Primary angiitis of the central nervous system in adults
- Rula A Hajj-Ali, MD
Rula A Hajj-Ali, MD
- Associate Professor of Medicine
- Cleveland Clinic Lerner College of Medicine
- Leonard H Calabrese, DO
Leonard H Calabrese, DO
- Professor of Medicine
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
- Section Editors
- Gene G Hunder, MD
Gene G Hunder, MD
- Section Editor — Vasculitis
- Emeritus Consultant
- Professor Emeritus
- Mayo Clinic College of Medicine
- Scott E Kasner, MD
Scott E Kasner, MD
- Section Editor — Stroke
- Professor of Neurology
- University of Pennsylvania School of Medicine
Central nervous system (CNS) vasculitis refers to a broad spectrum of diseases that result in inflammation and destruction of the blood vessels of the brain, spinal cord, and meninges. Angiitis, a synonym for vasculitis, refers generally to blood vessels on both the arterial and venous sides of the circulation.
Primary angiitis of the CNS (PACNS) is the preferred name for vasculitis that is confined to the CNS. CNS vasculitis is considered secondary when it occurs in the context of a systemic inflammatory disease, such as a systemic vasculitis or systemic lupus erythematosus (SLE), or an infectious process such as varicella zoster virus.
PACNS predominantly affects small- and medium-sized arteries of the brain parenchyma, spinal cord, and leptomeninges, resulting in symptoms and signs of CNS dysfunction. It is defined by inflammation of the cerebral vasculature without angiitis in other organs.
The protean manifestations of PACNS, along with the nonspecificity of available investigational modalities, pose a challenge for accurate diagnosis. Clinicians caring for patients with suspected PACNS should be familiar with its mimics to avoid misdiagnosis. PACNS can be mimicked closely in both its clinical presentation and radiologic manifestations by a number of other disorders. The most frequent mimic of PACNS is a group of disorders known collectively as the reversible cerebral vasoconstriction syndromes (RCVS). (See "Reversible cerebral vasoconstriction syndromes".)
The clinical characteristics, diagnosis, and treatment of PACNS will be reviewed here. PACNS in children is discussed separately. (See "Vasculitis in children: Classification and incidence", section on 'Primary angiitis of the central nervous system'.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol 2007; 62:442.
- Calabrese LH, Duna GF, Lie JT. Vasculitis in the central nervous system. Arthritis Rheum 1997; 40:1189.
- Sigal LH. The neurologic presentation of vasculitic and rheumatologic syndromes. A review. Medicine (Baltimore) 1987; 66:157.
- Thomas L, Davidson M, McCluskey RT. Studies of PPLO infection. I. The production of cerebral polyarteritis by Mycoplasma gallisepticum in turkeys; the neurotoxic property of the Mycoplasma. J Exp Med 1966; 123:897.
- Alexander JJ, Lasky AS, Graf WD. Stroke associated with central nervous system vasculitis after West Nile virus infection. J Child Neurol 2006; 21:623.
- Outteryck O, Sénéchal O, Berteloot D, et al. [Cerebral vasculitis secondary to Varicella-Zoster virus infection]. Rev Neurol (Paris) 2005; 161:836.
- Bhat G, Mathur DS, Saxena GN, et al. Granulomatous angiitis of the central nervous system associated with herpes zoster. J Assoc Physicians India 2002; 50:977.
- Brannagan TH 3rd. Retroviral-associated vasculitis of the nervous system. Neurol Clin 1997; 15:927.
- Nogueras C, Sala M, Sasal M, et al. Recurrent stroke as a manifestation of primary angiitis of the central nervous system in a patient infected with human immunodeficiency virus. Arch Neurol 2002; 59:468.
- Kossorotoff M, Touzé E, Godon-Hardy S, et al. Cerebral vasculopathy with aneurysm formation in HIV-infected young adults. Neurology 2006; 66:1121.
- van der Ven AJ, van Oostenbrugge RJ, Kubat B, Tervaert JW. Cerebral vasculitis after initiation antiretroviral therapy. AIDS 2002; 16:2362.
- Scolding NJ, Joseph F, Kirby PA, et al. Abeta-related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy. Brain 2005; 128:500.
- Hashizume Y, Yoshida M, Suzuki E, Hirayama M. A 65-year-old man with headaches and left homonymous hemianopsia. Neuropathology 2004; 24:350.
