Cluster headache: insights from resting-state functional magnetic resonance imaging

Ferraro, Stefania; Nigri, Anna; Bruzzone, Maria Grazia; Demichelis, Greta; Pinardi, Chiara; Brivio, Luca; Giani, Luca; Proietti, Alberto; Leone, Massimo; Chiapparini, Luisa

doi:10.1007/s10072-019-03874-8

Cited by 11 publications

(12 citation statements)

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“…The posterior part of the hypothalamus has been shown to be activated during acute cluster headache attacks in various studies, starting with early H 2 O-PET studies and continuing to recent fMRI studies [1][2][3][16][17][18]. To date, no studies exist which investigated cluster headache patients using task related designs in functional imaging.…”

Section: Discussionmentioning

confidence: 99%

“…As there were patients taking medication within both cluster groups, it is rather unlikely that the difference we describe is simply due to an effect of medication. The hypothalamus is involved in processing and modulation of painful trigeminal stimuli via various fiber connections of different hypothalamic nuclei to the spinal trigeminal nucleus, the PAG, the posterior Raphe nucleus and others [10,18]. Additionally, there are efferent fiber connections of the spinal trigeminal nucleus that directly activate hypothalamic nuclei [19] and the hypothalamus has been shown to be activated in response to trigeminonociceptive stimulation in healthy subjects [10].…”

Section: Discussionmentioning

confidence: 99%

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Phase dependent hypothalamic activation following trigeminal input in cluster headache

2020

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Background: Task-free imaging approaches using PET have shown the posterior hypothalamus to be specifically activated during but not outside cluster headache attacks. Evidence from task related functional imaging approaches however is scarce. Methods: Twenty-one inactive cluster headache patients (episodic cluster headache out of bout), 16 active cluster headache patients (10 episodic cluster headache in bout, 6 chronic cluster headache) and 18 control participants underwent high resolution brainstem functional magnetic resonance imaging of trigeminal nociception using gaseous ammonia as a painful stimulus. Results: Following trigeminonociceptive stimulation with ammonia there was a significantly stronger activation within the posterior hypothalamus in episodic cluster headache patients out of bout when compared to controls. When contrasting estimates of the pain contrast, active cluster headache patients where in between the two other groups but did not differ significantly from either. Conclusion: The posterior hypothalamus might thus be hyperexcitable in cluster headache patients outside the bout while excitability to external nociceptive stimuli decreases during in bout periods, probably due to frequent hypothalamic activation and possible neurotransmitter exhaustion during cluster attacks.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Phase dependent hypothalamic activation following trigeminal input in cluster headache

2020

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“…As noted above, hypothalamic functional connectivity in CH with functional MRI brain studies suggested both the role of the hypothalamus and the diencephalic‐mesencephalic junction regions 49 . This altered connectivity, linked to both CH and suicidal bipolar patients, may play a role in suicidality in CH patients.…”

Section: Cgrp and Ch Pathophysiologymentioning

confidence: 79%

Peptides, MAbs, Molecules, Mechanisms, and More: Taking a Stab at Cluster Headache

Joshi

2020

Headache

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Background Cluster headache is a highly disabling neurological disorder. Purpose The purpose of this review is to highlight recent therapeutic advances in the treatment of cluster headache such as monoclonal antibodies as well as non‐invasive vagus nerve stimulation, and examine future potential therapeutic targets. Discussion Several therapeutic agents currently in use may have underlying mechanisms important to cluster headache pathophysiology and have yet to be completely elucidated. The psychobiological aspects of cluster headache have a significant impact on patients, as well as pose limitations for treatment. Neuropeptides may play a role in underlying mechanisms in why cluster headache patients are frequent tobacco smokers. Alterations in the hypothalamic‐pituitary‐adrenal axis and neuroinflammation may play a role in suicidality. The circadian nature of cluster headache may generate the development of future treatment options. New understanding of mechanisms underlying post‐traumatic headache may also provide insights into cluster headache pathophysiology. Conclusion Molecular targets and neuromodulation advances have paved the way for a new generation of therapeutic agents in cluster headache. There are several other potential targets.

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“…Several hypotheses have been already proposed with regard to the risk of affective disorders in CH patients: 1) neuroimaging findings have shown shared anatomical substrates for the pain matrix and depression processing; 2) similarities between CH and depression have been observed in terms of hypothalamic dysfunction and chronobiology; and 3) common mood changes are reported in the pre-and post-ictal phases of a CH attack [11,[28][29][30][31][32]. The possible mechanism underlying the improvement in anxiety and depression during remission periods has not been specifically addressed in the literature to date.…”

Section: Discussionmentioning

confidence: 99%

The impact of remission and coexisting migraine on anxiety and depression in cluster headache

et al. 2020

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Background: Our aim was to investigate the relationship between coexisting cluster headache (CH) and migraine with anxiety and depression during active cluster bouts, and how symptoms change during remission. Methods: We analyzed data from 222 consecutive CH patients and 99 age-and sex-matched controls using a prospective multicenter registry. Anxiety or depression was evaluated using the Generalized Anxiety Disorder-7 (GAD-7) or Patient Health Questionnaire-9 (PHQ-9), respectively. Moderate-to-severe anxiety or depression was defined as a score of ≥10 at baseline (during a cluster bout). We assessed for changes in anxiety and depression during CH remission periods. Results: Among the CH patients, the prevalence of moderate-to-severe anxiety and depression was seen in 38.2% and 34.6%, respectively. Compared with controls, CH patients were associated with moderate-to-severe anxiety and depression (multivariable-adjusted odds ratio [aOR] = 7.32, 95% confidence intervals [CI] = 3.35-15.99 and aOR = 4.95, 95% CI = 2.32-10.57, respectively). CH patients with migraine were significantly more likely to have moderate-tosevere anxiety and depression (aOR = 32.53, 95% CI = 6.63-159.64 and aOR = 16.88, 95% CI = 4.16-68.38, respectively), compared to controls without migraine. The GAD-7 and PHQ-9 scores were significantly reduced between cluster bout and remission periods (from 6.8 ± 5.6 to 1.6 ± 2.8; P < 0.001, and from 6.1 ± 5.0 to 1.8 ± 2.4; P < 0.001, respectively). Conclusions: Our results indicate that CH patients are at increased risk of anxiety and depression, especially in the presence of coexisting migraine. However, the anxiety and depression can improve during remission periods.

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Cluster headache: insights from resting-state functional magnetic resonance imaging

Cited by 11 publications

References 11 publications

Phase dependent hypothalamic activation following trigeminal input in cluster headache

Phase dependent hypothalamic activation following trigeminal input in cluster headache

Peptides, MAbs, Molecules, Mechanisms, and More: Taking a Stab at Cluster Headache

The impact of remission and coexisting migraine on anxiety and depression in cluster headache

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