Neurophysiologische Befunde bei Migräne - Spiegelbild der Pathophysiologie oder Epiphänomen?

Zusammenfassung

Neuronale Dysfunktionen von Kortex und Hirnstamm spielen für die Pathophysiologie der Migräne eine entscheidende Rolle. Funktionelle bildgebende Verfahren (fMRT), Perfusionsmessungen und elektrophysiologische Untersuchungsverfahren wie EEG und MEG, multimodal evozierte Potenziale, ereigniskorrelierte Potenziale und Reflexuntersuchungen haben bei Migränepatienten eine Vielzahl von auffälligen und teilweise widersprüchlichen Befunden erbracht. Diese hängen vom Zeitpunkt der Untersuchung innerhalb des Migränezyklus (interiktual, Aura, Kopfschmerzphase) und zum Teil vom Migränetyp (Migräne mit oder ohne Aura) ab. Dysfunktionen von Filter- und Schutzmechanismen, die das ZNS regulär vor einem exzessiven sensorischen Informationsfluss abschirmen, besitzen wahrscheinlich für die Auslösung von Migräneattacken eine große Bedeutung. In konkurrierenden Modellvorstellungen werden eine neuronale Hyperexzitabilität im ZNS, aber auch eine kortikale Hypoexzitabilität als Prädispositionsfaktoren für Migräneattacken propagiert.

Abstract

Neuronal dysfunctions of the cortex and brainstem play a major role in the pathophysiology of migraine. Functional brain imaging (fMRI), perfusion measurements and electrophysiological investigations such as EEG and MEG, multimodal evoked potentials, event-related potentials and reflex measurements have revealed many abnormal and even contradictory findings. These depend on the investigation time within the migraine cycle (interictual, aura and acute headache) and partly on the migraine subtype (migraine with or without aura). Dysfunctions of filter mechanisms protecting the brain from an overflow of sensory input might play a crucial role in inclucing migraine attacks. Competing pathophysiological models suggest neuronal hyperexcitability within the CNS, but also hypoexcitability of the cerebral cortex as predisposing factors in migraine.

Key words

Migraine - pathophysiology - cortex - hyperexcitability - evoked potentials

Literatur

• 1 Russell M B, Rasmussen B K, Thornvaldesen P, Olesen J. Prevalence and sex ratio of the subtypes of migraine.  Int J Epidemiol. 1995;  24 612-618
• 2 Göbel H, Petersen-Braun M, Soyka D. The epidemiology of headache in Germany: A nationwide survey of a representative sample on the basis of the headache classification of the International Headache Society.  Cephalalgia. 1994;  14 97-106
• 3 Stewart W F, Lipton R B, Simon D. Work-related disability: Results from the American migraine study.  Cephalalgia. 1996;  16 231-238
• 4 Spierings E L. Mechanism of migraine and action of antimigraine medications.  Med Clin North Am. 2001;  85 943-958
• 5 Goadsby P J, Lipton R B, Ferrari M D. Migraine-current understanding and treatment.  N Engl J Med. 2002;  346 257-269
• 6 Ferrari M. Migraine.  Lancet. 1998;  351 1043-1051
• 7 Headache classification committee of the international headache society . Classification and diagnosis criteria for headache disorders, cranial neuralgia and facial pain.  Cephalalgia. 1988;  8 (Suppl 7) 1-92
• 8 Tunis M M, Wolff H G. Long-term observations of the reactivity of the cranial arteries in subjects with vascular headache of the migraine type.  Arch Neurol Psychiatry. 1953;  70 551-557
• 9 Leao A AP, Morrison R S. Propagation of spreading cortical depression.  J Neurophysiol. 1945;  8 33-45
• 10 Gorji A. Spreading depression: a review of the clinical relevance.  Brain Res Brain Res Rev. 2001;  38 33-60
• 11 Sramka M, Brozek G, Bures J, Nadvornik P. Functional ablation by spreading depression: Possible use in human stereotaxic neurosurgery.  Appl Neurophysiol. 1977;  40 48-61
• 12 Mayevski A, Doron A, Manor T, Meilin S, Zarchin N, Ouaknine G E. Cortical spreading depression recorded from the human brain using a multipametric monitoring system.  Brain Res. 1996;  740 268-274
• 13 Gorji A, Scheller D, Straub H, Tegtmeier F, Kohling R, Hohling J M, Tuxhorn I, Ebner A, Wolf P, Werner Panneck H, Oppel F, Speckmann E J. Spreading depression in human neocortical slices.  Brain Res. 2001;  906 74-83
