Steroids for regressive autism?

Preliminary findings suggest steroid treatment could improve language and behavior in children with ASD.
Preliminary findings suggest that steroid treatment could improve language and behavior in children with regressive ASD.

In as many as a third of cases of autism spectrum disorder (ASD), children’s language and social skills develop normally at first. Then, between 1 and 2 ½ years of age, they begin to regress, losing words and retreating from interactions with parents—often abruptly. There has been some anecdotal evidence that steroid treatment can help these children, and a small retrospective study agrees—finding improved language and behavior and reversal of a characteristic abnormality in the language processing area of their brains.

Researchers led by Frank H. Duffy, MD, of the Epilepsy Center at Boston Children’s Hospital, looked back at 20 children 3 to 5 years old with documented regressive ASD who had received steroid therapy (prednisolone) under a neurologist’s supervision, generally starting several months after their regression was noted. For comparison, the team also reviewed data from 24 similar autistic children who did not receive steroids.

Both groups of children had data from at least two sequential EEG studies (often performed to rule out epilepsy, which is commonly suspected in children with regressive ASD) as well as a specialized neurophysiological test known as the Frequency Modulated Auditory Evoked Response (FMAER). The FMAER analyzes brainwaves induced by specialized sound stimuli in the brain’s receptive language processing region (the superior temporal gyrus). Boston Children’s often includes it in EEG testing for children with language deficits, and Duffy and colleagues have demonstrated its use in studying various kinds of language disorders.

As reported May 15 in the open-access journal BMC Neurology, the children treated with steroids showed a significant increase in the FMAER response in the superior temporal gyrus and significantly less distortion and “noise” in the FMAER signals after treatment. Compared with untreated children, they showed significant improvements in expressive and receptive language ratings (based on a specialized assessment tool), and most also showed significant improvement in behavioral symptoms (based on DSM-IV criteria). The language and behavior improvements still held one year after steroids were discontinued.

FMAER responses to 4 Hz FM auditory stimulation before and after steroid treatment in children with regressive autism. After treatment, the signals have a greater amplitude (shown at left) and show less distortion and noise by spectral analysis (shown at right).
FMAER responses to 4 Hz FM auditory stimulation before and after steroid treatment in children with regressive autism. After treatment, the signals have a greater amplitude (shown at left) and show less distortion and noise by spectral analysis (shown at right).

Based on the FMAER results, Duffy proposes that receptive language loss in regressive ASD is caused by distortion of receptive language processing in the brain. He speculates that the inability to begin to understand language may cause infants and toddlers to turn inward and develop stereotypical behaviors as a form of self-stimulation. “Without a properly functioning superior temporal gyrus, children hear sounds but cannot decode the unique auditory components of speech,” he says. “In our study, when language improved following steroids, ‘autistic’ behaviors typically diminished.”

Are these results too good to be true? Though this was a retrospective study, the children were selected carefully to ensure that none had a sensory disorder, a genetic or epilepsy disorder associated with autism, or any condition that might alter their EEG readings. The steroids were prescribed at the neurologists’ discretion and with family agreement, however, and factors affecting that choice may have somehow confounded the results. The steroids did cause side effects, primarily weight gain, though most were mild and went away when steroids were discontinued.

Many questions still need to be answered. What is the mechanism of steroids’ apparent benefit? Steroids have a multiplicity of actions, as discussed in the paper. Will results differ depending on how soon steroids are started and the length of treatment? Will the benefits extend beyond one year?

Duffy’s team is now in the process of planning a larger, more controlled study of steroid treatment in regressive autism. As Sailaja Golla, MD, and John Sweeney, PhD, of UT Southwestern/Children’s Medical Center at Dallas write in an accompanying editorial, “a detailed cost-benefit analysis of this treatment in a randomized trial is needed to establish that benefits outweigh risks in this population.”

In the meantime, the findings suggest that FMAER might have a place as a quantitative “biomarker” of treatment efficacy in ASD, at least for those children with ASD who have lost language skills.