Source: DGNews  |  Posted 1 year ago

NEW YORK -- October 4, 2010 -- A study published early online and appearing in an upcoming edition of The Lancet Neurologyshows that immunosuppressive therapy may improve long-term neurological outcome in children with primary angiitis of the central nervous system (CNS).

There are 2 types of childhood primary angiitis of the CNS: medium-large vessel and small vessel vasculitis. Only medium-large vessel vasculitis can be diagnosed using angiography (since it affects cerebral arteries large enough to be visualised), while small vessel vasculitis is diagnosed on brain biopsy, but has a negative angiography.

Small vessel childhood primary angiitis of the CNS has been described in a small number of case reports and case series, with little information known about its incidence and age distribution. Treatments have included corticosteroids, methotrexate, intravenous
gammaglobulin, oral or intravenous cyclophosphamide, and azathioprine, all at varying doses and for different durations.

In the current study, Clare Hutchinson, MD, and Susanne M. Benseler, MD, Hospital for Sick Children, Toronto, Ontario, and colleagues assessed a treatment regimen and describe long-term neurological outcomes in a cohort of children with this disorder.

The treatment protocol consisted of induction therapy with steroids and pulses of intravenous cyclophosphamide followed by maintenance therapy with either azathioprine or mycophenolate mofetil.

Clinical and neurological assessments, quality of life measures, and laboratory markers were done at baseline, 3, 6, 9, 12, 18, and 24 months, and every year thereafter. Brain imaging was done at baseline, 6, 12, 18, and 24 months. The primary outcome was the paediatric stroke outcome measure (PSOM) score at 24 months.

The study enrolled 127 children aged 5 to 17 years over a 7-year period from 2002 to 2009. Of these, 19 met the inclusion criteria and were given induction therapy with 7 monthly pulses of cyclophosphamide for 6 months.

Median follow-up was 33 months, and 14 patients completed induction and received maintenance therapy with azathioprine (n = 9) or mycophenolate mofetil (n = 5).

A total of 13 patients completed 24 months follow-up, 9 of whom had a good neurological outcome by PSOM. Eight of 19 patients experienced disease flares. Four patients achieved remission of disease off medication.

“In this relatively large cohort of children with small vessel childhood primary angiitis of the CNS we show the potential efficacy of an immunosuppressive protocol... The treatment protocol was effective in controlling the severe neurological manifestations of CNS vasculitis in the majority of our patients,” the authors wrote. “Our treatment regimen was well tolerated and effective in reversing neurological deficits. We therefore recommend this protocol for treatment of patients with small vessel childhood primary angiitis of the CNS.”

“Just 10 years ago, patients with childhood small vessel CNS vasculitis had a very high mortality; in fact the disease was most commonly diagnosed on autopsy,” added Dr. Benseler. “Len Calabrese was the first to teach us to look for CNS vasculitis in adults. From our work at The Hospital for Sick Children, we have learned that children with small vessel CNS vasculitis can present with severe neurological deficits including seizures, stroke features, and psychiatric manifestation. In previously healthy children that develop new deficits, inflammation must be considered and -- once confirmed -- rapidly treated. Our study confirmed that inflammation is reversible with the appropriate immunosuppressive medication. It allows the brain to heal and children to recover.”

In an accompanying comment, Neil R. Friedman, MD, Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, said: “The Article by Benseler and colleagues highlights the need for improved outcome measures and disease-specific quality of life questionnaires in paediatric stroke given the limitations of the paediatric stroke outcome measure in the assessment of cognitive, behavioural, neuropsychological, and seizure outcomes. This article will undoubtedly serve as the basis for ongoing study and future research into childhood primary angiitis of the CNS.”

SOURCE: The Lancet Neurology