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LETTERS TO THE EDITOR cha_1780 799..800

Dear Sir I read with extreme interest the paperfrom Rueda-Snchez and Daz-Martnez (1), in

which trhey contrasted demographic factors andexposures associated with episodic migraine andchronic daily headache (CDH) in the Colombianpopulation. From the many factors assessed, familyhistory of CDH figured prominently. Among indi-viduals with CDH, an astonishing 31.5% reported ahistory of daily headaches in their parents (con-trasted with 9.8% in controls). Furthermore, 20.7%of the CDH sufferers reported CDH in theirchildren, vs. 3.7% of controls. In individuals withmigraine, CDH in the family was more commonthan in controls, and less common than in families

of probands with CDH.Because the paper is so dense, these findings mayreceive less attention than they should. It is wellestablished that migraine aggregates within families(26) and that the rates of aggregation are higher inthe families of migraineurs that are severely dis-abled (4, 7). However, aggregation of CDH had notbeen described to the best of my knowledge. Fur-thermore, the aggregation of CDH in the families ofindividuals with episodic migraine offers furthersupport to migraine progression (episodic migraineevolving to CDH) (8). It is possible that, amongindividuals with migraine, presence of specific

genes (e.g. pain progression genes) and/or commonfamily exposure to exogenous factors (e.g. specificsocial or psychological stressors that affect theentire family) would predispose to CDH.

The findings from this study may also be rel-evant to studies designed to identify genes asso-ciated with CDH. A critical challenge in thesetypes of studies is to identify families with a highgenetic loading for disease. Using the high densityapproach, families with multiple affected indi-viduals are sought (7). However, this strategy isoften limited to a small number of relatively large

and difficult to find families. An alternativestrategy is to search for probands with CDH orhigh-severity migraine, or both, and to studytheir families.

References

1 Rueda-Snchez M, Daz-Martnez LA. Prevalence andassociated factors for episodic and chronic daily headachein the Colombian population. Cephalalgia 2008; 28:21625.

2 Russell MB, Hilden J, Sorensen SA, Olesen J. Familialoccurrence of migraine without aura and migraine with

aura. Neurology 1993; 43:1369973.3 Waters WE. Migraine, intelligence, social class, and famil-ial prevalence. BMJ 1971; 2:7781.

4 Russell MB, Olesen J. Increased familial risk and evidenceof genetic factors in migraine. BMJ 1995; 311:5414.

5 Steiner TJ, Guha P, Capildeo R, Rose FC. Migraine inpatients attending a migraine clinic: an analysis by com-puter of age, sex, and family history. Headache 1980;20:1905.

6 Baier WK. Genetics of migraine and migraine accompag-ne: a study of eighty-one children and their families.Neuropediatrics 1985; 16:8491.

7 Stewart WF, Bigal ME, Kolodner K, Dowson A, LibermanJN, Lipton RB. Familial risk of migraine: variation byproband age at onset and headache severity. Neurology2006; 66:3448.

8 Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ, Lipton RB.Chronic migraine is an earlier stage of transformedmigraine in adults. Neurology 2005; 65:155661.

ME Bigal, Global Director for Scientific Affairs Neuroscience,Merck Research Laboratories, Whitehouse Station, NJ andDepartment of Neurology, Albert Einstein College of Medicine,Bronx, NY, USA. E-mail: marcelo_bigal@merck.com

Authors reply

Dear Sir We appreciate the observations of DrBigal and we agree with him on the importance offamily aggregation of chronic daily headache(CDH). However, our study has methodologicallimitations, and the findings from our surveyshould be confirmed. First, family aggregation andthe strength of family aggregation of CDH shouldbe confirmed; future studies should determinethe familial recurrence risk ratio (lR) of CDH, ameasure that estimates the grade of family aggre-gation (1). Second, it should be determined if familyaggregation is caused by genetic or environmentalfactors. Generally, it is accepted that a greater recur-

rence risk ratio is related with a stronger geneticrole in the disease aetiology, and the reduction inrecurrence risk by degree of familiar relation isrelated to the mode of inheritance (1). The best wayto demonstrate the genetic component of CDH isthe study of twins, with a model of multiple thresh-old where you can consider the liability of episodicheadache and CDH simultaneously (2). Once thefamily aggregation of CDH is proven and that thisfamily aggregation is due to genetic factors, you

doi:10.1111/j.1468-2982.2008.01780.x

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would advance in the search of genes committed tothe process of chronification of episodic headache.

These proposals have important conceptualimplications, especially in the progression orchronification paradigm of episodic headache(migraine and episodic tension-type headache),since it would imply that only individuals with aspecial genetic background would be at risk ofchronification and that individuals without thisgenetic susceptibility would require strongerenvironmental stimuli to cause chronification ofepisodic headache.

References

1 Ashely-Koch A. Determining genetic component of todisease. In: Haines JL, Pericak-Vance M, eds. Geneticanalysis of complex diseases. Hoboken, NJ: John Wiley &Sons 2006:91115.

2 Todorov AA, Sarez VK. Liability model. In: Elston RC,

Olson JM, Palmer L, eds. Biostatistical genetics and geneticepidemiology. New York: Wiley 2002:4305.

M Rueda-Snchez and LA Daz-Martnez, Biomedical ResearchCentre, Health Sciences Faculty, Universidad Autnoma deBucaramanga, Bucaramanga, Colombia

800 Letters to the Editor

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