• 14 Lauritzen M. Cortical spreading depression in migraine.  Cephalalgia. 2001;  21 757-760
• 15 Cutrer F, O'Donnell A. Recent advances in functional neuroimaging.  Curr Opin Neurol. 1999;  12 255-259
• 16 O'Brien M D. Cerebral blood changes in migraine.  Headache. 1971;  10 139-143
• 17 Olesen J, Larsen B, Lauritzen M. Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine.  Ann Neurol. 1981;  9 344-352
• 18 Andersson J L, Muhr C, Lilja A, Valind S, Lundberg P O, Langstrom B. Regional cerebral blood flow and oxygen metabolism during migraine with and without aura.  Cephalalgia. 1997;  17 570-579
• 19 Hadjikhani N, Sanchez Del Rio M, Wu O, Schwartz D, Bakker D, Fischl B, Kwong K K, Cutrer F M, Rosen B R, Tootell R B, Sorensen A G, Moskowitz M A. Mechanisms of migraine aura revealed by functional MRI in human visual cortex.  Proc Natl Acad Sci USA. 2001;  98 4687-4692
• 20 Cao Y, Aurora S K, Nagesh V, Patel S C, Welch K M. Functional MRI-BOLD of brainstem structures during visually triggered migraine.  Neurology. 2002;  59 72-78
• 21 Aurora S K, Cao Y, Bowyer S M, Welch K MA. The occipitial cortex is hyperexcitable in migraine: Experimental evidence.  Headache. 1999;  39 469-476
• 22 Weiller C, May A, Limmroth V, Juptner M, Kaube H, Schayck R V, Coenen H H, Diener H C. Brainstem activation in spontaneous human migraine attacks.  Nat Med. 1995;  1 658-660
• 23 Bednarczyk E M, Remler B, Weikart C, Nelson A D, Reed R C. Global cerebral blood flow, blood volume, and oxygen metabolism in patients with migraine headache.  Neurology. 1998;  50 1736-1740
• 24 Bahra A, Matharu M, Buchel C, Frackowiak R S, Goadsby P J. Brainstem activation specific to migraine headache.  Lancet. 2001;  357 1016-1017
• 25 Woods R P, Iacoboni M, Mazziotta J C. Brief report: bilateral spreading cerebral hypoperfusion during spontaneous migraine headache.  N Engl J Med. 1994;  331 1689-1692
• 26 Smith M, Cros D, Sheen V. Hyperperfusion with vasogenic leakage by fMRI in migraine with prolonged aura.  Neurology. 2002;  58 1308-1310
• 27 Raskin N H, Hosobuchi Y, Lamb S. Headache may arise from perturbation of the brain.  Headache. 1987;  27 416-420
• 28 May A, Bahra A, Buchel C, Frackowiak R SJ, Goadsby P J. Hypothalamic activation in cluster headache attacks.  Lancet. 1998;  352 275-278
• 29 Moskowitz M A. The visceral organ brain: implications for the pathophysiology of vascular head pain.  Neurology. 1991;  41 182-186
• 30 Golla F L, Winter A L. Analysis of cerebral responses to flicker in patients complaining of episodic headache.  Electroencephalogr Clin Neurophysiol. 1959;  11 539-549
• 31 Smyth V OGS, Winter A L. The EEG in migraine.  Electroencephalogr Clin Neurophysiol. 1964;  16 194-202
• 32 Chorlton P, Kane N. Investigation of the cerebral response to flicker stimulation in patients with headache.  Clin Electroencephalogr. 2000;  31 83-87
• 33 Gronseth G S, Greenberg M K. The utility of the electroencephalogram in the evaluation of patients presenting with headache: a review of the literature.  Neurology. 1995;  45 1263-1267
• 34 De Tommaso M, Sciruicchio V, Bellotti R, Guido M, Sasanelli G, Specchio L M, Puca F. Photic driving response in primary headache: diagnostic value tested by discriminant analysis and artificial neural network classifiers.  Ital J Neurol Sci. 1999;  20 23-28
• 35 De Tommaso M, Sciruicchio V, Guido M, Sasanelli G, Specchio L M, Puca F M. EEG spectral analysis in migraine without aura attacks.  Cephalalgia. 1998;  18 324-328
• 36 Schachter S C, Ito M, Wannamaker B B, Rak I, Ruggles K, Matsuo F, Wilner A, Jackel R, Gilliam F, Morris G, Skantz J, Sperling M, Buchhalter J, Drislane F W, Ives J, Schomer D L. Incidence of spikes and paroxysmal rhythmic events in overnight ambulatory computer-assisted EEGs of normal subjects: a multicenter study.  J Clin Neurophysiol. 1998;  15 251-255
• 37 Vonderheid-Guth B, Todorova A, Wedekind W, Dimpfel W. Evidence for neuronal dysfunction in migraine: concurrence between specific qEEG findings and clinical drug response - a retrospective analysis.  Eur J Med Res. 2000;  5 473-483
