Reduced CSF hypocretin-1 levels are associated with cluster headache

Background Cluster headache (CH) is a debilitating disorder characterized by unilateral, severe pain attacks with accompanying autonomic symptoms, often waking the patient from sleep. As it exhibits strong chronobiological traits and genetic studies have suggested a link with the hypocretin (HCRT) system, the objective of this study was to investigate HCRT-1 in CH patients. Methods Cerebrospinal fluid HCRT-1 concentration was measured in 12 chronic and 14 episodic CH patients during an active bout, and in 27 healthy controls. The patients were well characterized and clinical features compared to the HCRT concentration. Results We found significantly lower HCRT levels both in chronic ( p = 0.0221) and episodic CH ( p = 0.0005) patients compared with controls. No significant relationship was found with other clinical features. Conclusions This is the first report of significantly reduced HCRT concentrations in CH patients. We speculate that decreased HCRT may reflect insufficient antinociceptive activity of the hypothalamus. The mechanism of the antinociceptive effect of HCRT is not known and requires further investigation. This study supports the hypothesis of a connection between arousal regulation and CH.

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Cerebrospinal fluid hypocretin-1 levels during the active period of cluster headache

Cephalalgia ◽

10.1177/0333102411403634 ◽

2011 ◽

Vol 31 (8) ◽

pp. 973-976 ◽

Cited By ~ 10

Author(s):

Sabina Cevoli ◽

Fabio Pizza ◽

Daniela Grimaldi ◽

Marianna Nicodemo ◽

Valentina Favoni ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Cluster Headache ◽

Slight Reduction ◽

Genetic Studies ◽

Physiological Processes ◽

Wide Range ◽

Functional Involvement ◽

Central Pain Processing ◽

Active Cluster ◽

Hypocretin 1

Background: Hypocretins (orexins) are hypothalamic neuropeptides which are involved in a wide range of physiological processes in mammals including central pain processing. Genetic studies in humans evidenced a role for the hypocretinergic system in cluster headache (CH). Patients and methods: We tested cerebrospinal fluid (CSF) hypocretin-1 (orexin-A) levels in 10 CH patients during an active cluster period. CSF hypocretin-1 levels were measured by radioimmunoassay. Results: CSF hypocretin-1 levels were within the normal range (mean 457.3 ± 104.98 pg/ml, range 304–639) in our 10 patients, with a slight reduction in one case (304 pg/ml). There were no associations between CSF hypocretin-1 levels and the clinical features of CH. A trend towards higher hypocretin-1 levels was disclosed in patients with chronic CH compared to episodic CH. Conclusions: CSF hypocretin-1 levels seem not to influence the clinical course of CH, but our results cannot completely exclude a functional involvement of the hypothalamic hypocretinergic system in the pathogenesis of CH.

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Clinical Features of Cluster Headache without Cranial Autonomic Symptoms: Results from a Prospective multicentre study

10.21203/rs.3.rs-127433/v1 ◽

2020 ◽

Author(s):

Min Kyung Chu ◽

Byung-Su Kim ◽

Pil-Wook Chung ◽

Byung-Kun Kim ◽

Mi Ji Lee ◽

...

Keyword(s):

