Primary Angiitis of the CNS

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Primary Angiitis of the CNS

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Primary angiitis of the central nervous system (PACNS) is frequently considered in the differential diagnosis in patients with cryptogenic neurologic illness or in young subjects with ischemic stroke. The absence of characteristic clinical, laboratory, or radiographic features of this rare disease make the diagnosis very difficult, and has contaminated the literature with unproven cases in which alternative diagnoses are plausible.

Vasculitis is inflammation of blood vessel walls leading to disruption of the normal structural and physiologic characteristics of the affected vessels, which in turn results in vascular occlusion and/or formation of aneurysms with consequent ischemia and hemorrhage.

Numerous forms of vasculitis can affect the central nervous system (CNS). This review focuses on primary angiitis of the central nervous system (PACNS), a rare form of vasculitis restricted to the brain and spinal cord. Only biopsy-proved case series are referenced in this report.

See Vasculitis: Case Presentations, a Critical Images slideshow, for more information on clinical, histologic, and radiographic imaging findings in various forms of vasculitis.

The etiology and pathogenesis of PACNS are unknown. The fundamental mechanism of all vasculitides is immunologic; Crowe discussed 4 different mechanisms of tissue injury that might apply to the pathogenesis of vasculitis: immune complexes, direct antibody-mediated damage, delayed hypersensitivity, and cytotoxic T lymphocytes. [1] With the limited knowledge we have about PACNS, no strong evidence supports any of these mechanisms in the pathogenesis of this disease, although the granulomatous nature of inflammation suggests a role of cell-mediated immunity. [2]

As in other autoimmune disorders, T cells that become sensitized in the course of systemic illness or viral infection probably later contribute to a cellular immune response directed against cross-reacting epitopes in CNS vessels. [3] Other authors propose that, in the setting of altered host defense mechanisms, a virus or other pathogen may lead directly or indirectly to diffuse cerebral vasculitis. [4]

The latter hypothesis is supported by the rare condition in which vasculitis involving mainly the ipsilateral anterior circulation with consequent infarcts occurs days to weeks following varicella-zoster infection of the first division of the trigeminal nerve. The mechanism seems to be retrograde spread of the virus from Gasserian ganglion to the arteries of the anterior circle of Willis. [5]

Pathologically confirmed cases of PACNS have been reported in patients with Hodgkin disease, amyloid angiopathy, and graft-versus-host disease. However, available information in these cases does not allow any conclusion about the causal relation between these diseases and PACNS. [2]

Regardless of the etiology of PACNS, the main mechanism of neurologic damage in these patients is ischemic. This results from 3 consequences of inflammation in the vascular wall: obstruction of the vessel lumen, increased local coagulation from the effects of proinflammatory cytokines on the endothelial surface, and alteration in vasomotor tone. [6]

United States

The rarity of PACNS and the lack of consensus on diagnostic criteria make incidence and prevalence of the disease difficult to estimate.

International

PACNS is reported more frequently in North America, Europe, Australia, and New Zealand. Whether the disease has a higher incidence in these regions or it has just been more successfully diagnosed and reported there is unclear.

Mortality and morbidity of PACNS are hard to determine due to the variability in diagnosis means and treatment among published series. However, treatment with steroids and immunosuppressants has improved the outcomes of the disease, which used to be fatal. In a recent report, 14% of 29 patients with biopsy-proven PACNS died or had severe morbidity (Modified Rankin Scale of 5) at follow-up of 1.14 years. [7]

Men are more commonly affected by PACNS than women; the male-to-female ratio is about 7:3. [4]

In most reported cases, patients were in the fourth to sixth decades of life at time of diagnosis. However, patients aged 7 months to 78 years have been described. [8, 9, 10]

Crowe WE. Immunopathogenesis and Diagnosis. Immunopathogenesis of Vasculitis. Littleton, MA: PSG Publishing Company; 1988. Chapter 1, Section 1.

Schmidley, James W. Central Nervous System Angiitis. USA: Butterworth-Heinemann; 2000. Chapters 1, 2, 3, 4.

Younger DS. Vasculitis of the nervous system. Curr Opin Neurol. 2004 Jun. 17(3):317-36. [Medline].

Calabrese LH, Duna GF, Lie JT. Vasculitis in the central nervous system. Arthritis Rheum. 1997 Jul. 40(7):1189-201. [Medline].

Moskowitz MA, Henrikson BM. Trigeminovascular neurons and the arteritis complicating herpes zoster ophthalmicus. Neurology. 1985 Mar. 35(3):444. [Medline].

F G. Joseph, N J. Scolding. Cerebral Vasculitis: A Practical Approach. Practical Neurology. 2002. 2:80.

Miller DV, Salvarani C, Hunder GG, Brown RD, Parisi JE, Christianson TJ. Biopsy findings in primary angiitis of the central nervous system. Am J Surg Pathol. 2009 Jan. 33(1):35-43. [Medline].

Benseler SM. Central nervous system vasculitis in children. Curr Rheumatol Rep. 2006 Dec. 8(6):442-9. [Medline].

Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis with prominent leptomeningeal enhancement: a subset with a benign outcome. Arthritis Rheum. 2008 Feb. 58(2):595-603. [Medline].

