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Alterations of the structural covariance network in the hypothalamus of patients with cluster headache

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Abstract

Objective

The hypothalamus is one of the key structures involved in the pathophysiology of cluster headaches. This study aimed to analyze the volume of hypothalamic subunits and structural covariance networks in the hypothalamus of patients with cluster headache.

Methods

We retrospectively enrolled 18 patients with episodic cluster headache and 18 age- and sex-matched healthy controls. We calculated individual structural volumes in ten hypothalamic subunits using three-dimensional T1-weighted imaging and the FreeSurfer program, which conducted an automated segmentation based on deep convolutional neural networks. We also performed an analysis of the structural covariance network in the hypothalamus using graph theory and the BRAPH program. We compared the volumes of hypothalamic subunits and structural covariance networks in the hypothalamus of patients with cluster headache versus those of healthy controls.

Results

There were no significant differences in the structural volumes of the whole hypothalamus and hypothalamic subunits between patients with cluster headache and healthy controls. However, patients with cluster headache had significant alterations of the structural covariance network in the hypothalamus compared to that of healthy controls. The network measure of small-worldness index in patients with cluster headache was lower than that in healthy controls (0.844 vs. 0.955, p = 0.004).

Conclusion

We demonstrated a significant difference in the structural covariance network in the hypothalamus of patients with cluster headache versus those of healthy controls. These findings could be related to the pathogenesis of cluster headache.

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Availability of data and material

Data that support the findings of this study are available upon reasonable request.

References

  1. May A, Schwedt TJ, Magis D, Pozo-Rosich P, Evers S, Wang S-J (2018) Cluster headache. Nat Rev Dis Primers 4(1):1–17

    Article  Google Scholar 

  2. Arnold M (2018) Headache classification committee of the international headache society (IHS) the international classification of headache disorders. Cephalalgia 38(1):1–211

    Article  Google Scholar 

  3. Eller M, Goadsby P (2016) Trigeminal autonomic cephalalgias. Oral Dis 22(1):1–8

    Article  CAS  Google Scholar 

  4. Goadsby PJ (2002) Pathophysiology of cluster headache: a trigeminal autonomic cephalgia. Lancet Neurol 1(4):251–257

    Article  Google Scholar 

  5. Goadsby PJ, Lipton RB (1997) A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. Brain J Neurol 120(1):193–209

    Article  Google Scholar 

  6. Akerman S, Holland PR, Summ O, Lasalandra MP, Goadsby PJ (2012) A translational in vivo model of trigeminal autonomic cephalalgias: therapeutic characterization. Brain 135(12):3664–3675

    Article  Google Scholar 

  7. Valet M, Sprenger T, Boecker H, Willoch F, Rummeny E, Conrad B, Erhard P, Tolle TR (2004) Distraction modulates connectivity of the cingulo-frontal cortex and the midbrain during pain—an fMRI analysis. Pain 109(3):399–408

    Article  Google Scholar 

  8. Teepker M, Menzler K, Belke M, Heverhagen JT, Voelker M, Mylius V, Oertel WH, Rosenow F, Knake S (2012) Diffusion tensor imaging in episodic cluster headache. Headache J Head Face Pain 52(2):274–282

    Article  Google Scholar 

  9. Yang F-C, Chou K-H, Fuh J-L, Huang C-C, Lirng J-F, Lin Y-Y, Lin C-P, Wang S-J (2013) Altered gray matter volume in the frontal pain modulation network in patients with cluster headache. PAIN® 154(6):801–807

    Article  Google Scholar 

  10. Absinta M, Rocca MA, Colombo B, Falini A, Comi G, Filippi M (2012) Selective decreased grey matter volume of the pain-matrix network in cluster headache. Cephalalgia 32(2):109–115

    Article  Google Scholar 

  11. Rocca MA, Valsasina P, Absinta M, Colombo B, Barcella V, Falini A, Comi G, Filippi M (2010) Central nervous system dysregulation extends beyond the pain-matrix network in cluster headache. Cephalalgia 30(11):1383–1391

    Article  Google Scholar 

  12. Ha SY, Park KM (2019) Alterations of structural connectivity in episodic cluster headache: a graph theoretical analysis. J Clin Neurosci 62:60–65

    Article  Google Scholar 

  13. May A, Bahra A, Büchel C, Frackowiak RS, Goadsby PJ (1998) Hypothalamic activation in cluster headache attacks. The Lancet 352(9124):275–278

    Article  CAS  Google Scholar 

  14. Holland PR, Goadsby PJ (2009) Cluster headache, hypothalamus, and orexin. Curr Pain Headache Rep 13(2):147–154

    Article  Google Scholar 

  15. Leone M, Bussone G (1993) A review of hormonal findings in cluster headache. Evidence for hypothalamic involvement. Cephalalgia 13(5):309–317

    Article  CAS  Google Scholar 

  16. Strittmatter M, Hamann G, Grauer M, Fischer C, Blaes F, Hoffmann K, Schimrigk K (1996) Altered activity of the sympathetic nervous system and changes in the balance of hypophyseal, pituitary and adrenal hormones in patients with cluster headache. NeuroReport 7(7):1229–1234