• 38 Siniatchkin M, Gerber W D, Kropp P, Vein A. How the brain anticipates an attack: a study of neurophysiological periodicity by migraine.  Functional Neurol. 1999;  14 69-77
• 39 Strenge H, Fritzer G, Goder R, Niederberger U, Gerber W D, Aldenhoff J. Non-linear electroencephalogram dynamics in patients with spontaneous nocturnal migraine attacks.  Neurosci Lett. 2001;  309 105-108
• 40 Schoenen J, Jamart B, Delwaide P J. Electroencephalographic mapping in migraine during the critical and intercritical periods.  Rev Electroencephalogr Neurophysiol Clin. 1987;  17 289-299
• 41 Thomaides T, Tagaris G, Karageorgiou C. EEG and topographic frequency analysis in migraine attack before and after sumatriptan infusion.  Headache. 1996;  36 111-114
• 42 Barkley G L, Tepley N, Nagel-Leiby S, Moran J E, Simkins R T, Welch K M. Magnetoencephalographic studies of migraine.  Headache. 1990;  30 428-434
• 43 Barkley G L, Tepley N, Simkins R, Moran J, Welch K M. Neuromagnetic fields in migraine: preliminary findings.  Cephalalgia. 1990;  10 171-176
• 44 Bowyer S M, Aurora K S, Moran J E, Tepley N, Welch K M. Magnetoencephalographic fields from patients with spontaneous and induced migraine aura.  Ann Neurol. 2001;  50 582-587
• 45 Connolly J F, Gawel M, Rose F C. Migraine patients exhibit abnormalities in the visual evoked potential.  J Neurol Neurosurg Psychiatry. 1982;  45 464-467
• 46 Diener H C, Scholz E, Dichgans J, Gerber W D, Jack A, Bille A, Niederberger U. Central effects of drugs used in migraine prophylaxis evaluated by visual evoked-potentials.  Ann Neurol. 1989;  25 125-130
• 47 Drake M E, Pakalnis A, Hietter S A, Padamadan H. Visual and auditory evoked potentials in migraine.  Electromyogr Clin Neurophysiol. 1990;  30 77-81
• 48 Gawell M, Connolly J, Clifford Rose F. Migraine patients exhibit abnormalities in the visual evoked potential.  Headache. 1983;  23 49-52
• 49 Khalil N M, Legg N J, Anderson D J. Long-term decline of P100 amplitude in migraine with aura.  J Neurol Neurosurg Psychiatry. 2000;  69 507-511
• 50 Kochar K, Srivastava T, Maurya R K, Jain R, Aggarwal P. Visual evoked potential & brainstem auditory evoked potentials in acute attack & after the attack of migraine.  Electromyogr Clin Neurophysiol. 2002;  42 175-179
• 51 Mariani E, Moschini V, Pastorino G C, Rizzi F, Severgnini A, Tiengo M. Pattern reversal visual evoked-potentials (Vep-Pr) in migraine subjects with visual aura.  Headache. 1990;  30 435-453
• 52 Moreira Filho P F, Dantas A M. Pattern reversal visual evoked potentials in migraine subjects without aura.  Arq Neuropsiquiatr. 1994;  52 484-488
• 53 Oelkers R, Grosser K, Lang E. et al . Visual evoked potentials in migraine patients alterations depend on pattern spatial frequency.  Brain. 1999;  122 1147-1155
• 54 Sener H O, Haktanir I, Demirci S. Pattern-reversal visual evoked potentials in migraineurs with or without visual aura.  Headache. 1997;  37 449-451
• 55 Afra J, Ambrosini A, Genicot R, Albert A, Schoenen J. Influence of colors on habituation of visual evoked potentials in patients with migraine with aura and in healthy volunteers.  Headache. 2000;  40 36-40
• 56 Afra J, Cecchini A P, Sandor P S, Schoenen J. Comparison of visual and auditory evoked potentials in migraine patients between attacks.  Clin Neurophysiol. 2000;  111 1124-1129
• 57 Bohotin V, Fumal A, Vandenheede M, Gerard P, Bohotin C, Maertens de Noordhout A, Schoenen J. Effects of repetitive transcranial magnetic stimulation on visual evoked potentials in migraine.  Brain. 2002;  125 912-922
• 58 Logi F, Bonfiglio L, Orlandi G, Bonanni E, Iudice A, Sartucci F. Asymmetric scalp distribution of pattern visual evoked potentials during interictal phases in migraine.  Acta Neurol Scand. 2001;  104 301-307
• 59 Shibata K, Osawa M, Iwata M. Simultaneous recording of pattern reversal electroretinograms and visual evoked potentials in migraine.  Cephalalgia. 1997;  17 742-747
