Revisiting the expanded use of hyperbaric oxygen therapy for treatment of resistant migraines

David V.Matera ,Brian Smith,Benjamin Lam

1 Department of General Surgery,Geisinger Wyoming Valley Medical Center,Wilkes-Barre,PA,USA

2 Philadelphia College of Osteopathic Medicine,Philadelphia,PA,USA

3 Division of Plastic and Reconstructive Surgery,Philadelphia College of Osteopathic Medicine,Philadelphia,PA,USA

Abstract

Key words:hyperbaric chambers;hyperbaric oxygen therapy;vascular headaches;migraines;aura;vasoconstriction;migraine with aura;indications for hyperbaric oxygen

I NTRODUCTION

The use of hyperbaric oxygen therapy (HBO) has been a widely-accepted form of treatment for certain conditions.Hyperbaric oxygen therapy involves the inhalation of 100%oxygen in a hyperbaric chamber at a pressure higher than 1 atm or 760 mmHg.The bene ficial effects of HBO results from generating physiologic hyperoxia in tissue by fully saturating hemoglobin molecules and increasing the amount of oxygen dissolved in the plasma.This allows tissue to meet its oxygen demand through the dissolved oxygen alone without the need to utilize the oxygen linked to hemoglobin.1-5As a class II medical device,hyperbaric chambers are currently approved for 13 indications by the U.S.Food and Drug Administration(FDA) and Hyperbaric Medical Society.6,7Indications currently include adjuvant therapy in wound ischemia,thermal burn treatment,blood loss anemia,air embolisms,carbon monoxide poisoning,clostridial myonecrosis,crush injury,decompression sickness,chronic refractory osteomyelitis,necrotizing soft-tissue infections,radiation tissue injury,ischemic skin grafts and flaps,and intracranial abscess (Table1),but does not include neurologic conditions.5,8-10The 2016 European Consensus Conference on Hyperbaric Medicine resulted in a list of 9 indications for HBO to be used as a primary therapy,with an additional 13 indications where there is acceptable evidence that HBO may be used as treatment,as well as 6 indications where HBO may be considered as an optional modality.Amongst the 13 FDA-approved indications and the 28 indications that resulted from the 2016 European Consensus Conference on Hyperbaric Medicine,neither group includes treatment for neurological conditions such as migraines with aura.5,8,9,11Current treatments for migraines and other headaches are based around relieving the symptoms through the reduction of cerebral blood flow.12HBO substantially increases the amount of arterial oxygen and therefore effectively achieves cerebral vasoconstriction,thus treating the migraine.1,13Based on this case report,we believe the current approved indications for HBO need to be expanded to include resistant migraines after further randomized control trials demonstrate efficacy in a larger patient population (Table1).

CASE HISTORY

We present a 23-year-old female with a self-reported history of migraines with aura since the age of 12 with no other relevant medical history.She described her migraines as severe in nature lasting 4-6 hours,3 times monthly on average.Her extreme pain and sensitivity to light and sound often impaired daily function,causing a loss of vision and inability to focus on tasks at hand.The patient also reported frequent abdominal pain leading to emesis during her migraine attacks.Overall,the migraines hindered her functional status as she had missedmany days of school and work due to her condition.She had been managed by her primary care physician since the onset of her migraines at an early age;however,she experienced migraines refractory to Imitrix and adjustments to birth control.The patient would typically get mild relief using Excedrin,caffeine consumption,removal of light,and use of ice packs.Evaluation of this patient prior to initiation of treatment revealed no contraindications to HBO.The patient underwent treatment at 1.5 absolute atmospheres in a hyperbaric chamber Monday through Friday for 1 hour each day,for a total of 40 sessions,but reported missing a few sessions over the 8-week period.No more than one session during a given week was missed and the patient received no other treatments for her migraines throughout this time period.By her 24thtreatment,the patient had only experienced a single migraine with aura but without debilitating pain.The patient stated she has never had a migraine with such little intensity prior to initiation of hyperbaric treatment and did not have to take any days off from work or school during treatment.Follow-up at the end of her 40-day treatment period revealed a highly-satisfied patient who had only experienced the single episode of a mild migraine during the entire course of treatment.It is important to indicate that the patient did not receive any additional therapy during HBO treatments.

