Background Primary CNS vasculitis in childhood (cPACNS) is a devastating inflammatory brain disease that is potentially reversible if recognized and treated early. Earlier recognition and treatment is preferred to optimize outcomes. Neuroimaging using MRI is considered highly sensitive in detecting parenchymal inflammatory lesions, but normal or non-specific neuroimaging does not rule out the diagnosis. If there is a high clinical suspicion, a brain biopsy for tissue diagnosis prior to commencing anti-inflammatory treatment should be strongly considered.
Objectives To report clinical, laboratory, imaging and brain biopsy findings, treatment response and long-term outcome of a cohort of children with cPACNS, who had repeatedly negative or non-diagnostic MRI studies at diagnosis.
Methods A prospective single center cohort study of children diagnosed with cPACNS based on Calabrese criteria between 2002 and 2010 was performed. The study included all patients with negative or non-diagnostic MRI studies (defined as no evidence of an inflammatory or ischemic lesion at diagnosis) with subsequent confirmatory brain biopsy for cPACNS. Clinical, laboratory, treatment and outcome data were collected from standardized assessments. MRI-studies were re-evaluated by the study neuroradiologist. Diagnostic tests were blindly reviewed by independent experts. Sensitivity of MRI was calculated.
Results Out of 72 patients diagnosed with cPACNS, 25 had diagnostic brain biopsies performed. Three patients fulfilled inclusion criteria, with angiography negative small vessel CNS vasculitis diagnosed from non-lesional brain biopsies. These patients were previously healthy 10, 11 and 13 year olds; 2 males, 1 female; presenting with acute onset seizures or status epilepticus. Bloodwork returned normal or with mild elevated inflammatory markers. CSF returned normal in one patient, elevated WCC in another, and elevated protein in the last patient, all with normal opening pressures. Extensive testing form infective aetiology in serology and CSF returned negative in one; one patient tested positive for Mycoplasma IgM in serology but negative in CSF; one patient tested positive for EBV IgG but negative for VCA IgM. An infective aetiology was not considered to be the primary cause in these patients. All patients were treated with corticosteroids, pulse IV cyclophosphamide for 6 months followed with maintenance Mycophenolate Mofetil treatment for 18 months. All three experienced significant improvement in neurologic outcomes: 1 had mild ongoing cognitive deficits but good seizure control on weaning antiepileptic medications; 2 had almost complete normalization of their neurologic deficits with no further seizures.
Conclusions Neuroimaging is a corner stone in the diagnostic evaluation of childhood CNS vasculitis. In children presenting with refractory seizures, raised inflammatory markers and no evidence of an infectious or neuronal autoantibody-mediated aetiology, a brain biopsy should be considered despite repeatedly negative or non-diagnostic MRI studies.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.