Intermediate hypocretin-1 cerebrospinal fluid levels and typical cataplexy: their significance in the diagnosis of narcolepsy type 1

Adrienne Elisabeth van der Hoeven; Rolf Fronczek; Mink Sebastian Schinkelshoek; Frederik Willem Cornelis Roelandse; Jaap Adriaan Bakker; Sebastiaan Overeem; Denise Bijlenga; Gert Jan Lammers

doi:10.1093/sleep/zsac052

Intermediate hypocretin-1 cerebrospinal fluid levels and typical cataplexy: their significance in the diagnosis of narcolepsy type 1

Adrienne Elisabeth van der Hoeven, Rolf Fronczek, Mink Sebastian Schinkelshoek, Frederik Willem Cornelis Roelandse, Jaap Adriaan Bakker, Sebastiaan Overeem, Denise Bijlenga, Gert Jan Lammers (Corresponding author)

Onderzoeksoutput: Bijdrage aan tijdschrift › Tijdschriftartikel › Academic › peer review

17 Citaten (Scopus)

13 Downloads (Pure)

Samenvatting

STUDY OBJECTIVES: The diagnosis of narcolepsy type 1 (NT1) is based upon the presence of cataplexy and/or a cerebrospinal fluid (CSF) hypocretin-1/orexin-A level ≤ 110 pg/mL. We determined the clinical and diagnostic characteristics of patients with intermediate hypocretin-1 levels (111-200 pg/mL) and the diagnostic value of cataplexy characteristics in individuals with central disorders of hypersomnolence.

METHODS: Retrospective cross-sectional study of 355 people with known CSF hypocretin-1 levels who visited specialized Sleep-Wake Centers in the Netherlands. For n = 271, we had full data on cataplexy type ("typical" or "atypical" cataplexy).

RESULTS: Compared to those with normal hypocretin-1 levels (>200 pg/mL), a higher percentage of individuals with intermediate hypocretin-1 levels had typical cataplexy (75% or 12/16 vs 9% or 8/88, p < .05), and/or met the diagnostic polysomnographic (PSG) and Multiple Sleep Latency Test (MSLT) criteria for narcolepsy (50 vs 6%, p < .001). Of those with typical cataplexy, 88% had low, 7% intermediate, and 5% normal hypocretin-1 levels (p < .001). Atypical cataplexy was also associated with hypocretin deficiency but to a lesser extent. A hypocretin-1 cutoff of 150 pg/mL best predicted the presence of typical cataplexy and/or positive PSG and MSLT findings.

CONCLUSION: Individuals with intermediate hypocretin-1 levels or typical cataplexy more often have outcomes fitting the PSG and MSLT criteria for narcolepsy than those with normal levels or atypical cataplexy. In addition, typical cataplexy has a much stronger association with hypocretin-1 deficiency than atypical cataplexy. We suggest increasing the NT1 diagnostic hypocretin-1 cutoff and adding the presence of clearly defined typical cataplexy to the diagnostic criteria of NT1. Clinical trial information: This study is not registered in a clinical trial register, as it has a retrospective database design.

Originele taal-2	Engels
Artikelnummer	zsac052
Aantal pagina's	10
Tijdschrift	Sleep
Volume	45
Nummer van het tijdschrift	5
DOI's	https://doi.org/10.1093/sleep/zsac052
Status	Gepubliceerd - 12 mei 2022
Extern gepubliceerd	Ja

Toegang tot document

10.1093/sleep/zsac052

pdfDefinitieve gepubliceerde versie, 359 KBLicentie: CC BY-NC

Andere bestanden en links

Link naar publicatie in Scopus

Sleep Medicine
van Gilst, M. M. (Content manager) & van der Hout-van der Jagt, M. B. (Content manager)
Impact: Research Topic/Theme (at group level)

