Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 1 (2014) 81–83

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Case Reports & Case Series Headache and focal neurologic signs following exposure to spicy aroma as an initial presentation of moyamoya disease☆,☆☆

Bilal A. Siddiqui, A.B. a, Vikram Jairam, B.S. a, Michele H. Johnson, M.D. b, David M. Greer, M.D., M.A., F.C.C.M., F.A.H.A. a,⁎

a Department of Neurology, Yale School of Medicine, New Haven, CT b Department of Diagnostic Radiology, Yale School of Medicine, New Haven, CT

article info abstract

Article history: Moyamoya disease is a condition of the cerebrovascular system that involves stenosis of the intracranial Received 22 June 2014 internal carotid arteries as well as their proximal branches, often leading to stroke in affected patients. Here Revised 3 July 2014 we describe the case of a patient with headache and focal neurologic signs following exposure to a spicy Accepted 6 July 2014 aroma, who initially had a negative vascular work-up and a preliminary diagnosis of a complex migraine syndrome. She subsequently developed infarction of the left frontal lobe, and imaging studies revealed the Keywords: diagnosis of moyamoya disease. She was treated with an encephalodurosynangiosis procedure, with notable Moyamoya disease Angiography improvement. This case highlights the importance of considering moyamoya disease in the differential Headache diagnosis of patients presenting with headaches with aura. Magnetic resonance imaging © 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license Stroke (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Introduction lism or vasospasm may lead to ischemic presentations. The molecular mechanisms include up-regulation of angiogenic factors and extra- Moyamoya disease is a condition of the cerebrovascular system cellular matrix metalloproteinases [1]. A genome-wide association that involves stenosis of the intracranial internal carotid arteries (ICA) study in 2012 identified RNF213, a gene encoding a specialized zinc- as well as their proximal branches, often leading to stroke in affected finger protein, as a possible predictive DNA biomarker for severe patients [1]. These narrowed vessels in turn are thought to trigger the forms of moyamoya [5]. growth of a network of collateral vessels from dilated perforating Common presentations include headaches, ischemic stroke, leptomeningeal arteries, visible on angiography [2], leading to the transient ischemic attack, or intracerebral hemorrhage, and infre- disease’s evocative name. In 1969, Suzuki and Takaku described quently, seizures, choreiform movements or cognitive changes [1]. moyamoya as “a Japanese expression for something hazy just like a Moyamoya may also be secondary to other causes, including radiation puff of cigarette smoke drifting in the air [3].” The major imaging therapy to the parasellar region, sickle cell disease, neurofibromatosis features suggestive of moyamoya disease include stenoses in the type 1, and trisomy 21 has also been reported in association with distal ICA and proximal middle cerebral (MCA) and anterior cerebral hyperthyroidism, and renal artery stenosis [1]. arteries (ACA), in addition to increased vascularity in the basal ganglia and thalamus from the collateral vessels [4].Itspredominant histologic features include smooth muscle cell proliferation in intimal Case report layers of vessels, without atheromatous plaques [1]. Thromboembo- A 50-year-old female accountant with hypertension, diabetes mellitus, and hyperlipidemia presented to an outside neurologist with multiple transient episodes of speech disturbance and right-sided ☆ Author Contributions: All of the authors have made substantial contributions to weakness over five months. With each spell, the symptoms came on fi this manuscript and provided their nal approval. Mr. Siddiqui, Mr. Jairam, and gradually and were followed by a holocephalic headache 45 minutes Dr. Greer contributed to the literature review, wrote the article, and critically revised it. Dr. Johnson contributed images and their interpretation to this paper. later. Two spells occurred shortly after the patient smelled a spicy ☆☆ Disclosures. Mr. Siddiqui reports no disclosures. Mr. Jairam reports no disclosures. aroma from her husband’s cooking. She underwent work-up for Dr. Johnson reports no disclosures. Dr. Greer reports no disclosures. transient ischemic attack (TIA) at an outside facility, which included ⁎ Corresponding author at: 15 York St., LCI 912A, New Haven, CT 06510. Tel.: +1 203 head computed tomographic (CT) and magnetic resonance imaging 785 5947. (MRI), cardiac rhythm monitoring, transthoracic and then trans- E-mail addresses: [email protected] (B.A. Siddiqui), [email protected] (V. Jairam), [email protected] (M.H. Johnson), [email protected] esophageal echocardiography, as well as carotid ultrasound. These (D.M. Greer). studies were all normal. She was started on topiramate by her http://dx.doi.org/10.1016/j.inat.2014.07.001 2214-7519/© 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). 