AANPAANP

2010-72010-7

Robert Corliss, MD, Shahriar Robert Corliss, MD, Shahriar Salamat, MD PhD, Sara Zydowicz, Salamat, MD PhD, Sara Zydowicz,

DODO

2010-72010-7

HistoryHistory A 3 1/2 old previously healthy girl had a sudden episode A 3 1/2 old previously healthy girl had a sudden episode

of unresponsiveness witnessed by her mother. Imaging of unresponsiveness witnessed by her mother. Imaging studies of the still unresponsive child revealed severe, studies of the still unresponsive child revealed severe, bilateral pulmonary edema (flash edema) and diffuse bilateral pulmonary edema (flash edema) and diffuse anoxic brain injury. Aggressive resuscitative efforts anoxic brain injury. Aggressive resuscitative efforts were unsuccessful and she was pronounced dead.were unsuccessful and she was pronounced dead.

External exam was unremarkable. Internal examination External exam was unremarkable. Internal examination of the head revealed diffuse, acute basilar subarachnoid of the head revealed diffuse, acute basilar subarachnoid blood originating from a collapsed 2 cm irregular blood originating from a collapsed 2 cm irregular aneurysm along the length of the basilar artery closer to aneurysm along the length of the basilar artery closer to the point of anastamosis with the vertebral artery. the point of anastamosis with the vertebral artery. Additionally, multiple calcified subpleural, parenchymal Additionally, multiple calcified subpleural, parenchymal and hilar pulmonary granulomas were found. and hilar pulmonary granulomas were found.

H&E

10x

Diagnosis?Diagnosis?DiscussionDiscussion

Special Stains and immunohistochemical Special Stains and immunohistochemical studies and EMstudies and EM Pulmonary Pulmonary

Multinucleated giant cells and Multinucleated giant cells and lymphocyteslymphocytes

Fungal organisms consistent with Fungal organisms consistent with HistoplasmaHistoplasma species species

AneurysmAneurysm No evidence of fungal organisms via No evidence of fungal organisms via

special stains and special stains and immunohistochemical studiesimmunohistochemical studies

No microorganisms via EMNo microorganisms via EM

Differential diagnosis of granulomatous Differential diagnosis of granulomatous inflammation and aneurysm in medium inflammation and aneurysm in medium sized muscular arteriessized muscular arteries Takayasu’s arteritisTakayasu’s arteritis Kawasaki diseaseKawasaki disease Varicella-zoster virus (VSV)Varicella-zoster virus (VSV) Isolated angiitis of the CNSIsolated angiitis of the CNS Polyarteritis nodosaPolyarteritis nodosa Churg-Strauss syndromeChurg-Strauss syndrome Wegener’s granulomatosisWegener’s granulomatosis SLESLE Sjogren’s syndromeSjogren’s syndrome Rheumatoid arthritisRheumatoid arthritis Bechet’s diseaseBechet’s disease NeurosarcoidosisNeurosarcoidosis Various infectionsVarious infections

Diagnosis:Diagnosis: Rupture of vertebrobasilar artery Rupture of vertebrobasilar artery

aneurysm due to isolated intracranial aneurysm due to isolated intracranial giant cell arteritisgiant cell arteritis

2010-72010-7

Intracranial aneurysms in the pediatric Intracranial aneurysms in the pediatric populationpopulation Rare during the first few years of lifeRare during the first few years of life Usually symptomaticUsually symptomatic Usually involvesUsually involves

Carotid arteryCarotid artery Anterior communicating arteryAnterior communicating artery Vertebrobasilar systemVertebrobasilar system

Case reports describe loss of tunica media and Case reports describe loss of tunica media and absent or discontinuous internal elastic mediaabsent or discontinuous internal elastic media

Pathogenesis of Giant Cell Arteritis Pathogenesis of Giant Cell Arteritis (GCA)(GCA)

Innate and adaptive immune Innate and adaptive immune responses lead to vascular damage in responses lead to vascular damage in GCAGCA

Injury of the vascular wall is the result Injury of the vascular wall is the result of the cumulative effect of a cascade of the cumulative effect of a cascade of immune eventsof immune events

Early ‘danger’ signals trigger artery Early ‘danger’ signals trigger artery intrinsic dendritic cells (DC)intrinsic dendritic cells (DC)

Adaptive immune system is induced Adaptive immune system is induced with resultant granulomatous with resultant granulomatous infiltratesinfiltrates

Vascular wall responds with Vascular wall responds with maladaptive remodeling endangering maladaptive remodeling endangering dependent organsdependent organs

Vascular DC dictate the arrangement Vascular DC dictate the arrangement and composition of T-cell responses in and composition of T-cell responses in the arterial wallthe arterial wall

Triggering of the DC by various TLR Triggering of the DC by various TLR ligands leading to vessel wall ligands leading to vessel wall inflammationinflammation

TLR4 ligands induce release of CCL20 TLR4 ligands induce release of CCL20 with subsequent recruitment of CCR6with subsequent recruitment of CCR6+ +

T-cells and establishment of wall- T-cells and establishment of wall-penetrating inflammationpenetrating inflammation

TRL5 agonists facilitate recruitment of TRL5 agonists facilitate recruitment of T-cells with clustering in the adventitiaT-cells with clustering in the adventitia

Immune cells and vessel wall cells Immune cells and vessel wall cells collaborate in mediating vascular collaborate in mediating vascular damage in GCAdamage in GCA

REFERENCESREFERENCES

Piggot, K. et al Piggot, K. et al Vascular damage in giant cell artertitisVascular damage in giant cell artertitis. . Autoimmunity, October 2009; 42(7): 596-604Autoimmunity, October 2009; 42(7): 596-604

Lasjaunias, P. et al Lasjaunias, P. et al Intracraninal aneurysms in children aged under Intracraninal aneurysms in children aged under 15 years: review of 59 consecutive children with 75 aneurysms15 years: review of 59 consecutive children with 75 aneurysms. . Childs Nervous system (2005) 21: 437-350Childs Nervous system (2005) 21: 437-350

Love, S. et al Love, S. et al Ruptured vertebrobasilar aneurysm associated with Ruptured vertebrobasilar aneurysm associated with giant cell arteritis in a young boygiant cell arteritis in a young boy. Clinical Neurology and . Clinical Neurology and Neurosurgery 110 (2008) 92-96Neurosurgery 110 (2008) 92-96

Salvarani, C. et al Salvarani, C. et al Giant Cell Arteritis: Involvement of Intracranial Giant Cell Arteritis: Involvement of Intracranial ArteriesArteries Arthritis & Rheumatism Vol. 55, No. 6, December 2006, pp Arthritis & Rheumatism Vol. 55, No. 6, December 2006, pp 985-989985-989

During the DSS discussion, testing for During the DSS discussion, testing for possible viral etiologies was possible viral etiologies was

recommended. Both the aneurysm and recommended. Both the aneurysm and selected CNS samples were probed for selected CNS samples were probed for

varicella zoster virus varicella zoster virus (immunohistochemically & by tissue (immunohistochemically & by tissue PCR), as well as herpes simpex virus, PCR), as well as herpes simpex virus,

Epstein-Barr virus, and cytomegalovirus Epstein-Barr virus, and cytomegalovirus (tissue PCR). All viral studies were (tissue PCR). All viral studies were

negative.negative.