Table 4.

Corticosteroid-Sparing Agents (Therapies Used in Conjunction with Steroids or to Replace Corticosteroids) That Have Been Used in Pediatric Acute-Onset Neuropsychiatric Syndrome/Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection

	IVIG	TPE	Rituximab or MMFa
New onset.	One to six monthly courses of IVIG in moderate-to-severe disease or in severe-to-extreme if TPE not available.	Use in severe-to-extreme cases if patient has life-threatening disease.	Patient has moderate-to-extreme impairment. and patient has proven (documented by mental health professional) responsiveness to corticosteroids, IVIG, or TPE. and patient has evidence of inflammation/autoimmunity and objective signs of organic brain disease.
Relapsing-remitting course.	Consider repeated dosing of IVIG if patient meets criteria for an immunodeficiency syndrome.	Not indicated unless patient is in a severe-to-extreme flare.	Consider use if patient has a deteriorating baseline (i.e., each flare leaves the patient with permanent deficits) or frequent relapses. and patient has proven responsiveness to corticosteroids, IVIG, or TPE. and patient has evidence of inflammation/autoimmunity and objective signs of organic brain disease.
Very delayed care, chronic-static, or chronic-progressive course.	Trial of IVIG. If patient responds, then symptoms recrudesce then patient is deemed immune therapy responsive, thus consider (A), (B), or (C).	Response to TPE may be transient. Consider introduction of rituximab or MMF if there is evidence of autoimmunity.	Patient has moderate-to-extreme impairment. and patient has proven responsiveness to corticosteroids, IVIG, or TPE. and patient has evidence of inflammation/autoimmunity and objective signs of organic brain disease.
	(A) Monthly IVIG until patient is no longer having period of improvement after IVIG and recrudescence as IVIG effect wanes.
	(B) Rituximab, MMF, etc.
	(C) (A)+(B).

Goal is to achieve remission with minimal corticosteroids.

^a Rituximab and MMF are generally used when the patient has demonstrated steroid/IVIG responsiveness, but the patient is steroid/IVIG dependent and there is a chronic course. Duration of therapy needed is unknown. For other inflammatory brain diseases, MMF is used for up to 5 years and rituximab is used for 1–3 years ± additional years of MMF.

IVIG, intravenous immunoglobulins; MMF, mycophenylate mofetil; PANS, pediatric acute-onset neuropsychiatric syndrome; TPE, therapeutic plasma exchange.