Elsevier

Sleep Medicine

Volume 15, Issue 5, May 2014, Pages 502-507
Sleep Medicine

Review Article
Delayed diagnosis of narcolepsy: characterization and impact

https://doi.org/10.1016/j.sleep.2014.01.015Get rights and content

Highlights

  • Narcolepsy is a chronic neurologic condition, which frequently has an early onset.

  • A long delay until diagnosis has been consistently reported in the literature.

  • Studies report a mean delay of up to 15 years, with individual cases of >60 years.

  • The underlying reason for diagnosis delay is likely a lack of symptom recognition.

  • We highlight closing this diagnostic gap through awareness of narcolepsy symptoms.

Abstract

Narcolepsy, a chronic neurologic condition resulting from dysregulation of the sleep–wake cycle, usually has an onset at an early age. However, a long delay until diagnosis has been consistently reported in the literature across countries and several publications have focused on characterizing this delay. Most studies report a mean delay to diagnosis of up to 15 years, with individual cases of >60 years, although a trend over time toward a shorter diagnostic delay has been suggested. While variables associated with this delay have been identified, a lack of symptom recognition resulting in misdiagnosis prior to reaching the narcolepsy diagnosis is the likely underlying reason. This lack of symptom recognition is especially relevant considering the high comorbidity burden that has been shown in patients with narcolepsy as some disorders manifest with symptoms that overlap with narcolepsy. A consequence of delayed diagnosis is delayed treatment, which affects the burden of disease. Substantial detrimental effects on health-care resource utilization, employment, and quality of life have been described after narcolepsy onset and prior to the diagnosis of narcolepsy. This review highlights the importance of closing the diagnostic gap by expanding awareness of narcolepsy and its symptoms.

Introduction

Narcolepsy is a chronic neurologic condition resulting from dysregulation of the sleep–wake cycle [1]. Evidence indicates an autoimmune component linked to specific genotypes including human leukocyte antigen (HLA DQB1∗06:02) and T-cell receptor alpha variants associated with loss of orexin (hypocretin)-producing neurons [2], [3], [4]. However, not all cases are associated with loss of hypocretin neurons. Narcolepsy can also be precipitated by seasonal Streptococcus infections, H1N1 influenza, and H1N1 vaccination in genetically predisposed individuals [5].

The estimated prevalence of narcolepsy is 0.05% in the United States [6] and 0.02–0.067% worldwide [7], and it is associated with a substantial socioeconomic burden. This burden results from increased health care resource utilization; reductions in patient function, quality of life, and productivity; and an adverse impact on the patient’s partner and family [8], [9], [10], [11], [12], [13]. Reduced employment and income can be present before diagnosis [11], and an early diagnosis leading to appropriate treatment may lessen the burden.

Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic or hypnopompic hallucinations, and sleep paralysis, although not all symptoms are present in all patients. Recognition of disturbed nocturnal sleep (DNS) as a patient-reported symptom and as a polysomnography (PSG)-characterized feature suggests that DNS can be added to the other symptoms to form a symptom pentad [14].

While narcolepsy onset can occur in children <10 years of age [15], [16], [17], symptom onset typically peaks during the second decade of life [15], with a main peak at approximately 15 years of age and possibly a lesser secondary peak at approximately 35 years [18]. However, evidence suggests that few patients are diagnosed within the first 10 years as indicated by the disproportionate number of patients who report onset prior to 20 years of age relative to those who have been diagnosed (Fig. 1) [19].

Numerous publications have reported the discordance between narcolepsy onset and its diagnosis. Because such a diagnostic gap results in delay of treatment and increases the disease burden, it is important to characterize this gap and identify factors that may potentially reduce it. Therefore, the purpose of this article is to provide an overview of the diagnostic delay between symptom onset and diagnosis, including discussion of the potential reasons and implications of this delay.

Section snippets

Methods

Articles reporting on the diagnostic delay were identified from several sources. Although the primary source was the authors’ knowledge of the narcolepsy literature, searches were also performed in PubMed. The PubMed searches, with no publication date limits and for English language articles, used the search term “narcolepsy” in combination with “delayed diagnosis,” “diagnostic delay,” and “diagnosis delay.” The PubMed searches returned 39 unique citations, of which 10 were relevant for

Delay duration

A delay between symptom onset and diagnosis was mentioned in the narcolepsy literature as early as 1976, with 5 years reported as the average time between symptom onset and a correct diagnosis [20]. Consistent with this duration, a 1995 study anecdotally reported survey results that stratified the delay between symptom onset and narcolepsy diagnosis at a single sleep disorders clinic in the UK by years of delay duration in 132 patients [21]. While the majority of patients (66%) were diagnosed

Conclusions

The long duration between symptom onset and diagnosis indicates that many narcolepsy patients remain undiagnosed or misdiagnosed, resulting in an increased burden of narcolepsy and a barrier to patient management.

Although the lack of an easy, accurate diagnostic test for narcolepsy may in part contribute to the diagnostic delay, this delay more likely results from the lack of diagnostic consideration, since these symptoms may be suggestive of other conditions for which there is greater

Conflict of interest

Dr. Thorpy is a consultant and on the speakers bureau for Jazz Pharmaceuticals, Inc., and Teva Pharmaceuticals. Dr. Krieger has nothing to disclose.

The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2014.01.015.

. ICMJE Form for Disclosure of Potential Conflicts of Interest form.

Acknowledgment

E. Jay Bienen, PhD, of The Curry Rockefeller Group, LLC (CRG), provided editorial assistance in developing this manuscript, which was funded by Jazz Pharmaceuticals, Inc.

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