Role of Immunotherapy in Down Syndrome Disintegrative Disorder (DSDD)

Objective To describe case series of patients with DSDD, successfully treated with immunotherapy including Intravenous Immunoglobulin (IVIG) at a single academic center. Background Down syndrome is the most common chromosomal disorder, and in most cases, is due to trisomy of chromosome 21. DSDD is underrecognized, rapidly progressive neuropsychiatric syndrome with various postulated etiology including psychological stress, primary psychiatric disorder and autoimmunity. Design/Methods 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. Results 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. Conclusions DSDD should be considered in patients with down syndrome with rapid regression. It is often associated with positive thyroid peroxidase antibody suggesting immune mediated etiology. Various immunotherapy treatments have been reported in literature including steroid, IVIG, mycophenolate and rituximab with significant improvement in selected patient with autoimmunity.