“Dangerous practices” – keeping the mind open till the brain falls out

Dr. Frederick G. Freitag is an authority in primary headache research, and, I am delighted that he came forward to comment on my article. The review is mixed, as the reviewer found the article “new and original” and structurally sound with an excellent discussion, but, has severe reservations about the case report itself. The reviewer is also critical of the forum presented by WebmedCentral to would-be authors/scientists and (even more critical of its “stupid”) format provided for its reviewers. There are several crucial aspects involved:

(i) Any medical science article (particularly, case report) that is interdisciplinary – as is this article, that crosses the borders of gastroenterology, neurology, ophthalmology, neuro-ophthalmology, cardiology – finds great difficulty in getting published in the more conventional periodicals. Although Dr Freitag finds the article “new and original”, this article was summarily (within 24 hours) rejected by several neurological and three headache-devoted periodicals without even undergoing peer review or the journal offering reasons for rejection. In migraine research, it is very clear that the immeasurable is more important that the measurable (see Gupta, Adaptive Mechanisms in Migraine, Nova Science Publishers, New York, 2008). In fact, even the measurable is rejected when it is unexpected by the herd/peers, e.g., the prolongation of bleeding times by aspirin. Science (and, unfortunately, peer-review) is always subjective to vogue – from case reports, to randomised clinical trials (see Gupta, Exp. Rev. Neurother., 2010; 10(9): 1409-1422), to FDA decisions. In reversing its ban on midodrine, the FDA publically acknowledged that all its decisions had an element of subjectivity. Peter Medawar emphasized the subjective nature of medical science. WebmedCentral offers the only platform to discuss both the measurable and the immeasurable aspects of illnesses. While one might discuss a new theory in journals such as Medical Hypotheses or Theoretical Biology and Medical Modelling, case reports have become increasingly difficult to publish, and, a case report like the one I have presented is impossible to publish in regular journals. There is a single-point agenda for WebmedCentral – and, that is to make reviewers accountable, thereby eliminating bias through anonymity in peer review. The seemingly clumsy format for reviewers compels response – responses that explore hidden biases and that are/can not be filed away secretly but are open to public scrutiny as well as to the scientific community. "At every crossways on the road that leads to the future, tradition has placed against each of us 10,000 men to guard the past -- Maurice Maeterlinck. WebmedCentral has challenged these 10,000 men head-on.

(ii) There is an even more important aspect relevant to migraine research. High-tech or advanced ‘gadgetery’ or statistical legerdemain is not always synonymous with good medicine or superlative research. Migraine is a “low-tech” disorder that has, predictably, not yielded its secrets to high-tech maneuvering over the last three decades. That a case report must be embellished with non-invasive or invasive high-tech features is but a poor reflection on medicine itself. Part of Dr. Freitag’s disgust with the case report itself stems from the disappointing lack of display of the “wow” factor – high-tech investigations. The high-tech factor has run out of gas in migraine. What remains is in-depth contemplation and reflection – terms alien to this generation of scientists. Much of high-tech publication in migraine is based purely on pathophysiologic speculation and to the linked pillars of nosologic sophistication (see below) and empiric pharmacotherapy – an unpalatable but intrinsic and absolute truth. 

(iii) The classification of primary headaches (including migraine) is entirely symptomatic, and, the diagnosis of migraine and all its variants – till yet -- does not involve any physical sign that might be elicited by an examiner or any investigations that might conclusively diagnose the entity. Dr Freitag raises the spectre of “dangerous practices” that are difficult to comprehend but must be spelled out clearly by himself in this clinical context. Is keeping the mouth open or the eyes tight shut during straining at bowels “dangerous”; or is it “dangerous” for a qualified internist with two decades of direct personal experience of migraine – and with a not inconsiderable log of publication in the same field -- not to rush for neuroimaging at the first experience of constipation-related migrainous headache? The clinical rule of thumb for headache patients (and their therapists) runs as follows: The longer a patient has the same or partly-same type of headache – whether episodic or persistent/chronic, the less likely is the possibility of any underlying serious secondary intracranial aberration. Recent worsening of a long-standing headache or an accelerating clinical course of a headache is certainly alarming. That science and common sense or face-value must diverge is an unfortunate very common misperception amongst medical researchers. When science filters down to commonsense or “face-value”, the clearest guidelines emerge. The scientist is not merely a gadeteer; the tool must be appropriate for the illness. “All sizes fit one” – is a catastrophic bent of mind for science and its investigators. Expert/consensus guidelines are no substitute for thinking carefully about the research or therapeutic question.  The basic difference between migraine and exertional headache is purely nosological; the fundamental pathogenetic anomaly in both “entities” or more correctly, clinical expressions of the same disease process will ultimately emerge to be the same.  

