Letter to the Editor |
Reply: Migraine, cortical excitability, and evoked potentials: a clinico-pharmacological perspective
Headache Research Unit, University Departments of 1 Neurology and 2 Neuroanatomy, University of Liège, Liège, Belgium and 3 Department of Neurology and Otolaryngology, University ‘La Sapienza’, Rome, Italy
Correspondence to: Professor J. Schoenen, University Department of Neurology, CHR Citadelle, Bld. du 12ème de Ligne 1B-4000, Liège, Belgium E-mail: jean.schoenen{at}chrcitadelle.be; jschoenen{at}ulg.ac.be
Received January 7, 2005. Accepted February 1, 2005.
We thank Dr Gupta for his comments, which are, as usual, comprehensive and thought-provoking. We will focus on responses to queries about experimental data and not discuss in detail hypotheses the main purpose of which is to design research protocols to prove or disprove them.
Dr Gupta rightly points out the necessity to distinguish between the interictal state and the attack period in any pathophysiological study of migraineurs. We and others have underscored this for physiological studies and shown dramatic changes in the habituation pattern of cortical evoked potentials during the attack where habituation actually normalizes (Maertens et al., 1986
; Áfra et al., 2000; Kropp and Gerber, 1995; Evers et al., 1999). Several of these studies have shown that the change in evoked potentials may start 24–48 h before the attack and persist for 24–48 h after the attack. The delay of 72 h chosen in our study is based on these experimental data and minimizes the risk that an attack-related phenomenon influences the results.
The suggestion that reduced cortical activation and activity in thalamocortical afferents might be an adaptive mechanism in subjects with increased arousal and stress sensitivity is interesting, the more so because a reduced mitochondrial phosphorylation potential has been found in the brain and muscles of migraineurs (Montagna et al., 1994). However, there is no experimental evidence of increased interictal arousal or stress sensitivity in migraine. Moreover, such mental traits can be found in other headache types, e.g. tension-type headache, in which evoked potentials are normal (Maertens et al., 1986). While photo-, phono- and osmophobia may be pronounced during an attack, interictal sensitivity to various environmental stimuli also exists in migraine (Hay et al., 1994). Finally, the evoked potential abnormalities, i.e. lack of habituation and increased amplitude, can be detected within migraine families in presymptomatic subjects (Siniatchkin et al., 2000).
For most hypotheses on migraine pathogenesis, it is common practice to select those data that fit with the proposal. Dr Gupta's ‘peripheral theory’ does not fail to respect this tradition. Among his clinico-pharmacological arguments, some controversial statements can be pointed out: atenolol, though poorly lipophilic, penetrates the brain and can produce CNS side-effects; propranolol and metoprolol are able to normalize evoked potentials in migraineurs (Schoenen et al., 1986; Diener et al., 1989; Nyrke et al., 1984; Sándor et al., 2000); ß-blockers, besides their effect on adrenoreceptors, are active at other receptor sites and may change cerebral 5-HT turnover (Chugani et al., 1999); amitriptyline, besides its effect on noradrenaline reuptake, also blocks 5-HT reuptake and acts on sodium channels; among effective prophylactic anti-migraine drugs, methysergide, for example, and its chief metabolite are 5-HT1B/D agonists able to block transmission at the level of the trigeminovascular system. It seems most difficult to explain the migrainous aura by a peripheral mechanism and there is no evidence-based data showing that nifedipine, nitrates or isoproterenol abort migraine aura. There are only some anecdotal reports, which is also the case for ketamine or naloxone. Headache is not necessarily migraine and it is likely that after supraorbital application, as after brachial application, nitroglycerin produces headache because of its absorption into the general circulation.
To sum up, migraine pathophysiology is not, as Dr Gupta states, a ‘network of assumptions’, but a puzzle of experimental data, most of which have been collected over the last decade. There is no doubt that the relative contributions to pathogenesis of the various pieces of this puzzle differ between patient groups. Our study was part of a number of others exploring scientifically which cerebral mechanisms may explain the habituation deficit of evoked responses, an interictal hallmark of migraine. The results do not favour thalamocortical hyperactivity or lack of intracortical inhibition. Further experimental studies are needed to determine the possible role of the habituation deficit in migraine pathogenesis.
References
Áfra J, Sándor PS, Schoenen J. Habituation of visual and intensity dependence of auditory evoked cortical potentials tend to normalize just before and during the migraine attack. Cephalalgia 2000; 20: 714–9.[CrossRef][Web of Science][Medline]
Chugani DC, Niimura K, Chaturvedi S, Muzik O, Fakhouri M, Lee ML, et al. Increased brain serotonin synthesis in migraine. Neurology 1999; 53: 1473–9.
Diener HC, Scholus E, Dichgans J, Gerber WD. Central effects of drugs used in migraine prophylaxis evaluated by visual evoked potentials. Ann Neurol 1989; 25: 125–30.[CrossRef][Web of Science][Medline]
Evers S, Quibeldey F, Grotemeyer KH, Suhr B, Husstedt IW. Dynamic changes of cognitive habituation and serotonin metabolism during the migraine interval. Cephalalgia 1999; 19: 485–91.[CrossRef][Web of Science][Medline]
Hay KM, Mortimer MJ, Barker DC, Debney LM, Good PA. 1044 women with migraine: the effect of environmental stimuli. Headache 1994; 34: 166–8.[CrossRef][Web of Science][Medline]
Kropp P, Gerber WD. Contingent negative variation during migraine attack and interval: evidence for normalization of slow cortical potentials during the attack. Cephalalgia 1995; 15: 123–8.[CrossRef][Web of Science][Medline]
Maertens de Noordhout A, Timsit-Berthier M, Timsit M, Schoenen J. Contingent negative variation in headache. Ann Neurol 1986; 1: 78–80.
Montagna P, Cortelli P, Monari L, et al. 31P-Magnetic resonance spectroscopy in migraine without aura. Neurology 1994; 44: 666–8.
Nyrke T, Kangasniemi P, Lang AH, Petersen E. Steady-state visual evoked potentials during migraine prophylaxis by propranolol and femoxetine. Acta Neurol Scand 1984; 69: 9–14.[Medline]
Sándor P, Áfra J, Ambrosini A, Schoenen J. Intensity dependence of auditory evoked cortical potentials. Headache 2000; 40: 30–5.[CrossRef][Web of Science][Medline]
Schoenen J, Maertens de Noordout A, Timsit-Bertheir M, Timsit M. Contingent negative variation and efficacy of ß-blockers agents in migraine. Cephalalgia 1986; 6: 231–3.
Siniatchkin M, Kirsch E, Kropp P, Stephani U, Gerber WD. Slow cortical potentials in migraine families. Cephalalgia 2000; 20: 881–92.[CrossRef][Web of Science][Medline]
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