|Year : 2017 | Volume
| Issue : 5 | Page : 186-189
Bacterial flora of the migraine nose: Pilot case–control study of nasal bacteria in migraine headache
Sundarachary Nagarjunakonda1, Sridhar Amalakanti1, Aruna Siddabathuni2, Neelima Pantagada2
1 Department of Neurology, Guntur Medical College, Guntur, Andhra Pradesh, India
2 Department of Microbiology, Guntur Medical College, Guntur, Andhra Pradesh, India
|Date of Submission||06-Jan-2017|
|Date of Decision||02-Mar-2017|
|Date of Acceptance||17-May-2017|
|Date of Web Publication||9-Oct-2017|
Department of Neurology, Guntur Medical College, Guntur - 522 002, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background: In spite of being the oldest neurological disorder to be recorded in human history, the pathophysiology of migraine headache is not clear. In recent times, hereto unexplored mechanisms are being pursued to explain the disorder. Novel thinkers have ventured to associate migraine with chronic infection induced hypersensitivity. Infections such as Helicobacter pylori and Chlamydia have been found to be more common in migraine patients. We wanted to know whether there is any abnormal nasal bacterial colonization associated with migraine. Methods: As a single-blinded, cross-sectional, observational case–control pilot study in a tertiary government hospital neurology outpatient department in India, we analyzed the nasal bacterial flora of 27 migraine patients and ten relatives of these patients without migraine headache by nasal swab smear and culture. Results: The organisms detected in the participants were coagulase negative Staphylococcus and Staphylococcus aureus, Viridans streptococci, diphtheroids, micrococci, bacteroides, and Klebsiella by culture. Bacterial flora of the migraine patients was different from that of the controls, especially diphtheroids (migraine = 11% vs. control = 40%, P = 0.06) and micrococci (migraine = 30% versus control = 60%, P = 0.13) seem to be lower in migraineurs than in controls. Conclusions: From our pilot case–control study, although a small sample size of patients, migraineurs appear to have altered bacterial flora in their nose.
Keywords: Migraine headache, headache, bacterial flora, commensal bacteria, nasal swab, case–control study
|How to cite this article:|
Nagarjunakonda S, Amalakanti S, Siddabathuni A, Pantagada N. Bacterial flora of the migraine nose: Pilot case–control study of nasal bacteria in migraine headache. J Med Sci 2017;37:186-9
|How to cite this URL:|
Nagarjunakonda S, Amalakanti S, Siddabathuni A, Pantagada N. Bacterial flora of the migraine nose: Pilot case–control study of nasal bacteria in migraine headache. J Med Sci [serial online] 2017 [cited 2019 Oct 22];37:186-9. Available from: http://www.jmedscindmc.com/text.asp?2017/37/5/186/214397
| Introduction|| |
Migraine headache is a debilitating attack of severe pain in the head striking about one-fourth of the people over the life time in the world. It causes disruption in family relationships, social communication and sickness absenteeism from schools, colleges, and offices.
Migraine headache has been described in the most ancient of human civilizations such as the Mesopotamian and Babylonian settlements. It was once thought to be due to the wrath of the Egyptian Gods. In those primeval days, a clay crocodile was placed on the patients' head for its cure. Migraine was later believed to be due to trapped evil spirits in the cranium. Shamans bored the skull of live patients to make burr holes, a process called trephination to allow these spirits to escape. In the 17th century, Thomas Willis proposed that migraine was caused due to vasodilatation of cerebral vessels, closely afterward Eulenberg tried to explain the disorder by strategically placing vasoconstriction and vasodilatation mechanisms at different stages of the phenomenon. Now, we believe the neurovascular theory of migraine where neurogenic inflammation activates a vascular cascade and the symptoms produced thereof are a consequence of the two pathways. However, the pathogenesis of the disorder has not yet been elucidated.
A fundamental conceptual framework that can explain this enigmatic disease is still enshrouded in mystery. A clear cut pathophysiologic explanation can unleash a torrent of therapies, which are specific and can greatly alleviate the ailing millions of migraineurs. Sometimes a completely novel approach may be necessary to throw light on such perplexing diseases. The now established Helicobacter pylori gastritis was once such an approach. In recent years, researchers have noticed an increased association of migraine headache with different types of infections in the body. Migraine headache has been shown to be more common in people with infections such as H. pylorii, Toxoplasma gondii, Chlamydia and Leptospira.
The underlying hypothesis behind these studies is the theory that chronic infection in the body alters the profile and concentration of circulating cytokines in the blood and tissues. Many of these cytokines are shown to be associated with migraine. Hence, an increased circulating cytokines might predispose to a higher sensitivity of the trigeminovascular system to triggering stimuli. Hence, people with infections might have more common attacks of migraine headache. However, the hypothesis stands untested.
