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Migraine, White Matter Lesions and Subarachnoid Hemorrhage: Analysis Ofa Large Pedigree Migren, Ak Madde Ve Subaraknoid Kanama: Bir Aile Analizi

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Migraine, White Matter Lesions and Subarachnoid Hemorrhage: Analysis Ofa Large Pedigree Migren, Ak Madde Ve Subaraknoid Kanama: Bir Aile Analizi 162 Case Report / Olgu Sunumu DOi: 10.4274inpa 47 5425 Migraine, White Matter Lesions and Subarachnoid Hemorrhage: Analysis ofa Large Pedigree Migren, Ak Madde ve Subaraknoid Kanama: Bir Aile Analizi Zeliha MATUR, Mürüwet POYRAZ*, Oya UYGUNER**, Hülya KAYSERiLi, Betül GÜVELi***, Betül BAYKAN lstanbul Üniversitesi lstanbul Fakültesi, Nöroloji Ana bilim lstanbul, Türkiye Hatun Merkezi, Nöroloji Bölümü, lstanbul, Türkiye ''lstanbul Üniversitesi lstanbul Fakültesi, Genetik Anabilim lstanbul, Türkiye Gureba Egitim ve Hastanesi, Nöroloji Klinigi, lstanbul, Türkiye ABSTRACT ÖZET Patients with migraine are at increased risk tor white matter hyperintensities Migrenli hastalarda manyetik rezonans görüntülemede IMRG) ak madde detected on magnetic resonance imaging (MAii. A 46-year-old woman had a tensitelerin saptanma 20 history of migraine with and without aura tor 20 years. Bilateral prominent ve migreni 12 ve FLAIR MRG hyperintense lesions were seen in centrum semiovale, posterior corona radia- sentrum semiovale, posterior korona radiata, trontal ak madde ve ta, frontal white matter and periventricular regions on her T2- and triküler bölgelerde hiperintens lezyonlar görüldü. On üç aile bireyinde öy- FLAIA-weighted cranial MRls. Thirteen members of her family, including her küsü ve benzer MAG lezyonlan migrenli oQlunda da görüldü. ilginç olarak üç son, hada history of migraine and similar brain MRI lesions. Furthermore, three aile bireyinde subaraknoid kanama (SAKI ve bir aile bireyinde intrakranyal anev- family members had a history of subarachnoid hemorrhage (SAH) and one rizma öyküsü mevcuttu. Önemi bilinmeyen ak madde olan migrenli has- member had intracranial aneurysm. Dur current knowledge on associations, olduQu durumlar, inceleme ve tedavileri bugünkü investigation plan and of patients with migraine with white matter bilgilerimiz Bu durumun ailesel SAK ile birlikteliQi ilk kez bu of unknown is limited. Herein, tor the first time, we repon bir ailede (Nöropsikiyatri 2010; 47: 162-5/ the of this condition with familial SAH in a large pedigree. Anahtar kelimeler: Migren, ak madde subaraknoid kanama, (Archives of Neuropsychiatry ailesel 2010; 47: 162-5) intrakranyal anevrizma, CADASIL Key words: Migraine, white matter lesions, subarachnoid hemorrhage, familial aneurysm, CADASIL --------------------------------------------------- lntroduction lesions relate to a higher risk of cerebrovascular disease. There is evidence tor an association between migraine and Patients with migraine are at increased risk tor white ischemic stroke, but not tor migraine and subarachnoid matter lesions (WMLs) detected on magnetic resonance hemorrhage (SAH) (Jt. imaging (MRI) and these lesions are common, especially in in this study, we reported an index female patient who has females having migraine with aura (MA) (1). Many studies MA with WMLs on MRI and her family members suffering from have reported that brain MRI of migraine patients demonstrated migraine and SAH (Figure 1). focal cerebral areas appearing as ischaemia-like lesions and Report of the lndex Patient and Her Family prevalence of this finding varies, ranging from 6% to 46% (2-6). A 46-year-old woman suffered from headache with The origin and nature of WMLs in migraine patients remain stili paresthesia of the perioral region and hands. She had a history unclear (1). it is controversial, whether these subclinical brain of MA with visual and paresthetic aura lasting 5-7 minutes and Address lor Adresi: Dr. Zeliha Matur, lstanbul Üniversitesi lstanbul Fakültesi, Nöroloji Anabilim lstanbul, E-mail: [email protected] tarihi: 23.10.2009 Acceptedll(abul tarihi: 19.12.2009 This study was asa poster in of Neurological in 7-12, 2008. © Archives of Neurnpsychiatry. by Galenos / © Nöropsikiyatri Galenos Archives of Neuropsychiatry 2010; 47: 162-5 et al. Nöropsikiyatri 2010; 47: 162-5 Migraine, White Matter Lesions and Subarachnoid Hemorrhage: Analysis ofa Large Pedigree 163 migraine without aura (according to the lnternational of vasculitis (anticardiolipin antibodies, rheumatoid factor, Classification of Headache Disorders published in 2004) for 20 ANA, and procoagulant factors (protein C, protein years (8). Her visual auras were shaped as black spots in front S, antithrombin 111) were ali found negative. Homocysteine of one eye, stereotypic for every migraine atta ek and preceding levels were normal. Wright agglutination test (diagnostic test headache . Paresthetic auras were rare, bilateral, not for Brucellosis), TPHA and VDRL tests were negative; the levels stereotypical and also preceding headache. of vitamin B 