ArticleThe journal of headache and pain2024
Involvement of the ipsilateral-to-the-pain anterior-superior hypothalamic subunit in chronic cluster headache.
Article in The journal of headache and pain, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 15 citations in OpenAlex.
- Sleep and Headache Disorders: What a Clinician Needs to Know.Current neurology and neuroscience reports · 2026Review
- Hypothalamic subregional volume in relation to VSS-C total symptom burden in women with migraine: an exploratory cross-sectional MRI study.Frontiers in neurology · 2026Article
- Hypothalamic subunit atrophy and glymphatic dysfunction in idiopathic hypogonadotropic hypogonadism: associations with cognitive impairment.BMC medical imaging · 2025Article
- Neurotransmitter Imbalance in Cluster Headache: A Systematic Review of Mechanisms and Therapeutic Targets.Pain and therapy · 2025Review
- Hallmarks of primary headache: part 3 - cluster headache.The journal of headache and pain · 2025Review
- Dysfunctional mesocorticolimbic circuitry in cluster headache.The journal of headache and pain · 2025Article
- Limbic system abnormalities in episodic cluster headache: a 7T MRI multimodal study.The journal of headache and pain · 2025Article
- Cluster Headache and Migraine Shared and Unique Insights: Neurophysiological Implications, Neuroimaging, and Biomarkers: A Comprehensive Review.Journal of clinical medicine · 2025Review
- Cluster Headache and Hypoxia: Breathing New Life into an Old Theory, with Novel Implications.Neurology international · 2024Review
- Hyperalgesia, Increased Temporal Summation and Impaired Inhibitory Mechanisms in Episodic and Chronic Cluster Headache: An Observational Study.Biomedicines · 2024Article
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13 authors at 6 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition.
methodsWe used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models. Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients.
resultsPatients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior-superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found.
conclusionsWe identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache.
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