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The Maintenance of Wakefulness Test in Pediatric Narcolepsy
Pediatric Neurology 48 (2013) 443e446
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Original Article
The Maintenance of Wakefulness Test in Pediatric Narcolepsy Stephanie Zandieh MD a, b, Sriram Ramgopal MD b, Umakanth Khatwa MD a, c, Michelle SanGiuliano RPSGT a, Michael Gunnuscio RPSGT a, Marcin Zarowski MD PhD d, Sanjeev V. Kothare MD a, b, * a
Center for Pediatric Sleep Disorders, Boston Children’s Hospital, Boston, Massachusetts Department of Neurology, Boston Children’s Hospital, Boston, Massachusetts c Division of Respiratory Medicine, Department of Medicine, Boston Children’s Hospital, Boston, Massachusetts d Department of Developmental Neurology, Poznan University of Medical Sciences, Poznan, Poland b
article information
abstract
Article history: Received 12 February 2013 Accepted 13 February 2013
Objective tools are needed to assess the response to treatment in pediatric narcolepsy. This article presents a single-center experience documenting the use of the maintenance of wakefulness test (MWT) in a pediatric series. This study reviewed the charts of children with narcolepsy who had an MWT performed between January 2008 and June 2012. A cutoff was used for mean sleep latency: <8 minutes for inadequate control of hypersomnia, and >20 minutes to indicate adequate control on medications. Thirteen tests were performed on 10 children (median age 15.8 years, range 8.7-20.3 years) with narcolepsy, of which six had cataplexy and three were boys. Comorbid conditions included Prader-Willi syndrome, bipolar affective disorder, and epilepsy (n ¼ 1 each). The median mean sleep latency for all studies was 16 minutes (range 5.8-40 minutes). Sleep-onset rapid eye movement sleep events were seen in three of 13 studies. In seven patients, findings from the MWT resulted in changes in management. These data suggest that the MWT may be a useful and feasible test for assessing response to treatment in children with narcolepsy. Future research is needed to obtain normative MWT data on children with and without narcolepsy. Ó 2013 Elsevier Inc. All rights reserved.
Introduction
Narcolepsy is characterized by hypersomnia along with sleep attacks. Population studies have estimated the incidence of narcolepsy to be 0.05-0.067% [1,2]. Although the disease is better characterized in adults, it has been noted to follow a bimodal distribution in its ages of presentation: a Canadian/French epidemiologic study found that the first Sanjeev Kothare is funded by the following grants: National Institutes of Health: 1 RC1 HL099749-01 (R21), and RFA-HL-09-001, and an investigatorinitiated grant from Eisai Pharma, Inc, to assess safety and efficacy of rufinamide in children, and the Harvard Catalyst to assess cardiorespiratory abnormalities during seizures in children.
* Communications should be addressed to: Dr. Kothare; Division of Epilepsy and Clinical Neurophysiology; Fegan 9; Boston Children’s Hospital; 300 Longwood Avenue; Boston, MA 02115. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2013.02.007
peak in onset occurred at 14.7 years followed by a second peak at 35 years [3]. Many adult cases are noted to have their onset in the second decade of life [2]. Of the diagnoses resulting from visits to pediatric sleep clinics for evaluation of hypersomnia, narcolepsy accounts for approximately 15% [4]. The multiple sleep latency test (MSLT) is a diagnostic test used to confirm the diagnosis of narcolepsy. During the MSLT, patients undergo an overnight polysomnogram to document a minimum of 6 hours of sleep, after which they undergo five nap trials of 20 minutes’ duration each, 2 hours apart. The mean sleep latency during these trials is calculated, and the presence of sleep-onset rapid eye movement sleep (REM), defined as REM sleep occurring within 15 minutes after sleep onset, is also determined. The mean sleep latency is subsequently determined. Previous work has demonstrated the feasibility and utility of the MSLT in children [4].
444
S. Zandieh et al. / Pediatric Neurology 48 (2013) 443e446
Table 1. Descriptive and maintenance of wakefulness test data for this series of 10 patients
Patient* Age Sex Diagnosis (years) 1 Repeat 2 Repeat
9.7
F
Comorbidities
Narcolepsy with cataplexy
10.7 12.3
M
Narcolepsy with cataplexy
13.4
MSL
Sleep Onset REM
Prestudy Treatment
Poststudy Treatment
Medication 13.5 efficacy Medication 16 efficacy Medication 9 efficacy Medication 29 efficacy Medication 5.82 efficacy
0
Modafinil 100 mg
Modafinil 200 mg
0
Aripiprazole 2.5 mg Sod. oxybate 3.75 mg b.i.d. Sod. oxybate 4.5 mg b.i.d.