(iv) Three weeks ago, I developed a protracted syncope (around 30 minutes) and was examined by another physician; I regained full senses and physical and mental faculties during the examination. I duly underwent investigations; an MRI of the brain (on day three) and carotid Doppler examination (on day seven) both were found normal. Despite pressure from colleagues and family, I decided to skip the MRA of brain.      

(v) I have also experienced pre-ejaculatory coital headache during two periods in the last five years. As is typical for migraine as well as for exertional headache, the headache does not develop at all occasions. I have used ocular compression very effectively to immediately abort my headaches during coitus and avoided use of the recommended oral medications. There is a very long history of physicians coming forward with their own illnesses and of even administering the disease agent to themselves in order to study science. The impetus for scientific discovery is the sceptical, disbelieving mass of other scientists – an extremely useful and necessary restraint. Illness, nevertheless, is nothing to be coy about. A most dramatic and historic demonstration on the self by a physician was the injection by Dr. Giles Brindley of the drug phentolamnine into his own penis and dropping his pants before an incredulous audience of urologists to display one of the first drug-induced erections. So much for “form” or “format” in science.

(vi) The case report is simply a (Trojan-horse a la penile-phentolamine injection) prelude to the heart of the matter – the discussion – and it is the discussion that Dr. Freitag found excellent. The scientific issue of importance is the clearest and hitherto unknown exposition of Valsalva-maneuver related headaches. The maneuvers are simple and uncomplicated – but, of course, rather new for the vast majority of scientists immersed in headache research and fixated on Cortical Spreading Depression (CSD). “Keeping the mouth open” or “squeezing the eyes tightly” are surely not associated with any major or minor complications. Equally surely, the physical maneuvers are not associated with CSD. Dr. Freitag should put forward “why” he perceives the disseminated public use of these simple maneuvers as dangerous; he would then indeed be doing a great public service. The fact of the matter is that these simple maneuvers helped to explore an occult pathophysiological phenomenon in migraine. Most scientists revolt against simplicity in science. There is a subtle difference between “simplicity” and “simplisticity” – that gap separates the original from the mundane. At this level, there is absolutely no need to get lost in the vague neural links between the vagus and the trigeminal nerve/nucleus. For over sixty years, the neural/neuronal theory has dominated the thinking of migraine researchers without evolution of any overarching theory. The only neuronal mechanism in contention is CSD – a notion that has severe limitations and has been found untenable (see Gupta, Exp. Rev. Neurother. 2009; 9(11): 1595-1614). The first mention of this occult mechanism was made in 1990 (Spirit of Enterprise; The 1990 Rolex Awards. The credit for the discovery of this occult disease mechanism goes to the team at WebmedCentral; such publications are a stunning reversal of the style-over-substance controversy. The purist (or the professional researcher) who gathers grants and must publish papers to show results, sees style as overly important. Style (of publication) has little bearing on scientific truth or any other form of truth – ranging from political to spiritual.

(vii) Dr. Freitag has missed the essence of this article. According to my proposed model for migraine / exertional headache, the primary aberration lies in the oculo-cranial plumbing (hydro/hemostatic) and not the cranial electrical mains (neuronal/neural). Trigeminal activation in this disease model for migraine is secondary, not primary. The afferent and efferent limbs of the proposed neural arc run through the ophthalmic division of the trigeminal nerve and have nothing to do with the vagus nerve. Mechanical deformity of the ocular trigeminal fibers is a clinical reality in humans expressed through migraine and its variants – a futuristic concept that has allowed an overarching theory for migraine to emerge (see Gupta, Med Hypotheses, 2006: 66: 454-460). True to all that is original (in medicine or otherwise), the theory has been greeted till now with deafening silence by the (migraine) establishment. Priority and originality in science – battling with rivalry and jealousy -- lie at the razor’s edge of comprehension and acceptance, both individual and collective. Whatever science may be, it is not democratic. Also, science – particularly scientific discovery -- does not follow any plan. True breakthroughs in science often come from unexpected quarters. Fundamental scientific advances, more often than not, prove a very large majority of the scientific establishment to be in error. Discovery and consensus lie at the opposite ends of the science spectrum.

• competing interests: Nil
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  I have published in the field.

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