Childhood Cerebral Vasculitis : A Multidisciplinary Approach

Abstract

Cerebral vasculitis is increasingly recognized as a common cause of pediatric arterial stroke. It can present with focal neurological deficits, psychiatric manifestations, seizures, and encephalopathy. The etiopathogenesis of childhood cerebral vasculitis (CCV) is multifactorial, making an inclusive classification challenging. In this review, we describe the common and uncommon CCV with a comprehensive discussion of etiopathogenesis, the role of various imaging modalities, and advanced techniques in diagnosing CCV. We also highlight the implications of relevant clinical, laboratory, and genetic findings to reach the final diagnosis. Based on the clinicoradiological findings, a stepwise diagnostic approach is proposed to facilitate CCV diagnosis and rule out potential mimics. Identification of key clinical manifestations, pertinent blood and cerebrospinal fluid results, and evaluation of central nervous system vessels for common and disease-specific findings will be emphasized. We discuss the role of magnetic resonance imaging, MR angiography, and vessel wall imaging as the imaging investigation of choice, and reservation of catheter angiography as a problem-solving tool. We emphasize the utility of brain and leptomeningeal biopsy for diagnosis and exclusion of imitators and masqueraders.

Keywords: COL-gene related disorder; Non-inflammatory vasculopathy; Primary angiitis of CNS; Systemic vasculitis; TGF β-signaling pathway.

Fig. 1

Diagnostic algorithm for the evaluation of suspected Childhood Cerebral Vasculitis. CSF cerebrospinal fluid, vWF von Willebrand factor, MRI magnetic resonance imaging, MRA magnetic resonance angiography, VWI vessel wall imaging, CNS central nervous system, cPACNS childhood primary angiitis of the central nervous system

Fig. 2

APP-cPACNS in a 10-year-old boy presented with recurrent stroke. Axial DWI (a) image shows multifocal right frontoparietal border-zone infarcts (arrows). MRA (b) shows diffuse narrowing of the right distal internal carotid artery (ICA), middle cerebral artery (MCA), and anterior cerebral artery (ACA) (arrows). Previous MRI, 4 years ago reveals left periventricular (arrow) white matter infarct on DWI (c) and occlusion of A1 segment of left ACA (dashed arrow in b)

Fig. 3

AN-cPACNS in a 16-year-old girl presented with left-sided clumsiness. Axial DWI image (a) shows multiple tiny acute infarcts of bilateral subcortical white matter (arrows) with normal course and caliber of the intracranial arteries on MRA (b) favoring the diagnosis of small vessel vasculitis

Fig. 4

a 11-year-old girl with group A streptococcal meningitis. TOF-MRA reveals attenuation of bilateral MCA, right (arrows) more than left. Enhancing basal exudates and leptomeningeal enhancement are also noted in postcontrast T1W image (inset image). b,c 6-year-old boy with left hemiparesis and history of varicella. Axial DWI image (b) shows acute infarction of the right posterior gangliocapsular region (arrow in b) with narrowing and irregularity of the distal most intracranial segment of the right ICA and origin of right ACA (dashed oval in c) in keeping with post-varicella focal cerebral arteriopathy

Fig. 5

4‑year-old male with ADA2 mutation. Axial DWI image (a) reveals acute infarct of the posterior limb of left internal capsule (arrow). Axial VWI image (b) shows wall thickening and enhancement (arrows) of the intracranial vessels. Contrast MRA (c) shows a small saccular aneurysm of the left anterior choroidal artery with a filling defect from thrombus (arrow) that was not appreciated on the TOF-MRA (not shown). MRA of the abdominal vessels revealed multiple aneurysms of the gastric, renal, and splenic arteries (not shown) in keeping with PAN

Fig. 6

a,b 8-year-old boy, ANCA-positive glomerulonephritis with headache and seizures. Axial FLAIR image (a) shows multiple bilateral subcortical and deep white matter hyperintensities, few involving the cortex (arrows) with restricted diffusion on DWI (not shown). TOF-MRA (b) depicts mild irregularity of bilateral ACA, most prominently involving the A1 segment of right ACA (arrow). c 11-year-old boy, known Behçet disease presented with right trochlear nerve palsy and anterior uveitis. Axial FLAIR image shows mildly expansile hyperintense lesion of the midbrain, centered over left inferior colliculus (arrow) suggestive of neuroBehçet

Fig. 7

14-year-old female with SLE, recent onset behavioral changes and positive APLA titer. TOF-MRA (a) demonstrates mild irregularity of intracranial arteries especially the M1 segments of the bilateral MCA (arrows) with poor visualization of peripheral arteries and normal brain parenchyma (not shown), similar to previous MRI. TOF-MRV (b) and post-gd T1W (c) images show interval development of the narrowing of right internal jugular vein (IJV), starting from the junction of IJV & sigmoid sinus (arrows) with non-visualization at the level of C1–C2 (arrow) compared to normal IJV on left side (dashed arrow) in keeping with clinical diagnosis of APLA syndrome

Fig. 8

9‑year-old girl with Sjögren syndrome and anti-Ro positive, presents with vomiting and gait disturbance. Axial FLAIR images show multiple cortical-subcortical white matter hyperintensities involving bilateral cerebral (arrows in a), brainstem, and cerebellar hemispheres (arrows in b). Imaging of the spine demonstrated similar changes in the distal cord and conus (not shown)

Fig. 9

18-year-old cocaine abuser with severe headache and facial weakness. Axial DWI image (a) shows right peri-insular cortical and subcortical infarct. CTA (b) correlation shows paucity of the vessels in the territory of inferior division of MCA (dashed oval)

Fig. 10

25-year-old girl, treated brainstem glioma (post-chemoradiation) in childhood. Axial T2W image (a) shows bilateral prominent folia and cerebellar volume loss. MRA (b) reveals multifocal stenosis of the basilar artery (arrows) in keeping with radiation vasculopathy

Fig. 11

13-year-old boy with ACTA2 mutation. Axial T1W image (a) shows V‑shaped anterior corpus callosum (dashed line) and thickened fornix (arrow). Axial T2W image (b) shows twin peaks sign from impression of the stretched basilar artery (dashed oval). TOF-MRA (c) depicts fusiform dilatation of the bilateral proximal ICAs (arrows), with tapering of terminal segments. Bilateral ACA, MCA, PCA, and their branches appear attenuated and stretched

Fig. 12

a Moyamoya syndrome in an 11-year-old boy with sickle cell disease. TOF-MRA shows marked narrowing and beaded appearance of the bilateral MCA with asymmetric narrowing of the supraclinoid ICA, right $\gg$ left (arrows) and multiple tiny basal collaterals (dashed oval). b Idiopathic Moyamoya disease in 10-year-old boy presented with progressive right-sided weakness. TOF-MRA reveals narrowing and irregularity of the supraclinoid portion of both ICA. The origin of bilateral MCA (arrows) and ACA are not well seen (R > L) and are replaced by a network of tiny tortuous collaterals (dashed oval). Left PCA also appears attenuated (dashed arrow) with prominent and tortuous posterior communicating arteries

Fig. 13

14-year-old with Marfan syndrome and headache, to rule out intracranial aneurysms. TOF-MRA (a) reveals marked tortuosity of the bilateral ICA with no definite intracranial aneurysms noted. Axial FLAIR image (b) shows associated focal infarction of posterior limb of left internal capsule and left thalamus (arrow)