0 2
3
15.9
F
Narcolepsy
4
15.8
F
Narcolepsy
Medication 40 efficacy
0
5
14.2
M
Narcolepsy with cataplexy
Medication 5.8 efficacy Medication 22 efficacy
2
Repeat
14.9
6
16.2
M
7
20.3
F
8
15.9
F
9
18.1
F
10
8.7
F
Prader-Willi syndrome, short acyl CoA dehydrogenase deficiency
Indication
Narcolepsy
Safety and 24.9 medication efficacy Medication 40 Narcolepsy with ADHD, bipolar cataplexy affective disorder, efficacy epilepsy Narcolepsy with Medication 22.8 cataplexy efficacy Narcolepsy with Safety and 9.6 cataplexy medication efficacy Narcolepsy Medication 13.7 efficacy
4
0
0
Aripiprazole 2.5 mg Sod. oxybate 4.5 mg b.i.d. Sod. oxybate 4.5 mg b.i.d. and 15-min afternoon nap Sod. oxybate 4.5 mg b.i.d. þ No change 15-min afternoon nap Modafinil 200 mg am No change
Modafinil 100 mg am, 50 mg pm Venlafaxine 75 mg Modafinil 200 mg b.i.d. Venlafaxine 150 mg Sod. oxybate 200 mg Modafinil 200 mg b.i.d. Venlafaxine 75 mg Modafinil 200 mg b.i.d.
Venlafaxine 115 mg (increased for management of psychiatric comorbidity) Sod. oxybate 4.5 mg 2 No change
No change
0
Sod. oxybate 4.5 2 Lamictal 100 mg Zoloft Modafinil 200 mg
0
Amphetamine salt XR 20 mg Amphetamine salt XR 30 mg
0
Modafinil 100 mg
0
No change
No change
No change
Abbreviations: ADHD ¼ Attention deficit hyperactivity disorder b.i.d. ¼ Twice daily CoA ¼ Coenzyme A MSL ¼ Mean sleep latency REM ¼ Rapid eye movement sleep Sod. ¼ Sodium XR ¼ Extended release * Three patients had two studies.
Narcolepsy is often a difficult disease to treat. A number of first-line drugs are available, including modafinil, sodium oxybate, venlafaxine, and methylphenidate [5]. Treatments must often be tailored to specific patient needs. The maintenance of wakefulness test (MWT) is recommended by the American Academy of Sleep Medicine to assess the efficacy of treatment for hypersomnia secondary to narcolepsy or obstructive sleep apnea on continuous positive airway pressure therapy [6]. In contrast to the MSLT, the MWT involves 40-minute trials in which the patient is required to stay awake with eyes open in a seated position in a lit room. To date, no data have been published on the use of the MWT in the pediatric population. With the increased recognition of narcolepsy at younger ages, objective tools to assess the treatment efficacy of narcolepsy are necessary. This study presents a singlecenter experience of maintenance of wakefulness tests in pediatric patients diagnosed with narcolepsy.
Patients and Methods Patient population
We have been performing MWTs at our institution over the past 4 years. Prior to data collection for this study, approval was sought and obtained by an institutional review board. Procedure codes were used to identify patients who had undergone MWT. MWT study
MWTs were performed in accordance with American Academy of Sleep Medicine practice guidelines [6]. Because the purpose of the MWT is to assess the response to treatment, medications were not changed prior to testing. Studies were initiated in the morning, between 9 and 10 am. Each study consisted of four trials, each lasting 40 minutes, 2 hours apart. Patients were not allowed to sleep between trials. Medications were not adjusted prior to testing. Ambient temperature was set to a comfortable temperature. Patients were instructed to have breakfast prior to coming for the study and were provided with lunch following the noon trial. Prior to initiation of the test, patients were verbally given the following instructions: “Please sit quietly in a relaxed position. Don’t
S. Zandieh et al. / Pediatric Neurology 48 (2013) 443e446 sleep and do your best to stay awake. You may not talk, sing, pinch, or slap yourself. You may not move or twitch rhythmically. Keep your eyes open.” Lights were situated above and behind the patient and kept on a dim setting (7.5 W). All MWTs were interpreted by board-certified sleep clinicians using normative data from adult 40-minute MWT studies. Sleep onset was defined as three epochs of stage 1 sleep in 30-second epochs or one epoch of stage 2 sleep. Parameters recorded include the start and stop times for each trial, sleep latency, total sleep time, the presence of sleeponset REM sleep, and REM latency for each trial. The mean sleep latency was defined as the arithmetic mean of the sleep latency of the four trials. A cutoff for mean sleep latency of <8 minutes was used to indicate inadequate control of hypersomnia. A mean sleep latency of >20 minutes was used to indicate adequate hypersomnia control. Data acquisition
A retrospective chart review was done that included patient demographics, diagnosis, indication for MWT, study results, and the manner in which the study affected management. Additionally, any patient comorbidity was reported.
