Migraine Disorders: Sakai F

Anonymous00401, Olesen J, Bousser MG, Diener HC, Dodick D, First M, Goadsby PJ, Göbel H, Lainez MJ, Lance JW, Lipton RB, Nappi G, Sakai F, Schoenen J, Silberstein SD, Steiner TJ. · Department of Neurology, University of Copenhagen, Glostrup Hospital, Demark. · Cephalalgia. · Pubmed #16686915 No free full text.

Abstract: After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.

Sakai F. · Department of Neurology, Kitasato University. · Rinsho Shinkeigaku. · Pubmed #19198084 No free full text.

Abstract: While interest in headache research started early in Japan, headache cares did not develop until recently. Patients with migraine did not visit doctors for headache, and physicians were unaware of the prevalence and disability of migraine in Japan for a long time. Studies in Japan on migraine epidemiology revealed that the prevalence of migraine was 8.4% of the population, demonstrating 8.4 million people are suffering from migraine. These results gave impact to young scientists in Japan and encouraged them to do clinical and experimental studies on headache. One of the barriers for studying headache was a difficulty in communication to obtain enough information by the physicians. Patients usually suffered in silence. New medication for migraine, triptan, increased the number of patients visiting physicians. Physicians also developed such communication tools as headache diary, migraine screening tools helping physicians to obtain good amount of information on headache. The purpose of this communication is to present the author's experience in the study of mechanism and treatment of headache based on headache diary. The importance for future progress of migrainology was emphasized.

Martelletti P, Haimanot RT, Láinez MJ, Rapoport AM, Ravishankar K, Sakai F, Silberstein SD, Vincent M, Steiner TJ. · ITSE 2nd School of Medicine, Rome University La Sapienza, Via Vitorchiano 81, I-00189, Rome, Italy. · J Headache Pain. · Pubmed #16362681 No free full text.

Abstract: The social perception of headache, everywhere at low levels in industrialised countries, becomes totally absent in developing ones. Headache disorders came into the World Health Organization's strategic priorities after publication of the 2001 World Health Report. Among the leading causes of disability, migraine was ranked 19th for adults of both sexes together and 12th for females. The Global Campaign (GC) to Reduce the Burden of Headache Worldwide was planned by the major international headache organizations together with WHO in order to identify and remove those cultural, social and educational barriers recognised as responsible factors for the inadequate treatment of headache disorders worldwide. Within the GC activities, the education of the medical body will represents a central pillar. An International Team for Specialist Education (ITSE) has been created to train physicians from all over the world through the acquisition of a university level Master Degree in Headache Medicine. Once trained as headache specialists, physicians will become trainers, offering education in this field to other health care providers in their own countries. In this way they will give life to a cultural chain raising awareness locally of headache, its burden and its medical control.

Suzuki K, Iizuka T, Sakai F. · Department of Neurology, School of Medicine, Kitasato University. · Nippon Rinsho. · Pubmed #16218396 No free full text.

Abstract: Migraine is a common neurological disorder, characterized by recurrent attacks of severe headache. Its prevalence is estimated 8.4% of general population in Japan. Acute migraine treatment has dramatically improved with the development of a novel class of selective 5-HT1B/1D/1F receptor agonists, known as the triptans, but prophylactic treatment still remains limited. Botulinum toxin type A(BoNT-A) has recently been shown to be effective in randomized control trials, but no prospective study has been conducted yet in Japan. In this paper, we review the results of recently published controlled trials, touching on its methodology, optimal dose, patient selection, and possible mechanisms, as well as on going clinical trial in our university.

Sakai F. · Department of Neurology, Kitasato University. · Rinsho Shinkeigaku. · Pubmed #15651298 No free full text.

