Tool #3 refers to biomarkers of disease, which may be found in the cerebrospinal fluid or serum. These may include specific cytokines and chemokines (interleukin [IL]-6, IL-1β, tumor necrosis factor-alpha (TNF-α), interferon gamma and monocyte chemoattractant protein-1), brain-specific proteins (such as neurofilament light chain that can indicate axonal injury, glial fibrillary acidic protein that reflects astrocytic activation and YKL-40 that is linked to microglial activation and disease progression in multiple sclerosis), and emerging markers, such as sTREM2 (soluble triggering receptor expressed on myeloid cells 2), osteopontin and macrophage migration inhibitory factor, that are being studied for their roles in neuroinflammatory processes.4 Dr. Muscal noted that clinicians should look to the serum to evaluate for signs of organ dysfunction that may help inform the differential diagnosis and to think about complement activation as may be involved in conditions like antiphospholipid syndrome, thrombotic microangiopathies and macrophage activation syndrome.
Tool #4 is tissue, which Dr. Muscal says does not always have to be the issue because most inflammatory brain diseases do not require brain biopsy to prove the diagnosis.
Dr. Muscal provided clinical pearls related to several specific rheumatic diseases that can involve the nervous system. For sarcoidosis, neurologic involvement is much less common in children than in adults. Neurosarcoidosis occurs in approximately 5–10% of adult patients with sarcoidosis (most often as part of systemic disease) and only about 6% of adult cases are isolated to the nervous system.5,6 Although nervous system involvement is seen in fewer than 5% of pediatric patients, children are more likely to present with isolated neurosarcoidosis.7,8 Behçet’s disease is one of few rheumatic conditions that can involve both the arteries and the veins when involving the CNS. Among systemic vasculitides, CNS involvement is rarer than involvement of other organ systems, but Takayasu arteritis, giant cell arteritis (GCA), polyarteritis nodosa and anti-neutrophil cytoplasmic antibody–associated vasculitis can do so (in a patient age 50 or above with vision changes, clinicians should thoroughly seek to rule out GCA in particular). About 5–10% of patients with IgG4-related disease will have nervous system involvement, and pachymeningitis is a specific manifestation that may be seen.9,10 Autoinflammatory conditions, such as neonatal-onset multisystem inflammatory disease, tumor necrosis factor receptor-associated periodic syndrome, deficiency of adenosine deaminase 2 (DADA2) and VEXAS (vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome), can all involve the nervous system, and diagnosing these conditions may have significant implications for therapy, such as the indication for TNF inhibitor therapy in cases of DADA2).