Results Patient population
A total of 10 patients had 13 MWTs over the review period (Table 1). All patients had undergone a standard polysomnogram and MSLT prior to the MWT. Three patients in the series were boys. The median age at first study was 15.8 years (range 8.7-20.3 years). All patients in the series were diagnosed with narcolepsy. Cataplexy was documented in six of 10 patients. Comorbid conditions included Prader-Willi syndrome, bipolar affective disorder, epilepsy, and attention deficit hyperactivity disorder. Mean sleep latency and sleep onset REM
The median mean sleep latency for all studies was 16 minutes (range, 5.8-40 minutes). One study had a mean sleep latency of <8 minutes, six studies had mean sleep latencies between 8 and 20 minutes, and six studies had mean a sleep latency of >20 minutes. Sleep-onset REM was documented in three patients. Multiple MWTs
Three patients underwent two MWTs over the course of their clinical care. The indication for repeat testing in all patients was for evaluation of medication efficacy. Repeat testing showed improvement in mean sleep latency in all patients. One patient required medication adjustment following the second test. Management
In seven patients, findings from the MWTs resulted in changes in management after study results. Interpretation of the MWTs included reduced sleep latency in the morning naps, leading to counseling on improving sleep schedules and circadian patterns of sleepewake schedules, and possibly increasing morning doses of stimulants. Discussion
This study demonstrates the feasibility and utility of the MWT in a pediatric population diagnosed with narcolepsy.
445
Additionally, the results of the MWT may be useful in making objective treatment recommendations, although research is still needed to identify ideal protocols and interpretation of normative data in the pediatric population. Reduced sleep latency in morning naps can be managed with counseling on improving sleep schedules and circadian patterns and possibly increasing morning doses of stimulants. Patients with reduced sleep latency in afternoon naps can be counseled to have noontime or afterschool power naps and possibly by adding an afternoon dose of a stimulant. An overall reduced mean sleep latency with reduced sleep latency in all naps indicates treatment failure or noncompliance. Population demographics
The data from this study are consistent with previously acquired knowledge about pediatric narcolepsy. The majority of patients were adolescents, consistent with population studies [2]. This study also contained a preponderance of girls, which, while consistent with a published study, may not be representative of the pediatric narcolepsy population at large [7,8]. This finding may be the result of the low numbers of patients in this series. MWT protocols
Although this study suggests that the MWT may be a useful clinical tool to study the efficacy of treatment, its use is difficult because of the lack of established protocols and normative data. At least four protocols have been established for the MWT [6]. The most consistent protocol defines sleep onset as three continuous epochs of stage 1 sleep or any single epoch of stage 2 sleep. Normative data in the pediatric population
As illustrated in a questionnaire survey, narcolepsy can cause significant quality-of-life issues in children and teenagers, including behavioral problems, depression, and education issues [9]. Because adequate treatment can significantly improve quality of life in children with narcolepsy, tools are needed to assess the effectiveness of treatment in this condition. This problem is further compounded by the wide variety of medications available for treatment of narcolepsy and the lack of sound recommendations regarding their use in the pediatric population [5]. Although the MWT may be able to partially address some of these issues, to date no normative data have been reported for this test in children. Normative data on the MWT have been evaluated in several adult studies using a 40minute protocol [10-12]. Data have also been published on the 20-minute MWT, although this test is not advocated by the American Academy of Sleep Medicine [13]. It is not yet known if these findings extend to the pediatric population. Limitations
The findings from this series should be interpreted in the context of data acquisition and analysis. This is a retrospective study and may be limited by referral bias. This study used adult normative data, and the limited numbers
446
S. Zandieh et al. / Pediatric Neurology 48 (2013) 443e446
in this study precluded statistical analysis. Although its findings should be confirmed with further prospective analysis, this study is the first to document the use of the MWT test in pediatric narcolepsy. Conclusions
The MWT may be a useful test to monitor the efficacy of treatment in narcolepsy. As in adults, the results of the MWT may impact changes in medication and other management and thereby improve outcomes and quality of life. However, before its use in pediatrics can be advocated on a larger scale, more data are needed to establish agerelated changes in MWT findings. Future research is needed to obtain normative MWT data in children without narcolepsy. With the availability of such data and the use of more uniform protocols, the test may be better able to provide objective data toward improving clinical care for children with this disorder. References [1] Dement W, Carskadon M, Ley R. The prevalence of narcolepsy. Sleep Res 1973;2:147. [2] Silber MH, Krahn LE, Olson EJ, Pankratz VS. The epidemiology of narcolepsy in Olmsted County, Minnesota: A population-based study. Sleep 2002;25:197e202.
