Diagnosis of childhood immune-mediated CNS vasculitides


Dr. Yeh of the University of Toronto has received a research grant from Biogen and honorariums from Alexion, Biogen, Hoffman/LaRoche, and Novartis for scientific advisory service.

Francesc Graus MD PhD, editor. (

Dr. Graus, Emeritus Professor, Laboratory Clinical and Experimental Neuroimmunology, Institut D’Investigacions Biomédiques August Pi I Sunyer, Hospital Clinic, Spain, has no relevant financial relationships to disclose.

Originally released June 12, 2018; updated August 6, 2020; expires August 6, 2023


Interest in pediatric onset inflammatory disorders of the CNS has grown in recent years, related partially to increasing use of MRI in the pediatric population as well as increased awareness that recurrent inflammatory disorders of the CNS may include etiologies outside of demyelinating disorders and knowledge that disorders once deemed to be due to possible infection may have immune-related etiologies (Granerod et al 2010; Gable et al 2012). With this has come attention to pediatric-onset CNS immune-mediated vasculitides, a heterogeneous group of disorders that may result from either autoimmune (aberrant activation of the adaptive immune system) or autoinflammatory (aberrant activation of the innate immune system) etiologies, with clinical presentations that vary according to the size of the vessels involved and the presence or absence of accompanying systemic (extra-CNS) manifestations (Kastner et al 2010; Ozen and Bilginer 2014; Martinon and Aksentijevich 2015). These heterogeneous disorders represent an important subgroup of inflammatory disorders of the CNS, given the potential for irreversible injury and, therefore, a high potential for long-term cognitive or motor disability. The incidence and prevalence of childhood immune-mediated CNS vasculitides is unknown, although 1 adult study confirms the rarity of primary CNS vasculitis, with an incidence of 1:1,000,000 persons per year (Salvarani et al 2007). With this in mind, in this article, the author provides details of known clinical CNS vasculitic syndromes and an overview of the clinical and diagnostic approach. Included in the article is a review of primary (or isolated) CNS vasculitides, a discussion of CNS vasculitides associated with systemic involvement, and an examination of monogenic autoinflammatory disorders associated with CNS vasculitis. In the vast majority of disorders, no specific biomarker of disease is known and the final diagnosis is based on recognizable syndromic characteristics. Therefore, familiarity with the related presentations can improve a timely diagnosis.

Key points


• Childhood CNS immune-mediated vasculitides include a broad spectrum of rare immune-mediated disorders, defined pathologically by inflammation of the vascular wall and resulting in tissue ischemia, necrosis, and inflammation.


• Childhood CNS vasculitides, which may remain isolated within the CNS or be associated with systemic involvement, are traditionally classified based on the size of the primary vessel involved (small-vessel or medium-large vessel vasculitis).


• Irreversible neurologic impairment occurs commonly in this population. As these disorders may be amenable to treatment, prompt recognition by the practicing clinician has the potential to improve clinical outcomes.


• In the vast majority of disorders, no specific biomarker of disease is known, and the final diagnosis is based on recognizable syndromic characteristics. Next-generation sequencing techniques may prove useful in the future in uncharacterized CNS vasculitides.


• Treatment is based on a few open label studies and on small case series and reports but mainly is derived from evidence obtained from adult patients. Data are reviewed in this article regarding specific agents and therapeutic management approaches.

Historical note and terminology

In 1988, a case series of 8 adults found to have primary vasculitis of the CNS was published together with proposed diagnostic criteria (Calabrese and Mallek 1988). The criteria were revised in 1992 in a new publication from Calabrese and colleagues (Calabrese et al 1992). The criteria proposed in 1992 are widely used for adults and children but have not been validated. They include the following: “(1) the presence of an acquired, otherwise unexplained neurologic or psychiatric deficit; (2) the presence of either classic angiographic or histopathological features of angiitis within the CNS; and (3) no evidence of systemic vasculitis or any disorder that could cause or mimic the angiographic or pathological features of the disease” (Calabrese et al 1992). These criteria were formulated prior to the advent of knowledge about specific antibody-mediated processes leading to inflammatory CNS insults, such as NMDAR encephalitis, and growing knowledge about monogenic etiologies of CNS inflammation. It is possible that the coming years will see a significant evolution in the understanding of the etiopathogenesis of these clinically described syndromes.

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