Migraine Disorders: Bousser MG

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.

Kurth T, Tzourio C, Bousser MG. · No affiliation provided · Circulation. · Pubmed #18824652 No free full text.

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Bousser MG, Geraud G. · No affiliation provided · Rev Neurol (Paris). · Pubmed #16141948 No free full text.

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Vahedi K, Depienne C, Le Fort D, Riant F, Chaine P, Trouillard O, Gaudric A, Morris MA, Leguern E, Tournier-Lasserve E, Bousser MG. · APHP-Lariboisière Hospital, Department of Neurology, 2 rue Ambroise Paré, 75010 Paris, France. · Neurology. · Pubmed #19332696 No free full text.

Abstract: OBJECTIVE: Familial hemiplegic migraine (FHM) is a genetically heterogeneous disorder in which three genes, CACNA1A, ATP1A2, and SCN1A, are currently known to be involved. FHM is occasionally associated with other neurologic symptoms such as cerebellar ataxia or epileptic seizures. A unique eye phenotype of elicited repetitive daily blindness (ERDB) has also been reported to be cosegregating with FHM in a single Swiss family. METHODS: We report an additional family in whom the proband had, in addition to FHM, typical ERDB. In this family and the previously reported Swiss family, the whole coding region of the SCN1A gene was screened after exclusion of mutation in CACNA1A and ATP1A2 genes. RESULTS: We identified two novel SCN1A mutations (c.4495T>C/p.Phe1499Leu and c.4467G>C/p.Gln1489His missense substitutions) in exons 24 and 23, respectively, segregating with the disease in all living affected members. Both mutations were absent from 180 healthy Caucasian controls and were located in an intracellular loop highly conserved throughout evolution. CONCLUSION: We report new clinical data supporting cosegregation of familial hemiplegic migraine and the new eye phenotype of elicited repetitive daily blindness and two novel SCN1A mutations as the underlying genetic defect in two unrelated families. SCN1A encodes the voltage-gated sodium channel Nav1.1 that is highly expressed in the CNS including the retina. This remarkably stereotyped new eye phenotype has clinical characteristics of abnormal propagation of the retinal electrical signal that may be a retinal spreading depression. These results suggest that SCN1A mutations, which alter neuronal brain excitability, may occasionally alter retinal cell excitability.

Bousser MG. · Hôpital Lariboisière AP-HP, Université Paris Diderot, Paris, France. · Cerebrovasc Dis. · Pubmed #18724046 links to  free full text

Abstract: 'Translation' in medicine immediately suggests 'translational research', but there are many other varieties of 'translation'. I have selected 4 translations in the field of vascular neurology in which I have been involved in different respects: (1) the translation of results from men to women, taking the example of aspirin which, in primary prevention, decreases the risk of myocardial infarction in men and the risk of cerebral infarction in women, the reason for this sex difference being so far unknown; (2) the 'inverse translational research', from bedside to bench, taking the example of the disease we have identified--CADASIL--and showing how the study of one patient and his family led to the identification of a gene, Notch3, so far unknown in humans and to the discovery of its key role in the physiology of vascular smooth muscle cells; (3) the translation from individual case reports to multidisciplinary trials taking the example of hemicraniectomy in malignant cerebral infarction and emphasizing the interest in such rare and severe conditions of pooling and reporting the results of randomized clinical trials before the results of individual trials, and (4) the translation from research to practice, emphasizing not the well-known 'evidence to practice gap' but the slippery slope of 'lack of evidence to overpractice', taking the example of patent foramen ovale closure in migraine.

Chabriat H, Bousser MG. · Department of Neurology, Hopital Lariboisière, Université Paris VII, Denis Diderot, Paris, France. · Dialogues Clin Neurosci. · Pubmed #17726918 No free full text.

Abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-artery disease of mid-adulthood caused by mutations of the NOTCH3 gene. The disease is responsible for widespread white-matter lesions associated with lacunar infarctions in various subcortical areas. The disease is responsible for migraine with aura and ischemic strokes, and is associated with various degrees of cognitive impairment and with mood disturbances. CADASIL is considered as a unique model to investigate what is known as "subcortical ischemic vascular dementia." Recent data suggest that the number of lacunar infarctions and severity of cerebral atrophy are the main magnetic resonance imaging markers associated with cognitive and motor disabilities in this disorder. Mood disturbances are reported in 10% to 20% of patients, most often in association with cognitive alterations. Their exact origin remains unknown; the presence of ischemic lesions within the basal ganglia or the frontal white matter may promote the occurrence of these symptoms. Further studies are needed to better understand the relationships between cerebral lesions and both cognitive and psychiatric symptoms in this small-vessel disease of the brain.