[3] Dauvilliers Y, Montplaisir J, Molinari N, et al. Age at onset of narcolepsy in two large populations of patients in France and Quebec. Neurology 2001;57:2029e33. [4] Vendrame M, Havaligi N, Matadeen-Ali C, Adams R, Kothare SV. Narcolepsy in children: A single-center clinical experience. Pediatr Neurol 2008;38:314e20. [5] Aran A, Einen M, Lin L, Plazzi G, Nishino S, Mignot E. Clinical and therapeutic aspects of childhood narcolepsy-cataplexy: A retrospective study of 51 children. Sleep 2010;33:1457e64. [6] Littner MR, Kushida C, Wise M, et al. Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test. Sleep 2005;28:113e21. [7] Han F, Chen E, Wei H, et al. Childhood narcolepsy in North China. Sleep 2001;24:321e4. [8] Peterson PC, Husain AM. Pediatric narcolepsy. Brain Dev 2008;30: 609e23. [9] Stores G, Montgomery P, Wiggs L. The psychosocial problems of children with narcolepsy and those with excessive daytime sleepiness of uncertain origin. Pediatrics 2006;118: e1116e23. [10] Hakkanen H, Summala H, Partinen M, Tiihonen M, Silvo J. Blink duration as an indicator of driver sleepiness in professional bus drivers. Sleep 1999;22:798e802. [11] Banks S, Barnes M, Tarquinio N, Pierce RJ, Lack LC, McEvoy RD. The maintenance of wakefulness test in normal healthy subjects. Sleep 2004;27:799e802. [12] Doghramji K, Mitler MM, Sangal RB, et al. A normative study of the maintenance of wakefulness test (MWT). Electroencephalogr Clin Neurophysiol 1997;103:554e62. [13] Browman CP, Mitler MM. Hypersomnia and the perception of sleep-wake states: Some preliminary findings. Percept Mot Skills 1988;66:463e70.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Original Article
The Maintenance of Wakefulness Test in Pediatric Narcolepsy Stephanie Zandieh MD a, b, Sriram Ramgopal MD b, Umakanth Khatwa MD a, c, Michelle SanGiuliano RPSGT a, Michael Gunnuscio RPSGT a, Marcin Zarowski MD PhD d, Sanjeev V. Kothare MD a, b, * a
Center for Pediatric Sleep Disorders, Boston Children’s Hospital, Boston, Massachusetts Department of Neurology, Boston Children’s Hospital, Boston, Massachusetts c Division of Respiratory Medicine, Department of Medicine, Boston Children’s Hospital, Boston, Massachusetts d Department of Developmental Neurology, Poznan University of Medical Sciences, Poznan, Poland b
article information
abstract
Article history: Received 12 February 2013 Accepted 13 February 2013
Objective tools are needed to assess the response to treatment in pediatric narcolepsy. This article presents a single-center experience documenting the use of the maintenance of wakefulness test (MWT) in a pediatric series. This study reviewed the charts of children with narcolepsy who had an MWT performed between January 2008 and June 2012. A cutoff was used for mean sleep latency: <8 minutes for inadequate control of hypersomnia, and >20 minutes to indicate adequate control on medications. Thirteen tests were performed on 10 children (median age 15.8 years, range 8.7-20.3 years) with narcolepsy, of which six had cataplexy and three were boys. Comorbid conditions included Prader-Willi syndrome, bipolar affective disorder, and epilepsy (n ¼ 1 each). The median mean sleep latency for all studies was 16 minutes (range 5.8-40 minutes). Sleep-onset rapid eye movement sleep events were seen in three of 13 studies. In seven patients, findings from the MWT resulted in changes in management. These data suggest that the MWT may be a useful and feasible test for assessing response to treatment in children with narcolepsy. Future research is needed to obtain normative MWT data on children with and without narcolepsy. Ó 2013 Elsevier Inc. All rights reserved.
