Primary CNS Vasculitis of Childhood

Primary CNS Vasculitis of Childhood

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Primary CNS vasculitis of childhood is a serious but potentially reversible inflammatory brain disease. With early recognition of this rare condition, effective treatment can be instituted in a timely manner.

CNS vasculitis in children can occur as a primary disease that is isolated to the CNS or as a secondary manifestation of an underlying systemic condition. Although numerous systemic inflammatory diseases and infections have long been recognized as responsible for causing secondary CNS vasculitis, primary CNS vasculitis of childhood has only recently been described as a reversible inflammatory brain disease in case reports and case series. [1, 2, 3]

CNS vasculitis was first described in an adult in 1959. [4] In 1992 the Calabrese diagnostic criteria for primary angiitis of the CNS in adults were described. [5] These consist of the following:

A newly acquired neurological deficit

Angiographic and/or histologic evidence of CNS vasculitis

The absence of a systemic condition associated with these findings

To date no diagnostic criteria for children are available; thus, the adult definition is applied in practice. [6, 7] There are 2 main diagnostic categories: large-medium vessel disease and small vessel disease.

The diagnosis of large-medium disease is based on magnetic resonance angiography and conventional angiography evidence of vasculitis in the CNS, in the absence of underlying systemic inflammatory disease. [8] Lesions typically conform to the territory defined by a particular arterial distribution.

Small vessel CNS vasculitis affects vessels smaller than those seen by magnetic resonance angiography and conventional angiography. Therefore, by definition, this condition has negative angiography findings. [9] Lesions can be multifocal and bilateral and tend not to conform to a distinct vascular distribution. The diagnosis is confirmed by brain biopsy findings.

Large-medium vessel disease has been further subdivided into progressive and nonprogressive groups, which are defined by evidence of disease progression on angiography findings 3 months after diagnosis. Nonprogressive large-medium vessel vasculitis shares many similarities with both postvaricella angiopathy and transient cerebral arteriopathy of childhood. A significant overlap in the presentation and imaging findings among these conditions is often observed. Studies are needed to define the differences in pathophysiology and treatment requirements for each clinical disorder and to determine whether these are, in fact, distinct disease entities.

Children with progressive large-medium vessel disease typically have neurocognitive dysfunction at presentation, multifocal lesions on MRI, and evidence of distal stenosis on angiography. [8]

The risk of progression in terms of new vascular lesions is considered to be low when the presentation consists of an isolated stroke and imaging reveals evidence of unilateral, proximal vessel stenosis. [8] However, the risk of recurrent stroke due to the initial vascular injury in the same distribution is thought to be significant. Decreasing the subsequent stroke risk is the rationale for treating these patients with immunosuppressive therapy. [10]


Because of the small of number of cases that have been described to date, estimating the frequency is not possible. As recognition of this condition increases, the number of cases that are diagnosed and treated appropriately also increases.

A small number of case reports have described fatalities resulting from this disease. [11] However, although the neurological compromise observed at initial presentation may be very grave and even life-threatening, most children survive. In the past, this condition may have gone unrecognized, meaning severe, refractory, and even fatal cases of status epilepticus or stroke in the pediatric population may have been attributable to undiagnosed primary CNS vasculitis. Practice guidelines to aid in the diagnosis of status epilepticus have been established. [12]

Morbidity is not uncommon, and includes a wide variety of diffuse and focal neurological deficits. Expectations for neurological improvement should be guided by the principal that although brain inflammation is reversible, ischemia is not. With early recognition and prompt treatment, including immunosuppression and anticoagulation when appropriate, the morbidity related to this disease can be greatly decreased. In current studies, good neurological outcome has been reported in 45% of patients with progressive large-medium vessel disease, in 31% of patients with nonprogressive large-medium vessel disease, and in 69% of patients with small vessel disease. [8, 13] Tools such as the Pediatric Stroke Outcome Measure can be used to quantify neurological deficits on serial clinical assessments.

No race predilection has yet been identified.

Currently, no evidence suggests that one sex is affected more frequently than the other.

This disease has been described in children as young as infancy and as old as adolescence. No peak in age distribution has been identified.

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Twilt M, Benseler SM. Central nervous system vasculitis in adults and children. Handb Clin Neurol. 2016. 133:283-300. [Medline].

Cravioto H, Feigin I. Noninfectious granulomatous angiitis with a predilection for the nervous system. Neurology. 1959 Sep. 9:599-609. [Medline].

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 May-Jun. 59(3):293-306. [Medline].