Cluster Headache ◽

Clinical Features ◽

Rating Scale ◽

Significant Proportion ◽

Numeric Rating Scale ◽

Autonomic Symptoms ◽

General Anxiety Disorder ◽

General Anxiety ◽

Headache Intensity ◽

Cranial Autonomic Symptoms

Abstract Background: Although cranial autonomic symptoms are typical in cluster headache, some individuals with cluster headache show no cranial autonomic symptoms during their headache attacks. Probable cluster headache is a subtype of cluster headache that fulfils all but one of the five criteria for cluster headache. This study aimed to investigate the frequency and clinical features of cluster headache and probable cluster headache without cranial autonomic symptoms in comparison to those with cranial autonomic symptoms.Methods: We analysed data from the Korea Cluster Headache Registry, a prospective multicentre registry involving data from 16 hospitals.Results: Of the 216 participants with cluster headache and 26 with probable cluster headache, 19 (8.8%) and 7 (26.9%), respectively, did not have cranial autonomic symptoms. Participants with cluster headache without cranial autonomic symptoms exhibited less severe anxiety (General Anxiety Disorder-7 score, median [interquartile range], 2.0 [1.0-6.0] vs 8.0 [3.0-12.0], p = 0.001) and depression (Patient Health Questionnaire-9 score, 3.0 [1.0-7.0] vs 7.0 [3.0-11.0], p = 0.042) than those with cranial autonomic symptoms. Other clinical features, including headache intensity, daily headache frequency, attack duration, bout duration, and location of the pain, did not differ between participants with cluster headache with and without cranial autonomic symptoms. Headache intensity was less severe in participants with probable cluster headache without cranial autonomic symptoms than in those with cranial autonomic symptoms (numeric rating scale, 8.0 [7.0-8.0] vs 9.5 [8.0-10.0], p = 0.015).Conclusions: A significant proportion of participants with cluster headache and probable cluster headache did not have cranial autonomic symptoms. Some clinical features of cluster headache and probable cluster headache differed based on the presence of cranial autonomic symptoms.

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Clinical features of cluster headache without cranial autonomic symptoms: results from a prospective multicentre study

Scientific Reports ◽

10.1038/s41598-021-86408-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Min Kyung Chu ◽

Byung-Su Kim ◽

Pil-Wook Chung ◽

Byung-Kun Kim ◽

Mi Ji Lee ◽

...

Keyword(s):

Cluster Headache ◽

Clinical Features ◽

Rating Scale ◽

Significant Proportion ◽

Numeric Rating Scale ◽

Autonomic Symptoms ◽

General Anxiety Disorder ◽

General Anxiety ◽

Prospective Multicentre Study ◽

Cranial Autonomic Symptoms

AbstractAlthough cranial autonomic symptoms (CAS) are typical in cluster headache (CH), some individuals with CH show no CAS during their headache attacks. Probable cluster headache (PCH) is a subtype of CH that fulfils all but one criterion of CH. This study aimed to investigate the frequency and clinical features of CH and PCH without CAS in comparison to those with CAS. We analysed data from the Korea Cluster Headache Registry, a prospective multicentre registry involving data from 16 hospitals. Of the 216 participants with CH and 26 with PCH, 19 (8.8%) and 7 (26.9%), respectively, did not have CAS. Participants with CH without CAS exhibited less severe anxiety (General Anxiety Disorder-7 score, median [interquartile range], 2.0 [1.0–6.0] vs 8.0 [3.0–12.0], p = 0.001) and depression (Patient Health Questionnaire-9 score, 3.0 [1.0–7.0] vs 7.0 [3.0–11.0], p = 0.042) than those with CAS. Among participants with PCH, headache intensity was less severe in participants without CAS than in those with CAS (numeric rating scale, 8.0 [7.0–8.0] vs 9.5 [8.0–10.0], p = 0.015). In conclusion, a significant proportion of participants with CH and PCH did not have CAS. Some clinical features of CH and PCH differed based on the presence of CAS.

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Beta-Endorphin Levels are Reduced in Peripheral Blood Mononuclear Cells of Cluster Headache Patients

Cephalalgia ◽

10.1046/j.1468-2982.1993.1306413.x ◽

1993 ◽

Vol 13 (6) ◽

pp. 413-416 ◽

Cited By ~ 12

Author(s):

M Leone ◽

P Sacerdote ◽

D D'Amico ◽

AE Panerai ◽

G Bussone

Keyword(s):

Cerebrospinal Fluid ◽

Cluster Headache ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Healthy Controls ◽

Peripheral Blood Mononuclear ◽

Beta Endorphin ◽

Blood Mononuclear Cells ◽

Headache Patients

Opioid system hypofunction has been postulated in cluster headache (CH) on the basis of reduced opioid levels found in the cerebrospinal fluid (CSF). In this study beta-endorphin levels were monitored in the peripheral blood mononuclear cells of 65 episodic CH patients (32 in remission and 33 in cluster period) and 50 healthy controls. Beta-endorphin levels were significantly lower than controls in CH patients experiencing both phases of the illness (ANOVA, p < 0.0001). The persistence of this abnormality during pain-free remission suggests a primary alteration in the regulation of beta-endorphin in peripheral blood mononuclear cells. We speculate that these findings reflect reduced CNS levels of beta-endorphin in CH.

