Childhood CNS vasculitis is a newly recognized disease entity, which can occur in isolation as a primary disorder – childhood primary angiitis of the CNS (cPACNS)–or secondary to systemic diseases. Since early initiation of treatment is associated with improved disease outcome, rapid evaluation and timely diagnosis are essential. The clinical presentation can be highly variable. Children present with newly acquired focal and/or diffuse neurological deficits and/or psychiatric symptoms. Inflammatory markers and CSF analysis are essential, but show limited sensitivity and specificity. MRI studies are highly sensitive for areas of focal inflammation, however lack specificity. Negative MRI studies do not exclude inflammatory brain disease. Angiography is the key diagnostic modality for large to medium vessel cPACNS. Characteristic angiographic findings include segmental cerebral vessel stenoses and corresponding contrast enhancement in the vessel wall. In children with normal angiography, confirmation of small vessel cPACNS requires brain biopsy. A thorough diagnostic evaluation for cPACNS should include a workup for causes of secondary CNS vasculitis, evaluation for CNS vasculitis mimics, and analysis of markers of nonvasculitic inflammatory brain diseases when appropriate. Early recognition with timely treatment of childhood CNS vasculitis can significantly alter the course of this potentially devastating disease.
Systemic disorders with possible involvement of the nervous system include a variety of diseases with presumed inflammatory and autoimmune pathomechanisms, among them Behçet disease, sarcoidosis, systemic lupus erythematosus, juvenile idiopathic arthritis, scleroderma, and Sjögren syndrome. This disease group encompasses systemic inflammatory disorders with a genetically defined dysregulation of the innate immune system as well as systemic autoimmune disorders characterized by alterations of the adaptive immunity such as autoantibodies and autoreactive T cells. Although more commonly diagnosed in adults, all of these diseases can manifest in childhood and some as early as infancy. Neurological involvement may represent the initial manifestation, and nearly every neurological symptom can be caused by inflammatory/autoimmune diseases. In a child with (sub)acute onset of otherwise unexplained neurological findings, consideration of inflammatory/autoimmune disorders may be of crucial therapeutic and prognostic importance. In the absence of disease-specific clinical features, the initial diagnostic workup is broad. Basic blood tests include inflammatory markers and autoantibodies. Cerebral magnetic resonance imaging and a lumbar puncture with measurement of opening pressure as well as cerebrospinal fluid analysis are indicated in most patients with central nervous system (CNS) involvement. Skin, muscle, or organ biopsies (e.g., renal) may provide additional information. Especially in patients with isolated CNS involvement, a brain biopsy may be indicated. Timely recognition and treatment of CNS inflammation may improve or even reverse clinical symptoms and prevent secondary brain injury.
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