Abstract: Triptan therapy results in good relief of headache in 68% of the patients. For many of the patients with migraine, triptan provides complete pain relief in some attacks but not in others. A recent theory proposes that allodynia (pain sensitization) develops in the brain during migraine to increase the intensity of headache significantly. The presence of cutaneous allodynia, an exaggerated painful sensation resulting from a no noxious stimulus to normal skin, is reported in more than 70% of the patients. In our prospective study with 41 patients with migraine, 54.2% presented with skin allodynia. Triptan was effective in 77% of the patients without allodynia which was higher than the base line efficacy rate of 68% in all the patients. Our data support the hypothesis that the development and maintenance of cutaneous allodynia is propelled by sensitization of central trigeminal nucleus. It is suggested that the pain-free outcome increases drastically if triptan therapy is given before the phenomenon of allodynia develops during the attacks of migraine.

Iizuka T, Sakai F. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #15007953 No free full text.

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Gono Y, Sakai F. · Third Department of Internal Medicine, Kitasato University School of Medicine. · Ryoikibetsu Shokogun Shirizu. · Pubmed #12483910 No free full text.

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Igarashi H, Sakai F. · Department of Medicine, Kitasato University. · Nippon Rinsho. · Pubmed #11808276 No free full text.

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Sakai F. · Department of Medicine, Kitasato University, Sagamihara, Kanagawa, Japan. · Cephalalgia. · Pubmed #11078005 No free full text.

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Sakai F, Dobashi K, Igarashi H. · Department of Neurology, Kitasato University, Japan. · Cephalalgia. · Pubmed #10099849 No free full text.

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Suzuki K, Iizuka T, Sakai F. · Department of Neurology, School of Medicine, Kitasato University, Sagamihara. · Intern Med. · Pubmed #17603233 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy and tolerability of Botulinum Toxin Type A (BoNT-A) for migraine prophylaxis. METHODS: Nineteen Japanese adult patients (50 +/- 10 years old), who met the International Classification of Headache Disorders 2nd Edition (ICHD II) criteria for migraine and had five or more migraine attacks a month, were enrolled in this open-label prospective study. A total of 50 units of BoNT-A were injected in 19-fixed sites of the muscles including procerus, corrugator, frontalis, temporalis and occipitalis. All participants were advised to stop taking preventive medicine from one month before and three months after BoNT-A injection. Migraine disability assessment (MIDAS), migraine questionnaire and headache diary were used for the evaluation of efficacy. Seven patients received repeated injection combined with prophylactic medication. RESULT: We excluded five patients from the analysis because four patients had medication overuse headache and one continued preventive medicine. Mean MIDAS score decreased significantly two months after the injection. Thirteen of 14 patients stated subjective improvement after the injection on the migraine questionnaire. The amount of analgesics consumption or headache frequency did not change after injection, but the frequency of severe migraine attacks decreased significantly. No serious adverse event was reported. Repeated injections also showed significant reduction in MIDAS score three months after the second and third injections. CONCLUSION: BoNT-A injection was an effective and safe treatment for migraine prophylaxis among the Japanese population. A randomized placebo control trial is necessary to confirm its efficacy.

Sakai F, Diener HC, Ryan R, Poole P. · Department of Medicine, Kitasato University Hospital, Sagamihara City, Kanagawa Prefecture, Japan. · Curr Med Res Opin. · Pubmed #15025836 No free full text.

Abstract: OBJECTIVE: To compare the efficacy, safety and tolerability of eletriptan (20, 40 and 80 mg) to placebo when given to Japanese and Western patients for the acute treatment of migraine. METHODS: A double-blind, randomized, parallel-group trial with the aforementioned therapeutic objectives was conducted in Japan (N = 321). By bridging analysis, data from this study were compared to two migraine trials previously conducted in the US (N = 1190) and Europe (N = 563). RESULTS: The 2-h post-dose headache response rates (i.e., the primary efficacy endpoint) of Japanese migraineurs to eletriptan 20, 40 and 80 mg were 64, 67 and 76%, respectively; European and American migraineurs showed similar trends and, in these studies, eletriptan was significantly superior to placebo (p < 0.05). Japanese patients did demonstrate a higher placebo response than Westerners, possibly due to differences in previous triptan exposure or expectation. Adverse events were generally mild to moderate, were comparable in all three studies, and showed a modest dose-response effect. CONCLUSION: The efficacy and tolerability of eletriptan for the acute treatment of migraine is comparable in Japan, Europe and the US.