- Harkness KA, Coles A, Pohl U, et al. Rapidly reversible dementia in cerebral amyloid inflammatory vasculopathy. Eur J Neurol 2004; 11:59.
- Tamargo RJ, Connolly ES Jr, McKhann GM, et al. Clinicopathological review: primary angiitis of the central nervous system in association with cerebral amyloid angiopathy. Neurosurgery 2003; 53:136.
- Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-2000. A 63-year-old man with changes in behavior and ataxia. N Engl J Med 2000; 342:957.
- Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis: comparison of patients with and without cerebral amyloid angiopathy. Rheumatology (Oxford) 2008; 47:1671.
- Fountain NB, Eberhard DA. Primary angiitis of the central nervous system associated with cerebral amyloid angiopathy: report of two cases and review of the literature. Neurology 1996; 46:190.
- Hajj-Ali RA, Calabrese LH. Primary angiitis of the central nervous system. Autoimmun Rev 2013; 12:463.
- Hajj-Ali RA, Calabrese LH. Diagnosis and classification of central nervous system vasculitis. J Autoimmun 2014; 48-49:149.
- de Boysson H, Zuber M, Naggara O, et al. Primary angiitis of the central nervous system: description of the first fifty-two adults enrolled in the French cohort of patients with primary vasculitis of the central nervous system. Arthritis Rheumatol 2014; 66:1315.
- Salvarani C, Brown RD Jr, Christianson TJ, et al. Adult primary central nervous system vasculitis treatment and course: analysis of one hundred sixty-three patients. Arthritis Rheumatol 2015; 67:1637.
- Giannini C, Salvarani C, Hunder G, Brown RD. Primary central nervous system vasculitis: pathology and mechanisms. Acta Neuropathol 2012; 123:759.
- Salvarani C, Brown RD Jr, Calamia KT, et al. Primary CNS vasculitis with spinal cord involvement. Neurology 2008; 70:2394.
- Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB. Narrative review: reversible cerebral vasoconstriction syndromes. Ann Intern Med 2007; 146:34.
- Belmont HM, Abramson SB, Lie JT. Pathology and pathogenesis of vascular injury in systemic lupus erythematosus. Interactions of inflammatory cells and activated endothelium. Arthritis Rheum 1996; 39:9.
- Ellis SG, Verity MA. Central nervous system involvement in systemic lupus erythematosus: a review of neuropathologic findings in 57 cases, 1955--1977. Semin Arthritis Rheum 1979; 8:212.
- Hanly JG, Walsh NM, Sangalang V. Brain pathology in systemic lupus erythematosus. J Rheumatol 1992; 19:732.
- Lyons MK, Caselli RJ, Parisi JE. Nonvasculitic autoimmune inflammatory meningoencephalitis as a cause of potentially reversible dementia: report of 4 cases. J Neurosurg 2008; 108:1024.
- Barinagarrementeria F, Cantú C. Frequency of cerebral arteritis in subarachnoid cysticercosis: an angiographic study. Stroke 1998; 29:123.
- Calabrese LH, Mallek JA. Primary angiitis of the central nervous system. Report of 8 new cases, review of the literature, and proposal for diagnostic criteria. Medicine (Baltimore) 1988; 67:20.
- Horowitz DR, Tuhrim S, Budd J, Goldman ME. Aortic plaque in patients with brain ischemia: diagnosis by transesophageal echocardiography. Neurology 1992; 42:1602.
- Lie JT. Malignant angioendotheliomatosis (intravascular lymphomatosis) clinically simulating primary angiitis of the central nervous system. Arthritis Rheum 1992; 35:831.
- Demirer T, Dail DH, Aboulafia DM. Four varied cases of intravascular lymphomatosis and a literature review. Cancer 1994; 73:1738.
- Nakahara T, Saito T, Muroi A, et al. Intravascular lymphomatosis presenting as an ascending cauda equina: conus medullaris syndrome: remission after biweekly CHOP therapy. J Neurol Neurosurg Psychiatry 1999; 67:403.
- Susac JO, Hardman JM, Selhorst JB. Microangiopathy of the brain and retina. Neurology 1979; 29:313.
- Kleffner I, Deppe M, Mohammadi S, et al. Diffusion tensor imaging demonstrates fiber impairment in Susac syndrome. Neurology 2008; 70:1867.
- Do TH, Fisch C, Evoy F. Susac syndrome: report of four cases and review of the literature. AJNR Am J Neuroradiol 2004; 25:382.
