Pathophysiology of Migraine - Kompetenznetz Parkinson

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Another study indicates that the b-1-adrenergic antagonists, propranolol and atenolol, inhibit firing of third-order thalamocortical neurons to dural (sagittal sinus) stimulation and L-glutamate injection suggesting that these drugs, which are of known efficacy in migraine, might act to negatively modulate and perhaps suppress the tendency toward central sensitization in higher-order neurons. 93 Other interesting data indicate that in recurrent migraine there is deposition of nonheme iron within areas of periaqueductal gray that directly correlates with the total duration of illness. 94 It has been suggested that these changes result from repeated attacks. These findings have recently been confirmed in migraine sufferers under the age of 50 in a large population-based cohort (migraine cases n ¼ 178 and controls n ¼ 75). 95 When stratified by age, subjects under the age of 50 (n ¼ 50) had lower T2 values on MR imaging suggesting iron deposition in the putamen (p ¼ 0.02), globus pallidus (p ¼ 0.03), and red nucleus (p ¼ 0.03). When subjects over the age of 50 were included, no differences were seen. However, whether these findings of apparent iron accumulation represent injury in response to repeated activation of the pain system and its modulation in periaqueductal gray or alternatively represent the cause of dysfunctional control within the trigeminovascular nociceptive system is unclear. In a similar vein, a subsequent PET-based study 96 has suggested altered brainstem function in patients with chronic migraine. White Matter Changes in Migraine Patients Over the past few years, there has been increased interest in an apparent increased occurrence of small foci T2 signal on MRI (presumed infarctions) and in white matter lesions in migraine patients compared with the nonmigrainous population. In a large study of randomly selected, age- and gender-matched patients with migraine with aura (n ¼ 161), migraine without aura (n ¼ 134), and controls (n ¼ 140), the investigators found no significant difference between patients with migraine and controls in overall infarct prevalence (8.1% vs. 5.0%). However, in the cerebellar region of the posterior circulation territory, they found that patients with migraine had a higher prevalence of infarct than controls (5.4% vs. 0.7%; P =.02). The adjusted odds ratios (ORs) for posterior infarction varied based on migraine subtype and attack frequency. Patients with migraine with aura and those with greater that one attack per month had the highest risk of infarct compared with controls. Among women, the risk of deep white matter lesions (DWML) was increased in patients with migraine compared with controls (OR 2.1; 95% confidence interval [CI] 1.0–4.1); this risk increased with attack frequency (highest in those with one attack per month: OR 2.6; 95% CI 1.2–5.7), but was similar in patients with migraine with or without aura. In men, controls and patients with migraine did not differ in the prevalence of DWMLs. None of the cerebellar lesions correlated with clinical symptoms. 97,98 The cause of the lesions remains unclear, although ischemia resulting from the recurrent periods of hypoperfusion during aura has been suggested. However, one report suggests that these lesions may be transient, 99 which would be unexpected were ischemia to be their underlying cause. Another proposed explanation is that the subclinical lesions observed in the posterior circulation of migraine sufferers might result from recurrent microemboli that gain access to cerebral circulation through a patent foramen ovale (PFO). An increased prevalence of PFO in migraine with aura sufferers has been reported by several investigators, 100 and several uncontrolled trials have suggested that PFO closure resulted in a decrease in migraine attack frequency. 101,102 However, the MIST study, the first controlled trial, did not meet its primary efficacy endpoint. 103 Other controlled trials are currently underway. A recent study in migraine patients which used transcranial Doppler techniques to detect gaseous microemboli arising from right to left shunts due to PFO concluded that the presence of right-to-left shunt does not increase white matter lesion load in patients who have migraine with aura. 104 CONCLUSIONS The past two decades have seen a significant increase in our understanding of several important aspects of migraine pathophysiology. However, attempts to identify a single unifying theory that encompasses and accounts for all that we know about migraine continue to be unsuccessful. The increasing evidence of genetic heterogeneity which underpins migraine, combined with the wide clinical variation seen in the disorder argues for a syndromic approach to migraine. A syndromic approach recognizes an acute migraine attack as a clinical ‘‘final common pathway’’ reflecting a recurrent maladaptive activation of the trigeminocervical pain apparatus which may arise from more than one initiating process. Research based on a syndromic view of migraine may ultimately aid in the identification of clinically and perhaps genetically definable subgroups that may allow for more effective, individualized therapy for this very common, disabling disorder. REFERENCES PATHOPHYSIOLOGY OF MIGRAINE/CUTRER 127 1. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders, 2nd edition. Cephalalgia 2004;24(Suppl 1): 9–160 2. Penfield W. A contribution to the mechanism of intracranial pain. Association for Research in Nervous and Mental Disease Proceedings (1934) 1935;15:399–416 Downloaded by: Universitätsbibliothek Marburg. Copyrighted material.
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Evidence for allelic association of the dopamine beta-hydroxylase gene (DBH) with susceptibility to typical migraine. Neurogenetics 2000;3(1):35–40 36. Cader ZM, Noble-Topham S, Dyment DA, et al. Significant linkage to migraine with aura on chromosome 11q24. Hum Mol Genet 2003;12(19):2511–2517 37. Mochi M, Cevoli S, Cortelli P, et al. A genetic association study of migraine with dopamine receptor 4, dopamine transporter and dopamine-beta-hydroxylase genes. Neurol Sci 2003;23(6):301–305 Downloaded by: Universitätsbibliothek Marburg. Copyrighted material.
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