Introduction
Narcolepsy is characterized by hypersomnia along with sleep attacks. Population studies have estimated the incidence of narcolepsy to be 0.05-0.067% [1,2]. Although the disease is better characterized in adults, it has been noted to follow a bimodal distribution in its ages of presentation: a Canadian/French epidemiologic study found that the first Sanjeev Kothare is funded by the following grants: National Institutes of Health: 1 RC1 HL099749-01 (R21), and RFA-HL-09-001, and an investigatorinitiated grant from Eisai Pharma, Inc, to assess safety and efficacy of rufinamide in children, and the Harvard Catalyst to assess cardiorespiratory abnormalities during seizures in children.
* Communications should be addressed to: Dr. Kothare; Division of Epilepsy and Clinical Neurophysiology; Fegan 9; Boston Children’s Hospital; 300 Longwood Avenue; Boston, MA 02115. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2013.02.007
peak in onset occurred at 14.7 years followed by a second peak at 35 years [3]. Many adult cases are noted to have their onset in the second decade of life [2]. Of the diagnoses resulting from visits to pediatric sleep clinics for evaluation of hypersomnia, narcolepsy accounts for approximately 15% [4]. The multiple sleep latency test (MSLT) is a diagnostic test used to confirm the diagnosis of narcolepsy. During the MSLT, patients undergo an overnight polysomnogram to document a minimum of 6 hours of sleep, after which they undergo five nap trials of 20 minutes’ duration each, 2 hours apart. The mean sleep latency during these trials is calculated, and the presence of sleep-onset rapid eye movement sleep (REM), defined as REM sleep occurring within 15 minutes after sleep onset, is also determined. The mean sleep latency is subsequently determined. Previous work has demonstrated the feasibility and utility of the MSLT in children [4].
444
S. Zandieh et al. / Pediatric Neurology 48 (2013) 443e446
Table 1. Descriptive and maintenance of wakefulness test data for this series of 10 patients
Patient* Age Sex Diagnosis (years) 1 Repeat 2 Repeat
9.7
F
Comorbidities
Narcolepsy with cataplexy
10.7 12.3
M
Narcolepsy with cataplexy
13.4
MSL
Sleep Onset REM
Prestudy Treatment
Poststudy Treatment
Medication 13.5 efficacy Medication 16 efficacy Medication 9 efficacy Medication 29 efficacy Medication 5.82 efficacy
0
Modafinil 100 mg
Modafinil 200 mg
0
Aripiprazole 2.5 mg Sod. oxybate 3.75 mg b.i.d. Sod. oxybate 4.5 mg b.i.d.
0 2
3
15.9
F
Narcolepsy
4
15.8
F
Narcolepsy
Medication 40 efficacy
0
5
14.2
M
Narcolepsy with cataplexy
Medication 5.8 efficacy Medication 22 efficacy
2
Repeat
14.9
6
16.2
M
7
20.3
F
8
15.9
F
9
18.1
F
10
8.7
F
Prader-Willi syndrome, short acyl CoA dehydrogenase deficiency
Indication
Narcolepsy
Safety and 24.9 medication efficacy Medication 40 Narcolepsy with ADHD, bipolar cataplexy affective disorder, efficacy epilepsy Narcolepsy with Medication 22.8 cataplexy efficacy Narcolepsy with Safety and 9.6 cataplexy medication efficacy Narcolepsy Medication 13.7 efficacy
4
0
0
Aripiprazole 2.5 mg Sod. oxybate 4.5 mg b.i.d. Sod. oxybate 4.5 mg b.i.d. and 15-min afternoon nap Sod. oxybate 4.5 mg b.i.d. þ No change 15-min afternoon nap Modafinil 200 mg am No change
Modafinil 100 mg am, 50 mg pm Venlafaxine 75 mg Modafinil 200 mg b.i.d. Venlafaxine 150 mg Sod. oxybate 200 mg Modafinil 200 mg b.i.d. Venlafaxine 75 mg Modafinil 200 mg b.i.d.