Bousser MG. · Service de Neurologie, Hôpital Lariboisière, Paris. · Rev Neurol (Paris). · Pubmed #17304169 No free full text.

Abstract: Recent epidemiological data suggest a bidirectional link between patent foramen ovale (PFO) and migraine with aura (MA) with a relative risk of 2 for PFO in subjects with MA and for MA in subjects with PFO. There is no evidence for a link between PFO and migraine without aura. This link is not systematic and applies only to subsets of PFO, mostly large ones, and to subsets of patients with MA. Although comorbidity cannot be ruled out, it may be that this link is partly causal and that some large PFOs may favor MA attacks in genetically predisposed subjects, by allowing vasoactive substances, platelet emboli or paradoxical emboli to bypass the lung filter and trigger the cortical spreading depression of the aura. The first double blind randomised trial of PFO closure in refractory MA, "MIST", has failed to show a benefit on the primary efficacy end point: cessation of attacks during the analysis period included between 3 and 6 months after the procedure. There is thus at present no scientific reason to look for PFO or to close PFO in migraine patients.

Massiou H, Bousser MG. · Service de Neurologie, Hôpital Lariboisière, Paris, France. · Rev Neurol (Paris). · Pubmed #16141958 No free full text.

Abstract: Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks. Based on the results of published controlled trials, the main prophylactic drugs are some beta-blockers, methysergide, pizotifene, oxetorone, flunarizine, amitriptyline, NSAIDs, sodium valproate and topiramate. With these drugs, the frequency of attacks can be reduced by half in 50 percent of patients. Some less evaluated substances such as aspirin, DHE, indoramine, and angiotensin II inhibitors may be useful. The decision to treat with drugs and the choice of a prophylactic drug are made together with the patient. The superiority of one major drug over another has never been demonstrated in a comparative trial, thus the choice of the drug to start with depends on the possible side effects and contraindications, the characteristics of the migraine attacks, and the associated morbidities and possible interactions with abortive medications. Doses should be increased gradually, in order to reach the recommended daily dose, only if tolerance permits. Treatment efficacy has to be assessed after 2 or 3 months, and in case of failure or poor tolerance, another treatment should be started. If the treatment is successful, it should be continued for 6 to 12 months, and then tapered off. The moderate efficacy and the frequency of the side effects observed with prophylactic drugs explain the high rate of withdrawals. Some patients nevertheless dramatically improve, warranting trying several drugs successively in order to find the most appropriate one.

Bousser MG, Welch KM. · Hôpital Lariboisière, Service de Neurologie, Paris, France. · Lancet Neurol. · Pubmed #16109360 No free full text.

Abstract: A complex bidirectional relation between migraine, mostly migraine with aura (MA), and ischaemic stroke is known. A cerebral infarction can occur during a MA, and MA is a risk factor for ischaemic stroke, particularly in young women. Conversely, cerebral ischaemia can induce MA. Both ischaemic stroke and MA might be consequences of many underlying vascular disorders. Despite the relation between migraine and stroke, migraine as a primary headache disorder is mostly benign.

Bousser MG. · Department of Neurology, Lariboisière Hospital, 2 Rue Ambroise Paré, Paris Cédex 10, France 75571. · Stroke. · Pubmed #15459439 links to  free full text

Abstract: Epidemiological studies suggest the existence of close but complex relationships between estrogens, migraine, and stroke in women before menopause. Migraine, particularly without aura, is strongly influenced by estrogens as illustrated by the frequency of onset at puberty, of menstrual migraine, and of improvement during pregnancy. Migraine, particularly with aura, is a risk factor for ischemic stroke with a relative risk of 3, further increased by tobacco smoking and oral contraceptive use. The pathophysiological mechanism underlying these close relationships remains unknown. In practice, given the very low absolute risk of stroke in young women, there is no systematic contraindication to oral contraceptive use in young female migraineurs but rather a firm recommendation for no smoking and for the use of low-estrogen-content pills or progestogens only, particularly in migraine with aura.

Ducros A, Tournier-Lasserve E, Bousser MG. · Headache Emergency Department, Lariboisière Hospital, Paris, France. · Lancet Neurol. · Pubmed #12849426 No free full text.

