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Neurobiology and sleep disorders in cluster headache.

Barloese MC - J Headache Pain (2015)

Bottom Line: Supported by endocrinological and radiological findings as well as the chronobiological features, predominant theories revolve around central pathology of the hypothalamus.The findings include: A distinct circannual connection between cluster occurrence and the amount of daylight, substantially poorer sleep quality in patients compared to controls which was present not only inside the clusters but also outside, affected REM-sleep in patients without a particular temporal connection to nocturnal attacks, equal prevalence of sleep apnea in both patient and control groups, reduced levels of hypocretin-1 in the cerebrospinal fluid of patients and finally a blunted response to the change from supine to tilted position in the head-up tilt table test indicating a weakened sympathoexcitatory or stronger parasympathetic drive.Future endeavors should focus on pathological changes which persist in the attack-free periods but also heed the possibility of long-lived, cluster-induced pathology.

View Article: PubMed Central - PubMed

Affiliation: Danish Headache Center, Glostrup Hospital, Nordre Ringvej 57, Glostrup, DK-2600, Denmark, mads@barloese.net.

ABSTRACT
Cluster headache is characterized by unilateral attacks of severe pain accompanied by cranial autonomic features. Apart from these there are also sleep-related complaints and strong chronobiological features. The interaction between sleep and headache is complex at any level and evidence suggests that it may be of critical importance in our understanding of primary headache disorders. In cluster headache several interactions between sleep and the severe pain attacks have already been proposed. Supported by endocrinological and radiological findings as well as the chronobiological features, predominant theories revolve around central pathology of the hypothalamus. We aimed to investigate the clinical presentation of chronobiological features, the presence of concurrent sleep disorders and the relationship with particular sleep phases or phenomena, the possible role of hypocretin as well as the possible involvement of cardiac autonomic control. We conducted a questionnaire survey on 275 cluster headache patients and 145 controls as well an in-patient sleep study including 40 CH-patients and 25 healthy controls. The findings include: A distinct circannual connection between cluster occurrence and the amount of daylight, substantially poorer sleep quality in patients compared to controls which was present not only inside the clusters but also outside, affected REM-sleep in patients without a particular temporal connection to nocturnal attacks, equal prevalence of sleep apnea in both patient and control groups, reduced levels of hypocretin-1 in the cerebrospinal fluid of patients and finally a blunted response to the change from supine to tilted position in the head-up tilt table test indicating a weakened sympathoexcitatory or stronger parasympathetic drive. Overall, these findings support a theory of involvement of dysregulation in hypothalamic and brainstem nuclei in cluster headache pathology. Further, it is made plausible that the headache attacks are but one aspect of a more complex syndrome of central dysregulation manifesting as sleep-related complaints, sub-clinical autonomic dysregulation and of course the severe attacks of unilateral headache. Future endeavors should focus on pathological changes which persist in the attack-free periods but also heed the possibility of long-lived, cluster-induced pathology.

No MeSH data available.


Related in: MedlinePlus

Schematic depiction of the trigeminal-autonomic reflex and related areas. Sensory afferents from cranial structures synapse in the trigeminal nucleus caudatus. Input is relayed to the brainstem and higher structures including the periaqueductal grey (PAG) and hypothalamus. Likewise, descending modulatory hypocretinergic connections are received from the hypothalamus. SSN – superior salivatory nucleus, TNC – trigeminal nucleus caudalis (trigeminal complex), PG – ptyrogopalatine (sphenopalatine) ganglion, TG – trigeminal ganglion. With permission from Holland et al. 2009 (Springer)
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Fig1: Schematic depiction of the trigeminal-autonomic reflex and related areas. Sensory afferents from cranial structures synapse in the trigeminal nucleus caudatus. Input is relayed to the brainstem and higher structures including the periaqueductal grey (PAG) and hypothalamus. Likewise, descending modulatory hypocretinergic connections are received from the hypothalamus. SSN – superior salivatory nucleus, TNC – trigeminal nucleus caudalis (trigeminal complex), PG – ptyrogopalatine (sphenopalatine) ganglion, TG – trigeminal ganglion. With permission from Holland et al. 2009 (Springer)

Mentions: Hypocretins (HCRT) 1 and 2 (also known as orexin A and B) are neuropeptides produced by 10–20,000 neurons in the lateral and perifornical areas of the hypothalamus [29]. Caused by the complete loss of HCRT neurons, perhaps by an autoimmune process, the HCRT concentration in cerebrospinal fluid (CSF) of patients suffering from narcolepsy with cataplexy is low to undetectable [30]. The HCRT-1 and −2 receptors are G-protein coupled, and located widely throughout the neuroaxis [31]. HCRT-1 binds to both the HCRT-1 and −2 receptor with equal affinity whereas HCRT-2 binds to the HCRT-2 receptor with ten times greater affinity [31]. Crucial for the normal function of arousal control, sleep regulation, homeostatic maintenance and possibly pain processing [29], the HCRTs may be involved in CH pathology by way of a polymorphism of the HCRT-2 receptor gene [32–35] or an otherwise related mechanism, possibly involving descending connections from the hypothalamus to brainstem circuits involved in trigeminal nociception (Fig. 1).Fig. 1


Neurobiology and sleep disorders in cluster headache.