Sakai F, Iwata M, Tashiro K, Itoyama Y, Tsuji S, Fukuuchi Y, Sobue G, Nakashima K, Morimatsu M. · Department of Neurology, Kitasato University, Kitasato 1-15-1, Sagamihara-Shi, Kanagawa, Japan. · Cephalalgia. · Pubmed #12110113 No free full text.

Abstract: This phase II study investigated the efficacy, tolerability and dose-response relationship of oral zolmitriptan in the treatment of a single migraine attack in Japanese patients. A bridging analysis then assessed the validity of extrapolating western clinical data to these Japanese patients. In this multicentre, randomized, double-blind, placebo-controlled study, patients received a single dose of placebo or zolmitriptan 1, 2.5 or 5 mg. The primary endpoints were 2-h headache response and the tolerability of zolmitriptan. A statistically significant dose-response relationship was observed for the 2-h headache response (P=0.003). The 2.5 mg group had significantly greater 2-h headache response than the placebo group (P=0.032). The adverse event profile was similar to that reported in western patients, and no adverse events unique to the Japanese population were observed. The bridging analysis report confirmed similar efficacy and tolerability of zolmitriptan in Japanese and western populations. In the Japanese patients, the estimated response rates were 34.3%, 45.2%, 57.7% and 66.2% for placebo, and zolmitriptan 1, 2.5 and 5 mg, respectively, while in the western population the corresponding rates were 39.9%, 49.6%, 61.2% and 71.7%. Zolmitriptan is effective and well tolerated in the acute treatment of migraine in Japanese patients. The optimal dose was 2.5 mg, although the 5 mg dose may provide further benefit for some patients. The bridging analysis supports extrapolation of data from western to Japanese patients.

Wang SJ, Chung CS, Chankrachang S, Ravishankar K, Merican JS, Salazar G, Siow C, Cheung RT, Phanthumchinda K, Sakai F. · Neurological Institute, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, Taipei, Taiwan. · Headache. · Pubmed #19031500 No free full text.

Abstract: OBJECTIVES: This study aimed to survey the headache diagnoses and consequences among outpatients attending neurological services in 8 Asian countries. METHODS: This survey recruited patients who consulted neurologists for the first time with the chief complaint of headache. Patients suffering from headaches for 15 or more days per month were excluded. Patients answered a self-administered questionnaire, and their physicians independently completed a separate questionnaire. In this study, the migraine diagnosis given by the neurologists was used for analysis. The headache symptoms collected in the physician questionnaire were based on the diagnostic criteria of migraine proposed by the International Classification of Headache Disorders, second edition (ICHD-2). RESULTS: A total of 2782 patients (72% females; mean age 38.1 15.1 years) finished the study.Of them, 66.6% of patients were diagnosed by the neurologists to have migraine, ranging from 50.9% to 85.8% across different countries.Taken as a group, 41.4% of those patients diagnosed with migraine had not been previously diagnosed to have migraine prior to this consultation. On average, patients with migraine had 4.9 severe headaches per month with 65% of patients missing school,work, or household chores. Most (87.5%) patients with migraine took medications for acute treatment. Thirty-six percent of the patients had at least one emergency room consultation within one year. Only 29.2% were on prophylactic medications. Neurologists recommended pharmacological prophylaxis in 68.2% of patients not on preventive treatment. In comparison, migraine prevalence was the highest with ICHD-2 "any migraine" (ie, migraine with or without migraine and probable migraine) (73.3%) followed by neurologist-diagnosed migraine (66.6%) and ICHD-2 "strict migraine" (ie, migraine with or without aura only) (51.3%). About 88.6% patients with neurologist-diagnosed migraine fulfilled ICHD-2 any migraine but only 67.1% fulfilled the criteria of ICHD-2 strict migraine. CONCLUSIONS: Migraine is the most common headache diagnosis in neurological services in Asia. The prevalence of migraine was higher in countries with higher referral rates of patients to neurological services. Migraine remains underdiagnosed and under-treated in this region even though a high disability was found in patients with migraine. Probable migraine was adopted into the migraine diagnostic spectrum by neurologists in this study.