• 60 Tagliati M, Sabbadini M, Bernardi G, Silvestrini M. Multichannel visual evoked potentials in migraine.  Electroencephalogr Clin Neurophysiol. 1995;  96 1-5
• 61 Tsounis S, Milonas J, Gilliam F. Hemi-field pattern-reversal visual-evoked potentials in migraine.  Cephalalgia. 1993;  13 267-271
• 62 Yilmaz M, Bayazit Y A, Erbagci I, Pence S. Visual evoked potential changes in migraine: influence of migraine attack and aura.  J Neurol Sci. 2001;  184 139-141
• 63 Woestenburg J C, Kramer C J, Orlebeke J F, Passchier J. Brain potential differences related to spatial attention in migraineurs with and without aura symptoms support supposed differences in activation.  Headache. 1993;  33 413-416
• 64 Yucesan C, Sener O, Mutluer N. Influence of disease duration on visual evoked potentials in migraineurs.  Headache. 2000;  40 384-388
• 65 Marrelli A, Tozzi E, Porto C, Cimini N, Aloisi P, Valenti M. Spectral analysis of visual potentials evoked by pattern-reversal checkerboard in juvenile patients with headache.  Headache. 2001;  41 792-797
• 66 Brinciotti M, Guidetti V, Matricardi M, Cortesi F. Responsiveness of the visual system in childhood migraine studied by means of VEPs.  Cephalalgia. 1986;  6 183-185
• 67 Sand T, Vingen J V. Visual, long-latency auditory and brainstem auditory evoked potentials in migraine: relation to pattern size, stimulus intensity, sound and light discomfort thresholds and pre-attack state.  Cephalalgia. 2000;  20 804-820
• 68 Shibata K, Osawa K, Iwata M. Pattern reversal visual evoked potentials in migraine with aura and migraine aura without headache.  Cephalalgia. 1998;  18 319-323
• 69 Afra J, Cecchini A P, De Pasqua V, Albert A, Schoenen J. Visual evoked potentials during long periods of pattern-reversal stimulation in migraine.  Brain. 1998;  121 233-241
• 70 Judit A, Sandor P, Schoenen J. Habituation of visual and intensity dependence of cortical auditory evoked potentials tend to normalise just before and during migraine attacks.  Cephalalgia. 2000;  20 714-719
• 71 Puca F M, De Tommaso M, Tota P, Sciruicchio V. Photic driving in migraine: correlations with clinical features.  Cephalalgia. 1996;  16 246-250
• 72 Mortimer M J, Good P A, Marsters J B. The VEP in acephalgic migraine.  Headache. 1990;  30 285-288
• 73 Van Dijk J G, Dorresteijn M, Haan J, Ferrari M D. No confirmation of visual evoked potential diagnostic test for migraine.  Lancet. 1991;  337 517-518
• 74 Van Dijk J G, Dorresteijn M, Haan J, Ferrari M D. Visual evoked potentials and background EEG activity in migraine.  Headache. 1991;  31 392-395
• 75 De Tommaso M, Sciruicchio V, Tota P, Megna M, Guido M, Genco S, Puca F. Somatosensory evoked potentials in migraine.  Funct Neurol. 1997;  12 77-82
• 76 Ozkul Y, Uckardes A. Median nerve somatosensory evoked potentials in migraine.  Eur J Neurol. 2002;  9 227-232
• 77 Reisecker F. Frühe somatosensorisch evozierte Potentiale bei zerebrovaskulär ischämischen Erkrankungen - Teil II: Normwerte und Befunde bei asymptomatischen Gefäßstenosen/Verschlüssen, komplizierter Migräne, transitorisch-ischämischen Attacken, reversiblem ischämischen neurologischen Defizit, komplettem Schlaganfall und Multiinfarktdemenz.  EEG EMG. 1988;  19 61
• 78 Marlowe N. Somatosensory evoked potentials and headache: a further examination of the central theory.  J Psychosom Res. 1995;  39 119-131
• 79 Chayasirisobhon S. Somatosensory evoked potentials in acute migraine with sensory aura.  Clin Electroencephalogr. 1995;  26 65-69
• 80 Altenmüller E. Ereigniskorrelierte Potentiale. In: Stöhr M, Dichgans J, Buettner UW, Hess CW, Altenmüller E (Hrsg) Evozierte Potenziale. Berlin, Heidelberg, New York; Springer 1996: 557-587
• 81 Buettner U W. Akustisch evozierte Potenziale. In: Stöhr M, Dichgans J, Buettner UW, Hess CW, Altenmüller E (Hrsg) Evozierte Potenziale. Berlin, Heidelberg, New York; Springer 1996: 411-486
• 82 Maurer K. Akustisch evozierte Potentiale (AEP) und ereigniskorrelierte Potentiale (P300). In: Lowitzsch K, Maurer K, Hopf HC, Tackmann W, Claus D (Hrsg) Evozierte Potentiale bei Erwachsenen und Kindern. Stuttgart, New York; Thieme 1993: 142-212
