We thank Dr. Gupta for the comments on our article. [1] We agree that neither aura nor headache mark the true onset of a migraine attack. We disagree, however, that the examples presented by Dr. Gupta contradict the hypothesis of central migraine mediators.
All named triggers, including stress and exercise, are dependent on the threshold or susceptibility for attack generation, which varies over time. [2] This threshold variation is, per definition, based on central neuronal changes. Moreover, most reported triggers may not be triggers at all, but misinterpreted (premonitory) migraine symptoms. Delayed headache onset after trigger exposure is thus merely an observation which supports, rather than contradicts, the hypothesis of a central mediator in migraine pathophysiology.
The distinct clinical presentation of the premonitory phase of migraine strongly suggests hypothalamic and central dopaminergic involvement; [3,4] although, at present, involvement of peripheral changes cannot be ruled out.
A unilateral or side-locked headache is not pathognomonic of migraine. Bilateral neuronal activations are, consequently, not contradictory to the clinical presentation of migraine headaches.
The fact that a prophylactic treatment does not cross the blood brain barrier does not contradict the hypothesis that central mechanisms are crucially involved in migraine [5] and chronic migraine [1] pathophysiology: central mechanisms lead to peripheral changes and vice versa. Inhibition of the peripheral side will, based on feed-back mechanisms, alter central modulators and does not contradict a central modulator of migraine.
1. Schulte LH, Allers A, May A. Hypothalamus as a mediator of chronic migraine: Evidence from high-resolution fMRI. Neurology 2017;88:2011-2016.
2. May A, Schulte LH. Chronic migraine: risk factors, mechanisms and
treatment. Nat Rev Neurol 2016;12:455-464.
3. Akerman S, Goadsby PJ. Dopamine and migraine: biology and clinical
implications. Cephalalgia 2007;27:1308-1314.
4. Charbit AR, Akerman S, Goadsby PJ. Dopamine: what's new in migraine?
Curr Opin Neurol 2010;23:275-281.
5. Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain 2016;139:1987-1993.
For disclosures, please contact the editorial office at journal@neurology.org.
We thank Dr. Gupta for the comments on our article. [1] We agree that neither aura nor headache mark the true onset of a migraine attack. We disagree, however, that the examples presented by Dr. Gupta contradict the hypothesis of central migraine mediators.
All named triggers, including stress and exercise, are dependent on the threshold or susceptibility for attack generation, which varies over time. [2] This threshold variation is, per definition, based on central neuronal changes. Moreover, most reported triggers may not be triggers at all, but misinterpreted (premonitory) migraine symptoms. Delayed headache onset after trigger exposure is thus merely an observation which supports, rather than contradicts, the hypothesis of a central mediator in migraine pathophysiology.
The distinct clinical presentation of the premonitory phase of migraine strongly suggests hypothalamic and central dopaminergic involvement; [3,4] although, at present, involvement of peripheral changes cannot be ruled out.
A unilateral or side-locked headache is not pathognomonic of migraine. Bilateral neuronal activations are, consequently, not contradictory to the clinical presentation of migraine headaches.
The fact that a prophylactic treatment does not cross the blood brain barrier does not contradict the hypothesis that central mechanisms are crucially involved in migraine [5] and chronic migraine [1] pathophysiology: central mechanisms lead to peripheral changes and vice versa. Inhibition of the peripheral side will, based on feed-back mechanisms, alter central modulators and does not contradict a central modulator of migraine.
1. Schulte LH, Allers A, May A. Hypothalamus as a mediator of chronic migraine: Evidence from high-resolution fMRI. Neurology 2017;88:2011-2016.
2. May A, Schulte LH. Chronic migraine: risk factors, mechanisms and treatment. Nat Rev Neurol 2016;12:455-464.
3. Akerman S, Goadsby PJ. Dopamine and migraine: biology and clinical implications. Cephalalgia 2007;27:1308-1314.
4. Charbit AR, Akerman S, Goadsby PJ. Dopamine: what's new in migraine? Curr Opin Neurol 2010;23:275-281.
5. Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain 2016;139:1987-1993.
For disclosures, please contact the editorial office at journal@neurology.org.