Inflammatory Manifestations of Systemic Diseases in the Central Nervous System

Abstract

Purpose of Review This review presents the current recommended therapeutic interventions for inflammatory disease in the central nervous system (CNS) secondary to systemic diseases of immune dysregulation. Treatment recommendations for CNS inflammation associated with rheumatologic conditions, immune-related adverse effects from immune checkpoint inhibitors (ICIs), and demyelinating disease from tumor necrosis factor-α (anti-TNFs) are explored. Additional therapeutic options for inflammation related to postviral syndromes and genetic immunodeficiencies are also discussed. Recent Findings In addition to treatment of mild, moderate, and severe CNS rheumatologic disease as guided by the European League Against Rheumatism (EULAR), early consideration of rituximab for severe IgG4-related disease and induction with anti-TNF therapy for severe neurosarcoidosis should be considered. Although often not first line, treatment options for CNS inflammatory diseases based on disease mechanism are emerging, including tocilizumab for Behcet's disease, natalizumab for ICI associated autoimmune encephalitis, and abatacept for treatment of infiltrative disease secondary to CTLA-4 deficiency. Hematopoietic stem cell treatments represent highly efficacious but risky options for autoimmunity related to genetic immunodeficiency. Summary While early high dose steroids remains first line therapy for most CNS inflammatory conditions, a rapidly expanding arsenal of immune targeted therapies offers clinicians tailored disease specific options for treatment.

Autoimmune encephalopathies presenting as dementia of subacute onset and rapid progression

“… 61 , 62 Thus, serum testing for non-neural antibodies such as antinuclear antibody, double-stranded DNA antibodies, antibodies to the extractable nuclear antigen, anti-neutrophilic cytoplasmic antibodies (ANCA), rheumatoid factor, phospholipid antibodies, beta 2 glycoprotein-1 antibodies, lupus anticoagulant, and IgG4 can be considered when clinical features are suggestive to assess for neurologic involvement of rheumatologic disorders. 63 …”

Pituitary Sarcoidosis in a Pediatric Patient Successfully Treated With Adalimumab and Methotrexate

“…2 Hypothalamic/pituitary dysfunction, headaches, meningismus, central nervous system mass lesions, and peripheral neuropathies are other manifestations that can occur across all ages. 1,2,18 Our patient had chronic, unrelenting headaches with poor response to oral analgesics, vision changes, and gait instability, which were concerning for an intracranial process, and her amenorrhea hinted at an underlying hormonal dysfunction, later confirmed by biochemical testing. Even though decreased levels of free T4 with normal TSH can be observed in obese individuals, she had normal studies in the setting of similar weight 2 years earlier.…”

“…Due to the paucity of data specific to pediatric neurosarcoidosis, there are no standardized protocols and treatment is largely based on case series, most oriented to adults with systemic disease. 5 , 18 Corticosteroids and other immunosuppressive agents have been used for disease management with variable response. A stepwise approach has been proposed, starting with oral corticosteroids (IV for severe disease) as first-line therapy.…”

“… 4 These are usually tapered slowly for months; 80% of patients of all ages are reported to fail steroid therapy due to progression of disease or toxicity. 4 , 18 In contrast, many pediatric cases have been reported to have long-term resolution (up to 8 years) on steroid monotherapy; a few patients did not receive any immunosuppression. 5 The timing and indications of steroid-sparing agents are less clear.…”

“…Infliximab is proposed as a third-line agent, while adalimumab, cyclophosphamide, and rituximab are considered fourth line. 4 , 18 In our patient, an aggressive treatment approach aiming at complete lesion resolution was taken, given the potential for long-term morbidity from central nervous system lesions. Accordingly, she received high doses of IV followed by oral corticosteroids, and was simultaneously started on methotrexate and adalimumab.…”