Iizuka T, Sakai F, Suzuki K, Igarashi H, Suzuki N. · Department of Neurology, School of Medicine, Kitasato University, Kanagawa, Japan. · Cephalalgia. · Pubmed #16472342 No free full text.

Abstract: The aim of this study is to report a possible implication of augmented vasogenic leakage in the mechanism of prolonged aura in sporadic hemiplegic migraine. A 35-year-old woman with sporadic hemiplegic migraine presented with headache followed by right arm weakness, right visual field defect, aphasia and confusion that persisted for 1 week. During the acute stage, focal hyperaemia was seen in the left cerebral hemisphere corresponding to persistent aura symptoms. Augmented vasogenic leakage was demonstrated on delayed enhanced fluid-attenuated inversion recovery image. Magnetic resonance angiography showed dilation of the left middle cerebral artery. During the convalescent stage, such abnormal findings were not seen. Based on these results, we speculate that augmented vasogenic leakage from the leptomeningeal vessels, probably associated with activation of the trigeminovascular system, may delay the recovery of hemiplegic migraine aura.

Ohbu S, Igarashi H, Okayasu H, Sakai F, Green J, Heller RF, Fukuhara S, Patrick DL. · Department of Neurology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan. · Qual Life Res. · Pubmed #15503844 No free full text.

Abstract: We developed and tested a version of the migraine-specific quality of life (MSQOL) instrument for use in Japan. The MSQOL was translated into Japanese, evaluated by physicians and nurses who has experienced migraine headaches, 'backtranslated', approved by the author of the original version, and tested in 70 out-patients with migraine. There were no ceiling or floor effects. All three subscales were found to be internally consistent: alpha > or = 0.76. The patients' scores were similar to those reported in the user's manual, with the exception of a difference of about 11 points on the Avoidance Behaviors subscale. Some correlations between MSQOL scores and SF-36 scores were statistically significant, although none exceeded 0.52. Linear associations between some measures of symptoms and some MSQOL scales were statistically significant, but those associations were consistent neither for the two kinds of symptom reports (severity and frequency) nor across all MSQOL subscales. Low MSQOL scores in early 1999 correlated with more return visits for medication and with greater amounts of triptan (anti-migraine) medication in 2001 and 2002. Overall, we interpret these results as indicating that, while they cannot be used as substitutes for reports of symptoms, scores on the Japanese version of the MSQOL can be used to assess the impact of migraine headaches on patients' lives.

Kusumi M, Araki H, Ijiri T, Kowa H, Adachi Y, Takeshima T, Sakai F, Nakashima K. · Department of Neurology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago, Japan. · Acta Neurol Scand. · Pubmed #15147464 No free full text.

Abstract: OBJECTIVES: The goal of this study is to clarify the association between migraine and Serotonin 2C receptor Cys23Ser polymorphism in Japanese population. MATERIALS AND METHOD: This study included 37 individuals with migraine with aura (MWA), 80 with migraine without aura, 43 with tension type headache (TH) and 360 with controls. The genotypes of Cys23Ser polymorphism were confirmed by polymerase chain reaction-restriction fragment length polymorphism techniques. RESULTS: The Ser allele frequency in control subjects is much less than that in Caucasian population. The Ser allele frequency in patients with MWA was higher than that in control subjects. CONCLUSION: The present study provides that 5HTR2c Cys23Ser polymorphism may be associated with MWA in Japanese population.

Kusumi M, Ishizaki K, Kowa H, Adachi Y, Takeshima T, Sakai F, Nakashima K. · Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan. · Eur Neurol. · Pubmed #12736537 No free full text.