Abstract: The search for genes involved in the pathophysiology of migraine poses major difficulties. First, there is no objective diagnostic method to assess the status of the individuals studied. Second, migraine is a polygenic multifactorial disorder. Familial hemiplegic migraine (FHM) is the only known autosomal dominant subtype of migraine. In half the families with FHM who have been studied, there are mutations in the calcium-channel gene CACNA1A, located on chromosome 19. In other families, a locus has been mapped on chromosome 1. The role of these loci in typical migraine is still unknown. A susceptibility locus for migraine with aura has been located on chromosome 19 (but is distinct from CACNA1A) and a genome-wide linkage analysis has mapped a susceptibility locus on chromosome 4. Another locus for migraine may be on the X chromosome. Finally, many positive association studies have been published, but few have been replicated.

Guillon B, Bousser MG. · Service de Neurologie, Hôpital G. et R. Laënnec, 44093 Nantes. · J Neuroradiol. · Pubmed #12538941 links to  free full text

Abstract: Spontaneous cervical artery dissections are produced by the penetration of circulating blood into the vessel wall of one or more cervical arteries, without a preceding major trauma. Dissection is one of the most frequent etiologies of ischemic stroke in young patients. Its annual incidence is about 3 per 100,000. Pathophysiology of cervical artery dissection remains misunderstood. Triggering factors such as minor trauma and infection have been identified. However, they are too trivial to explain alone the occurrence of a mural hematoma. Several abnormalities suggesting an underlying arteriopathy related to an extracellular matrix defect which could predispose to dissection have been reported: arterial redundancies, intracranial aneurysms, aortic root dilatation, common carotid artery distensibility increase, fibromuscular dysplasia, inherited connective tissue disorders, ultrastructural dermal connective tissue abnormalities. Other factors associated with dissection, such as migraine, hyperhomocysteinemia and alpha-1 antitrypsin deficiency, suggest arterial wall fragility secondary to hyperactivity of some proteases. If an underlying arteriopathy is likely, its nature remains unidentified to date and does not seem to be unique.

Crassard I, Conard J, Bousser MG. · Service de Neurologie, Hôpital Lariboisière, Paris, France. · Cephalalgia. · Pubmed #11531894 No free full text.

Abstract: Migraine is a risk factor for cerebral infarction in young women. The nature of the connection between these diseases remains however essentially unknown. Abnormalities of haemostasis leading to an increased thrombotic risk would provide a logical link. Platelets, antiphospholipid antibodies and more recently congenital thrombophilia have thus successively been implicated. The different studies concerning these topics have been reviewed. Because of the conflicting results obtained and because of the numerous methodological shortcomings of many of these studies, no definite conclusion can be reached. It is possible that these 3 factors play a role in the ischemic risk of migraine, but it is as likely or even more likely that other factors (inside or outside the hemostatic system) play a more important role. Further studies are thus deeply needed.

Chabriat H, Joutel A, Vahedi K, Iba-Zizen MT, Tournier-Lasserve E, Bousser MG. · Service de Neurologie, Hôpital Lariboisière, 2, rue Ambroise Paré-75010 Paris. · Bull Acad Natl Med. · Pubmed #11261256 No free full text.

Abstract: Recently identified in a french family, CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a generalised disease of small arteries, largely predominating in the brain. Its clinical manifestations start during mid-adulthood and include recurrent ischaemic subcortical events, attacks of migraine with aura, severe mood disorders, subcortical dementia, and, at magnetic resonance imaging, widespread leuko-encephalopathy. There is so far no specific treatment and the mean duration of the disease is 20 years. CADASIL is most frequently a familial disorder with an autosomal dominant mode of transmission. Its responsible gene, Notch 3, is located on Chromosome 19. By the identification of its gene, CADASIL, (which is now known to affect over 400 families worldwide) is a unique variety of cerebro-vascular disease, affecting mainly the subcortical white matter.

Bousser MG. · Service de Neurologie, Hôpital Lariboisière, 2, rue Ambroise Paré, F 75475 Paris Cedex 10. · Ann Pharm Fr. · Pubmed #11148371 No free full text.

Abstract: In the past ten years, migraine has really entered the field of science, with a number of major advances Despite theses advances, a lot has still to be done to understand what migraine really is and to improve the management of migraine sufferers.

