Table 3.

General Approach to Using Induction Corticosteroids and/or Nonsteroidal Anti-Inflammatory Drug Therapies in Pediatric Acute-Onset Neuropsychiatric Syndrome/Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection

	Mild-to-moderate flare	Moderate-to-severe flare	Severe-to-extreme flare a
Early in flare or early in initial presentation (<14 days). Early application of corticosteroids (once infection is ruled out) and NSAIDs may abort or limit duration of disease flares.	(A) Refer to CBT and supportive therapy. or (B) NSAIDs+(A). or if no improvement or deteriorating baseline then (C) ↓.	(A) Refer to CBT and supportive therapy. or (B) prednisone 1–2 mg/kg/day × 5 days+(A). or (C) oral dexamethasone pulse (20 mg/m2 divided twice daily for 3 days)+(A). or (D) IV MP pulse × 1 (30 mg/kg/dose)+(A).	(A) Refer to CBT and supportive therapy. or (B) oral dexamethasone pulse (20 mg/m2 divided twice daily for 3 days) alone or in combination with adjunct therapy (Table 4)+(A). (C) IV MP one to three consecutive daily pulses (30 mg/kg·dose·day × 3 days) alone or in combination with adjunct therapy (Table 4)+(A).
Late in flare (2–4 weeks).	(A) Refer to CBT and supportive therapy. or (B) NSAIDs+A. or (C) prednisone 1–2 mg/kg·day × 5 days+(A). If no response, re-evaluate for underlying infection per guidelines. If no infection and baseline worsening, go to next column.	Same as above box, except: (B) consider adding a 1-month prednisone taper (see Appendix B2 for taper) to oral prednisone burst. The mentioned pulse therapy approaches do not need tapers.	(A) Refer to CBT and supportive therapy. or (B) oral dexamethasone pulse (20 mg/m2 divided twice daily for 3 days) alone or in combination with steroid-sparing agent (Table 4)+(A). Long-standing disease will likely need more persistent corticosteroids. (C) IV MP one to five consecutive daily pulses (30 mg/kg·dose·day for up to 5 days) alone or in combination with adjunct therapy (Table 4). Consider weekly IV MP pulses for up to 6 weeks (if tolerated)+(A).
Very delayed care (>4 weeks). Application of corticosteroids late into the disease often requires higher dosing and/or more prolonged tapers. Steroid bursts may be followed by NSAIDS, with caution (see Appendix Tables A1 and A2).		(A) Refer to CBT and supportive therapy. or (B) prednisone 1–2 mg/kg·day × 5 days+(A). Consider adding a 1–2-month prednisone taper. or (C) oral dexamethasone pulse (20 mg/m2 divided twice daily for 3 days)+(A). or (D) IV MP one to three consecutive daily pulses (30 mg/kg·dose·day × 3 days)+(A). patient may need weekly or monthly pulses to maintain effect. Add steroid-sparing agent (Table 4) if patient is responsive to steroids but does not hold.

Optimal dosing approaches and utilization of adjunct immunomodulation have not been determined for PANS, but the approaches outlined in this table serve as a starting point for clinicians and academicians who treat patients with PANS and who are planning trials.

Important steroid warning: Most patients have transient worsening of psychiatric symptoms while on corticosteroids. If patient has rage/violence, life-threatening impulsivity, mood instability, suicidality, etc. and caregivers (including medical personnel) are unable to manage potentiation of these behaviors, give corticosteroids in psychiatric unit or medical-psychiatric unit or bypass corticosteroids and go straight to IVIG or other steroid-sparing agent (Table 4).

If no response to initial corticosteroid burst/pulse or relapse after steroid burst/pulse, consider reassessing for underlying infection per guidelines (Chang et al. 2015; Cooperstock et al. 2017) with attention to the possibility of sinusitis or close contact with GAS or asymptomatic acquisition of GAS. If no infection, repeat steroid bursts/pulses and/or give corticosteroid sparing agent (Table 4).

For details regarding side effects and dosing of NSAIDs and corticosteroids (including maximum dosing) go to Appendix Tables A1 and A2.

^a If patient meets criteria for another brain inflammatory disease, use said treatment protocol.

AE, autoimmune encephalitis; CBT, cognitive behavioral therapy; GAS, group A Streptococcus; IV, intravenous; IVIG, intravenous immunoglobulins; MP, methylprednisolone; NSAIDs, nonsteroidal anti-inflammatory drugs; PANS, pediatric acute-onset neuropsychiatric syndrome.