Primary Angiitis of the Central Nervous System: Neurologic Deterioration Despite Treatment

Abstract

Primary angiitis of the central nervous system (PACNS) is an idiopathic vasculitis confined to the central nervous system. In children with PACNS, small-vessel (SV) involvement is characterized clinically by progressive neurologic symptoms, multifocal lesions on brain imaging, occasional pseudo-tumor presentation, and normal angiogram results in most patients. Small case series of patients with SV PACNS with short follow-up usually reveal favorable outcomes in children treated with immunosuppressive therapy. We report here the cases of 3 children with biopsy-confirmed SV PACNS and long-term follow-up who developed different patterns of neurologic deterioration despite immunosuppressive therapy. One patient had transient ischemic attacks shortly after initiation of corticosteroid treatment. Early ischemic events probably result from residual thrombogenicity or residual inflammation of recently affected vessels, which supports the use of antiplatelet agents and suggests potential benefits of stronger immunosuppressive therapy. In contrast, the other 2 patients had later neurologic deterioration after corticosteroid withdrawal, which suggests failure of initial immunosuppressant treatment and the need for stronger agents, longer treatment duration, or both. All patients responded to long-term treatment with corticosteroids combined with cytotoxic agents. This particular combination is probably indicated in many cases of SV PACNS, including those with neurologic deterioration that occurs during maintenance corticotherapy or after corticosteroid withdrawal. In 1 case, SV PACNS recurred several years after discontinuation of combination therapy. Long-term relapses may reflect intrinsic predispositions to SV PACNS rather than treatment failure. These cases highlight different chronological patterns of neurologic deterioration despite immunosuppressive therapy, which supports the relevance of monitoring clinical, laboratory, and radiologic responses to treatment and of long-term follow-up of patients with SV PACNS.

Small vessel primary angiitis of the central nervous system: Rapidly progressing disease in a child

“…Steroids had already been started in an attempt to control neurological deterioration, after infectious causes were excluded with a reasonable degree of confidence. Steroids alone were able to control initial symptoms in other reported children [3,9]. However, in this patient, clinical stabilization was only achieved when cyclophosphamide was added.…”

“…Inflammatory diseases of the CNS can have multiple etiologies, including infection, malignancy, neurometabolic and neurodegenerative diseases, systemic vascular disorders and there are no sufficiently sensitive or specific inflammatory markers or imaging features that can distinguish SVcPACNS from other conditions [3,9]. Therefore, the work-up for patients who may have PACNS must proceed simultaneously with plans for the systematic evaluation and exclusion of other disorders.…”

“…However, in this patient, clinical stabilization was only achieved when cyclophosphamide was added. In fact, other immunosuppressive agents than steroids might be needed in combination to achieve better disease control [2,3,9]. A protocol of treatment that includes cyclophosphamide plus corticosteroids as induction therapy, followed by an 18month maintenance therapy with mycophenolate mophetil has been suggested by Hutchinson et al [2].…”

Primary Angiitis of the Central Nervous System - Clinical Approaches, Challenges and Controversies

“…32,40 Some authors have also proposed using brain L-[methyl-11C] methionine positron emission tomography as an adjunct to MRI in order to identify metabolically active brain lesions and thereby guide biopsy towards affected regions so as to possibly improve diagnostic yield. 41…”

“…Stereotactic needle biopsy can be used for deep-seated lesions but the risk of sampling error increases with this technique. 40,41 False-negative biopsy is not uncommon, owing to the patchy nature of vasculitic changes and sensitivity of biopsy ranges from 53-74 % in studies that used post-mortem tissue as a gold standard for diagnosis. 1,8 Rates of false-negative biopsy increase when disease is limited to large-and medium-sized arteries not sampled by this procedure, and if obtained tissue is restricted to the brain, 31 leptomeninges, 50,51 or evacuated necrotic tissue from cerebral infarctions.…”