- Susac JO, Murtagh FR, Egan RA, et al. MRI findings in Susac's syndrome. Neurology 2003; 61:1783.
- Dimauro S, Hirano M. Pedaling from genotype to phenotype. Arch Neurol 2006; 63:1679.
- Richards A, van den Maagdenberg AM, Jen JC, et al. C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat Genet 2007; 39:1068.
- Singhal AB, Hajj-Ali RA, Topcuoglu MA, et al. Reversible cerebral vasoconstriction syndromes: analysis of 139 cases. Arch Neurol 2011; 68:1005.
- Alhalabi M, Moore PM. Serial angiography in isolated angiitis of the central nervous system. Neurology 1994; 44:1221.
- Pomper MG, Miller TJ, Stone JH, et al. CNS vasculitis in autoimmune disease: MR imaging findings and correlation with angiography. AJNR Am J Neuroradiol 1999; 20:75.
- Molloy ES, Singhal AB, Calabrese LH. Tumour-like mass lesion: an under-recognised presentation of primary angiitis of the central nervous system. Ann Rheum Dis 2008; 67:1732.
- Kadkhodayan Y, Alreshaid A, Moran CJ, et al. Primary angiitis of the central nervous system at conventional angiography. Radiology 2004; 233:878.
- Calabrese LH, Furlan AJ, Gragg LA, Ropos TJ. Primary angiitis of the central nervous system: diagnostic criteria and clinical approach. Cleve Clin J Med 1992; 59:293.
- Vollmer TL, Guarnaccia J, Harrington W, et al. Idiopathic granulomatous angiitis of the central nervous system. Diagnostic challenges. Arch Neurol 1993; 50:925.
- Bai HX, Zou Y, Lee AM, et al. Diagnostic Value and Safety of Brain Biopsy in Patients With Cryptogenic Neurological Disease: A Systematic Review and Meta-analysis of 831 Cases. Neurosurgery 2015; 77:283.
- Alrawi A, Trobe JD, Blaivas M, Musch DC. Brain biopsy in primary angiitis of the central nervous system. Neurology 1999; 53:858.
- Chu CT, Gray L, Goldstein LB, Hulette CM. Diagnosis of intracranial vasculitis: a multi-disciplinary approach. J Neuropathol Exp Neurol 1998; 57:30.
- Parisi JE, Moore PM. The role of biopsy in vasculitis of the central nervous system. Semin Neurol 1994; 14:341.
- Miller DV, Salvarani C, Hunder GG, et al. Biopsy findings in primary angiitis of the central nervous system. Am J Surg Pathol 2009; 33:35.
- Lie JT. Classification and histopathologic spectrum of central nervous system vasculitis. Neurol Clin 1997; 15:805.
- Guillevin L, Pagnoux C. When should immunosuppressants be prescribed to treat systemic vasculitides? Intern Med 2003; 42:313.
- Gayraud M, Guillevin L, Cohen P, et al. Treatment of good-prognosis polyarteritis nodosa and Churg-Strauss syndrome: comparison of steroids and oral or pulse cyclophosphamide in 25 patients. French Cooperative Study Group for Vasculitides. Br J Rheumatol 1997; 36:1290.
- De Boysson H, Arquizan C, Guillevin L, Pagnoux C. Rituximab for primary angiitis of the central nervous system: report of 2 patients from the French COVAC cohort and review of the literature. J Rheumatol 2013; 40:2102.
- Salvarani C, Brown RD Jr, Huston J 3rd, et al. Treatment of primary CNS vasculitis with rituximab: case report. Neurology 2014; 82:1287.
- CLINICAL MANIFESTATIONS
- DIAGNOSTIC APPROACH
- When to suspect the diagnosis
- Alternative diagnoses
- - Laboratory testing to exclude alternative diagnoses
- - Lumbar puncture
- - Neuroimaging
- MR angiography and CT angiography
- Conventional angiography
- - Brain and leptomeningeal biopsy
- Selecting patients for brain biopsy
- Establishing the diagnosis
- Initial therapy of suspected PACNS
- Treatment of PACNS
- - Glucocorticoids
- - Cyclophosphamide
- - Rituximab
- Prophylactic therapies
- - Osteoporosis prevention
- - Opportunistic infections
- - Other
- Monitoring treatment
- Duration of therapy and management of recurrent disease
- - Glucocorticoid taper
- - Discontinuing cyclophosphamide
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS