Moyamoya disease (MMD) is a rare vasculopathy characterized by bilateral stenosis of the distal internal carotid arteries and the proximal vessels of the circle of Willis, accompanied by collateral circulation pathways.1 These vascular changes can lead to stroke, transient ischemic attack, and seizures due to impaired cerebral function. The condition is reported primarily in children aged 5 to 9 years and in adults, with the highest incidence observed in Asian populations.

We present a unique case of MMD manifested by focal seizures during the acute phase of brain ischemia in a child with a notable genotype.

The patient was a girl who was born after an uneventful pregnancy and had a normal neonatal period. She had achieved all her developmental milestones. The patient’s family history regarding vascular diseases, congenital defects, and genetic disorders was negative. At the age of 11 months, she experienced prolonged right-sided focal seizures, followed by right-sided hemiplegia and convergent strabismus of the left eye due to infarct in the left hemisphere. Computed tomography of the head showed hyperdense bands in the cerebral sulci of both hemispheres and in the region of the subcortical nuclei, as well as a fluid cavity in ​​the left lateral ventricle. Magnetic resonance imaging and magnetic resonance angiography of the head identified multifocal ischemic lesions in the left hemisphere, bilateral stenosis of the terminal branches of the middle cerebral arteries, along with stenosis of the internal carotid arteries and its branches (Figure 1A and 1B). Based on the imaging results, MMD was suspected.1,2

Figure 1. A – T1-weighted contrast-enhanced magnetic resonance imaging scan demonstrating subacute ischemia in the left middle cerebral artery territory with an “ivy sign” (arrow); B – magnetic resonance angiography showing multiple areas of vessel narrowing (arrows)

Laboratory test results showed markedly elevated liver enzymes: alanine transaminase (2239 U/l; reference range [RR], 10–35 U/l) and aspartate transaminase (758 U/l; RR, 10–60 U/l). Abdominal ultrasound demonstrated hepatomegaly with a homogeneously increased echogenic pattern and evidence of steatosis. Metabolic, infectious, hematologic, gastroenterological, and structural causes of abnormal liver function were excluded. Due to persistently abnormal liver function test results (significantly elevated levels of alanine transaminase and aspartate transaminase) and the liver-related adverse effects of acetylsalicylic acid, aspirin was not administered. Whole-exome sequencing identified a de novo RNF213 mutation: c.12341C>T p.(Thr4114Ile).

At 16 months of age, the patient experienced second stroke with rapid clinical recovery. Follow-up brain imaging confirmed vessel narrowing and collateral formation characteristic of MMD.3

In the acute stage, the treatment included neurorehabilitation, steroid therapy, and low-molecular-weight heparin at a prophylactic dose, resulting in an almost complete resolution of the right-sided paresis. Convergent strabismus of the left eye persisted. After discharge, aminotransferase levels were monitored and gradually normalized. Currently, mild right-sided hemiparesis, convergent strabismus, and delayed speech development are observed, although the patient is able to walk independently. Due to the high probability of recurrent ischemic stroke, secondary prophylaxis with acetylsalicylic acid was initiated, and the patient continues rehabilitation.3,4 Considering her good clinical condition, interventional treatment was deemed unnecessary.

MMD is an uncommon cause of seizures and stroke in children. Rare genetic variants can contribute to early-onset and recurrent ischemic attacks secondary to cerebral hypoperfusion, and are often associated with a poor prognosis. The c.12341C>T p.(Thr4114lle) variant of the RNF213 gene is associated with early-onset MMD type 2. Neurological symptoms may be accompanied by liver injury, and similar cases have been reported in the literature.5