• 83 Hegerl U, Juckel G. Intensity dependence of auditory evoked potentials as an indicator of central serotonergic neurotransmission: a new hypothesis.  Biol Psychiatry. 1993;  33 173-187
• 84 Bhargava V K, McKean C M. Role of 5-hydroxytryptamine in the modulation of acoustic brainstem (farfield) potentials.  Neuropharmacology. 1977;  16 447-449
• 85 Bhargava V K, Salamy A, McKean C M. Effect of cholinergic drugs on the brainstem auditory evoked responses (far-field) in rats.  Neuroscience. 1978;  3 821-826
• 86 Bank J. Brainstem auditory evoked potentials in migraine after Rausedyl provocation.  Cephalalgia. 1991;  11 277-279
• 87 Podoshin L, Ben-David J, Pratt H, Fradis M, Sharf B, Weller B. et al . Auditory brainstem and visual evoked potentials in patients with migraine.  Headache. 1987;  27 27-29
• 88 Schlake H P, Grotemeyer K H, Hofferberth B, Husseth I W, Wiesner S. Brainstem auditory evoked potentials in migraine: evidence of increased side differences during the pain-free interval.  Headache. 1990;  30 129-132
• 89 Wang W, Timsit-Berthier M, Schoenen J. Intensity dependence of auditory evoked potentials is pronounced in migraine: an indication of cortical potentiation and low serotonergic transmission?.  Neurology. 1996;  46 1404-1409
• 90 Bickford-Wimer P C, Nagamoto H, Johnson R, Adler L E, Egan M, Rose G M, Freedman R. Auditory sensory gating in hippocampal neurons: a model system in the rat.  Biol Psychiatry. 1990;  27 183-192
• 91 Reese N B, Garcia-Rill E, Skinner R D. Auditory input to the pedunculopontine nucleus: I. Evoked potentials.  Brain Res Bull. 1995;  37 257-264
• 92 Miyazato H, Skinner R D, Crews T, Williams K, Garcia-Rill E. Serotonergic modulation of the P13 midlatecy auditory evoked potential in the rat.  Brain Res Bull. 2000;  51 387-391
• 93 Ambrosini A, De Pasqua V, Afra J, Sandor P S, Schoenen J. Reduced gating of middle-latency auditory evoked potentials (P50) in migraine patients: another indication of abnormal sensory processing?.  Neurosci Lett. 2001;  306 132-134
• 94 Wang W, Schoenen J. Interictal potentiation of passive „oddball” auditory event-related potentials in migraine.  Cephalalgia. 1998;  18 261-265
• 95 Wang W, Wang Y H, Fu X M, Sun Z M, Schoenen J. Auditory evoked potentials and multiple personality measures in migraine and post-traumatic headaches.  Pain. 1999;  79 235-242
• 96 Siniatchkin M, Kropp P, Neumann M, Gerber W, Stephani U. Intensity dependence of auditory evoked cortical potentials in migraine families.  Pain. 2000;  85 247-254
• 97 Sandor P S, Afra J, Cecchini A P, Albert A, Schoenen J. From neurophysiology to genetics: cortical information processing in migraine underlies familial influences: a novel approach.  Funct Neurol. 2000;  15 (Suppl 3) 68-72
• 98 Walter G, Cooper R, Aldridge V J, Mc Callum W C. Contingent negative variation: An electrical sign of sensorimotor association and expectancy in human brain.  Nature. 1964;  203 380-384
• 99 Nagel-Leiby S, Welch K MA, D'Andrea G, Grunfeld S, Brown E. Event-related potentials and associated catecholamine function in migraine.  Cephalalgia. 1990;  10 317-329
• 100 Kropp P, Gerber W D. Contingent negative-variation during migraine attack and interval: evidence for normalization of slow cortical potentials during the attack.  Cephalalgia. 1995;  15 123-128
• 101 Ahmed I. Contingent negative variation in migraine: effect of beta blocker therapy.  Clin Electroencephalogr. 1999;  30 21-23
• 102 Kropp P, Kirbach U, Detlefsen J O, Siniatchkin M, Gerber W D, Stephani U. Slow cortical potentials in migraine: a comparison of adults and children.  Cephalalgia. 1999;  19 (Suppl 25) 60-64
• 103 Maertens de Noordhout A, Timsit-Berthier M, Schoenen J, Timsit M. Contingent negative-variation in headache.  Ann Neurology. 1986;  19 78-80
• 104 Siniatchkin M, Kirsch E, Kropp P, Stephani U, Gerber W D. Slow cortical potentials in migraine families.  Cephalalgia. 2000;  20 881-892
• 105 Siniatchkin M, Kropp P, Gerber W D. Contingent negative variation in subjects at risk for migraine without aura.  Pain. 2001;  94 159-167