82 B.A. Siddiqui et al. / Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 1 (2014) 81–83 neurologist for possible migraine triggered by odor [6]. She had no prior history of migraine. She was given aspirin in addition to her amlodipine, atorvastatin, lisinopril, metformin, and vilazodone. She had no family history of stroke, did not use tobacco or illicit drugs, and occasionally consumed alcohol. Three days prior to being seen at this center, she then experienced motor aphasia, weakness and numbness of the right face and right arm, and headache not associated with external triggers. The event lasted less than one hour. She then experienced two days of progressive difficulties with speech expression, math, and typing. On examination, she was alert Fig. 2. Magnetic resonance angiogram demonstrating stenoses of the internal carotid and oriented to year but not place. She was cooperative, but had halting, and middle cerebral arteries. non-fluent speech. She followed cross-body commands and repeated phrases without difficulty. Her naming was intact for high- but not low- frequency objects. Her visual fields and extraocular movements were appearance of the collateral vessels at the base of the brain in intact without nystagmus. She had slight flattening of the right nasolabial moyamoya (Fig. 3). fold. Rapid finger tapping, pronator drift testing, and finger-nose-finger testing were all normal. Discussion A repeat MRI demonstrated interval infarction in the left frontal lobe (Fig. 1). Aspirin was changed to aspirin plus extended-release Thekeyclinicalfeatureisthepresenceofastrokedespitenormal dipyridamole for secondary stroke prevention [7], and she partially cervical carotid imaging and cardiac monitoring, which is suggestive of improved. Magnetic resonance angiography was performed, demon- intracranial stenotic disease. The differential diagnosis is broad including strating stenoses of the internal carotid and middle cerebral arteries, intracranial atheromatous disease, vasculitides (including CADASIL), worse on the left side, raising suspicion for moyamoya disease (Fig. 2). moyamoya disease, fibromuscular dysplasia, and, less likely in this patient, The patient demonstrated enhancement on vessel wall imaging, phakomatoses and infections (e.g. tuberculosis, syphilis). Normal inflam- concerning for a cerebral angiitis. However, both erythrocyte matory markers, autoimmune antibodies and cerebrospinal fluid (CSF) sedimentation rate and C-reactive protein level were only mildly analysis may help eliminate these other causes, as described in her work- elevated. Anti-nuclear antibody titer was negative, with a negative up above. Until our patient developed a confirmed infarction, the presence extractable nuclear antigen panel. Rheumatoid factor was negative. of focal neurologic signs in the setting of headache was suggestive of a IgM and IgG antibody titers for Lyme disease were negative. CSF complex migraine syndrome, such as hemiplegic migraine. Indeed, revealed normal cell counts, protein and glucose, and was negative for headache has been reported as a presenting symptom of moyamoya angiotensin converting enzyme, varicella zoster, West Nile and disease and persists in up to 63% of patients following surgical Epstein-Barr viruses, and syphilis. The possibility of an isolated revascularization [9]. Case reports in the literature have described cerebral angiitis affecting small- and medium-sized vessels was migraines with aura in association with moyamoya disease – in one, therefore unlikely [8]. Conventional catheter-based angiography migraine was preceded by photopsia, followed by infarction of the left was then performed on the patient, which revealed the characteristic occipital lobe [10]. It was postulated that borderline perfusion of the stenosis of the ICAs intracranially and the classic “puff of smoke” occipital lobe contributed to the visual auras in that case [10].Giventhe distribution of the infarction in our patient, a similar mechanism may have been in effect. Treatment options for moyamoya center around increasing blood flow to the affected areas and reducing ischemia. Antiplatelet therapy is considered in asymptomatic patients or high-risk surgical candidates. Calcium channel blockers may help headaches. However, few studies report long-term benefit from medical management of moyamoya [1].In

