Management of Autoimmune Encephalitis in a 7-Year-Old Child With CTLA-4 Haploinsufficiency and AMPA Receptor Antibodies: A Case Report.

OBJECTIVES: We report on the therapeutic management of early-onset severe neurologic symptoms in cytotoxic T lymphocyte antigen-4 haploinsufficiency (CTLA-4h) and the presence of antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) as an important finding. METHODS: This is a case report from a Dutch academic hospital. Repeated clinical examinations, repeated brain MRI and extended diagnostics on serum and CSF were performed. We used the CARE checklist. RESULTS: A 7-year-old boy was diagnosed with CTLA-4h based on family screening. On diagnosis, he had mild chronic diarrhea and autism spectrum disorder, but no abnormalities in extensive laboratory screening. Six months later, he presented with sudden-onset autoimmune encephalitis. Repeated brain MRI revealed no abnormalities, but immunohistochemistry analysis on serum and CSF showed the presence of AMPAR antibodies. Treatment was initially focused on immunomodulation and targeted CTLA-4 replacement therapy. Because of the persistent fluctuating cerebellar and neuropsychiatric symptoms and the potential clinical significance of the AMPAR antibodies, treatment was intensified with repetition of first-line immunomodulation and rituximab. This combined therapy resulted in sustained clinical improvement and served as a bridge to curative hematopoietic stem cell transplantation. DISCUSSION: This case illustrates the rare early onset of autoimmune encephalitis and presence of AMPAR antibodies in CTLA-4h. Targeted CTLA-4 replacement therapy resulted in a partial response. However, awaiting its optimal therapeutic effect, refractory CNS symptoms required intensification of immunomodulation. The identification of AMPAR antibodies guided our treatment decisions. CLASSIFICATION OF EVIDENCE: This provides Class IV evidence. It is a single observational study without controls.

Early MRI diagnosis of Sturge Weber Syndrome type 1 in infants.

BACKGROUND: Patients with Sturge-Weber syndrome type 1 (SWS1) have a port-wine birthmark (PWB) as cutaneous hallmark. Up to 35% of neonates with a high risk PWB develop SWS1. Clinical manifestations are severe and often progressive. Especially early onset seizures are associated with worse neurocognitive outcome. Identification of pre-symptomatic SWS1 patients is hampered because brain MRI in the first months of life does not always show the for SWS1 characteristic leptomeningeal capillary malformation (LMC). OBJECTIVES: Identification of sensitive and specific MRI predictors for early SWS1 diagnosis. METHODS: In this retrospective single centre study, we included 24 SWS1 patients and 20 controls. We studied specificity and sensitivity for SWS1 diagnosis of LMC and indirect MRI signs such as choroid plexus (CP) size and thickness, abnormal white matter signal, lobar cerebral atrophy, ischemia and cortical calcifications. RESULTS: In SWS1 patients CP thickness and CP thickness ratio on non-contrast brain MRI was significantly increased. The optimal cut-off value of 5.6 mm on the affected side corresponded with a sensitivity of 91.7% and a specificity of 100% for confirmation of SWS1 diagnosis. In 21% of children aged ≤3 months with a later confirmed SWS1 diagnosis, LMC on initial MRI could not be discerned but CP thickness ≥5.6 mm on the affected side confirmed SWS1 diagnosis. CONCLUSIONS: In this study, CP size ratio and thickness were found to be sensitive and specific signs additional to earlier described criteria to support SWS1 diagnosis in neonates and infants which need to be confirmed in other series.