Citeer dit

@article{c4b704e1b2cf4b7e8d495b90a33af576,

title = "Intermediate hypocretin-1 cerebrospinal fluid levels and typical cataplexy: their significance in the diagnosis of narcolepsy type 1",

abstract = "STUDY OBJECTIVES: The diagnosis of narcolepsy type 1 (NT1) is based upon the presence of cataplexy and/or a cerebrospinal fluid (CSF) hypocretin-1/orexin-A level ≤ 110 pg/mL. We determined the clinical and diagnostic characteristics of patients with intermediate hypocretin-1 levels (111-200 pg/mL) and the diagnostic value of cataplexy characteristics in individuals with central disorders of hypersomnolence.METHODS: Retrospective cross-sectional study of 355 people with known CSF hypocretin-1 levels who visited specialized Sleep-Wake Centers in the Netherlands. For n = 271, we had full data on cataplexy type ({"}typical{"} or {"}atypical{"} cataplexy).RESULTS: Compared to those with normal hypocretin-1 levels (>200 pg/mL), a higher percentage of individuals with intermediate hypocretin-1 levels had typical cataplexy (75% or 12/16 vs 9% or 8/88, p < .05), and/or met the diagnostic polysomnographic (PSG) and Multiple Sleep Latency Test (MSLT) criteria for narcolepsy (50 vs 6%, p < .001). Of those with typical cataplexy, 88% had low, 7% intermediate, and 5% normal hypocretin-1 levels (p < .001). Atypical cataplexy was also associated with hypocretin deficiency but to a lesser extent. A hypocretin-1 cutoff of 150 pg/mL best predicted the presence of typical cataplexy and/or positive PSG and MSLT findings.CONCLUSION: Individuals with intermediate hypocretin-1 levels or typical cataplexy more often have outcomes fitting the PSG and MSLT criteria for narcolepsy than those with normal levels or atypical cataplexy. In addition, typical cataplexy has a much stronger association with hypocretin-1 deficiency than atypical cataplexy. We suggest increasing the NT1 diagnostic hypocretin-1 cutoff and adding the presence of clearly defined typical cataplexy to the diagnostic criteria of NT1. Clinical trial information: This study is not registered in a clinical trial register, as it has a retrospective database design.",

keywords = "Cataplexy/cerebrospinal fluid, Cross-Sectional Studies, Humans, Intracellular Signaling Peptides and Proteins, Narcolepsy/cerebrospinal fluid, Neuropeptides, Orexins/cerebrospinal fluid, Retrospective Studies, cataplexy, orexin-A, central disorders of hypersomnolence, sleep disorder",

author = "{van der Hoeven}, {Adrienne Elisabeth} and Rolf Fronczek and Schinkelshoek, {Mink Sebastian} and Roelandse, {Frederik Willem Cornelis} and Bakker, {Jaap Adriaan} and Sebastiaan Overeem and Denise Bijlenga and Lammers, {Gert Jan}",

