Neuroradiological signs of encephalopathy in children with autism spectrum disorders associated with genetic folate deficiency

Abstract

The results of five meta‑analyzes indicate the association of autism spectrum disorders (ASD) with genetic deficiency of the folate cycle (GDFC) in children. In such cases, specific encephalopathy is formed with predominant immune‑dependent pathways of pathogenesis, the radiological signs of which are insufficiently studied.
 Objective —— to describe the typical neuroimaging signs of encephalopathy in children with GDFC suffering from ASD, and to find correlations between clinical signs, mechanisms of nervous system damage and neuroimaging data to optimize the algorithm of diagnosis, monitoring and treatment.
 Methods and subjects. The retrospective analysis of medical data of 225 children aged 2 to 9 years with GDFC, in which there were clinical manifestations of ASD (183 boys and 42 girls). The diagnosis of ASD was made by child psychiatrists according to the criteria of DSM‑IV‑TR (Diagnostic and Statistical Manual of mental disorders) and ICD‑10 (The International Statistical Classification of Diseases and Related Health Problems). Pathogenic polymorphic variants of folate cycle genes were determined by PCR with restriction. Neuroimaging was performed by MRI of the brain in conventional modes (T1‑ and T2‑weighted, FLAIR) on tomographs with a magnetic induction of 1.5 T. To study the associations between the indicators, the odds ratio (OR) and the 95 % confidence interval (95 % SI) were used.
 Results. There are 5 main groups of neuroimaging signs characteristic of leukoencephalopathy, temporal mesial sclerosis, PANS/PITANDS/PANDAS, congenital CMV neuroinfection and postnatal encephalitis, mild congenital CNS abnormalities. Neuroimaging signs are closely associated with the results of special laboratory tests that characterize the known immune‑dependent mechanisms of CNS damage, and with the emergence of relevant clinical syndromes, consistent with modern concepts of major infectious or autoimmune lesions of the nervous system in immunosuppressed patients. Laboratory‑radiological‑clinical complexes (virus‑induced temporal mesial sclerosis, autoimmune limbic encephalitis, autoimmune subcortical encephalitis, autoimmune or virus‑induced demyelinating lesions of the cerebral hemispheres and mild congenital malformations) have been identified.
 Conclusions. Encephalopathy in children with ASD associated with GDFC has a complex pathogenesis and is the result of combining a number of immune‑dependent forms of CNS damage in different ways in different patients, leading to a heterogeneous clinic‑radiological phenotype.