Major Finding: At a median follow-up of 33 months, 9 of 19 children studied had a good neurologic outcome based on the PSOM after treatment with steroid- and cyclophosphamide-based induction therapy, followed by maintenance therapy with azathioprine or mycophenolate mofetil.
Data Source: A single-center, open-label cohort study of 19 children with small-vessel childhood primary angiitis of the CNS.
Disclosures: The study authors had no disclosures to report.
An immunosuppressive treatment regimen was effective for reversing neurological deficits and controlling severe neurologic manifestations of small-vessel childhood primary angiitis of the central nervous system in a relatively large cohort study of the rare inflammatory brain disease.
At a median follow-up of 33 months in the single-center, open-label study, 9 of 19 children studied had a good neurologic outcome based on the pediatric stroke outcome measure (PSOM) after treatment with steroid- and cyclophosphamide-based induction therapy, followed by maintenance therapy with azathioprine or mycophenolate mofetil.
Four of the children remained in remission after as long as 57 months off treatment, reported Dr. Clare Hutchinson and her colleagues at the Hospital for Sick Children, Toronto.
This cohort is the largest to date to prospectively follow children with this recently recognized disease, and it is the first to demonstrate the potential efficacy of immunosuppressive treatment, they wrote (Lancet 2010 Oct. 4 [doi:10.1016/S1474-4422(10)70243-X]).
To date, a variety of treatments have been tried, but no standardized protocol or documentation of neurologic outcomes have been described.
The 6-month induction phase used in the current study included seven pulses of 500–750 mg/m
The 18-month maintenance phase included 800–1,200 mg/m
The regimen was well tolerated; two infections requiring hospitalization occurred, including one during induction, and one during maintenance, but there were no deaths. However, a high proportion of patients experienced a flare of neurologic symptoms or significant adverse events such as lymphopenia, pancytopenia, and infection while on azathioprine. All of these events resolved after the patients were switched to mycophenolate mofetil, prompting the investigators to recommend that mycophenolate mofetil be used during the maintenance phase of this protocol rather than azathioprine.
This immunosuppressive therapy regimen has the potential for improving long-term neurologic outcomes. “We therefore recommend this protocol for treatment of patients with small-vessel childhood primary angiitis of the CNS,” they wrote.
Children in the study were aged 5–17 years, with a median age of 9.8 years. Patients were assessed using clinical, neurologic, and quality of life measures, and laboratory markers were done at baseline, and at 3, 6, 9, 12, 18, and 24 months, and then yearly for the duration of follow-up. Brain imaging was done at baseline and then every 6 months for 24 months.
The number of patients in the study was small largely because of the requirement of a brain biopsy to confirm the diagnosis, the investigators said.
Another limitation is that the PSOM, although a useful measure of neurologic deficits on the basis of clinical findings, does not measure quality of life or account for other neurologic sequelae such as academic impairments, psychiatric manifestations, and ongoing seizure disorder.
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A Useful Framework
These promising findings are “a crucial and necessary first step in identifying the optimum treatment for children with small-vessel childhood primary angiitis of the CNS and will provide a useful reference for future studies of similar or alternative treatment options,” according to Dr. Neil. R. Friedman.
In fact, the study will undoubtedly serve as the basis for ongoing and future studies of this disease, he added, noting that although the small sample size precludes the recommended treatment regimen from being considered the standard of care in patients with small-vessel primary angiitis of the CNS, the study does provide a useful framework for managing and treating childhood stroke.
Questions that remain unanswered about the disease, according to Dr. Friedman, include whether it is homogenous, which potential risk factors at presentation affect disease course and outcome, and whether thrombosis contributes to stroke risk because of vascular inflammation.
DR. FRIEDMAN is with the Center for Pediatric Neurology at the Cleveland Clinic. His comments are derived from an accompanying editorial (Lancet 2010 Oct. 4 [doi:10.1016/S1474-4422(10)70244-1]). He has served as a speaker for Genzyme.