Arterioectatic Spinal Angiopathy of Childhood: Clinical, Imaging, Laboratory, Histologic, and Genetic Description of a Novel CNS Vascular Pathology

Abstract

Pediatric patients with myelopathy expressing intradural spinal vascular ectasia without arteriovenous shunting were studied at four tertiary referral neuropediatric centers. Patients were identified by retrospective review of institutional records and excluded if spinal vascular pathology could be classified into a previously described category of spinal vascular malformation. Four patients meeting the study criteria were enrolled in the study. Clinical, magnetic resonance imaging, catheter-directed angiography, laboratory, histological and genetic data were analyzed to characterize the disease process and elucidate underlying pathomechanisms. Our study revealed a highly lethal, progressive multi-segmental myelopathy associated with a unique form of non-inflammatory spinal angiopathy featuring diffuse enlargement and tortuosity of spinal cord arteries, spinal cord hyperemia, and spinal cord edema (Arterioectatic Spinal Angiopathy of Childhood). The condition was shown to mimic venous congestive myelopathy associated with pediatric spinal cord arteriovenous shunts on MRI but to have distinct pathognomonic findings on catheter-directed angiography. Clinicopathological, genetic, and neuroimaging features, which are described in detail, closely overlap with those of mitochondrial disease. ABBREVIATIONS: AESA ¼ arterioectatic spinal angiopathy; AV ¼ arteriovenous; CPA ¼ cerebral proliferative angiopathy; RMA ¼ radiculomedullary artery; WES ¼ whole exome sequencing S pinal cord arteriovenous (AV) shunts, including AV malformations (AVM) and AV fistulae (AVF) are a rare but treatable cause of myelopathy. [1][2][3][4] Marked ectasia of the spinal cord vasculature on MR imaging is traditionally considered pathognomonic. In children with spinal cord AV shunts, subarachnoid hemorrhage is the clinical presentation in two-thirds, while venous congestive myelopathy is the presentation in one-third. 1,2 Notably, venous congestive myelopathy due to a spinal cord AV shunt is more common in children younger than 2 years of age and features cord edema that spares the cord periphery. 3 A definitive diagnosis relies on demonstration of an AV shunt by catheter-directed DSA. Children with venous congestive myelopathy due to a spinal cord AV shunt most often present with progressive episodic neurologic decline, culminating in complete loss of spinal cord function within months to years. [1][2][3][4] If the diagnosis is established early, treatment of the underlying AV shunt by embolization or microsurgical ligation leads to neurologic stabilization with varying degrees of functional recovery. 1,5 Recognized forms of spinal cord vascular malformations include AV shunt lesions and nonshunting lesions. While multiple classification systems have been proposed, none account for spinal cord vascular ectasia in the absence of an AV shunt. 6 The authors of this report have encountered pediatric patients with myelopathy presenting with striking enlargement of the spinal cord vasculature and vasogenic edema of the central spinal cord in the abse...