Abstract: Migraine is considered to be a polygenic multifactorial disease with various environmental and genetic etiologies. We investigated glutathione S-transferase (GST) P1 Ile(105)Val, T1 and M1 polymorphisms in 174 Japanese headache sufferers and 372 Japanese controls. The headache group consisted of 38 cases of migraine with aura, 95 migraine without aura (MWOA) and 41 tension-type headache sufferers. The M1 homozygous deletion genotype was significantly higher in MWOA (64%) compared with controls (46%; p < 0.01; odds ratio = 2.18, 95% confidence interval: 1.32-3.61, adjusted for age and gender). In a comparison of the current smokers, the M1 null frequencies in MWOA were further increased. GSTM1 may be one of the genetic risk factors for MWOA in the Japanese population.

Iigaya M, Sakai F, Kolodner KB, Lipton RB, Stewart WF. · Department of Neurology, Kitasato University, Kitasato 1-15-1, Sagamihara-shi, Kanagawa, Japan. · Headache. · Pubmed #12656705 No free full text.

Abstract: OBJECTIVE: This study was designed to assess the test-retest reliability, internal consistency, and validity of a Japanese translation of the Migraine Disability Assessment (MIDAS) Questionnaire in a sample of Japanese patients with headache. BACKGROUND: Previous studies have demonstrated that the English-language version of the MIDAS Questionnaire is a reliable and valid instrument for the assessment of migraine-related disability. Any translations of the MIDAS Questionnaire must also be assessed for reliability and validity. METHODS: Study participants were recruited from the patient population attending either the Neurology Department of Kitasato University or an affiliated clinic. Participants were eligible for study entry if they had 6 or more primary headaches per year. For reliability testing, participants completed the MIDAS Questionnaire on 2 occasions, exactly 2 weeks apart. To assess validity, patients were also invited to participate in a 90-day daily diary study. Composite measures from the 90-day diaries were compared to equivalent MIDAS measures (ie, 5 questions on headache-related disability and 1 question each on average pain intensity and headache frequency in the last 3 months) and to the total MIDAS score obtained from a third MIDAS Questionnaire completed at the end of this 90-day period. RESULTS: One hundred one patients between the ages of 21 and 77 years were recruited (81 women and 20 men). Ninety-nine patients (80 women and 19 men) participated in the diary study. At baseline, 46.5% of patients were MIDAS grade I or II (minimal, mild, or infrequent disability), 22.2% were MIDAS grade III (moderate disability), and 31.3% were MIDAS grade IV (severe disability). Test-retest Spearman correlations for the 5 disability questions and the questions on average pain intensity and headache frequency ranged from 0.59 to 0.80 (P<.0001). The test-retest Spearman correlation coefficient for the total MIDAS score was 0.83 (P<.0001). The degree to which individual MIDAS questions correlated with the diary-based measures ranged from 0.36 to 0.88. The correlation between the total MIDAS score and the equivalent diary-based measure was 0.66. In general, the mean and median values for the MIDAS items and total MIDAS score were similar to the means and medians for the diary-based measures. However, the mean MIDAS scores for the number of days on which headache was experienced and the number of missed workdays were significantly different compared to the diary-based estimates for these items (P<.05). In addition, the mean MIDAS score for the number of days of missed housework was significantly higher than the corresponding diary-based estimate (P<.01). CONCLUSIONS: The results from this study show that the Japanese translation of the MIDAS Questionnaire is comparable with the English-language version in terms of reliability and validity.

Tomita M, Suzuki N, Igarashi H, Endo M, Sakai F. · No affiliation provided · Intern Med. · Pubmed #12211529 links to  free full text

Abstract: OBJECTIVE: To evaluate the adverse events possibly caused by sumatriptan injection and explore the relationship between chest symptoms along with sumatriptan injection and coronary ischemia among Japanese patients with migraine. METHODS: A cumulative total of 112 subcutaneous injections in 62 patients were evaluated. ECG was continuously monitored before and until 5 minutes after injection on 92 occasions. PATIENTS: Sixteen men and 46 women aged from 16 to 60 (mean 39+/-12) years. Their clinical diagnoses were migraine with aura, migraine without aura, cluster headache, and others. RESULTS: Chest symptoms occurred following 17% of all injections and in 15% of all patients. None of these chest symptoms was accompanied by ECG changes. CONCLUSIONS: Although the risk of coronary ischemia with sumatriptan treatment is commonly stated, our data suggest that chest symptoms following sumatriptan injection are not strongly associated with coronary ischemia in the Japanese population. The mechanism of chest symptoms following sumatriptan administration should be further elucidated.