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Cerebrospinal fluid hypocretin-1 (orexin A) levels in mania compared to unipolar depression and healthy controls

Pharmacopsychiatry ◽

10.1055/s-0031-1292541 ◽

2011 ◽

Vol 44 (06) ◽

Author(s):

FM Schmidt ◽

M Bruegel ◽

J Kratzsch ◽

M Strauß ◽

C Sander ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Unipolar Depression ◽

Healthy Controls ◽

Orexin A ◽

Hypocretin 1

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Cerebrospinal fluid hypocretin-1 (orexin A) levels in mania compared to unipolar depression and healthy controls

Neuroscience Letters ◽

10.1016/j.neulet.2010.07.038 ◽

2010 ◽

Vol 483 (1) ◽

pp. 20-22 ◽

Cited By ~ 13

Author(s):

Frank M. Schmidt ◽

Matthias Brügel ◽

Jürgen Kratzsch ◽

Maria Strauß ◽

Christian Sander ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Unipolar Depression ◽

Healthy Controls ◽

Orexin A ◽

Hypocretin 1

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Association between Hypocretin-1 and Amyloid-β42 Cerebrospinal Fluid Levels in Alzheimer’s Disease and Healthy Controls

Current Alzheimer Research ◽

10.2174/156720512804142840 ◽

2012 ◽

Vol 9 (10) ◽

pp. 1119-1125 ◽

Cited By ~ 32

Author(s):

Diane Slats ◽

Jurgen A.H.R. Claassen ◽

Gert Jan Lammers ◽

Rene J. Melis ◽

Marcel M. Verbeek ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Amyloid Beta ◽

Healthy Controls ◽

Cerebrospinal Fluid Levels ◽

Amyloid Beta 42 ◽

Fluid Levels ◽

Hypocretin 1

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Cluster headache beyond the pain phase

Neurology ◽

10.1212/01.wnl.0000542491.92981.03 ◽

2018 ◽

Vol 91 (9) ◽

pp. e822-e831 ◽

Cited By ~ 8

Author(s):

Agneta Snoer ◽

Nunu Lund ◽

Rasmus Beske ◽

Andreas Hagedorn ◽

Rigmor Højland Jensen ◽

...

Keyword(s):

Observational Study ◽

Cluster Headache ◽

Clinical Features ◽

Prospective Observational Study ◽

Treatment Strategies ◽

Duration Of Symptoms ◽

Autonomic Symptoms ◽

Mood Changes ◽

Abortive Treatment ◽

The Given

ObjectiveTo describe the nature, prevalence, and duration of symptoms in the preictal, ictal, and postictal phases of cluster headache (CH) attacks.MethodsFifty-seven patients with episodic or chronic CH participated in this prospective, observational study. In a questionnaire concerning 33 CH and migraine-related symptoms, patients reported the clinical features of up to 10 CH attacks/patient. The questionnaire was divided into 3 sections: a preictal phase, ictal phase, and postictal phase. For each phase, patients documented whether the given symptom was present, and if possible estimated the duration of the symptom.ResultsIn total, 500 CH attack descriptions were obtained. In the preictal phase, general symptoms (most frequently concentration difficulties, restlessness, and mood changes) occurred 20 minutes prior to 46.0% of attacks. Local painful and autonomic symptoms were observed 10 minutes prior to 54.6% and 35% of attacks, respectively. Postictally, pain and autonomic symptoms resolved over 20 minutes, leaving patients with fatigue (36.2%), decreased energy (39.0%), and concentration difficulties (27.6%), lasting a median of 60 minutes.ConclusionsPreictal and postictal symptoms are very frequent in CH, demonstrating that CH attacks are not composed of a pain phase alone. Since the origin of CH attacks is unresolved, studies of preictal and postictal symptoms could contribute to the understanding of CH pathophysiology and, potentially, early, abortive treatment strategies.

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