• 106 Mulder E, Linssen W, Passchier J, de Geus E JC. Interictal and postictal contingent negative variation migraine without aura.  Headache. 2001;  41 72-78
• 107 Mulder E J, Linssen W H, de Geus E I. Reduced sensory anticipation in migraine.  Psychophysiology. 2002;  39 166-174
• 108 Siniatchkin M, Gerber W D, Kropp P, Voznesenskaya T, Vein A M. Are the periodic changes of neurophysiological parameters during the pain-free interval in migraine related to abnormal orienting activity?.  Cephalalgia. 2000;  20 20-29
• 109 Siniatchkin M, Kropp P, Gerber W D, Stephani U. Migraine in childhood - are periodically occurring migraine attacks related to dynamic changes of cortical information processing?.  Neurosci Lett. 2000;  279 1-4
• 110 Evers S, Bauer B, Suhr B, Husstedt I W, Grotemeyer K H. Cognitive processing in primary headache: a study on event-related potentials.  Neurology. 1997;  48 108-113
• 111 Evers S, Bauer B, Grotemeyer K H, Kurlemann G, Husstedt I W. Event-related potentials (P300) in primary headache in childhood and adolescence.  Child Neurol. 1998;  13 322-326
• 112 Grosser K, Oelkers R, Hummel T, Geisslinger G, Brune K, Kobal G, Lotsch J. Olfactory and trigeminal event-related potentials in migraine.  Cephalalgia. 2000;  20 621-631
• 113 Muller B W, Sartory G, Tackenberg A. The movement-related potential in children with migraine and tension-type headache.  Cephalalgia. 2002;  22 125-131
• 114 Kropp P, Gerber W D. Prediction of migraine attacks using a slow cortical potential, the contingent negative variation.  Neurosci Lett. 1998;  257 73-76
• 115 Evers S, Quibeldey F, Grotemeyer K H. et al . Dynamic changes of cognitive habituation and serotonin metabolism during the migraine interval.  Cephalalgia. 1999;  19 485-491
• 116 Aurora S K, Welch K MA. Brain excitability in migraine: evidence from transcranial magnetic stimulation studies.  Curr Opin Neurol. 1998;  11 205-209
• 117 Battelli L, Black K R, Wray S H. Transcranial magnetic stimulation of visual area V5 in migraine.  Neurology. 2002;  58 1066-1069
• 118 Afra J, Mascia A, Gerard P, Maertens de Noordhout A, Schoenen J. Interictal cortical excitability in migraine: a study using transcranial magnetic stimulation of motor and visual cortices.  Ann Neurol. 1998;  44 209-215
• 119 Aurora S K, Ahmad B K, Welch K M, Bhardhwaj P, Ramadan N M. Transcranial magnetic stimulation confirms hyperexcitability of visual cortex in migraine.  Neurology. 1998;  50 1105-1110
• 120 Brighina F, Piazza A, Daniele O, Fierro B. Modulation of visual cortical excitability in migraine with aura: effects of 1 Hz repetitive transcranial magnetic stimulation.  Exp Brain Res. 2002;  145 177-181
• 121 Mulleners W M, Chronicle E P, Palmer J E, Koehler P J, Vredeveld J W. Visual cortex excitability in migraine with and without aura.  Headache. 2001;  41 565-572
• 122 Mulleners W M, Chronicle E P, Vredeveld J W, Koehler P J. Visual cortex excitability in migraine before and after valproate prophylaxis: a pilot study using TMS.  Eur J Neurol. 2002;  9 35-40
• 123 Mulleners W M, Chronicle E P, Palmer J E, Koehler P J, Vredeveld J W. Suppression of perception in migraine: evidence for reduced inhibition in the visual cortex.  Neurology. 2001;  56 178-183
• 124 Palmer J E, Chronicle E P, Rolan P, Mulleners W M. Cortical hyperexcitability is cortical under-inhibition: evidence from a novel functional test of migraine patients.  Cephalalgia. 2000;  20 525-532
• 125 McColl S L, Wilkinson F. Visual contrast gain control in migraine: measures of visual cortex excitability and inhibition.  Cephalalgia. 2000;  20 74-84
• 126 Hallett M. Transcranial magnetic stimulation and the human brain.  Nature. 2000;  406 147-150
• 127 Rossini P M, Barker A T, Berardelli A, Caramia M D, Caruso G, Cracco R Q, Dimitrijevic M R, Hallett M, Katayama Y, Lucking C H. et al . Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee.  Electroencephalogr Clin Neurophysiol. 1994;  91 79-92