Barloese MC - J Headache Pain (2015)

Schematic depiction of the trigeminal-autonomic reflex and related areas. Sensory afferents from cranial structures synapse in the trigeminal nucleus caudatus. Input is relayed to the brainstem and higher structures including the periaqueductal grey (PAG) and hypothalamus. Likewise, descending modulatory hypocretinergic connections are received from the hypothalamus. SSN – superior salivatory nucleus, TNC – trigeminal nucleus caudalis (trigeminal complex), PG – ptyrogopalatine (sphenopalatine) ganglion, TG – trigeminal ganglion. With permission from Holland et al. 2009 (Springer)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542772&req=5

Fig1: Schematic depiction of the trigeminal-autonomic reflex and related areas. Sensory afferents from cranial structures synapse in the trigeminal nucleus caudatus. Input is relayed to the brainstem and higher structures including the periaqueductal grey (PAG) and hypothalamus. Likewise, descending modulatory hypocretinergic connections are received from the hypothalamus. SSN – superior salivatory nucleus, TNC – trigeminal nucleus caudalis (trigeminal complex), PG – ptyrogopalatine (sphenopalatine) ganglion, TG – trigeminal ganglion. With permission from Holland et al. 2009 (Springer)
Mentions: Hypocretins (HCRT) 1 and 2 (also known as orexin A and B) are neuropeptides produced by 10–20,000 neurons in the lateral and perifornical areas of the hypothalamus [29]. Caused by the complete loss of HCRT neurons, perhaps by an autoimmune process, the HCRT concentration in cerebrospinal fluid (CSF) of patients suffering from narcolepsy with cataplexy is low to undetectable [30]. The HCRT-1 and −2 receptors are G-protein coupled, and located widely throughout the neuroaxis [31]. HCRT-1 binds to both the HCRT-1 and −2 receptor with equal affinity whereas HCRT-2 binds to the HCRT-2 receptor with ten times greater affinity [31]. Crucial for the normal function of arousal control, sleep regulation, homeostatic maintenance and possibly pain processing [29], the HCRTs may be involved in CH pathology by way of a polymorphism of the HCRT-2 receptor gene [32–35] or an otherwise related mechanism, possibly involving descending connections from the hypothalamus to brainstem circuits involved in trigeminal nociception (Fig. 1).Fig. 1

Bottom Line: Supported by endocrinological and radiological findings as well as the chronobiological features, predominant theories revolve around central pathology of the hypothalamus.The findings include: A distinct circannual connection between cluster occurrence and the amount of daylight, substantially poorer sleep quality in patients compared to controls which was present not only inside the clusters but also outside, affected REM-sleep in patients without a particular temporal connection to nocturnal attacks, equal prevalence of sleep apnea in both patient and control groups, reduced levels of hypocretin-1 in the cerebrospinal fluid of patients and finally a blunted response to the change from supine to tilted position in the head-up tilt table test indicating a weakened sympathoexcitatory or stronger parasympathetic drive.Future endeavors should focus on pathological changes which persist in the attack-free periods but also heed the possibility of long-lived, cluster-induced pathology.

View Article: PubMed Central - PubMed

Affiliation: Danish Headache Center, Glostrup Hospital, Nordre Ringvej 57, Glostrup, DK-2600, Denmark, mads@barloese.net.

ABSTRACT
Cluster headache is characterized by unilateral attacks of severe pain accompanied by cranial autonomic features. Apart from these there are also sleep-related complaints and strong chronobiological features. The interaction between sleep and headache is complex at any level and evidence suggests that it may be of critical importance in our understanding of primary headache disorders. In cluster headache several interactions between sleep and the severe pain attacks have already been proposed. Supported by endocrinological and radiological findings as well as the chronobiological features, predominant theories revolve around central pathology of the hypothalamus. We aimed to investigate the clinical presentation of chronobiological features, the presence of concurrent sleep disorders and the relationship with particular sleep phases or phenomena, the possible role of hypocretin as well as the possible involvement of cardiac autonomic control. We conducted a questionnaire survey on 275 cluster headache patients and 145 controls as well an in-patient sleep study including 40 CH-patients and 25 healthy controls. The findings include: A distinct circannual connection between cluster occurrence and the amount of daylight, substantially poorer sleep quality in patients compared to controls which was present not only inside the clusters but also outside, affected REM-sleep in patients without a particular temporal connection to nocturnal attacks, equal prevalence of sleep apnea in both patient and control groups, reduced levels of hypocretin-1 in the cerebrospinal fluid of patients and finally a blunted response to the change from supine to tilted position in the head-up tilt table test indicating a weakened sympathoexcitatory or stronger parasympathetic drive. Overall, these findings support a theory of involvement of dysregulation in hypothalamic and brainstem nuclei in cluster headache pathology. Further, it is made plausible that the headache attacks are but one aspect of a more complex syndrome of central dysregulation manifesting as sleep-related complaints, sub-clinical autonomic dysregulation and of course the severe attacks of unilateral headache. Future endeavors should focus on pathological changes which persist in the attack-free periods but also heed the possibility of long-lived, cluster-induced pathology.

No MeSH data available.


Related in: MedlinePlus