Tzourio C, Bousser MG. · INSERM U360 Recherches épidémiologiques en neurologie et psychopathologie, Hôpital de la Salpêtrière, Paris. · Rev Neurol (Paris). · Pubmed #11139748 No free full text.

Abstract: In this paper we review the evidence that migraine is associated with ischemic stroke, emphasizing potential biases, factors which may influence the association, potential mechanisms, and potential public health impact. Consistency of case-control findings from several countries and supporting evidence from prospective data suggest that the association is not an artifact of study design or execution. However, it is less clear whether migraine without aura is associated with stroke or whether the association is restricted to migraine with aura. Similarly, there are few data examining the magnitude of the association among nonusers of oral contraceptives compared to those who use low estrogen oral contraceptives. Moreover, there is still no convincing evidence on the mechanisms that would be implied and on the groups of migraineurs really at risk of ischemic stroke. Despite the considerable advances in our understanding of the relationship between migraine and stroke, there are many gaps in the data needed for public health recommendations.

Tzourio C, Kittner SJ, Bousser MG, Alpérovitch A. · INSERM U360 Recherches Epidémiologiques en Neurologie et Psychopathologie, Hôpital de la Salpêtrière, Paris, France. · Cephalalgia. · Pubmed #10997773 No free full text.

Abstract: In this paper we review the evidence that migraine is associated with ischaemic stroke in young women, emphasizing potential biases, factors that may influence the association, potential mechanisms, and potential public health impact. Consistency of case-control findings from several countries and supporting evidence from prospective data suggest that the association is not an artifact of study design or execution, although, due to methodological limitations, none of the studies mentioned can be considered definite proof of the association. However, it is less clear whether migraine without aura is associated with stroke or whether the association is restricted to migraine with aura. Similarly, there are few data examining the magnitude of the association among nonusers of oral contraceptives compared with those who use low oestrogen oral contraceptives. As a consequence, there is a lack of data concurrently stratifying both by the presence vs. the absence of aura and by the use of low oestrogen oral contraceptives vs. non-use of oral contraceptives. Moreover, there is still no convincing evidence on the mechanisms that would be implied and on the groups of migraineurs really at risk of ischaemic stroke. Despite the considerable advances in our understanding of the relationship between migraine and stroke, there are many gaps in the data needed for public health recommendations.

Bousser MG, Kittner SJ. · Hôpital Lariboisière, Service de Neurologie, Paris, France. · Cephalalgia. · Pubmed #10997772 No free full text.

Abstract: Since 1962, more than 25 studies have been devoted to the relationship between oral contraceptives and stroke. They are all case-control or cohort epidemiological studies and thus contain the difficulties and biases that are inherent in these types of studies. The following conclusions can be drawn from these studies: High oestrogen content (> or = 50 microg) increases the risk of stroke, all stroke subtypes, and stroke death. Low oestrogen content (<50 microg) carries a very low or no risk of stroke. There are no data on progestogen only oral contraceptives. Stroke risk is greatly increased if associated risk factors are present, in particular hypertension, cigarette smoking and migraine. Oral contraceptives, even at low doses, significantly increase the risk of cerebral venous thrombosis, which is further enhanced if congenital thrombophilia is present. The attributable risk of stroke in young women using oral contraceptives is about 1 per 200000 woman-years. The contraceptive and non-contraceptive benefits of low dose oral contraceptives vastly outweigh their risks provided that other risk factors are absent or well controlled.

Bousser MG. · Hospital Lariboisière, Paris, France. · Cephalalgia. · Pubmed #10214531 No free full text.

This publication has no abstract.

Dib M, Massiou H, Weber M, Henry P, Garcia-Acosta S, Bousser MG, Anonymous00268. · Service de Neurologie, Hôpital Lariboisière, 2 rue Ambroise Paré, 75475 Paris Cedex, France. · Neurology. · Pubmed #12058095 No free full text.

