7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Corpus Callosum Agenesis: Neuroanatomical Model of Autism Spectrum Disorder?

      letter

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Sir, The neuroanatomical basis of autism spectrum disorder (ASD) remains undeciphered. Neural system disconnection of the brain is hypothesized as causative. A substrate of this disconnection is agenesis of corpus callosum (AgCC). It is a very rare condition and is consistently reported with autism. However, cause–effect relationship remains to be established. A meta-analysis of 10 studies on magnetic resonance imaging (MRI) of 253 patients with AgCC and ASD showed a reduction in the size of corpus callosum.[1] Corpus callosum is responsible for functional interaction between the hemispheres in cognitive processes such as executive functions, abstract reasoning, speed of processing, and problem solving. It is also important for the development of social competence, emotional maturity, and communication of emotions.[2] However, AgCC can be asymptomatic or present with one or more neurodevelopmental disorders.[3] While symptoms of autism have been reported in children with AgCC, syndromic ASD has never been reported. We report a case of a toddler with AgCC meeting Diagnostic and Statistical Manual 5 criteria for ASD. CASE HISTORY A 2-year-old male child was brought to the Child Psychiatry Out Patient Department of our tertiary care centre with symptoms of hyperactivity, impulsivity, and inability to speak. Often, he would be moving aimlessly, flapping his hands. He would be fidgety and would not engage in any play activity for long. He would not play with any child and would not respond to being called. He made poor eye contact and would be engaged in solitary activities of arranging and stacking up objects. He would never share his interests or excitement, would not point at things of his interest, nor would he look at things shown by his mother. He would indicate his needs by pulling his mother's hands and using them for pointing. He would demand immediate fulfilment of his needs, and in case of any delay, would start banging his head. He was born of a nonconsanguineous marriage, with uneventful antenatal and postnatal course. His birth cry was delayed, with significantly difficult labor, but no other significant postnatal adverse events. He had delayed development in motor, speech, communication, and social domains. Currently, he was able to walk independently and would utter a few bi-syllables. He would not recognize his parents and would be hardly bothered by their absence. Childhood Autism Rating Scale score was 34, indicating moderate autism.[4] On Vineland Social Maturity Scale, he had the social age of 20 months, with Social Quotient (SQ) of 49, indicating moderate intellectual disability.[5] He had macrocephaly (head circumference was 51 cm, above WHO third percentile), but no other dysmorphic features were noticed. Macrocephaly prompted an evaluation for a structural neurological cause. T1 and T2-weighted MRI images showed partial agenesis of CC [Figure 1]. Figure 1 Cranial MRI, (a) Sagittal T2W MRI showing absent posterior body and splenium of corpus callosum (arrow), cingulate gyrus and the medial hemispheric sulci reaching upto the 3rd ventricular surface. (b) Coronal T2WI showing Probst bundle indenting medial aspect of the body of lateral ventricles. (c) Axial T1WI showing parallel orientation of ventricles He met the DSM 5 criteria for ASD, intellectual disability, and attention deficit hyperactivity disorder.[6] Absence of characteristic dysmorphic features and a normal karyotype ruled out genetic syndromes. A hearing evaluation was within normal limits, and he did not have any history of seizures. His thiamine and pyridoxine levels and thyroid profile were within normal limits. We could not find any genetic or toxic cause for AgCC in our case, nor could we identify any other independent risk factor for developmental delay. Hence, we considered a diagnosis of ASD and intellectual disability secondary to AgCC. We started risperidone at 0.5 mg/day for managing hyperactivity and repetitive motor behavior. Speech therapy, occupational therapy, and behavioral therapy were also started. The child is on regular follow-up in our centre: his hyperactivity is currently manageable, and he is being engaged in multiple behavioral and educational interventions. DISCUSSION Our patient had socio-communicative deficits with stimming behavior characteristic of ASD before 3 years of age, which is considered to be a diagnostic hallmark of syndromic ASD. He also had moderate intellectual disability. Presence of partial AgCC could be understood as the proximal risk factor for the autistic symptoms. The absence of posterior body can explain his moderate autism as this is the region vital for self-referential and social cognitive development.[7] Presence of Probst bundle is further evidence of AgCC, as the white matter tract, which has failed to form interhemispheric connection, has instead remained in the longitudinal orientation. This structural evidence of partial disconnection of the corpus callosum can be considered causative of ASD symptoms in the index case. Symptoms of ASD have been reported in AgCC on parent-reported scales and screening instruments; syndromic ASD has never been reported in children.[8 9] Only two adult cases with syndromic ASD in association with AgCC have been reported till date, which includes “Rainman” Kim Peek.[7] AgCC associated with extracallosal brain lesions is associated with poor prognosis and has an adverse impact on clinical outcome. ASD with AgCC is associated with a partial/total reduction of corpus callosum volume; structural dysconnectivity dysfunction is hypothesized to be causal for ASD.[7] Our case is unique by the fact that the diagnosis of ASD and comorbid intellectual disability has been made with AgCC in early childhood, reinforcing the structural etiological role of corpus callosum. Recent neuroimaging findings have corroborated the role of the corpus callosum in sociocognitive and self-referential deficits in autism. AgCC is being increasingly understood as a neurological model for deficits of autism. However, exact mechanisms still remain to be identified. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

          Related collections

          Most cited references9

          • Record: found
          • Abstract: found
          • Article: not found

          A meta-analysis of the corpus callosum in autism.

