N-Methyl-d-aspartate (NMDA) receptor antibody in relation to autism spectrum disorder (ASD): presence and association with symptom profile

Background Several studies pointed to immune dysregulation abnormalities linked to autism spectrum disorders (ASD). Of those, several autoantibodies had been identified. Recent findings of N-methyl d-aspartate (NMDA) antibodies in autoimmune encephalitis suggested that it caused symptoms like autistic regression. Thus, the purpose of the study was to test for the presence of anti-NMDAR antibodies in the ASD disorder population and to correlate this with the clinical findings. Results Eighty-seven autistic children, 4–12 years old, were enrolled in the study and were matched with sixty typically developing children used as controls. The diagnosis of cases was confirmed by ADOS-2 and clinical evaluation. None of the control children had positive anti-NMDAR antibodies, while 26.4% (23 children) of the patients’ group were positive for serum anti-NMDA receptor antibodies (> 200 pg/ml, p = 0.0157). The positive anti-NMDAR antibody was statistically correlated with better speech stage (p = 0.017), more severe stereotyped behavior (p ≤ 0.001), and abnormal EEG findings (p = 0.025). Conclusions There is a possibility of the presence of anti-NMDAR antibodies in the autism spectrum disorder population with certain characteristics, especially the severity of the stereotyped behaviors.

Retinol-binding protein 4 in combination with lipids to predict the regression phenomenon of autism spectrum disorders

Background About 20–40 % of autistic people experience a phenomenon of regression. Retinol binding protein 4 (RBP4) plays an important role as an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis. Abnormal fatty acid metabolism and lipid mediators have been reported to be related to the etiological mechanism in autism, and amelioration of impaired lipid metabolism can be recognized as a treatment strategy for autism. The purpose of this study is to explore the relationship between RBP4, lipids, and the autistic regression phenomenon, and to discuss their potentials as biomarkers for the autistic regression phenomenon. Methods A total of 60 autistic individuals (18 with regression phenomenon, 42 without regression phenomenon) (ASD group) and 36 healthy controls were enrolled in this case-control study. The levels of RBP4, total cholesterol (TC), high-density lipoprotein (HDLC), low–density lipoprotein (LDLC), and triglyceride (TG) were measured. Childhood Autism Rating Scale (CARS) is used to assess the severity of autism. Ethical measures were performed in compliance with the current Declaration of Helsinki and written informed consent was obtained from the parents before enrollment of the children and adolescents. Results Compared with control subjects, autistic individuals had lower levels of TC (P = 0.007), RBP4 (P = 0.001), and HDLC (P = 0.027). The levels of RBP4 in ASD group were positively correlated with TG (r = 0.355, P = 0.005), HDLC (r = 0.257, P = 0.047), TG/TC (r = 0.376, P = 0.003) and TG/LDLC (r = 0.363, P = 0.004), and were negatively correlated with CARS (r=-0.296, P = 0.003). Further logistic regression demonstrated that decreased RBP4 concentration was associated with the presentation of the autistic regression phenomenon even after the adjustment of the potential confounding factors. Conclusions Serum RBP4 is associated with the autistic regression phenomenon and the severity of ASD. Further studies are needed to expound whether decreased RBP4 participates in the development of the autistic regression phenomenon.

Autism, Epilepsy, and Neuroregression: Photosensitivity on Electroencephalography Solved the Riddle

Autistic epileptiform regression is an uncommon but extensively described malady in children. The clinico-etiological spectrum of this entity ranges from electrical status epilepticus in sleep to various neurogenetic and neurodegenerative disorders. Identification of these disorders is crucial considering their therapeutic and prognostic implications. Simple investigations such as neuroimaging and electroencephalography with activation procedures can provide valuable diagnostic clues in resource-limited settings; facilitating targeted genetic/metabolic testing. Here we report a 3.5-year-old girl with autistic regression and epilepsy. Neuronal ceroid lipofuscinosis was suspected as her electroencephalogram showed photoparoxysmal response on low-frequency (1-3 Hz) intermittent photic stimulation. A deficient leukocyte tripeptidyl peptidase 1 enzyme confirmed the diagnosis of late infantile neuronal ceroid lipofuscinosis.