Predisposition to autoimmunity, and immune/inflammatory activation, is associated with autistic regression, study reveals.

‘Autistic regression’ is a phenomenon where a previously normally developing child suddenly loses his or her developmental milestones and previously acquired language and social skills, and regresses into autism. While the majority of patients who are later diagnosed with autism present with developmental delay from the time of their birth, about a third of all autism cases demonstrate normal, that is neurotypical, development for the first 12-24 months of age, followed by a regression and loss of previously achieved developmental and verbal skills. Those children who lose their previously acquired skills and regress into autism comprise over 30% of all autism cases.

Symptoms such as fever, irritability, vomiting, incessant crying, sudden changes in sleep patterns and emergence of motor abnormalities are often noted around the time of autistic regression. There are also an increasing number of reports of unusual patterns of regression—including repeated regressions, regressions involving loss of gross motor function, and/or regressions after age three years, and there seems to be a clear association between regression and negative long-term functional outcomes.

The reasons why autistic regression happens are largely unknown, as regressions are rarely a subject of detailed clinical investigations.

Emerging evidence suggests that immune dysregulation may be involved in the pathogenesis of at least some cases of autistic regression. Scientific literature abounds with case studies describing autistic regression following viral and bacterial encephalitis in previously healthy and typical children and even adolescents, as well as regression into autism in cases of autoimmune proliferative syndrome, or autoimmune anti-N-methyl-D-aspartate receptor encephalitis. In some of these recorded cases the patients respond remarkably well to corticosteroid or IVIG treatment. One such example is a case reported by Akcakaya and colleagues of a previously normally functioning girl who lost all eye-contact, ability to communicate, interest in socializing, and whose interests and behaviours became extremely restrictive and repetitive following viral encephalitis. In addition, this patient also displayed rigid hand postures and abnormal gait and motor function, lack of attention, all frequently present in children and adults with idiopathic autism. In this case the patient was given a prolonged hospital treatment of IVIG injections, resulting in full recovery from all autism symptoms.

Literature from the wider field of psychiatry points to the presence of pathological antineuronal antibodies in some patients with sudden-onset psychiatric symptoms, and resolution of those symptoms following immunological treatments.

Our study demonstrated that children with autistic regression differ from those with ASD with respect to family history of autoimmunity – and, in particular, maternal autoimmunity – and occurrence of a febrile illness in the 6 months prior to first concern. (Scott 2017)

In the most recent study by Scott and colleagues the authors reviewed the medical records of 240 children diagnosed with an autism spectrum disorder, including 33 cases with a documented “autistic regression variant”. The results from their analysis indicate significant associations between autistic regression and family history of autoimmunity, such as Type 1 diabetes and autoimmune thyroiditis, as well as preceding febrile illnesses in the child. Other non-immune risk factors did not differ between the two groups.

• Familial autoimmunity is more prevalent in autistic regression variant compared
with autism spectrum disorders (ASDs).
• A higher rate of familial type 1 diabetes and autoimmune thyroid disease is
seen in autistic regression variant than in ASDs.
• Incidence of febrile illness preceding symptom onset is higher in autistic
regression variant than in ASDs.
• We suggest immune activation as a possible aetiology of autistic
regression.

Also see: Autoimmune encephalitis mimicks autistic regression

Also see: Inflammation, inflammation, inflammation

This article is part of Treating Autism Clinical & Research Newsletter: Issue 2

References:

Scott O., Shi D., Andriashek D., et al. (2017) Clinical clues for autoimmunity and neuroinflammation in patients with autistic regression. Dev Med Child Neurol. 2017 Apr 6. doi: 10.1111/dmcn.13432.

Further reading:

Akcakaya N.H., Tekturk P., Cagatay A., et al. (2016) Atypical enterovirus encephalitis causing behavioral changes and autism-like clinical manifestations: case report. Acta Neurol Belg. Dec;116(4):679-681. doi: 10.1007/s13760-016-0614-5.

