Narcolepsy: a review

Figures & data

Table 1 Primary and secondary etiologies of narcolepsy

Hypocretin deficiency

Hypothalamic lesions

Inherited disorders eg Neimann–Pick disease type C

Brain tumors

Craniocerebral trauma

Cerebrovascular disorders

Encephalomyelitis

Neurodegenerative diseases

Demyelinating disorders

Table 2 The International Classification of Sleep Disorders for narcolepsy⁵⁹

Narcolepsy with cataplexy

Excessive daytime sleepiness almost daily for at least 3 months

Definite history of cataplexy

Diagnosis should be confirmed, whenever possible, by one of the following:

Polysomnography^a and MSLT^b; mean sleep latency should be ≤8 minutes and at least 2 SOREMS^c

CSF^d hypocretin level ≤110 pg/mL or 1/3 of mean normal controls

Hypersomnia is not better explained by another disorder or medication

Narcolepsy without cataplexy

Excessive daytime sleepiness almost daily for at least 3 months

Definite cataplexy is not present

Diagnosis must be confirmed by polysomnography or MSLT

Mean sleep latency should be ≤8 minutes and ≥2 SOREMs

Hypersomnia is not better explained by another disorder or medication

Secondary narcolepsy (narcolepsy due to medical condition)

Excessive daytime sleepiness almost daily for at least 3 months

One of the following is present: definite history of cataplexy; if cataplexy is not present, diagnosis must be confirmed by polysomnography and MSLT; mean sleep latency should be ≤8 minutes and at least 2 SOREMS; CSF hypocretin level ≤110 pg/mL

Underlying medical or neurological condition accounts for the sleepiness

Hypersomnia is not better explained by another disorder or medication

Abbreviations: MSLT, Multiple Sleep Latency Time; SOREM, sleep onset REM; CSF, cerebrospinal fluid.

Note: Reproduced with permission from American Academy of Sleep Medicine. The International Classification of Sleep Disorders, Diagnostic and Coding Manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005.

Table 3 Oxford Centre evidence-based medicine levels of evidence⁹⁸

Evidence level study design or description Randomized controlled trial with narrow confidence intervals Randomized trials without narrow confidence intervals, or with methodological problems, or cohort studies Nonrandomized concurrently controlled studies or case-control studies Case-control or cohort studies with methodological problems, or case series Expert opinion, or studies based on physiology or bench research

Note: Abbreviated with permission from Centre for Evidence-based Medicine. Levels of evidence 2009 [web page on the Internet]. Oxford: Centre for Evidencebased Medicine; 2009 [updated April 15, 2011]. Available from: http://www.cebm.net/index.aspx?o=1025. Accessed April 20, 2011.

Table 4 Double-blind randomized controlled studies of modafinil

Study	Placebo group	Treatment group 1	Treatment group 2	Outcome measures	Duration	Results	Drawbacks
US 18-center study^Citation121	n = 92	Modafinil 200 mg n = 96	Modafinil 400 mg as a single dose n = 95	MWT, MSLT, ESS, CGI-S	0, 3, 6, 9 weeks	MWT, MSLT, CGI-S, ESS, significantly reduced in the 2 treatment groups compared with placebo but no significant difference between the 2 treatment groups (P < 0.001)	Drug company sponsored Short follow-up
US 21-center study^Citation122	n = 93	Modafinil 200 mg n = 89	Modafinil 400 mg as a single dose n = 89	MWT, MSLT, ESS, CGI-S	9 weeks	MWT, MSLT, CGI-S, ESS, significantly improved in the 2 treatment groups compared with placebo but no significant difference between the 2 treatment groups (P < 0.001). Dropout rate 6%, return of EDS after discontinuation of modafinil but no withdrawal effect	Drug company sponsored Short follow-up MWT tested 1 hour after
Canadian nine-center crossover study^Citation123	Each of 75 patients received in order: Placebo first 2-week	Second 2-week period 200 mg of modafinil	Third 2-week period 200 mg twice daily of modafinil	MWT, ESS, patient sleep diary	6 weeks	MWT and ESS significantly improved. No significant difference between the doses, 5% dropout rate, well tolerated by patients	Drug company sponsored No washout periods MWT tested 1 hour after administering medication

Abbreviations: EDS, excessive daytime sleepiness; MWT, maintenance of wakefulness test; MSLT, multiple sleep latency time; ESS, Epworth Sleepiness scale; CGI-S, Clinical Global Impression of Change.

American Academy of Sleep MedicineThe International Classification of Sleep Disorders, Diagnostic and Coding Manual2nd edWestchester, ILAmerican Academy of Sleep Medicine2005

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Centre for Evidence-based MedicineLevels of evidence 2009 [web page on the Internet]OxfordCentre for Evidence-based Medicine2009 [updated April 15, 2011]. Available from: http://www.cebm.net/index.aspx?o=1025Accessed April 20, 2011

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