Table1:Current U.S.Food and Drug Administration approved indications and recommended update to the current indications for hyperbaric oxygen therapy6,7

DISCUSSION

The most recent guidelines for management of acute migraine attacks involve use of triptans,non-steroidal anti-inflammatory drugs and antiemetics.Prophylactic treatment often includes the use of beta blockers,tricyclic antidepressants,and anticonvulsants.Response to such therapies is highly variable and is often effective only in a select group of patients.They are often prescribed based upon the patient’s tolerability of the medication and comorbid conditions.Migraine attacks with aura are often less responsive to triptans and carry an even more differentiated response when compared to a migraine without aura.12,14Thus,a great need for alternative treatments for migraines exists,especially for patients whose migraines are refractory to current pharmacologic therapies.

As illustrated by this report,HBO may provide a novel approach in reducing the disability of the migraineur by providing relief,and by reducing the frequency of attacks refractory to pharmacologic therapy.While the exact inflammatory mediators responsible for migraine headaches are still unknown,it is known that inflammation plays a role in the activation of the trigeminovascular system leading to migraines with the characteristic throbbing pain.13,15,16The peripheral activation of the trigeminovascular nociceptors in the dura mater leads the release of vasoactive dilators including calcitonin generelated peptide causing long lasting stimulation and vasodilation.16-18The beneficial effects of HBO are caused through the physiologic consequences of 100% inspired oxygen and exposure to elevated atmospheric pressures.This leads to higher levels of dissolved oxygen in plasma and subsequent arterial constriction in the brain,thus aborting and preventing the migraine.1-4,15,19

The current understanding of the pathophysiology behind migraines with aura combined with the increasing evidence supporting the anti-inflammatory and anti-vasodilatory effects of HBO,suggests that our patients’ relief could be related to HBO decreasing the inflammatory response that leads to the activation of the trigeminovascular pathway.10,13,15,20A study by Myers et al.21demonstrated a significant reduction (P＜0.05) in migraine relief in patients undergoing HBO versus those who underwent normobaric oxygen therapy.Wilson et al.15showed a significant decrease in subjective pain in those who underwent HBO versus the control group of females with migraine with aura.Other studies by Eftedal et al.1,22,23showed insignificant prophylactic measure against migraines with the use of HBO.It is important to note that these studies have limited sample sizes.A Cochrane review on the usage of HBO to prevent migraines showed no evidence to suggest that HBO could prevent migraine attacks,reduce the incidence of nausea and vomiting,or reduce the requirement for rescue medication based upon 11 trials.23On the contrary,we present a patient who had a reduction in frequency,intensity,symptomatology,and need for rescue medications after HBO treatment.To truly judge the efficacy of HBO and take to into account the inherent variability in response to different treatments,larger studies are needed.Our case of this 23-year-old female who experienced a reduction in the frequency and intensity of her migraines after HBO provides the evidence for the use of HBO in the management of chronic migraine.Of note,there has been a limited follow up time with the patient so we are unable to determine how long this treatment modality will remain effective in the long term.The purpose of this article is to expand the currently FDA-approved indications for HBO,such as migraine,headaches based on randomized controlled studies addressing long lasting efficacy in large patient populations.While there has been progress both in the understanding of migraine pathophysiology and the mechanism of action of HBO over the past few years,further research is needed to expand our knowledge and create better treatments for patients with migraines.

Author contributions

DVM wrote the initial draft, and completed the final draft;DVM,BS,BL participated in the literature search;BS and BL participated in the proofread the initial draft.All authors read and approved the final manuscript for publication.

Conflicts of interest

None.

Financial support

None.

Institutional review board statement

Prior to publication,the Committee of Oxygen Oasis Hyperbaric Wellness Center,USA approved this study.

Declaration of patient consent

Prior to publication of this article,informed consent was obtained from the patient this study focuses on.

Copyright transfer agreement

The Copyright License Agreement has been signed by all authors before publication.

Data sharing statement

Datasets analyzed during the current study are available from the corresponding author on reasonable request.

Plagiarism check

Checked twice by iThenticate.

Peer review

Externally peer reviewed.

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