We supposed that one approach would be to see whether a proximate infection can be seen more commonly in migraineurs. A nearby infection will obviously have a more profound effect on the trigeminovascular system than a distant one, be it mediated by any inflammatory mediators. Accessing the trigeminovascular system is an operating procedure and so we thought of an easily accessible proximate orifice to detect microbes/infection.
It is well known that Neisseria meningitides can penetrate the cribriform plate and reach the meninges causing meningitis. Hence, we supposed that such a mechanism might be plausible in migraine also. As nasopharyngeal swab is a cumbersome, semi-operative theater procedure we took nasal swabs from migraineurs. Since the nose communicates with the brain through the olfactory mucosa and the cribriform plate, any nasal infection can easily enter the cranium. We hypothesized, therefore, that abnormal bacterial infection of the nasal chamber in migraine patients may point toward a new direction in the disease pathophysiology. We sought to find if any new pattern of nasal bacteria that might be different to control population as a pilot study.
| Methods|| |
Participants and setting
Based on previous data of association between migraine and infection, for our study, we estimated a sample size of 51 cases and 51 controls with 95% confidence level and 80% power for detecting an odd's ratio of 3.4 in an unmatched case–control study. Over 1 month at the Department of Neurology, Government General Hospital, Guntur, India from August 2014 to September 2014, consecutive patients diagnosed with migraine and controls were recruited for a case–control study [Figure 1]. Migraine was diagnosed according to the International classification of headache disorders 3rd edition. As bacterial flora might be similar from same households, household contacts were used as controls when available. Subjects exposed to antibiotics within the previous 15 days were excluded from the study.
Method of collecting nasal swabs
After the patient was comfortably seated, the head was tilted back and a sterile trans tube swab treated with 2–3 drops of saline was inserted onto the middle turbinate, it was then slowly withdrawn by rotating on its axis. The swab was carefully inserted back into the screw-cap tube. The tube was labeled with patient's name, specimen type, and date of collection. The clinical diagnosis was not tagged to the vial. Hence, the microbiologist was blinded from the clinical scenario. Two such swabs are taken for each person. At the microbiology laboratory, nasal swabs from each patient were received in duplicate. One of them was used for direct smear preparation and the other for aerobic and anaerobic culture on blood agar, chocolate agar and MacConkey agar. Plates were examined for bacterial growth and colonies were identified based on staining and biochemical reactions.
The data on bacterial profile in patients and controls was analyzed using Fisher's exact test for categorical variables along with calculation of odds ratio. The null hypothesis was that there was no difference in organisms from patients and controls. Statistics were performed online through vassarstats.net accessed on July 27, 2015. Statistical significance was set at P < 0.05. Apart from statistical significance, we assumed that more than 20% difference in bacterial floral pattern between migraineurs and controls would be clinically noteworthy.
This study was approved by the Institutional Ethical Committee of Guntur Medical College, Guntur. Written informed consent was obtained from all participants. The methods were carried out in “accordance” with the approved guidelines.
| Results|| |
We obtained 27 (M:F = 1:26) cases and 10 (M:F = 5:5) controls for the study [Figure 1]. The mean age of our migraine patients was 35 (±12) years. Most (16) of the patients had a history of migrainous headache under 1-year duration. [Table 1] depicts the clinical features in migraine patients.
The organisms detected in the participants were coagulase positive and coagulase negative Staphylococcus aureus, Viridans streptococci, diphtheroids, micrococci, bacteroides, and Klebsiella spp.
The bacterial flora of the migraine patients is quite clearly different from the normal person [Table 2]. Diptheroids (migraine = 11% vs. control = 40%, P = 0.06) and Micrococci (migraine = 30% versus. control = 60%, P = 0.13) seem to be lower in migraineurs than in controls. There were eight households where each household had one case and one control. Out these eight households, in six households, the case and the control had same nasal bacterial flora when residing in the same household.
Three patients had an associated seizure disorder, and two patients had hypothyroidism. Amitriptyline and propranolol were the chief drugs prescribed for migraine prophylaxis, whereas paracetamol was the drug used for relief in acute attacks.
| Discussion|| |
The study showed a difference in the commensal bacterial flora of the migraine patients from the control population.
Change in commensal bacteria is key to the inflammatory processes and are also altered in the presence of inflammation. The neuroinflammation characteristic of migraine may also be subject to this association.
Stress also significantly alters the pattern of commensal organisms. In our study, commensals such as diphtheroids, micrococci, and bacteroides were noted in less number of migraine patients. As stress and migraine are closely linked – bacterial flora also correspondingly might have changed in distribution. IgE-mediated hypersensitivity has been noted in many migraineurs in the past. It is now studied that commensal organisms can produce such hypersensitivity. The altered flora might predispose to a sensitive trigeminovascular system.
