RESEARCH HIGHLIGHTS Differences in the Pathogenesis of Migraine

RESEARCH HIGHLIGHTS www.nature.com/clinicalpractice/neuro

lacunar infarction, presence of headache phase. In the inactive phase, differences at stroke onset decreased early neurological between migraine patients and controls were recovery from 26.2% to 19.2%. Absence of significant (P <0.001), but there was no signifi- limitation at discharge was less frequent in sub- cant difference between controls and patients jects with supratentorial white matter lesions with cluster headache. than in those with other types of infarction The authors state that the bilateral nature of (15.1% vs 25.1%); this result was duplicated the abnormal response and the persistence in the subgroup of patients without headache. of the abnormality in the inactive phase indicate In multivariate analysis, both absence of head- a centrally located brainstem dysfunction in ache in deep brain gray matter or brainstem and patients with migraine and suggest the involve- presence of dysarthria-clumsy hand syndrome ment of central pain mechanisms in the dis- predicted good outcome. ease. The results of the study offer support for These results, say the authors, point to an the theory that abnormal brainstem modulation important role for glutamate in lacunar infarc- of nociceptive afferent neurons is involved in tion and cerebral ischemia; synaptic gluta- migraine pathogenesis. The authors say that dif- mate receptors are mostly located in the deep ferent mechanisms are likely to be responsible brain gray matter or brainstem, and headache for cluster headache, however. in patients with lacunar infarction could be Original article Nardone R et al. (2006) Trigemino-cervical due to biomechanical (inflammatory or neuro- reflex abnormalities in patients with migraine and cluster excitotoxic) rather than mechanical aspects. headache. Headache [doi: 10.1111/j.1526-4610.2006.00529.x] Glutamate has additionally been proposed to exert a neurotoxic effect in deep brain regions but not white matter ischemic lesions. Further Increase in seizure frequency research into the excitotoxic activity of gluta- associated with common mate in patients with lacunar infarction could hormone replacement therapy therefore be beneficial. Original article Arboix A et al. (2006) Clinical implications Results of a recent double-blind, placebo- of headache in lacunar stroke: relevance of site of infarct. controlled trial indicate that hormone replace- Headache 46: 1172–1180 ment therapy (HRT) can increase seizure frequency in patients with epilepsy. Harden and colleagues recruited post- Differences in the pathogenesis menopausal women with partial epilepsy (mean of migraine and cluster age 53 years) who were within 10 years of their headache last menses and were taking stable doses of antiepileptic drugs. After a 3-month prospective Abnormalities in the trigemino-cervical reflex baseline period, 21 patients were randomized to have been associated with headache. To receive daily placebo (n = 6), a daily single dose assess the role of the trigeminal system in head of conjugated equine estrogens plus medroxy- pain, researchers in Italy studied the response progesterone acetate (CEE/MPA; n = 8), or a daily in the sternocleidomastoid muscle to stimula- double dose of CEE/MPA (n = 7). Patients were tion of the infraorbital nerve in 30 patients with using an average of one antiepileptic drug (range migraine, 10 patients with cluster headache 0–3), and all met the standard medical criteria for and 15 healthy controls. the use of HRT prior to July 2002. Compared with controls, the trigemino- Five out of seven subjects taking double cervical response was abnormal during head- doses of CEE/MPA experienced increased ache in 25 patients with migraine and 5 patients seizure frequency of at least one seizure type, with cluster headache. In the inactive phase, compared with four out of eight subjects taking an abnormal response was found in 20 patients single doses of CEE/MPA and one out of six with migraine and 1 patient with cluster head- subjects taking placebo. Two patients who were ache. The observed abnormalities were uni- taking lamotrigine and CEE/MPA experienced a lateral in cluster headache and bilateral in reduction in their lamotrigine levels. migraine. Differences in responses were sig- The authors conclude that CEE/MPA might nificant (P <0.001) between all patients with not be the best HRT regimen for women with headache and controls during the headache partial epilepsy, although they note that their

584 NATURE CLINICAL PRACTICE NEUROLOGY NOVEMBER 2006 VOL 2 NO 11