Conference Coverage

Which Factors Predict an Autism Diagnosis in Children With Tuberous Sclerosis Complex?

And Other News From the 43rd Annual Meeting of the Child Neurology Society


 

References

COLUMBUS, OHIO—Cognitive impairment at age 12 months predicts a subsequent diagnosis of autism spectrum disorder in children with tuberous sclerosis complex, according to researchers.

The relationship between intellectual disability and social-communication deficits among children with tuberous sclerosis complex, however, requires further investigation, said the investigators.

Shafali S. Jeste, MD, Assistant Professor in Psychiatry and Neurology at the University of California, Los Angeles, and colleagues conducted a longitudinal cohort study of infants with tuberous sclerosis complex to determine early clinical predictors of autism spectrum disorder and characterize the phenotype of autism in young children with tuberous sclerosis complex.

The researchers recruited infants with tuberous sclerosis complex and typically developing infants as young as 3 months and followed them longitudinally until age 36 months. They gathered data including standard cognitive and social-communication measures (ie, Mullen Scales of Early Learning, Autism Observation Scale of Infancy, and the Early Social Communication Scales), comorbidities questionnaires, and a detailed seizure history. Autism spectrum diagnosis was made using the Autism Diagnostic Observation Schedule and confirmed using best clinical estimate at ages 18, 24, and 36 months.

Of a population of 40 infants, 22 received a diagnosis of autism spectrum disorder. Children with autism had significantly greater cognitive delays by age 12 months and a significant decline in nonverbal IQ from ages 12 to 36 months, compared with children without autism. At 24 months, children with autism had significantly greater cognitive impairment, higher anxiety symptoms, more sleep impairment, and a trend toward greater seizure severity. Children not diagnosed with autism had subclinical evidence of social-communication impairment, particularly in language and play.

Do rTMS and Constraint Therapy Reduce Perinatal Stroke Hemiparesis?
Children with hemiparesis resulting from perinatal stroke perceive marked increases in goal-specific function following treatment with repetitive transcranial magnetic stimulation (rTMS) and constraint therapy, investigators reported.

Further study of noninvasive brain stimulation is feasible and may enhance motor learning therapy in such patients, according to the researchers.

Researchers previously had studied rTMS and constraint therapy in adults with stroke, but the treatments had not been examined in perinatal stroke. Adam Kirton, MD, Associate Professor of Pediatrics and Clinical Neurosciences at the University of Calgary in Canada, and colleagues conducted a blinded factorial trial of rTMS and constraint therapy in 45 children with perinatal stroke hemiparesis. Eligible participants were between ages 6 and 18, and the sample’s mean age was 11.

The children were randomized to daily inhibitory rTMS (ie, 1,200 stimulations at 1 Hz) over contralesional M1, constraint therapy, both treatments, or neither treatment. All interventions were administered for two weeks as part of a goal-directed, peer-supported motor learning camp.

The study’s primary outcome measure was the Canadian Occupational Performance Measure (COPM) at one, eight, and 24 weeks. Secondary outcomes included Assisting Hand Assessment (AHA), Melbourne Assessment (MA), safety, and tolerability. The researchers assessed change across treatment groups from baseline to six months and across all time points.

For all participants, COPM performance and satisfaction scores increased, and maximal gains were observed at six months. Linear mixed effects model analysis demonstrated effects of combined rTMS and constraint therapy on AHA gains at all time points. Constraint therapy alone increased AHA at two months, rTMS alone increased AHA at one week, and neither treatment decreased normal hand function. Affected hand function did not decrease with rTMS in children with ipsilateral corticospinal tract arrangements. The procedures were well tolerated.

Arbaclofen May Not Reduce Social Avoidance in Fragile X Syndrome
Arbaclofen may not reduce social avoidance among patients with fragile X syndrome, according to clinical trial results presented. The drug may modify the disease’s trajectory, however, and deserves further testing, said Elizabeth Berry-Kravis, MD, PhD.

Arbaclofen is a specific GABA-B agonist that has been approved to treat spasticity in multiple sclerosis. The drug improved several abnormal phenotypes in animal models of fragile X syndrome and showed promise in a phase II clinical trial. Dr. Berry-Kravis, Associate Professor of Biochemistry, Neurological Sciences, and Pediatrics at Rush Medical College in Chicago, and colleagues conducted two phase III placebo-controlled trials to determine the drug’s safety and efficacy for social avoidance in fragile X syndrome.

The investigators randomized 125 patients to arbaclofen or placebo in a flexible-dose trial. Eligible patients were between ages 12 and 50. In a separate fixed-dose trial, the researchers randomized 172 participants to 5 mg of arbaclofen twice per day, 10 mg of arbaclofen twice per day, 10 mg of arbaclofen three times per day, or placebo. Eligible subjects in this trial were between ages 5 and 11.

The primary end point for both trials was the Fragile X Syndrome Social Avoidance subscale of the Aberrant Behavior Checklist (ABC). Secondary outcomes included other ABC subscale scores, Clinical Global Impression–Improvement score, Clinical Global Impression-Severity score, and Vineland Socialization domain score.

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