To describe case series of patients with DSDD, successfully treated with immunotherapy including Intravenous Immunoglobulin (IVIG) at a single academic center. 

Case-1: A 20-year-old fun loving female with trisomy-21 and infantile spasms started having complex partial seizures, hallucinations, speech regression, tics, abnormal head movement and obsessive-compulsive behavior.  

Case-2: A 20-year-old female cheerleader with trisomy-21, started having rapid regression in language, cognition, social skills and agitation over one year. 

Case-3: A 22-year-old female dancer with trisomy-21, started having subacute onset depression, hallucinations, sleep changes, anorexia and speech regression over one year. 

Case-1: MRI brain and cerebrospinal fluid (CSF) studies were normal including negative autoimmune encephalitis panel. Serum thyroglobulin and thyroid peroxidase antibody were high.  Prolonged oral steroid therapy helped but caused adverse effects. She was able to return to her premorbid baseline with chronic IVIG therapy every 10 weeks.

Case-2: MRI brain and CSF were normal. Serum autoimmune encephalitis panel, thyroglobulin antibody and thyroid peroxidase antibody were negative. Pulse IV steroids improved symptoms, however she regressed after stopping steroids. IVIG every 6 weeks along with electroconvulsive therapy improved neurological symptoms.

Case-3: MRI brain and EEG were normal. CSF showed elevated white blood cell count. Serum Thyroid antimicrosomal and thyroglobulin antibody were high. One dose of IVIG caused significant improvement in neurological symptoms for 6 weeks