MRI Findings in 77 Children with Non-Syndromic Autistic Disorder

International audienceBACKGROUND: The clinical relevance of MR scanning in children with autism is still an open question and must be considered in light of the evolution of this technology. MRI was judged to be of insufficient value to be included in the standard clinical evaluation of autism according to the guidelines of the American Academy of Neurology and Child Neurology Society in 2000. However, this statement was based on results obtained from small samples of patients and, more importantly, included mostly insufficient MRI sequences. Our main objective was to evaluate the prevalence of brain abnormalities in a large group of children with a non-syndromic autistic disorder (AD) using T1, T2 and FLAIR MRI sequences. METHODOLOGY: MRI inspection of 77 children and adolescents with non-syndromic AD (mean age 7.4+/-3.6) was performed. All met the DSM-IV and ADI -R criteria for autism. Based on recommended clinical and biological screenings, we excluded patients with infectious, metabolic or genetic diseases, seizures or any other neurological symptoms. Identical MRI inspections of 77 children (mean age 7.0+/-4.2) without AD, developmental or neurological disorders were also performed. All MRIs were acquired with a 1.5-T Signa GE (3-D T1-FSPGR, T2, FLAIR coronal and axial sequences). Two neuroradiologists independently inspected cortical and sub-cortical regions. MRIs were reported to be normal, abnormal or uninterpretable. PRINCIPAL FINDINGS: MRIs were judged as uninterpretable in 10% (8/77) of the cases. In 48% of the children (33/69 patients), abnormalities were reported. Three predominant abnormalities were observed, including white matter signal abnormalities (19/69), major dilated Virchow-Robin spaces (12/69) and temporal lobe abnormalities (20/69). In all, 52% of the MRIs were interpreted as normal (36/69 patients). CONCLUSIONS: An unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in non-syndromic autism. These results could contribute to further etiopathogenetic research into autism

Impairment of cerebello-thalamo-frontal pathway in Rab-GDI mutated patients with pure mental deficiency

International audienceBackground: Rab-GDI mutations are responsible for "pure" mental deficiency, without any specific clinical features or brain malformation. Therefore, screening for mutations in mentally retarded patients is not available on a routine basis. Moreover, neuronal networks involved in mental deficiency still remain largely unknown.Methods: We performed a fine neuropsychological and imaging study in five patients from two unrelated families, affected with mental deficiency due to a mutation in the Rab-GDI gene. High resolution 3D brain MRI of the five mentally retarded adult males (mean age 33 years) were compared to MRI of 14 healthy males (mean age 35 years) using a Voxel-Based Morphometric analysis (VBM).Results: All patients had isolated moderate mental retardation (WAIS-III IQ range, 41-50; mean 45) without specific morphological or behavioural features. No obvious brain abnormality was observed on visual inspection of individual scans. Using VBM analysis, Rab-GDI mutated patients' MRIs exhibited significant brain changes compared to normal subjects (p < 0.05, corrected for multiple comparisons): increased grey matter density in left cerebellum and in left angular gyrus, decreased grey matter volume in thalami, decreased white matter density in prefrontal lobes, right fusiform occipito-temporal gyrus, and decreased white matter volume in cerebellar peduncles.Conclusions: These morphological changes observed in Rab-GDI mutated patients, mainly localized in the cerebello-thalamo-prefrontal pathway, are consistent with the hypothesis that the cerebellum is one of the critical components of a global learning network. Our results open new avenues in the diagnosis of non-specific mental deficiency using gene-specific "brain maps" as endophenotypes. (C) 2008 Elsevier Masson SAS. All rights reserved

Intensive Versus Subcutaneous Insulin in Patients With Hyperacute Stroke

Background and Purpose— Intensive insulin therapy (IIT) has not yet proven its efficacy on stroke prognosis or in the reduction of MRI infarct growth. The INSULINFARCT study aims at determining in patients with hyperacute stroke whether IIT, with a better control of poststroke hyperglycemia, would reduce subsequent MRI infarct growth than usual care with subcutaneous insulin. Methods— One hundred eighty patients with MRI-proven ischemic stroke and with National Institutes of Health Stroke Scale from 5 to 25 at admission (&lt;6 hours) were randomized to receive IIT or usual subcutaneous insulin for 24 hours. Admission hyperglycemia was not required for recruitment. Control MRI and 3-month follow-up (with functional outcome and serious adverse events) were planned. The primary objective was to detect a difference in the proportion of patients with mean capillary glucose test &lt;7 mmol/L during 24 hours. The secondary objective was to investigate whether IIT would reduce infarct growth. The analysis was planned in intention-to-treat. Patients with &gt;3 missing capillary glucose test were excluded (n=4). Results— The proportion of patients with mean capillary glucose test &lt;7 mmol/L in the first 24 hours was higher in the IIT group (95.4% [83 of 87] versus 67.4% [60 of 89]; P &lt;0.0001). The infarct growth was lower in the subcutaneous insulin group (median, 10.8 cm 3 ; 95% CI, 6.5–22.4 versus 27.9 cm 3 ; 14.6–40.7; 60% of increase; P =0.04). The 3-month functional outcome (45.6% [41 of 90] versus 45.6% [41 of 90]), death (15.6% [14 of 90] versus 10% [9 of 90]), and serious adverse events (38.9% [35 of 90] versus 35.6% [32 of 90]) were similar in the subcutaneous insulin and IIT group. Conclusion— The IIT regimen improved glucose control in the first 24 hours of stroke but was associated with larger infarct growths. IIT cannot be recommended in hyperacute ischemic stroke. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique Identifier: NCT00472381. </jats:sec

White matter abnormalities in autism.

<p>Two children illustrating the principal categories of white matter signal abnormalities. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004415#pone-0004415-g001" target="_blank">Figure 1A</a>. Punctate T2 Hyperintensity: Abnormal findings were placed in this category when small (<2 mm) rounded abnormalities were found scattered bilaterally in the white matter (white arrow). They were asymmetric and homogeneous, and no findings suggest that necrosis was present. They were very intense compared with adjacent white matter on T2 and FLAIR sequences, and did not involve the basal ganglia, the periventricular white matter fibers or the sub-cortical U fibers. These abnormalities were generally found in association with other supratentorial abnormalities. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004415#pone-0004415-g001" target="_blank">Figure 1B</a>. Posterior T2 Hyperintensity. Abnormalities placed in this category were “plaque-like areas” of mild white matter hyperintensity relatively symmetrical bilaterally at the posterior horns of the lateral ventricles (black arrow). There was no deformation of the lateral ventricular contour adjacent to these lesions. No abnormality of the sub-cortical U fibers was observed.</p

Temporal pole abnormalities in a child with autism.

<p>Example of a typical sub-cortical hyperintensities on T2-weighted coronal images localized in the temporal poles observed in children with autism (red arrows) and a normal image of a control child without autism.</p

Clinical characteristics of the group of 77 children with autistic disorder.

<p>ADI-R = Autism Diagnosis Interview – Revised</p>*<p>Scores obtained in 42 children with sufficient verbal capacities</p

Clinical and sociodemographic characteristics of children with AD related to normal and abnormal MRIs.

<p>Clinical and sociodemographic characteristics of children with AD related to normal and abnormal MRIs.</p