Two cases of histologically confirmed childhood primary angiitis of the central nervous system (PACNS) are reported from the University of California-San Diego, and Children’s Hospital, San Diego, CA. Patient 1, a 12-year-old boy presented with morning headaches, vomiting, and perioral dysesthesias. Examination showed papilledema, ataxia, focal weakness, and brisk reflexes. CSF contained 16 white cells/mm3 (89% lmphocytes). Infections were excluded. Von Willebrand factor antigen was persistently elevated, and ESR was normal. MRI showed white matter abnormalities. Despite a normal angiogram, brain biopsy showed vasculitis involving larger leptomeningeal vessels. Treatment with steroids and cyclophosphamide resulted in resolution of weakness and ataxia and reduction of papilledema, with one period of relapse. Patient 2, a 3-year, 9-month-old girl presented with intermittent fever, vomiting, somnolence, and arthralgias. The child had chicken pox at 3 weeks of age. Blood count showed 13,000 leukocytes/mm3, and ESR was 81 mm/h. Infectious disease evaluation was negative. Symptoms resolved without treatment but recurred 3 months later. CSF revealed 150 WBC/mm3 (83% lymphocytes) but no pathogens. MRI was normal at first but 3 months later, showed hyperintense, nonenhancing foci in the deep white matter. Eye exam showed anterior uveitis, responsive to topical corticosteroids. Within one month, a third episode with similar features, complicated by meningismus and photophobia, developed 3 days following a varicella zoster virus rash in the distribution of the left 4th thoracic root dermatome. CSF revealed 416 WBC/mm3 (31% neutrophils, 61% monocytes); PCR tests for VZV and HSV were negative. Angiogram was normal. Resolution of symptoms and MRI white matter changes followed steroid and methotrexate treatment. She was stable for 1 year and then relapsed with recurrence of fever, vomiting, meningismus, and uveitis, and also focal seizures. A right frontal brain and meningeal biopsy revealed perivascular lymphocytic infiltration of small to medium-sized vessels positive for CD4 lymphocytes. Remission followed treatment with steroids and methotrexate. [1]

COMMENT. These cases of primary CNS angiitis demonstrate the difficulties in diagnosis and the importance of early brain biopsy despite a normal angiogram. CSF examinations are typical of aseptic meningitis. The diagnosis of PACNS is based on clinical, radiographic, and biopsy correlation and exclusion of infection, toxin, drugs, neoplasm, or systemic disease. Ten previous references to cases with histological confirmation are cited. Treatment recommended is a combination of corticosteroid and cyclophosphamide. A VZV-induced vasculitis is a possible explanation in case 2; the negative CSF VZV PCR is against the diagnosis but CSF antiviral antibody titers were not known.