:429-441, 1980.

Linkage of human narcolepsy with HLA association to chromosome 4p13-q21.
Nakayama J, Miura M, Honda M, Miki T, Honda Y, Arinami T.

[MEDLINE record in process]

Genomics. 2000 Apr 1;65(1):84-6.

Hypocretin (orexin) deficiency in human narcolepsy.
Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E.

[MEDLINE record in process]

Lancet. 2000 Jan 1;355(9197):39-40.