Venlafaxine 115 mg (increased for management of psychiatric comorbidity) Sod. oxybate 4.5 mg 2 No change
No change
0
Sod. oxybate 4.5 2 Lamictal 100 mg Zoloft Modafinil 200 mg
0
Amphetamine salt XR 20 mg Amphetamine salt XR 30 mg
0
Modafinil 100 mg
0
No change
No change
No change
Abbreviations: ADHD ¼ Attention deficit hyperactivity disorder b.i.d. ¼ Twice daily CoA ¼ Coenzyme A MSL ¼ Mean sleep latency REM ¼ Rapid eye movement sleep Sod. ¼ Sodium XR ¼ Extended release * Three patients had two studies.
Narcolepsy is often a difficult disease to treat. A number of first-line drugs are available, including modafinil, sodium oxybate, venlafaxine, and methylphenidate [5]. Treatments must often be tailored to specific patient needs. The maintenance of wakefulness test (MWT) is recommended by the American Academy of Sleep Medicine to assess the efficacy of treatment for hypersomnia secondary to narcolepsy or obstructive sleep apnea on continuous positive airway pressure therapy [6]. In contrast to the MSLT, the MWT involves 40-minute trials in which the patient is required to stay awake with eyes open in a seated position in a lit room. To date, no data have been published on the use of the MWT in the pediatric population. With the increased recognition of narcolepsy at younger ages, objective tools to assess the treatment efficacy of narcolepsy are necessary. This study presents a singlecenter experience of maintenance of wakefulness tests in pediatric patients diagnosed with narcolepsy.
Patients and Methods Patient population
We have been performing MWTs at our institution over the past 4 years. Prior to data collection for this study, approval was sought and obtained by an institutional review board. Procedure codes were used to identify patients who had undergone MWT. MWT study
MWTs were performed in accordance with American Academy of Sleep Medicine practice guidelines [6]. Because the purpose of the MWT is to assess the response to treatment, medications were not changed prior to testing. Studies were initiated in the morning, between 9 and 10 am. Each study consisted of four trials, each lasting 40 minutes, 2 hours apart. Patients were not allowed to sleep between trials. Medications were not adjusted prior to testing. Ambient temperature was set to a comfortable temperature. Patients were instructed to have breakfast prior to coming for the study and were provided with lunch following the noon trial. Prior to initiation of the test, patients were verbally given the following instructions: “Please sit quietly in a relaxed position. Don’t
S. Zandieh et al. / Pediatric Neurology 48 (2013) 443e446 sleep and do your best to stay awake. You may not talk, sing, pinch, or slap yourself. You may not move or twitch rhythmically. Keep your eyes open.” Lights were situated above and behind the patient and kept on a dim setting (7.5 W). All MWTs were interpreted by board-certified sleep clinicians using normative data from adult 40-minute MWT studies. Sleep onset was defined as three epochs of stage 1 sleep in 30-second epochs or one epoch of stage 2 sleep. Parameters recorded include the start and stop times for each trial, sleep latency, total sleep time, the presence of sleeponset REM sleep, and REM latency for each trial. The mean sleep latency was defined as the arithmetic mean of the sleep latency of the four trials. A cutoff for mean sleep latency of <8 minutes was used to indicate inadequate control of hypersomnia. A mean sleep latency of >20 minutes was used to indicate adequate hypersomnia control. Data acquisition
A retrospective chart review was done that included patient demographics, diagnosis, indication for MWT, study results, and the manner in which the study affected management. Additionally, any patient comorbidity was reported.