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Saini AG, Sankhyan N, Bhattad S, Vyas S, Saikia B, Singhi P. CNS vasculitis and stroke in neonatal lupus erythematosus: A case report and review of literature. Eur J Paediatr Neurol. 2014 Jan 25. [Medline].

Matsell DG, Keene DL, Jimenez C, Humphreys P. Isolated angiitis of the central nervous system in childhood. Can J Neurol Sci. 1990 May. 17(2):151-4. [Medline].

[Guideline] Riviello JJ Jr, Ashwal S, Hirtz D, et al. Practice parameter: diagnostic assessment of the child with status epilepticus (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2006 Nov 14. 67(9):1542-50. [Medline].

Hutchinson C, Elbers J, Halliday W, Branson H, Laughlin S, Armstrong D, et al. Treatment of small vessel primary CNS vasculitis in children: an open-label cohort study. Lancet Neurol. 2010 Nov. 9(11):1078-84. [Medline].

Cekinmez EK, Cengiz N, Erol I, Kizilkilic O, Uslu Y. Unusual cause of acute neurologic deficit in childhood: primary central nervous system vasculitis presenting with basilar arterial occlusion. Childs Nerv Syst. 2009 Jan. 25(1):133-6. [Medline].

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Wilson N, Pohl D, Michaud J, Doja A, Miller E. MRI and clinicopathological correlation of childhood primary central nervous system angiitis. Clin Radiol. 2016 Nov. 71 (11):1160-7. [Medline].

Aviv RI, Benseler SM, Silverman ED, et al. MR imaging and angiography of primary CNS vasculitis of childhood. AJNR Am J Neuroradiol. 2006 Jan. 27(1):192-9. [Medline].

Schuster S, Bachmann H, Thom V, Kaufmann-Buehler AK, Matschke J, Siemonsen S, et al. Subtypes of primary angiitis of the CNS identified by MRI patterns reflect the size of affected vessels. J Neurol Neurosurg Psychiatry. 2017 Sep. 88 (9):749-755. [Medline].

Aviv RI, Benseler SM, DeVeber G, et al. Angiography of primary central nervous system angiitis of childhood: conventional angiography versus magnetic resonance angiography at presentation. AJNR Am J Neuroradiol. 2007 Jan. 28(1):9-15. [Medline].

Peng LJ, Qian HR, Mao LL, Xia DY, Qi XK. [A clinical analysis of 5 patients with infratentorial primary angiitis of central nervous system]. Zhonghua Nei Ke Za Zhi. 2017 Apr 1. 56 (4):284-289. [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. 2016 Jun 28. [Medline].

Bitter KJ, Epstein LG, Melin-Aldana H, Curran JG, Miller ML. Cyclophosphamide treatment of primary angiitis of the central nervous system in children: report of 2 cases. J Rheumatol. 2006 Oct. 33(10):2078-80. [Medline].

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Jefferson R Roberts, MD Chief of Rheumatology Service, Tripler Army Medical Center; Assistant Clinical Professor of Medicine, Uniformed Services University of the Health Sciences

Jefferson R Roberts, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Society for Simulation in Healthcare

Disclosure: Nothing to disclose.

Phalgoon A Shah, MD Resident Physician, Department of Medicine, Tripler Army Medical Center

Phalgoon A Shah, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

James J Kim, MD Resident Physician, Department of Internal Medicine, Tripler Army Medical Center

James J Kim, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lawrence K Jung, MD Chief, Division of Pediatric Rheumatology, Children’s National Medical Center

Lawrence K Jung, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Rheumatology, Clinical Immunology Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Jayant Deodhar, MD Associate Professor in Pediatrics, BJ Medical College, India; Honorary Consultant, Departments of Pediatrics and Neonatology, King Edward Memorial Hospital, India

Disclosure: Nothing to disclose.

Clare M Hutchinson, MD Lecturer, Part-Time Faculty, Department of Pediatrics, University of Toronto Faculty of Medicine; Pediatrician, Pediatric Education Co-Lead, Department of Child and Teen Health, North York General Hospital, Canada

Disclosure: Nothing to disclose.

Susanne Maria Benseler, MD Pediatric Rheumatologist, Section Chief, Alberta Children’s Hospital; Associate Professor, Department of Pediatrics, University of Calgary Faculty of Medicine, Canada

Disclosure: Nothing to disclose.

The authors thank Jorina Elbers, William Halliday, Suzanne Laughlin, Helen Branson, Harvey Lim, Robyn Westmacott, and Derek Armstrong for their significant contributions.

Primary CNS Vasculitis of Childhood

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