Takayasu arteritis presenting as cerebral aneurysms in an 18 month old: A case report
© Weiss et al; licensee BioMed Central Ltd. 2008
Received: 13 October 2007
Accepted: 31 January 2008
Published: 31 January 2008
Central nervous system involvement occurs in as many as twenty percent of Takayasu arteritis cases. When central nervous system disease is present, it typically manifests as cerebral ischemia or stroke. There are rare reports of intracranial aneurysms in adults with Takayasu arteritis, but none in children.
We describe a case of Takayasu arteritis in an 18 month old girl who presented with a ruptured cerebral aneurysm. Full body magnetic resonance angiography revealed bilateral iliac, pelvic and intragluteal aneurysms, irregular terminal aorta, and stenotic renal arteries. Iliac vessel biopsy showed a lymphocytic infiltrate and giant cells localized to the internal elastica.
This case highlights cerebral aneurysm as a highly unusual initial manifestation of Takayasu arteritis and demonstrates the challenges of diagnosis, treatment, and assessment of response to therapy in TA in children.
Takayasu arteritis (TA) is a large vessel systemic granulomatous vasculitis primarily involving the aorta and its major branches. TA is the third most common childhood vasculitis worldwide, but it is relatively rare in North America and accounts for 2% of all childhood vasculitis in the United States[1, 2]. The majority of pediatric patients with TA present during adolescence . Using the American College of Rheumatology (ACR) TA classification criteria, the presence of 3 of the 6 following features is diagnostic: (1) age of onset before 40 years, (2) claudication, (3) decreased brachial artery pulse, (4) blood pressure difference of >10 mm Hg between the arms, (5) bruit over the subclavian arteries or aorta and (6) arteriogram abnormality . According to the more recent EULAR (European League Against Rheumatism)/PReS (Paediatric Rheumatology European Society) consensus criteria, diagnosis of TA requires angiographic abnormalities (conventional, CT, or MRI/A) of the aorta or one of its major branches plus one or more of the following: (1) claudication or decreased peripheral artery pulses, (2) blood pressure difference >10 mm Hg, (3) bruits of the aorta or its major branches, (4) hypertension . However, diagnosis is challenging in the early inflammatory phase when only non-specific symptoms are present and imaging is non-diagnostic. Twenty percent of TA patients have central nervous system (CNS) involvement, usually manifesting as cerebral ischemia or stroke [6, 7]. There are 19 reports of intracranial aneurysms in TA, but none in individuals younger than 15 years [8–11]. Ringleb et al. reported that middle cerebral artery (MCA) involvement was most common .
The gold standard for TA imaging is angiography. However, it is invasive and cannot detect thickened vessel walls, an early sign of inflammation. MRI/A and PET scan can detect luminal diameter changes and disparities in vessel metabolic activity, respectively, indicative of early inflammation [12, 13]. Once the diagnosis of TA is made, treatment is challenging. Corticosteroids may achieve remission rates of 60%, although more than half of these patients flare with tapering . There are case reports of treatment with methotrexate, azathioprine, infliximab [14, 15] and adalimumab . Cyclophosphamide is reserved for recalcitrant cases or severe, systemic involvement .
Three weeks later, she developed vomiting and irritability. Significant laboratories included white count 9,500/μl, hemoglobin 9.7 g/dl, platelet count 737,000/μl, ESR 37 mm/hr, and CRP 2.7 mg/dl. Head CT showed a new hemorrhage, and angiography showed recurrence of the clipped ACA aneurysm. Full body MRA revealed iliac artery aneurysms, aortic narrowing (Fig 1D), and gluteal aneurysms. Blood pressure remained normal and there were no audible bruits. At this point, suspicion for a genetic vasculopathy was high and systemic vasculitis was not suspected. Repeat imaging showed progression in the left common iliac artery (Fig 1E) and narrowing of the renal arteries. A hip effusion was noted. Renal ultrasound and blood pressure were normal. Laboratory studies included a normal chromosomal variant (46, XX, inv(9) (p13q21)), and normal elastin gene and JAG1 locus. Collagen synthesis, sequencing of TGFBR2, urine copper and serum ceruloplasmin were normal. The left iliac artery aneurysm was repaired; pathology showed non-specific changes of elastic lamina disruption and chronic inflammatory infiltrate. At discharge 3 months later, she had spastic quadriparesis but was sitting with assistance. Five months after presentation, the right iliac artery aneurysm was repaired. Pathology demonstrated a transmural vasculitis with intimal thickening, giant cells (Fig 2A, B) and elastic lamina disruption (Fig 2C). Despite the presence of giant cells, suspicion for a genetic vasculopathy remained high.
This patient did not fulfill the ACR criteria for TA, which were primarily designed for adult TA detection . She did, however, fulfill the revised EULAR/PReS criteria for TA , given (1) radiographic narrowing of the aorta and renal arteries, and (2) undetectable radial and tibial pulses. Her presentation highlights the diagnostic challenges in a young child since, unfortunately, TA was not considered until late in her clinical course. Our patient presented with her first aneurysm at 18 months. Signs of inflammation were, however, present at 10 months, manifesting as failure to thrive. This case demonstrates that TA can cause cerebral aneurysms in children and raises the following question: should all patients with cerebral aneurysms be evaluated for systemic aneurysms and/or vasculitis?
The differential diagnosis of cerebral aneurysms in children is large and includes genetic, infectious and inflammatory causes. Systemic non-inflammatory vasculopathies associated with cerebral abnormalities include fibromuscular dysplasia, polycystic kidney disease, Rendu-Osler-Weber disease, and moyamoya syndrome. Genetic associations include Ehlers-Danlos, tuberous sclerosis, neurofibromatosis, Seckle and Alagille syndromes. Infectious etiologies are HIV, mycotic infections, tuberculous meningitis, and CNS Lyme disease. Systemic inflammatory vasculitides such as TA, Kawasaki disease, Behçet's, primary angiitis of the central nervous system, and polyarteritis nodosa are unusual etiologies of cerebral aneurysms. In this case, the evaluation initially centered upon genetic and non-inflammatory etiologies. As the case evolved, the underlying diagnosis was determined pathologically. When multiple cerebral aneurysms are present, screening for systemic vasculopathy should be considered. If systemic aneurysms are found, as in this case, an extensive investigation is warranted and should include evaluation for inflammatory vasculopathies.
Once diagnosis of TA is made, assessing response to treatment is challenging. Prior studies have shown clinical signs and symptoms of disease and elevated acute phase reactants are poorly correlated with disease activity. In the presence of hardware or clips from aneurysmal repair, non-invasive studies such as MRA and CTA are limited due to artifact. One recent report discussed the utility of non-invasive measurement of aortic arterial elastic properties with M-mode echocardiographic images in children with TA . Furthermore, the optimal interval for serial imaging during remission is uncertain.
This case highlights cerebral aneurysm as an initial manifestation of systemic vasculitis and demonstrates the challenges of diagnosis, treatment, and assessment of response to therapy in TA in children.
List of abbreviations
magnetic resonance angiography
central nervous system
middle cerebral artery
anterior cerebral artery
anterior communicating artery
digital subtraction angiogram
internal carotid artery
magnetic resonance imaging
posterior cerebral artery
erythrocyte sedimentation rate
time of flight
Oral consent for publication was obtained from the parents of the deceased patient reported herein.
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