AANP

1. AANP 2010-7 Robert Corliss, MD, Shahriar Salamat, MD PhD, Sara Zydowicz, DO

2. 2010-7 • History • A 3 1/2 old previously healthy girl had a sudden episode of unresponsiveness witnessed by her mother. Imaging studies of the still unresponsive child revealed severe, bilateral pulmonary edema (flash edema) and diffuse anoxic brain injury. Aggressive resuscitative efforts were unsuccessful and she was pronounced dead. • External exam was unremarkable. Internal examination of the head revealed diffuse, acute basilar subarachnoid blood originating from a collapsed 2 cm irregular aneurysm along the length of the basilar artery closer to the point of anastamosis with the vertebral artery. Additionally, multiple calcified subpleural, parenchymal and hilar pulmonary granulomas were found.

5. H&E 10x

6. Diagnosis?Discussion

8. Special Stains and immunohistochemical studies and EM • Pulmonary • Multinucleated giant cells and lymphocytes • Fungal organisms consistent with Histoplasma species • Aneurysm • No evidence of fungal organisms via special stains and immunohistochemical studies • No microorganisms via EM

9. Differential diagnosis of granulomatous inflammation and aneurysm in medium sized muscular arteries • Takayasu’s arteritis • Kawasaki disease • Varicella-zoster virus (VSV) • Isolated angiitis of the CNS • Polyarteritis nodosa • Churg-Strauss syndrome • Wegener’s granulomatosis • SLE • Sjogren’s syndrome • Rheumatoid arthritis • Bechet’s disease • Neurosarcoidosis • Various infections

10. Diagnosis: • Rupture of vertebrobasilar artery aneurysm due to isolated intracranial giant cell arteritis

11. 2010-7 • Intracranial aneurysms in the pediatric population • Rare during the first few years of life • Usually symptomatic • Usually involves • Carotid artery • Anterior communicating artery • Vertebrobasilar system • Case reports describe loss of tunica media and absent or discontinuous internal elastic media

12. Innate and adaptive immune responses lead to vascular damage in GCA Injury of the vascular wall is the result of the cumulative effect of a cascade of immune events Early ‘danger’ signals trigger artery intrinsic dendritic cells (DC) Adaptive immune system is induced with resultant granulomatous infiltrates Vascular wall responds with maladaptive remodeling endangering dependent organs Vascular DC dictate the arrangement and composition of T-cell responses in the arterial wall Triggering of the DC by various TLR ligands leading to vessel wall inflammation TLR4 ligands induce release of CCL20 with subsequent recruitment of CCR6+ T-cells and establishment of wall-penetrating inflammation TRL5 agonists facilitate recruitment of T-cells with clustering in the adventitia Immune cells and vessel wall cells collaborate in mediating vascular damage in GCA Pathogenesis of Giant Cell Arteritis (GCA)

13. REFERENCES • Piggot, K. et al Vascular damage in giant cell artertitis. Autoimmunity, October 2009; 42(7): 596-604 • Lasjaunias, P. et al Intracraninal aneurysms in children aged under 15 years: review of 59 consecutive children with 75 aneurysms. Childs Nervous system (2005) 21: 437-350 • Love, S. et al Ruptured vertebrobasilar aneurysm associated with giant cell arteritis in a young boy. Clinical Neurology and Neurosurgery 110 (2008) 92-96 • Salvarani, C. et al Giant Cell Arteritis: Involvement of Intracranial Arteries Arthritis & Rheumatism Vol. 55, No. 6, December 2006, pp 985-989

14. During the DSS discussion, testing for possible viral etiologies was recommended. Both the aneurysm and selected CNS samples were probed for varicella zoster virus (immunohistochemically & by tissue PCR), as well as herpes simpex virus, Epstein-Barr virus, and cytomegalovirus (tissue PCR). All viral studies were negative.