Results Patient population
A total of 10 patients had 13 MWTs over the review period (Table 1). All patients had undergone a standard polysomnogram and MSLT prior to the MWT. Three patients in the series were boys. The median age at first study was 15.8 years (range 8.7-20.3 years). All patients in the series were diagnosed with narcolepsy. Cataplexy was documented in six of 10 patients. Comorbid conditions included Prader-Willi syndrome, bipolar affective disorder, epilepsy, and attention deficit hyperactivity disorder. Mean sleep latency and sleep onset REM
The median mean sleep latency for all studies was 16 minutes (range, 5.8-40 minutes). One study had a mean sleep latency of <8 minutes, six studies had mean sleep latencies between 8 and 20 minutes, and six studies had mean a sleep latency of >20 minutes. Sleep-onset REM was documented in three patients. Multiple MWTs
Three patients underwent two MWTs over the course of their clinical care. The indication for repeat testing in all patients was for evaluation of medication efficacy. Repeat testing showed improvement in mean sleep latency in all patients. One patient required medication adjustment following the second test. Management
In seven patients, findings from the MWTs resulted in changes in management after study results. Interpretation of the MWTs included reduced sleep latency in the morning naps, leading to counseling on improving sleep schedules and circadian patterns of sleepewake schedules, and possibly increasing morning doses of stimulants. Discussion
This study demonstrates the feasibility and utility of the MWT in a pediatric population diagnosed with narcolepsy.
445
Additionally, the results of the MWT may be useful in making objective treatment recommendations, although research is still needed to identify ideal protocols and interpretation of normative data in the pediatric population. Reduced sleep latency in morning naps can be managed with counseling on improving sleep schedules and circadian patterns and possibly increasing morning doses of stimulants. Patients with reduced sleep latency in afternoon naps can be counseled to have noontime or afterschool power naps and possibly by adding an afternoon dose of a stimulant. An overall reduced mean sleep latency with reduced sleep latency in all naps indicates treatment failure or noncompliance. Population demographics
The data from this study are consistent with previously acquired knowledge about pediatric narcolepsy. The majority of patients were adolescents, consistent with population studies [2]. This study also contained a preponderance of girls, which, while consistent with a published study, may not be representative of the pediatric narcolepsy population at large [7,8]. This finding may be the result of the low numbers of patients in this series. MWT protocols
Although this study suggests that the MWT may be a useful clinical tool to study the efficacy of treatment, its use is difficult because of the lack of established protocols and normative data. At least four protocols have been established for the MWT [6]. The most consistent protocol defines sleep onset as three continuous epochs of stage 1 sleep or any single epoch of stage 2 sleep. Normative data in the pediatric population
As illustrated in a questionnaire survey, narcolepsy can cause significant quality-of-life issues in children and teenagers, including behavioral problems, depression, and education issues [9]. Because adequate treatment can significantly improve quality of life in children with narcolepsy, tools are needed to assess the effectiveness of treatment in this condition. This problem is further compounded by the wide variety of medications available for treatment of narcolepsy and the lack of sound recommendations regarding their use in the pediatric population [5]. Although the MWT may be able to partially address some of these issues, to date no normative data have been reported for this test in children. Normative data on the MWT have been evaluated in several adult studies using a 40minute protocol [10-12]. Data have also been published on the 20-minute MWT, although this test is not advocated by the American Academy of Sleep Medicine [13]. It is not yet known if these findings extend to the pediatric population. Limitations
The findings from this series should be interpreted in the context of data acquisition and analysis. This is a retrospective study and may be limited by referral bias. This study used adult normative data, and the limited numbers
446
S. Zandieh et al. / Pediatric Neurology 48 (2013) 443e446
in this study precluded statistical analysis. Although its findings should be confirmed with further prospective analysis, this study is the first to document the use of the MWT test in pediatric narcolepsy. Conclusions
The MWT may be a useful test to monitor the efficacy of treatment in narcolepsy. As in adults, the results of the MWT may impact changes in medication and other management and thereby improve outcomes and quality of life. However, before its use in pediatrics can be advocated on a larger scale, more data are needed to establish agerelated changes in MWT findings. Future research is needed to obtain normative MWT data in children without narcolepsy. With the availability of such data and the use of more uniform protocols, the test may be better able to provide objective data toward improving clinical care for children with this disorder. References [1] Dement W, Carskadon M, Ley R. The prevalence of narcolepsy. Sleep Res 1973;2:147. [2] Silber MH, Krahn LE, Olson EJ, Pankratz VS. The epidemiology of narcolepsy in Olmsted County, Minnesota: A population-based study. Sleep 2002;25:197e202.
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