Abstract: BACKGROUND: Certain nonsteroidal anti-inflammatory drugs are effective in the acute treatment of migraine attacks. The authors report a double-blind, placebo-controlled, randomized cross-over trial of a dual-release formulation of oral ketoprofen in the acute treatment of migraine attacks. METHODS: The authors compared the efficacy of two doses of ketoprofen (75 or 150 mg) with that of placebo (primary analysis) and zolmitriptan 2.5 mg (secondary analysis) on one to four consecutive attacks in 235 intent-to-treat patients (out of 257 randomized patients) with migraine with or without aura. The principal efficacy outcome was headache relief (reduction in headache severity from severe or moderate to mild or absent at 2 hours). RESULTS: Results are based on 838 attacks with a severe or moderate headache that were evaluable at 2 hours. Relief was reported for 62.6% of headaches treated with ketoprofen 75 mg, 61.6% with ketoprofen 150 mg, and 66.8% with zolmitriptan. The difference between the three active treatments and placebo (27.8% relief) was highly significant, both tests of ketoprofen vs placebo being globally controlled at a 5% level for the type I error (primary analysis). Headaches at 2 hours disappeared more frequently for the active treatments than for placebo. The authors also demonstrated efficacy on most other secondary outcomes. The tolerance of ketoprofen was good (similar to that of placebo). CONCLUSIONS: Oral ketoprofen (75 mg or 150 mg) in a dual-release formulation is an effective and well-tolerated drug in the acute treatment of migraine attacks.

Vahedi K, Taupin P, Djomby R, El-Amrani M, Lutz G, Filipetti V, Landais P, Massiou H, Bousser MG, Anonymous00228. · Service de Neurologie Hĵpital Lariboisière, Paris, France. · J Neurol. · Pubmed #11985388 No free full text.

Abstract: BACKGROUNDS: Familial hemiplegic migraine and episodic ataxia type 2 (EA2) are allelic disorders with distinct types of mutations in the CACNA1A gene. EA2 attacks are remarkably sensitive to acetazolamide, a carbonic anhydrase inhibitor. The effectiveness of acetazolamide in migraine prophylaxis is unknown. OBJECTIVES: To evaluate the efficacy and the tolerability of acetazolamide in migraine prophylaxis. METHODS: We compared daily oral 500 mg acetazolamide and placebo in patients with migraine in a multicentre, double-blind, randomised trial of 12 weeks duration after a run-in period of 4 weeks without treatment. Frequency of attacks at the last trial period of 4 weeks was the primary efficacy criterion. Secondary efficacy criteria were the frequency of attacks per 4 weeks, the severity and duration of attacks, the number of hours with migraine as well as the number of responders with more than 50% reduction in attack frequency. RESULTS: 53 patients had been enrolled when the study was prematurely stopped because of a high number of withdrawals (34%), primarily linked to acetazolamide related side effects. Considering the primary and secondary efficacy criteria, among the 53 included patients (27 in the placebo group and 26 in the acetazolamide group), no difference between the 2 study groups could be demonstrated. The most frequent adverse events related to acetazolamide were paresthesias and asthenia. CONCLUSIONS: In this trial, migraine sufferers poorly tolerated acetazolamide given in an oral dose of 500 mg daily. No obvious prophylactic beneficial effect of acetazolamide appeared on migraine attacks.

Arnold M, De Marchis GM, Stapf C, Baumgartner RW, Nedeltchev K, Buffon F, Galimanis A, Sarikaya H, Mattle HP, Bousser MG. · Assistance Publique, Hôpitaux de Paris, Department of Neurology, University Hospital Lariboisière, Paris. · J Neurol Neurosurg Psychiatry. · Pubmed #18977815 No free full text.

Abstract: BACKGROUND: Spontaneous cervicocephalic artery dissection (sCAD) of more than two cervical arteries is rare. PATIENTS AND METHODS: Vascular and potential sCAD risk factors, triggering events, clinical and neuroimaging findings, and outcome of patients with multiple sCAD were studied. Patients were drawn from prospective hospital-based sCAD registries. RESULTS: Of 740 consecutive patients with sCAD, 11 (1.5%) had three, and one had four (0.1%) sCAD. Eight of these 12 patients were women. One patient had additional dissections of the celiac trunk and hepatic artery. Vascular risk factors included hypertension (n = 1), hypercholesterolaemia (n = 6), current smoking (n = 5) and migraine (n = 6). No patient had a family history of sCAD, fibromuscular dysplasia (FMD) or connective tissue disease. SCAD was preceded by a minor trauma in five and infection in four patients. Clinical manifestations included ischaemic stroke (n = 8), transient ischaemic attack (n = 3), headache (n = 9), neck pain (n = 4), Horner syndrome (n = 5), pulsatile tinnitus (n = 2) and dysgeusia (n = 1). Brain MRI revealed ischaemic infarcts that affected one vessel territory in seven and two territories in two patients. The 3-month outcome was favourable (modified Rankin scale score 0-1) in 10 patients (83%). No new recurrent stroke or sCAD occurred during a mean follow-up of 50 (SD 29) months. CONCLUSION: Multiple sCAD occurred preferentially in women and caused clinical symptoms and signs mainly in one vascular territory. In none of the patients was FMD or any other underlying arteriopathy apparent. The majority of multiple sCAD was preceded by a minor trauma or infection. Clinical outcome was favourable in most patients, and long-term prognosis benign. The data suggest that transient vasculopathy may be a major mechanism for multiple sCAD.

