Cerebrospinal Fluid Findings of 36 Adult Patients with Autism Spectrum Disorder.

Kimon Runge,Thomas Blank,Rick Dersch,Simon Maier,Hanna Kuzior,Dominique Endres,Kathrin Nickel,Ludger Tebartz Van Elst,Miriam Matysik,Tilman Robinson,Dominik Denzel,Katharina Domschke

doi:10.3390/brainsci10060355

Abstract

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by difficulties with social interaction, repetitive behavior, and additional features, such as special interests. Its precise etiology is unclear. Recently, immunological mechanisms, such as maternal autoantibodies/infections, have increasingly been the subject of discussion. Cerebrospinal fluid (CSF) investigations play a decisive role in the detection of immunological processes in the brain. This study therefore retrospectively analyzed the CSF findings of adult patients with ASD. CSF basic measures (white blood cell count, total protein, albumin quotient, immunoglobulin G (IgG) index, and oligoclonal bands) and various antineuronal antibody findings of 36 adult patients with ASD, who had received lumbar puncture, were compared with an earlier described mentally healthy control group of 39 patients with idiopathic intracranial hypertension. CSF protein concentrations and albumin quotients of patients with ASD were significantly higher as compared to controls (age corrected: p = 0.003 and p = 0.004, respectively); 17% of the patients with ASD showed increased albumin quotients. After correction for age and gender, the group effect for total protein remained significant (p = 0.041) and showed a tendency for albumin quotient (p = 0.079). In the CSF of two ASD patients, an intrathecal synthesis of anti-glutamate decarboxylase 65 (GAD65) antibodies was found. In total, more of the ASD patients (44%) presented abnormal findings in CSF basic diagnostics compared to controls (18%; p = 0.013). A subgroup of the patients with adult ASD showed indication of a blood–brain barrier dysfunction, and two patients displayed an intrathecal synthesis of anti-GAD65 antibodies; thus, the role of these antibodies in patients with ASD should be further investigated. The results of the study are limited by its retrospective and open design. The group differences in blood–brain barrier markers could be influenced by a different gender distribution between ASD patients and controls.

Highlights

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by deficits in social interaction and communication, unusually narrowed interests, and repetitive behavior in different situations [1]
The presence of other common comorbid conditions in patients with ASD was not defined as an exclusion criterion; examples include affective disorders (ICD-10: F30-F39), or neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD; ICD-10: F90.x), or Tourette syndrome (ICD-10: F95.2)
The control group comprised 39 mentally healthy controls with idiopathic intracranial hypertension (IIH; ICD-10: G93.2), a non-inflammatory neurological disease characterized by increased intracranial pressure of unknown origin

Summary

Introduction

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by deficits in social interaction and communication, unusually narrowed interests, and repetitive behavior in different situations [1]. The description of ASD in the Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5) demonstrates the clear tendency of the scientific community to subsume the various previous autism subtypes of the DSM-IV and of the International Statistical. Classification of Diseases and Related Health Problems, version 10 (ICD-10) F84.0, corresponding in the DSM-IV to autistic disorder 299.00), atypical autism (ICD-10 F84.1, not listed in the DSM-IV), and Asperger syndrome (ICD-10 F84.5, DSM-IV 299.80)) under a single diagnostic category [1,3,4]. Despite the growing public and scientific interest in ASD over the past decades [5], which reflects increasing prevalence rates that are well above 1% and up to 2.7% depending on the populations studied [6,7], the disorder’s precise etiology and pathophysiology remain elusive.

Methods

Results

Discussion

Conclusion