Carotid dissection in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare, genetic etiology of stroke in young individuals. The most commonly associated genetic mutation is an adenine to guanine transition at nucleotide 3243 in the mitochondrial genome [1]. The pathogenesis of stroke-like episodes is not fully understood, but is believed to be due to mitochondrial angiopathy, metabolic defects, or neuronal hyperexcitability [2]. Mitochondrial angiopathy has largely been attributed to small vessel disease. In this report, we describe a patient with MELAS who presented with multiple strokes and was also found to have bilateral pseudoaneurysm formation of the internal carotid arteries with accompanying dissection. A 47-year-old female originally presented to an outside hospital with a two day history of word finding difficulties, headache, and right upper extremity weakness. Imaging confirmed a left middle cerebral artery (MCA) stroke. Her past medical history is significant for an episode of eclampsia complicated by bilateral visual and hearing loss. Her vision gradually improved but her hearing loss became progressively worse with time. Her family medical history includes adult onset hearing loss and diabetes in her mother. Initial stroke evaluation included magnetic resonance angiography (MRA) of the head and neck that demonstrated minimal atherosclerotic changes in the left middle cerebral artery with otherwise normal vessels, a normal transesophageal echocardiogram, and a normal cerebrospinal fluid profile. She had mildly elevated cholesterol and heterozygous inheritance of the prothrombin gene mutation. She initially recovered partially, but one week later, she had progressive decline in her mental status and subsequently decreased oral intake, prompting transfer to our facility for further evaluation. At presentation, she was found to be encephalopathic with infrequent, non-sensical speech. Initial labs were significant for a bicarbonate of 19 mmol/L with an anion gap of 13 mmol/L, hemoglobin A1c of 6.1%, and normal serum lactate (Table 1). A head CT showed bilateral basal ganglia and thalamic calcifications in addition to her stroke, and an EEG revealed bilateral slowing. Her vessels were re-examined with a CT angiogram of the head and neck that revealed a right internal carotid artery dissection with pseudoaneurysm and evidence of chronic dissection on the left carotid artery (Fig. 1a). The outside hospital MRA was reviewed and did not reveal any dissections. A lumbar puncture was performed and revealed an elevated lactic acid of 5.4 mmol/L. Repeat MRI/MRA with spectroscopy revealed a normal lactate peak and extension of the left MCA stroke involving the full MCA territory, new left PCA stroke, and a new right hemisphere infarct consistent with a right embolic phenomenon, possibly to the anterior choroidal artery, or an atypical lipohyalinosis of the lenticulostriates from the right MCA (Fig. 1b). A muscle biopsy was performed showing ragged red fibers. MELAS genetic testing was ordered and was positive for the mtA3243G mitochondrial mutation. In the setting of bilateral carotid dissections, genetic test for Ehlers–Danlos Syndrome Type IV was also ordered and was negative. No history of head or neck trauma was elicited. CT angiogram of the chest, abdomen and pelvis did not reveal any other R. C. C. Ryther Department of Child Neurology, Massachusetts General Hospital for Children, Harvard Medical School, Boston, MA, USA