    Article  CAS  Google Scholar 

  17. Arkink EB, Schmitz N, Schoonman GG, van Vliet JA, Haan J, van Buchem MA, Ferrari MD, Kruit MC (2017) The anterior hypothalamus in cluster headache. Cephalalgia 37(11):1039–1050

    Article  Google Scholar 

  18. Billot B, Bocchetta M, Todd E, Dalca AV, Rohrer JD, Iglesias JE (2020) Automated segmentation of the hypothalamus and associated subunits in brain MRI. Neuroimage 223:117287

    Article  Google Scholar 

  19. Mijalkov M, Kakaei E, Pereira JB, Westman E, Volpe G, Alzheimer’s Disease Neuroimaging I (2017) BRAPH: a graph theory software for the analysis of brain connectivity. PLoS ONE 12(8):e0178798. https://doi.org/10.1371/journal.pone.0178798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Farahani FV, Karwowski W, Lighthall NR (2019) Application of graph theory for identifying connectivity patterns in human brain networks: a systematic review. Front Neurosci 13:585

    Article  Google Scholar 

  21. Bernhardt B, Hong S-J, Bernasconi A, Bernasconi N (2013) Imaging structural and functional brain networks in temporal lobe epilepsy. Front Hum Neurosci 7:624

    Article  Google Scholar 

  22. Chou K-H, Yang F-C, Fuh J-L, Kuo C-Y, Wang Y-H, Lirng J-F, Lin Y-Y, Wang S-J, Lin C-P (2017) Bout-associated intrinsic functional network changes in cluster headache: a longitudinal resting-state functional MRI study. Cephalalgia 37(12):1152–1163

    Article  Google Scholar 

  23. Qiu E, Wang Y, Ma L, Tian L, Liu R, Dong Z, Xu X, Zou Z, Yu S (2013) Abnormal brain functional connectivity of the hypothalamus in cluster headaches. PLoS ONE 8(2):e57896

    Article  CAS  Google Scholar 

  24. Yang F-C, Chou K-H, Fuh J-L, Lee P-L, Lirng J-F, Lin Y-Y, Lin C-P, Wang S-J (2015) Altered hypothalamic functional connectivity in cluster headache: a longitudinal resting-state functional MRI study. J Neurol Neurosurg Psychiatry 86(4):437–445

    Article  Google Scholar 

  25. May A, Ashburner J, Büchel C, McGonigle D, Friston K, Frackowiak R, Goadsby P (1999) Correlation between structural and functional changes in brain in an idiopathic headache syndrome. Nat Med 5(7):836–838

    Article  CAS  Google Scholar 

  26. May A, Goadsby PJ (2001) Hypothalamic involvement and activation in cluster headache. Curr Pain Headache Rep 5(1):60–66. https://doi.org/10.1007/s11916-001-0011-4

    Article  CAS  PubMed  Google Scholar 

  27. Chong CD, Aguilar M, Schwedt TJ (2020) Altered hypothalamic region covariance in migraine and cluster headache: a structural MRI study. Headache 60(3):553–563. https://doi.org/10.1111/head.13742

    Article  PubMed  Google Scholar 

  28. Giorgio A, Lupi C, Zhang J, De Cesaris F, Alessandri M, Mortilla M, Federico A, Geppetti P, De Stefano N, Benemei S (2020) Changes in grey matter volume and functional connectivity in cluster headache versus migraine. Brain Imaging Behav 14(2):496–504

    Article  Google Scholar 

  29. Steffen N, Dagny H, Obermann M (2014) Structural Imaging in Cluster Headache. Curr Pain Headache Rep 18:415

    Article  Google Scholar 

  30. Yang F-C, Chou K-H, Kuo C-Y, Lin Y-Y, Lin C-P, Wang S-J (2018) The pathophysiology of episodic cluster headache: insights from recent neuroimaging research. Cephalalgia 38(5):970–983

    Article  Google Scholar 

  31. Naegel S, Holle D, Desmarattes N, Theysohn N, Diener H-C, Katsarava Z, Obermann M (2014) Cortical plasticity in episodic and chronic cluster headache. NeuroImage Clin 6:415–423

    Article  Google Scholar 

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Funding

None.

Author information

Author notes

  1. Dong Ah Lee, Ho-Joon Lee have contributed equally to this study.

Authors and Affiliations

  1. Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Haeundae-ro 875, Haeundae-gu, Busan, 48108, Republic of Korea

    Dong Ah Lee, Hyung Chan Kim & Kang Min Park

  2. Department of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea

    Ho-Joon Lee

Authors
  1. Dong Ah Lee
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  2. Ho-Joon Lee
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  3. Hyung Chan Kim
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  4. Kang Min Park
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by DAL, H-JL, HCK and KMP. The first draft of the manuscript was written by KMP and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kang Min Park.

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Conflicts of interest

Neither of the authors has any conflict of interest to disclose.

Ethical standards

This protocol was approved and carried out in accordance with the recommendation of the local Institutional Review Board (Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea).

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Lee, D.A., Lee, HJ., Kim, H.C. et al. Alterations of the structural covariance network in the hypothalamus of patients with cluster headache. J Neurol 269, 316–322 (2022). https://doi.org/10.1007/s00415-021-10629-z

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  • DOI: https://doi.org/10.1007/s00415-021-10629-z

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