Fig. 1. Fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging scan demonstrating interval infarction in the left frontal lobe. Fig. 3. Left internal carotid angiogram demonstrating classic “puff of smoke” collateral vessels. B.A. Siddiqui et al. / Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 1 (2014) 81–83 83 fact, a retrospective review revealed that 38% of 651 medically-treated after her surgery–her right side is completely improved, and her moyamoya patients later required surgical treatment [6]. aphasia has recovered with speech therapy. She has had no headaches Surgical revascularization is the definitive treatment method for or new neurological symptoms, and she will continue to be followed both children and adults. Indirect revascularization involves place- clinically. As of this writing, she has remained symptom-free for six ment of vascularized tissue in direct contact with the brain by creating months after her surgery. burr holes, encouraging neovascularization in the cerebral cortex [1]. This technique is used when the recipient cortical artery is unavailable Acknowledgments for anastomosis, as in children with small vessels. Another indirect revascularization technique, encephaloduroarteriosynangiosis, is usu- We thank our patient for providing her permission to share this case. ally the first step in surgical management; here, a scalp artery is sutured directly to a distal MCA branch. Another option is encepha- References lomyosynangiosis, in which a flap of muscle is laid on the cortical surface. Direct revascularization involves end-to-side anastomosis of [1] Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med the superficial temporal artery (STA) to middle cerebral artery (MCA). 2009;360(12):1226–37. [2] Achrol AS, Guzman R, Lee M, Steinberg GK. Pathophysiology and genetic factors in Overall, outcomes for surgical revascularization treatments are good, moyamoya disease. Neurosurg Focus 2009;26(4):1–6. with no significant difference between direct and indirect procedures. [3] Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing The stroke risk is highest in the first 30 days, after which 96% of abnormal net-like vessels in base of brain. Arch Neurol 1969;20(3):288–99. [4] Yamada I, Matsushima Y, Suzuki S. Moyamoya disease: diagnosis with three- patients remain stroke-free after 5 years [1]. dimensional time-of-flight MR angiography. Radiology 1992;184(3):773–8. [5] Miyatake S, Miyake N, Touho H, Nishimura-Tadaki A, Kondo Y, Okada I, et al. Conclusion Homozygous c.14576G N A variant of RNF213 predicts early-onset and severe form of moyamoya disease. Neurology 2012;78(11):803–10. [6] Fernandes PM, Whiteley WN, Hart SR, Al-Shahi Salman R. Strokes: mimics and This case illustrates a remarkable presentation of moyamoya chameleons. Pract Neurol 2013;13(1):21–8. disease, in which headache and focal neurologic signs associated with [7] Verro P, Gorelick PB, Nguyen D. Aspirin plus dipyridamole versus aspirin for a spicy aroma, coupled with normal carotid imaging and cardiac prevention of vascular events after stroke or TIA: a meta-analysis. Stroke 2008;39 (4):1358–63. monitoring despite vascular risk factors made intracranial athero- [8] Berlit P. Review: diagnosis and treatment of cerebral vasculitis. Ther Adv Neurol sclerotic disease unlikely and initially led to the diagnosis of a Disord 2010;3(1):29–42. complex migraine syndrome. [9] Zach V, Bezov D, Lipton RB, Ashina S. Headache associated with moyamoya disease: a case story and literature review. J Headache Pain 2010;11(1):79–82. In the case of our patient, she underwent an encephalodurosy- [10] Park-Matsumoto YC, Tazawa T, Shimizu J. Migraine with aura-like headache nangiosis procedure, which she tolerated well. She has done very well associated with moyamoya disease. Acta Neurol Scand 1999;100(2):119–21.