Gordian knot of migraine: serendipity, empiricism, hope, hype, hokum, and randomized controlled clinical trials
Vinod Gupta, Dubai Police Medical Services, P.O. Box 12005, Dubai, United Arab Emirates
6 June 2006
Leiper, Elliott, and Hannaford present a qualitative picture of headache patients’ perspective [1]. The intensity of the quest of many individuals for an increased understanding of their condition and the development of their own explanations for their headaches is in direct proportion to the limitation of definitive knowledge about the origin or genesis of primary or vascular headaches. Migraine (and related idiopathic vascular headaches) is one entity in which technological, taxonomic, methodological (including statistical), and tautological sophistication has failed to offer any insight into disease mechanisms; also, the reductionist nature of ‘hard’ laboratory or epidemiological or clinical trials data has eluded researchers [2][3][4][5][6][7].
Whether migraine is a specific disorder or a non-specific response to a variety of responses is also undecided. Consequently, efforts to prevent migraine vary widely and might involve pharmacological agents [8] or scalp injection of botulinum toxin [9] or closure of patent foramen ovale or atrial septal defect [10] or greater occipital nerve injection [11]. The advent of beta-blockers for migraine prevention was also a serendipitous event. To believe that a distinct pathophysiologic mechanism will be ultimately discovered for each of the nosologic entities currently delineated by the new version of the classification of the International Headache Society [12] appears to be a form of irrational scepticism [13]. Further elucidation of the “what” of migraine carries the unfortunate but subtle paradox that additional data will make little headway in understanding migraine unless the extant data is arranged into a vast intelligible synthesis ( “why” and “how”) that places key elements of migraine in a logically-defensible perspective-enhancing and hopefully insight-and experiment-generating bio-compatible model. Such conceptual groundwork is an important part of the migraine research process that cannot be supplanted by epidemiological data, laboratory studies or randomized controlled clinical trials.
Key issues that might signpost the evolution of an overarching theory for migraine and other primary headaches have been underscored [14][15][16][17]. The basic obstacle to this process is the willingness of migraine researchers and therapists to comprehend how far assumptions and extrapolations ostensibly supported by non-directed accumulation of data in clinical trials or observational studies have removed current perception of primary vascular headaches from the biological truth. That migraine is a primary disorder of the brain remains a purely speculative hypothesis. Lay comprehension of any disease naturally follows and extrapolates from contemporary mainstream scientific concepts.
References
1. Leiper DA, Elliott AM, Hannaford PC. Experiences and perceptions of people with headache: a qualitative study. BMC Family Practice 2006;7: 27 doi:10.1186/1471-2296-7-27
2. Gupta VK. Menstrual migraine is not pathogenetically related to premenstrual syndrome. Cephalalgia 1994; 14: 411-412 (comments 413-414).
3. Gupta VK. Migraine following haemorrhage in brain stem cavernous angioma: pathophysiological considerations. J Neurol Neurosurg Psychiatry. [23 June 2003] Available at: http://jnnp.bmjjournals.com/cgi/eletters/74/5/680#55
4. Gupta VK. Classification of primary headaches: pathophysiology versus nosology? BMJ [22 Jan 2004]. Available at:
7. Gupta VK. Magnesium therapy for migraine: do we need more trials or more reflection? Headache 2004;44:445-446
8. Goadsby PJ, Lipton RB, Ferrari MD. Migraine – current understanding and treatment. N Eng J Med 2002; 346: 257-270
9. Dodick DW. Botulinum neurotoxin for the treatment of migraine and other primary headache disorders: from bench to bedside. Headache 2003; 43(Suppl 1): 25-33
10. Wilmshurst PT, Nightingale S, Walsh KP, Morrison WL. Clopidogrel reduces migraine with aura after transcatheter closure of persistent foramen ovale and atrial septal defects. Heart 2005; 9: 1173-1175
11. Afridi SK, Shields KG, Bhola R, Goadsby PJ. Greater occipital nerve injection in primary headache syndromes – prolonged effects from a single injection. Pain 2006; 122: 126-129
12. Headache Classification Subcommittee of the International Headache Society: The International Classification of Headache Disorders. 2nd edition. Cephalalgia 2004: 24(Suppl 1): 9-160
13. Gupta VK. Migraine: “how” versus “what” of a disease process. BMJ [8 February 2006]. Available at: http://bmj.bmjjournals.com/cgi/eletters/332/7532/25#127734
14. Gupta VK. Migraine, cortical excitability, and evoked potentials: a clinico-pharmacological perspective. Brain 2005; 128: E36
15. Gupta VK. Glyceryl trinitrate and migraine: nitric oxide donor precipitating and aborting migrainous aura. J Neurol Neurosurg Psychiatry (22 October 2005). Available at: http://www.jnnp.com/cgi/eletters/76/8/1158#708
16. Gupta VK. Topiramate for migraine prophylaxis: addressing the blood-brain barrier related pharmacokinetic-pathophysiological disconnect. Int J Clin Pract 2006;60:367-368
17. Gupta VK. Migrainous scintillating scotoma and headache is ocular in origin: a new hypothesis. Med Hypotheses 2006; 66:454-460
Gordian knot of migraine: serendipity, empiricism, hope, hype, hokum, and randomized controlled clinical trials
6 June 2006
Leiper, Elliott, and Hannaford present a qualitative picture of headache patients’ perspective [1]. The intensity of the quest of many individuals for an increased understanding of their condition and the development of their own explanations for their headaches is in direct proportion to the limitation of definitive knowledge about the origin or genesis of primary or vascular headaches. Migraine (and related idiopathic vascular headaches) is one entity in which technological, taxonomic, methodological (including statistical), and tautological sophistication has failed to offer any insight into disease mechanisms; also, the reductionist nature of ‘hard’ laboratory or epidemiological or clinical trials data has eluded researchers [2][3][4][5][6][7].