• 128 Werhahn K J, Kunesch E, Noachtar S, Benecke R, Classen J. Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans.  J Physiol. 1999;  517 591-597
• 129 Aurora S K, al-Sayeed F, Welch K M. The cortical silent period is shortened in migraine with aura.  Cephalalgia. 1999;  19 708-712
• 130 Bettucci D, Cantello M, Gianelli M, Naldi P, Mutani R. Menstrual migraine without aura: cortical excitability to magnetic stimulation.  Headache. 1992;  32 345-347
• 131 Maertens de Noordhout A, Pepin J, Schoenen J, Delwaide P. Percutaneous magnetic stimulation of the motor cortex in migraine.  Electroencephalogr Clin Neurophysiol. 1992;  85 110-115
• 132 Van der Kamp W, Maassen VanDenBrink A, Ferrari M D, van Dijck J G. Interictal cortical excitability to magnetic stimulation in familial hemiplegic migraine.  Neurology. 1997;  48 1462-1464
• 133 Ozturk V, Cakmur R, Donmez B, Yener G G, Kursad F, Idiman F. Comparison of cortical excitability in chronic migraine (transformed migraine) and migraine without aura. A transcranial magnetic stimulation study.  J Neurol. 2002;  249 1268-1271
• 134 Van der Kamp W, Maassen VanDenBrink A, Ferrari M D, van Dijck J G. Interictal cortical excitability in migraine patients demonstrated with transcranial magnetic stimulation.  J Neurol Sci. 1996;  139 106-110
• 135 Werhahn K J, Wisemann K, Herzog J, Förderreuther S, Dichgans M, Straube A. Motor cortex excitability in patients with migraine with aura and hemiplegic migraine.  Cephalalgia. 2000;  20 45-50
• 136 Schoenen J. Exteroceptive suppression of temporalis muscle activity in patients with chronic headache and in normal volunteers: methodology, clinical and pathophysiological relevance.  Headache. 1993;  33 3-17
• 137 Berardelli A, Cruccu G, Kimura J, Ongerboer de Visser B W, Valls-Solé J. The orbicularis oculi reflexes.  Electroenzephalogr Clin Neurophysiol. 1999;  52, Suppl 249-253
• 138 Rossi B, Vignocchi M G. Methodological considerations of the use of blink reflex R3-Komponent in the assessment of pain in man.  Int J Neurol Sci. 1993;  14 217-224
• 139 Aktekin B, Yaltkaya K, Ozkaynak S, Oguz Y. Recovery cycle of the blink reflex and exteroceptive suppression of temporalis muscle activity in migraine and tension-type headache.  Headache. 2001;  41 142-149
• 140 De Tommaso M, Guido M, Libro G, Sciruicchio V, Puca F. The three responses of the blink reflex in adult and juvenile migraine.  Acta Neurol Belg. 2000;  100 96-102
• 141 De Tommaso M, Guido M, Libro G. et al . Zolmitriptan reverses blink reflex changes induced during the migraine attack in humans.  Neurosci Lett. 2000;  289 57-60
• 142 Kaube H, Katsarava Z, Przywara S, Drepper J, Ellrich J, Diener H C. A cute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus?.  Neurology. 2002;  58 1234-1238
• 143 De Tommaso M, Murasecco D, Libro G, Guido M, Sciruicchio V, Specchio L M, Gallai V, Puca F. Modulation of trigeminal reflex excitability in migraine: effects of attention and habituation on the blink reflex.  Int J Psychophysiol. 2002;  44 239-249
• 144 Sandrini G, Proietti Cecchini A, Milanov I, Tassorelli C, Buzzi M G, Nappi G. Electrophysiological evidence for trigeminal neuron sensitization in patients with migraine.  Neurosci Lett. 2002;  317 135-138
• 145 Kors E E, van den Maagdenberg A M, Plomp J J, Frants R R, Ferrari M D. Calcium channel mutations and migraine.  Curr Opin Neurol. 2002;  15 311-316
• 146 May A, Ophoff R A, Terwindt G M, Urban C, Van Eijk R, Haan J, Diener H C, Lindhout D, Frants R R, Sandkuijl L A. et al . Familial hemiplegic migraine locus on 19p13 is involved in the common forms of migraine with and without aura.  Hum Genet. 1995;  96 604-608
• 147 Nyholt D R, Lea R A, Goadsby P J, Brimage P J, Griffiths L. Familial typical migraine: linkage to chromosome 19p13 and evidence for genetic heterogeneity.  Neurology. 1998;  50 1428-1432
• 148 Ambrosini A, de Noordhout A M, Schoenen J. Neuromuscular transmission in migraine patients with prolonged aura.  Acta Neurol Belg. 2001;  101 166-170
• 149 Ambrosini A, Maertens de Noordhout A, Schoenen J. Neuromuscular transmission in migraine: a single-fiber EMG study in clinical subgroups.  Neurology. 2001;  56 1038-1043