Arnold M, Camus-Jacqmin M, Stapf C, Ducros A, Viswanathan A, Berthet K, Bousser MG. · No affiliation provided · Stroke. · Pubmed #18535274 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Cervicocephalic artery dissection (CAD) after childbirth is rare. The objective of this study was to determine differences between postpartum and nonpostpartum CAD. METHODS: We compared consecutive patients with postpartum CAD with a control group of women with nonpostpartum CAD. RESULTS: Of 245 patients with CAD, 102 women <50 years (6 with postpartum CAD and 96 with nonpostpartum CAD) were identified. Vascular risk factors and presenting characteristics did not differ significantly between postpartum CAD and nonpostpartum CAD women. By contrast, patients with postpartum CAD had more often coexisting conditions such as reversible cerebral vasoconstriction syndrome (2 of 6 versus 2 of 96; P=0.017), reversible posterior leukoencephalopathy syndrome (2 of 6 versus one of 96; P=0.009), and subarachnoid hemorrhage without signs of intracranial extension of CAD (2 of 6 versus zero of 96; P=0.003). CONCLUSIONS: CAD and associated conditions should be looked for in women with unusual headache after childbirth.

Riant F, De Fusco M, Aridon P, Ducros A, Ploton C, Marchelli F, Maciazek J, Bousser MG, Casari G, Tournier-Lasserve E. · Laboratoire de Génétique Moléculaire, Hôpital Lariboisière AP-HP, Paris, France. · Hum Mutat. · Pubmed #16088919 No free full text.

Abstract: Familial hemiplegic migraine (FHM) is an autosomal dominant form of migraine with aura. The disease is caused by mutations of at least three genes among which two have been identified, CACNA1A and ATP1A2. Very few mutations have been identified so far in ATP1A2. We screened the coding sequence of ATP1A2 in 26 unrelated FHM probands in whom CACNA1A screening was negative. A total of eight different mutations were identified in 11 of the probands (41%), including six missense mutations, one small deletion leading to a frameshift, and one in frame deletion. All were novel mutations. Two mutations were recurrent, in three and two families, respectively. Genotyping of 94 relatives of these 11 probands identified 47 mutation carriers, among whom 36 were clinically affected. Sequencing of all 23 exons in an ethnically matched panel detected only one exonic coding polymorphism.

Vahedi K, Chabriat H, Levy C, Joutel A, Tournier-Lasserve E, Bousser MG. · Service de Neurologie, Assistance Publique--Hôpitaux de Paris, Hôpital Lariboisière, Paris, France. · Arch Neurol. · Pubmed #15313840 links to  free full text

Abstract: BACKGROUND: Migraine with aura (MA) is one of the clinical hallmarks of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a small vessel disease of the brain caused by mutations in the NOTCH3 gene, but its exact mechanisms are unknown. OBJECTIVES: To describe the patterns of MA in CADASIL and to compare brain magnetic resonance signal abnormalities between CADASIL patients with and without MA. DESIGN: Comparison of brain magnetic resonance signal abnormalities between cases and controls. SETTING: Patients with CADASIL seen at Lariboisière Hospital. PATIENTS: Forty-one CADASIL patients with MA and 31 age-matched CADASIL controls without MA. RESULTS: The mean age at onset of MA was significantly younger in women compared with men and occurred a mean of 15 years prior to stroke onset. A majority of patients (56%) reported at least 1 migraine attack with atypical aura. All CADASIL patients either with or without MA had white matter signal abnormalities on T2-weighted imaging. There was no difference in the frequency and distribution of brain signal abnormalities between CADASIL patients with and without MA. CONCLUSIONS: In CADASIL, MA is characterized by an unusually high frequency of attacks of migraine with atypical aura. The distribution and extent of magnetic resonance signal abnormalities did not differ according to migraine phenotype.