Whether migraine is a specific disorder or a non-specific response to a variety of responses is also undecided. Consequently, efforts to prevent migraine vary widely and might involve pharmacological agents [8] or scalp injection of botulinum toxin [9] or closure of patent foramen ovale or atrial septal defect [10] or greater occipital nerve injection [11]. The advent of beta-blockers for migraine prevention was also a serendipitous event. To believe that a distinct pathophysiologic mechanism will be ultimately discovered for each of the nosologic entities currently delineated by the new version of the classification of the International Headache Society [12] appears to be a form of irrational scepticism [13]. Further elucidation of the “what” of migraine carries the unfortunate but subtle paradox that additional data will make little headway in understanding migraine unless the extant data is arranged into a vast intelligible synthesis ( “why” and “how”) that places key elements of migraine in a logically-defensible perspective-enhancing and hopefully insight-and experiment-generating bio-compatible model. Such conceptual groundwork is an important part of the migraine research process that cannot be supplanted by epidemiological data, laboratory studies or randomized controlled clinical trials.
Key issues that might signpost the evolution of an overarching theory for migraine and other primary headaches have been underscored [14][15][16][17]. The basic obstacle to this process is the willingness of migraine researchers and therapists to comprehend how far assumptions and extrapolations ostensibly supported by non-directed accumulation of data in clinical trials or observational studies have removed current perception of primary vascular headaches from the biological truth. That migraine is a primary disorder of the brain remains a purely speculative hypothesis. Lay comprehension of any disease naturally follows and extrapolates from contemporary mainstream scientific concepts.
References
1. Leiper DA, Elliott AM, Hannaford PC. Experiences and perceptions of people with headache: a qualitative study. BMC Family Practice 2006;7: 27 doi:10.1186/1471-2296-7-27
2. Gupta VK. Menstrual migraine is not pathogenetically related to premenstrual syndrome. Cephalalgia 1994; 14: 411-412 (comments 413-414).
3. Gupta VK. Migraine following haemorrhage in brain stem cavernous angioma: pathophysiological considerations. J Neurol Neurosurg Psychiatry. [23 June 2003] Available at: http://jnnp.bmjjournals.com/cgi/eletters/74/5/680#55
4. Gupta VK. Classification of primary headaches: pathophysiology versus nosology? BMJ [22 Jan 2004]. Available at:
http://bmj.bmjjournals.com/cgi/eletters/328/7432/119
5. Gupta VK. Randomized controlled trials versus clinical realities: prostate cancer screening. BMJ [11 February 2004]. Available at:
http://bmj.bmjjournals.com/cgi/eletters/328/7435/301#50002
6. Gupta VK. Randomized controlled trials: the hijacking of basic sciences by mathematical logic. BMJ [6 July 2004]. Available at:
http://bmj.bmjjournals.com/cgi/eletters/329/7456/2#65969
7. Gupta VK. Magnesium therapy for migraine: do we need more trials or more reflection? Headache 2004;44:445-446
8. Goadsby PJ, Lipton RB, Ferrari MD. Migraine – current understanding and treatment. N Eng J Med 2002; 346: 257-270
9. Dodick DW. Botulinum neurotoxin for the treatment of migraine and other primary headache disorders: from bench to bedside. Headache 2003; 43(Suppl 1): 25-33
10. Wilmshurst PT, Nightingale S, Walsh KP, Morrison WL. Clopidogrel reduces migraine with aura after transcatheter closure of persistent foramen ovale and atrial septal defects. Heart 2005; 9: 1173-1175
11. Afridi SK, Shields KG, Bhola R, Goadsby PJ. Greater occipital nerve injection in primary headache syndromes – prolonged effects from a single injection. Pain 2006; 122: 126-129
12. Headache Classification Subcommittee of the International Headache Society: The International Classification of Headache Disorders. 2nd edition. Cephalalgia 2004: 24(Suppl 1): 9-160
13. Gupta VK. Migraine: “how” versus “what” of a disease process. BMJ [8 February 2006]. Available at: http://bmj.bmjjournals.com/cgi/eletters/332/7532/25#127734
14. Gupta VK. Migraine, cortical excitability, and evoked potentials: a clinico-pharmacological perspective. Brain 2005; 128: E36
15. Gupta VK. Glyceryl trinitrate and migraine: nitric oxide donor precipitating and aborting migrainous aura. J Neurol Neurosurg Psychiatry (22 October 2005). Available at: http://www.jnnp.com/cgi/eletters/76/8/1158#708
16. Gupta VK. Topiramate for migraine prophylaxis: addressing the blood-brain barrier related pharmacokinetic-pathophysiological disconnect. Int J Clin Pract 2006;60:367-368
17. Gupta VK. Migrainous scintillating scotoma and headache is ocular in origin: a new hypothesis. Med Hypotheses 2006; 66:454-460
Competing interests
Nil