Defective functional connectivity between posterior hypothalamus and regions of the diencephalic-mesencephalic junction in chronic cluster headache

Ferraro, Stefania; Nigri, Anna; Bruzzone, Maria Grazia; Brivio, Luca; Cecchini, Alberto Proietti; Verri, Mattia; Chiapparini, Luisa; Leone, Massimo

doi:10.1177/0333102418761048

Cited by 26 publications

(17 citation statements)

References 49 publications

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“…Positron emission tomography (PET) and functional MRI studies demonstrated that the posterior HTH is activated during attacks of CH and some other TACs (24, 25). Resting-state functional MRI studies also found altered FC of HTH with the salience network (SN) (26) and a number of diencephalic-mesencephalic dopaminergic structures (27) in CH. VBM MRI has found significant structural differences in the HTH posterior gray matter compared with controls (28).…”

Section: Discussionmentioning

confidence: 98%

Volume of Hypothalamus as a Diagnostic Biomarker of Chronic Migraine

Chen

Liu

et al. 2019

Front. Neurol.

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It is believed than hypothalamus (HTH) might be involved in generation of migraine, and evidence from high resolution fMRI reported that the more anterior part of HTH seemed to play an important role in migraine chronification. The current study was aimed to identify the alteration of morphology and resting-state functional connectivity (FC) of the hypothalamus (HTH) in interictal episodic migraine (EM) and chronic migraine (CM). High-resolution structural and resting-state functional magnetic resonance images were acquired in 18 EM patients, 16 CM patients, and 21 normal controls (NC). The volume of HTH was calculated and voxel-based morphometry (VBM) was performed over the whole HTH. Receiver operating characteristics (ROC) curve analysis was applied to evaluate the diagnostic efficacy of HTH volume. Correlation analyses with clinical variables were performed and FC maps were generated for positive HTH regions according to VBM comparison. The volume of the HTH significantly decreased in both EM and CM patients compared with NC. The cut-off volume of HTH as 1.429 ml had a good diagnostic accuracy for CM with sensitivity of 81.25% and specificity of 100%. VBM analyses identified volume reduction of posterior HTH in EM vs. NC which was negatively correlated with headache frequency. The posterior HTH presented decreased FC with the left inferior temporal gyrus (Brodmann area 20) in EM. Decreased volume of anterior HTH was identified in CM vs. NC and CM vs. EM which was positively correlated with headache frequency in CM. The anterior HTH presented increased FC with the right anterior orbital gyrus (AOrG) (Brodmann area 11) in CM compared with NC and increased FC with the right medial orbital gyrus (MOrG) (Brodmann area 11) in CM compared with EM. Our study provided evidence of structural plasticity and FC changes of HTH in the pathogensis of migraine generation and chronification, supporting potential therapeutic target toward the HTH and its peptide.

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Section: Discussionmentioning

confidence: 98%

Volume of Hypothalamus as a Diagnostic Biomarker of Chronic Migraine

Chen

Liu

et al. 2019

Front. Neurol.

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“…Third, the abnormal FC between the hypothalamus and the midbrain dopaminergic system (in particular the ventral tegmental area) in chronic CH patients ( 18 ) suggests that the possible pathways of chronicization pass through the mesocorticolimbic system also in CH. It is now accepted that the midbrain dopaminergic system is also stimulated by aversive stimuli such as pain ( 61 ), and the nucleus accumbens, a key component of the mesocorticolimbic system receiving direct projections from the ventral tegmental area, seems to be involved in the chronicization of pain in humans ( 62 – 64 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is important to note that dysfunctional connectivity between the posterior hypothalamic regions and the midbrain areas was observed in chronic CH patients out of attacks (18). The authors showed an increased FC between the ipsilateral posterior hypothalamus and several diencephalic-mesencephalic structures as the ventral tegmental area, the dorsal nuclei of raphe, and the bilateral substantia nigra, the subthalamic nucleus, and the red nucleus.…”

Section: Neuroimaging Studies Investigating the Hypothalamus/midbrainmentioning

confidence: 95%

Understanding Cluster Headache Using Magnetic Resonance Imaging

et al. 2020

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Cluster headache is an excruciating pain syndrome characterized by unilateral head pain attacks, lasting between 15 and 180 min, accompanied by marked ipsilateral cranial autonomic symptoms, such as lacrimation and conjunctival injection. Despite important insights provided by neuroimaging studies and deep brain stimulation findings, the pathophysiology of cluster headache and its pathways of chronicization are still elusive. In this mini-review, we will provide an overview of the functional and structural neuroimaging studies in episodic and chronic cluster headache conditions conducted to clarify the underlying pathophysiology.

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“…Attention has recently shifted to structural and functional connectivity studies revealing changes in the pain matrix [21,22]. Alterations in non-traditional pain-processing networks, including the hypothalamic-cerebellar network and occipital networks have also been reported [23][24][25][26][27].…”

Section: Cluster Headachementioning

confidence: 99%

Pharmacotherapy for Cluster Headache

et al. 2020

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Cluster headache is characterised by attacks of excruciating unilateral headache or facial pain lasting 15 min to 3 h and is seen as one of the most intense forms of pain. Cluster headache attacks are accompanied by ipsilateral autonomic symptoms such as ptosis, miosis, redness or flushing of the face, nasal congestion, rhinorrhoea, peri-orbital swelling and/or restlessness or agitation. Cluster headache treatment entails fast-acting abortive treatment, transitional treatment and preventive treatment. The primary goal of prophylactic and transitional treatment is to achieve attack freedom, although this is not always possible. Subcutaneous sumatriptan and high-flow oxygen are the most proven abortive treatments for cluster headache attacks, but other treatment options such as intranasal triptans may be effective. Verapamil and lithium are the preventive drugs of first choice and the most widely used in first-line preventive treatment. Given its possible cardiac side effects, electrocardiogram (ECG) is recommended before treating with verapamil. Liver and kidney functioning should be evaluated before and during treatment with lithium. If verapamil and lithium are ineffective, contraindicated or discontinued because of side effects, the second choice is topiramate. If all these drugs fail, other options with lower levels of evidence are available (e.g. melatonin, clomiphene, dihydroergotamine, pizotifen). However, since the evidence level is low, we also recommend considering one of several neuromodulatory options in patients with refractory chronic cluster headache. A new addition to the preventive treatment options in episodic cluster headache is galcanezumab, although the long-term effects remain unknown. Since effective preventive treatment can take several weeks to titrate, transitional treatment can be of great importance in the treatment of cluster headache. At present, greater occipital nerve injection is the most proven transitional treatment. Other options are high-dose prednisone or frovatriptan.

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Defective functional connectivity between posterior hypothalamus and regions of the diencephalic-mesencephalic junction in chronic cluster headache

Cited by 26 publications

References 49 publications

Volume of Hypothalamus as a Diagnostic Biomarker of Chronic Migraine

Volume of Hypothalamus as a Diagnostic Biomarker of Chronic Migraine

Understanding Cluster Headache Using Magnetic Resonance Imaging

Pharmacotherapy for Cluster Headache

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