12, thyroid hormon es and thyroid autoantibodies Her past medical history was uneventful, except for having were within the normal range. Echocardiography, carotid depression. She had been using amitriptyline and paroxetine duplex ultrasonography and vertebral artery investigations lor the last three years. Her neurological examination was were also found normal. She was admitted to our department normal. She had no additional vascular risk factors, such as and the cranial MRI investigation was repeated. No new WMLs hypertension, diabetes mellitus and hyperlipidemia, other than were observed (Figure 2b). lntracranial MR angiography, smoking (20 pack-years). performed to reveal the possible presence of aneurysm or Three years ago, she had been admitted to another hospital atherosclerosis, gave normal results. Pattern VEP and SEP due to headache and T2- and FLAIR-weighted cranial MRI had examinations were within normal limits. Cerebrospinal fluid showed bilateral hyperintense lesions in centrum semiovale, examination for the presence of oligoclonal bands was also normal. posterior corona radiata, frontal white matter and periventricular Exons 2, 3, 4, 5, 6 and 11 of NDTCH3 gene were sequenced, regions (Figure 2a). She had been investigated in order to but no mutation was revealed. Heterozygous synonymous SNP exclude multiple sclerosis (MS) and related diseases. Markers (rs1043994) in exon 4 and heterozygous synonymous variation il lll V VI VII : Migrenous headache +: Subarachnoidal hemorrhage -: lschemic white matter lesions O: lschemic cerebrovascular disease Figure 1. The Pedigree showing the patients with migraine and subarachnoid Figu re 2a-b. Cranial MRI study of the index case in 2004 (a) and 2006 (b) Axial FLAIR sequences of Neuropsychiatry 2010; 47- 162-5 Matur et al. Archives 164 Migraine, White Matter Lesions and Subarachnoid Hemorrhage: Analysis ofa Large Pedigree Nöropsikiyatri 2010; 47: 162-5 (c .G1725A; p.T575T) in exon 11, which have not been previously Discussion described in SNP database by NCBI (http://www.nlm.nih.gov1, were shown. Skin biopsy specimens from the patient and her son Migraine is a primary neurovascular headache affecting were analyzed by electron microscopy. The diagnosis of cerebral approximately 19,3% ofthe adult population (9). Cerebral WMLs autosomal dominant arteriopathy with subcortical infarcts and with unknown significance can be observed on cerebral MRI leukoencephalopathy (CADASIL) was excluded with high seans. Some clinical studies and anecdotal case reports certainty, because granular osmiophilic deposits in the capillaries, suggest that WMLs are more frequently observed in patients which are diagnostic far CADASIL, were not observed. with migraine than in the general population . However, their Deterioration in elementary attention and verbal fluency, clinical relevance and causes remain to be uncovered. Future borderline impairments of visuospatial functions were detected studies should alsa investigate, whether these WMLs are on her neuropsychological evaluation. predictors ofa subsequent cerebrovascular disease in patients Four members of the family had an additional clinical with migraine (1). The presence ot white matter faci was history of SAH as depicted in the pedigree (Figurell. Dne of significantly higher in the migraineurs with aura (40%) than in them, a 66-year-old woman (V:4), had migraine without aura far those without aura (20%) (1.10). A new meta-analysis reported farty-two years and hypertension far twenty years. She by Schürks and colleagues showed that MA is with had presented with a seizure and left hemiparesis in 2003. An a twofald increased risk of ischaemic stroke and their results aneurysm in the lateral wall of the right internal cerebral artery alsa suggested a higher risk among women who were aged (ICA) was detected by cerebral digital subtraction angiography less than 45, smokers and women who used oral contracepti- (DSA). She was operated and has left slight hemiparesis. She ves (11 ). Dur patient was aged around 45 and a smoker. has not suffered from headaches since the operation . The lschaemic cerebral vascular disease caused by vasculitis, and died far that reason at patient (V:8) had suffered from SAH antiphospholipid syndrome, CADASIL, leukoaraisosis, or MS have any history of headache. farty-two years of age. He did not should be kept in mind in the differential diagnosis ot cerebral subject (Vl:6) alsa had died when she was thirty-two The third WMLs. MS was excluded in our case by the history and years old due ta SAH. The fourth subject (Vl :7) was examined in laboratory results showing absence ot oligoclonal bands the asymptomatic period by cerebral DSA, since her sister and normal SEP and VEP studies. Furthermore, ali markers far (Vl:6) had SAH, and an aneurysm at the bifurcation of the right vasculitis and procoagulant tactors were negative, ICA was observed, far which she was operated in 2007
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