This is the first attempt to associate nasal bacteria with migraine. Previous studies show that infections are more common in migraine patients. It is also seen that the most severe migraine attacks occur after infection. Either migraine is associated with infection predisposition or infections cause increased sensitivity of the trigeminovascular system. Our findings show the association with altered nasal bacterial flora.
In support of the hypothesis, antibiotic therapy based on the sensitivity pattern of the organisms and the effect of the treatment on the migraine could provide corollary evidence for our hypothesis. Antibiotic therapy against H. pylori has shown to reduce migraine attacks. The alteration of commensal flora may also have contributed to the result.
In our study, culture and smear were both done to confirm the microbial colonization. The microbiologist was blinded to the clinical data. Hence, bias was minimized. Ours is a very small sample, essentially a pilot to the full study. Since subjects from same households had similar bacterial flora irrespective of disease status, the result might simply be due to different environments of the subjects. Most of our migraine patients were women, the difference in commensals of the nose may be due to the sex difference.
Altered commensal bacterial pattern might inflame, irritate, and sensitize the trigeminovascular system. They may simply be a manifestation of abnormal stress and immunity status of migraine patients.
| Conclusions|| |
The study showed an association between altered bacterial flora and migraine, but confirmation of the findings requires further work in a full-scale study, elucidation of the pathogenesis needs translational work and clinical trials of antibiotic treatment in migraine.
We are indebted to Dr. K Prasanthi MD Associate Professor, Department of Microbiology, Guntur Medical College and Dr. P Mohan Rao MD, HOD, Department of Internal Medicine, Guntur Medical College for internal peer review and Dr. T Narayana Rao MD, Specialist Medical officer, ESIC, Vijayawada for critical external peer review. We would like to thank Mr. T Madhu Babu for data entry and clerical offices.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Leonardi M, Steiner TJ, Scher AT, Lipton RB. The global burden of migraine: Measuring disability in headache disorders with WHO's Classification of Functioning, Disability and Health (ICF). J Headache Pain 2005;6:429-40.
Magiorkinis E, Diamantis A, Mitsikostas DD, Androutsos G. Headaches in antiquity and during the early scientific era. J Neurol 2009;256:1215-20.
Eadie MJ. The pathogenesis of migraine-17th
to early 20th
century understandings. J Clin Neurosci 2005;12:383-8.
Goadsby PJ. Pathophysiology of migraine. Ann Indian Acad Neurol 2012;15 Suppl 1:S15-22.
Parsonnet J. Clinician-discoverers – Marshall, Warren, and H. pylori
Engl J Med 2005;353:2421-3.
Su J, Zhou XY, Zhang GX. Association between Helicobacter pylori
infection and migraine: A meta-analysis. World J Gastroenterol 2014;20:14965-72.
Koseoglu E, Yazar S, Koc I. Is Toxoplasma gondii
a causal agent in migraine? Am J Med Sci 2009;338:120-2.
Lu Q, Xu J, Liu H. Association between Chlamydia pneumoniae
IgG antibodies and migraine. J Headache Pain 2009;10:121-4.
Atkins JB. Migraine as a sequel to infection by L. icterohaemorrhagiae. Br Med J 1955;1:1011-2.
Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd
edition (beta version). Cephalalgia 2013;33:629-808.
Stecher B. The roles of inflammation, nutrient availability and the commensal microbiota in enteric pathogen infection. Microbiol Spectr 2015;3:1-17.
Galley JD, Bailey MT. Impact of stressor exposure on the interplay between commensal microbiota and host inflammation. Gut Microbes 2014;5:390-6.
Idris AS, Ishak R, Hassan K. Platelet function and allergic tendency in migraine patients before treatment: A preliminary study. Cephalalgia 1989;9 10 Suppl:95.
Hill DA, Siracusa MC, Abt MC, Kim BS, Kobuley D, Kubo M, et al.
Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med 2012;18:538-46.
Chabriat H, Danchot J, Michel P, Joire JE, Henry P. Precipitating factors in migraineurs: A reappraisal in a national control-matched survey. Cephalalgia 1997;17:318-9.
Covelli V, Massari F, Conrotto L, DAndrea L, Maffione AB, Jirillo E, et al
. Demonstration of an elevated frequency of infectious events in patients with migraine without aura – A correlation with their altered immune status. EOS Riv Immunol Immunofarmacol 1993;13:173-5.
Faraji F, Zarinfar N. The effect of Helicobacter pylori
eradication on migraine: A randomized, double blind, controlled trial. Pain Physician 2012;15:495-8.
[Table 1], [Table 2]