Atladottir H.O., Pedersen M.G., Thorsen P., et al. (2009) Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics; 124: 687–94. doi: 10.1542/peds.2008-2445.

Baldaçara L., Diniz T., Parreira B., et al. (2011) Organic mental disorder after pneumococcal meningoencephalitis with autism-like symptoms. Rev Bras Psiquiatr. Dec;33(4):410-1. doi: 10.1590/S1516-44462011000400016.

Barger, B.D., Campbell, J.M. and McDonough, J.D. (2012) Prevalence and Onset of Regression within Autism Spectrum Disorders: A Meta-analytic Review. J Autism Dev Disord. 1-12. doi: 10.1007/s10803-012-1621-x.

DeLong G.R., Bean S.C., & Brown F.R. 3rd. (1981) Acquired reversible autistic syndrome in acute encephalopathic illness in children. Arch Neurol. Mar;38(3):191-4. doi: 10.1001/archneur.1981.00510030085013.

Duffy F.H., Shankardass A., McAnulty G.B., et al. (2014) Corticosteroid therapy in regressive autism: a retrospective study of effects on the Frequency Modulated Auditory Evoked Response (FMAER), language, and behavior. BMC Neurol; 14: 70. doi: 10.1186/1741-7015-12-79.

Ghaziuddin M., Al-Khouri I., & Ghaziuddin N.. (2002) Autistic symptoms following herpes encephalitis. Eur Child Adolesc Psychiatry. Jun;11(3):142-6.doi: 10.1007/s00787-002-0271-5.

Gillberg C. (1986) Onset at age 14 of a typical autistic syndrome. A case report of a girl with herpes simplex encephalitis. J Autism Dev Disord. Sep;16(3):369-75. doi: 0162-3257/86/0900-0369505.00/0.

Gillberg C. (1991) Autistic syndrome with onset at age 31 years: herpes encephalitis as a possible model for childhood autism. Dev Med Child Neurol. Oct;33(10):920-4. doi: 10.1111/j.1469-8749.1991.tb14804.

Goin-Kochel R., Esler, A.N., Kanne, S., et al. (2014) Developmental regression among children with autism spectrum disorder: Onset, duration, and effects on functional outcomes. Res Autism Spec Disord. 8:890-898. doi: 10.1016/j.rasd.2014.04.002.

Hacohen Y., Wright S., Gadian J., et al. (2016) N-methyl-Daspartate (NMDA) receptor antibodies encephalitis mimicking an autistic regression. Dev Med Child Neurol; 58: 1092–94. doi: 10.1111/dmcn.13169.

Mankoski R.E., Collins M., Ndosi N.K., et al. (2006) Etiologies of autism in a case-series from Tanzania. J Autism Dev Disord. Nov;36(8):1039-51. doi: 10.1007/s10803-006-0143-9.

Marques F., Brito M.J., Conde M., et al. (2014) Autism spectrum disorder secondary to enterovirus encephalitis. J Child Neurol. May;29(5):708-14. doi: 10.1177/0883073813508314.

Scott O., Richer L., Forbes K., et al. (2014) Anti-N-methyl-Daspartate (NMDA) receptor encephalitis: an unusual cause of autistic regression in a toddler. J Child Neurol; 29: 691–94. doi: 10.1177/0883073813501875.

Stefanatos G.A., Grover W., & Geller E. (1995) Case study: corticosteroid treatment of language regression in pervasive developmental disorder. J Am Acad Child Adolesc Psychiatry; 34: 1107–11. doi: 10.1097/00004583-199508000-00022.

Vinet E, Pineau C.A., Clarke A.E., et al. (2015) Increased risk of autism spectrum disorders in children born to women with systemic lupus erythematosus: results from a large population-based cohort. Arthritis Rheumatol; 67: 3201–08. doi: 10.1002/art.39320.