Katsetos CD, Poletto E, Kasmire KE, Walleigh D, Kumar I, Pascasio JM, et al. Childhood primary angiitis of the central nervous system with metachronous hemorrhagic infarcts: a postmortem study with clinicopathologic correlation. Semin Pediatr Neurol. 2014 Jun. 21(2):184-94. [Medline].

Wiszniewska M, Devuyst G, Bogousslavsky J. Giant cell arteritis as a cause of first-ever stroke. Cerebrovasc Dis. 2007. 24(2-3):226-30. [Medline].

Salvarani C, Brown RD Jr, Calamia KT, et al. Primary CNS vasculitis with spinal cord involvement. Neurology. 2008 Jun 10. 70(24 Pt 2):2394-400. [Medline].

Elbers J, Halliday W, Hawkins C, Hutchinson C, Benseler SM. Brain biopsy in children with primary small-vessel central nervous system vasculitis. Ann Neurol. 2010 Nov. 68(5):602-10. [Medline].

Salvarani C, Brown RD Jr, Calamia KT, Christianson TJ, Weigand SD, Miller DV. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol. 2007 Nov. 62(5):442-51. [Medline].

Scolding NJ, Jayne DR, Zajicek JP, et al. Cerebral vasculitis–recognition, diagnosis and management. QJM. 1997 Jan. 90(1):61-73. [Medline].

Call GK, Fleming MC, Sealfon S, Levine H, Kistler JP, Fisher CM. Reversible cerebral segmental vasoconstriction. Stroke. 1988 Sep. 19(9):1159-70. [Medline].

Hajj-Ali RA, Furlan A, Abou-Chebel A, et al. Benign angiopathy of the central nervous system: cohort of 16 patients with clinical course and long-term followup. Arthritis Rheum. 2002 Dec 15. 47(6):662-9. [Medline].

White ML, Hadley WL, Zhang Y, et al. Analysis of central nervous system vasculitis with diffusion-weighted imaging and apparent diffusion coefficient mapping of the normal-appearing brain. AJNR Am J Neuroradiol. 2007 May. 28(5):933-7. [Medline].

Singh S, John S, Joseph TP, et al. Primary angiitis of the central nervous system: MRI features and clinical presentation. Australas Radiol. 2003 Jun. 47(2):127-34. [Medline].

Rosati A, Pianigiani N, Pagnini I, Guerrini R, Cimaz R, Simonini G. Sequential MR angiography in childhood primary angiitis of the CNS. Pediatr Neurol. 2013 Aug. 49(2):127-9. [Medline].

Kadkhodayan Y, Alreshaid A, Moran CJ, et al. Primary angiitis of the central nervous system at conventional angiography. Radiology. 2004 Dec. 233(3):878-82. [Medline].

Alrawi A, Trobe JD, Blaivas M, et al. Brain biopsy in primary angiitis of the central nervous system. Neurology. 1999 Sep 11. 53(4):858-60. [Medline].

Torres J, Loomis C, Cucchiara B, Smith M, Messé S. Diagnostic Yield and Safety of Brain Biopsy for Suspected Primary Central Nervous System Angiitis. Stroke. June 28, 2016. 47:2127-9. [Medline].

Kolodny EH, Rebeiz JJ, Caviness VS Jr, et al. Granulomatous angiitis of the central nervous system. Arch Neurol. 1968 Nov. 19(5):510-24. [Medline].

Schwab P, Lidov HG, Schwartz RB, Anderson RJ. Cerebral amyloid angiopathy associated with primary angiitis of the central nervous system: report of 2 cases and review of the literature. Arthritis Rheum. 2003 Jun 15. 49(3):421-7. [Medline].

Scolding NJ, Joseph F, Kirby PA, Mazanti I, Gray F, Mikol J, et al. Abeta-related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy. Brain. 2005 Mar. 128:500-15. [Medline].

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. The Journal of Rheumatology. December 2013. 40:2102-3. [Medline].

Calabrese LH, Gragg LA, Furlan AJ. Benign angiopathy: a distinct subset of angiographically defined primary angiitis of the central nervous system. J Rheumatol. 1993 Dec. 20(12):2046-50. [Medline].

Ducros A, Bousser MG. Reversible cerebral vasoconstriction syndrome. Pract Neurol. 2009 Oct. 9(5):256-67. [Medline].

Duna GF, Calabrese LH. Limitations of invasive modalities in the diagnosis of primary angiitis of the central nervous system. J Rheumatol. 1995 Apr. 22(4):662-7. [Medline].

Lie JT. Classification and histopathologic spectrum of central nervous system vasculitis. Neurol Clin. 1997 Nov. 15(4):805-19. [Medline].

Mazen Noufal, MD Neurologist, Baptist Health Medical Center

Mazen Noufal, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

James W Schmidley, MD Professor of Neurology, Virginia Tech Carilion School of Medicine

James W Schmidley, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Heart Association, American Neurological Association, Phi Beta Kappa

Disclosure: Received stipend from Oakstone medical publishing for review panel membership.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Helmi L Lutsep, MD Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center

Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology, American Stroke Association

Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Executive Committee for the NINDS-funded DEFUSE3 Trial; Physician Advisory Board for Coherex Medical.

Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison School of Medicine and Public Health

Christopher Luzzio, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Primary Angiitis of the CNS

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