Table 1.

General Strategies for Management of Pediatric Acute-Onset Neuropsychiatric Syndrome Based on Disease Trajectory

Disease trajectory	Recommendations
New-onset or acute flare	(1) Work-up infections and other causes of acute neuropsychiatric deteriorations per guidelinesa (Van Mater 2014; Chang et al. 2015; Graus et al. 2016; Cooperstock et al. 2017; Dale et al. 2017).
	(2) Refer for CBT and provide other supportive therapies (Thienemann et al. 2017).
	(3) Consider early use of corticosteroids (oral bursts or IV pulses) to abort or shorten flares (Tables 2 and 3).
	(4) Consider high-dose IVIG or other immunomodulatory therapies in moderate-to-severe cases (Tables 2 and 4).
Relapsing-remitting	(1)–(4) as above.
	(5) Evaluate for possibility of recurrent infections/exposures triggering flares.
	(a) If GAS infection is a frequent trigger for relapses, evaluate/treat close contacts and consider prophylaxis according to guidelines (Cooperstock et al. 2017).
	(b) Keep in mind that most flares are viral triggers. See (2)–(4) above for treatment of each flare.
	(c) Evaluate immune system competency: pursue immunodeficiency work-up if patient has recurrent sinopulmonary disease or fevers per guidelines (Chang et al. 2015). If immunodeficiency is present, IVIG may reduce the number and severity of intercurrent infections (Cooperstock et al. 2017).
Chronic-static or chronic-progressive Initial therapy is proposed in the box to the right. Patients with chronic-static or progressive disease may respond to corticosteroids or other induction immunotherapies but then relapse if therapy is stopped. Some patients need repeated doses of steroids and/or other immunotherapies (IVIG or other steroid-sparing agent).	(1)–(4) as mentioned.
	(5) Pursue immunomodulatory therapies according to symptom categories below:
	Mild-to-moderate neuropsychiatric symptoms:
	NSAIDs (Table 3).
	Oral corticosteroid burst (Table 3) to see whether baseline improves.
	Caution: use of combination NSAIDs+corticosteroids may result in gastritis; but these medications can be used safely in tandem.
	Mild-to-moderate neuropsychiatric symptoms with no response to NSAIDs and/or short burst of corticosteroids:
	(Repeat) oral prednisone ± prolonged taper (Table 3).
	Pulse corticosteroids (oral dexamethasone or IV methylprednisolone) (Table 3).
	Moderate-to-severe neuropsychiatric symptoms:
	Oral prednisone±taper or pulse corticosteroids (Table 3).
	High-dose IVIG or other induction steroid-sparing agent (Table 4).
	Severe-to-extreme neuropsychiatric symptoms:
	Refer to subspecialists for further evaluation for AE, NPSLE, CNS vasculitis, and consideration of using established (published and institutionally based) treatment protocols.
	Consider high-dose IV corticosteroids and/or other immunotherapies (Tables 3 and 4).
	Refractory disease course (i.e., psychiatric symptoms not responsive to initial immunomodulatory approaches already mentioned and no improvement in neurological signs):
	Refer to subspecialist for consideration of additional agentsb and/or combination therapy (up to four immunomodulatory therapies are used simultaneously to treat inflammatory brain diseases; that is, corticosteroids+TPE+IVIG+rituximab).
	Consider possibility of injured neurocircuitry and need for shifting to primary rehabilitation mode.

^a If the patient meets criteria for another brain inflammatory disease, follow the corresponding treatment guidelines (when published guidelines are not available, use institutionally based guidelines).

^b Rituximab, combination immunotherapy, or other aggressive immunomodulation regimens should be managed by clinicians with experience using these therapies, either as the primary prescriber or in close consultation with those managing the patient. There are no reported clinical trials and only limited clinical experience to support these approaches. This is not a definitive treatment algorithm; rather, it is a framework to aid in clinical decision-making. Before initiating any of the therapies, clinicians must consider the risk/benefit ratio for their individual patients and provide careful/informed counseling about risk of side effects (see Appendix Tables A1–A3 for detailed discussion of side effects).

AE, autoimmune encephalitis; CBT, cognitive behavioral therapy; CNS, central nervous system; GAS, group A Streptococcus; IV, intravenous; IVIG, intravenous immunoglobulins; NPSLE, neuropsychiatric systemic lupus erythematosus; NSAIDs, nonsteroidal anti-inflammatory drugs; PANS, pediatric acute-onset neuropsychiatric syndrome; TPE, therapeutic plasma exchange.