Agespecific association of migraine with cryptogenic TIA and

Age-specific association of migraine with cryptogenic TIA and stroke Sammy Ming Hin Lee, MD, Ph. D Neurology Residency Journal Club 6/28/2016

Etiology of Stroke Hemorrhagic Cryptogenic Examples: Dissection Vasculitis RCVS Prothrombotic state Fibromuscular dysplasia Moyamoya Other Small vessel disease Cardioembolic Large vessel atherosclerotic disease Singer DE et al. , Chest 2004 http: //www. ncbi. nlm. nih. gov/pubmed/15383480

Cryptogenic Stroke SURPRISE RESPECT Carroll et al. , NEJM 2013 http: //www. nejm. org/doi/full/10. 1056/NEJMoa 1301440#t=abstract Homma and Sacco, Circulation 2005 http: //circ. ahajournals. org/content/112/7/1063. full Homma et al. , Circulation 2002 http: //circ. ahajournals. org/content/105/22/2625. abstract? ijkey=5 a 568 ab 3 a 5 d 40 aff 21694 f 1 ae 42 e 897 b 93 db 2863&keytype 2=tf_ipsecsha Christensen et al. , Eur J Neurol 2014 http: //www. ncbi. nlm. nih. gov/pubmed/24628954

Migrainous Stroke ICHD-3 Criteria 1) The present attack in a patient with Migraine with aura is typical of previous attacks except that one or more aura symptoms persists for >60 minutes 2) Neuroimaging demonstrates ischaemic infarction in a relevant area 3) Not attributed to another disorder International Classification of Headache Disorders, 3 rd Edition

Risk Factors? Migraine • • • Stroke Migraine with aura with OR of 2 Genetic associations: MTHFR gene Endothelial dysfunction: high CRP and low NO Coagulation abnormalities: high platelet-activating factor (p. AF), v. WF Arterial dissection Patent foreman ovale Lee et al. , J Stroke 2016 http: //www. ncbi. nlm. nih. gov/pmc/articles/PMC 4901947/

Risk Factors? Migraine Stroke Common Risk Factors • • • Migraine with aura with OR of 2 Genetic associations: MTHFR gene Endothelial dysfunction: high CRP and low NO Coagulation abnormalities: high platelet-activating factor (p. AF), v. WF Arterial dissection Patent foreman ovale Lee et al. , J Stroke 2016 http: //www. ncbi. nlm. nih. gov/pmc/articles/PMC 4901947/

Migraine Treatment as a Risk for Stroke Hall et al. , Neurology 2004 http: //www. neurology. org/content/62/4/563. abstract

Pathophysiology of Migraine Aura Cortical spreading depression is characterized by near-complete breakdown of ion gradients, near-complete sustained depolarization in individual recordings of neurons, extreme shunt of neuronal membrane resistance, loss of electrical activity. This causes spreading depression of brain electrical activity by Aristides Leão in 1944. Dreier, Nature Medicine 2011 http: //www. nature. com. proxy. library. emory. edu/nm/journal/v 17/n 4/full/nm. 2333. html

Pathophysiology of Migraine Aura Neurovascular coupling describes increased regional cerebral blood flow (r. CBF) in response to physiological neuronal activation and decreased r. CBF in response to neuronal deactivation. This is more pronounced in cortical spreading depression. Dreier, Nature Medicine 2011 http: //www. nature. com. proxy. library. emory. edu/nm/journal/v 17/n 4/full/nm. 2333. html

Pathophysiology of Migraine Aura Cortical spreading depression is associated with hypoperfusion and hypoxia as demonstrated by f. MRI and MRI perfusion studies Hadjikhaul et al. , PNAS 2001 http: //www. pnas. org/content/98/8/4687. full. pdf Forster et al. , Cephalagia 2014 http: //www. ncbi. nlm. nih. gov/pubmed/24554619

Oxfordshire, England

Famous Residents of Oxfordshire

63 PCPs from 9 Practices, 94% Caucasians

• Lifelong records including general practice and hospital records, including brain and vessel imaging, echocardiogram • Compiled consecutive cases with a first TIA or ischemic stroke from 2002 to 2012 of the OXVASC (Oxford Vascular Study)

Senior Neurologist – TOAST Criteria 1810 patients total Stroke 1, 114; TIA 696 668 (36. 9%) cryptogenic 534 (29. 5%) cardioembolic 236 (13. 0%) large artery disease 277 (15. 3%) small vessel disease 65 (3. 6%) multiple causes 30 (1. 7%) other causes 1 patient had migrainous infarct

Risk Factor: Migraine • Have you ever been diagnosed with migraine? • Have you ever had any aura (visual/sensory/speech disturbance/limb weakness) associated with the migraine? • Have you ever had any aura lasting for longer than 1 hour?

Goods

Goods • Interesting and important topic, raises awareness with the need to find etiologies for cryptogenic strokes/TIA • Homogeneous population • Found that elderly with first stroke/TIA are more likely to have migraines, suggest that migraine is an important risk factor to obtain for older stroke/TIA patients

Bads

Bads • Diagnosing patients with TIAs AND migraines is a difficult task • Migraine is classified by patient report of previous diagnosis • Lack of generalizability • Not establishing cause and effect • What are we going to do about this? Does treating migraine help with preventing strokes?