year = "2022",

month = may,

day = "12",

doi = "10.1093/sleep/zsac052",

language = "English",

volume = "45",

journal = "Sleep",

issn = "0161-8105",

publisher = "Oxford University Press",

number = "5",

}

TY - JOUR

T1 - Intermediate hypocretin-1 cerebrospinal fluid levels and typical cataplexy

T2 - their significance in the diagnosis of narcolepsy type 1

AU - van der Hoeven, Adrienne Elisabeth

AU - Fronczek, Rolf

AU - Schinkelshoek, Mink Sebastian

AU - Roelandse, Frederik Willem Cornelis

AU - Bakker, Jaap Adriaan

AU - Overeem, Sebastiaan

AU - Bijlenga, Denise

AU - Lammers, Gert Jan

PY - 2022/5/12

Y1 - 2022/5/12

N2 - STUDY OBJECTIVES: The diagnosis of narcolepsy type 1 (NT1) is based upon the presence of cataplexy and/or a cerebrospinal fluid (CSF) hypocretin-1/orexin-A level ≤ 110 pg/mL. We determined the clinical and diagnostic characteristics of patients with intermediate hypocretin-1 levels (111-200 pg/mL) and the diagnostic value of cataplexy characteristics in individuals with central disorders of hypersomnolence.METHODS: Retrospective cross-sectional study of 355 people with known CSF hypocretin-1 levels who visited specialized Sleep-Wake Centers in the Netherlands. For n = 271, we had full data on cataplexy type ("typical" or "atypical" cataplexy).RESULTS: Compared to those with normal hypocretin-1 levels (>200 pg/mL), a higher percentage of individuals with intermediate hypocretin-1 levels had typical cataplexy (75% or 12/16 vs 9% or 8/88, p < .05), and/or met the diagnostic polysomnographic (PSG) and Multiple Sleep Latency Test (MSLT) criteria for narcolepsy (50 vs 6%, p < .001). Of those with typical cataplexy, 88% had low, 7% intermediate, and 5% normal hypocretin-1 levels (p < .001). Atypical cataplexy was also associated with hypocretin deficiency but to a lesser extent. A hypocretin-1 cutoff of 150 pg/mL best predicted the presence of typical cataplexy and/or positive PSG and MSLT findings.CONCLUSION: Individuals with intermediate hypocretin-1 levels or typical cataplexy more often have outcomes fitting the PSG and MSLT criteria for narcolepsy than those with normal levels or atypical cataplexy. In addition, typical cataplexy has a much stronger association with hypocretin-1 deficiency than atypical cataplexy. We suggest increasing the NT1 diagnostic hypocretin-1 cutoff and adding the presence of clearly defined typical cataplexy to the diagnostic criteria of NT1. Clinical trial information: This study is not registered in a clinical trial register, as it has a retrospective database design.

AB - STUDY OBJECTIVES: The diagnosis of narcolepsy type 1 (NT1) is based upon the presence of cataplexy and/or a cerebrospinal fluid (CSF) hypocretin-1/orexin-A level ≤ 110 pg/mL. We determined the clinical and diagnostic characteristics of patients with intermediate hypocretin-1 levels (111-200 pg/mL) and the diagnostic value of cataplexy characteristics in individuals with central disorders of hypersomnolence.METHODS: Retrospective cross-sectional study of 355 people with known CSF hypocretin-1 levels who visited specialized Sleep-Wake Centers in the Netherlands. For n = 271, we had full data on cataplexy type ("typical" or "atypical" cataplexy).RESULTS: Compared to those with normal hypocretin-1 levels (>200 pg/mL), a higher percentage of individuals with intermediate hypocretin-1 levels had typical cataplexy (75% or 12/16 vs 9% or 8/88, p < .05), and/or met the diagnostic polysomnographic (PSG) and Multiple Sleep Latency Test (MSLT) criteria for narcolepsy (50 vs 6%, p < .001). Of those with typical cataplexy, 88% had low, 7% intermediate, and 5% normal hypocretin-1 levels (p < .001). Atypical cataplexy was also associated with hypocretin deficiency but to a lesser extent. A hypocretin-1 cutoff of 150 pg/mL best predicted the presence of typical cataplexy and/or positive PSG and MSLT findings.CONCLUSION: Individuals with intermediate hypocretin-1 levels or typical cataplexy more often have outcomes fitting the PSG and MSLT criteria for narcolepsy than those with normal levels or atypical cataplexy. In addition, typical cataplexy has a much stronger association with hypocretin-1 deficiency than atypical cataplexy. We suggest increasing the NT1 diagnostic hypocretin-1 cutoff and adding the presence of clearly defined typical cataplexy to the diagnostic criteria of NT1. Clinical trial information: This study is not registered in a clinical trial register, as it has a retrospective database design.

KW - Cataplexy/cerebrospinal fluid

KW - Cross-Sectional Studies

KW - Humans

KW - Intracellular Signaling Peptides and Proteins

KW - Narcolepsy/cerebrospinal fluid

KW - Neuropeptides

KW - Orexins/cerebrospinal fluid

KW - Retrospective Studies

KW - cataplexy

KW - orexin-A

KW - central disorders of hypersomnolence

KW - sleep disorder

UR - http://www.scopus.com/inward/record.url?scp=85130016663&partnerID=8YFLogxK

U2 - 10.1093/sleep/zsac052

DO - 10.1093/sleep/zsac052

M3 - Article

C2 - 35554594

SN - 0161-8105

VL - 45

JO - Sleep

JF - Sleep

IS - 5

M1 - zsac052

ER -

Intermediate hypocretin-1 cerebrospinal fluid levels and typical cataplexy: their significance in the diagnosis of narcolepsy type 1

Samenvatting

Toegang tot document

Andere bestanden en links

Vingerafdruk

Impact

Sleep Medicine

Citeer dit