Kate Johnson

June 12, 2014

ST. LOUIS — Brain images of neuroinflammation in children with Tourette syndrome are different from those in children with neuropsychiatric disorders related to streptococcal infections, new research shows.

The finding has fueled the debate about whether the 2 conditions are part of a single spectrum.

"This is just one step in unraveling the puzzle," said researcher Ajay Kumar, MD, PhD, from the Children's Hospital of Michigan and Detroit Medical Center. The imaging differences suggest that there is something different between these 2 conditions, he said.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, known as PANDAS, are associated with the abrupt postinfection development of obsessive–compulsive disorder and motor tics. The diagnosis remains controversial, however, and "some people think that PANDAS might be a part of Tourette syndrome," explained Dr. Kumar.

He presented the results of the study here at the Society of Nuclear Medicine and Molecular Imaging 2014 Annual Meeting.

The controversy over whether PANDAS is a separate entity or an extreme form of Tourette syndrome has led to questions about optimal management. "Is there a role for antibiotics or anti-inflammatories in PANDAS? Because those things are not used routinely in Tourette syndrome," said Dr. Kumar.

This is first study to compare imaging of neuroinflammation in the 2 conditions.

The 17 children with PANDAS (mean age, 11.4 years) and the 12 children with Tourette syndrome (mean age, 11.0 years) underwent PET scanning after receiving an injection of 11C-[R]-PK11195.

Disease onset occurred at an older age in the PANDAS group than in the Tourette group (7.7 vs 5.6 years; P = .09), but the duration of illness was not significantly different between the 2 groups (3.7 vs 4.7 years).

In the Tourette group, there were "some neuroinflammatory changes in the bilateral caudate nuclei," Dr. Kumar reported. However, in PANDAS group, "neuroinflammatory changes were seen not only in the bilateral caudate, but also in the bilateral lentiform nuclei."

"This may signify a possible pathophysiological difference between the conditions," he said.

In addition, in the PANDAS group, neuroinflammatory changes tended to diminish as the duration of illness increased. In contrast, in the Tourette group, the changes tended to actually increase as the duration of illness increased.

"This may indicate 2 mechanistically different entities, or it may be related to the sudden onset of seizure symptoms in the PANDAS group and the more insidious onset in the Tourette group," said Dr. Kumar. It is possible that symptoms are so severe in PANDAS that the substantial neuroinflammatory changes subside over time, he added.

This study "provides support for significant heterogeneity of disease mechanisms in children with tics," said Nicolaas Bohnen, MD, PhD, from the Departments of Radiology and Neurology at the University of Michigan in Detroit.

In PANDAS, "the decreased correlation between inflammation and longer duration of disease suggests an acute or more isolated immunogenic exposure, similar to what is seen in children with Sydenham's chorea," he explained.

It has been suggested that genetics play a role in Tourette syndrome, but questions remain. "Most likely we are dealing with a multifactorial etiopathogenesis," said Dr. Bohnen. As Dr. Kumar and colleagues point out, neuroinflammation plays an important role in these children, he added.

It is noteworthy that not only is the striatal pattern different in the Tourette group than in the PANDAS group, the longer duration of disease is associated with more inflammation in the Tourette group.

This suggests that in Tourette syndrome, the inflammatory response is less likely to reflect a single and acute immunogenic event. It "may either reflect increased susceptibility to possibly repeated external immunogenic factors or, perhaps, internal metabolic proinflammatory disease responses related to altered gene expression," Dr. Bohnen explained.

The study was supported by the Mental Illness Research Association and the Baiardi Family Foundation. Dr. Kumar and Dr. Bohnen have disclosed no relevant financial relationships.

Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2014 Annual Meeting: Abstract 306. Presented June 10, 2014.

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