094 Novel NOTCH1 variant in a patient with spontaneous internal carotid artery dissection

Introduction We report a case of spontaneous left internal carotid artery (ICA) dissection associated with a novel NOTCH1 variant. Case A 43-year-old lady presented with a 3-day history of severe headache and transient expressive dysphasia. There was no history of preceding trauma. CT brain (CTB) and carotid angiography (CTA) demonstrated small areas of established subcortical infarction with occlusion of the M1-segment of the left middle cerebral artery (LMCA). CT cerebral perfusion (CTP) displayed a region of increased mean transit time and cerebral blood volume consistent with a large ischaemic penumbra. Digital subtraction angiography confirmed an occlusion of the LMCA with luminal irregularity of the supraclinoid ICA suggestive of arterial dissection. An intracranial stent was deployed from the superior M2-division of the LMCA to the cavernous ICA. Progress CTA and CTP demonstrated reperfusion of the LMCA territory. Six-months later, she remains well with no recurrence of symptoms or detectable neurological signs. Targeted gene panel demonstrated a novel heterozygous missense variant (c.56C>T;p.Ala19Val) in exon-1 of the NOTCH1 gene. Segregation testing demonstrated an identical variant in her mother. Conclusion Spontaneous intracranial ICA dissection is a rare condition described mostly in single case reports. Mortality rates have been reported of up to 75%. The NOTCH-signalling pathway is involved in the embryonic development of arterial endothelium. NOTCH1 variants have been associated with autosomal dominant bicuspid aortic valve aortopathy, and rarely in extracranial arterial dissection. To our knowledge; this is the first reported case of intracranial dissection where a previously undescribed NOTCH1 variant is identified.