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What is the practical value of genetic analysis to comprehension of migraine?

  • Vinod K. Gupta, Physician, Gupta Medical Center (New Delhi, India)
Submitted April 01, 2018

I read with interest the article of Pelzer et al. [1] Migraine research is based on a long, extremely tenuous chain of poorly linked assumptions about the related basic sciences. [2,3] The authors concluded that most patients with hemiplegic migraine without a mutation in CACNA1A, ATP1A2, or SCN1A display a mild phenotype that is more akin to that of common (nonhemiplegic) migraine.

It is uncommon for a patient with migraine to demonstrate a definitive and protracted link with head trauma over decades, or to present with extensive motor weakness, brainstem features, confusion, and brain edema. Headache-related mental retardation and progressive ataxia exclusively found in patients with a mutation appear to be an outlier -- a very uncommon phenomenon -- that cannot be related to the larger cohort and has but little relevance in genetic counselling. No genetic mutation can explain the unpredictable, but typical, remissions of attacks experienced by patients with migraine in the second and third trimester of pregnancy, after menopause, or advancing age.

Migraine pathophysiology is in its infancy and all therapy is empirical. At this stage, all genetic studies are likely to add to the extant confusion. Even for a polygenic disease with established histopathologic anomaly and endocrine deficiency, such as diabetes mellitus, genetic counselling adds little clinical or practical value.

1. Pelzer N, Haan J, Stam AH et al. Clinical spectrum of hemiplegic migraine and chances of finding a pathogenic mutation. Neurology 2018;90:e575-e582.

2. Gupta VK. Genetics and biology of migraine: how far are we from the truth? BMC Med Genet 2005;6:32. Comment.

3. Gupta VK. CSD, BBB and MMP-9 elevations: animal experiments versus clinical phenomena in migraine. Expert Rev Neurother 2009;9:1595-1614.

For disclosures, please contact the editorial office at journal@neurology.org.

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Neurology | Print ISSN:0028-3878
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