Case Reports / Journal of Clinical Neuroscience 22 (2015) 407–408 407 Vasodilatation of multiple cerebral arteries in early stage of stroke-like episode with MELAS Shoko Minobe a, Akiko Matsuda a, Tetsuya Mitsuhashi a, Motonao Ishikawa a, Yoshiko Nishimura a, Koichi Shibata a,⇑, Eiichi Ito b, Yu-ichi Goto c, Takashi Nakaoka a, Hiroshi Sakura a a Department of Internal Medicine, Tokyo Woman’s Medical University Medical Center East, 2-1-10 Nishiogu, Arakawa, Tokyo 116-8567, Japan Department of Neurology, Tokyo Woman’s Medical University, Shinjuku, Tokyo, Japan c Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan b a r t i c l e i n f o Article history: Received 16 January 2014 Accepted 4 May 2014 Keywords: CTA MELAS MRA Stroke-like episode Vasodilatation a b s t r a c t We describe a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), with multiple cerebral vasodilatations in a stroke-like episode visualised by using magnetic resonance angiography (MRA) and CT angiography (CTA). In the acute stroke-like episode stage, T2-weighted and fluid-attenuated inversion recovery MRI showed high-intensity areas in the left occipital area. In addition, MRA and CTA revealed prominent dilatation of the left posterior cerebral artery and temporal branches of the middle cerebral artery with focal hyperperfusions using CT perfusion (CTP) that corresponded to the MRI. After 10 days, with the development of aphasia, MRI indicated the lesions had spread to the temporal and parietal regions, and this distribution was not confined to major vascular territories. The patient’s symptoms gradually improved, accompanied by the attenuation of MRI, CTA, and CTP findings. These characteristic features along with the MRI changes that spread beyond vascular boundaries and the multiple cerebral vasodilatations prior to the development of clinical symptoms are not fully explained by the mitochondrial angiopathy or cytopathy theories. These findings provide further evidence supporting neuronal hyperexcitability in stroke-like episodes of MELAS. Ó 2014 Elsevier Ltd. All rights reserved. 1. Introduction Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial syndrome characterised by headaches, stroke-like episodes, and epilepsy [1]. The pathogenesis of stroke-like episodes is not fully understood [2]. Here, we report a patient with acute stage MELAS presenting with multiple cerebral artery dilatations seen on magnetic resonance angiography (MRA) and CT angiography (CTA). 2. Case report A 22-year-old woman was admitted to our hospital because she had developed a throbbing headache and a visual disturbance. Neurological examination revealed a right homonymous hemianopia and conjugate eye deviation to the right, which was considered to indicate a simple partial seizure. MRI (3.0 Tesla) on day 2 showed high-intensity areas in the left occipital region on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images (Fig. 1). On the MRA, the left posterior cerebral artery and temporal branches of the left middle cerebral artery were prominently dilated (Fig. 1). On day 3, CTA demonstrated vasodilatation that was identical to the MRA findings. CT perfusion (CTP) revealed focal hyperperfusion that corresponded with the FLAIR image (Fig. 2). An A3243G point mutation in the patient’s mitochondrial DNA was identified, confirming the diagnosis of MELAS. Electroencephalography revealed no epileptic seizure activity and the patient’s symptoms improved in the following days. On day 10, her headaches deteriorated and aphasia developed. On day 16, these symptoms reached a peak and then gradually improved after administration of vitamin B and L-arginine. MRI acquired on day 16 ⇑ Corresponding author. Tel.: +81 3 3810 1111; fax: +81 3 5855 6258. E-mail address: kshbtgm@dnh.twmu.ac.jp (K. Shibata). indicated the high-intensity areas had spread to the temporal and parietal regions on the T2-weighted (not shown) and FLAIR images (Fig. 1). At the time of discharge, on day 29, MRI, CTA, and CTP showed reduction of the dilation of the blood vessels and hyperperfusion (Fig. 1, CTA and CTP have been omitted). 3. Discussion Concerning the pathophysiology of stroke-like episodes in MELAS, three theories have been proposed: (1) ischaemic vascular mechanism (‘‘mitochondrial angiopathy’’); (2) neuronal metabolic mechanism (‘‘mitochondrial cytopathy’’); and (3) non-ischaemic neurovascular cellular mechanism (‘‘neuronal hyperexcitability’’) [2]. Our patient with stroke-like lesions was characterised as having a distribution that was not confined to major vascular territories, progressively spreading to the adjacent cortex, and hyperperfusion. There have been controversial reports regarding vascular images acquired in the early stage of stroke-like episodes including the dilatation of cortical arteries by cerebral angiography [3], partial vascular narrowing [4], vasodilatation of major arteries [2] on MRA, and no remarkable findings [5] on angiography and MRA. To our knowledge, this is the first report demonstrating vasodilatation on both CTA and higher resolution MRA images. Our patient’s initial stroke-like episode symptoms were headache, visual disturbance, and partial seizure. Vasodilatation was revealed in not only the posterior cerebral artery, but also in the temporal branches of the middle cerebral artery. The characteristic features of multiple cerebral vasodilatations prior to the development of clinical symptoms, followed by additional MRI changes that spread beyond vascular boundaries, are not fully explained by either the mitochondrial angiopathy or cytopathy theory. However, these features would be compatible with the neuronal hyperexcitability theory proposed by Iizuka et al. [2]. Neuronal hyperexcitability consists of the core element of increased capillary 408 Case Reports / Journal of Clinical Neuroscience 22 (2015) 407–408 Fig. 1. Axial MRI (3.0 Tesla) on day 2: T2-weighted (A) and fluid-attenuated inversion recovery (FLAIR; B) images revealed high signal intensity in the left occipital lesion (A, arrow) localised to the superficial layers of cortex (B, arrows), and magnetic resonance angiography (C) showed prominent dilatation of the left posterior cerebral artery (small arrows) and the left middle cerebral artery temporal branches (long tail arrow). The additional high-intensity lesions on coronal FLAIR MRI had spread to the temporal and parietal regions on day 16 (D), but were attenuated by day 29 (E). B L episodes of MELAS, cerebral vasodilatation is considered to be supporting evidence of the neuronal hyperexcitability theory. Further research on the acute stages of stroke-like episodes needs to be conducted to fully understand their pathophysiology. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References Fig. 2. Axial cerebral blood volume map on CT perfusion (CTP). On day 3, focal CTP hyperperfusion was noted in the left occipital lesions (arrows). (This figure is available in colour at http://www.sciencedirect.com.) permeability, as well as increased local cerebral blood flow, neural vulnerability, and increased neural excitability [2]. In stroke-like http://dx.doi.org/10.1016/j.jocn.2014.05.021 [1] Pavlakis SG, Phillips PC, DiMauro S, et al. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol 1984;16:481–8. [2] Iizuka T, Sakai F. Pathophysiology of stroke-like episodes in MELAS: neuronastrocyte uncoupling in neuronal hyperexcitability. Future Neurol 2010;5: 61–83. [3] Amagasaki K, Shimizu T, Suzuki Y, et al. Focal hyperperfusion in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. J Neurosurg 2001;94:133–6. [4] Yoshida T, Ouchi A, Miura D, et al. MELAS and reversible vasoconstriction of the major cerebral arteries. Intern Med 2012;52:1389–92. [5] Yeh HL, Chen YK, Chen WH, et al. Perfusion status of the stroke-like lesion at the hyperacute stage in MELAS. Brain Dev 2013;35:158–64.