          Previous magnetic resonance imaging (MRI) studies have reported reductions in corpus callosum (CC) total area and CC regions in individuals with autism. However, studies have differed concerning the magnitude and/or region contributing to CC reductions. The present study determined the significance and magnitude of reductions in CC total and regional area measures in autism. PubMed and PsycINFO databases were searched to identify MRI studies examining corpus callosum area in autism. Ten studies contributed data from 253 patients with autism (mean age = 14.58, SD = 6.00) and 250 healthy control subjects (mean age = 14.47, SD = 5.31). Of these 10 studies, 8 reported area measurements for corpus callosum regions (anterior, mid/body, and posterior), and 6 reported area for Witelson subdivisions. Meta-analytic procedures were used to quantify differences in total and region CC area measurements. Total CC area was reduced in autism and the magnitude of the reduction was medium (weighted mean d = .48, 95% confidence interval [CI] = .30-.66). All regions showed reductions in size with the magnitude of the effect decreasing caudally (anterior d = .49, mid/body d = .43, posterior d = .37). Witelson subdivision 3 (rostral body) showed the largest effect, indicating greatest reduction in the region containing premotor/supplementary motor neurons. Corpus callosum reductions are present in autism and support the aberrant connectivity hypothesis. Future diffusion tensor imaging studies examining specific fiber tracts connecting the hemispheres are needed to identify the cortical regions most affected by CC reductions.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Agenesis of the corpus callosum and autism: a comprehensive comparison.

            The corpus callosum, with its ∼200 million axons, remains enigmatic in its contribution to cognition and behaviour. Agenesis of the corpus callosum is a congenital condition in which the corpus callosum fails to develop; such individuals exhibit localized deficits in non-literal language comprehension, humour, theory of mind and social reasoning. These findings together with parent reports suggest that behavioural and cognitive impairments in subjects with callosal agenesis may overlap with the profile of autism spectrum disorders, particularly with respect to impairments in social interaction and communication. To provide a comprehensive test of this hypothesis, we directly compared a group of 26 adults with callosal agenesis to a group of 28 adults with a diagnosis of autism spectrum disorder but no neurological abnormality. All participants had full-scale intelligence quotient scores >78 and groups were matched on age, handedness, and gender ratio. Using the Autism Diagnostic Observation Schedule together with current clinical presentation to assess autistic symptomatology, we found that 8/26 (about a third) of agenesis subjects presented with autism. However, more formal diagnosis additionally involving recollective parent-report measures regarding childhood behaviour showed that only 3/22 met complete formal criteria for an autism spectrum disorder (parent reports were unavailable for four subjects). We found no relationship between intelligence quotient and autism symptomatology in callosal agenesis, nor evidence that the presence of any residual corpus callosum differentiated those who exhibited current autism spectrum symptoms from those who did not. Relative to the autism spectrum comparison group, parent ratings of childhood behaviour indicated children with agenesis were less likely to meet diagnostic criteria for autism, even for those who met autism spectrum criteria as adults, and even though there was no group difference in parent report of current behaviours. The findings suggest two broad conclusions. First, they support the hypothesis that congenital disruption of the corpus callosum constitutes a major risk factor for developing autism. Second, they quantify specific features that distinguish autistic behaviour associated with callosal agenesis from autism more generally. Taken together, these two findings also leverage specific questions for future investigation: what are the distal causes (genetic and environmental) determining both callosal agenesis and its autistic features, and what are the proximal mechanisms by which absence of the callosum might generate autistic symptomatology? © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Social and behavioral problems of children with agenesis of the corpus callosum.

              Archival data from a survey of parent observations was used to determine the prevalence of social and behavioral problems in children with agenesis of the corpus callosum (ACC). Parent observations were surveyed using the Child Behavior Checklist (CBCL) for 61 children with ACC who were selected from the archive based on criteria of motor development suggesting a relatively high general level of functioning. Younger children with ACC (ages 2-5) were rated as primarily having problems with sleep. Older children with ACC (ages 6-11) manifested problems in attention, social function, thought, and somatic complaints. The older children with ACC were also compared to CBCL data from 52 children with autism who were selected from a previous study. Children with ACC were generally less impaired than children with autism on nearly all scales, with significantly less severe problems in the areas of attention, anxiety/depression, social function, and unusual thoughts. A further questionnaire related to diagnostic criteria for autism indicated that some children with ACC had traits that are among those that contribute to the diagnosis of autism within the domains of social interaction and social communication, but fewer who manifest repetitive and restricted behaviors.
                Bookmark

                Author and article information

                Journal
                Indian J Psychol Med
                Indian J Psychol Med
                IJPsyM
                Indian Journal of Psychological Medicine
                Wolters Kluwer - Medknow (India )
                0253-7176
                0975-1564
                May-Jun 2019
                : 41
                : 3
                : 284-286
                Affiliations
                [1]Department of Psychiatry, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
                [1 ]Department of Radiodiagnosis, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
                [2 ]Department of Neurology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
                Author notes
                Address for correspondence: Dr. Suravi Patra Department of Psychiatry, All India Institute of Medical Sciences, Bhubaneswar - 751 019, Odisha, India. E-mail: patrasuravi@ 123456gmail.com
                Article
                IJPsyM-41-284
                10.4103/IJPSYM.IJPSYM_281_18
                6532376
                978fc73c-7b50-48fc-bfee-eba6f984211d
                Copyright: © 2019 Indian Psychiatric Society - South Zonal Branch

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                Categories
                Letters to Editor

                Clinical Psychology & Psychiatry
                Clinical Psychology & Psychiatry

                Comments

                Comment on this article