Background/Purpose:

Primary CNS vasculitis in childhood (cPACNS) is a devastating inflammatory brain disease mandating rapid and accurate diagnostic evaluation, in order to optimize neurologic outcomes.  Traditional investigations including inflammatory markers are often abnormal, but not specific.  Neuroimaging using MRI is considered the gold standard for detecting parenchymal inflammatory lesions, but is also not specific for cPACNS.  We hypothesize that patients can still be diagnosed with cPACNS even if they have normal initial MRI studies, hence consideration of brain biopsy is vital.  The aims of our study are:  (1)  To determine the proportion of children with confirmed cPACNS with normal initial MRI studies, and secondly, to calculate MRI sensitivity; (2)  To report their presenting clinical, laboratory and brain histopathology findings, treatment response and long-term outcome.

Methods:

We conducted a single centre cohort study of children diagnosed with cPACNS satisfying modified Calabrese criteria between 1990 and 2010.  The study included all patients with normal MRI studies (defined as no evidence of an inflammatory or ischemic lesion at diagnosis) with subsequent confirmatory brain biopsy.  Clinical, laboratory, histopathologic, treatment and patient outcome data was collected for these patients.  MRI-studies were evaluated by a neuroradiologist, and histopathology by a neuropathologist. 

Results:

Out of 107 children diagnosed with cPACNS, 80 children were diagnosed with angiography-positive cPACNS; all had abnormal MRIs.  27 patients were diagnosed with angiography-negative cPACNS; 25 (93%) had abnormal MRIs.  MRI sensitivity for the overall cohort was 98%, 100% for angiography-positive and 93% for angiography-negative cPACNS.  Two children fulfilled inclusion criteria:  previously healthy 11 and 13 year old males, both presenting with acute onset seizures progressing to refractory status epilepticus.  Both patients had elevated serum inflammatory markers.  One had a slightly raised WBC in CSF, the other had two normal CSF studies.  Both patients had extensive workup for infection and rheumatologic disease, returning negative.  Extensive imaging including CT, conventional angiogram, MRA, MRI, and MR spectroscopy returned normal.  Treatment was with a standardized protocol of small vessel cPACNS, including corticosteroids, pulse IV cyclophosphamide for 6 months, followed by maintenance Mycophenolate Mofetil for 18 months.  On last follow-up, one patient had mild residual neurologic deficits and intermittent seizures on anti-epileptics; the second had an excellent outcome with no neurologic deficit and seizure-free on Topiramate monotherapy. 

Conclusion:

Neuroimaging is a corner stone in the diagnostic evaluation of childhood CNS vasculitis.  In our cohort, MRI was highly sensitive, however, a negative MRI does not rule out the diagnosis of cPACNS.  In children presenting with refractory seizures, and/or if there is a high clinical suspicion, a brain biopsy should be considered despite repeatedly negative or non-diagnostic MRI studies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/brain-biopsy-diagnosis-in-magnetic-resonance-imaging-negative-childhood-primary-angiitis-of-the-central-nervous-system/