Fukuda M, Suzuki N, Maruyama S, Dobashi K, Kitamura A, Sakai F. · Department of Internal Medicine, School of Medicine, Kitasato University, Sagamihara, Japan. · Cephalalgia. · Pubmed #12133047 No free full text.

Abstract: To investigate further the pharmacological mechanism of an anti-migraine drug, sumatriptan, a 5-HT1B/1D receptor agonist, we studied its effect on the cerebral circulation in seven anaesthetized rats, particularly during hypercapnia. After injection of 0.6 or 6.0 microg/kg sumatriptan succinate, no significant change in cerebral blood flow (CBF) was observed either in the striatum or in the parietal cortex. The increase in CBF both in the parietal cortex and the striatum during 5% CO2 inhalation was significantly less when sumatriptan succinate 6.0 microg/kg was injected. Sumatriptan appeared to have a vasoconstrictor effect on the relaxed vessels by CO2 inhalation. This mechanism might be attributable to vasoconstriction through activation of 5-HT1B receptors located in the vascular smooth muscle rather than 5-HT1B receptors in the vascular adventitia.

Takeshima T, Fukuhara Y, Adachi Y, Ishizaki K, Kusumi M, Kowa H, Iigaya M, Sakai F, Nakashima K. · Division of Neurology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago, Japan. · Cephalalgia. · Pubmed #11843871 No free full text.

Abstract: Mitochondrial dysfunction has been reported in patients with migraine. We investigated leukocyte mitochondrial DNA 11084 A to G polymorphism in 166 Japanese migraineurs and 483 Japanese controls. The migraine group consisted of 43 patients suffering from migraine with aura (MWA) and 123 from migraine without aura (MOA). The frequency of the transition was 7.2% (12/166) in the migraine group and 7.3% (35/483) in the controls. The frequency of the transition was 4.7% in MWA and 8.1% in MOA. There was no significant difference among the groups (chi-square test). The mitochondrial DNA 11084 A to G transition was more common in Japanese subjects than reported in Caucasians; however, this polymorphism is not a genetic risk factor for migraine in Japanese patients.

Sakai F, Murai M, Manaka S, Miyakawa Y, Nakashima K. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #11391916 No free full text.

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Kowa H, Yasui K, Takeshima T, Urakami K, Sakai F, Nakashima K. · Division of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan. · Am J Med Genet. · Pubmed #11121176 No free full text.

Abstract: Increased homocysteine levels are associated with various pathological conditions in humans, including stroke and cardiovascular disorders. Homocysteine acts as an excitatory amino acid in vivo and may influence the threshold of migraine headache. Frosst et al. [1995] reported an association between the homozygous C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and serum homocysteine levels. This study was designed to determine the prevalence of the MTHFR mutation in Japanese patients with migraine and tension-type headache (TH). Seventy-four patients with migraine headaches (22 with aura and 52 without aura), 47 with THs, and 261 normal controls were recruited. Genotyping of MTHFR C677T polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. We detected that the incidence of the homozygous transition (T/T) in migraine sufferers (20.3%) was significantly higher than that in controls (9.6%). Moreover, the frequency of the T/T genotype in individuals with migraine headaches with aura was remarkably high (40.9%). The MTHFR T allele was more frequent in the migraine group than in the control group. Our results support the conclusion that the MTHFR gene, causing mild hyperhomocysteinemia may be a genetic risk factor for migraine. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:762-764, 2000.

Iizuka T, Sakai F, Yamakawa K, Suzuki K, Suzuki N. · No affiliation provided · Cephalalgia. · Pubmed #15315534 No free full text.

This publication has no abstract.