Table 2.

Considerations Before Pursuing Immunomodulatory Therapy

Further work-up	Rationales
Lumbar puncture, EEG, MRI, and sleep study (if feasible).	It is imperative to rule out more specific disorders before starting immunomodulatory therapy (AE, CNS vasculitis, NPSLE, ADEM, infectious encephalitis, etc.) (Graus et al. 2016).
	Corticosteroids may mask/treat another brain inflammatory disease and impede accurate diagnosis of another disorder.
	Rule out seizure disorders (i.e., ESES) and metabolic/genetic disorders.
	Follow established guidelines (institutionally based or published) for evaluation of these other brain diseases.
	If mild-to-moderate disease, no memory impairment or encephalopathy, the clinician may choose to defer the LP.
Evaluate for immunodeficiency.	Inflammatory diseases/autoimmunity are more common in patients with immunodeficiency.
	Immunodeficiency predisposes to infection and infection may worsen on corticosteroids.
Obtain serum IgA before giving IVIG.	If deficient (<10 mg/dL), use IgA-depleted IVIG. If possible store a serum sample (one red top) in case further infectious or autoimmune work-up is needed.
Screen for:  (1) Tuberculosis: PPD or interferon-gamma release assay such as Quantiferon (R) or T spot assay (R); see age-appropriate guidelines.  (2) Endemic fungi if indicated: For United States, Coccidioidomycosis in Northern California and the Southwest; Blastomyces in the Midwest, South-central, and Southeast; Histoplasma in Central and Eastern states.  (3) Parasitic diseases if indicated: Toxoplasma gondii (worldwide with high prevalence in people with cat interactions and rare meat consumption); Trypanosoma cruzi (Chagas disease endemic in Mexico, Central, and South America).	Corticosteroids may activate infection.
Hepatitis B serology.	Rituximab can reactivate hepatitis B virus.
	If patient has already had IVIG and has positive hepatitis B serology, check hepatitis B PCR.
Ensure that the patient's environment (family and/or medical setting) is equipped to handle escalation in psychiatric symptoms.	Many patients have transient worsening of psychiatric symptoms after corticosteroid burst/pulse and occasionally after initiation of other immunomodulators. If patient has rage/violence, life-threatening impulsivity, mood instability, suicidality, etc., ensure that the environment can maintain safety in case the patient has escalated behavior.

ADEM, acute disseminated encephalomyelitis; AE, autoimmune encephalitis; CNS, central nervous system; EEG, electroencephalography; ESES, electrical status epilepticus in sleep; IgA, immunoglobulin A; IVIG, intravenous immunoglobulins; LP, lumbar puncture, MRI, magnetic resonance imaging; NPSLE, neuropsychiatric systemic lupus erythematosus; PCR, polymerase chain reaction; PPD, purified protein derivative.