• 150 Welch K, D'Andrea G, Tepley N, Barkley G, Ramadan N M. The concept of migraine as a state of central neuronal hyperexcitability.  Neurol Clin. 1989;  8 817-828
• 151 Chronicle E P, Mulleners W M. Visual system dysfunction in migraine: a review of clinical and psychophysical findings.  Cephalalgia. 1996;  16 525-535
• 152 Wray S H, Mijovicprelec D, Kossyln S M. Visual processing in migraineurs.  Brain. 1995;  118 25-35
• 153 Wilkins A, Nimmo-Smith I, Tait A, McManus C, Della Sala S, Tilley A, Arnold K, Barrie M, Scott S. A neurological basis for visual discomfort.  Brain. 1984;  107 989-1017
• 154 Hay K M, Mortimer M J, Barker D C, Debney L M, Good P A. 1044 women with migraine: the effects of environmental stimuli.  Headache. 1994;  34 166-168
• 155 Andermann F. Migraine and the benign partial epilepsies of childhood: evidence for an association.  Epileptic Disord. 2000;  2 (Suppl 1) S37-39
• 156 Donnet A, Bartolomei F. Migraine with visual aura and photosensitive epileptic seizures.  Epilepsia. 1997;  38 1032-1034
• 157 Martinovic Z. Clinical correlations of electroencephalographic occipital epileptiform paroxysms in children.  Seizure. 2001;  10 379-381
• 158 Ogunyemi A, Adams D. Migraine-like symptoms triggered by occipital lobe seizures: response to sumatriptan.  Can J Neurol Sci. 1998;  25 151-153
• 159 Velioglu S K, Ozmenoglu M. Migraine-related seizures in an epileptic population.  Cephalalgia. 1999;  19 797-801
• 160 Maertens de Noordhout A, Schoenen J. Transcranial magnetic stimulation in migraine.  Electroencephalogr Clin Neurophysiol. 1999;  51, Suppl 260-264
• 161 Chronicle E, Mulleners W. Might migraine damage the brain?.  Cephalalgia. 1994;  14 415-418
• 162 Kruger H, Luhmann H J, Heinemann U. Repetitive spreading depression causes selective suppression of GABA-ergic function.  Neuroreport. 1996;  7 2733-2736
• 163 Ramadan N M, Halvorson H, Vande-Linde A, Levine S R, Helpern J A, Welch K MA. Low brain magnesium in migraine.  Headache. 1989;  29 590-593
• 164 Montagna P, Cortelli P, Monari L. et al . 31P-magnetic resonance spectroscopy in migraine without aura.  Neurology. 1994;  44 666-669
• 165 Boska M D, Welch K M, Barker P B, Nelson J A, Schultz L. Contrasts in cortical magnesium, phospholipid and energy metabolism between migraine syndromes.  Neurology. 2002;  58 1227-1233
• 166 Lodi R, Lotti S, Cortelli P, Pierangeli G, Cevoli S, Clementi V, Soriani S, Montagna P, Barbiroli B. Deficient energy metabolism is associated with low free magnesium in the brains of patients with migraine and cluster headache.  Brain Res Bull. 2001;  54 437-441
• 167 Sandor P S, Mascia A, Seidel L, De Pasqua V, Schoenen J. Subclinical cerebellar impairment in the commont types of migraine: a three-dimensional analysis of reaching movements.  Ann Neurol. 2001;  49 668-672
• 168 Ophoff R A, Terwindt G M, Vergouwe M N. et al . Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4.  Cell. 1996;  87 543-552
• 169 D'Andrea G, Cananzi A R, Joseph R, Morra M, Zamberlan F, Ferro Milone F, Grunfeld S, Welch K M. Platelet glycine, glutamate and aspartate in primary headache.  Cephalalgia. 1991;  11 197-200
• 170 Hughes A M, Dixon R, Dane A, Kemp J, Cummings L, Yates R A. Effects of zolmitriptan (Zomig) on central serotonergic neurotransmission as assessed by active oddball auditory event-related potentials in volunteers without migraine.  Cephalalgia. 1999;  19 100-106
• 171 Schoenen J, Maertens de Noordhout A, Timsit-Berthier M, Timsit M. Contingent negative variation and efficacy of beta-blocking agents in migraine.  Cephalalgia. 1986;  6 229-233
• 172 Sandor P S, Afra J, Ambrosini A, Schoenen J. Prophylactic treatment of migraine with beta-blockers and riboflavin: differential effects on the intensity dependence of auditory evoked cortical potentials.  Headache. 2000;  40 30-35
• 173 Siniatchkin M, Gerber W D, Vein A. Clinical efficacy and central mechanisms of cyclandelate in migraine: a double-blind placebo-controlled study.  Funct Neurol. 1998;  13 47-56