The likelihood of progression of primary angiitis of the central nervous system in children can be predicted by using a high-risk profile comprising clinical features seen at diagnosis and on follow-up, according to new findings.
Dr. Susanne M. Benseler of the Hospital for Sick Children in Toronto and her colleagues found that in their study's cohort of patients with childhood primary angiitis of the central nervous system (cPACNS), progressive disease was associated with neurocognitive dysfunction, multifocal lesions as seen on MRI, and angiographic evidence of distal stenoses at presentation. Thus, they devised a high-risk profile encompassing those factors; the profile for their cohort had a high predictive value of disease progression (predicted P = .002; odds ratio 3.47; 95% confidence interval 2.11–8.24).
The investigators retrospectively assessed data from a consecutive cohort of children younger than 18 years who had been diagnosed with cPACNS over a 12-year period (1990–2002). Cases came from the institution's rheumatology database, as well as from the Canadian Pediatric Ischemic Stroke Registry (Arthritis Rheum. 2006;54:1291–7).
Criteria for having cPACNS were a clinical diagnosis of PACNS vasculitis and conventional CNS angiography and/or magnetic resonance angiography (MRA) findings of arterial stenosis that were not explained by other causes. The investigators excluded neonates and children with any various confounding conditions, such as systemic vasculitis.
The study's primary outcome was the presence or absence of stenosis progression more than 3 months after initial angiography. The researchers defined progression as “a decrease of at least 25% in the diameter at sites of initial stenosis or the appearance of new areas of stenosis.”
Specialists in stroke, neurology, and rheumatology followed up on all patients, collecting data on clinical presentation, underlying disease, stroke risk, and treatments from the databases.
Antithrombotic treatment had been administered according to established protocols; immunosuppressive treatment had been given in some individual cases. There were three treatment categories: antithrombotic therapy (heparin, aspirin, or warfarin) alone; antithrombotic therapy plus steroids; and antithrombotic therapy with steroids and intravenous cyclophosphamide.
The investigators then prospectively assessed patients in the stroke clinic at 3–6 months, 12 months, and 24 months post diagnosis, using the Pediatric Stroke Outcome Measure, an examination with five neurocognitive domains. They defined complete recovery as a neurologic deficit severity score of 0, with any other score indicating incomplete recovery.
In addition, laboratory tests were conducted, comprising an assessment of inflammatory markers, blood testing, prothrombotic testing, antibody profiling, and detection of abnormalities in cerebrospinal fluid. All children received MRI, MRA, or conventional cerebral angiography at diagnosis and follow-up, with results analyzed by blinded neuroradiologists.
Of the 62 children included in the study (38 boys and 24 girls), 20 patients (32%) were deemed to have progressive cPACNS, with the remaining 42 classified as nonprogressive. Among the most common symptoms in both groups were focal neurologic deficits: Hemiparesis was experienced by 60% of patients with progressive disease and 88% of those with nonprogressive disease; hemifacial weakness by 60% and 57%, respectively; hemisensory loss by 95% and 71%; and deficits in fine motor skills by 75% and 71%.
The differences between the two groups were more pronounced in their incidence of diffuse neurologic deficit. For progressive-disease patients, incidence in all three categories ranged from 60% to 75%, whereas in the nonprogressive group, incidence in those categories ranged from 7% to 19%. Likewise, progressive-disease patients experienced far more headaches than did children with nonprogressive cPACNS (95% vs. 38%).
Lesions and especially stenoses were more common in the progressive-cPACNS group. The largest lesion disparity was seen in the incidence of gray-matter lesions (90% for progressive vs. 48% for nonprogressive). For stenoses, as assessed via MRA, incidence was much greater among patients with progressive disease in all stenosis categories, except for proximal stenoses, for which the groups were equal. For multiple, bilateral, and distal stenoses, however, the differences in incidence were 30%, 33%, and 59%, respectively, between the two patient groups.
The researchers called for future trials assessing immunosuppressive therapy in children with features of nonprogressive disease.