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Headache Medicine Connections


Headache Medicine Connections

Year: 2021, Volume: 1, Issue: 2, Pages: 6-11

Original Article

Treatment of Refractory Chronic Migraine with Worm Eggs: A Therapy Rooted in Evolution

Received Date:13 October 2021, Accepted Date:05 December 2021, Published Date:14 December 2021


Introduction: This was a small open label study designed to determine efficacy of helminth egg therapy in refractory chronic migraine (RCM) patients. It is probable that the immune system is involved in migraine. 1 Helminth worms have populated the GI tract of primates for millions of years. They downregulate the immune response. When the helminths (and other parasites) are removed, the result may be an increase in autoimmune illness. The immune system and inflammation are involved in migraine pathophysiology. Study design: Eleven RCM patients were enrolled. After the run-in period, patients ingested the helminth eggs every 2 weeks for 5 months. These eggs were from the pig whipworm, T. suris. The primary endpoint involved the number of moderate or severe headache days per month. The first (run-in) month was compared to the last 2 months of active therapy. Secondary endpoints included disability, depression, anxiety, and quality of life. Results: 5 of 11 patients met the primary endpoint (a reduction in moderate or severe headache days by at least 3 per month). The number of moderate or severe headache days decreased by 14, 10, 8, 7, and 3 in these patients. The patients who met the primary endpoint all began with essentially no clinical depression at baseline. Disability declined in all 5 patients, as did anxiety. Quality of life (number of unhealthy days per month) improved in 2 of the 5 patients who met the primary endpoint. 4 of 11 patients who completed the study did not meet the primary endpoint. 1 other patient did not supply data, and another discontinued treatment due to diarrhea. Analysis of their secondary endpoints did not result in any definitive conclusions as to why they did not improve. Conclusion: This study indicates that there may possibly be a role for helminth therapy in treating refractory chronic migraineurs. 5 of 11 patients did well. This treatment is rooted in evolution. The presence of helminths results in a downregulation of certain aspects of our immune system. By re-introducing helminths into the GI system, we may dampen our immune response. This may possibly help in the treatment of conditions that involve the immune system, such as migraine.

Keywords: Migraine, Refractory Migraine, Headache, Helminth, Evolution, Chronic Migraine


  1. Arumugam M, Narayan SK. Rethinking of the concepts: Migraine is an autoimmune disease? Neurology, Psychiatry and Brain Research. 2019;31:20–26. Available from: https://dx.doi.org/10.1016/j.npbr.2018.11.003
  2. Sacco S, Braschinsky M, Ducros A, Lampl C, Little P, Brink AMvd, et al. European headache federation consensus on the definition of resistant and refractory migraine. The Journal of Headache and Pain. 2020;21(1):76. Available from: https://dx.doi.org/10.1186/s10194-020-01130-5
  3. Schulman EA, Lake AE, Goadsby PJ, Peterlin BL, Siegel SE, Markley HG, et al. Defining Refractory Migraine and Refractory Chronic Migraine: Proposed Criteria From the Refractory Headache Special Interest Section of the American Headache Society. Headache: The Journal of Head and Face Pain. 2008;48(6):778–782. Available from: https://dx.doi.org/10.1111/j.1526-4610.2008.01132.x
  4. Robbins L. Refractory Chronic Migraine: mild, moderate or severe. Practical Pain Management Published. 2019;19(4).
  5. Malhotra R. Understanding migraine: Potential role of neurogenic inflammation. Ann Indian Acad Neurol. 2016;19(2):175–182. doi: 10.4103/0972-2327.182302
  6. Irmak DK, Kilinc E, Tore F. Shared Fate of Meningeal Mast Cells and Sensory Neurons in Migraine. Frontiers in Cellular Neuroscience. 2019;13:136. Available from: https://dx.doi.org/10.3389/fncel.2019.00136
  7. Summers RW, Elliott DE, Urban JF, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn's disease. Gut. 2005;54(1):87–90. doi: 10.1136/gut.2004.041749
  8. Sandborn WJ, Elliott DE, Weinstock J, Summers RW, Landry-Wheeler A, Silver N, et al. Randomised clinical trial: the safety and tolerability ofTrichuris suisova in patients with Crohn's disease. Alimentary Pharmacology & Therapeutics. 2013;38(3):255–263. Available from: https://dx.doi.org/10.1111/apt.12366
  9. Smyth K, Morton C, Mathew A, Karuturi S, Haley C, Zhang M, et al. Production and Use of Hymenolepis diminuta Cysticercoids as Anti-Inflammatory Therapeutics. Journal of Clinical Medicine. 2017;6(10):98. Available from: https://dx.doi.org/10.3390/jcm6100098
  10. Zaccone P, Hall SW. Helminth Infection and Type 1 Diabetes. The Review of Diabetic Studies. 2012;9(4):272–286. Available from: https://dx.doi.org/10.1900/rds.2012.9.272
  11. Saunders KA, Raine T, Cooke A, Lawrence CE. Inhibition of Autoimmune Type 1 Diabetes by Gastrointestinal Helminth Infection. Infection and Immunity. 2007;75(1):397–407. Available from: https://dx.doi.org/10.1128/iai.00664-06
  12. Rodgers DT, Pineda MA, Suckling CJ, Harnett W, Harnett MM. Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus. Lupus. 2015;24(13):1437–1442. Available from: https://dx.doi.org/10.1177/0961203315591031
  13. Leroux LP, Nasr M, Valanparambil R, Tam M, Rosa BA, Siciliani E, et al. Analysis of the Trichuris suis excretory/secretory proteins as a function of life cycle stage and their immunomodulatory properties. Scientific Reports. 2018;8(1):15921. Available from: https://dx.doi.org/10.1038/s41598-018-34174-4
  14. Aprahamian TR, Zhong X, Amir S, Binder CJ, Chiang LK, Al-Riyami L, et al. The immunomodulatory parasitic worm product ES-62 reduces lupus-associated accelerated atherosclerosis in a mouse model. International Journal for Parasitology. 2015;45(4):203–207. Available from: https://dx.doi.org/10.1016/j.ijpara.2014.12.006
  15. Huang X, Zeng LR, Chen FS, Zhu JP, Zhu MH. Trichuris suis ova therapy in inflammatory bowel disease. Medicine. 2018;97(34):e12087. Available from: https://dx.doi.org/10.1097/md.0000000000012087
  16. Maizels RM, McSorley HJ. Regulation of the host immune system by helminth parasites. Journal of Allergy and Clinical Immunology. 2016;138(3):666–675. Available from: https://dx.doi.org/10.1016/j.jaci.2016.07.007


© 2021 Published by World Headache Society. This is an open-access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/)


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